Riboflavin: The Health Benefits of a Forgotten Natural Vitamin
Identifieur interne : 000A30 ( Pmc/Corpus ); précédent : 000A29; suivant : 000A31Riboflavin: The Health Benefits of a Forgotten Natural Vitamin
Auteurs : Nittiya Suwannasom ; Ijad Kao ; Axel Pru ; Radostina Georgieva ; Hans B UmlerSource :
- International Journal of Molecular Sciences [ 1422-0067 ] ; 2020.
Abstract
Riboflavin (RF) is a water-soluble member of the B-vitamin family. Sufficient dietary and supplemental RF intake appears to have a protective effect on various medical conditions such as sepsis, ischemia etc., while it also contributes to the reduction in the risk of some forms of cancer in humans. These biological effects of RF have been widely studied for their anti-oxidant, anti-aging, anti-inflammatory, anti-nociceptive and anti-cancer properties. Moreover, the combination of RF and other compounds or drugs can have a wide variety of effects and protective properties, and diminish the toxic effect of drugs in several treatments. Research has been done in order to review the latest findings about the link between RF and different clinical aberrations. Since further studies have been published in this field, it is appropriate to consider a re-evaluation of the importance of RF in terms of its beneficial properties.
Url:
DOI: 10.3390/ijms21030950
PubMed: 32023913
PubMed Central: 7037471
Links to Exploration step
PMC:7037471Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Riboflavin: The Health Benefits of a Forgotten Natural Vitamin</title><author><name sortKey="Suwannasom, Nittiya" sort="Suwannasom, Nittiya" uniqKey="Suwannasom N" first="Nittiya" last="Suwannasom">Nittiya Suwannasom</name><affiliation><nlm:aff id="af1-ijms-21-00950">Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-ijms-21-00950">School of Medical Sciences, University of Phayao, Phayao 56000, Thailand</nlm:aff></affiliation></author><author><name sortKey="Kao, Ijad" sort="Kao, Ijad" uniqKey="Kao I" first="Ijad" last="Kao">Ijad Kao</name><affiliation><nlm:aff id="af1-ijms-21-00950">Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation></author><author><name sortKey="Pru, Axel" sort="Pru, Axel" uniqKey="Pru A" first="Axel" last="Pru">Axel Pru</name><affiliation><nlm:aff id="af1-ijms-21-00950">Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation></author><author><name sortKey="Georgieva, Radostina" sort="Georgieva, Radostina" uniqKey="Georgieva R" first="Radostina" last="Georgieva">Radostina Georgieva</name><affiliation><nlm:aff id="af1-ijms-21-00950">Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation><affiliation><nlm:aff id="af3-ijms-21-00950">Biophysics and Radiology, Department of Medical Physics, Faculty of Medicine, Trakia University, 6000 Stara Zagora, Bulgaria</nlm:aff></affiliation></author><author><name sortKey="B Umler, Hans" sort="B Umler, Hans" uniqKey="B Umler H" first="Hans" last="B Umler">Hans B Umler</name><affiliation><nlm:aff id="af1-ijms-21-00950">Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32023913</idno><idno type="pmc">7037471</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037471</idno><idno type="RBID">PMC:7037471</idno><idno type="doi">10.3390/ijms21030950</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000A30</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000A30</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Riboflavin: The Health Benefits of a Forgotten Natural Vitamin</title><author><name sortKey="Suwannasom, Nittiya" sort="Suwannasom, Nittiya" uniqKey="Suwannasom N" first="Nittiya" last="Suwannasom">Nittiya Suwannasom</name><affiliation><nlm:aff id="af1-ijms-21-00950">Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-ijms-21-00950">School of Medical Sciences, University of Phayao, Phayao 56000, Thailand</nlm:aff></affiliation></author><author><name sortKey="Kao, Ijad" sort="Kao, Ijad" uniqKey="Kao I" first="Ijad" last="Kao">Ijad Kao</name><affiliation><nlm:aff id="af1-ijms-21-00950">Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation></author><author><name sortKey="Pru, Axel" sort="Pru, Axel" uniqKey="Pru A" first="Axel" last="Pru">Axel Pru</name><affiliation><nlm:aff id="af1-ijms-21-00950">Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation></author><author><name sortKey="Georgieva, Radostina" sort="Georgieva, Radostina" uniqKey="Georgieva R" first="Radostina" last="Georgieva">Radostina Georgieva</name><affiliation><nlm:aff id="af1-ijms-21-00950">Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation><affiliation><nlm:aff id="af3-ijms-21-00950">Biophysics and Radiology, Department of Medical Physics, Faculty of Medicine, Trakia University, 6000 Stara Zagora, Bulgaria</nlm:aff></affiliation></author><author><name sortKey="B Umler, Hans" sort="B Umler, Hans" uniqKey="B Umler H" first="Hans" last="B Umler">Hans B Umler</name><affiliation><nlm:aff id="af1-ijms-21-00950">Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</nlm:aff></affiliation></author></analytic><series><title level="j">International Journal of Molecular Sciences</title><idno type="eISSN">1422-0067</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Riboflavin (RF) is a water-soluble member of the B-vitamin family. Sufficient dietary and supplemental RF intake appears to have a protective effect on various medical conditions such as sepsis, ischemia etc., while it also contributes to the reduction in the risk of some forms of cancer in humans. These biological effects of RF have been widely studied for their anti-oxidant, anti-aging, anti-inflammatory, anti-nociceptive and anti-cancer properties. Moreover, the combination of RF and other compounds or drugs can have a wide variety of effects and protective properties, and diminish the toxic effect of drugs in several treatments. Research has been done in order to review the latest findings about the link between RF and different clinical aberrations. Since further studies have been published in this field, it is appropriate to consider a re-evaluation of the importance of RF in terms of its beneficial properties.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Cardoso, D R" uniqKey="Cardoso D">D.R. Cardoso</name></author><author><name sortKey="Libardi, S H" uniqKey="Libardi S">S.H. Libardi</name></author><author><name sortKey="Skibsted, L H" uniqKey="Skibsted L">L.H. Skibsted</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dym, O" uniqKey="Dym O">O. Dym</name></author><author><name sortKey="Eisenberg, D" uniqKey="Eisenberg D">D. Eisenberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Buehler, B A" uniqKey="Buehler B">B.A. Buehler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author><author><name sortKey="Zhou, W E" uniqKey="Zhou W">W.E. Zhou</name></author><author><name sortKey="Yan, J Q" uniqKey="Yan J">J.Q. Yan</name></author><author><name sortKey="Liu, M" uniqKey="Liu M">M. Liu</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y. Zhou</name></author><author><name sortKey="Shen, X" uniqKey="Shen X">X. Shen</name></author><author><name sortKey="Ma, Y L" uniqKey="Ma Y">Y.L. Ma</name></author><author><name sortKey="Feng, X S" uniqKey="Feng X">X.S. Feng</name></author><author><name sortKey="Yang, J" uniqKey="Yang J">J. Yang</name></author><author><name sortKey="Li, G H" uniqKey="Li G">G.H. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gul, W N" uniqKey="Gul W">W.N. Gul</name></author><author><name sortKey="Anwar, Z" uniqKey="Anwar Z">Z. Anwar</name></author><author><name sortKey="Qadeer, K" uniqKey="Qadeer K">K. Qadeer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Antal, I P" uniqKey="Antal I">I.P. Antal</name></author><author><name sortKey="Bazel, Y R" uniqKey="Bazel Y">Y.R. Bazel</name></author><author><name sortKey="Kormosh, Z A" uniqKey="Kormosh Z">Z.A. Kormosh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Powers, H J" uniqKey="Powers H">H.J. Powers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Toyosawa, T" uniqKey="Toyosawa T">T. Toyosawa</name></author><author><name sortKey="Suzuki, M" uniqKey="Suzuki M">M. Suzuki</name></author><author><name sortKey="Kodama, K" uniqKey="Kodama K">K. Kodama</name></author><author><name sortKey="Araki, S" uniqKey="Araki S">S. Araki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Toyosawa, T" uniqKey="Toyosawa T">T. Toyosawa</name></author><author><name sortKey="Suzuki, M" uniqKey="Suzuki M">M. Suzuki</name></author><author><name sortKey="Kodama, K" uniqKey="Kodama K">K. Kodama</name></author><author><name sortKey="Araki, S" uniqKey="Araki S">S. Araki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Toyasaki, T" uniqKey="Toyasaki T">T. Toyasaki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zou, Y" uniqKey="Zou Y">Y. Zou</name></author><author><name sortKey="Ruan, M" uniqKey="Ruan M">M. Ruan</name></author><author><name sortKey="Luan, J" uniqKey="Luan J">J. Luan</name></author><author><name sortKey="Feng, X" uniqKey="Feng X">X. Feng</name></author><author><name sortKey="Chen, S" uniqKey="Chen S">S. Chen</name></author><author><name sortKey="Chu, Z" uniqKey="Chu Z">Z. Chu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cheung, I M Y" uniqKey="Cheung I">I.M.Y. Cheung</name></author><author><name sortKey="Mcghee, C N J" uniqKey="Mcghee C">C.N.J. Mcghee</name></author><author><name sortKey="Sherwin, T" uniqKey="Sherwin T">T. Sherwin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sanches, S C" uniqKey="Sanches S">S.C. Sanches</name></author><author><name sortKey="Naira, L" uniqKey="Naira L">L. Naira</name></author><author><name sortKey="Ramalho, Z" uniqKey="Ramalho Z">Z. Ramalho</name></author><author><name sortKey="Mendes Braz, M" uniqKey="Mendes Braz M">M. Mendes-Braz</name></author><author><name sortKey="Terra, V A" uniqKey="Terra V">V.A. Terra</name></author><author><name sortKey="Cecchini, R" uniqKey="Cecchini R">R. Cecchini</name></author><author><name sortKey="Augusto, M J" uniqKey="Augusto M">M.J. Augusto</name></author><author><name sortKey="Ramalho, F S" uniqKey="Ramalho F">F.S. Ramalho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pompella, A" uniqKey="Pompella A">A. Pompella</name></author><author><name sortKey="Visvikis, A" uniqKey="Visvikis A">A. Visvikis</name></author><author><name sortKey="Paolicchi, A" uniqKey="Paolicchi A">A. Paolicchi</name></author><author><name sortKey="De Tata, V" uniqKey="De Tata V">V. De Tata</name></author><author><name sortKey="Casini, A F" uniqKey="Casini A">A.F. Casini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tripathi, A K" uniqKey="Tripathi A">A.K. Tripathi</name></author><author><name sortKey="Dwivedi, A" uniqKey="Dwivedi A">A. Dwivedi</name></author><author><name sortKey="Pal, M K" uniqKey="Pal M">M.K. Pal</name></author><author><name sortKey="Rastogi, N" uniqKey="Rastogi N">N. Rastogi</name></author><author><name sortKey="Gupta, P" uniqKey="Gupta P">P. Gupta</name></author><author><name sortKey="Ali, S" uniqKey="Ali S">S. Ali</name></author><author><name sortKey="Prabhu Bh, M" uniqKey="Prabhu Bh M">M. Prabhu Bh</name></author><author><name sortKey="Kushwaha, H N" uniqKey="Kushwaha H">H.N. Kushwaha</name></author><author><name sortKey="Singh Ray, R" uniqKey="Singh Ray R">R. Singh Ray</name></author><author><name sortKey="Singh, S K" uniqKey="Singh S">S.K. Singh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, G" uniqKey="Wang G">G. Wang</name></author><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author><author><name sortKey="Lu, X" uniqKey="Lu X">X. Lu</name></author><author><name sortKey="Zhao, X" uniqKey="Zhao X">X. Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alam, M M" uniqKey="Alam M">M.M. Alam</name></author><author><name sortKey="Iqbal, S" uniqKey="Iqbal S">S. Iqbal</name></author><author><name sortKey="Naseem, I" uniqKey="Naseem I">I. Naseem</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Indumathi, U" uniqKey="Indumathi U">U. Indumathi</name></author><author><name sortKey="Kanchana, K" uniqKey="Kanchana K">K. Kanchana</name></author><author><name sortKey="Sachdanandam, P" uniqKey="Sachdanandam P">P. Sachdanandam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Naz Ro Lu, M" uniqKey="Naz Ro Lu M">M. Nazıroğlu</name></author><author><name sortKey="Celik, O" uniqKey="Celik O">Ö. Çelik</name></author><author><name sortKey="U Uz, A C" uniqKey="U Uz A">A.C. Uğuz</name></author><author><name sortKey="Butun, A" uniqKey="Butun A">A. Bütün</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Butun, A" uniqKey="Butun A">A. Bütün</name></author><author><name sortKey="Naz Ro Lu, M" uniqKey="Naz Ro Lu M">M. Nazıroğlu</name></author><author><name sortKey="Demirci, S" uniqKey="Demirci S">S. Demirci</name></author><author><name sortKey="Celik, O" uniqKey="Celik O">Ö. Çelik</name></author><author><name sortKey="U Uz, A C" uniqKey="U Uz A">A.C. Uğuz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, Y" uniqKey="Lin Y">Y. Lin</name></author><author><name sortKey="Desbois, A" uniqKey="Desbois A">A. Desbois</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author><author><name sortKey="Hou, S T" uniqKey="Hou S">S.T. Hou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoane, M R" uniqKey="Hoane M">M.R. Hoane</name></author><author><name sortKey="Wolyniak, J G" uniqKey="Wolyniak J">J.G. Wolyniak</name></author><author><name sortKey="Akstulewicz, S L" uniqKey="Akstulewicz S">S.L. Akstulewicz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barbre, A B" uniqKey="Barbre A">A.B. Barbre</name></author><author><name sortKey="Hoane, M R" uniqKey="Hoane M">M.R. Hoane</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Seekamp, A" uniqKey="Seekamp A">A. Seekamp</name></author><author><name sortKey="Hultquist, D E" uniqKey="Hultquist D">D.E. Hultquist</name></author><author><name sortKey="Till, G O" uniqKey="Till G">G.O. Till</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Betz, A L" uniqKey="Betz A">A.L. Betz</name></author><author><name sortKey="Ren, X D" uniqKey="Ren X">X.D. Ren</name></author><author><name sortKey="Ennis, S R" uniqKey="Ennis S">S.R. Ennis</name></author><author><name sortKey="Hultquist, D E" uniqKey="Hultquist D">D.E. Hultquist</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mack, C P" uniqKey="Mack C">C.P. Mack</name></author><author><name sortKey="Hultquist, D E" uniqKey="Hultquist D">D.E. Hultquist</name></author><author><name sortKey="Shlafer, M" uniqKey="Shlafer M">M. Shlafer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kulkarni, A G" uniqKey="Kulkarni A">A.G. Kulkarni</name></author><author><name sortKey="Suryakar, A N" uniqKey="Suryakar A">A.N. Suryakar</name></author><author><name sortKey="Sardeshmukh, A S" uniqKey="Sardeshmukh A">A.S. Sardeshmukh</name></author><author><name sortKey="Rathi, D B" uniqKey="Rathi D">D.B. Rathi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Akompong, T" uniqKey="Akompong T">T. Akompong</name></author><author><name sortKey="Ghori, N" uniqKey="Ghori N">N. Ghori</name></author><author><name sortKey="Haldar, K" uniqKey="Haldar K">K. Haldar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="George, B O" uniqKey="George B">B.O. George</name></author><author><name sortKey="Ojegbemi, O" uniqKey="Ojegbemi O">O. Ojegbemi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Araki, S" uniqKey="Araki S">S. Araki</name></author><author><name sortKey="Suzuki, M" uniqKey="Suzuki M">M. Suzuki</name></author><author><name sortKey="Fujimoto, M" uniqKey="Fujimoto M">M. Fujimoto</name></author><author><name sortKey="Kimura, M" uniqKey="Kimura M">M. Kimura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mazur Bialy, A I" uniqKey="Mazur Bialy A">A.I. Mazur-Bialy</name></author><author><name sortKey="Buchala, B" uniqKey="Buchala B">B. Buchala</name></author><author><name sortKey="Plytycz, B" uniqKey="Plytycz B">B. Plytycz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qureshi, A A" uniqKey="Qureshi A">A.A. Qureshi</name></author><author><name sortKey="Reis, J C" uniqKey="Reis J">J.C. Reis</name></author><author><name sortKey="Qureshi, N" uniqKey="Qureshi N">N. Qureshi</name></author><author><name sortKey="Papasian, C J" uniqKey="Papasian C">C.J. Papasian</name></author><author><name sortKey="Morrison, D C" uniqKey="Morrison D">D.C. Morrison</name></author><author><name sortKey="Schaefer, D M" uniqKey="Schaefer D">D.M. Schaefer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Verdrengh, M" uniqKey="Verdrengh M">M. Verdrengh</name></author><author><name sortKey="Tarkowski, A" uniqKey="Tarkowski A">A. Tarkowski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Iwanaga, K" uniqKey="Iwanaga K">K. Iwanaga</name></author><author><name sortKey="Hasegawa, T" uniqKey="Hasegawa T">T. Hasegawa</name></author><author><name sortKey="Hultquist, D E" uniqKey="Hultquist D">D.E. Hultquist</name></author><author><name sortKey="Harada, H" uniqKey="Harada H">H. Harada</name></author><author><name sortKey="Yoshikawa, Y" uniqKey="Yoshikawa Y">Y. Yoshikawa</name></author><author><name sortKey="Yanamadala, S" uniqKey="Yanamadala S">S. Yanamadala</name></author><author><name sortKey="Liao, H" uniqKey="Liao H">H. Liao</name></author><author><name sortKey="Visovatti, S H" uniqKey="Visovatti S">S.H. Visovatti</name></author><author><name sortKey="Pinsky, D J" uniqKey="Pinsky D">D.J. Pinsky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qureshi, A A" uniqKey="Qureshi A">A.A. Qureshi</name></author><author><name sortKey="Tan, X" uniqKey="Tan X">X. Tan</name></author><author><name sortKey="Reis, J C" uniqKey="Reis J">J.C. Reis</name></author><author><name sortKey="Badr, M Z" uniqKey="Badr M">M.Z. Badr</name></author><author><name sortKey="Papasian, C J" uniqKey="Papasian C">C.J. Papasian</name></author><author><name sortKey="Morrison, D C" uniqKey="Morrison D">D.C. Morrison</name></author><author><name sortKey="Qureshi, N" uniqKey="Qureshi N">N. Qureshi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bertollo, C M" uniqKey="Bertollo C">C.M. Bertollo</name></author><author><name sortKey="Oliveira, A C P" uniqKey="Oliveira A">A.C.P. Oliveira</name></author><author><name sortKey="Rocha, L T S" uniqKey="Rocha L">L.T.S. Rocha</name></author><author><name sortKey="Costa, K A" uniqKey="Costa K">K.A. Costa</name></author><author><name sortKey="Nascimento, E B" uniqKey="Nascimento E">E.B. Nascimento</name></author><author><name sortKey="Coelho, M M" uniqKey="Coelho M">M.M. Coelho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Franca, D S" uniqKey="Franca D">D.S. França</name></author><author><name sortKey="Souza, A L S" uniqKey="Souza A">A.L.S. Souza</name></author><author><name sortKey="Almeida, K R" uniqKey="Almeida K">K.R. Almeida</name></author><author><name sortKey="Dolabella, S S" uniqKey="Dolabella S">S.S. Dolabella</name></author><author><name sortKey="Martinelli, C" uniqKey="Martinelli C">C. Martinelli</name></author><author><name sortKey="Coelho, M M" uniqKey="Coelho M">M.M. Coelho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mazur Bialy, A I" uniqKey="Mazur Bialy A">A.I. Mazur-Bialy</name></author><author><name sortKey="Majka, A" uniqKey="Majka A">A. Majka</name></author><author><name sortKey="Wojtas, L" uniqKey="Wojtas L">L. Wojtas</name></author><author><name sortKey="Kolaczkowska, E" uniqKey="Kolaczkowska E">E. Kolaczkowska</name></author><author><name sortKey="Plytycz, B" uniqKey="Plytycz B">B. Plytycz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mazur, A I" uniqKey="Mazur A">A.I. Mazur</name></author><author><name sortKey="Natorska, J" uniqKey="Natorska J">J. Natorska</name></author><author><name sortKey="Wypasek, E" uniqKey="Wypasek E">E. Wypasek</name></author><author><name sortKey="Kolaczkowska, E" uniqKey="Kolaczkowska E">E. Kołaczkowska</name></author><author><name sortKey="Plytycz, B" uniqKey="Plytycz B">B. Płytycz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mazur Bialy, A I" uniqKey="Mazur Bialy A">A.I. Mazur-Bialy</name></author><author><name sortKey="Kolaczkowska, E" uniqKey="Kolaczkowska E">E. Kolaczkowska</name></author><author><name sortKey="Plytycz, B" uniqKey="Plytycz B">B. Plytycz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Granados Soto, V" uniqKey="Granados Soto V">V. Granados-Soto</name></author><author><name sortKey="Teran Rosales, F" uniqKey="Teran Rosales F">F. Terán-Rosales</name></author><author><name sortKey="Rocha Gonzalez, H I" uniqKey="Rocha Gonzalez H">H.I. Rocha-González</name></author><author><name sortKey="Reyes Garcia, G" uniqKey="Reyes Garcia G">G. Reyes-García</name></author><author><name sortKey="Medina Santillan, R" uniqKey="Medina Santillan R">R. Medina-Santillán</name></author><author><name sortKey="Rodriguez Silverio, J" uniqKey="Rodriguez Silverio J">J. Rodríguez-Silverio</name></author><author><name sortKey="Flores Murrieta, F J" uniqKey="Flores Murrieta F">F.J. Flores-Murrieta</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Toyosawa, T" uniqKey="Toyosawa T">T. Toyosawa</name></author><author><name sortKey="Suzuki, M" uniqKey="Suzuki M">M. Suzuki</name></author><author><name sortKey="Kodama, K" uniqKey="Kodama K">K. Kodama</name></author><author><name sortKey="Araki, S" uniqKey="Araki S">S. Araki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kodama, K" uniqKey="Kodama K">K. Kodama</name></author><author><name sortKey="Suzuki, M" uniqKey="Suzuki M">M. Suzuki</name></author><author><name sortKey="Toyosawa, T" uniqKey="Toyosawa T">T. Toyosawa</name></author><author><name sortKey="Araki, S" uniqKey="Araki S">S. Araki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shih, C K" uniqKey="Shih C">C.K. Shih</name></author><author><name sortKey="Chen, C M" uniqKey="Chen C">C.M. Chen</name></author><author><name sortKey="Chen, C Y O" uniqKey="Chen C">C.Y.O. Chen</name></author><author><name sortKey="Liu, J F" uniqKey="Liu J">J.F. Liu</name></author><author><name sortKey="Lin, H W" uniqKey="Lin H">H.W. Lin</name></author><author><name sortKey="Chou, H T" uniqKey="Chou H">H.T. Chou</name></author><author><name sortKey="Li, S C" uniqKey="Li S">S.C. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Harbi, N O" uniqKey="Al Harbi N">N.O. Al-Harbi</name></author><author><name sortKey="Imam, F" uniqKey="Imam F">F. Imam</name></author><author><name sortKey="Nadeem, A" uniqKey="Nadeem A">A. Nadeem</name></author><author><name sortKey="Al Harbi, M M" uniqKey="Al Harbi M">M.M. Al-Harbi</name></author><author><name sortKey="Korashy, H M" uniqKey="Korashy H">H.M. Korashy</name></author><author><name sortKey="Sayed Ahmed, M M" uniqKey="Sayed Ahmed M">M.M. Sayed-Ahmed</name></author><author><name sortKey="Hafez, M M" uniqKey="Hafez M">M.M. Hafez</name></author><author><name sortKey="Al Shabanah, O A" uniqKey="Al Shabanah O">O.A. Al-Shabanah</name></author><author><name sortKey="Nagi, M N" uniqKey="Nagi M">M.N. Nagi</name></author><author><name sortKey="Bahashwan, S" uniqKey="Bahashwan S">S. Bahashwan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mazur Bialy, A I" uniqKey="Mazur Bialy A">A.I. Mazur-bialy</name></author><author><name sortKey="Pochec, E" uniqKey="Pochec E">E. Pochec</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, X H" uniqKey="Chen X">X.-H. Chen</name></author><author><name sortKey="Yin, Y J" uniqKey="Yin Y">Y.-J. Yin</name></author><author><name sortKey="Zhang, J X" uniqKey="Zhang J">J.-X. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mal, P" uniqKey="Mal P">P. Mal</name></author><author><name sortKey="Ghosh, D" uniqKey="Ghosh D">D. Ghosh</name></author><author><name sortKey="Bandyopadhyay, D" uniqKey="Bandyopadhyay D">D. Bandyopadhyay</name></author><author><name sortKey="Dutta, K" uniqKey="Dutta K">K. Dutta</name></author><author><name sortKey="Bishayi, B" uniqKey="Bishayi B">B. Bishayi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dey, S" uniqKey="Dey S">S. Dey</name></author><author><name sortKey="Bishayi, B" uniqKey="Bishayi B">B. Bishayi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mal, P" uniqKey="Mal P">P. Mal</name></author><author><name sortKey="Dutta, K" uniqKey="Dutta K">K. Dutta</name></author><author><name sortKey="Bandyopadhyay, D" uniqKey="Bandyopadhyay D">D. Bandyopadhyay</name></author><author><name sortKey="Basu, A" uniqKey="Basu A">A. Basu</name></author><author><name sortKey="Khan, R" uniqKey="Khan R">R. Khan</name></author><author><name sortKey="Bishayi, B" uniqKey="Bishayi B">B. Bishayi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schramm, M" uniqKey="Schramm M">M. Schramm</name></author><author><name sortKey="Wiegmann, K" uniqKey="Wiegmann K">K. Wiegmann</name></author><author><name sortKey="Schramm, S" uniqKey="Schramm S">S. Schramm</name></author><author><name sortKey="Gluschko, A" uniqKey="Gluschko A">A. Gluschko</name></author><author><name sortKey="Herb, M" uniqKey="Herb M">M. Herb</name></author><author><name sortKey="Utermohlen, O" uniqKey="Utermohlen O">O. Utermöhlen</name></author><author><name sortKey="Kronke, M" uniqKey="Kronke M">M. Krönke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wooley, J G" uniqKey="Wooley J">J.G. Wooley</name></author><author><name sortKey="Sebrell, W" uniqKey="Sebrell W">W. Sebrell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thaimuta, Z L" uniqKey="Thaimuta Z">Z.L. Thaimuta</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corbin, F" uniqKey="Corbin F">F. Corbin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ruane, P H" uniqKey="Ruane P">P.H. Ruane</name></author><author><name sortKey="Edrich, R" uniqKey="Edrich R">R. Edrich</name></author><author><name sortKey="Gampp, D" uniqKey="Gampp D">D. Gampp</name></author><author><name sortKey="Keil, S D" uniqKey="Keil S">S.D. Keil</name></author><author><name sortKey="Leonard, R L" uniqKey="Leonard R">R.L. Leonard</name></author><author><name sortKey="Goodrich, R P" uniqKey="Goodrich R">R.P. Goodrich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cardo, L J" uniqKey="Cardo L">L.J. Cardo</name></author><author><name sortKey="Rentas, F J" uniqKey="Rentas F">F.J. Rentas</name></author><author><name sortKey="Ketchum, L" uniqKey="Ketchum L">L. Ketchum</name></author><author><name sortKey="Salata, J" uniqKey="Salata J">J. Salata</name></author><author><name sortKey="Harman, R" uniqKey="Harman R">R. Harman</name></author><author><name sortKey="Melvin, W" uniqKey="Melvin W">W. Melvin</name></author><author><name sortKey="Weina, P J" uniqKey="Weina P">P.J. Weina</name></author><author><name sortKey="Mendez, J" uniqKey="Mendez J">J. Mendez</name></author><author><name sortKey="Reddy, H" uniqKey="Reddy H">H. Reddy</name></author><author><name sortKey="Goodrich, R" uniqKey="Goodrich R">R. Goodrich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pelletier, J P R" uniqKey="Pelletier J">J.P.R. Pelletier</name></author><author><name sortKey="Transue, S" uniqKey="Transue S">S. Transue</name></author><author><name sortKey="Snyder, E L" uniqKey="Snyder E">E.L. Snyder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shrubsole, M J" uniqKey="Shrubsole M">M.J. Shrubsole</name></author><author><name sortKey="Shu, X O" uniqKey="Shu X">X.O. Shu</name></author><author><name sortKey="Li, H L" uniqKey="Li H">H.L. Li</name></author><author><name sortKey="Cai, H" uniqKey="Cai H">H. Cai</name></author><author><name sortKey="Yang, G" uniqKey="Yang G">G. Yang</name></author><author><name sortKey="Gao, Y T" uniqKey="Gao Y">Y.T. Gao</name></author><author><name sortKey="Gao, J" uniqKey="Gao J">J. Gao</name></author><author><name sortKey="Zheng, W" uniqKey="Zheng W">W. Zheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chaves Neto, A H" uniqKey="Chaves Neto A">A.H. Chaves Neto</name></author><author><name sortKey="Pelizzaro Rocha, K J" uniqKey="Pelizzaro Rocha K">K.J. Pelizzaro-Rocha</name></author><author><name sortKey="Fernandes, M N" uniqKey="Fernandes M">M.N. Fernandes</name></author><author><name sortKey="Ferreira Halder, C V" uniqKey="Ferreira Halder C">C.V. Ferreira-Halder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Machado, D" uniqKey="Machado D">D. Machado</name></author><author><name sortKey="Shishido, S M" uniqKey="Shishido S">S.M. Shishido</name></author><author><name sortKey="Queiroz, K C S" uniqKey="Queiroz K">K.C.S. Queiroz</name></author><author><name sortKey="Oliveira, D N" uniqKey="Oliveira D">D.N. Oliveira</name></author><author><name sortKey="Faria, A L C" uniqKey="Faria A">A.L.C. Faria</name></author><author><name sortKey="Catharino, R R" uniqKey="Catharino R">R.R. Catharino</name></author><author><name sortKey="Spek, C A" uniqKey="Spek C">C.A. Spek</name></author><author><name sortKey="Ferreira, C V" uniqKey="Ferreira C">C.V. Ferreira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Vogel, S" uniqKey="De Vogel S">S. De Vogel</name></author><author><name sortKey="Dindore, V" uniqKey="Dindore V">V. Dindore</name></author><author><name sortKey="Van Engeland, M" uniqKey="Van Engeland M">M. van Engeland</name></author><author><name sortKey="Goldbohm, R A" uniqKey="Goldbohm R">R.A. Goldbohm</name></author><author><name sortKey="Van Den Brandt, P A" uniqKey="Van Den Brandt P">P.A. van den Brandt</name></author><author><name sortKey="Weijenberg, M P" uniqKey="Weijenberg M">M.P. Weijenberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zsch Bitz, S" uniqKey="Zsch Bitz S">S. Zschäbitz</name></author><author><name sortKey="Cheng, T D" uniqKey="Cheng T">T.D. Cheng</name></author><author><name sortKey="Neuhouser, M L" uniqKey="Neuhouser M">M.L. Neuhouser</name></author><author><name sortKey="Zheng, Y" uniqKey="Zheng Y">Y. Zheng</name></author><author><name sortKey="Ray, R M" uniqKey="Ray R">R.M. Ray</name></author><author><name sortKey="Miller, J W" uniqKey="Miller J">J.W. Miller</name></author><author><name sortKey="Song, X" uniqKey="Song X">X. Song</name></author><author><name sortKey="Maneval, D R" uniqKey="Maneval D">D.R. Maneval</name></author><author><name sortKey="Beresford, S A A" uniqKey="Beresford S">S.A.A. Beresford</name></author><author><name sortKey="Lane, D" uniqKey="Lane D">D. Lane</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kabat, G C" uniqKey="Kabat G">G.C. Kabat</name></author><author><name sortKey="Miller, A B" uniqKey="Miller A">A.B. Miller</name></author><author><name sortKey="Jain, M" uniqKey="Jain M">M. Jain</name></author><author><name sortKey="Rohan, T E" uniqKey="Rohan T">T.E. Rohan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takata, Y" uniqKey="Takata Y">Y. Takata</name></author><author><name sortKey="Cai, Q" uniqKey="Cai Q">Q. Cai</name></author><author><name sortKey="Beeghly Fadiel, A" uniqKey="Beeghly Fadiel A">A. Beeghly-Fadiel</name></author><author><name sortKey="Li, H" uniqKey="Li H">H. Li</name></author><author><name sortKey="Shrubsole, M J" uniqKey="Shrubsole M">M.J. Shrubsole</name></author><author><name sortKey="Ji, B T" uniqKey="Ji B">B.T. Ji</name></author><author><name sortKey="Yang, G" uniqKey="Yang G">G. Yang</name></author><author><name sortKey="Chow, W H" uniqKey="Chow W">W.H. Chow</name></author><author><name sortKey="Gao, Y T" uniqKey="Gao Y">Y.T. Gao</name></author><author><name sortKey="Zheng, W" uniqKey="Zheng W">W. Zheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hernandez, B Y" uniqKey="Hernandez B">B.Y. Hernandez</name></author><author><name sortKey="Mcduffie, K" uniqKey="Mcduffie K">K. McDuffie</name></author><author><name sortKey="Wilkens, L R" uniqKey="Wilkens L">L.R. Wilkens</name></author><author><name sortKey="Kamemoto, L" uniqKey="Kamemoto L">L. Kamemoto</name></author><author><name sortKey="Goodman, M T" uniqKey="Goodman M">M.T. Goodman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Powers, H J" uniqKey="Powers H">H.J. Powers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rivlin, R S" uniqKey="Rivlin R">R.S. Rivlin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Foy, H" uniqKey="Foy H">H. Foy</name></author><author><name sortKey="Kondi, A" uniqKey="Kondi A">A. Kondi</name></author><author><name sortKey="Verjee, Z H M" uniqKey="Verjee Z">Z.H.M. Verjee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bareford, L M" uniqKey="Bareford L">L.M. Bareford</name></author><author><name sortKey="Phelps, M A" uniqKey="Phelps M">M.A. Phelps</name></author><author><name sortKey="Foraker, A B" uniqKey="Foraker A">A.B. Foraker</name></author><author><name sortKey="Swaan, P W" uniqKey="Swaan P">P.W. Swaan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Webster, R P" uniqKey="Webster R">R.P. Webster</name></author><author><name sortKey="Gawde, M D" uniqKey="Gawde M">M.D. Gawde</name></author><author><name sortKey="Bhattacharya, R K" uniqKey="Bhattacharya R">R.K. Bhattacharya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hassan, I" uniqKey="Hassan I">I. Hassan</name></author><author><name sortKey="Chibber, S" uniqKey="Chibber S">S. Chibber</name></author><author><name sortKey="Naseem, I" uniqKey="Naseem I">I. Naseem</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Naseem, I" uniqKey="Naseem I">I. Naseem</name></author><author><name sortKey="Hassan, I" uniqKey="Hassan I">I. Hassan</name></author><author><name sortKey="Alhazza, I M" uniqKey="Alhazza I">I.M. Alhazza</name></author><author><name sortKey="Chibber, S" uniqKey="Chibber S">S. Chibber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xuan, Z" uniqKey="Xuan Z">Z. Xuan</name></author><author><name sortKey="An, Y" uniqKey="An Y">Y. An</name></author><author><name sortKey="Yang, D" uniqKey="Yang D">D. Yang</name></author><author><name sortKey="Wang, S" uniqKey="Wang S">S. Wang</name></author><author><name sortKey="Xu, Q" uniqKey="Xu Q">Q. Xu</name></author><author><name sortKey="Yuan, S" uniqKey="Yuan S">S. Yuan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Harbi, N O" uniqKey="Al Harbi N">N.O. Al-Harbi</name></author><author><name sortKey="Imam, F" uniqKey="Imam F">F. Imam</name></author><author><name sortKey="Nadeem, A" uniqKey="Nadeem A">A. Nadeem</name></author><author><name sortKey="Al Harbi, M M" uniqKey="Al Harbi M">M.M. Al-Harbi</name></author><author><name sortKey="Iqbal, M" uniqKey="Iqbal M">M. Iqbal</name></author><author><name sortKey="Ahmad, S F" uniqKey="Ahmad S">S.F. Ahmad</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thakur, K" uniqKey="Thakur K">K. Thakur</name></author><author><name sortKey="Tomar, S K" uniqKey="Tomar S">S.K. Tomar</name></author><author><name sortKey="Singh, A K" uniqKey="Singh A">A.K. Singh</name></author><author><name sortKey="Mandal, S" uniqKey="Mandal S">S. Mandal</name></author><author><name sortKey="Arora, S" uniqKey="Arora S">S. Arora</name></author><author><name sortKey="Division, D M" uniqKey="Division D">D.M. Division</name></author><author><name sortKey="Division, D T" uniqKey="Division D">D.T. Division</name></author><author><name sortKey="Division, D C" uniqKey="Division D">D.C. Division</name></author><author><name sortKey="Microbiology, D" uniqKey="Microbiology D">D. Microbiology</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sparaco, M" uniqKey="Sparaco M">M. Sparaco</name></author><author><name sortKey="Feleppa, M" uniqKey="Feleppa M">M. Feleppa</name></author><author><name sortKey="Lipton, R B" uniqKey="Lipton R">R.B. Lipton</name></author><author><name sortKey="Rapoport, A M" uniqKey="Rapoport A">A.M. Rapoport</name></author><author><name sortKey="Bigal, M E" uniqKey="Bigal M">M.E. Bigal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sherwood, M" uniqKey="Sherwood M">M. Sherwood</name></author><author><name sortKey="Goldman, R D" uniqKey="Goldman R">R.D. Goldman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cond, M" uniqKey="Cond M">M. Condó</name></author><author><name sortKey="Posar, A" uniqKey="Posar A">A. Posar</name></author><author><name sortKey="Arbizzani, A" uniqKey="Arbizzani A">A. Arbizzani</name></author><author><name sortKey="Parmeggiani, A" uniqKey="Parmeggiani A">A. Parmeggiani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maizels, M" uniqKey="Maizels M">M. Maizels</name></author><author><name sortKey="Blumenfeld, A" uniqKey="Blumenfeld A">A. Blumenfeld</name></author><author><name sortKey="Burchette, R" uniqKey="Burchette R">R. Burchette</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gaul, C" uniqKey="Gaul C">C. Gaul</name></author><author><name sortKey="Diener, H C" uniqKey="Diener H">H.-C. Diener</name></author><author><name sortKey="Danesch, U" uniqKey="Danesch U">U. Danesch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jacques, P F" uniqKey="Jacques P">P.F. Jacques</name></author><author><name sortKey="Chylack, L T" uniqKey="Chylack L">L.T. Chylack</name></author><author><name sortKey="Hankinson, S E" uniqKey="Hankinson S">S.E. Hankinson</name></author><author><name sortKey="Khu, P M" uniqKey="Khu P">P.M. Khu</name></author><author><name sortKey="Rogers, G" uniqKey="Rogers G">G. Rogers</name></author><author><name sortKey="Friend, J" uniqKey="Friend J">J. Friend</name></author><author><name sortKey="Tung, W" uniqKey="Tung W">W. Tung</name></author><author><name sortKey="Wolfe, J K" uniqKey="Wolfe J">J.K. Wolfe</name></author><author><name sortKey="Padhye, N" uniqKey="Padhye N">N. Padhye</name></author><author><name sortKey="Willett, W C" uniqKey="Willett W">W.C. Willett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Skalka, H W" uniqKey="Skalka H">H.W. Skalka</name></author><author><name sortKey="Prchal, J T" uniqKey="Prchal J">J.T. Prchal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Seetharam Bhat, K" uniqKey="Seetharam Bhat K">K. SEETHARAM BHAT</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chocano Bedoya, P O" uniqKey="Chocano Bedoya P">P.O. Chocano-bedoya</name></author><author><name sortKey="Manson, J E" uniqKey="Manson J">J.E. Manson</name></author><author><name sortKey="Hankinson, S E" uniqKey="Hankinson S">S.E. Hankinson</name></author><author><name sortKey="Willett, W C" uniqKey="Willett W">W.C. Willett</name></author><author><name sortKey="Johnson, S R" uniqKey="Johnson S">S.R. Johnson</name></author><author><name sortKey="Chasan Taber, L" uniqKey="Chasan Taber L">L. Chasan-taber</name></author><author><name sortKey="Ronnenberg, A G" uniqKey="Ronnenberg A">A.G. Ronnenberg</name></author><author><name sortKey="Bigelow, C" uniqKey="Bigelow C">C. Bigelow</name></author><author><name sortKey="Bertone Johnson, E R" uniqKey="Bertone Johnson E">E.R. Bertone-johnson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chaves Neto, A H" uniqKey="Chaves Neto A">A.H. Chaves Neto</name></author><author><name sortKey="Yano, C L" uniqKey="Yano C">C.L. Yano</name></author><author><name sortKey="Paredes Gamero, E J" uniqKey="Paredes Gamero E">E.J. Paredes-Gamero</name></author><author><name sortKey="Machado, D" uniqKey="Machado D">D. Machado</name></author><author><name sortKey="Justo, G Z" uniqKey="Justo G">G.Z. Justo</name></author><author><name sortKey="Peppelenbosch, M P" uniqKey="Peppelenbosch M">M.P. Peppelenbosch</name></author><author><name sortKey="Ferreira, C V" uniqKey="Ferreira C">C.V. Ferreira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ogunleye, A J" uniqKey="Ogunleye A">A.J. Ogunleye</name></author><author><name sortKey="Odutuga, A A" uniqKey="Odutuga A">A.A. Odutuga</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Foley, A R" uniqKey="Foley A">A.R. Foley</name></author><author><name sortKey="Menezes, M P" uniqKey="Menezes M">M.P. Menezes</name></author><author><name sortKey="Pandraud, A" uniqKey="Pandraud A">A. Pandraud</name></author><author><name sortKey="Gonzalez, M A" uniqKey="Gonzalez M">M.A. Gonzalez</name></author><author><name sortKey="Al Odaib, A" uniqKey="Al Odaib A">A. Al-Odaib</name></author><author><name sortKey="Abrams, A J" uniqKey="Abrams A">A.J. Abrams</name></author><author><name sortKey="Sugano, K" uniqKey="Sugano K">K. Sugano</name></author><author><name sortKey="Yonezawa, A" uniqKey="Yonezawa A">A. Yonezawa</name></author><author><name sortKey="Manzur, A Y" uniqKey="Manzur A">A.Y. Manzur</name></author><author><name sortKey="Burns, J" uniqKey="Burns J">J. Burns</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boisvert, W A" uniqKey="Boisvert W">W.A. Boisvert</name></author><author><name sortKey="Casta Eda, C" uniqKey="Casta Eda C">C. Castañeda</name></author><author><name sortKey="Mendoza, I" uniqKey="Mendoza I">I. Mendoza</name></author><author><name sortKey="Langeloh, G" uniqKey="Langeloh G">G. Langeloh</name></author><author><name sortKey="Solomons, N W" uniqKey="Solomons N">N.W. Solomons</name></author><author><name sortKey="Gershoff, S N" uniqKey="Gershoff S">S.N. Gershoff</name></author><author><name sortKey="Russell, R M" uniqKey="Russell R">R.M. Russell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Powers, H J" uniqKey="Powers H">H.J. Powers</name></author><author><name sortKey="Weaver, L T" uniqKey="Weaver L">L.T. Weaver</name></author><author><name sortKey="Austin, S" uniqKey="Austin S">S. Austin</name></author><author><name sortKey="Beresford, J K" uniqKey="Beresford J">J.K. Beresford</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Powers, H J" uniqKey="Powers H">H.J. Powers</name></author><author><name sortKey="Bates, C J" uniqKey="Bates C">C.J. Bates</name></author><author><name sortKey="Prentice, A M" uniqKey="Prentice A">A.M. Prentice</name></author><author><name sortKey="Lamb, W H" uniqKey="Lamb W">W.H. Lamb</name></author><author><name sortKey="Jepson, M" uniqKey="Jepson M">M. Jepson</name></author><author><name sortKey="Bowman, H" uniqKey="Bowman H">H. Bowman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Powers, H J" uniqKey="Powers H">H.J. Powers</name></author><author><name sortKey="Hill, M H" uniqKey="Hill M">M.H. Hill</name></author><author><name sortKey="Mushtaq, S" uniqKey="Mushtaq S">S. Mushtaq</name></author><author><name sortKey="Dainty, J R" uniqKey="Dainty J">J.R. Dainty</name></author><author><name sortKey="Majsak Newman, G" uniqKey="Majsak Newman G">G. Majsak-Newman</name></author><author><name sortKey="Williams, E A" uniqKey="Williams E">E.A. Williams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lopez, A D" uniqKey="Lopez A">A.D. Lopez</name></author><author><name sortKey="Mathers, C D" uniqKey="Mathers C">C.D. Mathers</name></author><author><name sortKey="Ezzati, M" uniqKey="Ezzati M">M. Ezzati</name></author><author><name sortKey="Jamison, D T" uniqKey="Jamison D">D.T. Jamison</name></author><author><name sortKey="Murray, C J" uniqKey="Murray C">C.J. Murray</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lawes, C M M" uniqKey="Lawes C">C.M.M. Lawes</name></author><author><name sortKey="Vander Hoorn, S" uniqKey="Vander Hoorn S">S. Vander Hoorn</name></author><author><name sortKey="Rodgers, A" uniqKey="Rodgers A">A. Rodgers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Franca, C F" uniqKey="Franca C">C.F. França</name></author><author><name sortKey="Vianna, L M" uniqKey="Vianna L">L.M. Vianna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leblanc, J G" uniqKey="Leblanc J">J.G. Leblanc</name></author><author><name sortKey="Lai O, J E" uniqKey="Lai O J">J.E. Laiño</name></author><author><name sortKey="Del Valle, M J" uniqKey="Del Valle M">M.J. del Valle</name></author><author><name sortKey="Vannini, V" uniqKey="Vannini V">V. Vannini</name></author><author><name sortKey="Van Sinderen, D" uniqKey="Van Sinderen D">D. van Sinderen</name></author><author><name sortKey="Taranto, M P" uniqKey="Taranto M">M.P. Taranto</name></author><author><name sortKey="De Valdez, G F" uniqKey="De Valdez G">G.F. de Valdez</name></author><author><name sortKey="De Giori, G S" uniqKey="De Giori G">G.S. de Giori</name></author><author><name sortKey="Sesma, F" uniqKey="Sesma F">F. Sesma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mensink, G B M" uniqKey="Mensink G">G.B.M. Mensink</name></author><author><name sortKey="Fletcher, R" uniqKey="Fletcher R">R. Fletcher</name></author><author><name sortKey="Gurinovic, M" uniqKey="Gurinovic M">M. Gurinovic</name></author><author><name sortKey="Huybrechts, I" uniqKey="Huybrechts I">I. Huybrechts</name></author><author><name sortKey="Lafay, L" uniqKey="Lafay L">L. Lafay</name></author><author><name sortKey="Serra Majem, L" uniqKey="Serra Majem L">L. Serra-Majem</name></author><author><name sortKey="Szponar, L" uniqKey="Szponar L">L. Szponar</name></author><author><name sortKey="Tetens, I" uniqKey="Tetens I">I. Tetens</name></author><author><name sortKey="Verkaik Kloosterman, J" uniqKey="Verkaik Kloosterman J">J. Verkaik-Kloosterman</name></author><author><name sortKey="Baka, A" uniqKey="Baka A">A. Baka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Flynn, A" uniqKey="Flynn A">A. Flynn</name></author><author><name sortKey="Moreiras, O" uniqKey="Moreiras O">O. Moreiras</name></author><author><name sortKey="Stehle, P" uniqKey="Stehle P">P. Stehle</name></author><author><name sortKey="Fletcher, R J" uniqKey="Fletcher R">R.J. Fletcher</name></author><author><name sortKey="Muller, D J G" uniqKey="Muller D">D.J.G. Müller</name></author><author><name sortKey="Rolland, V" uniqKey="Rolland V">V. Rolland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ashoori, M" uniqKey="Ashoori M">M. Ashoori</name></author><author><name sortKey="Saedisomeolia, A" uniqKey="Saedisomeolia A">A. Saedisomeolia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leblanc, J G" uniqKey="Leblanc J">J.G. LeBlanc</name></author><author><name sortKey="Burgess, C" uniqKey="Burgess C">C. Burgess</name></author><author><name sortKey="Sesma, F" uniqKey="Sesma F">F. Sesma</name></author><author><name sortKey="De Giori, G S" uniqKey="De Giori G">G.S. de Giori</name></author><author><name sortKey="Van Sinderen, D" uniqKey="Van Sinderen D">D. van Sinderen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Capozzi, V" uniqKey="Capozzi V">V. Capozzi</name></author><author><name sortKey="Menga, V" uniqKey="Menga V">V. Menga</name></author><author><name sortKey="Digesu, A M" uniqKey="Digesu A">A.M. Digesù</name></author><author><name sortKey="De Vita, P" uniqKey="De Vita P">P. De Vita</name></author><author><name sortKey="Van Sinderen, D" uniqKey="Van Sinderen D">D. Van Sinderen</name></author><author><name sortKey="Cattivelli, L" uniqKey="Cattivelli L">L. Cattivelli</name></author><author><name sortKey="Fares, C" uniqKey="Fares C">C. Fares</name></author><author><name sortKey="Spano, G" uniqKey="Spano G">G. Spano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Juarez Del Valle, M" uniqKey="Juarez Del Valle M">M. Juarez del Valle</name></author><author><name sortKey="Lai O, J E" uniqKey="Lai O J">J.E. Laiño</name></author><author><name sortKey="Savoy De Giori, G" uniqKey="Savoy De Giori G">G. Savoy de Giori</name></author><author><name sortKey="Leblanc, J G" uniqKey="Leblanc J">J.G. LeBlanc</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Russo, P" uniqKey="Russo P">P. Russo</name></author><author><name sortKey="De Chiara, M L V" uniqKey="De Chiara M">M.L.V. de Chiara</name></author><author><name sortKey="Capozzi, V" uniqKey="Capozzi V">V. Capozzi</name></author><author><name sortKey="Arena, M P" uniqKey="Arena M">M.P. Arena</name></author><author><name sortKey="Amodio, M L" uniqKey="Amodio M">M.L. Amodio</name></author><author><name sortKey="Rasc N, A" uniqKey="Rasc N A">A. Rascón</name></author><author><name sortKey="Due As, M T" uniqKey="Due As M">M.T. Dueñas</name></author><author><name sortKey="L Pez, P" uniqKey="L Pez P">P. López</name></author><author><name sortKey="Spano, G" uniqKey="Spano G">G. Spano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Russo, P" uniqKey="Russo P">P. Russo</name></author><author><name sortKey="Capozzi, V" uniqKey="Capozzi V">V. Capozzi</name></author><author><name sortKey="Arena, M P" uniqKey="Arena M">M.P. Arena</name></author><author><name sortKey="Spadaccino, G" uniqKey="Spadaccino G">G. Spadaccino</name></author><author><name sortKey="Due As, M T" uniqKey="Due As M">M.T. Dueñas</name></author><author><name sortKey="L Pez, P" uniqKey="L Pez P">P. López</name></author><author><name sortKey="Fiocco, D" uniqKey="Fiocco D">D. Fiocco</name></author><author><name sortKey="Spano, G" uniqKey="Spano G">G. Spano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Burgess, C M" uniqKey="Burgess C">C.M. Burgess</name></author><author><name sortKey="Smid, E J" uniqKey="Smid E">E.J. Smid</name></author><author><name sortKey="Rutten, G" uniqKey="Rutten G">G. Rutten</name></author><author><name sortKey="Van Sinderen, D" uniqKey="Van Sinderen D">D. van Sinderen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leblanc, J G" uniqKey="Leblanc J">J.G. LeBlanc</name></author><author><name sortKey="Rutten, G" uniqKey="Rutten G">G. Rutten</name></author><author><name sortKey="Bruinenberg, P" uniqKey="Bruinenberg P">P. Bruinenberg</name></author><author><name sortKey="Sesma, F" uniqKey="Sesma F">F. Sesma</name></author><author><name sortKey="De Giori, G S" uniqKey="De Giori G">G.S. de Giori</name></author><author><name sortKey="Smid, E J" uniqKey="Smid E">E.J. Smid</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Berry Ottaway, P" uniqKey="Berry Ottaway P">P. Berry Ottaway</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bou, R" uniqKey="Bou R">R. Bou</name></author><author><name sortKey="Cofrades, S" uniqKey="Cofrades S">S. Cofrades</name></author><author><name sortKey="Jimenez Colmenero, F" uniqKey="Jimenez Colmenero F">F. Jiménez-Colmenero</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, L" uniqKey="Chen L">L. Chen</name></author><author><name sortKey="Subirade, M" uniqKey="Subirade M">M. Subirade</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, L" uniqKey="Chen L">L. Chen</name></author><author><name sortKey="Subirade, M" uniqKey="Subirade M">M. Subirade</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="O Eill, G J" uniqKey="O Eill G">G.J. O’Neill</name></author><author><name sortKey="Jacquier, J C" uniqKey="Jacquier J">J.C. Jacquier</name></author><author><name sortKey="Mukhopadhya, A" uniqKey="Mukhopadhya A">A. Mukhopadhya</name></author><author><name sortKey="Egan, T" uniqKey="Egan T">T. Egan</name></author><author><name sortKey="O Ullivan, M" uniqKey="O Ullivan M">M. O’Sullivan</name></author><author><name sortKey="Sweeney, T" uniqKey="Sweeney T">T. Sweeney</name></author><author><name sortKey="O Iordan, E D" uniqKey="O Iordan E">E.D. O’Riordan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hu, H" uniqKey="Hu H">H. Hu</name></author><author><name sortKey="Zhu, X" uniqKey="Zhu X">X. Zhu</name></author><author><name sortKey="Hu, T" uniqKey="Hu T">T. Hu</name></author><author><name sortKey="Cheung, I W Y" uniqKey="Cheung I">I.W.Y. Cheung</name></author><author><name sortKey="Pan, S" uniqKey="Pan S">S. Pan</name></author><author><name sortKey="Li Chan, E C Y" uniqKey="Li Chan E">E.C.Y. Li-Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Azevedo, M A" uniqKey="Azevedo M">M.A. Azevedo</name></author><author><name sortKey="Bourbon, A I" uniqKey="Bourbon A">A.I. Bourbon</name></author><author><name sortKey="Vicente, A A" uniqKey="Vicente A">A.A. Vicente</name></author><author><name sortKey="Cerqueira, M A" uniqKey="Cerqueira M">M.A. Cerqueira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jin, B" uniqKey="Jin B">B. Jin</name></author><author><name sortKey="Zhou, X" uniqKey="Zhou X">X. Zhou</name></author><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author><author><name sortKey="Lin, W" uniqKey="Lin W">W. Lin</name></author><author><name sortKey="Chen, G" uniqKey="Chen G">G. Chen</name></author><author><name sortKey="Qiu, R" uniqKey="Qiu R">R. Qiu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, P" uniqKey="Zhang P">P. Zhang</name></author><author><name sortKey="Zhao, S R" uniqKey="Zhao S">S.R. Zhao</name></author><author><name sortKey="Li, J X" uniqKey="Li J">J.X. Li</name></author><author><name sortKey="Hong, L" uniqKey="Hong L">L. Hong</name></author><author><name sortKey="Raja, M A" uniqKey="Raja M">M.A. Raja</name></author><author><name sortKey="Yu, L J" uniqKey="Yu L">L.J. Yu</name></author><author><name sortKey="Liu, C G" uniqKey="Liu C">C.G. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Couto, R" uniqKey="Couto R">R. Couto</name></author><author><name sortKey="Alvarez, V" uniqKey="Alvarez V">V. Alvarez</name></author><author><name sortKey="Temelli, F" uniqKey="Temelli F">F. Temelli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suwannasom, N" uniqKey="Suwannasom N">N. Suwannasom</name></author><author><name sortKey="Smuda, K" uniqKey="Smuda K">K. Smuda</name></author><author><name sortKey="Kloypan, C" uniqKey="Kloypan C">C. Kloypan</name></author><author><name sortKey="Kaewprayoon, W" uniqKey="Kaewprayoon W">W. Kaewprayoon</name></author><author><name sortKey="Baisaeng, N" uniqKey="Baisaeng N">N. Baisaeng</name></author><author><name sortKey="Prapan, A" uniqKey="Prapan A">A. Prapan</name></author><author><name sortKey="Chaiwaree, S" uniqKey="Chaiwaree S">S. Chaiwaree</name></author><author><name sortKey="Georgieva, R" uniqKey="Georgieva R">R. Georgieva</name></author><author><name sortKey="B Umler, H" uniqKey="B Umler H">H. Bäumler</name></author><author><name sortKey="Suwannasom, N" uniqKey="Suwannasom N">N. Suwannasom</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Mol Sci</journal-id><journal-id journal-id-type="iso-abbrev">Int J Mol Sci</journal-id><journal-id journal-id-type="publisher-id">ijms</journal-id><journal-title-group><journal-title>International Journal of Molecular Sciences</journal-title></journal-title-group><issn pub-type="epub">1422-0067</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32023913</article-id><article-id pub-id-type="pmc">7037471</article-id><article-id pub-id-type="doi">10.3390/ijms21030950</article-id><article-id pub-id-type="publisher-id">ijms-21-00950</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Riboflavin: The Health Benefits of a Forgotten Natural Vitamin</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-7069-5990</contrib-id><name><surname>Suwannasom</surname><given-names>Nittiya</given-names></name><xref ref-type="aff" rid="af1-ijms-21-00950">1</xref><xref ref-type="aff" rid="af2-ijms-21-00950">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-8447-2491</contrib-id><name><surname>Kao</surname><given-names>Ijad</given-names></name><xref ref-type="aff" rid="af1-ijms-21-00950">1</xref></contrib><contrib contrib-type="author"><name><surname>Pruß</surname><given-names>Axel</given-names></name><xref ref-type="aff" rid="af1-ijms-21-00950">1</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0003-1546-5540</contrib-id><name><surname>Georgieva</surname><given-names>Radostina</given-names></name><xref ref-type="aff" rid="af1-ijms-21-00950">1</xref><xref ref-type="aff" rid="af3-ijms-21-00950">3</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-2573-2289</contrib-id><name><surname>Bäumler</surname><given-names>Hans</given-names></name><xref ref-type="aff" rid="af1-ijms-21-00950">1</xref><xref rid="c1-ijms-21-00950" ref-type="corresp">*</xref></contrib></contrib-group><aff id="af1-ijms-21-00950"><label>1</label>Institute of Transfusion Medicine, Center of Tumor Medicine, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;<email>nittiya.suwannasom@charite.de</email> (N.S.);<email>ijad.kao@charite.de</email> (I.K.);<email>axel.pruss@charite.de</email> (A.P.);<email>radostina.georgieva@charite.de</email> (R.G.)</aff><aff id="af2-ijms-21-00950"><label>2</label>School of Medical Sciences, University of Phayao, Phayao 56000, Thailand</aff><aff id="af3-ijms-21-00950"><label>3</label>Biophysics and Radiology, Department of Medical Physics, Faculty of Medicine, Trakia University, 6000 Stara Zagora, Bulgaria</aff><author-notes><corresp id="c1-ijms-21-00950"><label>*</label>Correspondence: <email>hans.baeumler@charite.de</email></corresp></author-notes><pub-date pub-type="epub"><day>31</day><month>1</month><year>2020</year></pub-date><pub-date pub-type="collection"><month>2</month><year>2020</year></pub-date><volume>21</volume><issue>3</issue><elocation-id>950</elocation-id><history><date date-type="received"><day>03</day><month>1</month><year>2020</year></date><date date-type="accepted"><day>29</day><month>1</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 by the authors.</copyright-statement><copyright-year>2020</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>Riboflavin (RF) is a water-soluble member of the B-vitamin family. Sufficient dietary and supplemental RF intake appears to have a protective effect on various medical conditions such as sepsis, ischemia etc., while it also contributes to the reduction in the risk of some forms of cancer in humans. These biological effects of RF have been widely studied for their anti-oxidant, anti-aging, anti-inflammatory, anti-nociceptive and anti-cancer properties. Moreover, the combination of RF and other compounds or drugs can have a wide variety of effects and protective properties, and diminish the toxic effect of drugs in several treatments. Research has been done in order to review the latest findings about the link between RF and different clinical aberrations. Since further studies have been published in this field, it is appropriate to consider a re-evaluation of the importance of RF in terms of its beneficial properties.</p></abstract><kwd-group><kwd>riboflavin</kwd><kwd>vitamin B2</kwd><kwd>complementary medicine</kwd><kwd>functional food</kwd><kwd>oxidative stress</kwd><kwd>cancer</kwd><kwd>neurodegeneration</kwd><kwd>muscular degeneration</kwd></kwd-group></article-meta></front><body><sec sec-type="intro" id="sec1-ijms-21-00950"><title>1. Introduction</title><p>Riboflavin (RF) was first documented in 1879 by Blythto as a yellow pigment found in milk [<xref rid="B1-ijms-21-00950" ref-type="bibr">1</xref>]. RF, chemically, is 7, 8-dimethyl-10-ribityl-isoalloxazine which consists of a flavin isoalloxazine ring bound to a sugar side chain, Ribitol [<xref rid="B2-ijms-21-00950" ref-type="bibr">2</xref>]. RF is also known as an essential vitamin B<sub>2</sub>, a water-soluble vitamin, is heat stable. Cooking does not lower levels of RF, however exposure to light could destroy it. RF can be found in a wide variety of foods and natural sources, especially milk, organ meats—mostly in calf liver, egg, fish, nuts, certain fruits and legumes, wild rice, mushrooms, dark green leafy vegetables, yeast, beer, cheese and dietary products [<xref rid="B1-ijms-21-00950" ref-type="bibr">1</xref>,<xref rid="B3-ijms-21-00950" ref-type="bibr">3</xref>]. RF is poorly stored by vertebrates because of its limited absorption in humans. Therefore, orally supplied RF by a healthy diet is required to avoid ariboflavinosis which causes cheilitis, sore tongue, and a scaly rash on the scrotum or vulva. RF causes no known toxicity, since at higher intakes it is excreted in the urine and not stored [<xref rid="B3-ijms-21-00950" ref-type="bibr">3</xref>]. RF is found in different concentrations in various human body fluids and organs (<xref rid="ijms-21-00950-t001" ref-type="table">Table 1</xref>). Recent analytical procedures developed for detection of RF in biological samples were described in several reviews [<xref rid="B4-ijms-21-00950" ref-type="bibr">4</xref>,<xref rid="B5-ijms-21-00950" ref-type="bibr">5</xref>,<xref rid="B6-ijms-21-00950" ref-type="bibr">6</xref>].</p><p>RF is phosphorylated intracellular to flavin mononucleotide (FMN) and further metabolized to flavin adenine dinucleotide (FAD) (<xref ref-type="fig" rid="ijms-21-00950-f001">Figure 1</xref>).</p><p>Both FMN and FAD play a key role as cofactors in energy metabolism and are required for co-enzyme function in numerous oxidation and reduction reactions in all aerobic forms of life. RF has been used in dietary supplements and for inflammatory disease treatments such as angulus infectious, cheilitis, glossitis [<xref rid="B7-ijms-21-00950" ref-type="bibr">7</xref>], sepsis [<xref rid="B8-ijms-21-00950" ref-type="bibr">8</xref>,<xref rid="B9-ijms-21-00950" ref-type="bibr">9</xref>], cataracts and migraine headaches [<xref rid="B3-ijms-21-00950" ref-type="bibr">3</xref>] (<xref ref-type="fig" rid="ijms-21-00950-f002">Figure 2</xref>).</p></sec><sec id="sec2-ijms-21-00950"><title>2. Beneficial Health Effects of RF</title><sec id="sec2dot1-ijms-21-00950"><title>2.1. Antioxidant Properties</title><p>Oxidative stress plays a crucial functional role in the pathogenesis of various human disease states including ischemia-reperfusion injury, diabetes and angina pectoris [<xref rid="B10-ijms-21-00950" ref-type="bibr">10</xref>]. Oxidative stress is a key effect of aging and degenerative diseases along with aging. The authors have demonstrated that supplementation of RF significantly extended the lifetime and strengthened the reproduction of fruit flies via enhancing the activity of antioxidant enzymes [<xref rid="B11-ijms-21-00950" ref-type="bibr">11</xref>]. RF also activates the synthesis of a normal extracellular matrix and reduces reactive oxygen species (ROS) levels in keratoconus [<xref rid="B12-ijms-21-00950" ref-type="bibr">12</xref>]. The evidence of the effect of RF and its roles for reactive oxygen species in various symptoms and diseases is summarized in <xref rid="ijms-21-00950-t002" ref-type="table">Table 2</xref>.</p><p>RF was used for its potent antioxidant and anti-inflammatory effects in the ischaemic liver, protecting hepatic parenchymal cells against I/R injury [<xref rid="B13-ijms-21-00950" ref-type="bibr">13</xref>].</p><p>Other antioxidant enzymes concentrations—like superoxide dismutase (SOD), catalase and glutathione peroxidase—are also influenced by RF concentration. RF plays an important role for the antioxidant status inside cell systems as well as being part of the glutathione reductase (GR) and xanthine oxidase system. RF in the form of FAD is necessary for GR enzyme to convert oxidized glutathione (GSSG) to the reduced glutathione (GSH) (<xref ref-type="fig" rid="ijms-21-00950-f003">Figure 3</xref>). It then functions as an endogenous antioxidant in different cells [<xref rid="B14-ijms-21-00950" ref-type="bibr">14</xref>].</p></sec><sec id="sec2dot2-ijms-21-00950"><title>2.2. Reperfusion Oxidative Injury</title><p>Reperfusion oxidative injuries refer to the tissue damages which occur after ischemia when free radicals and inflammatory cytokines are increased (<xref rid="ijms-21-00950-t003" ref-type="table">Table 3</xref>). RF can attenuate oxidative injuries through its ability to scavenge free radicals and therefore decrease re-oxygenation injuries. New evidence suggests that ROS have a crucial role in the pathogenesis of ischemia/reperfusion injury. Studies in various cell cultures and animal species have shown a variety of protective actions of RF in many organs, e.g., the neuroprotective effect of cerebral ischemia [<xref rid="B15-ijms-21-00950" ref-type="bibr">15</xref>]. The authors showed that pre-treatment of the SH-SY5Y cells with RF before oxygen glucose deprivation (OGD) experiments significantly reduced the OGD-induced lactate dehydrogenase (LDH) release and significantly increased cell viability. The cell viability and LDH secretion were quantified in the SH-SY5Y cell line and cortical neuron cultures using the cell counting Kit-8 and the LDH quantification kit compared to that treated-OGD group. In vivo study showed a significant neuroprotective activity via the modulation of the miR-203/c-Jun signalling pathway [<xref rid="B15-ijms-21-00950" ref-type="bibr">15</xref>].</p><table-wrap id="ijms-21-00950-t002" orientation="portrait" position="float"><object-id pub-id-type="pii">ijms-21-00950-t002_Table 2</object-id><label>Table 2</label><caption><p>Evidence on effect of RF and its roles for reactive oxygen species in various symptoms and diseases. Upregulation ↑, downregulation ↓.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Model</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Dose</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Antioxidant Enzymes</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Key Findings</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-aging in Drosophila melanogaster (fruit fly)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 120 µg/mL</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SOD1 ↑; CAT ↑; lipofuscin (LF) ↓</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF prolonged the life span and increased reproductive capacity through anti-oxidative stress pathway involving enhancing the activity of SOD1 and CAT and inhibiting lipofuscin accumulation</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B11-ijms-21-00950" ref-type="bibr">11</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Keratoconus corneal stroma cells</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Keratoconus cells were treated with low dose of RF at 0.167 µg/mL</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Increasing gene expression of antioxidant enzymes: aldehyde dehydrogenase 3A1, CAT, enolase 1, GPx 1, haem oxygenase 1, SOD 1 and transketolase</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF improved the synthesis of a normal extracellular matrix and downregulated ROS level in keratoconus. It was quatified by the total collagen protein in the keratoconic stroma.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B12-ijms-21-00950" ref-type="bibr">12</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Diabetes-induced cardiac dysfunction</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 20 mg/kg was treated after streptozotocin-induced diabetes type I.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SOD↑, MDA↓, HO-1 protein level↑</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RFK can reduced the risk of cardiac dysfunction by increasing antioxidant, HO-1 and decreasing CTGF levels as well as improving lipid profile</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B16-ijms-21-00950" ref-type="bibr">16</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Diabetes mellitus type-2</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 10 and 20 mg/kg was treated after alloxan-induced DM</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SOD↑, catalase↑, GSH↑, MDA↓</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Decreased pancreatic activity, restored ant-oxidant enzyme activity, decreased FBG level while calcium level and GLUT-4 expression was increased</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B17-ijms-21-00950" ref-type="bibr">17</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cardiac abnormalities in experimental atherosclerosis in rat</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 40 mg/kg together with CoRNS after hypolipidemic induction</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SOD↑, CAT↑, GPx↑</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CoRNS significant reduced lipid profile: LDL and cardiac enzymes (LDH, ALT, AST, ALP) with enhanced levels of HDL and antioxidants.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B18-ijms-21-00950" ref-type="bibr">18</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">GTN-induced brain oxidative toxicity</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 100 mg/kg was treated before GTN-induced migraine</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Lipid peroxidation↓, GSH↑, GPx↑</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF with selenium administration protected against GTN-induced brain oxidative toxicity by protecting brain MMCA activity, inhibiting free radicals and supporting the antioxidant redox system.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B19-ijms-21-00950" ref-type="bibr">19</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Migraine model</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF 100 mg/kg was treated before GTN-induced migraine</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Lipid peroxidation↓, GSH↑</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF and vitamin E had a protective effect on the GTN-induced brain injury by inhibiting free radical production, regulation of calcium-dependent processes, and supporting the antioxidant redox system.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B20-ijms-21-00950" ref-type="bibr">20</xref>]</td></tr></tbody></table></table-wrap><table-wrap id="ijms-21-00950-t003" orientation="portrait" position="float"><object-id pub-id-type="pii">ijms-21-00950-t003_Table 3</object-id><label>Table 3</label><caption><p>Evidence of RF on the attenuation of reperfusion oxidative injury.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Model</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">RF Dose</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Key findings</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Conclusions</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Stroke-induced brain damage (neuroprotection against excitotoxicity)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 0.05–0.5 mM before glutamate or NMDA treatment</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at the concentrations of 0.2, 0.3, and 0.4 mM were significantly neuroprotective against glutamate and NMDA.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF ameliorate glutamate or NMDA-mediated excitotoxicity to CGCs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B21-ijms-21-00950" ref-type="bibr">21</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cortical contusion injury (CCI)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF treatment with 7.5 mg/kg, i.p; n = 7, 15 min after injury. A second dose was applied after 24h after injury.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Reducing brain edema formation, and inhibit GFAP+ expression, improve behavioral function.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Administration of RF following CCI of the frontal cortex improves recovery of function following injury</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B22-ijms-21-00950" ref-type="bibr">22</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cortical contusion injury (CCI).</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF was treated after CCI:a combination of 1 mmol/kg MgCl2 and 7.5 mg/kg RF</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The combination of MgCl<sub>2</sub> and RF improved the functional recovery while the half-dose combination did not.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF and magnesium infusions improved functional recovery to a greater extent than either alone following a frontal cortical contusion injury in rats</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B23-ijms-21-00950" ref-type="bibr">23</xref>]</td></tr></tbody></table></table-wrap><p>RF can significantly protect against oxidant-mediated inflammatory injury in the lungs of Long-Evans rats caused by cobra venom factor or IgG immune complexes, or ischemia-perfusion [<xref rid="B24-ijms-21-00950" ref-type="bibr">24</xref>]. RF has also been reported to have a protective role in focal ischemia with decreasing brain injury and oedema formation in rats [<xref rid="B25-ijms-21-00950" ref-type="bibr">25</xref>]. RF also has cardio-protective effects in isolated rabbit cardiomyocytes, reducing elevated ferrylmyoglobulin induced by cardiac re-oxygenation damage. This effect is mediated by Flavin reductase [<xref rid="B26-ijms-21-00950" ref-type="bibr">26</xref>].</p></sec><sec id="sec2dot3-ijms-21-00950"><title>2.3. Malaria Infection</title><p>Infections with malaria parasites may stimulate the immune system leading to ROS formation, which can attack the plasma membrane of the erythrocyte compromising its integrity [<xref rid="B27-ijms-21-00950" ref-type="bibr">27</xref>]. RF reduced the level of methaemoglobin content, decreased food vacuole size and inhibited asexual parasite growth in erythrocytes infested with <italic>P. falciparum</italic> [<xref rid="B28-ijms-21-00950" ref-type="bibr">28</xref>].</p><p>In addition, co-treatment of RF and Chloroquine tablets against malaria infection significantly increased the packed cell volume and haemoglobin (Hb) levels, but reduced lipid peroxidation, contributing to maintaining the redox integrity of cells, protecting them against ROS generated during the inflammatory response [<xref rid="B29-ijms-21-00950" ref-type="bibr">29</xref>]. </p></sec><sec id="sec2dot4-ijms-21-00950"><title>2.4. Immune System</title><p>RF activates phagocytic activity of neutrophils and macrophages, and stimulates the multiplication of neutrophils and monocytes [<xref rid="B30-ijms-21-00950" ref-type="bibr">30</xref>]. It has also been shown that RF is important for the survival of macrophage RAW 264.7 cells. The reduction in RF concentration resulted in a decreased rate of cell proliferation [<xref rid="B31-ijms-21-00950" ref-type="bibr">31</xref>]. A combined supplementation—consisting of RF, delta-tocotrienol and quercetin—improved the inhibition of serum tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) levels in a chicken model [<xref rid="B32-ijms-21-00950" ref-type="bibr">32</xref>]. </p><p>However, RF administration affects neutrophil migration, inhibiting the infiltration and accumulation of activated granulocytes into peripheral sites, which may lead to a decreased inflammatory influx and, thereby, a decrease in inflammatory symptoms [<xref rid="B33-ijms-21-00950" ref-type="bibr">33</xref>]. RF is a potential substance for use in virus inactivation, or as an adjuvant in chemo radiotherapy for cancer treatment because of its toxicological and photosensitizing attributes. RF suppressed T-cells infiltration and donor-reactive alloantibody formation during the early period after allotransplantation [<xref rid="B34-ijms-21-00950" ref-type="bibr">34</xref>].</p><p>The pro-inflammatory transcription nuclear factor kappa B (NF-κB) is normally activated by degradation of inhibitory kappa B (IκB). When this occurs, NF-κB translocates to the nucleus and binds to specific promoter regions of genes encoding pro-inflammatory proteins. Proteasomes are key regulators of lipopolysaccharide (LPS)-stimulated inflammatory signalling pathways. RF, as proteasome inhibitor, possibly down-regulates the NF-κB activation initiated by ROS, which are the potent activators of a plethora of general pro-inflammatory cytokines such as interleukin-6 (IL-6), TNF-α, etc. Therefore, ultimately, as proteasome inhibitor RF suppresses the production of TNF-α and NO, and exerts anti-inflammatory effects by inhibiting NF-κB, activation. As was recently reported, RF may protect against multitude of age-associated diseases by inhibition levels of secretion of TNF-α, NO production, activation of NF-κB, and degradation [<xref rid="B35-ijms-21-00950" ref-type="bibr">35</xref>].</p><p>In recent years, there has been much interest in the anti-nociceptive and anti-inflammatory effects of RF (<xref rid="ijms-21-00950-t004" ref-type="table">Table 4</xref>). RF helps in reducing inflammatory nociceptive pain [<xref rid="B36-ijms-21-00950" ref-type="bibr">36</xref>,<xref rid="B37-ijms-21-00950" ref-type="bibr">37</xref>]. Several animal models have been used to study the possible role in anti-nociceptive and anti-inflammatory effects of RF. It has been indicated that RF could inhibit nociceptive responses induced by a number of inflammatory agents in a variety of structures. For example, RF inhibited the formalin-induced hind paw oedema [<xref rid="B37-ijms-21-00950" ref-type="bibr">37</xref>]. Moreover, RF can improve the anti-nociceptive effect when combined with low-dose morphine in a formalin test model [<xref rid="B38-ijms-21-00950" ref-type="bibr">38</xref>], as well as in a zymosan-induced peritonitis model [<xref rid="B39-ijms-21-00950" ref-type="bibr">39</xref>]. The anti-inflammatory studies of RF on the zymosan-induced peritonitis model showed that RF effects were dependent on the time of administration and dose [<xref rid="B40-ijms-21-00950" ref-type="bibr">40</xref>], as well as strain-specific differences in mice [<xref rid="B38-ijms-21-00950" ref-type="bibr">38</xref>].</p><p>Another study showed that oral administration of RF reduced inflammation and nociception, which were induced by formalin via the activation of ATP-sensitive K<sup>+</sup>- channels or NO release [<xref rid="B41-ijms-21-00950" ref-type="bibr">41</xref>]. </p><p>Sepsis is attributed to a systemic inflammatory response to bacterial infection, leading to multiple system dysfunctions in the body. Many pro-inflammatory mediators play a role in immune reaction during septic shock with release of inflammation cytokines, e.g., TNF-α, IL-1, IL-6, chemokines (monocyte chemo attractant protein 1 (MCP-1), macrophage inflammatory protein (MIP-2)), and NO production, including high-mobility group protein B1 (HMGB1) [<xref rid="B47-ijms-21-00950" ref-type="bibr">47</xref>]. The beneficial effects of RF are based on its anti-inflammatory capability. Several experimental animal models have shown that RF has a potent effect against mortality rates from LPS-induced septic shock, exotoxin and exotoxin-induced shock, Gram-positive and Gram-negative bacterial infections via reduction the elevated level of TNF-α, IL-1, IL-1β, IL-6, gamma interferon (IFN-γ), MCP-1, and 2 MIP-2 as well as NO levels [<xref rid="B8-ijms-21-00950" ref-type="bibr">8</xref>,<xref rid="B42-ijms-21-00950" ref-type="bibr">42</xref>,<xref rid="B43-ijms-21-00950" ref-type="bibr">43</xref>]. </p><p>In terms of the efficacy of treatment with RF in combination with antibiotics (ampicillin [<xref rid="B48-ijms-21-00950" ref-type="bibr">48</xref>,<xref rid="B49-ijms-21-00950" ref-type="bibr">49</xref>], azithromycin [<xref rid="B50-ijms-21-00950" ref-type="bibr">50</xref>], Ciprofloxacin [<xref rid="B49-ijms-21-00950" ref-type="bibr">49</xref>]) or amino acids [<xref rid="B8-ijms-21-00950" ref-type="bibr">8</xref>] on septic arthritis, RF has been reported as causing an increase in the survival rate of mice [<xref rid="B50-ijms-21-00950" ref-type="bibr">50</xref>].</p><p>Therefore, RF might represent a promising new therapeutic strategy for the treatment of sepsis and septic shock. However, to our knowledge, there are a limited number of studies that have examined the anti-inflammatory and anti-nociceptive effects of RF in humans. Most of the evidence that RF reduces inflammation and nociception responses comes from laboratory animal studies. It has been demonstrated that RF reduced the hepatocellular injury and hepatotoxicity induced by LPS through elevation of malondialdehyde (MDA) level and myeloperoxidase (MPO) activity, whereas a marked decrease in GSH content, GR and glutathione peroxidase (GPx) activity. Moreover, expression of inducible nitric oxide synthase (iNOS) and catalase (CAT) gene expression was improved via RF administration [<xref rid="B45-ijms-21-00950" ref-type="bibr">45</xref>]. In addition, RF reduces mortality rates through the reduction of the expression and release of high-mobility group protein B1 (HMGB1); however, the effect of RF was time-dependent [<xref rid="B46-ijms-21-00950" ref-type="bibr">46</xref>]. A high dose of RF was also indicated to decrease LPS-induced mortality by increasing the expression of heat shock protein 25 (HSP25) [<xref rid="B44-ijms-21-00950" ref-type="bibr">44</xref>].</p><p>RF, the precursor of FAD and FMN, is converted by riboflavin kinase (RFK) into FMN and FAD, which are essential cofactors of the phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2). In particular, it has been shown that RF deficiency using conditional RFK knockout strains of mice impairs Nox2 priming. Such an effect may have implications for ROS production which impairs defence against <italic>Listeria monocytogene</italic> [<xref rid="B51-ijms-21-00950" ref-type="bibr">51</xref>]. These data show that TNF priming of Nox2 represents a RF-dependent mechanism that is crucial for optimal ROS production in innate immune responses (<xref ref-type="fig" rid="ijms-21-00950-f004">Figure 4</xref>).</p><p>As mentioned above, RF plays a crucial role in Nox2. The experiment of Dey and Bishayi [<xref rid="B49-ijms-21-00950" ref-type="bibr">49</xref>] showed that RF pre-treated macrophages lead to elevated levels of H<sub>2</sub>O<sub>2</sub>, O<sub>2</sub><sup>−</sup> as well as ROS and cause direct oxidative damage to many pathogens (<xref ref-type="fig" rid="ijms-21-00950-f005">Figure 5</xref>). RF along with antibiotics balances ROS and inflammatory cytokines and controls <italic>S. aureus</italic> infection by boosting murine macrophage function and regulates inflammation [<xref rid="B49-ijms-21-00950" ref-type="bibr">49</xref>]. </p><p>Wooley and Sebrell have shown that RF-deficient mice are more susceptible to fetal experimental pneumococcus infection than control groups [<xref rid="B52-ijms-21-00950" ref-type="bibr">52</xref>].</p><p>The deleterious toxic effects of many toxic substances have been linked to an increased production of free radicals and/or ROS. Some reports have indicated that RF has a protective effect against mitochondrial toxicity and lipodystrophy when in combination with stavudine or both stavudine and lamivudine in animal models [<xref rid="B53-ijms-21-00950" ref-type="bibr">53</xref>].</p></sec><sec id="sec2dot5-ijms-21-00950"><title>2.5. Photosensitizing Properties of RF</title><p>As a photosensitizer, RF induces oxidative damage to light-exposed tissue by the degradation of proteins, unsaturated lipids, folate, thiamine and other vitamins. This is due to the triplet-excitation state of RF resulting from light exposure, which can then be deactivated by phenolic and N-heterocyclic amino acids as well as their compounds. The deactivation of triplet-excited state RF by oxygen under aerobic conditions is faster than by anaerobic conditions through polyunsaturated lipids. Carotenoids do not appear to have deactivation properties for the triplet-excited state of RF, while vitamin E and plant polyphenols deactivate triplet-excited state RF and, therefore, protect proteins and lipids from degradation. On the other hand, polyphenols and carotenoids have protective effects on the degradation processes brought by triplet-excited state RF, however by different mechanisms [<xref rid="B1-ijms-21-00950" ref-type="bibr">1</xref>]. Since RF acts as a photosensitizer it can be used with Long-wave-length ultraviolet irradiation in order to inactivate many pathogens like HIV, pseudorabies virus, West Nile virus, parvovirus, <italic>E.coli</italic>, and <italic>Leishmanial protozoa</italic> [<xref rid="B54-ijms-21-00950" ref-type="bibr">54</xref>,<xref rid="B55-ijms-21-00950" ref-type="bibr">55</xref>,<xref rid="B56-ijms-21-00950" ref-type="bibr">56</xref>,<xref rid="B57-ijms-21-00950" ref-type="bibr">57</xref>].</p></sec><sec id="sec2dot6-ijms-21-00950"><title>2.6. Cancer</title><p>RF deficiency has been implicated as a risk factor for cancer in general, although this has not been satisfactorily established and proved in humans [<xref rid="B7-ijms-21-00950" ref-type="bibr">7</xref>]. There have been several articles reporting results of randomized controlled trials of RF on risk of cancer incidence. There has been an experimental finding that high folate (B vitamin) intake may reduce breast cancer risk in Chinese women [<xref rid="B58-ijms-21-00950" ref-type="bibr">58</xref>]. The results of a study that has investigated the effect of RF on 786-O cells indicated that RF at the high dose can inhibit cell viability and has a significant reduction in the level of tumor necrosis factor receptor 1 (TNFR1) in 786-O cells [<xref rid="B59-ijms-21-00950" ref-type="bibr">59</xref>]. In a study carried out by Machado et al. [<xref rid="B60-ijms-21-00950" ref-type="bibr">60</xref>] showing a strong inhibitory effect of RF on melanoma metastasis formation in lung of animal model. In addition, RF is likely to decrease risk of colorectal cancer (CRC) among women. Methylenetetrahydrofolate reductase (MTHFR) is FAD-dependent and low intake of RF may disturb this enzyme activity and related with CRC [<xref rid="B61-ijms-21-00950" ref-type="bibr">61</xref>]. Moreover, in post-menopausal women, intake of RF and vitamin B-6 related to a decreased CRC risk [<xref rid="B62-ijms-21-00950" ref-type="bibr">62</xref>]. Few significant associations between the intake of RF and the risk of ovarian cancer were observed [<xref rid="B63-ijms-21-00950" ref-type="bibr">63</xref>].</p><p>In female non-smokers, a higher intake of RF was correlated with a decrease the risk of lung cancer. The RF intake of 1.2 mg per day was associated with a lower risk of developing lung cancer compared to an intake of 0.52 mg per day [<xref rid="B64-ijms-21-00950" ref-type="bibr">64</xref>]. There is a significant interest in RF in combination with thiamin, folate, and vitamin B12 from supplements and foods for a protective role in cervical carcinogenesis [<xref rid="B65-ijms-21-00950" ref-type="bibr">65</xref>]. The importance of flavins in the folate metabolism as well as the combined protective effect of RF and folate is well known [<xref rid="B66-ijms-21-00950" ref-type="bibr">66</xref>].</p><p>Further studies dealing with the RF doses are necessary to prove any efficacy in treatment such as cervical cancer or AIDS-related acidosis [<xref rid="B3-ijms-21-00950" ref-type="bibr">3</xref>]. RF is associated with the inhibition in tumour growth in experimental animals and possibly in man; however, the regularity behind has not been discovered. The deficiency of RF increases the risk of cancer, while others propose an attenuating effect of some carcinogens [<xref rid="B67-ijms-21-00950" ref-type="bibr">67</xref>]. A deficiency in RF can cause a disruption of the integrity of oesophageal epithelium and in some studies it is related to oesophageal cancer [<xref rid="B68-ijms-21-00950" ref-type="bibr">68</xref>], while others relate to an increased susceptibility to cancer [<xref rid="B69-ijms-21-00950" ref-type="bibr">69</xref>]. </p><p>A high dose of RF intake showed a reverse effect of hepato-carcinogens in rodents [<xref rid="B70-ijms-21-00950" ref-type="bibr">70</xref>]. One study proposed that a moderate amount of RF can initiate the extrinsic pathway of apoptosis. Higher levels of RF can trigger further cell death mechanisms like the intrinsic pathway by the action of down regulation of anti-apoptotic factors and by the upregulation of apoptotic factors (<xref ref-type="fig" rid="ijms-21-00950-f006">Figure 6</xref>) [<xref rid="B71-ijms-21-00950" ref-type="bibr">71</xref>]. </p><p>The overall outcomes in the available studies are optimistic but not yet convincing. There are further studies to be made to obtain more knowledge about the role and mechanism of action of vitamins and other micronutrients in terms of prevention and treatment of cancer. On the other hand, RF is considered to have an enormous capability to be used in improving the chemotherapeutic potential of anticancer drugs [<xref rid="B72-ijms-21-00950" ref-type="bibr">72</xref>].</p><p>In addition, RF laurate has protective and therapeutic properties against radiotherapy-induced toxicity on human embryonic lung fibroblasts (Helf cells) [<xref rid="B73-ijms-21-00950" ref-type="bibr">73</xref>].</p><p>The oxidative damage of cells from chemotherapeutic drugs can be ameliorated by RF administration. RF can improve the chemotherapeutic potential of major anticancer drugs like carbon tetrachloride (CCL<sub>4</sub>) via decreasing the hepatic oxidative stress and the release of pro-inflammatory cytokine TNF-α from leukocytes in CCl<sub>4</sub>-induced hepatic injury [<xref rid="B74-ijms-21-00950" ref-type="bibr">74</xref>].</p></sec><sec id="sec2dot7-ijms-21-00950"><title>2.7. Migraine</title><p>Currently it is not clear how RF contributes to migraine prevention. However, the reduction in oxygen metabolism due to a mitochondrial dysfunction may play a role in migraine prevention since an increase in RF concentration might enhance the brain mitochondrial functions [<xref rid="B76-ijms-21-00950" ref-type="bibr">76</xref>]. Studies have indicated a positive influence of RF in migraine prophylaxis, as RF is considered to play a potential role due to its attributes in the sense of safety, toleration and as an economically reasonable substance [<xref rid="B77-ijms-21-00950" ref-type="bibr">77</xref>]. A clinical study reported that RF is an effective and low-cost prophylactic treatment in children and adolescents suffering from migraine [<xref rid="B78-ijms-21-00950" ref-type="bibr">78</xref>]. In a study of migraine sufferers, RF combined with feverfew and magnesium showed a significant reduction in number of migraine attacks, migraine days and migraine index in the 3-month trial. When treatment response was compared, no significant differences were seen between the groups [<xref rid="B79-ijms-21-00950" ref-type="bibr">79</xref>]. It has also been demonstrated that RF supplemented with magnesium and Q10 ameliorates migraine symptoms [<xref rid="B80-ijms-21-00950" ref-type="bibr">80</xref>].</p></sec><sec id="sec2dot8-ijms-21-00950"><title>2.8. Cataract</title><p>Cataract formation is a result of protein aggregation which causes the lens to become cloudy. RF intake from food and supplements was associated with decreased risk of nuclear lens opacities [<xref rid="B81-ijms-21-00950" ref-type="bibr">81</xref>]. Cataract formation in the general public seemed not to be associated with RF deficiency while in the elderly it might be increased due to a RF deficiency [<xref rid="B82-ijms-21-00950" ref-type="bibr">82</xref>]. High dose of RF, 400 mg/d, appears to have a preventive effect or some beneficial effects on the development of age-related cataracts [<xref rid="B3-ijms-21-00950" ref-type="bibr">3</xref>]. RF concentration influences the GSH concentration in the lens, while GSH protects the lens against oxidative damage and cataract development. In total, 80% of the cataract patients showed a shortage of RF [<xref rid="B83-ijms-21-00950" ref-type="bibr">83</xref>]. </p></sec><sec id="sec2dot9-ijms-21-00950"><title>2.9. Premenstrual Syndrome (PMS)</title><p>Premenstrual syndrome (PMS) is a condition that refers to a complex of physical and psychological symptoms which occur during the luteal phase of the menstrual cycle and disappear when menstruation starts. An increased intake of RF from food sources was associated with a decrease in the risk of PMS. The intake of 2.52 mg RF per day was observed to lead to a 35% lower risk of developing PMS compared to the intake of 1.38 mg per day [<xref rid="B84-ijms-21-00950" ref-type="bibr">84</xref>].</p></sec><sec id="sec2dot10-ijms-21-00950"><title>2.10. Bone</title><p>Osteoporosis is a systemic skeletal disease. One of the most important factors to influence risk of fracture is vitamin intake. RF had an additive effect on ascorbate and β-glycerophosphate-induced osteoblast differentiation of MC3T3-E1 including intensifying G0/G arrest in pre-osteoblast cells [<xref rid="B85-ijms-21-00950" ref-type="bibr">85</xref>]. </p></sec><sec id="sec2dot11-ijms-21-00950"><title>2.11. Neuropathy</title><p>Indications have been made for RF being important in the early postnatal development of the brain [<xref rid="B86-ijms-21-00950" ref-type="bibr">86</xref>]. The reduction in RF uptake and decrease in RF transporter protein (RFVT2) expression due to mutations in SLC52A2 gen has been illustrated. Patients with these mutations have shown significant and sustained clinical and biochemical improvements after high-dose oral RF therapy [<xref rid="B87-ijms-21-00950" ref-type="bibr">87</xref>]. Moreover, RF co-treatment with selenium or vitamin E can have a protective effect on brain and microsomal membrane Ca<sup>2+</sup>-ATPase (MMCA) and oxidative damage caused by glyceryl trinitrate (GTN)-induced headaches in rat models. RF and selenium (SE) can decrease lipid peroxidation (LP) levels and increase glutathione and reduced glutathione levels in microsomal brains. The co-administration of RF and vitamin E induced a decrease in calcium and a decrease in brain and microsomal lipid peroxidation levels [<xref rid="B19-ijms-21-00950" ref-type="bibr">19</xref>,<xref rid="B20-ijms-21-00950" ref-type="bibr">20</xref>]. The brain and microsomal lipid peroxidation levels (LP) have been found to be higher in the GTN-induced rats with migraine headaches compared to healthy rats [<xref rid="B19-ijms-21-00950" ref-type="bibr">19</xref>]; whereas SE orally pre-treated rats with or without RF were protected against GTN-induced brain oxidative toxicity, by inhibiting free radicals and MMCA activity and supporting the antioxidant effect of RF [<xref rid="B19-ijms-21-00950" ref-type="bibr">19</xref>]. It has been demonstrated that RF plays a protective role in a time- and dose-dependent manner against excitotoxicity of cerebellar granule neurons induced by glutamate/NMDA in C57/B strain mice [<xref rid="B21-ijms-21-00950" ref-type="bibr">21</xref>]. It has been shown by authors [<xref rid="B22-ijms-21-00950" ref-type="bibr">22</xref>] that RF may have therapeutic potential for the treatment of traumatic brain injury. RF administration after frontal cortical contusion injury (CCI) in rats improved behavioural outcomes, reduced the number of glial fibrillary acidic protein (GFAP<sup>+</sup>) astrocytes, reduced brain oedema formation and reduced lesion size [<xref rid="B22-ijms-21-00950" ref-type="bibr">22</xref>]. In addition, it is also suggested to combine RF and MgCl<sub>2</sub> infusions, to be more effective in improving functional recovery after bilateral and unilateral cortical CCI in rats [<xref rid="B23-ijms-21-00950" ref-type="bibr">23</xref>].</p></sec><sec id="sec2dot12-ijms-21-00950"><title>2.12. Anemia</title><p>RF contributes to blood cells formation as it plays a role in erythropoiesis, improves iron absorption and helps in the mobilization of ferritin from tissues [<xref rid="B88-ijms-21-00950" ref-type="bibr">88</xref>]. The concentration of hemoglobin was able to be increased by RF supplementation. In an animal model, RF was also shown to enhance iron absorption [<xref rid="B89-ijms-21-00950" ref-type="bibr">89</xref>], while RF deficiency increases the rate of gastrointestinal loss of iron and decreases the mobilization of iron from its stores [<xref rid="B90-ijms-21-00950" ref-type="bibr">90</xref>].</p><p>A positive relation between RF intake and anemia in women, especially those below 50 years, was observed. Furthermore, a significant association between RF and iron intake in correspondence to the risk of anemia was detected. There have been cross-sectional studies to illustrate the link between RF intake and anemia, while prospective population studies are limited [<xref rid="B91-ijms-21-00950" ref-type="bibr">91</xref>]. </p></sec><sec id="sec2dot13-ijms-21-00950"><title>2.13. Diabetes Mellitus</title><p>Oxidative Stress is one of the major factors in the pathogenesis of type-2-diabetes mellitus (T2DM). The dietary intake of RF might lead to a reduction in diabetic complications because of the reduction in inflammatory processes triggered by oxidative stress and ROS formation. RF is indicated to have a positive effect on blood sugar. It plays a role in the absorption of sugar from the intestine and reduces hyperglycemia. It enhances the state of hyperglycaemias by increasing glucose uptake in skeletal muscles and white adipose tissue, as well as significantly ameliorating oxidative stress, tissue damage and cellular DNA damage in T2DM in mice. The ability of antioxidants to inhibit injury has raised the possibility of new therapeutic treatment for diabetic heart diseases. RF has shown promising beneficial effects on heart failure in type I diabetic cardiomyopathy in rats [<xref rid="B16-ijms-21-00950" ref-type="bibr">16</xref>,<xref rid="B17-ijms-21-00950" ref-type="bibr">17</xref>]. </p></sec><sec id="sec2dot14-ijms-21-00950"><title>2.14. Cardiac Abnormalities</title><p>RF as a single compound has shown promising results for protective actions in terms of cardiac abnormalities. Cardiac abnormalities could be avoided or reduced by using RF. RF may be combined with other compounds to have additive beneficial effects. RF combination with coenzyme Q10, niacin, selenium as CoRNS and Emblica officinalis has a protective effect on cardiac abnormalities in experimental atherosclerosis [<xref rid="B18-ijms-21-00950" ref-type="bibr">18</xref>]. RF also reduces subsequent acute rejection and early graft oxidant stress significantly after allotransplantation and coronary allograft vasculopathy as results of cardiac ischemia-reperfusion. Pre-treatment with RF in a murine heart transplantation model can protect tissues from oxidative damage by decreasing myocardial lipid peroxidation, leukocyte infiltration, cytokine production, and cardiac allograft vasculopathy [<xref rid="B34-ijms-21-00950" ref-type="bibr">34</xref>].</p></sec><sec id="sec2dot15-ijms-21-00950"><title>2.15. Hypertension</title><p>Hypertension is considered to be the leading risk factor for mortality worldwide [<xref rid="B92-ijms-21-00950" ref-type="bibr">92</xref>]. It is estimated to be responsible for 8 million premature deaths per year [<xref rid="B93-ijms-21-00950" ref-type="bibr">93</xref>]. A study has proposed an association of RF intake and blood pressure modulation. In animal studies, RF as supplementation did not provoke the side effects, but did provoke a significant systolic blood pressure reduction which was not age dependent between young and adult rats [<xref rid="B94-ijms-21-00950" ref-type="bibr">94</xref>].</p></sec></sec><sec id="sec3-ijms-21-00950"><title>3. Side Effects of Lack or Excess of RF </title><p>RF deficiency has been comprehensively reviewed elsewhere [<xref rid="B7-ijms-21-00950" ref-type="bibr">7</xref>]. RF is required in many oxidation-reduction reactions and, therefore, RF deficiency may affect many systems. RF is considered to be one of the most common vitamins with deficits in people of developing countries, particularly the ones with rice as their staple food. In those countries, important RF sources like milk and meat are not sufficiently consumed [<xref rid="B95-ijms-21-00950" ref-type="bibr">95</xref>]. However, ariboflavinosis is not a common deficiency in most societies. RF deficiency is only measurable by quantifying the vitamin concentration in body fluids like blood plasma, serum, etc. [<xref rid="B96-ijms-21-00950" ref-type="bibr">96</xref>] (<xref rid="ijms-21-00950-t001" ref-type="table">Table 1</xref>). </p><p>Ariboflavinosis in humans causes various symptoms like sore throat, hyperaemia, oedema of the oral and mucous membranes, cheilitis and glossitis, hair loss, inflammation of skin, cataract development, migraine and a decrease in Hb. RF deficiency has shown an influence on the iron absorption, metabolism of tryptophan, mitochondrial function, brain and the metabolism of other vitamins. The Food and Nutrition Board 1998 published that a balanced diet meets the recommended intake of 1.4 mg RF per day for an adult man. A study observed that approximately 60% of elderly people were at risk for RF deficiency [<xref rid="B97-ijms-21-00950" ref-type="bibr">97</xref>]. The shortage of RF could also be a consequence of the use of some drugs, alcohol consumption, increased need of RF due to physiological conditions like pregnancy or breastfeeding or childhood etc. (<xref ref-type="fig" rid="ijms-21-00950-f007">Figure 7</xref>) [<xref rid="B7-ijms-21-00950" ref-type="bibr">7</xref>,<xref rid="B75-ijms-21-00950" ref-type="bibr">75</xref>,<xref rid="B88-ijms-21-00950" ref-type="bibr">88</xref>].</p><p>RF deficiency rarely occurs alone and is usually part of generalized vitamin B deficiency because of a poor diet or malabsorption. Oral supplementation of RF alone is poorly absorbed, with only 15% of bioavailability. RF can be destroyed by UV light exposure; UV therapy in infants with hyperbilirubinemia could cause RF deficiency [<xref rid="B3-ijms-21-00950" ref-type="bibr">3</xref>]. </p></sec><sec id="sec4-ijms-21-00950"><title>4. Mechanism of Antioxidant Protection</title><p>RF has an antioxidant function that can destroy ROS [<xref rid="B10-ijms-21-00950" ref-type="bibr">10</xref>]. The powerful antioxidant activity is derived from its role as precursor to FMN and FAD as important coenzymes required by a number of enzymes involved in oxidative metabolism, particularly glutathione oxidase. On the other hand, GR—which is a free radical scavenger—also needs FAD as a cofactor. The protective role of RF against various diseases has been described previously [<xref rid="B98-ijms-21-00950" ref-type="bibr">98</xref>]. Several studies showed that RF is effective to reduce ROS in various diseases including anti-aging and it also helps to ameliorate the toxic effect of drugs in various treatments. Many studies investigated the antioxidant effect of some vitamins such as vitamin E, vitamin C, carotenoids and RF. RF effective mechanism has not been completely investigated. It acts as a coenzyme for redox enzymes in FAD and FMN forms and can have a potential effect on oxidative stress reduction as an antioxidant by prevention of lipid peroxidation and by attenuation of reperfusion oxidative injury. GR requires RF for its activity to convert GSSG to the GSH. FAD transports hydrogen from NADPH to GSSG to convert it into the GSH form (<xref ref-type="fig" rid="ijms-21-00950-f008">Figure 8</xref>). GSH acts intracellular as an endogenous antioxidant and deactivates ROS. Glutathione deactivates peroxides such as hydroperoxides by the action of GPx from GSH to lipid peroxide and produce GSSG and alcohol. Therefore, RF deficiency leads to an increase in lipid peroxidation.</p></sec><sec id="sec5-ijms-21-00950"><title>5. Perspective Use of RF in Complementary Medicine: Administration via Functional Food and Nanocapsules</title><sec id="sec5dot1-ijms-21-00950"><title>5.1. RF in Food</title><p>Biotechnological application is used for fermented RF-enriched functional foods. Lactic acid bacteria, can synthesize or utilize during food fermentation, are considered for the production of vitamin-enriched food (<xref ref-type="fig" rid="ijms-21-00950-f009">Figure 9</xref>). Using <italic>L. lactis</italic> to produce fermented milk overcomes ariboflavinosis in a RF-deficiency rat model [<xref rid="B99-ijms-21-00950" ref-type="bibr">99</xref>]. <italic>L. plantarum</italic> was used to produce fermented RF-enriched sourdough bread and pasta [<xref rid="B100-ijms-21-00950" ref-type="bibr">100</xref>], soymilk [<xref rid="B101-ijms-21-00950" ref-type="bibr">101</xref>], oat-based food [<xref rid="B102-ijms-21-00950" ref-type="bibr">102</xref>]. <italic>L. fermentun</italic> was found to produce RF to fortify bread [<xref rid="B103-ijms-21-00950" ref-type="bibr">103</xref>]. Furthermore, <italic>P. freudenreichii</italic> lead to an increase in RF content in yoghurt with <italic>P. freudenreichii</italic> [<xref rid="B104-ijms-21-00950" ref-type="bibr">104</xref>] or fermented milk with this <italic>Propionibacterium</italic> species reverted ariboflavinosis in mouse [<xref rid="B105-ijms-21-00950" ref-type="bibr">105</xref>].</p></sec><sec id="sec5dot2-ijms-21-00950"><title>5.2. RF Encapsulation</title><p>RF is sensitive to light, especially at high temperatures and in alkaline conditions [<xref rid="B106-ijms-21-00950" ref-type="bibr">106</xref>]. In food process modifications, fortification or encapsulation has the potential to alter the stability of RF in food (<xref ref-type="fig" rid="ijms-21-00950-f009">Figure 9</xref>). Therefore, to maintain the level of this vitamin, these factors need a consideration for its stability. Encapsulation has been proposed as a solution for its chemical instability [<xref rid="B107-ijms-21-00950" ref-type="bibr">107</xref>,<xref rid="B108-ijms-21-00950" ref-type="bibr">108</xref>,<xref rid="B109-ijms-21-00950" ref-type="bibr">109</xref>]. </p><p>Micro/nano-encapsulation was used to solve RF chemical instability. Numerous encapsulating techniques are currently implemented and selected according to the physical and chemical properties of core materials and encapsulating agents. Some example methods used for RF micro/nano-encapsulation are shown in <xref rid="ijms-21-00950-t005" ref-type="table">Table 5</xref>.</p><p>Blank whey microbeads manufactured using a cold-set gelation process, were placed in solutions of RF [<xref rid="B109-ijms-21-00950" ref-type="bibr">109</xref>]. As the volume of microbeads added to the solution was increased, the uptake of the compounds increased, to a maximum of 57%. The release kinetics of RF can be fitted by a pseudo first-order kinetic model very well. In addition, in vitro and in vivo release of RF from microbeads was evaluated [<xref rid="B110-ijms-21-00950" ref-type="bibr">110</xref>]. In the first hour, the release of RF from dried microbeads was decreased in comparison to wet microbeads in gastric and intestinal settings, with 58% and 34%, respectively. The in vivo release of RF from dried microbeads—microbeads fed to piglets were shown to be only partially degraded—demonstrating good resistance to gastrointestinal degradation after ingestion. These aspects led research interests towards dried whey microbeads able to effectively deliver these substances for oral delivery to the intestine.</p><p>Hydrogels of soy protein isolate (SPI) were prepared via high intensity ultrasound (HIU) and were cross-linked by transglutaminase (TGase) [<xref rid="B111-ijms-21-00950" ref-type="bibr">111</xref>]. Ultrasound treatment resulted in decreasing the RF release from TSGRs in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF) with or without digestive enzymes. In addition, both encapsulation efficiency and gelation yield increased after ultrasound treatment. </p><p>Azevedo et al. loaded RF in alginated-chitosan NPs prepared by ionic gelation [<xref rid="B112-ijms-21-00950" ref-type="bibr">112</xref>]. The average size of nanoparticles with RF was 104 ± 67 nm (PDI 0.32 ± 0.07) with a Zeta-potential of −29.6 ± 0.1 mV. The nanoparticles showed entrapment efficiency (EE%) and loading capacity (LC) values of 56 ± 6% and 2.2 ± 0.6%, respectively. The release profiles were affected by polymeric relaxation. In addition, the stability of alginate–chitosan was measured over a five-month period at 4 °C in solution.</p><table-wrap id="ijms-21-00950-t005" orientation="portrait" position="float"><object-id pub-id-type="pii">ijms-21-00950-t005_Table 5</object-id><label>Table 5</label><caption><p>Techniques and characteristic of micro/nanoencapsulation of encapsulated RF.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Encapsulation Techniques</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Wall<break></break>Material</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Illustration of Characteristics</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Purpose</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Size</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cold-set gelation</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Whey protein<break></break>isolated</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><inline-graphic xlink:href="ijms-21-00950-i001.jpg"></inline-graphic></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Proofing suitability of encapsulation system for intestinal delivery using in vitro and in vivo models</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1.8 mm</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B11-ijms-21-00950" ref-type="bibr">11</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cross-linking of HIU-treated SPI with TGase</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Soy protein isolated (SPI)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><inline-graphic xlink:href="ijms-21-00950-i002.jpg"></inline-graphic></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Demonstrating of HIU-treated SPI–TGase cold gel for longer retention in the gastrointestinal system</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3 mm</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B111-ijms-21-00950" ref-type="bibr">111</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ionotropic gelation</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Alginate/chitosan nanoparticles</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><inline-graphic xlink:href="ijms-21-00950-i003.jpg"></inline-graphic></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Establishing of alginate/chitosan nanoparticle for controlled release in different temperature and pH conditions</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">119.5 ± 49.9 nm</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B112-ijms-21-00950" ref-type="bibr">112</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ultrasonication</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Soy protein/dextran<break></break>nanogel</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><inline-graphic xlink:href="ijms-21-00950-i004.jpg"></inline-graphic></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Providing basic design of soy protein/dextran nanogel for effective and suitable carriers for bioactive compounds</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">143.3 nm</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B113-ijms-21-00950" ref-type="bibr">113</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Bioconjugation</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Phenylalanine ethyl ester–alginate conjugated (PEA)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><inline-graphic xlink:href="ijms-21-00950-i005.jpg"></inline-graphic></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Illustrating a sonication method of self-assembled nanoparticles formed by PEA conjugate without cytotoxicity against cell lines</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">200 nm</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B114-ijms-21-00950" ref-type="bibr">114</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Supercritical fluid technology</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fully hydrogenated canola oil</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><inline-graphic xlink:href="ijms-21-00950-i006.jpg"></inline-graphic></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Evaluating surfactant and molecular weight of stabilizer from supercritical fluid technology for development of solid lipid nanoparticles</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">104 ± 5.7 nm</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B115-ijms-21-00950" ref-type="bibr">115</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Coprecipitation-Crosslinking-Dissolution technique (CCD-technique)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Human serum albumin</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><inline-graphic xlink:href="ijms-21-00950-i007.jpg"></inline-graphic></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Demonstrating a simple coprecipitation method of albumin submicron particles with good biocompatibility</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">900 ± 1000 nm</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B116-ijms-21-00950" ref-type="bibr">116</xref>]</td></tr></tbody></table></table-wrap><p>Jin et al. [<xref rid="B113-ijms-21-00950" ref-type="bibr">113</xref>] encapsulated RF using modified soy protein/dextran with the range of 143.3 nm size. The EE% and LC values of nanogels were up to 65.9% and up to 12%, respectively. The release rate of RF was examined in SIF and SGF. Nanogels have a better sustained release in SGF than in SIF.</p><p>Recently, Zhang et al. [<xref rid="B114-ijms-21-00950" ref-type="bibr">114</xref>] produced phenylalanine ethyl ester–alginate conjugate (PEA) using EDC–NHS coupling reaction. Nano-encapsulated RF in PEA was synthesized via sonication. It was observed that the size of produced nanoparticles was 200 nm, meanwhile the LC and EE% were 3.53% and 91.48%, respectively. RF-loaded PEA-nanoparticles displayed pH-dependant release trend. By declining pH, the release rate of RF decreased. Moreover, the cytotoxicity of these particles to Caco-2 cells was used to investigate. There is no significant cytotoxicity against cell line in a wide range of concentration.</p><p>Solid lipid-based nanoparticles loaded with RF were prepared using fully hydrogenated canola oil-based lipids, sodium lauryl sulfate and polyethylene glycol as surfactant and stabilizer, respectively [<xref rid="B115-ijms-21-00950" ref-type="bibr">115</xref>]. An LC of 12% to 48% RF was reported while bioactive loads varied from 0.09 to 0.73 mg/g, with particle sizes in the range of 105 nm.</p><p>The Co-precipitation Crosslinking Dissolution technique (CCD-technique) was employed in the presence of human serum albumin (HSA) and RF to produce albumin submicron particles. The uniform peanut-like particles showed a narrow size distribution in the range of 0.9 to 1 µm and a negative zeta-potential. The RF-albumin submicron particles revealed a good hemocompatibility [<xref rid="B116-ijms-21-00950" ref-type="bibr">116</xref>].</p></sec></sec><sec sec-type="conclusions" id="sec6-ijms-21-00950"><title>6. Conclusions</title><p>RF is an important vitamin in the protection and treatment of various medical conditions. However, due to the few available studies on humans it is essential to have more data in terms of human clinical trials to conclude precise evidence and dosage information as recommendations for the treatment or prophylaxis of many diseases and conditions. The use of RF in fighting pathogens using UV-Light is a motivating approach, since it does not go along with adverse side effects. Through the consumption of functional RF-enriched foods, many diseases could possibly be prevented according to the currently available scientific evidence.</p></sec></body><back><ack><title>Acknowledgments</title><p>We acknowledge discussions with Ciro Isidoro, Università del Piemonte Orientale “A. Avogadro”, Novara, Italy.</p></ack><notes><title>Author Contributions</title><p>Writing, editing, and original draft preparation, N.S.; writing, and review and editing, I.K.; review and editing, A.P.; conceptualization, review and editing, R.G.; supervision, conceptualization, and final approval of the manuscript, H.B. All authors have read and agreed to the published version of the manuscript.</p></notes><notes><title>Funding</title><p>This research was funded by Horizon 2020-MSCA-RISE 2018, Oxigenated (823879). N.S. held an academic development scholarship from the University of Phayao, Thailand. We acknowledge support from the German Research Foundation (DFG) and the Open Access Publication Funds of Charité–Universitätsmedizin Berlin and the Hans-Joachim Hoster Foundation.</p></notes><notes notes-type="COI-statement"><title>Conflicts of Interest</title><p>The authors declare no conflict of interest.</p></notes><glossary><title>Abbreviations</title><array orientation="portrait"><tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">RF</td><td align="left" valign="top" rowspan="1" colspan="1">Riboflavin</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">FMN</td><td align="left" valign="top" rowspan="1" colspan="1">Flavin mononucleotide</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">FAD</td><td align="left" valign="top" rowspan="1" colspan="1">Flavin adenine dinucleotide</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">SOD</td><td align="left" valign="top" rowspan="1" colspan="1">Superoxide dismutase</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">ROS</td><td align="left" valign="top" rowspan="1" colspan="1">Reactive oxygen species</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">GR</td><td align="left" valign="top" rowspan="1" colspan="1">Glutathione reductase</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">GPx</td><td align="left" valign="top" rowspan="1" colspan="1">Glutathione peroxidase</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">GSSG</td><td align="left" valign="top" rowspan="1" colspan="1">Oxidized glutathione</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">GSH</td><td align="left" valign="top" rowspan="1" colspan="1">Reduced glutathione</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">OGD</td><td align="left" valign="top" rowspan="1" colspan="1">Oxygen glucose deprivation</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">LDH</td><td align="left" valign="top" rowspan="1" colspan="1">Lactate dehydrogenase</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Hb</td><td align="left" valign="top" rowspan="1" colspan="1">Haemoglobin</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">TNF-α</td><td align="left" valign="top" rowspan="1" colspan="1">Tumor necrosis factor alpha</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">NO</td><td align="left" valign="top" rowspan="1" colspan="1">Nitric oxide</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">NF-κB</td><td align="left" valign="top" rowspan="1" colspan="1">Nuclear factor factor kappa B</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">IκB</td><td align="left" valign="top" rowspan="1" colspan="1">Inhibitory kappa B</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">LPS</td><td align="left" valign="top" rowspan="1" colspan="1">Lipopolysaccharide</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">IL-6</td><td align="left" valign="top" rowspan="1" colspan="1">Interleukin-6</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">MCP-1</td><td align="left" valign="top" rowspan="1" colspan="1">Monocyte chemo attractant protein 1</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">MIP-2</td><td align="left" valign="top" rowspan="1" colspan="1">Macrophage inflammatory protein ()),</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">HMGB1</td><td align="left" valign="top" rowspan="1" colspan="1">High-mobility group protein B1</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">MDA</td><td align="left" valign="top" rowspan="1" colspan="1">Malondialdehyde level</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">MPO</td><td align="left" valign="top" rowspan="1" colspan="1">Myeloperoxidase</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">CAT</td><td align="left" valign="top" rowspan="1" colspan="1">Catalase</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">HSP25</td><td align="left" valign="top" rowspan="1" colspan="1">Heat shock protein 25</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">RFK</td><td align="left" valign="top" rowspan="1" colspan="1">Riboflavin Kinase</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">NADPH</td><td align="left" valign="top" rowspan="1" colspan="1">Nicotinamide adenine dinucleotide phosphate</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Nox2</td><td align="left" valign="top" rowspan="1" colspan="1">NADPH oxidase 2</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">TNFR1</td><td align="left" valign="top" rowspan="1" colspan="1">necrosis factor receptor 1</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">CRC</td><td align="left" valign="top" rowspan="1" colspan="1">Colorectal cancer</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">MTHFR</td><td align="left" valign="top" rowspan="1" colspan="1">Methylenetetrahydrofolate reductase</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">CCL<sub>4</sub></td><td align="left" valign="top" rowspan="1" colspan="1">Carbon tetrachloride</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">PMS</td><td align="left" valign="top" rowspan="1" colspan="1">Premenstrual syndrome</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">RFVT2</td><td align="left" valign="top" rowspan="1" colspan="1">RF transporter protein 2</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">MMCA</td><td align="left" valign="top" rowspan="1" colspan="1">Microsomal membrane Ca2+-ATPase</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">GTN</td><td align="left" valign="top" rowspan="1" colspan="1">Glyceryl trinitrate</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">SE</td><td align="left" valign="top" rowspan="1" colspan="1">Selenium</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">CCI</td><td align="left" valign="top" rowspan="1" colspan="1">Cortical contusion injury linear dichroism</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">GFAP+</td><td align="left" valign="top" rowspan="1" colspan="1">Glial fibrillary acidic protein</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">T2DM</td><td align="left" valign="top" rowspan="1" colspan="1">Type-2-diabetes mellitus</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">PTL</td><td align="left" valign="top" rowspan="1" colspan="1">Peritoneal leukocytes</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">SPI</td><td align="left" valign="top" rowspan="1" colspan="1">Soy protein isolate</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">HIU </td><td align="left" valign="top" rowspan="1" colspan="1">High intensity ultrasound</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">TGase</td><td align="left" valign="top" rowspan="1" colspan="1">Transglutaminase</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">SIF</td><td align="left" valign="top" rowspan="1" colspan="1">Simulated intestinal fluid</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">SGF</td><td align="left" valign="top" rowspan="1" colspan="1">Simulated gastric fluid</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">EE%</td><td align="left" valign="top" rowspan="1" colspan="1">Entrapment efficiency</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">LC</td><td align="left" valign="top" rowspan="1" colspan="1">Loading capacity</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">PEA</td><td align="left" valign="top" rowspan="1" colspan="1">Phenylalanine ethyl ester–alginate conjugate</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">CCD-technique</td><td align="left" valign="top" rowspan="1" colspan="1">Coprecipitation-Crosslinking-Dissolution technique</td></tr></tbody></array></glossary><ref-list><title>References</title><ref id="B1-ijms-21-00950"><label>1.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cardoso</surname><given-names>D.R.</given-names></name><name><surname>Libardi</surname><given-names>S.H.</given-names></name><name><surname>Skibsted</surname><given-names>L.H.</given-names></name></person-group><article-title>Riboflavin as a photosensitizer. Effects on human health and food quality</article-title><source>Food Funct.</source><year>2012</year><volume>3</volume><fpage>487</fpage><lpage>502</lpage><pub-id pub-id-type="doi">10.1039/c2fo10246c</pub-id><pub-id pub-id-type="pmid">22406738</pub-id></element-citation></ref><ref id="B2-ijms-21-00950"><label>2.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dym</surname><given-names>O.</given-names></name><name><surname>Eisenberg</surname><given-names>D.</given-names></name></person-group><article-title>Sequence-structure analysis of FAD-containing proteins</article-title><source>Protein Sci.</source><year>2001</year><volume>10</volume><fpage>1712</fpage><lpage>1728</lpage><pub-id pub-id-type="doi">10.1110/ps.12801</pub-id><pub-id pub-id-type="pmid">11514662</pub-id></element-citation></ref><ref id="B3-ijms-21-00950"><label>3.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Buehler</surname><given-names>B.A.</given-names></name></person-group><article-title>Vitamin B2: Riboflavin</article-title><source>J. Evid. Based. Complementary Altern. Med.</source><year>2011</year><volume>16</volume><fpage>88</fpage><lpage>90</lpage><pub-id pub-id-type="doi">10.1177/1533210110392943</pub-id></element-citation></ref><ref id="B4-ijms-21-00950"><label>4.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>Y.</given-names></name><name><surname>Zhou</surname><given-names>W.E.</given-names></name><name><surname>Yan</surname><given-names>J.Q.</given-names></name><name><surname>Liu</surname><given-names>M.</given-names></name><name><surname>Zhou</surname><given-names>Y.</given-names></name><name><surname>Shen</surname><given-names>X.</given-names></name><name><surname>Ma</surname><given-names>Y.L.</given-names></name><name><surname>Feng</surname><given-names>X.S.</given-names></name><name><surname>Yang</surname><given-names>J.</given-names></name><name><surname>Li</surname><given-names>G.H.</given-names></name></person-group><article-title>A review of the extraction and determination methods of thirteen essential vitamins to the human body: An update from 2010</article-title><source>Molecules</source><year>2018</year><volume>23</volume><elocation-id>1484</elocation-id><pub-id pub-id-type="doi">10.3390/molecules23061484</pub-id></element-citation></ref><ref id="B5-ijms-21-00950"><label>5.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gul</surname><given-names>W.N.</given-names></name><name><surname>Anwar</surname><given-names>Z.</given-names></name><name><surname>Qadeer</surname><given-names>K.</given-names></name></person-group><article-title>Methods of analysis of riboflavin ( vitamin B2 ): A review</article-title><source>J. Pharm. Pharm. Sci.</source><year>2014</year><volume>2</volume><fpage>10</fpage><lpage>21</lpage></element-citation></ref><ref id="B6-ijms-21-00950"><label>6.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Antal</surname><given-names>I.P.</given-names></name><name><surname>Bazel</surname><given-names>Y.R.</given-names></name><name><surname>Kormosh</surname><given-names>Z.A.</given-names></name></person-group><article-title>Electrochemical methods for determining group B vitamins</article-title><source>J. Anal. Chem.</source><year>2013</year><volume>68</volume><fpage>565</fpage><lpage>576</lpage><pub-id pub-id-type="doi">10.1134/S1061934813070034</pub-id></element-citation></ref><ref id="B7-ijms-21-00950"><label>7.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Powers</surname><given-names>H.J.</given-names></name></person-group><article-title>Riboflavin (vitamin B-2) and health</article-title><source>Am. J. Clin. Nutr.</source><year>2003</year><volume>77</volume><fpage>1352</fpage><lpage>1360</lpage><pub-id pub-id-type="doi">10.1093/ajcn/77.6.1352</pub-id><pub-id pub-id-type="pmid">12791609</pub-id></element-citation></ref><ref id="B8-ijms-21-00950"><label>8.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Toyosawa</surname><given-names>T.</given-names></name><name><surname>Suzuki</surname><given-names>M.</given-names></name><name><surname>Kodama</surname><given-names>K.</given-names></name><name><surname>Araki</surname><given-names>S.</given-names></name></person-group><article-title>Effects of intravenous infusion of highly purified vitamin B2 on lipopolysaccharide-induced shock and bacterial infection in mice</article-title><source>Eur. J. Pharmacol.</source><year>2004</year><volume>492</volume><fpage>273</fpage><lpage>280</lpage><pub-id pub-id-type="doi">10.1016/j.ejphar.2004.04.004</pub-id><pub-id pub-id-type="pmid">15178375</pub-id></element-citation></ref><ref id="B9-ijms-21-00950"><label>9.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Toyosawa</surname><given-names>T.</given-names></name><name><surname>Suzuki</surname><given-names>M.</given-names></name><name><surname>Kodama</surname><given-names>K.</given-names></name><name><surname>Araki</surname><given-names>S.</given-names></name></person-group><article-title>Potentiation by amino acid of the therapeutic effect of highly purified vitamin B2 in mice with lipopolysaccharide-induced shock</article-title><source>Eur. J. Pharmacol.</source><year>2004</year><volume>493</volume><fpage>177</fpage><lpage>182</lpage><pub-id pub-id-type="doi">10.1016/j.ejphar.2004.04.019</pub-id><pub-id pub-id-type="pmid">15189780</pub-id></element-citation></ref><ref id="B10-ijms-21-00950"><label>10.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Toyasaki</surname><given-names>T.</given-names></name></person-group><article-title>Antioxidant effect of riboflavin in enzymic lipid peroxidation</article-title><source>J. Agric. Food Chem.</source><year>1992</year><volume>40</volume><fpage>1727</fpage><lpage>1730</lpage><pub-id pub-id-type="doi">10.1021/jf00022a001</pub-id></element-citation></ref><ref id="B11-ijms-21-00950"><label>11.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zou</surname><given-names>Y.</given-names></name><name><surname>Ruan</surname><given-names>M.</given-names></name><name><surname>Luan</surname><given-names>J.</given-names></name><name><surname>Feng</surname><given-names>X.</given-names></name><name><surname>Chen</surname><given-names>S.</given-names></name><name><surname>Chu</surname><given-names>Z.</given-names></name></person-group><article-title>Anti-aging effect of riboflavin via endogenous antioxidant in fruit fly Drosophila melanogaster</article-title><source>J. Nutr. Health Aging</source><year>2015</year><volume>21</volume><fpage>314</fpage><lpage>319</lpage><pub-id pub-id-type="doi">10.1007/s12603-016-0752-8</pub-id><pub-id pub-id-type="pmid">28244572</pub-id></element-citation></ref><ref id="B12-ijms-21-00950"><label>12.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cheung</surname><given-names>I.M.Y.</given-names></name><name><surname>Mcghee</surname><given-names>C.N.J.</given-names></name><name><surname>Sherwin</surname><given-names>T.</given-names></name></person-group><article-title>Beneficial effect of the antioxidant riboflavin on gene expression of extracellular matirix elements, antioxidants and oxidases in keratoconic stromal cells</article-title><source>Clin. Exp. Optom.</source><year>2014</year><volume>97</volume><fpage>349</fpage><lpage>355</lpage><pub-id pub-id-type="pmid">24527696</pub-id></element-citation></ref><ref id="B13-ijms-21-00950"><label>13.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sanches</surname><given-names>S.C.</given-names></name><name><surname>Naira</surname><given-names>L.</given-names></name><name><surname>Ramalho</surname><given-names>Z.</given-names></name><name><surname>Mendes-Braz</surname><given-names>M.</given-names></name><name><surname>Terra</surname><given-names>V.A.</given-names></name><name><surname>Cecchini</surname><given-names>R.</given-names></name><name><surname>Augusto</surname><given-names>M.J.</given-names></name><name><surname>Ramalho</surname><given-names>F.S.</given-names></name></person-group><article-title>Riboflavin (vitamin B-2) reduces hepatocellular injury following liver ischaemia and reperfusion in mice</article-title><source>Food Chem. Toxicol.</source><year>2014</year><volume>67</volume><fpage>65</fpage><lpage>71</lpage><pub-id pub-id-type="doi">10.1016/j.fct.2014.02.013</pub-id><pub-id pub-id-type="pmid">24560968</pub-id></element-citation></ref><ref id="B14-ijms-21-00950"><label>14.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pompella</surname><given-names>A.</given-names></name><name><surname>Visvikis</surname><given-names>A.</given-names></name><name><surname>Paolicchi</surname><given-names>A.</given-names></name><name><surname>De Tata</surname><given-names>V.</given-names></name><name><surname>Casini</surname><given-names>A.F.</given-names></name></person-group><article-title>The changing faces of glutathione, a cellular protagonist</article-title><source>Biochem. Pharmacol.</source><year>2003</year><volume>66</volume><fpage>1499</fpage><lpage>1503</lpage><pub-id pub-id-type="doi">10.1016/S0006-2952(03)00504-5</pub-id><pub-id pub-id-type="pmid">14555227</pub-id></element-citation></ref><ref id="B15-ijms-21-00950"><label>15.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tripathi</surname><given-names>A.K.</given-names></name><name><surname>Dwivedi</surname><given-names>A.</given-names></name><name><surname>Pal</surname><given-names>M.K.</given-names></name><name><surname>Rastogi</surname><given-names>N.</given-names></name><name><surname>Gupta</surname><given-names>P.</given-names></name><name><surname>Ali</surname><given-names>S.</given-names></name><name><surname>Prabhu Bh</surname><given-names>M.</given-names></name><name><surname>Kushwaha</surname><given-names>H.N.</given-names></name><name><surname>Singh Ray</surname><given-names>R.</given-names></name><name><surname>Singh</surname><given-names>S.K.</given-names></name><etal></etal></person-group><article-title>Attenuated neuroprotective effect of riboflavin under UV-B irradiation via miR-203/c-Jun signaling pathway in vivo and in vitro</article-title><source>J. Biomed. Sci.</source><year>2014</year><volume>21</volume><fpage>1</fpage><lpage>10</lpage><pub-id pub-id-type="doi">10.1186/1423-0127-21-39</pub-id><pub-id pub-id-type="pmid">24397824</pub-id></element-citation></ref><ref id="B16-ijms-21-00950"><label>16.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>G.</given-names></name><name><surname>Li</surname><given-names>W.</given-names></name><name><surname>Lu</surname><given-names>X.</given-names></name><name><surname>Zhao</surname><given-names>X.</given-names></name></person-group><article-title>Riboflavin alleviates cardiac failure in Type I diabetic cardiomyopathy</article-title><source>Heart Int.</source><year>2011</year><volume>6</volume><fpage>75</fpage><lpage>80</lpage><pub-id pub-id-type="doi">10.4081/hi.2011.e21</pub-id></element-citation></ref><ref id="B17-ijms-21-00950"><label>17.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alam</surname><given-names>M.M.</given-names></name><name><surname>Iqbal</surname><given-names>S.</given-names></name><name><surname>Naseem</surname><given-names>I.</given-names></name></person-group><article-title>Ameliorative effect of riboflavin on hyperglycemia, oxidative stress and DNA damage in type-2 diabetic mice: Mechanistic and therapeutic strategies</article-title><source>Arch. Biochem. Biophys.</source><year>2015</year><volume>584</volume><fpage>10</fpage><lpage>19</lpage><pub-id pub-id-type="doi">10.1016/j.abb.2015.08.013</pub-id><pub-id pub-id-type="pmid">26319175</pub-id></element-citation></ref><ref id="B18-ijms-21-00950"><label>18.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Indumathi</surname><given-names>U.</given-names></name><name><surname>Kanchana</surname><given-names>K.</given-names></name><name><surname>Sachdanandam</surname><given-names>P.</given-names></name></person-group><article-title>Protective role of coenzyme Q10, riboflavin, niacin, selenium (CoRNS) and Emblica officinalis on cardiac abnormalities in experimental atherosclerosis</article-title><source>Biomed. Prev. Nutr.</source><year>2013</year><volume>3</volume><fpage>313</fpage><lpage>318</lpage><pub-id pub-id-type="doi">10.1016/j.bionut.2013.03.010</pub-id></element-citation></ref><ref id="B19-ijms-21-00950"><label>19.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nazıroğlu</surname><given-names>M.</given-names></name><name><surname>Çelik</surname><given-names>Ö.</given-names></name><name><surname>Uğuz</surname><given-names>A.C.</given-names></name><name><surname>Bütün</surname><given-names>A.</given-names></name></person-group><article-title>Protective effects of riboflavin and selenium on brain microsomal Ca2+-ATPase and oxidative damage caused by glyceryl trinitrate in a rat headache model</article-title><source>Biol. Trace Elem. Res.</source><year>2014</year><volume>164</volume><fpage>72</fpage><lpage>79</lpage><pub-id pub-id-type="doi">10.1007/s12011-014-0199-x</pub-id><pub-id pub-id-type="pmid">25492827</pub-id></element-citation></ref><ref id="B20-ijms-21-00950"><label>20.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bütün</surname><given-names>A.</given-names></name><name><surname>Nazıroğlu</surname><given-names>M.</given-names></name><name><surname>Demirci</surname><given-names>S.</given-names></name><name><surname>Çelik</surname><given-names>Ö.</given-names></name><name><surname>Uğuz</surname><given-names>A.C.</given-names></name></person-group><article-title>Riboflavin and vitamin E increase brain calcium and antioxidants, and microsomal calcium-ATP-ase values in rat headache models induced by glyceryl trinitrate</article-title><source>J. Membr. Biol.</source><year>2015</year><volume>248</volume><fpage>205</fpage><lpage>213</lpage><pub-id pub-id-type="pmid">25425044</pub-id></element-citation></ref><ref id="B21-ijms-21-00950"><label>21.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lin</surname><given-names>Y.</given-names></name><name><surname>Desbois</surname><given-names>A.</given-names></name><name><surname>Jiang</surname><given-names>S.</given-names></name><name><surname>Hou</surname><given-names>S.T.</given-names></name></person-group><article-title>Group B vitamins protect murine cerebellar granule cells from glutamate/NMDA toxicity</article-title><source>Neuroreport</source><year>2004</year><volume>15</volume><fpage>2241</fpage><lpage>2244</lpage><pub-id pub-id-type="doi">10.1097/00001756-200410050-00020</pub-id><pub-id pub-id-type="pmid">15371742</pub-id></element-citation></ref><ref id="B22-ijms-21-00950"><label>22.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hoane</surname><given-names>M.R.</given-names></name><name><surname>Wolyniak</surname><given-names>J.G.</given-names></name><name><surname>Akstulewicz</surname><given-names>S.L.</given-names></name></person-group><article-title>Administration of riboflavin improves behavioral outcome and reduces edema formation and glial fibrillary acidic protein expression after traumatic brain injury</article-title><source>J. Neurotrauma</source><year>2005</year><volume>22</volume><fpage>1112</fpage><lpage>1122</lpage><pub-id pub-id-type="doi">10.1089/neu.2005.22.1112</pub-id><pub-id pub-id-type="pmid">16238487</pub-id></element-citation></ref><ref id="B23-ijms-21-00950"><label>23.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barbre</surname><given-names>A.B.</given-names></name><name><surname>Hoane</surname><given-names>M.R.</given-names></name></person-group><article-title>Magnesium and riboflavin combination therapy following cortical contusion injury in the rat</article-title><source>Brain Res. Bull.</source><year>2006</year><volume>69</volume><fpage>639</fpage><lpage>646</lpage><pub-id pub-id-type="doi">10.1016/j.brainresbull.2006.03.009</pub-id><pub-id pub-id-type="pmid">16716831</pub-id></element-citation></ref><ref id="B24-ijms-21-00950"><label>24.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Seekamp</surname><given-names>A.</given-names></name><name><surname>Hultquist</surname><given-names>D.E.</given-names></name><name><surname>Till</surname><given-names>G.O.</given-names></name></person-group><article-title>Protection by vitamin B2 against oxidant-mediated acute lung injury</article-title><source>Inflammation</source><year>1999</year><volume>23</volume><fpage>449</fpage><lpage>460</lpage><pub-id pub-id-type="doi">10.1023/A:1021965026580</pub-id><pub-id pub-id-type="pmid">10466581</pub-id></element-citation></ref><ref id="B25-ijms-21-00950"><label>25.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Betz</surname><given-names>A.L.</given-names></name><name><surname>Ren</surname><given-names>X.D.</given-names></name><name><surname>Ennis</surname><given-names>S.R.</given-names></name><name><surname>Hultquist</surname><given-names>D.E.</given-names></name></person-group><article-title>Riboflavin reduces edema in focal cerebral ischemia</article-title><source>Acta Neurochir. Suppl. (Wien).</source><year>1994</year><volume>60</volume><fpage>314</fpage><lpage>317</lpage><pub-id pub-id-type="pmid">7976577</pub-id></element-citation></ref><ref id="B26-ijms-21-00950"><label>26.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mack</surname><given-names>C.P.</given-names></name><name><surname>Hultquist</surname><given-names>D.E.</given-names></name><name><surname>Shlafer</surname><given-names>M.</given-names></name></person-group><article-title>Myocardial flavin reductase and riboflavin: A potential role in decreasing reoxygenation injury</article-title><source>Biochem. Biophys. Res. Commun.</source><year>1995</year><volume>212</volume><fpage>35</fpage><lpage>40</lpage><pub-id pub-id-type="doi">10.1006/bbrc.1995.1932</pub-id><pub-id pub-id-type="pmid">7612015</pub-id></element-citation></ref><ref id="B27-ijms-21-00950"><label>27.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kulkarni</surname><given-names>A.G.</given-names></name><name><surname>Suryakar</surname><given-names>A.N.</given-names></name><name><surname>Sardeshmukh</surname><given-names>A.S.</given-names></name><name><surname>Rathi</surname><given-names>D.B.</given-names></name></person-group><article-title>Studies on biochemical changes with special reference to and antioxidants in malaria patients</article-title><source>Indian J. Clin. Biochem.</source><year>2003</year><volume>18</volume><fpage>136</fpage><lpage>149</lpage><pub-id pub-id-type="doi">10.1007/BF02867380</pub-id><pub-id pub-id-type="pmid">23105405</pub-id></element-citation></ref><ref id="B28-ijms-21-00950"><label>28.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Akompong</surname><given-names>T.</given-names></name><name><surname>Ghori</surname><given-names>N.</given-names></name><name><surname>Haldar</surname><given-names>K.</given-names></name></person-group><article-title>In vitro activity of riboflavin against the human malaria parasite Plasmodium falciparum</article-title><source>Antimicrob. Agents Chemother.</source><year>2000</year><volume>44</volume><fpage>88</fpage><lpage>96</lpage><pub-id pub-id-type="doi">10.1128/AAC.44.1.88-96.2000</pub-id><pub-id pub-id-type="pmid">10602728</pub-id></element-citation></ref><ref id="B29-ijms-21-00950"><label>29.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>George</surname><given-names>B.O.</given-names></name><name><surname>Ojegbemi</surname><given-names>O.</given-names></name></person-group><article-title>Oxidative stress and the effect of riboflavin supplementation in individuals with uncomplicated malaria infection</article-title><source>African J. Biotechnol.</source><year>2009</year><volume>8</volume><fpage>849</fpage><lpage>853</lpage></element-citation></ref><ref id="B30-ijms-21-00950"><label>30.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Araki</surname><given-names>S.</given-names></name><name><surname>Suzuki</surname><given-names>M.</given-names></name><name><surname>Fujimoto</surname><given-names>M.</given-names></name><name><surname>Kimura</surname><given-names>M.</given-names></name></person-group><article-title>Enhancement of resistance to bacterial infection in mice by vitamin b2</article-title><source>J. Vet. Med. Sci.</source><year>1995</year><volume>57</volume><fpage>599</fpage><lpage>602</lpage><pub-id pub-id-type="doi">10.1292/jvms.57.599</pub-id><pub-id pub-id-type="pmid">8519884</pub-id></element-citation></ref><ref id="B31-ijms-21-00950"><label>31.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mazur-Bialy</surname><given-names>A.I.</given-names></name><name><surname>Buchala</surname><given-names>B.</given-names></name><name><surname>Plytycz</surname><given-names>B.</given-names></name></person-group><article-title>Riboflavin deprivation inhibits macrophage viability and activity - a study on the RAW 264.7 cell line</article-title><source>Br. J. Nutr.</source><year>2013</year><volume>110</volume><fpage>509</fpage><lpage>514</lpage><pub-id pub-id-type="doi">10.1017/S0007114512005351</pub-id><pub-id pub-id-type="pmid">23415257</pub-id></element-citation></ref><ref id="B32-ijms-21-00950"><label>32.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Qureshi</surname><given-names>A.A.</given-names></name><name><surname>Reis</surname><given-names>J.C.</given-names></name><name><surname>Qureshi</surname><given-names>N.</given-names></name><name><surname>Papasian</surname><given-names>C.J.</given-names></name><name><surname>Morrison</surname><given-names>D.C.</given-names></name><name><surname>Schaefer</surname><given-names>D.M.</given-names></name></person-group><article-title>δ-Tocotrienol and quercetin reduce serum levels of nitric oxide and lipid parameters in female chickens</article-title><source>Lipids Health Dis.</source><year>2011</year><volume>10</volume><fpage>39</fpage><pub-id pub-id-type="doi">10.1186/1476-511X-10-39</pub-id><pub-id pub-id-type="pmid">21356098</pub-id></element-citation></ref><ref id="B33-ijms-21-00950"><label>33.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Verdrengh</surname><given-names>M.</given-names></name><name><surname>Tarkowski</surname><given-names>A.</given-names></name></person-group><article-title>Riboflavin in innate and acquired immune responses</article-title><source>Inflamm. Res.</source><year>2005</year><volume>9</volume><fpage>390</fpage><lpage>393</lpage><pub-id pub-id-type="doi">10.1007/s00011-005-1372-7</pub-id><pub-id pub-id-type="pmid">16273338</pub-id></element-citation></ref><ref id="B34-ijms-21-00950"><label>34.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Iwanaga</surname><given-names>K.</given-names></name><name><surname>Hasegawa</surname><given-names>T.</given-names></name><name><surname>Hultquist</surname><given-names>D.E.</given-names></name><name><surname>Harada</surname><given-names>H.</given-names></name><name><surname>Yoshikawa</surname><given-names>Y.</given-names></name><name><surname>Yanamadala</surname><given-names>S.</given-names></name><name><surname>Liao</surname><given-names>H.</given-names></name><name><surname>Visovatti</surname><given-names>S.H.</given-names></name><name><surname>Pinsky</surname><given-names>D.J.</given-names></name></person-group><article-title>Riboflavin-mediated reduction of oxidant injury, rejection, and vasculopathy after cardiac allotransplantation</article-title><source>Transplantation</source><year>2007</year><volume>83</volume><fpage>747</fpage><lpage>753</lpage><pub-id pub-id-type="doi">10.1097/01.tp.0000256283.06469.d4</pub-id><pub-id pub-id-type="pmid">17414708</pub-id></element-citation></ref><ref id="B35-ijms-21-00950"><label>35.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Qureshi</surname><given-names>A.A.</given-names></name><name><surname>Tan</surname><given-names>X.</given-names></name><name><surname>Reis</surname><given-names>J.C.</given-names></name><name><surname>Badr</surname><given-names>M.Z.</given-names></name><name><surname>Papasian</surname><given-names>C.J.</given-names></name><name><surname>Morrison</surname><given-names>D.C.</given-names></name><name><surname>Qureshi</surname><given-names>N.</given-names></name></person-group><article-title>Suppression of nitric oxide induction and pro-inflammatory cytokines by novel proteasome inhibitors in various experimental models</article-title><source>Lipids Health Dis.</source><year>2011</year><volume>10</volume><fpage>1</fpage><lpage>25</lpage><pub-id pub-id-type="doi">10.1186/1476-511X-10-177</pub-id><pub-id pub-id-type="pmid">21992595</pub-id></element-citation></ref><ref id="B36-ijms-21-00950"><label>36.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bertollo</surname><given-names>C.M.</given-names></name><name><surname>Oliveira</surname><given-names>A.C.P.</given-names></name><name><surname>Rocha</surname><given-names>L.T.S.</given-names></name><name><surname>Costa</surname><given-names>K.A.</given-names></name><name><surname>Nascimento</surname><given-names>E.B.</given-names></name><name><surname>Coelho</surname><given-names>M.M.</given-names></name></person-group><article-title>Characterization of the antinociceptive and anti-inflammatory activities of riboflavin in different experimental models</article-title><source>Eur. J. Pharmacol.</source><year>2006</year><volume>547</volume><fpage>184</fpage><lpage>191</lpage><pub-id pub-id-type="doi">10.1016/j.ejphar.2006.07.045</pub-id><pub-id pub-id-type="pmid">16962092</pub-id></element-citation></ref><ref id="B37-ijms-21-00950"><label>37.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>França</surname><given-names>D.S.</given-names></name><name><surname>Souza</surname><given-names>A.L.S.</given-names></name><name><surname>Almeida</surname><given-names>K.R.</given-names></name><name><surname>Dolabella</surname><given-names>S.S.</given-names></name><name><surname>Martinelli</surname><given-names>C.</given-names></name><name><surname>Coelho</surname><given-names>M.M.</given-names></name></person-group><article-title>B vitamins induce an antinociceptive effect in the acetic acid and formaldehyde models of nociception in mice</article-title><source>Eur. J. Pharmacol.</source><year>2001</year><volume>421</volume><fpage>157</fpage><lpage>164</lpage><pub-id pub-id-type="doi">10.1016/S0014-2999(01)01038-X</pub-id><pub-id pub-id-type="pmid">11516431</pub-id></element-citation></ref><ref id="B38-ijms-21-00950"><label>38.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mazur-Bialy</surname><given-names>A.I.</given-names></name><name><surname>Majka</surname><given-names>A.</given-names></name><name><surname>Wojtas</surname><given-names>L.</given-names></name><name><surname>Kolaczkowska</surname><given-names>E.</given-names></name><name><surname>Plytycz</surname><given-names>B.</given-names></name></person-group><article-title>Strain-specific effects of riboflavin supplementation on zymosan-induced peritonitis in C57BL/6J, BALB/c and CBA mice</article-title><source>Life Sci.</source><year>2011</year><volume>88</volume><fpage>265</fpage><lpage>271</lpage><pub-id pub-id-type="doi">10.1016/j.lfs.2010.11.016</pub-id><pub-id pub-id-type="pmid">21115019</pub-id></element-citation></ref><ref id="B39-ijms-21-00950"><label>39.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mazur</surname><given-names>A.I.</given-names></name><name><surname>Natorska</surname><given-names>J.</given-names></name><name><surname>Wypasek</surname><given-names>E.</given-names></name><name><surname>Kołaczkowska</surname><given-names>E.</given-names></name><name><surname>Płytycz</surname><given-names>B.</given-names></name></person-group><article-title>Anti-inflammatory effects of riboflavin and morphine on zymosan-induced peritonitis in Swiss mice</article-title><source>Cent. J. Immunol.</source><year>2008</year><volume>33</volume><fpage>98</fpage><lpage>101</lpage></element-citation></ref><ref id="B40-ijms-21-00950"><label>40.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mazur-Bialy</surname><given-names>A.I.</given-names></name><name><surname>Kolaczkowska</surname><given-names>E.</given-names></name><name><surname>Plytycz</surname><given-names>B.</given-names></name></person-group><article-title>Modulation of zymosan-induced peritonitis by riboflavin co-injection, pre-injection or post-injection in male Swiss mice</article-title><source>Life Sci.</source><year>2012</year><volume>91</volume><fpage>1351</fpage><lpage>1357</lpage><pub-id pub-id-type="doi">10.1016/j.lfs.2012.10.016</pub-id><pub-id pub-id-type="pmid">23123448</pub-id></element-citation></ref><ref id="B41-ijms-21-00950"><label>41.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Granados-Soto</surname><given-names>V.</given-names></name><name><surname>Terán-Rosales</surname><given-names>F.</given-names></name><name><surname>Rocha-González</surname><given-names>H.I.</given-names></name><name><surname>Reyes-García</surname><given-names>G.</given-names></name><name><surname>Medina-Santillán</surname><given-names>R.</given-names></name><name><surname>Rodríguez-Silverio</surname><given-names>J.</given-names></name><name><surname>Flores-Murrieta</surname><given-names>F.J.</given-names></name></person-group><article-title>Riboflavin reduces hyperalgesia and inflammation but not tactile allodynia in the rat</article-title><source>Eur. J. Pharmacol.</source><year>2004</year><volume>492</volume><fpage>35</fpage><lpage>40</lpage><pub-id pub-id-type="doi">10.1016/j.ejphar.2004.03.043</pub-id><pub-id pub-id-type="pmid">15145703</pub-id></element-citation></ref><ref id="B42-ijms-21-00950"><label>42.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Toyosawa</surname><given-names>T.</given-names></name><name><surname>Suzuki</surname><given-names>M.</given-names></name><name><surname>Kodama</surname><given-names>K.</given-names></name><name><surname>Araki</surname><given-names>S.</given-names></name></person-group><article-title>Highly Purified Vitamin B2 Presents a Promising Therapeutic Strategy for Sepsis and Septic Shock</article-title><source>Infect. Immun.</source><year>2004</year><volume>72</volume><fpage>1820</fpage><lpage>1823</lpage><pub-id pub-id-type="doi">10.1128/IAI.72.3.1820-1823.2004</pub-id><pub-id pub-id-type="pmid">14977995</pub-id></element-citation></ref><ref id="B43-ijms-21-00950"><label>43.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kodama</surname><given-names>K.</given-names></name><name><surname>Suzuki</surname><given-names>M.</given-names></name><name><surname>Toyosawa</surname><given-names>T.</given-names></name><name><surname>Araki</surname><given-names>S.</given-names></name></person-group><article-title>Inhibitory mechanisms of highly purified vitamin B2 on the productions of proinflammatory cytokine and NO in endotoxin-induced shock in mice</article-title><source>Life Sci.</source><year>2005</year><volume>78</volume><fpage>134</fpage><lpage>139</lpage><pub-id pub-id-type="doi">10.1016/j.lfs.2005.04.037</pub-id><pub-id pub-id-type="pmid">16112685</pub-id></element-citation></ref><ref id="B44-ijms-21-00950"><label>44.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shih</surname><given-names>C.K.</given-names></name><name><surname>Chen</surname><given-names>C.M.</given-names></name><name><surname>Chen</surname><given-names>C.Y.O.</given-names></name><name><surname>Liu</surname><given-names>J.F.</given-names></name><name><surname>Lin</surname><given-names>H.W.</given-names></name><name><surname>Chou</surname><given-names>H.T.</given-names></name><name><surname>Li</surname><given-names>S.C.</given-names></name></person-group><article-title>Riboflavin protects mice against liposaccharide-induced shock through expression of heat shock protein 25</article-title><source>Food Chem. Toxicol.</source><year>2010</year><volume>48</volume><fpage>1913</fpage><lpage>1918</lpage><pub-id pub-id-type="doi">10.1016/j.fct.2010.04.033</pub-id><pub-id pub-id-type="pmid">20430062</pub-id></element-citation></ref><ref id="B45-ijms-21-00950"><label>45.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Al-Harbi</surname><given-names>N.O.</given-names></name><name><surname>Imam</surname><given-names>F.</given-names></name><name><surname>Nadeem</surname><given-names>A.</given-names></name><name><surname>Al-Harbi</surname><given-names>M.M.</given-names></name><name><surname>Korashy</surname><given-names>H.M.</given-names></name><name><surname>Sayed-Ahmed</surname><given-names>M.M.</given-names></name><name><surname>Hafez</surname><given-names>M.M.</given-names></name><name><surname>Al-Shabanah</surname><given-names>O.A.</given-names></name><name><surname>Nagi</surname><given-names>M.N.</given-names></name><name><surname>Bahashwan</surname><given-names>S.</given-names></name></person-group><article-title>Riboflavin attenuates lipopolysaccharide-induced lung injury in rats</article-title><source>Toxicol. Mech. Methods</source><year>2015</year><volume>25</volume><fpage>417</fpage><lpage>423</lpage><pub-id pub-id-type="doi">10.3109/15376516.2015.1045662</pub-id><pub-id pub-id-type="pmid">26360969</pub-id></element-citation></ref><ref id="B46-ijms-21-00950"><label>46.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mazur-bialy</surname><given-names>A.I.</given-names></name><name><surname>Pochec</surname><given-names>E.</given-names></name></person-group><article-title>HMGB1 inhibition during zymosan-induced inflammation: The potential therapeutic action of riboflavin</article-title><source>Arch. Immunol. Ther. Exp.</source><year>2015</year><fpage>1</fpage><lpage>6</lpage><pub-id pub-id-type="doi">10.1007/s00005-015-0366-6</pub-id></element-citation></ref><ref id="B47-ijms-21-00950"><label>47.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>X.-H.</given-names></name><name><surname>Yin</surname><given-names>Y.-J.</given-names></name><name><surname>Zhang</surname><given-names>J.-X.</given-names></name></person-group><article-title>Sepsis and immune response</article-title><source>World J. Emerg. Med.</source><year>2011</year><volume>2</volume><fpage>88</fpage><lpage>92</lpage><pub-id pub-id-type="doi">10.5847/wjem.j.1920-8642.2011.02.002</pub-id><pub-id pub-id-type="pmid">25214990</pub-id></element-citation></ref><ref id="B48-ijms-21-00950"><label>48.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mal</surname><given-names>P.</given-names></name><name><surname>Ghosh</surname><given-names>D.</given-names></name><name><surname>Bandyopadhyay</surname><given-names>D.</given-names></name><name><surname>Dutta</surname><given-names>K.</given-names></name><name><surname>Bishayi</surname><given-names>B.</given-names></name></person-group><article-title>Ampicillin alone and in combination with riboflavin modulates Staphylococcus aureus infection induced septic arthritis in mice</article-title><source>Indian J. Exp. Biol.</source><year>2012</year><volume>50</volume><fpage>677</fpage><lpage>689</lpage><pub-id pub-id-type="pmid">23214260</pub-id></element-citation></ref><ref id="B49-ijms-21-00950"><label>49.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dey</surname><given-names>S.</given-names></name><name><surname>Bishayi</surname><given-names>B.</given-names></name></person-group><article-title>Riboflavin along with antibiotics balances reactive oxygen species and inflammatory cytokines and controls Staphylococcus aureus infection by boosting murine macrophage function and regulates inflammation</article-title><source>J. Inflamm.</source><year>2016</year><volume>13</volume><fpage>36</fpage><pub-id pub-id-type="doi">10.1186/s12950-016-0145-0</pub-id></element-citation></ref><ref id="B50-ijms-21-00950"><label>50.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mal</surname><given-names>P.</given-names></name><name><surname>Dutta</surname><given-names>K.</given-names></name><name><surname>Bandyopadhyay</surname><given-names>D.</given-names></name><name><surname>Basu</surname><given-names>A.</given-names></name><name><surname>Khan</surname><given-names>R.</given-names></name><name><surname>Bishayi</surname><given-names>B.</given-names></name></person-group><article-title>Azithromycin in combination with riboflavin decreases the severity of Staphylococcus aureus infection induced septic arthritis by modulating the production of free radicals and endogenous cytokines</article-title><source>Inflamm. Res.</source><year>2013</year><volume>62</volume><fpage>259</fpage><lpage>273</lpage><pub-id pub-id-type="doi">10.1007/s00011-012-0574-z</pub-id><pub-id pub-id-type="pmid">23229721</pub-id></element-citation></ref><ref id="B51-ijms-21-00950"><label>51.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schramm</surname><given-names>M.</given-names></name><name><surname>Wiegmann</surname><given-names>K.</given-names></name><name><surname>Schramm</surname><given-names>S.</given-names></name><name><surname>Gluschko</surname><given-names>A.</given-names></name><name><surname>Herb</surname><given-names>M.</given-names></name><name><surname>Utermöhlen</surname><given-names>O.</given-names></name><name><surname>Krönke</surname><given-names>M.</given-names></name></person-group><article-title>Riboflavin (vitamin B2) deficiency impairs NADPH oxidase 2 (Nox2) priming and defense against Listeria monocytogenes</article-title><source>Eur. J. Immunol.</source><year>2014</year><volume>44</volume><fpage>728</fpage><lpage>741</lpage><pub-id pub-id-type="doi">10.1002/eji.201343940</pub-id><pub-id pub-id-type="pmid">24272050</pub-id></element-citation></ref><ref id="B52-ijms-21-00950"><label>52.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wooley</surname><given-names>J.G.</given-names></name><name><surname>Sebrell</surname><given-names>W.</given-names></name></person-group><article-title>Nutritional deficiency and infection: I. influence of riboflavin or thiamin deficiency on fatal experimental pneumococcal infection in white mice</article-title><source>Public Health Rep.</source><year>1942</year><volume>57</volume><fpage>149</fpage><lpage>161</lpage><pub-id pub-id-type="doi">10.2307/4583995</pub-id><pub-id pub-id-type="pmid">19315854</pub-id></element-citation></ref><ref id="B53-ijms-21-00950"><label>53.</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Thaimuta</surname><given-names>Z.L.</given-names></name></person-group><article-title>Riboflavin protective role against mitochondrial toxicity and lipodystrophy due to stavudine and lamivudine</article-title><source>Ph.D. Thesis</source><publisher-name>University of Nairobi</publisher-name><publisher-loc>Eldoret, Kenya</publisher-loc><year>2014</year></element-citation></ref><ref id="B54-ijms-21-00950"><label>54.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Corbin</surname><given-names>F.</given-names></name></person-group><article-title>Pathogen inactivation of blood components: Current status and introduction of an approach using riboflavin as a photosensitizer</article-title><source>Int. J. Hematol.</source><year>2002</year><volume>76</volume><issue>Suppl. S2</issue><fpage>253</fpage><lpage>257</lpage><pub-id pub-id-type="doi">10.1007/BF03165125</pub-id><pub-id pub-id-type="pmid">12430933</pub-id></element-citation></ref><ref id="B55-ijms-21-00950"><label>55.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ruane</surname><given-names>P.H.</given-names></name><name><surname>Edrich</surname><given-names>R.</given-names></name><name><surname>Gampp</surname><given-names>D.</given-names></name><name><surname>Keil</surname><given-names>S.D.</given-names></name><name><surname>Leonard</surname><given-names>R.L.</given-names></name><name><surname>Goodrich</surname><given-names>R.P.</given-names></name></person-group><article-title>Photochemical inactivation of selected viruses and bacteria in platelet concentrates using riboflavin and light</article-title><source>Transfusion</source><year>2004</year><volume>44</volume><fpage>877</fpage><lpage>885</lpage><pub-id pub-id-type="doi">10.1111/j.1537-2995.2004.03355.x</pub-id><pub-id pub-id-type="pmid">15157255</pub-id></element-citation></ref><ref id="B56-ijms-21-00950"><label>56.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cardo</surname><given-names>L.J.</given-names></name><name><surname>Rentas</surname><given-names>F.J.</given-names></name><name><surname>Ketchum</surname><given-names>L.</given-names></name><name><surname>Salata</surname><given-names>J.</given-names></name><name><surname>Harman</surname><given-names>R.</given-names></name><name><surname>Melvin</surname><given-names>W.</given-names></name><name><surname>Weina</surname><given-names>P.J.</given-names></name><name><surname>Mendez</surname><given-names>J.</given-names></name><name><surname>Reddy</surname><given-names>H.</given-names></name><name><surname>Goodrich</surname><given-names>R.</given-names></name></person-group><article-title>Pathogen inactivation of Leishmania donovani infantum in plasma and platelet concentrates using riboflavin and ultraviolet light</article-title><source>Vox Sang.</source><year>2006</year><volume>90</volume><fpage>85</fpage><lpage>91</lpage><pub-id pub-id-type="doi">10.1111/j.1423-0410.2005.00736.x</pub-id><pub-id pub-id-type="pmid">16430665</pub-id></element-citation></ref><ref id="B57-ijms-21-00950"><label>57.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pelletier</surname><given-names>J.P.R.</given-names></name><name><surname>Transue</surname><given-names>S.</given-names></name><name><surname>Snyder</surname><given-names>E.L.</given-names></name></person-group><article-title>Pathogen inactivation techniques</article-title><source>Best Pract. Res. Clin. Haematol.</source><year>2006</year><volume>19</volume><fpage>205</fpage><lpage>242</lpage><pub-id pub-id-type="doi">10.1016/j.beha.2005.04.001</pub-id><pub-id pub-id-type="pmid">16377551</pub-id></element-citation></ref><ref id="B58-ijms-21-00950"><label>58.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shrubsole</surname><given-names>M.J.</given-names></name><name><surname>Shu</surname><given-names>X.O.</given-names></name><name><surname>Li</surname><given-names>H.L.</given-names></name><name><surname>Cai</surname><given-names>H.</given-names></name><name><surname>Yang</surname><given-names>G.</given-names></name><name><surname>Gao</surname><given-names>Y.T.</given-names></name><name><surname>Gao</surname><given-names>J.</given-names></name><name><surname>Zheng</surname><given-names>W.</given-names></name></person-group><article-title>Dietary B vitamin and methionine intakes and breast cancer risk among Chinese women</article-title><source>Am. J. Epidemiol.</source><year>2011</year><volume>173</volume><fpage>1171</fpage><lpage>1182</lpage><pub-id pub-id-type="doi">10.1093/aje/kwq491</pub-id><pub-id pub-id-type="pmid">21447479</pub-id></element-citation></ref><ref id="B59-ijms-21-00950"><label>59.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chaves Neto</surname><given-names>A.H.</given-names></name><name><surname>Pelizzaro-Rocha</surname><given-names>K.J.</given-names></name><name><surname>Fernandes</surname><given-names>M.N.</given-names></name><name><surname>Ferreira-Halder</surname><given-names>C.V.</given-names></name></person-group><article-title>Antitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-O</article-title><source>Tumor Biol.</source><year>2015</year><volume>36</volume><fpage>595</fpage><lpage>604</lpage><pub-id pub-id-type="doi">10.1007/s13277-014-2675-5</pub-id></element-citation></ref><ref id="B60-ijms-21-00950"><label>60.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Machado</surname><given-names>D.</given-names></name><name><surname>Shishido</surname><given-names>S.M.</given-names></name><name><surname>Queiroz</surname><given-names>K.C.S.</given-names></name><name><surname>Oliveira</surname><given-names>D.N.</given-names></name><name><surname>Faria</surname><given-names>A.L.C.</given-names></name><name><surname>Catharino</surname><given-names>R.R.</given-names></name><name><surname>Spek</surname><given-names>C.A.</given-names></name><name><surname>Ferreira</surname><given-names>C.V.</given-names></name></person-group><article-title>Irradiated riboflavin diminishes the aggressiveness of melanoma in vitro and in vivo</article-title><source>PLoS ONE</source><year>2013</year><volume>8</volume><fpage>1</fpage><lpage>12</lpage><pub-id pub-id-type="doi">10.1371/journal.pone.0054269</pub-id></element-citation></ref><ref id="B61-ijms-21-00950"><label>61.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>De Vogel</surname><given-names>S.</given-names></name><name><surname>Dindore</surname><given-names>V.</given-names></name><name><surname>van Engeland</surname><given-names>M.</given-names></name><name><surname>Goldbohm</surname><given-names>R.A.</given-names></name><name><surname>van den Brandt</surname><given-names>P.A.</given-names></name><name><surname>Weijenberg</surname><given-names>M.P.</given-names></name></person-group><article-title>Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectalc cancer</article-title><source>J. Nutr.</source><year>2008</year><volume>138</volume><fpage>2372</fpage><lpage>2378</lpage><pub-id pub-id-type="doi">10.3945/jn.108.091157</pub-id><pub-id pub-id-type="pmid">19022960</pub-id></element-citation></ref><ref id="B62-ijms-21-00950"><label>62.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zschäbitz</surname><given-names>S.</given-names></name><name><surname>Cheng</surname><given-names>T.D.</given-names></name><name><surname>Neuhouser</surname><given-names>M.L.</given-names></name><name><surname>Zheng</surname><given-names>Y.</given-names></name><name><surname>Ray</surname><given-names>R.M.</given-names></name><name><surname>Miller</surname><given-names>J.W.</given-names></name><name><surname>Song</surname><given-names>X.</given-names></name><name><surname>Maneval</surname><given-names>D.R.</given-names></name><name><surname>Beresford</surname><given-names>S.A.A.</given-names></name><name><surname>Lane</surname><given-names>D.</given-names></name><etal></etal></person-group><article-title>B vitamin intakes and incidence of colorectal cancer: Results from the women’s health initiative observational study cohort</article-title><source>Am. J. Clin. Nutr.</source><year>2013</year><volume>97</volume><fpage>332</fpage><lpage>343</lpage><pub-id pub-id-type="pmid">23255571</pub-id></element-citation></ref><ref id="B63-ijms-21-00950"><label>63.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kabat</surname><given-names>G.C.</given-names></name><name><surname>Miller</surname><given-names>A.B.</given-names></name><name><surname>Jain</surname><given-names>M.</given-names></name><name><surname>Rohan</surname><given-names>T.E.</given-names></name></person-group><article-title>Dietary intake of selected B vitamins in relation to risk of major cancers in women</article-title><source>Br. J. Cancer</source><year>2008</year><volume>99</volume><fpage>816</fpage><lpage>821</lpage><pub-id pub-id-type="doi">10.1038/sj.bjc.6604540</pub-id><pub-id pub-id-type="pmid">18665162</pub-id></element-citation></ref><ref id="B64-ijms-21-00950"><label>64.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Takata</surname><given-names>Y.</given-names></name><name><surname>Cai</surname><given-names>Q.</given-names></name><name><surname>Beeghly-Fadiel</surname><given-names>A.</given-names></name><name><surname>Li</surname><given-names>H.</given-names></name><name><surname>Shrubsole</surname><given-names>M.J.</given-names></name><name><surname>Ji</surname><given-names>B.T.</given-names></name><name><surname>Yang</surname><given-names>G.</given-names></name><name><surname>Chow</surname><given-names>W.H.</given-names></name><name><surname>Gao</surname><given-names>Y.T.</given-names></name><name><surname>Zheng</surname><given-names>W.</given-names></name><etal></etal></person-group><article-title>Dietary B vitamin and methionine intakes and lung cancer risk among female never smokers in China</article-title><source>Cancer Causes Control</source><year>2012</year><volume>23</volume><fpage>1965</fpage><lpage>1975</lpage><pub-id pub-id-type="doi">10.1007/s10552-012-0074-z</pub-id><pub-id pub-id-type="pmid">23065072</pub-id></element-citation></ref><ref id="B65-ijms-21-00950"><label>65.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hernandez</surname><given-names>B.Y.</given-names></name><name><surname>McDuffie</surname><given-names>K.</given-names></name><name><surname>Wilkens</surname><given-names>L.R.</given-names></name><name><surname>Kamemoto</surname><given-names>L.</given-names></name><name><surname>Goodman</surname><given-names>M.T.</given-names></name></person-group><article-title>Diet and premalignant lesions of the cervix: Evidence of a protective role for folate, riboflavin, thiamin, and vitamin B12</article-title><source>Cancer Causes Control</source><year>2003</year><volume>14</volume><fpage>859</fpage><lpage>870</lpage><pub-id pub-id-type="doi">10.1023/B:CACO.0000003841.54413.98</pub-id><pub-id pub-id-type="pmid">14682443</pub-id></element-citation></ref><ref id="B66-ijms-21-00950"><label>66.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Powers</surname><given-names>H.J.</given-names></name></person-group><article-title>Interaction among folate, riboflavin, genotype, and cancer, with reference to colorectal and cervical cancer</article-title><source>J. Nutr.</source><year>2005</year><volume>135</volume><fpage>2960S</fpage><lpage>2966S</lpage><pub-id pub-id-type="doi">10.1093/jn/135.12.2960S</pub-id><pub-id pub-id-type="pmid">16317155</pub-id></element-citation></ref><ref id="B67-ijms-21-00950"><label>67.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rivlin</surname><given-names>R.S.</given-names></name></person-group><article-title>Riboflavin and cancer: A review</article-title><source>Cancer Res.</source><year>1973</year><volume>33</volume><fpage>1977</fpage><lpage>1986</lpage><pub-id pub-id-type="pmid">4579772</pub-id></element-citation></ref><ref id="B68-ijms-21-00950"><label>68.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Foy</surname><given-names>H.</given-names></name><name><surname>Kondi</surname><given-names>A.</given-names></name><name><surname>Verjee</surname><given-names>Z.H.M.</given-names></name></person-group><article-title>Relation of riboflavin deficiency to corticosteroid metabolism and red cell hypoplasia in baboons</article-title><source>J. Nutr.</source><year>1972</year><volume>102</volume><fpage>571</fpage><lpage>582</lpage><pub-id pub-id-type="doi">10.1093/jn/102.4.571</pub-id><pub-id pub-id-type="pmid">4622279</pub-id></element-citation></ref><ref id="B69-ijms-21-00950"><label>69.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bareford</surname><given-names>L.M.</given-names></name><name><surname>Phelps</surname><given-names>M.A.</given-names></name><name><surname>Foraker</surname><given-names>A.B.</given-names></name><name><surname>Swaan</surname><given-names>P.W.</given-names></name></person-group><article-title>Intracellular processing of riboflavin in human breast cancer cells</article-title><source>Mol. Pharm.</source><year>2008</year><volume>5</volume><fpage>839</fpage><lpage>848</lpage><pub-id pub-id-type="doi">10.1021/mp800046m</pub-id><pub-id pub-id-type="pmid">18754669</pub-id></element-citation></ref><ref id="B70-ijms-21-00950"><label>70.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Webster</surname><given-names>R.P.</given-names></name><name><surname>Gawde</surname><given-names>M.D.</given-names></name><name><surname>Bhattacharya</surname><given-names>R.K.</given-names></name></person-group><article-title>Modulation of carcinogen-induced DNA damage and repair enzyme activity by dietary riboflavin</article-title><source>Cancer Lett.</source><year>1996</year><volume>98</volume><fpage>129</fpage><lpage>135</lpage><pub-id pub-id-type="doi">10.1016/S0304-3835(06)80022-4</pub-id><pub-id pub-id-type="pmid">8556699</pub-id></element-citation></ref><ref id="B71-ijms-21-00950"><label>71.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hassan</surname><given-names>I.</given-names></name><name><surname>Chibber</surname><given-names>S.</given-names></name><name><surname>Naseem</surname><given-names>I.</given-names></name></person-group><article-title>Vitamin B2: A promising adjuvant in cisplatin based chemoradiotherapy by cellular redox management</article-title><source>Food Chem. Toxicol.</source><year>2013</year><volume>59</volume><fpage>715</fpage><lpage>723</lpage><pub-id pub-id-type="doi">10.1016/j.fct.2013.07.018</pub-id><pub-id pub-id-type="pmid">23872133</pub-id></element-citation></ref><ref id="B72-ijms-21-00950"><label>72.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Naseem</surname><given-names>I.</given-names></name><name><surname>Hassan</surname><given-names>I.</given-names></name><name><surname>Alhazza</surname><given-names>I.M.</given-names></name><name><surname>Chibber</surname><given-names>S.</given-names></name></person-group><article-title>Protective effect of riboflavin on cisplatin induced toxicities: A gender-dependent study</article-title><source>J. Trace Elem. Med. Biol.</source><year>2015</year><volume>29</volume><fpage>303</fpage><lpage>314</lpage><pub-id pub-id-type="doi">10.1016/j.jtemb.2014.08.003</pub-id><pub-id pub-id-type="pmid">25242266</pub-id></element-citation></ref><ref id="B73-ijms-21-00950"><label>73.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Xuan</surname><given-names>Z.</given-names></name><name><surname>An</surname><given-names>Y.</given-names></name><name><surname>Yang</surname><given-names>D.</given-names></name><name><surname>Wang</surname><given-names>S.</given-names></name><name><surname>Xu</surname><given-names>Q.</given-names></name><name><surname>Yuan</surname><given-names>S.</given-names></name></person-group><article-title>Exploration of the protection of riboflavin laurate on oral mucositis induced by chemotherapy or radiotherapy at the cellular level: What is the leading contributor?</article-title><source>Int. J. Mol. Sci.</source><year>2013</year><volume>14</volume><fpage>4722</fpage><lpage>4733</lpage><pub-id pub-id-type="doi">10.3390/ijms14034722</pub-id><pub-id pub-id-type="pmid">23446867</pub-id></element-citation></ref><ref id="B74-ijms-21-00950"><label>74.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Al-Harbi</surname><given-names>N.O.</given-names></name><name><surname>Imam</surname><given-names>F.</given-names></name><name><surname>Nadeem</surname><given-names>A.</given-names></name><name><surname>Al-Harbi</surname><given-names>M.M.</given-names></name><name><surname>Iqbal</surname><given-names>M.</given-names></name><name><surname>Ahmad</surname><given-names>S.F.</given-names></name></person-group><article-title>Carbon tetrachloride-induced hepatotoxicity in rat is reversed by treatment with riboflavin</article-title><source>Int. Immunopharmacol.</source><year>2014</year><volume>21</volume><fpage>383</fpage><lpage>388</lpage><pub-id pub-id-type="doi">10.1016/j.intimp.2014.05.014</pub-id><pub-id pub-id-type="pmid">24874442</pub-id></element-citation></ref><ref id="B75-ijms-21-00950"><label>75.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thakur</surname><given-names>K.</given-names></name><name><surname>Tomar</surname><given-names>S.K.</given-names></name><name><surname>Singh</surname><given-names>A.K.</given-names></name><name><surname>Mandal</surname><given-names>S.</given-names></name><name><surname>Arora</surname><given-names>S.</given-names></name><name><surname>Division</surname><given-names>D.M.</given-names></name><name><surname>Division</surname><given-names>D.T.</given-names></name><name><surname>Division</surname><given-names>D.C.</given-names></name><name><surname>Microbiology</surname><given-names>D.</given-names></name></person-group><article-title>Riboflavin and health: A review of recent human research</article-title><source>Crit. Rev. Food Sci. Nutr.</source><year>2017</year><volume>57</volume><fpage>3650</fpage><lpage>3660</lpage><pub-id pub-id-type="doi">10.1080/10408398.2016.1145104</pub-id><pub-id pub-id-type="pmid">27029320</pub-id></element-citation></ref><ref id="B76-ijms-21-00950"><label>76.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sparaco</surname><given-names>M.</given-names></name><name><surname>Feleppa</surname><given-names>M.</given-names></name><name><surname>Lipton</surname><given-names>R.B.</given-names></name><name><surname>Rapoport</surname><given-names>A.M.</given-names></name><name><surname>Bigal</surname><given-names>M.E.</given-names></name></person-group><article-title>Mitochondrial dysfunction and migraine: Evidence and hypotheses</article-title><source>Cephalalgia</source><year>2006</year><volume>26</volume><fpage>361</fpage><lpage>372</lpage><pub-id pub-id-type="doi">10.1111/j.1468-2982.2005.01059.x</pub-id><pub-id pub-id-type="pmid">16556237</pub-id></element-citation></ref><ref id="B77-ijms-21-00950"><label>77.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sherwood</surname><given-names>M.</given-names></name><name><surname>Goldman</surname><given-names>R.D.</given-names></name></person-group><article-title>Effectiveness of riboflavin in pediatric migraine prevention</article-title><source>Can. Fam. Physician</source><year>2014</year><volume>60</volume><fpage>244</fpage><lpage>246</lpage><pub-id pub-id-type="pmid">24627379</pub-id></element-citation></ref><ref id="B78-ijms-21-00950"><label>78.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Condó</surname><given-names>M.</given-names></name><name><surname>Posar</surname><given-names>A.</given-names></name><name><surname>Arbizzani</surname><given-names>A.</given-names></name><name><surname>Parmeggiani</surname><given-names>A.</given-names></name></person-group><article-title>Riboflavin prophylaxis in pediatric and adolescent migraine</article-title><source>J. Headache Pain</source><year>2009</year><volume>10</volume><fpage>361</fpage><lpage>365</lpage><pub-id pub-id-type="doi">10.1007/s10194-009-0142-2</pub-id><pub-id pub-id-type="pmid">19649688</pub-id></element-citation></ref><ref id="B79-ijms-21-00950"><label>79.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Maizels</surname><given-names>M.</given-names></name><name><surname>Blumenfeld</surname><given-names>A.</given-names></name><name><surname>Burchette</surname><given-names>R.</given-names></name></person-group><article-title>A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: A randomized trial</article-title><source>Headache</source><year>2004</year><volume>44</volume><fpage>885</fpage><lpage>890</lpage><pub-id pub-id-type="doi">10.1111/j.1526-4610.2004.04170.x</pub-id><pub-id pub-id-type="pmid">15447697</pub-id></element-citation></ref><ref id="B80-ijms-21-00950"><label>80.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gaul</surname><given-names>C.</given-names></name><name><surname>Diener</surname><given-names>H.-C.</given-names></name><name><surname>Danesch</surname><given-names>U.</given-names></name></person-group><article-title>Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: A randomized, placebo-controlled, double-blind, multicenter trial</article-title><source>J. Headache Pain</source><year>2015</year><volume>16</volume><fpage>516</fpage><pub-id pub-id-type="doi">10.1186/s10194-015-0516-6</pub-id><pub-id pub-id-type="pmid">25916335</pub-id></element-citation></ref><ref id="B81-ijms-21-00950"><label>81.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jacques</surname><given-names>P.F.</given-names></name><name><surname>Chylack</surname><given-names>L.T.</given-names></name><name><surname>Hankinson</surname><given-names>S.E.</given-names></name><name><surname>Khu</surname><given-names>P.M.</given-names></name><name><surname>Rogers</surname><given-names>G.</given-names></name><name><surname>Friend</surname><given-names>J.</given-names></name><name><surname>Tung</surname><given-names>W.</given-names></name><name><surname>Wolfe</surname><given-names>J.K.</given-names></name><name><surname>Padhye</surname><given-names>N.</given-names></name><name><surname>Willett</surname><given-names>W.C.</given-names></name><etal></etal></person-group><article-title>Long-term nutrient intake and early age-related nuclear lens opacities</article-title><source>Arch. Ophthalmol.</source><year>2001</year><volume>119</volume><fpage>1009</fpage><lpage>1019</lpage><pub-id pub-id-type="doi">10.1001/archopht.119.7.1009</pub-id><pub-id pub-id-type="pmid">11448323</pub-id></element-citation></ref><ref id="B82-ijms-21-00950"><label>82.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Skalka</surname><given-names>H.W.</given-names></name><name><surname>Prchal</surname><given-names>J.T.</given-names></name></person-group><article-title>Cataracts and riboflavin deficiency</article-title><source>Am. J. Clin. Nutr.</source><year>1981</year><volume>34</volume><fpage>861</fpage><lpage>863</lpage><pub-id pub-id-type="doi">10.1093/ajcn/34.5.861</pub-id><pub-id pub-id-type="pmid">7234715</pub-id></element-citation></ref><ref id="B83-ijms-21-00950"><label>83.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>SEETHARAM BHAT</surname><given-names>K.</given-names></name></person-group><article-title>Nutritional status of thiamin riboflavin and pyridoxine in cataract patients</article-title><source>Nutr. Rep. Int.</source><year>1987</year><volume>36</volume><fpage>685</fpage><lpage>692</lpage></element-citation></ref><ref id="B84-ijms-21-00950"><label>84.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chocano-bedoya</surname><given-names>P.O.</given-names></name><name><surname>Manson</surname><given-names>J.E.</given-names></name><name><surname>Hankinson</surname><given-names>S.E.</given-names></name><name><surname>Willett</surname><given-names>W.C.</given-names></name><name><surname>Johnson</surname><given-names>S.R.</given-names></name><name><surname>Chasan-taber</surname><given-names>L.</given-names></name><name><surname>Ronnenberg</surname><given-names>A.G.</given-names></name><name><surname>Bigelow</surname><given-names>C.</given-names></name><name><surname>Bertone-johnson</surname><given-names>E.R.</given-names></name></person-group><article-title>Dietary B vitamin intake and incident premenstrual syndrome</article-title><source>Am. J. Clin. Nutr.</source><year>2011</year><volume>93</volume><fpage>1080</fpage><lpage>1086</lpage><pub-id pub-id-type="doi">10.3945/ajcn.110.009530</pub-id><pub-id pub-id-type="pmid">21346091</pub-id></element-citation></ref><ref id="B85-ijms-21-00950"><label>85.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chaves Neto</surname><given-names>A.H.</given-names></name><name><surname>Yano</surname><given-names>C.L.</given-names></name><name><surname>Paredes-Gamero</surname><given-names>E.J.</given-names></name><name><surname>Machado</surname><given-names>D.</given-names></name><name><surname>Justo</surname><given-names>G.Z.</given-names></name><name><surname>Peppelenbosch</surname><given-names>M.P.</given-names></name><name><surname>Ferreira</surname><given-names>C.V.</given-names></name></person-group><article-title>Riboflavin and photoproducts in MC3T3-E1 differentiation</article-title><source>Toxicol. Vitr.</source><year>2010</year><volume>24</volume><fpage>1911</fpage><lpage>1919</lpage><pub-id pub-id-type="doi">10.1016/j.tiv.2010.07.026</pub-id><pub-id pub-id-type="pmid">20688149</pub-id></element-citation></ref><ref id="B86-ijms-21-00950"><label>86.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ogunleye</surname><given-names>A.J.</given-names></name><name><surname>Odutuga</surname><given-names>A.A.</given-names></name></person-group><article-title>The effect of riboflavin deficiency on cerebrum and cerebellum of developing rat brain</article-title><source>J. Nutr. Sci. Vitaminol. (Tokyo).</source><year>1989</year><volume>35</volume><fpage>193</fpage><lpage>197</lpage><pub-id pub-id-type="doi">10.3177/jnsv.35.193</pub-id><pub-id pub-id-type="pmid">2760691</pub-id></element-citation></ref><ref id="B87-ijms-21-00950"><label>87.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Foley</surname><given-names>A.R.</given-names></name><name><surname>Menezes</surname><given-names>M.P.</given-names></name><name><surname>Pandraud</surname><given-names>A.</given-names></name><name><surname>Gonzalez</surname><given-names>M.A.</given-names></name><name><surname>Al-Odaib</surname><given-names>A.</given-names></name><name><surname>Abrams</surname><given-names>A.J.</given-names></name><name><surname>Sugano</surname><given-names>K.</given-names></name><name><surname>Yonezawa</surname><given-names>A.</given-names></name><name><surname>Manzur</surname><given-names>A.Y.</given-names></name><name><surname>Burns</surname><given-names>J.</given-names></name><etal></etal></person-group><article-title>Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2</article-title><source>Brain A J. Neurol.</source><year>2014</year><volume>137</volume><fpage>44</fpage><lpage>56</lpage><pub-id pub-id-type="doi">10.1093/brain/awt315</pub-id></element-citation></ref><ref id="B88-ijms-21-00950"><label>88.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Boisvert</surname><given-names>W.A.</given-names></name><name><surname>Castañeda</surname><given-names>C.</given-names></name><name><surname>Mendoza</surname><given-names>I.</given-names></name><name><surname>Langeloh</surname><given-names>G.</given-names></name><name><surname>Solomons</surname><given-names>N.W.</given-names></name><name><surname>Gershoff</surname><given-names>S.N.</given-names></name><name><surname>Russell</surname><given-names>R.M.</given-names></name></person-group><article-title>Prevalence of riboflavin deficiency among Guatemalan elderly people and its relationship to milk intake</article-title><source>Am. J. Clin. Nutr.</source><year>1993</year><volume>58</volume><fpage>85</fpage><lpage>90</lpage><pub-id pub-id-type="doi">10.1093/ajcn/58.1.85</pub-id><pub-id pub-id-type="pmid">8317395</pub-id></element-citation></ref><ref id="B89-ijms-21-00950"><label>89.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Powers</surname><given-names>H.J.</given-names></name><name><surname>Weaver</surname><given-names>L.T.</given-names></name><name><surname>Austin</surname><given-names>S.</given-names></name><name><surname>Beresford</surname><given-names>J.K.</given-names></name></person-group><article-title>A proposed intestinal mechanism for the effect of riboflavin deficiency on iron loss in the rat</article-title><source>Br. J. Nutr.</source><year>1993</year><volume>69</volume><fpage>553</fpage><lpage>561</lpage><pub-id pub-id-type="doi">10.1079/BJN19930055</pub-id><pub-id pub-id-type="pmid">8490008</pub-id></element-citation></ref><ref id="B90-ijms-21-00950"><label>90.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Powers</surname><given-names>H.J.</given-names></name><name><surname>Bates</surname><given-names>C.J.</given-names></name><name><surname>Prentice</surname><given-names>A.M.</given-names></name><name><surname>Lamb</surname><given-names>W.H.</given-names></name><name><surname>Jepson</surname><given-names>M.</given-names></name><name><surname>Bowman</surname><given-names>H.</given-names></name></person-group><article-title>The relative effectiveness of iron and iron with riboflavin in correcting a microcytic anaemia in men and children in rural Gambia</article-title><source>Hum. Nutr. Clin. Nutr.</source><year>1983</year><volume>37</volume><fpage>413</fpage><lpage>425</lpage><pub-id pub-id-type="pmid">6668226</pub-id></element-citation></ref><ref id="B91-ijms-21-00950"><label>91.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Powers</surname><given-names>H.J.</given-names></name><name><surname>Hill</surname><given-names>M.H.</given-names></name><name><surname>Mushtaq</surname><given-names>S.</given-names></name><name><surname>Dainty</surname><given-names>J.R.</given-names></name><name><surname>Majsak-Newman</surname><given-names>G.</given-names></name><name><surname>Williams</surname><given-names>E.A.</given-names></name></person-group><article-title>Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM)</article-title><source>Am. J. Clin. Nutr.</source><year>2011</year><volume>93</volume><fpage>1274</fpage><lpage>1284</lpage><pub-id pub-id-type="doi">10.3945/ajcn.110.008409</pub-id><pub-id pub-id-type="pmid">21525198</pub-id></element-citation></ref><ref id="B92-ijms-21-00950"><label>92.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lopez</surname><given-names>A.D.</given-names></name><name><surname>Mathers</surname><given-names>C.D.</given-names></name><name><surname>Ezzati</surname><given-names>M.</given-names></name><name><surname>Jamison</surname><given-names>D.T.</given-names></name><name><surname>Murray</surname><given-names>C.J.</given-names></name></person-group><article-title>Global and regional burden of disease and risk factors, 2001: Systematic analysis of population health data</article-title><source>Lancet</source><year>2006</year><volume>367</volume><fpage>1747</fpage><lpage>1757</lpage><pub-id pub-id-type="doi">10.1016/S0140-6736(06)68770-9</pub-id><pub-id pub-id-type="pmid">16731270</pub-id></element-citation></ref><ref id="B93-ijms-21-00950"><label>93.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lawes</surname><given-names>C.M.M.</given-names></name><name><surname>Vander Hoorn</surname><given-names>S.</given-names></name><name><surname>Rodgers</surname><given-names>A.</given-names></name></person-group><article-title>Global burden of blood-pressure-related disease, 2001</article-title><source>Lancet</source><year>2008</year><volume>371</volume><fpage>1513</fpage><lpage>1518</lpage><pub-id pub-id-type="doi">10.1016/S0140-6736(08)60655-8</pub-id><pub-id pub-id-type="pmid">18456100</pub-id></element-citation></ref><ref id="B94-ijms-21-00950"><label>94.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>França</surname><given-names>C.F.</given-names></name><name><surname>Vianna</surname><given-names>L.M.</given-names></name></person-group><article-title>The response of young and adult rats to the riboflavin supplementation</article-title><source>Braz. Arch. Biol. Technol.</source><year>2010</year><volume>53</volume><fpage>855</fpage><lpage>860</lpage><pub-id pub-id-type="doi">10.1590/S1516-89132010000400015</pub-id></element-citation></ref><ref id="B95-ijms-21-00950"><label>95.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Leblanc</surname><given-names>J.G.</given-names></name><name><surname>Laiño</surname><given-names>J.E.</given-names></name><name><surname>del Valle</surname><given-names>M.J.</given-names></name><name><surname>Vannini</surname><given-names>V.</given-names></name><name><surname>van Sinderen</surname><given-names>D.</given-names></name><name><surname>Taranto</surname><given-names>M.P.</given-names></name><name><surname>de Valdez</surname><given-names>G.F.</given-names></name><name><surname>de Giori</surname><given-names>G.S.</given-names></name><name><surname>Sesma</surname><given-names>F.</given-names></name></person-group><article-title>B-Group vitamin production by lactic acid bacteria—Current knowledge and potential applications</article-title><source>J. Appl. Microbiol.</source><year>2011</year><volume>111</volume><fpage>1297</fpage><lpage>1309</lpage><pub-id pub-id-type="doi">10.1111/j.1365-2672.2011.05157.x</pub-id><pub-id pub-id-type="pmid">21933312</pub-id></element-citation></ref><ref id="B96-ijms-21-00950"><label>96.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mensink</surname><given-names>G.B.M.</given-names></name><name><surname>Fletcher</surname><given-names>R.</given-names></name><name><surname>Gurinovic</surname><given-names>M.</given-names></name><name><surname>Huybrechts</surname><given-names>I.</given-names></name><name><surname>Lafay</surname><given-names>L.</given-names></name><name><surname>Serra-Majem</surname><given-names>L.</given-names></name><name><surname>Szponar</surname><given-names>L.</given-names></name><name><surname>Tetens</surname><given-names>I.</given-names></name><name><surname>Verkaik-Kloosterman</surname><given-names>J.</given-names></name><name><surname>Baka</surname><given-names>A.</given-names></name><etal></etal></person-group><article-title>Mapping low intake of micronutrients across Europe</article-title><source>Br. J. Nutr.</source><year>2013</year><volume>110</volume><fpage>755</fpage><lpage>773</lpage><pub-id pub-id-type="doi">10.1017/S000711451200565X</pub-id><pub-id pub-id-type="pmid">23312136</pub-id></element-citation></ref><ref id="B97-ijms-21-00950"><label>97.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Flynn</surname><given-names>A.</given-names></name><name><surname>Moreiras</surname><given-names>O.</given-names></name><name><surname>Stehle</surname><given-names>P.</given-names></name><name><surname>Fletcher</surname><given-names>R.J.</given-names></name><name><surname>Müller</surname><given-names>D.J.G.</given-names></name><name><surname>Rolland</surname><given-names>V.</given-names></name></person-group><article-title>Vitamins and minerals: A model for safe addition to foods</article-title><source>Eur. J. Nutr.</source><year>2003</year><volume>42</volume><fpage>118</fpage><lpage>130</lpage><pub-id pub-id-type="doi">10.1007/s00394-003-0391-9</pub-id><pub-id pub-id-type="pmid">12638033</pub-id></element-citation></ref><ref id="B98-ijms-21-00950"><label>98.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ashoori</surname><given-names>M.</given-names></name><name><surname>Saedisomeolia</surname><given-names>A.</given-names></name></person-group><article-title>Riboflavin (vitamin B2) and oxidative stress: A review</article-title><source>Br. J. Nutr.</source><year>2014</year><volume>111</volume><fpage>1985</fpage><lpage>1991</lpage><pub-id pub-id-type="doi">10.1017/S0007114514000178</pub-id><pub-id pub-id-type="pmid">24650639</pub-id></element-citation></ref><ref id="B99-ijms-21-00950"><label>99.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>LeBlanc</surname><given-names>J.G.</given-names></name><name><surname>Burgess</surname><given-names>C.</given-names></name><name><surname>Sesma</surname><given-names>F.</given-names></name><name><surname>de Giori</surname><given-names>G.S.</given-names></name><name><surname>van Sinderen</surname><given-names>D.</given-names></name></person-group><article-title>Ingestion of milk fermented by genetically modified Lactococcus lactis improves the riboflavin status of deficient rats</article-title><source>J. Dairy Sci.</source><year>2005</year><volume>88</volume><fpage>3435</fpage><lpage>3442</lpage><pub-id pub-id-type="doi">10.3168/jds.S0022-0302(05)73027-7</pub-id><pub-id pub-id-type="pmid">16162516</pub-id></element-citation></ref><ref id="B100-ijms-21-00950"><label>100.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Capozzi</surname><given-names>V.</given-names></name><name><surname>Menga</surname><given-names>V.</given-names></name><name><surname>Digesù</surname><given-names>A.M.</given-names></name><name><surname>De Vita</surname><given-names>P.</given-names></name><name><surname>Van Sinderen</surname><given-names>D.</given-names></name><name><surname>Cattivelli</surname><given-names>L.</given-names></name><name><surname>Fares</surname><given-names>C.</given-names></name><name><surname>Spano</surname><given-names>G.</given-names></name></person-group><article-title>Biotechnological production of vitamin B2-enriched bread and pasta</article-title><source>J. Agric. Food Chem.</source><year>2011</year><volume>59</volume><fpage>8013</fpage><lpage>8020</lpage><pub-id pub-id-type="doi">10.1021/jf201519h</pub-id><pub-id pub-id-type="pmid">21678896</pub-id></element-citation></ref><ref id="B101-ijms-21-00950"><label>101.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Juarez del Valle</surname><given-names>M.</given-names></name><name><surname>Laiño</surname><given-names>J.E.</given-names></name><name><surname>Savoy de Giori</surname><given-names>G.</given-names></name><name><surname>LeBlanc</surname><given-names>J.G.</given-names></name></person-group><article-title>Riboflavin producing lactic acid bacteria as a biotechnological strategy to obtain bio-enriched soymilk</article-title><source>Food Res. Int.</source><year>2014</year><volume>62</volume><fpage>1015</fpage><lpage>1019</lpage><pub-id pub-id-type="doi">10.1016/j.foodres.2014.05.029</pub-id></element-citation></ref><ref id="B102-ijms-21-00950"><label>102.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Russo</surname><given-names>P.</given-names></name><name><surname>de Chiara</surname><given-names>M.L.V.</given-names></name><name><surname>Capozzi</surname><given-names>V.</given-names></name><name><surname>Arena</surname><given-names>M.P.</given-names></name><name><surname>Amodio</surname><given-names>M.L.</given-names></name><name><surname>Rascón</surname><given-names>A.</given-names></name><name><surname>Dueñas</surname><given-names>M.T.</given-names></name><name><surname>López</surname><given-names>P.</given-names></name><name><surname>Spano</surname><given-names>G.</given-names></name></person-group><article-title>Lactobacillus plantarum strains for multifunctional oat-based foods</article-title><source>LWT Food Sci. Technol.</source><year>2016</year><volume>68</volume><fpage>288</fpage><lpage>294</lpage><pub-id pub-id-type="doi">10.1016/j.lwt.2015.12.040</pub-id></element-citation></ref><ref id="B103-ijms-21-00950"><label>103.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Russo</surname><given-names>P.</given-names></name><name><surname>Capozzi</surname><given-names>V.</given-names></name><name><surname>Arena</surname><given-names>M.P.</given-names></name><name><surname>Spadaccino</surname><given-names>G.</given-names></name><name><surname>Dueñas</surname><given-names>M.T.</given-names></name><name><surname>López</surname><given-names>P.</given-names></name><name><surname>Fiocco</surname><given-names>D.</given-names></name><name><surname>Spano</surname><given-names>G.</given-names></name></person-group><article-title>Riboflavin-overproducing strains of Lactobacillus fermentum for riboflavin-enriched bread</article-title><source>Appl. Microbiol. Biotechnol.</source><year>2014</year><volume>98</volume><fpage>3691</fpage><lpage>3700</lpage><pub-id pub-id-type="doi">10.1007/s00253-013-5484-7</pub-id><pub-id pub-id-type="pmid">24413973</pub-id></element-citation></ref><ref id="B104-ijms-21-00950"><label>104.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Burgess</surname><given-names>C.M.</given-names></name><name><surname>Smid</surname><given-names>E.J.</given-names></name><name><surname>Rutten</surname><given-names>G.</given-names></name><name><surname>van Sinderen</surname><given-names>D.</given-names></name></person-group><article-title>A general method for selection of riboflavin-overproducing food grade micro-organisms</article-title><source>Microb. Cell Fact.</source><year>2006</year><volume>5</volume><fpage>1</fpage><lpage>12</lpage><pub-id pub-id-type="doi">10.1186/1475-2859-5-24</pub-id><pub-id pub-id-type="pmid">16396686</pub-id></element-citation></ref><ref id="B105-ijms-21-00950"><label>105.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>LeBlanc</surname><given-names>J.G.</given-names></name><name><surname>Rutten</surname><given-names>G.</given-names></name><name><surname>Bruinenberg</surname><given-names>P.</given-names></name><name><surname>Sesma</surname><given-names>F.</given-names></name><name><surname>de Giori</surname><given-names>G.S.</given-names></name><name><surname>Smid</surname><given-names>E.J.</given-names></name></person-group><article-title>A novel dairy product fermented with Propionibacterium freudenreichii improves the riboflavin status of deficient rats</article-title><source>Nutrition</source><year>2006</year><volume>22</volume><fpage>645</fpage><lpage>651</lpage><pub-id pub-id-type="doi">10.1016/j.nut.2006.01.002</pub-id><pub-id pub-id-type="pmid">16533593</pub-id></element-citation></ref><ref id="B106-ijms-21-00950"><label>106.</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Berry Ottaway</surname><given-names>P.</given-names></name></person-group><article-title>Stability of vitamins during food processing and storage</article-title><source>Chemical Deterioration and Physical Instability of Food and Beverages</source><publisher-name>Elsevier</publisher-name><publisher-loc>Amsterdam, The Netherlands</publisher-loc><year>2010</year><fpage>539</fpage><lpage>560</lpage></element-citation></ref><ref id="B107-ijms-21-00950"><label>107.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bou</surname><given-names>R.</given-names></name><name><surname>Cofrades</surname><given-names>S.</given-names></name><name><surname>Jiménez-Colmenero</surname><given-names>F.</given-names></name></person-group><article-title>Physicochemical properties and riboflavin encapsulation in double emulsions with different lipid sources</article-title><source>LWT Food Sci. Technol.</source><year>2014</year><volume>59</volume><fpage>621</fpage><lpage>628</lpage><pub-id pub-id-type="doi">10.1016/j.lwt.2014.06.044</pub-id></element-citation></ref><ref id="B108-ijms-21-00950"><label>108.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>L.</given-names></name><name><surname>Subirade</surname><given-names>M.</given-names></name></person-group><article-title>Alginate-whey protein granular microspheres as oral delivery vehicles for bioactive compounds</article-title><source>Biomaterials</source><year>2006</year><volume>27</volume><fpage>4646</fpage><lpage>4654</lpage><pub-id pub-id-type="doi">10.1016/j.biomaterials.2006.04.037</pub-id><pub-id pub-id-type="pmid">16714058</pub-id></element-citation></ref><ref id="B109-ijms-21-00950"><label>109.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>L.</given-names></name><name><surname>Subirade</surname><given-names>M.</given-names></name></person-group><article-title>Effect of preparation conditions on the nutrient release properties of alginate-whey protein granular microspheres</article-title><source>Eur. J. Pharm. Biopharm.</source><year>2007</year><volume>65</volume><fpage>354</fpage><lpage>362</lpage><pub-id pub-id-type="doi">10.1016/j.ejpb.2006.10.012</pub-id><pub-id pub-id-type="pmid">17150342</pub-id></element-citation></ref><ref id="B110-ijms-21-00950"><label>110.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>O’Neill</surname><given-names>G.J.</given-names></name><name><surname>Jacquier</surname><given-names>J.C.</given-names></name><name><surname>Mukhopadhya</surname><given-names>A.</given-names></name><name><surname>Egan</surname><given-names>T.</given-names></name><name><surname>O’Sullivan</surname><given-names>M.</given-names></name><name><surname>Sweeney</surname><given-names>T.</given-names></name><name><surname>O’Riordan</surname><given-names>E.D.</given-names></name></person-group><article-title>In vitro and in vivo evaluation of whey protein hydrogels for oral delivery of riboflavin</article-title><source>J. Funct. Foods</source><year>2015</year><volume>19</volume><fpage>512</fpage><lpage>521</lpage><pub-id pub-id-type="doi">10.1016/j.jff.2015.09.043</pub-id></element-citation></ref><ref id="B111-ijms-21-00950"><label>111.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hu</surname><given-names>H.</given-names></name><name><surname>Zhu</surname><given-names>X.</given-names></name><name><surname>Hu</surname><given-names>T.</given-names></name><name><surname>Cheung</surname><given-names>I.W.Y.</given-names></name><name><surname>Pan</surname><given-names>S.</given-names></name><name><surname>Li-Chan</surname><given-names>E.C.Y.</given-names></name></person-group><article-title>Effect of ultrasound pre-treatment on formation of transglutaminase-catalysed soy protein hydrogel as a riboflavin vehicle for functional foods</article-title><source>J. Funct. Foods</source><year>2015</year><volume>19</volume><fpage>182</fpage><lpage>193</lpage><pub-id pub-id-type="doi">10.1016/j.jff.2015.09.023</pub-id></element-citation></ref><ref id="B112-ijms-21-00950"><label>112.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Azevedo</surname><given-names>M.A.</given-names></name><name><surname>Bourbon</surname><given-names>A.I.</given-names></name><name><surname>Vicente</surname><given-names>A.A.</given-names></name><name><surname>Cerqueira</surname><given-names>M.A.</given-names></name></person-group><article-title>Alginate/chitosan nanoparticles for encapsulation and controlled release of vitamin B2</article-title><source>Int. J. Biol. Macromol.</source><year>2014</year><volume>71</volume><fpage>141</fpage><lpage>146</lpage><pub-id pub-id-type="doi">10.1016/j.ijbiomac.2014.05.036</pub-id><pub-id pub-id-type="pmid">24863916</pub-id></element-citation></ref><ref id="B113-ijms-21-00950"><label>113.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jin</surname><given-names>B.</given-names></name><name><surname>Zhou</surname><given-names>X.</given-names></name><name><surname>Li</surname><given-names>X.</given-names></name><name><surname>Lin</surname><given-names>W.</given-names></name><name><surname>Chen</surname><given-names>G.</given-names></name><name><surname>Qiu</surname><given-names>R.</given-names></name></person-group><article-title>Self-assembled modified soy protein/dextran nanogel induced by ultrasonication as a delivery vehicle for riboflavin</article-title><source>Molecules</source><year>2016</year><volume>21</volume><elocation-id>282</elocation-id><pub-id pub-id-type="doi">10.3390/molecules21030282</pub-id><pub-id pub-id-type="pmid">26999081</pub-id></element-citation></ref><ref id="B114-ijms-21-00950"><label>114.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>P.</given-names></name><name><surname>Zhao</surname><given-names>S.R.</given-names></name><name><surname>Li</surname><given-names>J.X.</given-names></name><name><surname>Hong</surname><given-names>L.</given-names></name><name><surname>Raja</surname><given-names>M.A.</given-names></name><name><surname>Yu</surname><given-names>L.J.</given-names></name><name><surname>Liu</surname><given-names>C.G.</given-names></name></person-group><article-title>Nanoparticles based on phenylalanine ethyl ester-alginate conjugate asvVitamin B2 delivery system</article-title><source>J. Biomater. Appl.</source><year>2016</year><volume>31</volume><fpage>13</fpage><lpage>22</lpage><pub-id pub-id-type="doi">10.1177/0885328216630497</pub-id><pub-id pub-id-type="pmid">26916950</pub-id></element-citation></ref><ref id="B115-ijms-21-00950"><label>115.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Couto</surname><given-names>R.</given-names></name><name><surname>Alvarez</surname><given-names>V.</given-names></name><name><surname>Temelli</surname><given-names>F.</given-names></name></person-group><article-title>Encapsulation of vitamin B2 in solid lipid nanoparticles using supercritical CO2</article-title><source>J. Supercrit. Fluids</source><year>2017</year><volume>120</volume><fpage>432</fpage><lpage>442</lpage><pub-id pub-id-type="doi">10.1016/j.supflu.2016.05.036</pub-id></element-citation></ref><ref id="B116-ijms-21-00950"><label>116.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Suwannasom</surname><given-names>N.</given-names></name><name><surname>Smuda</surname><given-names>K.</given-names></name><name><surname>Kloypan</surname><given-names>C.</given-names></name><name><surname>Kaewprayoon</surname><given-names>W.</given-names></name><name><surname>Baisaeng</surname><given-names>N.</given-names></name><name><surname>Prapan</surname><given-names>A.</given-names></name><name><surname>Chaiwaree</surname><given-names>S.</given-names></name><name><surname>Georgieva</surname><given-names>R.</given-names></name><name><surname>Bäumler</surname><given-names>H.</given-names></name><name><surname>Suwannasom</surname><given-names>N.</given-names></name><etal></etal></person-group><article-title>Albumin Submicron Particles with Entrapped Riboflavin—Fabrication and Characterization</article-title><source>Nanomaterials</source><year>2019</year><volume>9</volume><elocation-id>482</elocation-id><pub-id pub-id-type="doi">10.3390/nano9030482</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="ijms-21-00950-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Structure of (<bold>a</bold>) Riboflavin (RF), (<bold>b</bold>) Flavin monophosphate (FMN), and (<bold>c</bold>) Flavin adenine dinucleotide (FAD). ChemDraw (PerkinElmer Informatics, Inc. MA, USA).</p></caption><graphic xlink:href="ijms-21-00950-g001"></graphic></fig><fig id="ijms-21-00950-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>RF is an essential vitamin for multiple physiological aspects in the body.</p></caption><graphic xlink:href="ijms-21-00950-g002"></graphic></fig><fig id="ijms-21-00950-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Flavin adenine dinucleotide (FAD) activates the glutathione reductase (GR) by transferring hydrogen for conversion of glutathione disulfide (GSSG) to glutathione (GSH).</p></caption><graphic xlink:href="ijms-21-00950-g003"></graphic></fig><fig id="ijms-21-00950-f004" orientation="portrait" position="float"><label>Figure 4</label><caption><p>RF is converted by RFK into FMN and FAD, which is essential cofactor the phagocytic NADPH oxidase 2 (Nox2) to generate ROS. Therefore, RF deficiency is incapable of ROS production by the phagocyte Nox2, which is crucial to inactivate phagocytosed microbes and to regulate the inflammatory response in innate immune cells. TNF, tumor necrosis factor; TNFR1, tumor necrosis factor receptor 1.</p></caption><graphic xlink:href="ijms-21-00950-g004"></graphic></fig><fig id="ijms-21-00950-f005" orientation="portrait" position="float"><label>Figure 5</label><caption><p>Activation of NADPH oxidase and microbicidal systems during phagocytosis. Complement and antibody receptors (CRs and FcRs) promote the uptake of micro-organisms by neutrophils, which, in turn, trigger the degranulation and production of ROS.</p></caption><graphic xlink:href="ijms-21-00950-g005"></graphic></fig><fig id="ijms-21-00950-f006" orientation="portrait" position="float"><label>Figure 6</label><caption><p>Role of RF as an adjuvant in cisplatin based chemo radiotherapy [<xref rid="B75-ijms-21-00950" ref-type="bibr">75</xref>]. RF stimulates apoptotic factors and downregulates anti-apoptotic factors. Additionally, it activates p53, which also results in an amplification of apoptosis. The inhibitory effects of RF in respect to the deteriorate effect of cisplatin are also shown. On the one hand, it inhibits the downregulation of antioxidant enzymes and proteins; on the other, RF downregulates pro-inflammatory cytokines.</p></caption><graphic xlink:href="ijms-21-00950-g006"></graphic></fig><fig id="ijms-21-00950-f007" orientation="portrait" position="float"><label>Figure 7</label><caption><p>Implications of RF deficiency on health [<xref rid="B75-ijms-21-00950" ref-type="bibr">75</xref>].</p></caption><graphic xlink:href="ijms-21-00950-g007"></graphic></fig><fig id="ijms-21-00950-f008" orientation="portrait" position="float"><label>Figure 8</label><caption><p>Conversion oxidized glutathione (GSSG) to the reduced form (GSH) by glutathione reductase requires RF in the FAD co-enzyme form for its activity. G-6P-D, glucose-6-phosphate dehydrogenase [<xref rid="B98-ijms-21-00950" ref-type="bibr">98</xref>].</p></caption><graphic xlink:href="ijms-21-00950-g008"></graphic></fig><fig id="ijms-21-00950-f009" orientation="portrait" position="float"><label>Figure 9</label><caption><p>RF in functional food and encapsulation products.</p></caption><graphic xlink:href="ijms-21-00950-g009"></graphic></fig><table-wrap id="ijms-21-00950-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">ijms-21-00950-t001_Table 1</object-id><label>Table 1</label><caption><p>Flavin content of selected human body fluids (mol L<sup>−1</sup>) and organs (mol per kg of dry matter) [<xref rid="B1-ijms-21-00950" ref-type="bibr">1</xref>].</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"></th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Riboflavin</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">FAD</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">FMN</th></tr></thead><tbody><tr><td align="center" valign="middle" rowspan="1" colspan="1">Skin</td><td align="center" valign="middle" rowspan="1" colspan="1">7.6 × 10<sup>−6</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">—</td><td align="center" valign="middle" rowspan="1" colspan="1">—</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Cerebral cortex</td><td align="center" valign="middle" rowspan="1" colspan="1">7.2 × 10<sup>−6</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">—</td><td align="center" valign="middle" rowspan="1" colspan="1">—</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Myocardium</td><td align="center" valign="middle" rowspan="1" colspan="1">3.2 × 10<sup>−5</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">—</td><td align="center" valign="middle" rowspan="1" colspan="1">—</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Pectoral muscle</td><td align="center" valign="middle" rowspan="1" colspan="1">7.2 × 10<sup>−6</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">—</td><td align="center" valign="middle" rowspan="1" colspan="1">—</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Aortic tissue</td><td align="center" valign="middle" rowspan="1" colspan="1">4.8 × 10<sup>−7</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">9.7 × 10<sup>−7</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">2.2 × 10<sup>−7</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Erythrocyte</td><td align="center" valign="middle" rowspan="1" colspan="1">1.4 × 10<sup>−7</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">4.3 × 10<sup>−7</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">2.8 × 10<sup>−8</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Plasma</td><td align="center" valign="middle" rowspan="1" colspan="1">1.0 × 10<sup>−8</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">6.3 × 10<sup>−8</sup></td><td align="center" valign="middle" rowspan="1" colspan="1">7.5 × 10<sup>−9</sup></td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Eye-fluid</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">4.5 × 10<sup>−6</sup></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">—</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">—</td></tr></tbody></table></table-wrap><table-wrap id="ijms-21-00950-t004" orientation="portrait" position="float"><object-id pub-id-type="pii">ijms-21-00950-t004_Table 4</object-id><label>Table 4</label><caption><p>Antinociception and anti-inflammation effects of RF in animal model.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Animal Model</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">RF Doses/Models</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Major Outcome</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Inflammation-Related Pain</bold></td><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"></td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Acetic acid-induced abdominal constructions, formaldehyde-induced nociceptive response and hot-plate models in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 3–100 mg/kg i.p. injection 1 h before acetic acid-induced model, RF at 6 or12 mg/kg i.p. injection 1 h before formaldehyde-induced nociceptive response, and RF at 50 mg/kg i.p. injection 1 h before formaldehyde-induced hindpaw edema</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">A dose-dependent RF inhibited the nociceptive response produced by acetic acid. Pre-treatment RF remarkably reduced the acute nociceptive response induced by formaldehyde in the second phase, but not in the hot-plate model. RF moderately inhibited formaldehyde-induced hindpaw edema.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B37-ijms-21-00950" ref-type="bibr">37</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Formalin-induced and carrageenan-induced paw edema, and spinal nerve ligation models in rat</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 1–50 mg/kg oral administration 30 min before formalin test and 6.25–150 mg/kg immediately after carrageenan injection</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Second phase treatment with RF produced a significant dose-dependent inhibition in flinching behavior produced by formalin and RF at 25 mg/kg dose had peak antinociceptive effect in formalin-induced model. RF reduced hyperalgesic effect, highest effect at 75 mg/kg dose. In addition, a dose- and time-dependent RF treatment reduced by carrageenan-induced edema, but not tactile allodynia in the spinal nerve ligation models. Moreover, antinociceptive effect of RF can be reversed by glibenclamide and NG-L-nitro-aeginie methyl ester.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B41-ijms-21-00950" ref-type="bibr">41</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Formalin-induced nociceptive response, carrageenan-induced paw edema, LPS-induced febrile response, and cotton pellet-induced formation of fibrovascular tissue models in rat</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 25, 50, 100 mg/kg i.p. injection 30 min before formalin-induced nociceptive response, carrageenan-induced paw edema, RF at 50 or 100 mg/kg immediately or 2 hr after LPS-induced the febrile response, and RF at 50 or 100 mg/kg i.p. 7 days after s.c. implantation of a cotton pellet-induced fibrovascular tissue</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF inhibited the nociceptive response in the mouse formalin test, markedly in second phase. RF was dose-dependently reduced the mechanical allodynia and the paw edema induced by carrageenan and inhibited the fever induced by LPS. Moreover, the formation of fibrovascular tissue induced by s.c. implant of a cotton pellet was inhibited. Therefore, RF prevents prolonged inflammatory response.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B36-ijms-21-00950" ref-type="bibr">36</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Zymosan-induced peritonitis in Swiss mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 20, 50, 100 mg/kg i.p. injection 30 min before zymosan administration; RF at 50 mg/kg in combination with 5 mg/kg morphine</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 50 and 100 mg/kg induced antinociceptive-related body writhes and RF at 100 mg/kg dose suppressed intraperitoneal PMN influx. On the other hand, RF co-injected with morphine at low dose had antinociceptive effect and also reduced levels of proinflammatory cytikines such as TNF-α, IL-12p07, and IFN-γ according to RF dose and the time of injection.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B39-ijms-21-00950" ref-type="bibr">39</xref>]</td></tr><tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Anti-Inflammatory Effect</bold></td><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"></td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Toxin-induced shock (LPS-induced shock and <italic>S. aureus</italic> enterotoxin B (SEB)-induced shock) and bacterial infection in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 2.5, 5, 10, and 20 mg/kg bolus injection 6 h after LPS injection or SEB–D-galactosamine injection. RF at 2.5, 5, 10, 20 mg/kg 1 day before <italic>E. coli</italic> inoculation or 1 and 2 days after <italic>S. aureus</italic> inoculation.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF decreased the mortality of endotoxin- and exotoxin-induced shock, gram-negative and gram-positive bacterial infection including long-term treatment. In addition, RF reduced levels of plasma inflammatory cytokines, including TNF-, IL-1β, IL-6, IFN-γ, MCP-1, MIP-2, and NO level. Moreover, co-administration RF with APC ameliorated survival rate of toxin-induced shock.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B42-ijms-21-00950" ref-type="bibr">42</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">LPS-induced shock model and bacterial infection model in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 2.5, 5, 10, 20, 40, and 80 mg/kg/6h i.v. infusion after 6 h LPS injection. RF at 80 mg/kg/6 h after 1 h <italic>E.coli</italic> infection or RF at 20, 40, 80 mg/kg/6 h after 1 h <italic>S.aureus</italic> infection.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF protected mice against the mortality in both toxin shock and infection models, but RF reduced only the level of IL-6 and NO in plasma. In addition, RF decreased the elevation of TNF-α, IL-1β, MPC-1, IL-6, and NO level in plasma.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B8-ijms-21-00950" ref-type="bibr">8</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">LPS-induced shock model in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 2.5 or 10 mg/kg for 6 h continuous i.v bolus administration with or without aminolevane<sup>®</sup> or single dose injection with or without amino acids or valine after 6 h LPS injection.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 10 mg/kg administered continuously for 6 h reduced morbidities on LPS- induced shock model, and was better with aminolevane<sup>®</sup> combination treatment. RF treatment in combination with tryptophan, isoleucine, proline, threonine, alanine or valine had improved the survival rate, but only valine was significantly effective. Moreover, RF reduced IL-6, lactic acid level, but increased glucose level.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B9-ijms-21-00950" ref-type="bibr">9</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Endotoxin-induced shock in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 20 mg/kg i.v. administered after 6 h LPS injection</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF decreased the number of IL-6 and MIP-2 and NO levels in plasma. RF also reduced IL-6 and MIP-2 levels in lung, but inhibited only MIP-2 level in liver. However, RF reduced IL-6 mRNA expression in lung, but MIP-2 mRNA expression was inhibited in liver and kidney. Additionally, iNO expression was inhibited by RF.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B43-ijms-21-00950" ref-type="bibr">43</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Olive oil-triggered paw swelling and collagen-induced arthritis models in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 20 mg/kg i.p. administration before oil injection or after collagen-induced arthritis</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF inhibited the paw swelling induced by olive oil, affecting a reduction in neutrophil-dependent reaction. However, RF could not inhibit delayed type hypersensitivity reactivity and collagen II arthritis.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B33-ijms-21-00950" ref-type="bibr">33</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">LPS-induced shock model in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 1 and 10 mg/kg i.p. injection at 2 and 0 h before LPS administration</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF significantly suppressed the LPS-induced lethality in mice septic shock model and RF have protective effect through up-regulated the expression of HSP25 in the lung and heart.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B44-ijms-21-00950" ref-type="bibr">44</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Zymosan-induced peritonitis in different C57BL/6J, BALB/c and CBA mice strains</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 50 mg/kg i.p. co-injection with zymosan (40 mg/kg)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF co-treatment with zymosan reduced pain symptoms. Anti-inflammatory effects of RF are strain-specific manner. Particularly, peritoneal leukocytes (PTL) accumulation was inhibited in BALB/c and CBA strains, but was prolonged in C57BL/6J strain. The expression of iNOS was delayed (C57BL/6J) or inhibited (BALB/c and CBA) in PTL lysates as well as the prolonged (C57BL/6) or inhibited (BALB/c) intraperitoneal accumulation of MMP-9.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B38-ijms-21-00950" ref-type="bibr">38</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Zymosan-induced peritonitis in Swiss mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 0, 20, 50, or 100 mg/kg by co-injection, pre-injection or post-injection in zymosan-induced peritonitis</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF itself induced nociceptive-related body writhes, but effectively reduces zymosan-induced writhing response on influence of pre-injection or post- injection. RF also reduced the evaluation number of PLTs, mainly PMN and an increase in inflammation-related cytokines and MMP-9 with dose- and administration time-dependent effect.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B40-ijms-21-00950" ref-type="bibr">40</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">LPS-induced acute lungs injury in rat</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 30 mg/kg, p.o. for 7 days before LPS intranasally (i.n.)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF reduced interstitial edema, hemorrhage, infiltration of inflammatory PMNs, and destruction of lung parenchyma as well as decreased the iNOS level, but enhanced GSH, GR, GRx, and CAT expression.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B45-ijms-21-00950" ref-type="bibr">45</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Zymosan-induced inflammation in mice and in vitro macrophages</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF at 50 mg/kg i.p. injection 30 min either before zymosan, together with zymosan, or 2, 4, 6 h after i.p. zymosan injection.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RF causes both the inhibition of expression and release of HMGB1 in time-dependent manner.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B46-ijms-21-00950" ref-type="bibr">46</xref>]</td></tr></tbody></table></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000A30 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000A30 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé= PMC:7037471
|texte= Riboflavin: The Health Benefits of a Forgotten Natural Vitamin
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:32023913" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a ChloroquineV1
| This area was generated with Dilib version V0.6.33. |  |