Folic acid as placebo in controlled clinical trials of hydroxychloroquine prophylaxis in COVID-19: Is it scientifically justifiable?
Identifieur interne : 000280 ( Main/Corpus ); précédent : 000279; suivant : 000281Folic acid as placebo in controlled clinical trials of hydroxychloroquine prophylaxis in COVID-19: Is it scientifically justifiable?
Auteurs : Hardeep Kaur ; Phulen Sarma ; Anusuya Bhattacharyya ; Manisha Prajapat ; Subodh Kumar ; Ajay Prakash ; Bikash MedhiSource :
- Medical hypotheses [ 1532-2777 ] ; 2021.
English descriptors
- KwdEn :
- Angiotensin-Converting Enzyme 2 (metabolism), COVID-19 (complications), COVID-19 (drug therapy), COVID-19 (prevention & control), Folic Acid (therapeutic use), Humans (MeSH), Hydroxychloroquine (therapeutic use), Hyperhomocysteinemia (complications), Hyperhomocysteinemia (drug therapy), Hypertension, Pulmonary (complications), Hypertension, Pulmonary (drug therapy), Methylenetetrahydrofolate Reductase (NADPH2) (genetics), Models, Theoretical (MeSH), Nitric Oxide Synthase Type III (metabolism), Placebos (MeSH), Protein Binding (MeSH), Randomized Controlled Trials as Topic (MeSH), Research Design (MeSH).
- MESH :
- chemical , genetics : Methylenetetrahydrofolate Reductase (NADPH2).
- chemical , metabolism : Angiotensin-Converting Enzyme 2, Nitric Oxide Synthase Type III.
- complications : COVID-19, Hyperhomocysteinemia, Hypertension, Pulmonary.
- drug therapy : COVID-19, Hyperhomocysteinemia, Hypertension, Pulmonary.
- prevention & control : COVID-19.
- chemical , therapeutic use : Folic Acid, Hydroxychloroquine.
- Humans, Models, Theoretical, Placebos, Protein Binding, Randomized Controlled Trials as Topic, Research Design.
Abstract
Using folic acid (FA) as placebo complicates the interpretation of the findings of few RCTs evaluating safety and efficacy of hydroxychloroquine prophylaxis in COVID-19. FA is found to bind to furin-protease and spike: ACE2 interface of SARS-CoV-2. In clinical studies, FA level was lowest among severe patients compared to mild and moderate disease. A single controlled study reported the benefit of combination of folic acid with Pyridoxine & cyanocobalamin in terms of clinical and laboratory cure parameters. One hypothesis associates the differences in geographical variation of disease severity with prevalence of methyl tertahydrofolic acid reductase (MTHFR) C677T polymorphism. Other possible domains, where FA is hypothesized to be beneficial are COVID-19 associated pulmonary hypertension and hyper-homocystinemia. So, scientific justification of using folic acid as placebo in COVID-19 trials seems scientifically not credible and this may be one of the major factors for failure of many agents. We need to be more careful in choosing our placebo especially when conducting a placebo controlled trial.
DOI: 10.1016/j.mehy.2021.110539
PubMed: 33662863
PubMed Central: PMC7896118
Links to Exploration step
pubmed:33662863Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Folic acid as placebo in controlled clinical trials of hydroxychloroquine prophylaxis in COVID-19: Is it scientifically justifiable?</title><author><name sortKey="Kaur, Hardeep" sort="Kaur, Hardeep" uniqKey="Kaur H" first="Hardeep" last="Kaur">Hardeep Kaur</name><affiliation><nlm:affiliation>Department of Pharmacology, PGIMER, Chandigarh, India.</nlm:affiliation></affiliation></author><author><name sortKey="Sarma, Phulen" sort="Sarma, Phulen" uniqKey="Sarma P" first="Phulen" last="Sarma">Phulen Sarma</name><affiliation><nlm:affiliation>Department of Pharmacology, PGIMER, Chandigarh, India.</nlm:affiliation></affiliation></author><author><name sortKey="Bhattacharyya, Anusuya" sort="Bhattacharyya, Anusuya" uniqKey="Bhattacharyya A" first="Anusuya" last="Bhattacharyya">Anusuya Bhattacharyya</name><affiliation><nlm:affiliation>Department of Ophthalmology, GMCH-32 Chandigarh, India.</nlm:affiliation></affiliation></author><author><name sortKey="Prajapat, Manisha" sort="Prajapat, Manisha" uniqKey="Prajapat M" first="Manisha" last="Prajapat">Manisha Prajapat</name><affiliation><nlm:affiliation>Department of Pharmacology, PGIMER, Chandigarh, India.</nlm:affiliation></affiliation></author><author><name sortKey="Kumar, Subodh" sort="Kumar, Subodh" uniqKey="Kumar S" first="Subodh" last="Kumar">Subodh Kumar</name><affiliation><nlm:affiliation>Department of Pharmacology, PGIMER, Chandigarh, India.</nlm:affiliation></affiliation></author><author><name sortKey="Prakash, Ajay" sort="Prakash, Ajay" uniqKey="Prakash A" first="Ajay" last="Prakash">Ajay Prakash</name><affiliation><nlm:affiliation>Department of Pharmacology, PGIMER, Chandigarh, India.</nlm:affiliation></affiliation></author><author><name sortKey="Medhi, Bikash" sort="Medhi, Bikash" uniqKey="Medhi B" first="Bikash" last="Medhi">Bikash Medhi</name><affiliation><nlm:affiliation>Department of Pharmacology, PGIMER, Chandigarh, India. Electronic address: drbikashus@yahoo.com.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:33662863</idno><idno type="pmid">33662863</idno><idno type="doi">10.1016/j.mehy.2021.110539</idno><idno type="pmc">PMC7896118</idno><idno type="wicri:Area/Main/Corpus">000280</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000280</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Folic acid as placebo in controlled clinical trials of hydroxychloroquine prophylaxis in COVID-19: Is it scientifically justifiable?</title><author><name sortKey="Kaur, Hardeep" sort="Kaur, Hardeep" uniqKey="Kaur H" first="Hardeep" last="Kaur">Hardeep Kaur</name><affiliation><nlm:affiliation>Department of Pharmacology, PGIMER, Chandigarh, India.</nlm:affiliation></affiliation></author><author><name sortKey="Sarma, Phulen" sort="Sarma, Phulen" uniqKey="Sarma P" first="Phulen" last="Sarma">Phulen Sarma</name><affiliation><nlm:affiliation>Department of Pharmacology, PGIMER, Chandigarh, India.</nlm:affiliation></affiliation></author><author><name sortKey="Bhattacharyya, Anusuya" sort="Bhattacharyya, Anusuya" uniqKey="Bhattacharyya A" first="Anusuya" last="Bhattacharyya">Anusuya Bhattacharyya</name><affiliation><nlm:affiliation>Department of Ophthalmology, GMCH-32 Chandigarh, India.</nlm:affiliation></affiliation></author><author><name sortKey="Prajapat, Manisha" sort="Prajapat, Manisha" uniqKey="Prajapat M" first="Manisha" last="Prajapat">Manisha Prajapat</name><affiliation><nlm:affiliation>Department of Pharmacology, PGIMER, Chandigarh, India.</nlm:affiliation></affiliation></author><author><name sortKey="Kumar, Subodh" sort="Kumar, Subodh" uniqKey="Kumar S" first="Subodh" last="Kumar">Subodh Kumar</name><affiliation><nlm:affiliation>Department of Pharmacology, PGIMER, Chandigarh, India.</nlm:affiliation></affiliation></author><author><name sortKey="Prakash, Ajay" sort="Prakash, Ajay" uniqKey="Prakash A" first="Ajay" last="Prakash">Ajay Prakash</name><affiliation><nlm:affiliation>Department of Pharmacology, PGIMER, Chandigarh, India.</nlm:affiliation></affiliation></author><author><name sortKey="Medhi, Bikash" sort="Medhi, Bikash" uniqKey="Medhi B" first="Bikash" last="Medhi">Bikash Medhi</name><affiliation><nlm:affiliation>Department of Pharmacology, PGIMER, Chandigarh, India. Electronic address: drbikashus@yahoo.com.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Medical hypotheses</title><idno type="eISSN">1532-2777</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Angiotensin-Converting Enzyme 2 (metabolism)</term><term>COVID-19 (complications)</term><term>COVID-19 (drug therapy)</term><term>COVID-19 (prevention & control)</term><term>Folic Acid (therapeutic use)</term><term>Humans (MeSH)</term><term>Hydroxychloroquine (therapeutic use)</term><term>Hyperhomocysteinemia (complications)</term><term>Hyperhomocysteinemia (drug therapy)</term><term>Hypertension, Pulmonary (complications)</term><term>Hypertension, Pulmonary (drug therapy)</term><term>Methylenetetrahydrofolate Reductase (NADPH2) (genetics)</term><term>Models, Theoretical (MeSH)</term><term>Nitric Oxide Synthase Type III (metabolism)</term><term>Placebos (MeSH)</term><term>Protein Binding (MeSH)</term><term>Randomized Controlled Trials as Topic (MeSH)</term><term>Research Design (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Methylenetetrahydrofolate Reductase (NADPH2)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Angiotensin-Converting Enzyme 2</term><term>Nitric Oxide Synthase Type III</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>COVID-19</term><term>Hyperhomocysteinemia</term><term>Hypertension, Pulmonary</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term><term>Hyperhomocysteinemia</term><term>Hypertension, Pulmonary</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Folic Acid</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Models, Theoretical</term><term>Placebos</term><term>Protein Binding</term><term>Randomized Controlled Trials as Topic</term><term>Research Design</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Using folic acid (FA) as placebo complicates the interpretation of the findings of few RCTs evaluating safety and efficacy of hydroxychloroquine prophylaxis in COVID-19. FA is found to bind to furin-protease and spike: ACE2 interface of SARS-CoV-2. In clinical studies, FA level was lowest among severe patients compared to mild and moderate disease. A single controlled study reported the benefit of combination of folic acid with Pyridoxine & cyanocobalamin in terms of clinical and laboratory cure parameters. One hypothesis associates the differences in geographical variation of disease severity with prevalence of methyl tertahydrofolic acid reductase (MTHFR) C677T polymorphism. Other possible domains, where FA is hypothesized to be beneficial are COVID-19 associated pulmonary hypertension and hyper-homocystinemia. So, scientific justification of using folic acid as placebo in COVID-19 trials seems scientifically not credible and this may be one of the major factors for failure of many agents. We need to be more careful in choosing our placebo especially when conducting a placebo controlled trial.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">33662863</PMID><DateCompleted><Year>2021</Year><Month>04</Month><Day>15</Day></DateCompleted><DateRevised><Year>2021</Year><Month>04</Month><Day>15</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1532-2777</ISSN><JournalIssue CitedMedium="Internet"><Volume>149</Volume><PubDate><Year>2021</Year><Month>Apr</Month></PubDate></JournalIssue><Title>Medical hypotheses</Title><ISOAbbreviation>Med Hypotheses</ISOAbbreviation></Journal><ArticleTitle>Folic acid as placebo in controlled clinical trials of hydroxychloroquine prophylaxis in COVID-19: Is it scientifically justifiable?</ArticleTitle><Pagination><MedlinePgn>110539</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0306-9877(21)00057-8</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.mehy.2021.110539</ELocationID><Abstract><AbstractText>Using folic acid (FA) as placebo complicates the interpretation of the findings of few RCTs evaluating safety and efficacy of hydroxychloroquine prophylaxis in COVID-19. FA is found to bind to furin-protease and spike: ACE2 interface of SARS-CoV-2. In clinical studies, FA level was lowest among severe patients compared to mild and moderate disease. A single controlled study reported the benefit of combination of folic acid with Pyridoxine & cyanocobalamin in terms of clinical and laboratory cure parameters. One hypothesis associates the differences in geographical variation of disease severity with prevalence of methyl tertahydrofolic acid reductase (MTHFR) C677T polymorphism. Other possible domains, where FA is hypothesized to be beneficial are COVID-19 associated pulmonary hypertension and hyper-homocystinemia. So, scientific justification of using folic acid as placebo in COVID-19 trials seems scientifically not credible and this may be one of the major factors for failure of many agents. We need to be more careful in choosing our placebo especially when conducting a placebo controlled trial.</AbstractText><CopyrightInformation>Copyright © 2021 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kaur</LastName><ForeName>Hardeep</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, PGIMER, Chandigarh, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sarma</LastName><ForeName>Phulen</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, PGIMER, Chandigarh, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bhattacharyya</LastName><ForeName>Anusuya</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Ophthalmology, GMCH-32 Chandigarh, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Prajapat</LastName><ForeName>Manisha</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, PGIMER, Chandigarh, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kumar</LastName><ForeName>Subodh</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, PGIMER, Chandigarh, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Prakash</LastName><ForeName>Ajay</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, PGIMER, Chandigarh, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Medhi</LastName><ForeName>Bikash</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, PGIMER, Chandigarh, India. Electronic address: drbikashus@yahoo.com.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016422">Letter</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>02</Month><Day>20</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Med Hypotheses</MedlineTA><NlmUniqueID>7505668</NlmUniqueID><ISSNLinking>0306-9877</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010919">Placebos</NameOfSubstance></Chemical><Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber><NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>935E97BOY8</RegistryNumber><NameOfSubstance UI="D005492">Folic Acid</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.13.39</RegistryNumber><NameOfSubstance UI="C496314">NOS3 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.13.39</RegistryNumber><NameOfSubstance UI="D052250">Nitric Oxide Synthase Type III</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.5.1.20</RegistryNumber><NameOfSubstance UI="C573423">MTHFR protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.5.1.20</RegistryNumber><NameOfSubstance UI="D042965">Methylenetetrahydrofolate Reductase (NADPH2)</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.17.23</RegistryNumber><NameOfSubstance UI="C000705307">ACE2 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.17.23</RegistryNumber><NameOfSubstance UI="D000085962">Angiotensin-Converting Enzyme 2</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Protocol" UI="C000705127">COVID-19 drug treatment</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000085962" MajorTopicYN="N">Angiotensin-Converting Enzyme 2</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005492" MajorTopicYN="N">Folic Acid</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020138" MajorTopicYN="N">Hyperhomocysteinemia</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006976" MajorTopicYN="N">Hypertension, Pulmonary</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D042965" MajorTopicYN="N">Methylenetetrahydrofolate Reductase (NADPH2)</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008962" MajorTopicYN="N">Models, Theoretical</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D052250" MajorTopicYN="N">Nitric Oxide Synthase Type III</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010919" MajorTopicYN="Y">Placebos</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011485" MajorTopicYN="N">Protein Binding</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016032" MajorTopicYN="N">Randomized Controlled Trials as Topic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012107" MajorTopicYN="N">Research Design</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">COVID-19</Keyword><Keyword MajorTopicYN="N">Folic acid</Keyword><Keyword MajorTopicYN="N">Hydroxychloroquine</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>12</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>02</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>3</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>4</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>3</Month><Day>4</Day><Hour>20</Hour><Minute>20</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33662863</ArticleId><ArticleId IdType="pii">S0306-9877(21)00057-8</ArticleId><ArticleId IdType="doi">10.1016/j.mehy.2021.110539</ArticleId><ArticleId IdType="pmc">PMC7896118</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/CovidChloroV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000280 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 000280 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= CovidChloroV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= pubmed:33662863
|texte= Folic acid as placebo in controlled clinical trials of hydroxychloroquine prophylaxis in COVID-19: Is it scientifically justifiable?
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Corpus/RBID.i -Sk "pubmed:33662863" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a CovidChloroV1
| This area was generated with Dilib version V0.6.38. |  |