Vitamin C and COVID-19
Harri Hemilä, Angelique M E De Man
Frontiers in Medicine, doi:10.3389/fmed.2020.559811
In numerous animal studies, vitamin C has prevented and alleviated viral and bacterial infections. In a few dozen placebo-controlled trials with humans, vitamin C has shortened infections caused by respiratory viruses, which indicates that the vitamin can also influence viral infections in humans. In critically ill patients, plasma vitamin C levels are commonly very low. Gram doses of vitamin C are needed to increase the plasma vitamin C levels of critically ill patients to the levels of ordinary healthy people. A meta-analysis of 12 trials with 1,766 patients calculated that vitamin C reduced the length of ICU stay on average by 8%. Another meta-analysis found that vitamin C shortened the duration of mechanical ventilation in ICU patients. Two randomized placebo-controlled trials found statistically significant reduction in the mortality of sepsis patients. The effects of vitamin C on acute respiratory distress syndrome (ARDS) frequently complicating COVID-19 pneumonia should be considered. Vitamin C is a safe and inexpensive essential nutrient.
AUTHOR CONTRIBUTIONS HH and AM participated in the revision of the manuscript.
Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
Arvinte, Singh, Marik, Serum levels of vitamin C and vitamin D in a cohort of critically ill COVID-19 patients of a north American community hospital intensive care unit in may 2020. A pilot study, Med Drug Discov,
doi:10.1016/j.medidd.2020.100064Atherton, Kratzing, Fisher, The effect of ascorbic acid on infection of chick-embryo ciliated tracheal organ cultures by coronavirus, Arch Virol,
doi:10.1007/bf01317848Carr, Rosengrave, Bayer, Chambers, Mehrtens et al., Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes, Crit Care,
doi:10.1186/s13054-017-1891-yCarr, Rowe, The emerging role of vitamin C in the prevention and treatment of COVID-19, Nutrients,
doi:10.3390/nu12113286Cerullo, Negro, Parimbelli, Pecoraro, Perna et al., The long history of vitamin C: from prevention of the common cold to potential aid in the treatment of COVID-19, Front Immunol,
doi:10.3389/fimmu.2020.574029Chiscano-Camón, Ruiz-Rodriguez, Ruiz-Sanmartin, Roca, Ferrer, Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome, Crit Care,
doi:10.1186/s13054-020-03249-yFisher, Kraskauskas, Martin, Farkas, Wegelin et al., Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid, Am J Physiol Lung Cell Mol Physiol,
doi:10.1152/ajplung.00300.2011Fisher, Seropian, Kraskauskas, Thakkar, Voelkel et al., Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury, Crit Care Med,
doi:10.1097/CCM.0b013e3182120cb8Fowler, Iii, Truwit, Hite, Morris et al., Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: the CITRIS-ALI randomized clinical trial, JAMA,
doi:10.1001/jama.2019.11825Grooth, Manubulu-Choo, Zandvliet, Spoelstra-De Man, Girbes et al., Vitamin C pharmacokinetics in critically ill patients: a randomized trial of four iv regimens, Chest,
doi:10.1016/j.chest.2018.02.025Hemilä, Chalker, Reanalysis of the effect of vitamin C on mortality in the CITRIS-ALI trial: important findings dismissed in the trial report, Front Med,
doi:10.3389/fmed.2020.590853Hemilä, Chalker, Vitamin C can shorten the length of stay in the ICU: a meta-analysis, Nutrients,
doi:10.3390/nu11040708Hemilä, Chalker, Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis, J Intensive Care,
doi:10.1186/s40560-020-0432-yHemilä, Do Vitamins C and E Affect Respiratory Infections?
Levine, Conry-Cantilena, Wang, Welch, Washko et al., Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance, Proc Natl Acad Sci,
doi:10.1073/pnas.93.8.3704Li, Maeda, Beck, Vitamin C deficiency increases the lung pathology of influenza virus-infected gulo-/-mice, J Nutr,
doi:10.1093/jn/136.10.2611Manning, Mitchell, Appadurai, Shakya, Pierce et al., Vitamin C promotes maturation of T-cells, Antioxid. Redox Signal,
doi:10.1089/ars.2012.4988Zabet, Mohammadi, Ramezani, Khalili, Effect of high-dose ascorbic acid on vasopressor's requirement in septic shock, J Res Pharm Pract,
doi:10.4103/2279-042X.179569{ 'indexed': { 'date-parts': [[2021, 11, 11]],
'date-time': '2021-11-11T15:48:34Z',
'timestamp': 1636645714107},
'reference-count': 27,
'publisher': 'Frontiers Media SA',
'license': [ { 'start': { 'date-parts': [[2021, 1, 18]],
'date-time': '2021-01-18T00:00:00Z',
'timestamp': 1610928000000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by/4.0/'}],
'content-domain': {'domain': ['frontiersin.org'], 'crossmark-restriction': True},
'short-container-title': ['Front. Med.'],
'abstract': '<jats:p>In numerous animal studies, vitamin C has prevented and alleviated viral and '
'bacterial infections. In a few dozen placebo-controlled trials with humans, vitamin C has '
'shortened infections caused by respiratory viruses, which indicates that the vitamin can also '
'influence viral infections in humans. In critically ill patients, plasma vitamin C levels are '
'commonly very low. Gram doses of vitamin C are needed to increase the plasma vitamin C levels '
'of critically ill patients to the levels of ordinary healthy people. A meta-analysis of 12 '
'trials with 1,766 patients calculated that vitamin C reduced the length of ICU stay on '
'average by 8%. Another meta-analysis found that vitamin C shortened the duration of '
'mechanical ventilation in ICU patients. Two randomized placebo-controlled trials found '
'statistically significant reduction in the mortality of sepsis patients. The effects of '
'vitamin C on acute respiratory distress syndrome (ARDS) frequently complicating COVID-19 '
'pneumonia should be considered. Vitamin C is a safe and inexpensive essential '
'nutrient.</jats:p>',
'DOI': '10.3389/fmed.2020.559811',
'type': 'journal-article',
'created': {'date-parts': [[2021, 1, 18]], 'date-time': '2021-01-18T05:01:36Z', 'timestamp': 1610946096000},
'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy',
'source': 'Crossref',
'is-referenced-by-count': 5,
'title': ['Vitamin C and COVID-19'],
'prefix': '10.3389',
'volume': '7',
'author': [ {'given': 'Harri', 'family': 'Hemilä', 'sequence': 'first', 'affiliation': []},
{'given': 'Angelique M. E.', 'family': 'de Man', 'sequence': 'additional', 'affiliation': []}],
'member': '1965',
'published-online': {'date-parts': [[2021, 1, 18]]},
'reference': [ { 'key': 'B1',
'doi-asserted-by': 'publisher',
'first-page': '339',
'DOI': '10.3390/nu9040339',
'article-title': 'Vitamin C and infections',
'volume': '9',
'author': 'Hemilä',
'year': '2017',
'journal-title': 'Nutrients'},
{ 'key': 'B2',
'unstructured': '10518\n'
' HemiläH\n'
' HelsinkiUniversity of HelsinkiDo Vitamins C and E Affect '
'Respiratory Infections2006'},
{ 'key': 'B3',
'doi-asserted-by': 'publisher',
'first-page': '495',
'DOI': '10.1177/014107680710001109',
'article-title': 'Vitamin C may affect lung infections',
'volume': '100',
'author': 'Hemilä',
'year': '2007',
'journal-title': 'J R Soc Med'},
{ 'key': 'B4',
'doi-asserted-by': 'publisher',
'first-page': 'CD005532',
'DOI': '10.1002/14651858.CD005532.pub3',
'article-title': 'Vitamin C for preventing and treating pneumonia',
'volume': '8',
'author': 'Hemilä',
'year': '2013',
'journal-title': 'Cochrane Database Syst Rev'},
{ 'key': 'B5',
'doi-asserted-by': 'publisher',
'first-page': '2054',
'DOI': '10.1089/ars.2012.4988',
'article-title': 'Vitamin C promotes maturation of T-cells',
'volume': '19',
'author': 'Manning',
'year': '2013',
'journal-title': 'Antioxid. Redox Signal'},
{ 'key': 'B6',
'doi-asserted-by': 'publisher',
'first-page': '1211',
'DOI': '10.3390/nu9111211',
'article-title': 'Vitamin C and immune function',
'volume': '9',
'author': 'Carr',
'year': '2017',
'journal-title': 'Nutrients'},
{ 'key': 'B7',
'doi-asserted-by': 'publisher',
'first-page': '195',
'DOI': '10.1007/bf01317848',
'article-title': 'The effect of ascorbic acid on infection of chick-embryo ciliated '
'tracheal organ cultures by coronavirus',
'volume': '56',
'author': 'Atherton',
'year': '1978',
'journal-title': 'Arch Virol'},
{ 'key': 'B8',
'doi-asserted-by': 'publisher',
'first-page': '581',
'DOI': '10.1080/03079459208418879',
'article-title': 'Ascorbic acid and infectious bronchitis infections in broilers',
'volume': '21',
'author': 'Davelaar',
'year': '1992',
'journal-title': 'Avian Pathol'},
{ 'key': 'B9',
'doi-asserted-by': 'publisher',
'first-page': '1454',
'DOI': '10.1097/CCM.0b013e3182120cb8',
'article-title': 'Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury',
'volume': '39',
'author': 'Fisher',
'year': '2011',
'journal-title': 'Crit Care Med'},
{ 'key': 'B10',
'doi-asserted-by': 'publisher',
'first-page': 'L20',
'DOI': '10.1152/ajplung.00300.2011',
'article-title': 'Mechanisms of attenuation of abdominal sepsis induced acute lung injury '
'by ascorbic acid',
'volume': '303',
'author': 'Fisher',
'year': '2012',
'journal-title': 'Am J Physiol Lung Cell Mol Physiol'},
{ 'key': 'B11',
'doi-asserted-by': 'publisher',
'first-page': '2611',
'DOI': '10.1093/jn/136.10.2611',
'article-title': 'Vitamin C deficiency increases the lung pathology of influenza '
'virus-infected gulo-/- mice',
'volume': '136',
'author': 'Li',
'year': '2006',
'journal-title': 'J Nutr'},
{ 'key': 'B12',
'doi-asserted-by': 'publisher',
'first-page': 'CD000980',
'DOI': '10.1002/14651858.CD000980.pub4',
'article-title': 'Vitamin C for preventing and treating the common cold',
'volume': '31',
'author': 'Hemilä',
'year': '2013'},
{ 'key': 'B13',
'doi-asserted-by': 'publisher',
'first-page': '708',
'DOI': '10.3390/nu11040708',
'article-title': 'Vitamin C can shorten the length of stay in the ICU: a meta-analysis',
'volume': '11',
'author': 'Hemilä',
'year': '2019',
'journal-title': 'Nutrients'},
{ 'key': 'B14',
'doi-asserted-by': 'publisher',
'first-page': '300',
'DOI': '10.1186/s13054-017-1891-y',
'article-title': 'Hypovitaminosis C and vitamin C deficiency in critically ill patients '
'despite recommended enteral and parenteral intakes',
'volume': '21',
'author': 'Carr',
'year': '2017',
'journal-title': 'Crit Care'},
{ 'key': 'B15',
'doi-asserted-by': 'publisher',
'first-page': '522',
'DOI': '10.1186/s13054-020-03249-y',
'article-title': 'Vitamin C levels in patients with SARS-CoV-2-associated acute '
'respiratory distress syndrome',
'volume': '24',
'author': 'Chiscano-Camón',
'year': '2020',
'journal-title': 'Crit Care'},
{ 'key': 'B16',
'doi-asserted-by': 'publisher',
'first-page': '100064',
'DOI': '10.1016/j.medidd.2020.100064',
'article-title': 'Serum levels of vitamin C and vitamin D in a cohort of critically ill '
'COVID-19 patients of a north American community hospital intensive care '
'unit in may 2020. A pilot study',
'volume': '8',
'author': 'Arvinte',
'year': '2020',
'journal-title': 'Med Drug Discov.'},
{ 'key': 'B17',
'doi-asserted-by': 'publisher',
'first-page': '3704',
'DOI': '10.1073/pnas.93.8.3704',
'article-title': 'Vitamin C pharmacokinetics in healthy volunteers: evidence for a '
'recommended dietary allowance',
'volume': '93',
'author': 'Levine',
'year': '1996',
'journal-title': 'Proc Natl Acad Sci USA'},
{ 'key': 'B18',
'doi-asserted-by': 'publisher',
'first-page': '1368',
'DOI': '10.1016/j.chest.2018.02.025',
'article-title': 'Vitamin C pharmacokinetics in critically ill patients: a randomized '
'trial of four iv regimens',
'volume': '153',
'author': 'De Grooth',
'year': '2018',
'journal-title': 'Chest'},
{ 'key': 'B19',
'doi-asserted-by': 'publisher',
'first-page': '15',
'DOI': '10.1186/s40560-020-0432-y',
'article-title': 'Vitamin C may reduce the duration of mechanical ventilation in '
'critically ill patients: a meta-regression analysis',
'volume': '8',
'author': 'Hemilä',
'year': '2020',
'journal-title': 'J Intensive Care'},
{ 'key': 'B20',
'doi-asserted-by': 'publisher',
'first-page': '94',
'DOI': '10.4103/2279-042X.179569',
'article-title': "Effect of high-dose ascorbic acid on vasopressor's requirement in "
'septic shock',
'volume': '5',
'author': 'Zabet',
'year': '2016',
'journal-title': 'J Res Pharm Pract'},
{ 'key': 'B21',
'doi-asserted-by': 'publisher',
'first-page': '1261',
'DOI': '10.1001/jama.2019.11825',
'article-title': 'Effect of vitamin C infusion on organ failure and biomarkers of '
'inflammation and vascular injury in patients with sepsis and severe '
'acute respiratory failure: the CITRIS-ALI randomized clinical trial',
'volume': '322',
'author': 'Fowler',
'year': '2019',
'journal-title': 'JAMA'},
{ 'key': 'B22',
'doi-asserted-by': 'publisher',
'first-page': '590853',
'DOI': '10.3389/fmed.2020.590853',
'article-title': 'Reanalysis of the effect of vitamin C on mortality in the CITRIS-ALI '
'trial: important findings dismissed in the trial report',
'volume': '7',
'author': 'Hemilä',
'year': '2020',
'journal-title': 'Front Med'},
{ 'key': 'B23',
'doi-asserted-by': 'publisher',
'first-page': '575',
'DOI': '10.1016/j.accpm.2019.10.004',
'article-title': 'CITRIS-ALI: how statistics were used to obfuscate the true findings',
'volume': '38',
'author': 'Marik',
'year': '2019',
'journal-title': 'Anaesth Crit Care Pain Med'},
{ 'key': 'B24',
'doi-asserted-by': 'publisher',
'first-page': '248',
'DOI': '10.1097/MCC.0000000000000510',
'article-title': 'Vitamin C: should we supplement?',
'volume': '24',
'author': 'Spoelstra-de Man',
'year': '2018',
'journal-title': 'Curr Opin Crit Care'},
{ 'key': 'B25',
'doi-asserted-by': 'publisher',
'first-page': '110948',
'DOI': '10.1016/j.nut.2020.110948',
'article-title': 'Vitamin C as prophylaxis and adjunctive medical treatment for COVID-19?',
'author': 'Feyaerts',
'year': '2020',
'journal-title': 'Nutrition'},
{ 'key': 'B26',
'doi-asserted-by': 'publisher',
'first-page': '574029',
'DOI': '10.3389/fimmu.2020.574029',
'article-title': 'The long history of vitamin C: from prevention of the common cold to '
'potential aid in the treatment of COVID-19',
'volume': '11',
'author': 'Cerullo',
'year': '2020',
'journal-title': 'Front Immunol'},
{ 'key': 'B27',
'doi-asserted-by': 'publisher',
'first-page': '3286',
'DOI': '10.3390/nu12113286',
'article-title': 'The emerging role of vitamin C in the prevention and treatment of '
'COVID-19',
'volume': '12',
'author': 'Carr',
'year': '2020',
'journal-title': 'Nutrients'}],
'container-title': ['Frontiers in Medicine'],
'original-title': [],
'link': [ { 'URL': 'https://www.frontiersin.org/articles/10.3389/fmed.2020.559811/full',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2021, 1, 18]],
'date-time': '2021-01-18T05:01:39Z',
'timestamp': 1610946099000},
'score': 1,
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2021, 1, 18]]},
'references-count': 27,
'alternative-id': ['10.3389/fmed.2020.559811'],
'URL': 'http://dx.doi.org/10.3389/fmed.2020.559811',
'relation': {},
'ISSN': ['2296-858X'],
'issn-type': [{'value': '2296-858X', 'type': 'electronic'}],
'subject': ['General Medicine'],
'published': {'date-parts': [[2021, 1, 18]]}}
