This article may be reprinted free of charge provided 1) that there is clear attribution to the Orthomolecular Medicine News Service, and 2) that both the OMNS free subscription link http://orthomolecular.org/subscribe.html and also the OMNS archive link http://orthomolecular.org/resources/omns/index.shtml are included.
FOR IMMEDIATE RELEASE
Estimating or Measuring? What is the true effect of vitamin D on COVID-19?
by Robert G. Smith, PhD
(OMNS June 12, 2021) A recent study used genetic methods to estimate the levels of vitamin D (blood levels of 25OHD) in individuals. The method is called "Mendelian Randomization" that estimates the metabolic activity in individuals using certain genetic mutations (SNPs) relevant to genes that are associated with 25OHD metabolism. By analyzing the genetic makeup of those who had COVID-19, the study concluded that vitamin D is not effective at reducing risk of COVID-19 infection. 
However, the study had several limitations. It did not actually test blood levels of 25OHD -- it only studied the genes involved in vitamin D metabolism. Although it was based on more than 14,000 individuals with COVID-19, and more than 1,200,000 individuals without COVID-19 from European ancestry, it excluded individuals of African and Asian ancestry. Moreover, the Mendelian Randomization method utilized in the study has not been shown to be effective for determining whether the estimated vitamin D status is associated with risk or severity of disease. 
The overriding problem with the study was that the vitamin D level of an individual (as opposed to a group) cannot be determined, even approximately, by their genetics. Someone who may be at risk of a low vitamin D level based on their genetic makeup may have sufficient sun exposure or adequate supplement doses to prevent a deficiency. Someone who is not at risk based on their genetic makeup may be deficient because of a lack of sun exposure or supplement doses. Further, by its exclusion of people with African or Asian ancestry, the study biased the accuracy of the analysis. Those individuals with dark skin living in at high latitudes such as Europe are well known by environmental studies to be at risk for a deficiency of vitamin D. [3-6] They can also prevent a vitamin D deficiency with sun exposure or supplements.
If the study had included people of African and/or Asian descent living in northern Europe, very likely it would have found a different conclusion -- that a deficiency of vitamin D contributes to risk of COVID-19. Certainly a study that would analyze the blood levels of 25OHD for risk of COVID-19 is likely to be more reliable.
Further, the study ignored other vitamins and minerals that are helpful for lowering risk of serious infection (levels of vitamin C, magnesium, zinc, selenium, etc) which are all synergistic. For example, the body's utilization of vitamin D is dependent on the level of magnesium, which is deficient in many individuals. 
In the last 6 months (Dec 2020 - May 2021), dozens of studies have been published showing a clear association between vitamin D deficiency and risk for COVID-19. [8-44] It seems unlikely that they are all wrong in the implication that there is a causal connection.
Vitamin D is not a drug, and its use should not be held up because of lack of causal proof of its efficacy in interventional trials. It is an essential nutrient, and its use as a supplement can safely and responsibly be recommended by doctors worldwide to assist in eliminating deficiency, improving health, and terminating the COVID-19 pandemic.
For the immune system to function well, the body requires adequate levels of many essential nutrients, not only vitamin D, but also magnesium, vitamin C, zinc, selenium, and other vitamins and minerals. Vitamin D supplements in safe, adequate doses along with other essential nutrients can aid and empower the immune system and prevent the cytokine storm that has caused so much mortality in severe pneumonia caused by COVID-19. [45-50]
For vitamin D, dose and blood level are important. The recommended adult dose is 5000 IU/day, but this should be adjusted for body weight. Since vitamin D is fat-soluble, heavier individuals may need a larger dose such as 10,000 IU/day. After taking a dose for several months, a blood test is advised; the ideal blood level of 25OHD is 50 - 60 ng/ml (125-150 nmol/L). A recommended adult dose of magnesium is 400-600 mg/day, including diet and supplements, but this also may need to be adjusted for weight. Recommended doses of vitamin C are 1500-3000 mg/day or more, taken in divided doses. You should discuss doses of essential nutrients with your doctor.
(Robert G. Smith is Research Associate Professor at the University of Pennsylvania, Perelman School of Medicine. He is the author of The Vitamin Cure for Eye Disease and coauthor of The Vitamin Cure for Arthritis. Dr. Smith is Associate Editor of the Orthomolecular Medicine News Service.)
1. Butler-Laporte G, Nakanishi T, Mooser V, et al. (2021) Vitamin D and COVID-19 susceptibility and severity in the COVID-19 Host Genetics Initiative: A Mendelian randomization study. PloS Medicine. https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003605
2. Grant WB (2021) Vitamin D status is inversely associated with risk and severity of COVID-19 despite the null findings in Mendelian randomization studies. PloS Medicine. https://journals.plos.org/plosmedicine/article/comment?id=10.1371/annotation/34201b86-79fe-45c4-ac7b-70a6580548cc
3. Harris SS (2006) Vitamin D and African Americans. J Nutr 136:1126-9. https://pubmed.ncbi.nlm.nih.gov/16549493
4. Khazai N, Judd SE, Tangpricha V (2008) Calcium and vitamin D: skeletal and extraskeletal health. Curr Rheumatol Rep. 10:110-7. https://pubmed.ncbi.nlm.nih.gov/18460265
5. Cashman KD, Ritz C, Adebayo FA, et al. (2019) Differences in the dietary requirement for vitamin D among Caucasian and East African women at Northern latitude. Eur J Nutr. 58:2281-2291. https://pubmed.ncbi.nlm.nih.gov/30022296
6. Meltzer DO, Best TJ, Zhang H, et al. (2021) Association of Vitamin D Levels, Race/Ethnicity, and Clinical Characteristics With COVID-19 Test Results. AMA Netw Open. 4:e214117. https://pubmed.ncbi.nlm.nih.gov/33739433
8. Baktash V, Hosack T, Patel N, et al. (2020) Vitamin D status and outcomes for hospitalised older patients with COVID-19. Postgrad Med J. postgradmedj-2020-138712. https://pubmed.ncbi.nlm.nih.gov/32855214
9. Merzon E, Tworowski D, Gorohovski A, et al. (2020) Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study. FEBS J. 287:3693-3702. https://pubmed.ncbi.nlm.nih.gov/32700398
10. Panagiotou G, Tee SA, Ihsan Y, et al. (2020) Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalized with COVID-19 are associated with greater disease severity. Clin Endocrinol (Oxf) 93:508-511. https://pubmed.ncbi.nlm.nih.gov/32621392
11. Grant WB, Lahore H, Rockwell MS (2020) The Benefits of Vitamin D Supplementation for Athletes: Better Performance and Reduced Risk of COVID-19. Nutrients. 12:3741. https://pubmed.ncbi.nlm.nih.gov/33291720
12. Mercola J, Grant WB, Wagner CL (2020) Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity. Nutrients. 12:3361. https://pubmed.ncbi.nlm.nih.gov/33142828
13. Meltzer DO, Best TJ, Zhang H, et al (2020) Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results. JAMA Netw Open 3:e2019722. https://pubmed.ncbi.nlm.nih.gov/32880651
14. Castillo ME, Entrenas Costa LM, Vaquero Barrios JM, et al. (2020). "Effect of Calcifediol Treatment and best Available Therapy versus best Available Therapy on Intensive Care Unit Admission and Mortality Among Patients Hospitalized for COVID-19: A Pilot Randomized Clinical study". The Journal of Steroid Biochemistry and Molecular Biology, 105751. https://doi.org/10.1016/j.jsbmb.2020.105751
15. Bossak BH, Turk CA (2021) Spatial Variability in COVID-19 Mortality. Int J Environ Res Public Health. 18:5892. https://pubmed.ncbi.nlm.nih.gov/34072646
16. AlSafar H, Grant WB, Hijazi R, et al. (2021) COVID-19 Disease Severity and Death in Relation to Vitamin D Status among SARS-CoV-2-Positive UAE Residents Nutrients. 13:1714. https://pubmed.ncbi.nlm.nih.gov/34069412
17. Chetty VV, Chetty M (2021) Potential benefit of vitamin d supplementation in people with respiratory illnesses, during the Covid-19 pandemic. Clin Transl Sci. https://pubmed.ncbi.nlm.nih.gov/34057814
18. Sánchez-Zuno GA, González-Estevez G, Matuz-Flores MG, et al. (2021) Vitamin D Levels in COVID-19 Outpatients from Western Mexico: Clinical Correlation and Effect of Its Supplementation. J Clin Med. 10:2378. https://pubmed.ncbi.nlm.nih.gov/34071293
19. Peng M-Y, Liu W-C, Zheng J-Q, et al. (2021) Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D. Int J Mol Sci 22:5251. https://pubmed.ncbi.nlm.nih.gov/34065735
20. Alcala-Diaz JF, Limia-Perez L, Gomez-Huelgas R, et al. (2021) Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study. Nutrients. 13:1760. https://pubmed.ncbi.nlm.nih.gov/34064175
21. Oristrell J, Oliva JC, Subirana I, et al. (2021) Association of Calcitriol Supplementation with Reduced COVID-19 Mortality in Patients with Chronic Kidney Disease: A Population-Based Study. Biomedicines. 9:509. https://pubmed.ncbi.nlm.nih.gov/34063015
22. Lagadinou M, Zorbas B, Velissaris D. (2021) Vitamin D plasma levels in patients with COVID-19: a case series. Infez Med. 29:224-228. https://pubmed.ncbi.nlm.nih.gov/34061787
23. Ceolin G, Rodrigues Mano GP, Schmitt Hames N, et al. (2021) Vitamin D, Depressive Symptoms, and Covid-19 Pandemic. Front Neurosci. 15:670879. https://pubmed.ncbi.nlm.nih.gov/34054418
24. Bui L, Zhu Z, Hawkins S, Cortez-Resendiz A, Bellon A. (2021) Vitamin D regulation of the immune system and its implications for COVID-19: A mini review. SAGE Open Med.9:20503121211014073. https://pubmed.ncbi.nlm.nih.gov/34046177
25. Bókkon I, Kapócs G, Vucskits A, et al. (2021) COVID-19: The significance of platelets, mitochondria, vitamin D, serotonin and the gut microbiota. Curr Med Chem. 2021 May 25. https://pubmed.ncbi.nlm.nih.gov/34042025
26. Shahvali Elham A, Azam K, Azam J, et al. (2021) Serum vitamin D, calcium, and zinc levels in patients with COVID-19. Clin Nutr ESPEN. 43:276-282. https://pubmed.ncbi.nlm.nih.gov/34024527
27. Lakkireddy M, Gadiga SG, Malathi RD, et al. (2021) Impact of daily high dose oral vitamin D therapy on the inflammatory markers in patients with COVID 19 disease. Sci Rep. 11:10641. https://pubmed.ncbi.nlm.nih.gov/34017029
28. Bychinin MV, Klypa TV, Mandel IA, et al. (2021) Low Circulating Vitamin D in Intensive Care Unit-Admitted COVID-19 Patients as a Predictor of Negative Outcomes. J Nutr 2021 May 12;nxab107. https://pubmed.ncbi.nlm.nih.gov/33982128
29. Oscanoa TJ, Amado J, Vidal X, et al. (2021) The relationship between the severity and mortality of SARS-CoV-2 infection and 25-hydroxyvitamin D concentration - a metaanalysis. Adv Respir Med 89:145-157. https://pubmed.ncbi.nlm.nih.gov/33966262
30. Faniyi AA, Lugg ST, Faustini SE, et al. (2021) Genetic polymorphisms, vitamin D binding protein and vitamin D deficiency in COVID-19. Eur Respir J. 57:2100653. https://pubmed.ncbi.nlm.nih.gov/33888522
31. Akbar MR, Wibowo A, Pranata R, Setiabudiawan B (2021) Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated With Susceptibility to COVID-19, Severity, and Mortality: A Systematic Review and Meta-Analysis. Front Nutr. 8:660420. https://pubmed.ncbi.nlm.nih.gov/33855042
32. Livingston M, Plant A, Dunmore S, et al. (2021) Detectable respiratory SARS-CoV-2 RNA is associated with low vitamin D levels and high social deprivation. Int J Clin Pract. 2021 Apr 2;e14166. https://pubmed.ncbi.nlm.nih.gov/33797849
33. Alguwaihes AM, Sabico S, Hasanato R, et al. (2021) Severe vitamin D deficiency is not related to SARS-CoV-2 infection but may increase mortality risk in hospitalized adults: a retrospective case-control study in an Arab Gulf country. Aging Clin Exp Res 33:1415-1422. https://pubmed.ncbi.nlm.nih.gov/33788172
34. Smith N, Sievert LL, Muttukrishna S, et al (2021) Mismatch: a comparative study of vitamin D status in British-Bangladeshi migrants Evol Med Public Health 9:164-173. https://pubmed.ncbi.nlm.nih.gov/33763230
35. Pugach IZ, Pugach S. (2021) Strong correlation between prevalence of severe vitamin D deficiency and population mortality rate from COVID-19 in Europe Wien Klin Wochenschr 133:403-405. https://pubmed.ncbi.nlm.nih.gov/33721102
36. Angelidi AM, Belanger MJ, Lorinsky MK, et al. (2021) Vitamin D Status Is Associated With In-Hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients. Mayo Clin Proc 96:875-886. https://pubmed.ncbi.nlm.nih.gov/33714594
37. Charoenngam N, Shirvani A, Reddy N, et al. (2021) Association of Vitamin D Status With Hospital Morbidity and Mortality in Adult Hospitalized Patients With COVID-19. Endocr Pract. 27:271-278. https://pubmed.ncbi.nlm.nih.gov/33705975
38. Mazziotti G, Lavezzi E, Brunetti A, et al. (2021) Vitamin D deficiency, secondary hyperparathyroidism and respiratory insufficiency in hospitalized patients with COVID-19. J Endocrinol Invest 2021 Mar 5;1-9. https://pubmed.ncbi.nlm.nih.gov/33666876
39. Basaran N, Adas M, Gokden Y, et al. (2021) The relationship between vitamin D and the severity of COVID-19. Bratisl Lek Listy 122:200-205. https://pubmed.ncbi.nlm.nih.gov/33618529
40. Gavioli EM, Miyashita H, Hassaneen O, Siau E (2021) An Evaluation of Serum 25-Hydroxy Vitamin D Levels in Patients with COVID-19 in New York City. J Am Coll Nutr. 2021 Feb 19;1-6. https://pubmed.ncbi.nlm.nih.gov/33605826
41. Infante M, Buoso A, Pieri M, et al. (2021) Low Vitamin D Status at Admission as a Risk Factor for Poor Survival in Hospitalized Patients With COVID-19: An Italian Retrospective Study. J Am Coll Nutr. 2021 Feb 18;1-16. https://pubmed.ncbi.nlm.nih.gov/33600292
42. Walrand S (2021) Autumn COVID-19 surge dates in Europe correlated to latitudes, not to temperature-humidity, pointing to vitamin D as contributing factor. Sci Rep 11:1981. https://pubmed.ncbi.nlm.nih.gov/33479261
43. Santaolalla A, Beckmann K, Kibaru J, et al. (2020) Association Between Vitamin D and Novel SARS-CoV-2 Respiratory Dysfunction - A Scoping Review of Current Evidence and Its Implication for COVID-19 Pandemic. Front Physiol 2020 Nov 26;11:564387. https://pubmed.ncbi.nlm.nih.gov/33324234
44. Ling SF, Broad E, Murphy R, et al. (2020) High-Dose Cholecalciferol Booster Therapy is Associated with a Reduced Risk of Mortality in Patients with COVID-19: A Cross-Sectional Multi-Centre Observational Study. Nutrients. 12:3799. https://pubmed.ncbi.nlm.nih.gov/33322317
45. Downing D (2020) How we can fix this pandemic in a Month. Orthomolecular Medicine News Service. http://orthomolecular.org/resources/omns/v16n49.shtml
46. Smith RG (2021) Vitamins and minerals for lowering risk of disease: Adding to the evidence. Orthomolecular Medicine News Service. http://orthomolecular.org/resources/omns/v17n10.shtml
47. Gonzalez MJ, Olalde J, Rodriguez JR, et al. (2018) Metabolic Correction and Physiologic Modulation as the Unifying Theory of the Healthy State: The Orthomolecular, Systemic and Functional Approach to Physiologic Optimization. J Orthomol Med. 33(1). https://isom.ca/article/metabolic-correction-physiologic-modulation-unifying-theory-healthy-state
48. Cámara M, Sánchez-Mata MC, Fernández-Ruiz V, et al. (2021) A Review of the Role of Micronutrients and Bioactive Compounds on Immune System Supporting to Fight against the COVID-19 Disease. Foods. 10:1088. https://pubmed.ncbi.nlm.nih.gov/34068930
49. Berger MM, Herter-Aeberli I, Zimmermann ME, et al. (2021) Strengthening the immunity of the Swiss population with micronutrients: A narrative review and call for action. Clin Nutr ESPEN. 43:39-48. https://pubmed.ncbi.nlm.nih.gov/34024545
50. Schuetz P, Gregoriano C, Keller U (2021) Supplementation of the population during the COVID-19 pandemic with vitamins and micronutrients - how much evidence is needed? Swiss Med Wkly. 151:w20522. https://pubmed.ncbi.nlm.nih.gov/34010429
Nutritional Medicine is Orthomolecular Medicine
Orthomolecular medicine uses safe, effective nutritional therapy to fight illness. For more information: http://www.orthomolecular.org
Find a Doctor
To locate an orthomolecular physician near you: http://orthomolecular.org/resources/omns/v06n09.shtml
The peer-reviewed Orthomolecular Medicine News Service is a non-profit and non-commercial informational resource.
Editorial Review Board:
Albert G. B. Amoa, MB.Ch.B, Ph.D. (Ghana)
Comments and media contact: firstname.lastname@example.org OMNS welcomes but is unable to respond to individual reader emails. Reader comments become the property of OMNS and may or may not be used for publication.
To Subscribe at no charge: http://www.orthomolecular.org/subscribe.html
To Unsubscribe from this list: http://www.orthomolecular.org/unsubscribe.html
This website is managed by Riordan Clinic
Information on Orthomolecular.org is provided for educational purposes only. It is not intended as medical advice.
A Non-profit 501(c)(3) Medical, Research and Educational Organization
3100 North Hillside Avenue, Wichita, KS 67219 USA
Phone: 316-682-3100; Fax: 316-682-5054
© (Riordan Clinic) 2004 - 2017
Consult your orthomolecular health care professional for individual guidance on specific health problems.
Information on Orthomolecular.org is provided for educational purposes only. It is not intended as medical advice.