Vitamins and minerals for lowering risk of disease: Adding to the evidence 維生素和礦物質可降低疾病風險

FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, April 15, 2021

by Robert G. Smith, PhD, Associate Editor

(OMNS Apr 15, 2021) There is still a huge suppression (抑制) of information about the vitamin C, D, magnesium, zinc, and selenium protocol for reducing risk of Covid-19. [1] For example, this suppression has been perpetuated (使繼續) by doctors who didn’t study nutrition in medical school, and government agencies that have promoted nutrient supplements only to prevent outright deficiencies like scurvy.

People are saying this protocol (方法) is not effective because there are no randomized (隨機的) , double-blind (雙盲 – 研究人員和參與者都不知道) studies showing its efficacy. That type of study has not been done for many reasons, including the prevailing (盛行) scientific method that only studies one nutrient at a time, the paucity (貧乏) of funding available for testing nutrient protocols — since most funding for medical treatments comes from drug companies, and the politics of the medical establishment. [1]

It would be helpful to organize a properly-done study that tests the efficacy of a supplementation protocol to prevent infection, hospitalization, and mortality. If the doses that we know are safe could be shown to be effective in a randomized double-blind study, then prophylactic supplementation could be supported by the authorities.

How can the Orthomolecular Medicine field organize such a study? With the coronavirus evolving into new variants, such a study would continue to be helpful for saving lives. And a properly organized study focused on adequate levels of essential nutrients can also test for reduction in risk for a wide variety of other diseases.

Efficacy

Clinical studies, case histories, and direct experience over many decades have shown the importance of adequate doses of essential nutrients in preventing and reversing disease. This needs to come into the public spotlight in the current COVID-19 pandemic. Nutrition therapy is firmly based on sound biological principles and established biochemical knowledge accumulated over the last century. For example, it is known that adequate doses of vitamin C, higher than the RDA, can prevent viral infection, and further can ameliorate (改善) recovery from infection and provide many other health benefits. [1-56]

In severe pneumonia caused by COVID-19 infection, vitamin C levels can drop precipitously, in effect causing local scurvy. [1-4]

Vitamin D is essential for a wide variety of hormone-like signaling in the body, and beyond its function in supporting bone health is necessary for a strong immune system. Vitamin D is known from a variety of studies to reduce the risk of viral infections such as flu and common cold, as well as COVID-19, and low levels of vitamin D are known to be a risk for worse hospital outcomes. [54-68]

Magnesium is essential for proper (恰當的) functioning of hundreds of biochemical pathways in the body, including many of those related to the function of vitamin D in the immune system and recovery from illness. [69-73]

Zinc and selenium are known to be important in the recovery from inflammation, infection, and sepsis. [55, 74, 75] And a protocol that includes all of these essential nutrients and others known to be important for health is likely to provide even greater synergistic benefits in supporting health and lowering the risk of disease. [7-9, 23-25, 58, 76]

Safety

Although clinically effective doses of vitamins and minerals are higher than the RDA, they are known to be safe for the overwhelming majority of the adult population.

Vitamin C taken a dose of 1000-3000 mg per day in divided doses is safe and well tolerated by most people. [6,20]

Vitamin D taken at a dose of 5,000 – 10,000 IU per day is safe. [58]

Magnesium at a dose of 400 – 600 mg per day in a readily absorbable form is safe for individuals except those with severely impaired kidney function, heart block, bowel obstruction, and myasthenia gravis. [73]

Zinc is safe at a dose of 20 – 50 mg per day in most individuals.

Selenium is safe at a dose of 200 mcg per day in most individuals. A protocol comprising at least these doses of essential nutrients can help to prevent and reverse viral infections.

How it’s done

Although randomized double-blind interventional studies are required to test the safety and efficacy of a potential new drug in lowering risk of infection, [77] a study of a nutritional protocol comprising essential nutrients differs in several ways.

First, since everyone requires all the essential nutrients, our bodies already contain some of each nutrient. Therefore it is necessary to take into account the existing levels and adjust doses accordingly for each individual in the study. Individuals who have adequate levels will likely not improve much, because the interventional doses will not decrease their risk as much as it will for others who are deficient. Also, the most effective protocols include several essential nutrients because they are symbiotic, so studies of one nutrient (as performed for drugs) will miss a large portion of the full efficacy. Thus the doses of all the nutrients in a study must be varied to test their combinations. Further, the absorption of nutrients from the diet or a specific protocol of supplements may differ between individuals for a variety of reasons, including lifestyle, age, normal diet, and genetic factors. Therefore, the study must determine the existing nutrient levels of each individual before and as a result of taking the vitamin and mineral protocol. [78,79]

Second, many studies of essential nutrients that are not performed according to a randomized double-blind (RCT) protocol, for example, environmental or epidemiological studies, are often observational. These do not comprise an interventional treatment, but carefully study the effect of an essential nutrient in the diet, taking into account other factors that might affect a risk. An observational study can determine the association of reduction in risk with living in a specific environment where a nutrient is present, for example, the benefit of living at a sunny equatorial latitude where vitamin D levels are generally higher. Although observational studies are often larger and more diverse, comprising more individuals and different environments or countries, they are widely considered not to be a valid test of a treatment’s efficacy, because no treatment is given and causality ostensibly cannot be determined.

However, observational studies can build on known biochemical knowledge to provide a likely cause for an observed effect. For example, since both vitamin C and vitamin D are known to be essential for the immune system, this supports findings of observational studies that these vitamins in adequate doses can lower risk of infection and ameliorate recovery. This knowledge also supports studies that show deficiencies of vitamin C and D, magnesium, zinc, and selenium in patients with severe pneumonia and/or sepsis. [1-75] Moreover, observational studies can extend the scientific knowledge relevant to a randomized double-blind study. For example, groups included in a RCT can be determined according to prior knowledge gathered from observational studies — in essence, testing whether the association proven by the wider observational studies is incidental or causal.

Ethics

Another important difference between studies of essential nutrients and drugs is that since the nutrients are known to be essential, it is unethical to allow individuals in a study to succumb to nutrient depletion. Therefore, any benefit of essential nutrients shown by prior studies must be taken into account. For example, the control group in a RCT that studies the effect of essential nutrients must receive at least the minimum daily intakes, from their normal diet and/or from supplementation, that are known to be essential. However, after testing of nutrient levels, each individual could in principle give permission to be blindly assigned into a control group that does not receive the highest doses. But those who have read up on optimal nutrient levels would likely not choose to be included in such a study that might assign lower nutrient levels. Therefore, an observational study that does not assign doses, but merely measures their levels, may be considered the most ethical. The exact methods used to set up the different control and treated groups, and the doses provided will require careful consideration.

Other conditions

Further, since excellent nutrition is widely known to enhance health, a study that tests the effect of a nutritional protocol on preventing infection could usefully be extended beyond its original intent. For example, if performed over a longer duration than 12 months, it could verify the doses required to reduce the risk of a variety of progressive diseases associated with aging, body mass index, or diet. Although small doses of essential nutrients are known to be beneficial, an interventional study testing different doses could be extended to test what reduction in risk of cardiovascular disease, diabetes, or cancer can be obtained with adequate, safe, higher doses.

The study must:

  1. Test the efficacy of the protocol using a dosing (i.e. interventional) paradigm for lowering risk of infection, need for hospitalization, and mortality. This is compatible with other forms of protection, e.g. vaccination, social distancing, and wearing masks.
  2. Be a double-blind, randomized controlled trial (RCT) study with several different dosage combinations, along with placebo controls.
  3. Measure and take into account the existing vitamin and mineral levels in the incoming study groups.
  4. Be of sufficient duration, preferably 6-12 months or more, that any incoming deficiencies of vitamins and minerals can be relieved. Notably, both vitamin D and magnesium are known to require in some cases several months of supplementation to achieve adequate levels when an individual is deficient.
  5. Be run with a sufficient number of individuals to show statistical significance.
  6. Include groups that differ in their status with respect to the condition of disease. Some groups should be in excellent health without symptoms, but other groups should include individuals with a variety of known risk factors. For example, groups comprising elderly or obese individuals, or groups that have symptoms, or who have been hospitalized.
  7. Test groups of several different populations, including different ethnic groups, in different countries, different geographic regions and climates.
  8. Include groups that have not been vaccinated for Covid-19.
  9. Check infection rates for different variants of the coronavirus.

How to organize

Since large clinical studies are generally very expensive, the study could start with several small groups comprising, for example, several hundred individuals. It could be funded by a public online funding campaign that is set up and publicized by a consortium of integrative and orthomolecular medical organizations. [e.g. 25, 80-83] Its methodology can be checked and verified by an independent group of nutrition-aware medical researchers who have experience from involvement in previous studies. The health status of participants will need to be checked upon entry by a team of medical professionals, to test existing nutrient levels and identify risk factors and potential disease conditions. An online website and phone and email hotlines can provide the support needed to answer questions about doses and complications. A sub-committee of integrative and orthomolecular medicine scientists and doctors can implement an outreach program to publicize the study for enrollment and fund-raising. It might even be possible to allow individuals to sign up for the study (as one category of included groups) after they have supported the study by donating funds at an online website.

Conclusion

The widespread use of a vitamin and mineral protocol can lower risk of virus infection and pneumonia, and can assist in stopping the pandemic. This can provide a tremendous boost in health worldwide. The protocol is safe. It does not require the type of clinical trial that establishes efficacy and safety of a new drug. Yet a double-blind randomized controlled clinical trial seems essential — if only to silence the doubt that currently exists about nutrition therapy. With a sound plan for organizing and funding a trial of this type of nutrition therapy, we can proceed to test its efficacy in fighting a variety of diseases, including viral infections.

References:

1. Doctor Y, Saul AW, Smith RG (2021) Nutrition to Treat and Prevent COVID-19. Orthomolecular Medicine News Service, http://orthomolecular.org/resources/omns/v17n03.shtml

2. Abobaker A, Alzwi A, Alraied AHA (2020) Overview of the possible role of vitamin C in management of COVID-19. Pharmacol Rep. 72:1517-1528. https://pubmed.ncbi.nlm.nih.gov/33113146

3. Holford P, Carr AC, Jovic TH, et al. (2020) Vitamin C–An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19. Nutrients, 12:3760. https://pubmed.ncbi.nlm.nih.gov/33297491

4. Xing Y, Zhao B, Yin L, et al. (2021) Vitamin C supplementation is necessary for patients with coronavirus disease: An ultra-high-performance liquid chromatography-tandem mass spectrometry finding. J Pharm Biomed Anal. 196:113927. https://pubmed.ncbi.nlm.nih.gov/33549875

5. Player G, Saul AW, Downing D, Schuitemaker G. (2020) Published Research and Articles on Vitamin C as a Consideration for Pneumonia, Lung Infections, and the Novel Coronavirus (SARS-CoV-2/COVID-19). Orthomolecular Medicine News Service. http://orthomolecular.org/resources/omns/v16n20.shtml

6. Rasmussen MPF (2020) Vitamin C Evidence for Treating Complications of COVID-19 and other Viral Infections. Orthomolecular Medicine News Service. http://orthomolecular.org/resources/omns/v16n25.shtml

7. Gonzalez MJ, Miranda-Massari JR, Rodriguez JR (2020) Antiviral Mechanisms of Vitamin C: A Short Communication ConsenThe Long Historysus Report. J Orthomol Med 35(2). https://isom.ca/article/antiviral-mechanisms-of-vitamin-c-a-short-communication-consensus-report

8. Riordan H, Riordan N, Casciari J, et al. (2021) The Riordan intravenous vitamin C (IVC) protocol for adjunctive cancer care: IVC as a chemotherapeutic and biologic response modifying agent. Riordan Clinic. https://riordanclinic.org/wp-content/uploads/2015/11/RiordanIVCprotocol_en.pdf

9. Saul AW (2020) Nutritional Treatment of Coronavirus. Orthomolecular Medicine News Service. http://orthomolecular.org/resources/omns/v16n06.shtml

10. Cerullo G, Negro M, Parimbelli M, et al. (2020) The Long History of Vitamin C: From Prevention of the Common Cold to Potential Aid in the Treatment of COVID-19. Front Immunol. 11:574029. https://pubmed.ncbi.nlm.nih.gov/33193359

11. Klenner FR. (1971) Observations On the Dose and Administration of Ascorbic Acid When Employed Beyond the Range of A Vitamin In Human Pathology. J Applied Nutrit. 23:61-87. https://seanet.com/~alexs/ascorbate/197x/klenner-fr-j_appl_nutr-1971-v23-n3&4-p61.htm

12. Klenner FR. (1948) Virus pneumonia and its treatment with vitamin C. J South Med Surg 110:36- https://www.seanet.com/~alexs/ascorbate/194x/klenner-fr-southern_med_surg-1948-v110-n2-p36.htm

13. Klenner, FR. (1951) Massive doses of vitamin C and the virus diseases. J South Med and Surg, 113:101-107. https://www.seanet.com/~alexs/ascorbate/195x/klenner-fr-southern_med_surg-1951-v103-n4-p101.htm

14. Klenner FR (1949) The Treatment of Poliomyelitis and other Virus Diseases with Vitamin C. South Med Surg. 111:209-214. https://pubmed.ncbi.nlm.nih.gov/18147027 https://vitamincfoundation.org/www.orthomed.com/polio.htm https://www.seanet.com/~alexs/ascorbate/194x/klenner-fr-southern_med_surg-1948-v110-n2-p36.htm

15. Hunt C, Chakravorty NK, Annan G, et al. (1994) The clinical effects of Vitamin C supplementation in elderly hospitalized patients with acute respiratory infections. Int J Vitam Nutr Res 64:212-219. https://www.ncbi.nlm.nih.gov/pubmed/7814237

16. Fowler AA, Truwit JD, Hite RD, et al. (2019) 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 322:1261-1270. https://pubmed.ncbi.nlm.nih.gov/31573637

17. Fowler AA, Syed AA, Knowlson S, et al. (2014) Phase I Safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med 12:32. https://pubmed.ncbi.nlm.nih.gov/24484547

18. DesBois M (2021) The Treatment of Infectious Disease Using Vitamin C and other Nutrients. Orthomolecular Medicine News Service. http://orthomolecular.org/resources/omns/v17n04.shtml

19. Jungeblut CW (1935) Inactivation of Poliomyelitis virus in vitro by crystalline vitamin C (ascorbic acid) J Exp Med. 62:517-521. https://pubmed.ncbi.nlm.nih.gov/19870431

20. Cathcart RF (1981) Vitamin C, titrating to bowel tolerance, anascorbemia, and acute induced scurvy. Med Hypotheses 7:1359-1376. https://pubmed.ncbi.nlm.nih.gov/7321921

21. McCormick WJ (1951) Vitamin C in the Prophylaxis and Therapy of Infectious Diseases. Arch Pediatr. 68:1-9. https://pubmed.ncbi.nlm.nih.gov/14800557 https://www.seanet.com/~alexs/ascorbate/195x/mccormick-wj-arch_pediatrics-1951-v68-n1-p1.htm

22. Riordan HD, Hunninghake RB, Riordan NH, et al. (2003) Intravenous ascorbic acid: protocol for its application and use. P R Health Sci J. 22:287-90. https://pubmed.ncbi.nlm.nih.gov/14619456

23. Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. (2017) Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest 151:1229-1238. https://pubmed.ncbi.nlm.nih.gov/27940189

24. Kory P, Meduri GU, Iglesias J, et al. (2021) Clinical and Scientific Rationale for the “MATH+” Hospital Treatment Protocol for COVID-19. J Intensive Care Med. 36:135-156. https://pubmed.ncbi.nlm.nih.gov/33317385

25. Front Line COVID-19 Critical Care Alliance (2021) EVMS COVID-19 Management Protocol: An overview of the MATH+ and I-MASK+ Protocols. https://covid19criticalcare.com https://www.evms.edu/media/evms_public/departments/internal_medicine/EVMS_Critical_Care_COVID-19_Protocol.pdf

26. Montel-Hagen A, Kinet S, Manel N, et al. (2008) Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C. Cell, 132:1039-1048. https://pubmed.ncbi.nlm.nih.gov/18358815

27. Nualart F, Mack L, Garcia A, et al. (2014) Vitamin C Transporters, Recycling and the Bystander Effect in the Nervous System: SVCT2 versus Gluts. J Stem Cell Res Ther 4:209. https://pubmed.ncbi.nlm.nih.gov/25110615

28. May JM, Harrison FE. (2013) Role of Vitamin C in the Function of the Vascular Endothelium. Antioxidants & Redox Signaling 19:2068-2083. https://pubmed.ncbi.nlm.nih.gov/23581713

29. Nabzdyk CS, Bittner EA. (2018) Vitamin C in the critically ill – indications and controversies. World J Crit Care Med 7:52-61. https://www.wjgnet.com/2220-3141/full/v7/i5/52.htm

30. Lee RE. (1961) Ascorbic Acid and the Peripheral Vascular System. Ann NY Acad Sci. 92:295-301. https://doi.org/10.1111/j.1749-6632.1961.tb46129.x

31. Lee RE, Holze EA. (1951) Nutritional factors in hemodynamics: dissociation of pressor response and hemorrhage resistance in avitaminosis C. Proc. Soc. Expt. Biol Med. 76:325-329. https://pubmed.ncbi.nlm.nih.gov/14827915

32. Barabutis N, Khangoora V, Marik PE, Catravas JD. (2017) Hydrocortisone and Ascorbic Acid Synergistically Prevent and Repair Lipopolysaccharide-Induced Pulmonary Endothelial Barrier Dysfunction. Chest 152:954-962. https://pubmed.ncbi.nlm.nih.gov/28739448

33. Parker WH, Rhea EM, Qu ZC. (2016) Intracellular ascorbate tightens the endothelial permeability barrier through Epac1 and the tubulin cytoskeleton. Am J Physiol Cell Physiol. 311:C652-C662. https://pubmed.ncbi.nlm.nih.gov/27605450

34. Gu W, Cheng A, Barnes H, et al. (2014) Vitamin C Deficiency Leading to Hemodynamically Significant Bleeding. JSM Clinical Case Reports 2:1046. https://www.jscimedcentral.com/CaseReports/casereports-2-1046.pdf

35. Zhao B, Fei J, Chen Y, et al. (2014) Vitamin C treatment attenuates hemorrhagic shock related multi-organ injuries through the induction of heme oxygenase-1. BMC Complementary and Alternative Medicine 14:442-454. https://pubmed.ncbi.nlm.nih.gov/25387896

36. Ladumer A, Schmitt CA, Schachner D, et al. (2012) Ascorbate stimulates endothelial nitric oxide synthase enzyme activity by rapid modulation of its phosphorylation status. Free Radic Biol Med. 52:2082-2090. https://pubmed.ncbi.nlm.nih.gov/22542797

37. Heller R, Munscher-Paulig F, Grabner R, Till V. (1999) L-Ascorbic Acid Potentiates Nitric Oxide Synthesis in Endothelial Cells. J Biol Chem 274:8254-8260. https://pubmed.ncbi.nlm.nih.gov/10075731

38. Dingchao H, Zhduan Q, Xiaodong F. (1994) The Protective Effects of High-Dose Ascorbic Acid on Myocardium against Reperfusion Injury During and After Cardiopulmonary Bypass. Thorac Cardiovasc Surg 42:276-278. https://pubmed.ncbi.nlm.nih.gov/7863489

39. Ichim TE, Minev B, Braciak T, et al. (2011) Intravenous ascorbic acid to prevent and treat cancer-associated sepsis? J Transl Med 9:25. https://pubmed.ncbi.nlm.nih.gov/21375761

40. Cisternas P, Silva-Alvarez C, Martinez F, et al. (2014) The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy metabolism. J Neurochem 129: 663-671. https://pubmed.ncbi.nlm.nih.gov/24460956

41. Wang Y, Lin H, Lin BW, et al. (2019) Effects of different ascorbic acid doses on the mortality of critically ill patients: a meta-analysis. Ann Intensive Care 9:58. https://pubmed.ncbi.nlm.nih.gov/31111241

42. Boretti A, Banik BK. (2020) Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome. PharmaNutrition 12:100190. https://pubmed.ncbi.nlm.nih.gov/32322486

43. Iglesias J, Vassallo AV, Patel V et al. (2020) Outcomes of metabolic resuscitation using ascorbic acid, thiamine, and glucocorticoids in the early treatment of sepsis. Chest 158:164-173. https://pubmed.ncbi.nlm.nih.gov/32194058

44. de Melo AF, Homem-de-Mello M. (2020) High-dose intravenous vitamin C may help in cytokine storm in severe SARS-CoV-2 infection. Crit Care 24:500. https://pubmed.ncbi.nlm.nih.gov/32792018

45. Zhang J, Rao X, Li Y et al. (2021) Pilot trial of high-dose vitamin C in critically ill COVID-19 patients. Ann Intenisve Care 11:5. https://pubmed.ncbi.nlm.nih.gov/33420963

46. Lankadeva YR, Peiris RM, Okazaki N, et al. (2021) Reversal of the pathophysiological responses to Gram-negative sepsis by megadose Vitamin C. Crit Care Med 49:e179-e190. https://pubmed.ncbi.nlm.nih.gov/33239507

47. Patterson G, Isales CM, Fulzele S. (2021) Low level of vitamin C and dysregulation of vitamin C transporter might be involved in the severity of COVID-19 infection. Aging and Disease 12:14-26. https://pubmed.ncbi.nlm.nih.gov/33532123

48. Tomassa-Irriguible TM, Lielsa-Berrocal L. (2020) COVID-19: Up to 87% critically ill patients had low vitamin C values. Research Square, preprint. https://www.researchsquare.com/article/rs-89413/v1

49. Wagas Khan HM, Parikh N, Megala SM, Predeteanu GS. (2020) Unusual Recovery of a Critical COVID-19 Patient After Administration of Intravenous Vitamin C. Am J Case Rep 21: e925521. https://pubmed.ncbi.nlm.nih.gov/32709838

50. Marik PE. (2018) Hydrocortisone, Ascorbic Acid and Thiamine (HAT therapy) for the treatment of sepsis. Focus on ascorbic acid. Nutrients 10:1762. https://pubmed.ncbi.nlm.nih.gov/30441816

51. May JM, Qu ZC. (2011) Ascorbic acid prevents oxidant-induced increases in endothelial permeability. Biofactors 37:46-50. https://pubmed.ncbi.nlm.nih.gov/21328627

52. Utoguchi N, Ikeda K, Saeki K et al. (1995) Ascorbic acid stimulates barrier function of cultured endothelial cell monolayer. J Cell Physiol 163:393-399. https://pubmed.ncbi.nlm.nih.gov/7706381

53. Han M, Pendem S, Teh SL, et al. (2010) Ascorbate protects endothelial barrier function during septic insult: Role of protein phosphatase type 2A. Free Radic Biol Med. 48:128-135. https://pubmed.ncbi.nlm.nih.gov/19840845

54. Arvinte C, Singh M, Marik PE. 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. Medicine in Drug Discovery 8:100064. https://pubmed.ncbi.nlm.nih.gov/32964205

55. Belsky JB, Wira CR, Jacob V, et al. (2018) A review of micronutrients in sepsis: the role of thiamine, l-carnitine, vitamin C, selenium and vitamin D. Nutr Res Rev. 31:281-290. https://pubmed.ncbi.nlm.nih.gov/29984680

56. Bae M, Kim H (2020) The Role of Vitamin C, Vitamin D, and Selenium in Immune System against COVID-19. Molecules, 25:5346. https://pubmed.ncbi.nlm.nih.gov/33207753

57. Moraes RB, Friedman G, Wawrzeniak IC, et al. (2015) Vitamin D deficiency is independently associated with mortality among critically ill patients. Clinics. 70:326-332. https://pubmed.ncbi.nlm.nih.gov/26039948

58. Downing D. (2020) How we can fix this pandemic in a month. Othomolecular Medicine News Service. http://orthomolecular.org/resources/omns/v16n49.shtml

59. Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JA, Bhattoa HP. (2020) Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients, 12:988. https://www.mdpi.com/2072-6643/12/4/988

60. Entrenas Castillo M, 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. J Steroid Biochem Mol Biol. 203:105751. https://pubmed.ncbi.nlm.nih.gov/32871238

61. Ilie, P., Stefanescu, S., Smith, L. (2020) The role of Vitamin D in the prevention of Coronavirus Disease 2019 infection and mortality. Aging Clinical and Experimental Research, 32:1195-1198 https://link.springer.com/article/10.1007/s40520-020-01570-8

62. 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

63. Kaufman HW, Niles JK, Kroll MH, et al. (2020) SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS One, 15(9):e0239252. https://pubmed.ncbi.nlm.nih.gov/32941512

64. Schwalfenberg, G. (2015). Vitamin D for influenza. Canadian Family Physician, 61: 507. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463890

65. Dancer, R. C. A., Parekh, D., Lax, S., et al (2015). Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS). Thorax, 70(7), 617-624. https://doi.org/10.1136/thoraxjnl-2014-206680

66. Sulli A, Gotelli E, Casabella A, et al. (2021) Vitamin D and Lung Outcomes in Elderly COVID-19 Patients. Nutrients, 13:717. https://pubmed.ncbi.nlm.nih.gov/33668240

67. Ames BN, Grant WB, Willett WC (2021) Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities? Nutrients 13:499. https://pubmed.ncbi.nlm.nih.gov/33546262

68. Mariani J, Gimenez VMM, Bergam I, et al. (2020) Association Between Vitamin D Deficiency and COVID-19 Incidence, Complications, and Mortality in 46 Countries: An Ecological Study. Health Secur. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/33325788

69. Noormandi A, Khalili H, Mohammadi M, et al. (2020) Effect of magnesium supplementation on lactate clearance in critically ill patients with severe sepsis: a randomized clinical trial. Eur J Clin Pharmacol 76:175-184. https://pubmed.ncbi.nlm.nih.gov/31814044

70. Velissaris D, Karamouzos V, Pierrakos C, et al. (2015) Hypomagnesemia in critically ill sepsis patients. J Clin Med Res 2015;7:911-918. https://pubmed.ncbi.nlm.nih.gov/26566403

71. Guerin C, Cousin C, Mignot F, et al. (1996) Serum and erythrocyte magnesium in critically ill patients. Intensive Care Med 22:724-727. https://pubmed.ncbi.nlm.nih.gov/8880238

72. Workinger JL, Doyle RP, Bortz J (2018) Challenges in the Diagnosis of Magnesium Status. Nutrients. 10:1202. https://pubmed.ncbi.nlm.nih.gov/30200431

73. Dean, C. (2017) The Magnesium Miracle. 2nd Ed., Ballantine Books, ISBN-13: 978-0399594441.

74. Alker W, Haase H. (2018) Zinc and Sepsis. Nutrients 10:976. https://pubmed.ncbi.nlm.nih.gov/30060473

75. Angstwurm MW, Engelmann L, Zimmermann T, et al. (2007) Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Crit Care Med. 35:118-26. https://pubmed.ncbi.nlm.nih.gov/17095947

76. 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

77. Matthews JNS (2006) Introduction to Randomized Controlled Clinical Trials, 2nd Ed., Chapman & Hall / CRC. ISBN-13: 9781-584886242.

78. Passwater M. (2021 The VICTAS Trial: Designed to Fail. Orthomolecular Medicine News Service. http://orthomolecular.org/resources/omns/v17n08.shtml

79. Heaney RP. (2014) Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr Rev 72:48-54. https://pubmed.ncbi.nlm.nih.gov/24330136

80. International Society of Orthomolecular Medicine. https://www.isom.ca

81. Vitamin C for COVID. https://www.vitaminc4covid.com

82. Alliance for Natural Health, International. https://www.anhinternational.org

83. Alliance for Natural Health, USA. https://anh-usa.org

Nutritional Medicine is Orthomolecular Medicine

Orthomolecular medicine uses safe, effective nutritional therapy to fight illness. For more information: http://www.orthomolecular.org

$$$ 如果你愿意,你可以在这捐款支持我们。谢谢。$$$
$$$ If you would, you can make a donation here to support us. Thank you. $$$

4