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FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, December 23, 2020

Do the Math: "MATH+" Saves Lives

by Michael Passwater

(OMNS Dec 23, 2020) As the SARS-CoV-2 pandemic moved into North America, five experienced critical care physicians formed the "Front Line Covid-19 Critical Care Alliance" (FLCCC Alliance). [1] This working group, initially composed of critical care physicians Pierre Kory, G. Umberto Meduri, Jose Iglesias, Joseph Varon, and Paul Marik, was and remains devoted to developing and refining treatment protocols against Covid-19. In 2017, with the addition of intravenous hydroxycortisone (cortisol), ascorbic acid (vitamin C), and thiamine (vitamin B1) to standard sepsis care, Dr. Paul Marik found great success against sepsis, including septic shock. This became known as "HAT" therapy for sepsis, and was a starting point for the FLCCC Alliance in the battle against Covid-19. Given the complexity of Covid-19, the "HAT" therapy was quickly expanded to the "MATH+" protocol for the care of hospitalized Covid-19 patients.

M = Methylprednisolone; 80 mg loading dose then 40 mg q 12 hours for at least 7 days and until transferred out of the ICU

A = Ascorbic acid; 3 g IV q 6 hours for at least 7 days and/or until transferred out of ICU.

T = Thiamine; 200 mg IV q 12 hours

H = Heparin (low molecular weight heparin); 1 mg/Kg subcutaneous q 12 hours, unless contraindicated

+ = Vitamin D3, melatonin, zinc, magnesium, B complex vitamins, atervastin, famotdine, and therpapeutic plasma exchange if indicated

"If what you are doing isn't working, change what you are doing." (Paul E. Marik, MD)

Early intervention and avoiding mechanical ventilation were also key aspects of their approach. The results through July 2020 at two hospitals implementing the MATH+ protocol have completed peer review and are now published online [2] What they found seems miraculous. Dr. Joseph Varon's team at United Memorial Medical Center in Houston, TX treated 140 hospitalized Covid-19 patients through July with a survival rate of 95.6%, and Dr. Paul Marik's team at Sentara Norfolk General Hospital in Norfolk, VA treated 191 hospitalized Covid-19 patients with a survival rate of 93.9%. A difference between the sites is that UMMC begins the protocol in the Emergency Department whereas Norfolk General begins the protocol in the ICU. In comparison, 461 other hospitals in the USA, UK, and China not using the MATH+ protocol had published survival rates ranging from 68% to 84.4%. With the CDC reporting over 5,000 hospitalized Covid-19 patients in the United States during the last week of November, wide use of the MATH+ could represent many thousands of additional survivors over the coming months. As of 12/18/2020, the number of physicians reporting using some or all of the MATH+ protocol has grown to above 120.

The article concludes:

"...the varied pathophysiologic mechanisms identified in COVID-19 likely require multiple therapeutic agents working in concert to counteract the diverse, deleterious consequences of this aberrant immune response. It is exceedingly unlikely that a "magic bullet" will be found, or even a medicine which would be effective at multiple stages of the disease. The Math+ treatment protocol instead offers an inexpensive combination of medicines with a well-known safety profile based on strong physiologic rationale and an increasing clinical evidence base which potentially offers a life-saving approach to the management of COVID-19 patients."

Surviving a hospital stay is great, but staying well enough to not need inpatient hospital care is even better. The FLCCC Alliance has developed the I-MASK protocol for outpatient care. [3] In October, the medication ivermectin was added to the inpatient (MATH+) and outpatient (I-MASK) protocols. Ivermectin is in inexpensive, widely available medication earning the 2015 Nobel Prize for Physiology or Medicine for its anti-parasitic effects. [4] It appears to be an effective anti-viral agent as well. [5-9]

This study adds to the pile of dozens of publications, including 2 prospective randomized controlled trials with vitamin D, associating better Covid-19 outcomes with sufficient vitamin D, zinc, vitamin C, and/or selenoproteins. [10-20]

Discoveries and reminders from the SARS-CoV-2 pandemic:

1. Ascorbic acid is very effective in the battle against known and unknown infectious agents. This has been known since the 1940s. Dr. Marik's recent work has helped expand our understanding of the anti-inflammatory and endothelial cell (blood vessel) healing synergism from co-administration of ascorbic acid and cortisol. [21-40]

  1. The three biggest life threatening aspects of serious Covid-19 disease are hyper-inflammation, hyper-coagulation, and severe hypoxia. Ascorbic acid's impact on immune cells, endothelial cells, and airway tissues helps to mitigate all three concerns. [21-23,31,41-53]
  2. In the critical care setting, the intravenous coadministration of cortisol and ascorbic acid has been shown to begin reversal of glycocalyx and endothelial cell damage within minutes.
  3. Frequent dosing to maintain a steady state is better, because ascorbic acid has a short half-life. Early intervention is better, because activated white blood cells are dependent on a high level of ascorbic acid. Taking gram quantities with each meal, and increasing intake to bowel tolerance during illness, is helpful. When ill, it is necessary to take ascorbic acid throughout the day, much more than can be absorbed in one sitting.

Dr. Joseph Varon has worked 270 consecutive days and counting. He and his team use the MATH+ protocol, and see >95% of their Covid-19 patients survive.

2. Nutrients do not work alone; observational and/or interventional studies that test the effect of administering single nutrients are likely to miss confounding factors and essential synergies needed for optimal benefit and accurate assessment. [54-56]

3. Maintaining a vitamin D blood level of 40 - 80 ng/mL is a key part of optimizing immune health.

  1. Vitamin D is a powerful hormone, impacting the expression and function of over 3,000 genes, and is a major component of the innate and adaptive immune systems. Dr. Will Taylor has shown two of these genes, TRXND1 and GCLC, become an important battleground during SARS-Cov-2 infection. He has shown that the virus suppresses expression of genes associated with key antioxidants, regulators of DNA synthesis, ferroptosis, and endoplasmic reticulum stress (TXNRD1, TXNRD3, GCLC, GPX4, SELENOF, SELENOK, SELENOM, SELENOS), while vitamin D significantly upregulates two of these genes: TXNRD1 and GCLC. [57]
  2. Studies of healthy tribal populations in non-industrialized countries have shown blood vitamin D levels of 40 ng/mL. [58]
  3. In 1903, Niels Ryberg Finsen received the Nobel Prize in Physiology and Medicine "in recognition of his contribution to the treatment of diseases...with concentrated light radiation, whereby he has opened a new avenue for medical science." [59]
  4. Vitamin D insufficiency and deficiency has been associated with increased risk of cardiovascular death, ICU death, and Covid-19 death. [15,60,61]
  5. Magnesium is an essential cofactor in vitamin D metabolism (as well as being an essential co-factor for biologically active ATP). [60]
  6. Balancing D3 intake with vitamin K2 is important for optimal calcium metabolism and distribution. A ratio of 125-250 mcg (5,000-10,000 IU) D3 to 100 mcg K2 MK7 is helpful. [62,63]
  7. Renal disease seriously impairs D3 and selenoprotein metabolism. [64,65]

4. Vitamin D and Selenium are intimately connected in human biochemistry.

  1. Dr. Schutze et al published in 1999 that the effective upregulation of TXNRD1 by vitamin D3 required an adequate level of selenium. [66]
  2. Both D3 and the essential amino acid selenocysteine must be present in adequate quantities for effective production of several selenoproteins in humans. [67]
  3. Co-supplementation with D3 and L-cysteine has been shown to improve the status of GSH, CYP24A1, and vitamin D regulatory genes including greater upregulation of PGC-1alpha, NRF2, and GLUT-4 gene expression compared to D3 alone. [68]
  4. GSH, in turn, increases circulating vitamin D and augments the actions of vitamin D. [69-71]

5. Vitamin D and selenoproteins are necessary for the formation and maintenance of immune memory cells. Not only does insufficiency increase the risk of infectious illness, it also impacts the lasting benefit of adaptive immunity from the infection. This may also have implications for the success of vaccination efforts. [12,13,72-75]

6. Selenium concentrations of 70 - 150 ng/mL are consistent with good health in the general population. Blood selenoprotein P levels of 4.3 +/- 1.0 mg/L have been associated with improved outcomes in Covid-19 patients; maintenance of Zn and SELENOP within the reference range has been shown to indicate high survival odds. [14,76-78]

7. Germ theory is helpful, but the host constitution still matters. Inadequate nutrition remains global and national public health enemy #1.

  1. Host factors impact the pathogenicity of many viruses. Many impactful host factors are modifiable and related to nutrition. [79-83]
  2. Some viruses mutate into more harmful strains when they replicate within a malnourished environment - particularly in selenium deficient environments. "Second-hand malnutrition" is an underappreciated concept. As long as people are malnourished, more virulent strains are likely to continue to emerge which then also put nourished people at risk due to the viral mutations. [84]
  3. Fighting infections greatly increases metabolic demand on the human body. Viruses need nutrients too; theft and/or destruction of host nutrients and essential proteins further impacts the need for additional nutrients for people to eliminate and recover from infections. [76, 85-87]

(Michael Passwater is certified by the American Society for Clinical Pathology as a Medical Technologist, a specialist in Immunohematology, and a diplomate in Laboratory Management. He has worked in clinical laboratories for 28 years, and has a Bachelor of Science degree in Medical Technology from the University of Delaware. The son of Dr. Richard Passwater, he has taken vitamin C and other nutrient supplements since before he was born.)


References

1. Front Line Covid-19 Critical Care Alliance https://covid19criticalcare.com

2. Kory P, Meduri GU, Iglesias J, Varon J, Marik PE. Clinical and Scientific Rationale for the "MATH+" Hospital Treatment Protocol for COVID-19. Journal of Intensive Care Medicine. https://doi.org/10.1177/0885066620973585

3. FLCC Alliance (2020) I-MASK+ Protocol. https://hardball.parkoffletter.org/wp-content/uploads/2020/12/FLCCC-I-MASK-Protocol-v6-2020-12-09-ENGLISH.pdf

4. The Nobel Prize in Physiology or Medicine 2015. NobelPrize.org. Nobel Media AB 2020. https://www.nobelprize.org/prizes/medicine/2015/summary

5. Tay MYF, Fraser JE, Chan WKK, et al. (2013) Nuclear localization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin. Antiviral Research. 99:301-306. https://pubmed.ncbi.nlm.nih.gov/23769930

6. Varghese FS, Kaukinen P, Gläsker S, et al. (2016) Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses. Antiviral Research. 126:117-124. https://pubmed.ncbi.nlm.nih.gov/26752081

7. Wagstaff KM, Sivakumaran H, Heaton SM, et al. (2012) Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochemical Journal. 443:851-856. https://pubmed.ncbi.nlm.nih.gov/22417684

8. King CR, Tessier TM, Dodge MJ, et al. (2020) Inhibition of Human Adenovirus Replication by the Importin alpha/beta1 Nuclear Import Inhibitor Ivermectin. Journal of Virology. 94:e00710-20. https://pubmed.ncbi.nlm.nih.gov/32641484

9. Caly L, Druce JD, Catton MG, et al. (2020) The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 178:104787. https://pubmed.ncbi.nlm.nih.gov/32251768

10. Kaufman HW, Niles JK, Kroll MH, Bi C, Holick MF (2020) SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS ONE 15:e0239252. https://doi.org/10.1371/journal.pone.0239252

11. Mercola J, Grant WB, Wagner CL. (2020) Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity. Nutrients, 12:3361. https://www.mdpi.com/2072-6643/12/11/3361

12. Zhang J, Taylor EW, Bennett K, Saad R, Rayman MP. (2020) Association between regional selenium status and reported outcome of COVID-19 cases in China. Am J Clin Nutr, 111:1297-1299. https://doi.org/10.1093/ajcn/nqaa095

13. Moghaddam A, Heller RA, Sun Q, et al. (2020) Selenium deficiency is associated with mortality risk from COVID-19. Nutrients 12:2098. https://doi.org/10.3390/nu12072098

14. Heller RA, Sun Q, Hackler J et al. (2021) Prediction of survival odds in COVID-19 by zinc, age, and selenoprotein P as composite biomarker. Redox Biology 38:101764. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/33126054

15. Merzon E. (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

16. Castillo ME, Costa LME, Barrios JMV, 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 203:105757. https://pubmed.ncbi.nlm.nih.gov/32871238

17. Jungreis I, Kellis M. (2020) Mathematical analysis of Cordoba calcifediol trial suggest strong role for vitamin D in reducing ICU admissions of hospitalized COVID-19 patients. MedRxiv preprint. https://doi.org/10.1101/2020.11.08.20222638

18. Grassroots Health Nutrient Research Institute. https://www.grassrootshealth.net

19. Polonikov, A. (2020) Endogenous deficiency of glutathione as the most likely cause of serious manifestations and death in COVID-19 patients. ACS Infect Dis 2020, 6, 7, 1558-1562. https://doi.org/10.1021/acsinfecdis.0c00288

20. Horowitz RI, Freeman PR, Bruzzese J. (2020) Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases. Respir Med Case Rep 2020, 101063. https://doi.org/10.1016/j.rmcr.2020.101063

21. 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 2014, 14:442-454. https://pubmed.ncbi.nlm.nih.gov/25387896

22. Oudemans-van Straaten HM, Spoelstra-de Man AME, de Waard MC. (2014) Vitamin C revisited. Critical Care 18:460-473. https://pubmed.ncbi.nlm.nih.gov/25185110

23. Fowler AA, Syed AA, Knowlson S, Natarajan R, et al. (2014) Phase I Safety trial of intravenous ascorbic acid in patients with severe sepsis. Journal of Translational Medicine, 12:32. https://pubmed.ncbi.nlm.nih.gov/24484547

24. Gu W, Cheng A, Barnes H, Kuhn B, Schivo M. (2014) Vitamin C Deficiency Leading to Hemodynamically Significant Bleeding. JSM Clinical Case Reports. 2:1046. http://www.jscimedcentral.com/CaseReports/casereports-2-1046.pdf

25. Manning J, Mitchell B, Appaduras DA, May JM, et al. (2013) Vitamin C Promotes Maturation of T-Cells. Antioxid Redox Signal. 19:2054-2067. https://pubmed.ncbi.nlm.nih.gov/23249337

26. 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. 2012 May 15; 52:2082-2090. https://pubmed.ncbi.nlm.nih.gov/22542797

27. Reddell L, Cotton BA. (2012) Antioxidant and micronutrient supplementation in trauma patients. Curr Opin Clin Nutr Metab Care. 15:181-187. https://pubmed.ncbi.nlm.nih.gov/22261953

28. May JM, Qu ZC. (2010) Ascorbic Acid Prevents Increased Endothelial Permeability Caused by Oxidized Low Density Lipoprotein. Free Radical Res. 44:1359-1368. https://pubmed.ncbi.nlm.nih.gov/20815791

29. Duconge J, Miranda-Massari JR, Gonzalez MJ, et al. (2008) Pharmacokinetics of vitamin C: insights into the oral and intravenous administration of ascorbate. P R Health Sci J. 27:7-19. http://prhsj.rcm.upr.edu/index.php/prhsj/article/view/13

30. Deicher R, Ziai F, Begknayer C, et al. (2005) Low Total Vitamin C Plasma Level Is a Risk Factor for Cardiovascular Morbidity and Mortality in Hemodialysis Patients. J Am Soc Nephrol. 16:1811-1818. https://pubmed.ncbi.nlm.nih.gov/15814831

31. 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

32. Leibovitz B, Siegel BV. (1978) Ascorbic acid, neutrophil function, and the immune response. Int J Vitam Nutr Res. 48:159-164. https://pubmed.ncbi.nlm.nih.gov/357320

33. 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 Nutrition, 1971, Vol 23:61-87. https://jeffreydachmd.com/wp-content/uploads/2013/07/Ascorbic_Acid_Fred_klenner_1971.pdf

34. Lee RE. (1961) Ascorbic Acid and the Peripheral Vascular System. Ann N Y Acad Sci. 92:295-301. https://pubmed.ncbi.nlm.nih.gov/13760268

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

36. McCormick WJ. (1951) Vitamin C in the Prophylaxis and Therapy of Infectious Diseases. Arch Pediatr, 68:1-9.

37. Klenner FR. (1949) The Treatment of Poliomyelitis and Other Virus Diseases with Vitamin C. Journal of Southern Medicine and Surgery, 111:209-214. https://pubmed.ncbi.nlm.nih.gov/18147027 https://www.seanet.com/~alexs/ascorbate/194x/klenner-fr-southern_med_surg-1949-v111-n7-p209.htm

38. Klenner FR. (19448) Virus Pneumonia and its Treatment with Vitamin C. Journal of Southern Medicine and Surgery, 110:36-38. https://pubmed.ncbi.nlm.nih.gov/18900646 https://www.mv.helsinki.fi/home/hemila/CP/Klenner_1948_ch.pdf

39. Lee RE, Lee NZ. (1947) The peripheral vascular system and its reactions in scurvy; an experimental study. Am J Physiol, 149:465-475. https://pubmed.ncbi.nlm.nih.gov/20239975

40. 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

41. Colunga Biancatelli RM, Berrill M, Catravas JD, Marik PE. (2020) Quercetin and Vitamin C: An experimental, synergistic therapy for the prevention and treatment of SARS-CoV-2 related disease (COVID-19). Front Immunol, 11:1451. https://pubmed.ncbi.nlm.nih.gov/32636851

42. Colunga Biancatelli RM, Berrill M, Marik PE. (2020) The antiviral properties of vitamin C. Expert Rev Anti Infect Ther, 18:99-101. https://pubmed.ncbi.nlm.nih.gov/31852327

43. Barabutis N, Khangoora V, Marik PE, Catravas JD. (2017) Hydrocortisone and Ascorbic Acid synergistically protect and repair lipopolysaccharide-induced pulmonary endothelial barrier dysfunction. Chest, 152:954-962. https://pubmed.ncbi.nlm.nih.gov/28739448

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. 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

45. 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

46. 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

47. Han M, Pendem S, Teh SL, Sukumaran DK, Wu F, Wilson JX. (2010) Ascorbate protects endothelial barrier function during septic insult: Role of protein phosphatase type 2A. Free Radic Biol Med 2010; 48:128-35. https://pubmed.ncbi.nlm.nih.gov/19840845

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

49. Bharara A, Grossman C, Grinnon D, et al. (2016) Intravenous Vitamin C Administered as Adjunctive Therapy for Recurrent Acute Respiratory Distress Syndrome. Case Rep Crit Care. 2016:8560871. https://pubmed.ncbi.nlm.nih.gov/27891260

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

51. Marik PE, Khangoora V, Rivera R, et al. (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

52. 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

53. Parker WH, Rhea EM, Qu ZC, Hecker MR, May JM. (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

54. Ferry M, Coley N, Andrieu S, et al. (2013) How to design nutritional intervention trials to populations and apply for efficacy claims: a statement from the international academy on nutrition and aging task force.J Nutr Heal Aging. 17:619-523. https://pubmed.ncbi.nlm.nih.gov/23933873

55. Bieri JG. (1964) Synergistic effects between antioxidants and selenium or vitamin E. Biochem Pharmacol. 13:1465-1470. https://pubmed.ncbi.nlm.nih.gov/14239620

56. Badmaev V, Majeed M, Passwater RA. (1996) Selenium: A Quest for Better Understanding. Altern Ther Health Med. 2:59-62, 65-67. https://pubmed.ncbi.nlm.nih.gov/8795924

57. Taylor, E.W. RNA viruses vs. DNA synthesis: a general viral strategy that may contribute to the protective antiviral effects of selenium. Preprints 2020, 10.20944/preprints202006.0069.v1, 2020060069, http://doi.org/10.20944/preprints202006.0069.v1

58. Luxwolda MF, Kuipers RS, Kema IP, Dijck-Brouwer DA, Muskiet FA. (2012) Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l. Br J Nutr. 108:1557-1561. https://pubmed.ncbi.nlm.nih.gov/22264449

59. The Nobel Prize in Physiology or Medicine 1903. NobelPrize.org. Nobel Media AB 2020. https://www.nobelprize.org/prizes/medicine/1903/summary

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

61. Deng X, Song Y, Manson JE, et al. (2013) Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III. BMC Med, 11:187. https://pubmed.ncbi.nlm.nih.gov/23981518

62. Flore R, Ponziani FR, Di Rienzo TA, et al. (2013) Something more to say about calcium homeostasis: the role of vitamin K2 in vascular calcification and osteoporosis. Eur Rev Med Pharmacol Sci. 17:2433-2440. https://pubmed.ncbi.nlm.nih.gov/24089220

63. Schwalfenberg GK. (2017) Vitamins K1 and K2: The Emerging Group of Vitamins Required for Human Health. J Nutr Metab. 2017:6254836. https://pubmed.ncbi.nlm.nih.gov/28698808

64. Bosworth C, de Boer IH. (2013) Impaired vitamin D metabolism in CKD. Semin Nephrol. 33:158-168. https://pubmed.ncbi.nlm.nih.gov/23465502

65. Reinhardt W, Dolff S, Benson S, et al. (2015) Chronic Kidney Disease Distinctly Affects Relationship Between Selenoprotein P Status and Serum Thyroid Hormone Parameters. Thyroid. 25:1091-1096. https://pubmed.ncbi.nlm.nih.gov/26348725

66. Schütze N, Fritsche J, Ebert-Dumig R, et al. (1999) The selenoprotein thioredoxin reductase is expressed in peripheral blood monocytes and THP1 human myeloid leukemia cells--regulation by 1,25-dihydroxyvitamin D3 and selenite. Biofactors, 10:329-338, https://pubmed.ncbi.nlm.nih.gov/10619700

67. Jain SK, Micinski D. (2013) Vitamin D upregulates glutamate cysteine ligase and glutathione reductase, and GSH formation, and decreases ROS and MCP-1 and IL-8 secretion in high-glucose exposed U937 monocytes. Biochem Biophys Res Commun 437:7-11, https://pubmed.ncbi.nlm.nih.gov/23770363

68. Alvarez JA, Chowdhury R, Jones DP, et al. (2014) Vitamin D status is independently associated with plasma glutathione and cysteine thiol/disulphide redox status in adults. Clin Endocrinol (Oxf) 81:458-466. https://pubmed.ncbi.nlm.nih.gov/24628365

69. Parsanathan R, Jain SK. (2019) Glutathione deficiency induces epigenetic alterations of vitamin D metabolism genes in the livers of high-fat diet-fed obese mice. Sci Rep. 9:14784. https://pubmed.ncbi.nlm.nih.gov/31616013

70. Fan YG, Pang ZQ, Wu TY, et al. (2020) Vitamin D deficiency exacerbates Alzheimer-like pathologies by reducing antioxidant capacity. Free Radic Biol Med. 161:139-149. https://pubmed.ncbi.nlm.nih.gov/33068737

71. Jain SK, Parsanathan R, Achari AE, et al. (2017) Glutathione Stimulates Vitamin D Regulatory and Glucose Metabolism Genes, Lowers Oxidative Stress and Inflammation, and Increases 25-Hydroxy-Vitamin D Levels in Blood: A Novel Approach to Treat 25-Hydroxyvitamin D Deficiency. Antioxid Redox Signal. 29:1792-1807. https://pubmed.ncbi.nlm.nih.gov/30160165

72. Guillin OM, Vindry C, Ohlmann T, Chavatte L. (2019) Selenium, Selenoproteins, and Viral Infection. Nutrients, 11:2101. https://doi.org/10.3390/null092101

73. Huang Z, Rose AH, Hoffman PR. (2012) The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities. Antioxid Redox Signal. 16:705-743. https://pubmed.ncbi.nlm.nih.gov/21955027

74. Cantorna MT, Snyder L, Lin Y0D, Yang L. (2015) Vitamin D and 1,25(OH)2D Regulation of T cells. Nutrients, 7:3011-3021. https://pubmed.ncbi.nlm.nih.gov/25912039

75. Looman KIM, Jansen MAE, Voortman T, et al. (2017) The role of vitamin D on circulating memory T cells in children: The generation R Study. Pediatr. Allergy Immunol. 28:579-587. https://pubmed.ncbi.nlm.nih.gov/28686349

76. Taylor EW, Radding W. (2020) Understanding Selenium and Glutathione as Antiviral Factors in COVID-19: Does the Viral M pro Protease Target Host Selenoproteins and Glutathione Synthesis? Front Nutr 7:143. https://pubmed.ncbi.nlm.nih.gov/32984400

77. Bellinger FP, Ramoy AV, Reeves MA, Berry MJ. (2009) Regulation and function of selenoproteins in human disease. Biochem J, 422:11-22. https://pubmed.ncbi.nlm.nih.gov/19627257

78. Hiffler L, Rakotoambinina B. (2020) Selenium and RNA viruses interactions: Potential implications for SARSCov-2 infection (COVID-19). Front Nutr. 7:164. https://pubmed.ncbi.nlm.nih.gov/33015130

79. Beck MA, Levander OA, Handy J. (2003) Selenium deficiency and viral infection. J Nutr. 133(5 Suppl 1):1463S-1467S. https://pubmed.ncbi.nlm.nih.gov/12730444

80. Cunningham-Rundles S, McNeeley DF, Moon A.(2005) Mechanisms of nutrient modulation of the immune response. J Allergy Clin Immunol. 115:1119-1128; quiz 1129. https://pubmed.ncbi.nlm.nih.gov/15940121

81. Hoffmann PR, Berry MJ. (2008) The influence of selenium on immune responses. Mol Nutr Food Res. 52:1273-1280. https://pubmed.ncbi.nlm.nih.gov/18384097

82. Taylor AK, Cao W, Vora KP, et al. (2013) Protein energy malnutrition decreases immunity and increases susceptibility to influenza infection in mice. J Infect Dis. 207:501-510. https://pubmed.ncbi.nlm.nih.gov/22949306

83. Beck MA, Handy J, Levander OA. (2004) Host nutritional status: the neglected virulence factor. Trends Microbiol, 12:417-423. https://pubmed.ncbi.nlm.nih.gov/15337163

84. Harthill M. (2011) Review: micronutrient selenium deficiency influences evolution of some viral infectious diseases. Biol Trace Elem Res. 143:1325-1336. https://pubmed.ncbi.nlm.nih.gov/21318622

85. Mak TW, Grusdat M, Duncan GS, et al. (2017) Glutathione Primes T cell Metabolism for Inflammation. Immunity. 46:675-689, 1089-1090. https://pubmed.ncbi.nlm.nih.gov/28423341, https://pubmed.ncbi.nlm.nih.gov/28636957

86. Leibovitz B, Siegel BV. (1978) Ascorbic acid, neutrophil function, and the immune response. Int J Vitam Nutr Res. 48:159-164. https://pubmed.ncbi.nlm.nih.gov/357320

87. Manning J, Mitchell B, Appadurai DA, et al. (2013) Vitamin C Promotes Maturation of T-Cells. Antioxid Redox Signal. 19:2054-2067. https://pubmed.ncbi.nlm.nih.gov/23249337



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