SARS-COVID-19: Possible Help for Protection and Prevention

Part 4: Make our immune and mitochondrial systems resistant to viral infections.

Posted Jun 24, 2020

Thiamine or vitamin B1 is central to mitochondrial and mental health. It was found deficient in 75 and 76 percent of type 1 and 2 diabetics, respectively, and 29 percent of obese people. “Without thiamine, the whole mitochondrial engine slows to a halt... can derail central and peripheral metabolism, induced tissue injury in regions with high metabolic demands, initiate buildup of toxic intermediates like lactate, and impair myelination.” Other vitamins, minerals, and nutrients that are supportive of mitochondrial function include niacin (B3), riboflavin, pantothenic (B5), folate (B9) where L-methyl folate may be better for genetic variation with a family history of depression, methylcobalamin (B12), vitamins C, E, and D3(1).

Vitamin D exerts its beneficial effects on the function of virtually every bodily tissue through its receptor VDR. Recent findings reveal its importance to cellular health and mitochondrial integrity and activity. VDR protects cells from the excessive production of ROS and respiration, which causes cellular damage.

Research with healthy and cancer cells demonstrated that silencing VDR “caused impairment of mitochondrial integrity and, finally, cell death”(2). Pertinently, low vitamin D levels are associated with the risk factors for COVID-19, including hypertension(3), diabetes(4), obesity(5, 6), and cardiovascular disease(7). There is an inverse relationship between vitamin D deficiency and increased thrombosis or clotting. A study of 18,791 people found increasing deep vein thrombosis for each lower level of vitamin D(7), as Dr. Anthony Fauci related recently(8).

I think it really relates to the importance of vitamin D in host defense against infection. There’s no doubt that if you are vitamin D deficient, you might have a poor outcome or a greater chance of getting into trouble with an infection. Most people in the developed world are not vitamin D deficient, so adding additional vitamin D may not actually have a substantial clinical effect. That doesn’t lessen the importance of a normal level of vitamin D. In some of the developing countries, there have been studies with tuberculosis and other diseases. Those who are vitamin deficient, including vitamin D and vitamin A, do worse.

Vitamin D deficiency undermines mitochondrial ATP production. Scientific American reports that “three-quarters of U.S. teens and adults are deficient in vitamin D…"(9). The suggested dose, based on current research, is 1,000 to 4,000 IU daily(10).

SARS-COV, and apparently COVID-19, can disrupt the intracellular balance between the neuroprotective BCL proteins and the neurotropic (death) BAX proteins, which can set off a cell death cascade associated with increased levels of tumor suppressor protein P53. This results in cytochrome C being released with cellular death(11). Valproate and lithium treatment, often used for bipolar disorder at therapeutic levels, suppresses P53 and Bax expression but increases BCL-2 expression in rat brain cell cultures(12). Lithium and valproate also protected against the methamphetamine-induced reduction of mitochondrial cytochrome C(13). There has been one report suggesting that lithium might be a potential treatment for COVID-19, but none of the referenced in vitro studies involved clinically therapeutic levels of lithium concentrations(14).

Curcumin, the most important component of the spice Turmeric, has also been shown to have anti-viral effects. It reduces the release of cytochrome C and mitochondrial cell death. Its bioavailability can be increased by using it with black pepper or cooking it in oil and pepper(15, 16). Curcumin can also decrease inflammation and mitochondrial dysfunction in obese mice with liver steatosis (i.e., excessive fat)(17)

Non-alcoholic fatty liver disease (NAFLD) is obesity-related, and excessive liver fat accumulation damages mitochondria. Curcumin also decreases obesity toxicity-induced mitochondrial dysfunction by protecting the liver(18). This allows healthier energy production reduced obesity, one of the main risk factors for COVID-19.

Physicians prescribe Aspirin 81 mg daily to prevent clotting and reduce the risk of heart attacks and stroke. However, it can increase the possibility of bleeding. Similarly, the Cleveland Clinic reports(19) that omega 3 fatty acids can reduce the risk of blood clotting because they help prevent blood platelets from clumping together. They are in higher concentration in fatty fish, such as mackerel, salmon, cod, and herring. The Cleveland Clinic suggests eating a three-ounce serving twice a week. High concentrations of course are available in omega 3 fatty acid supplements. High levels of these essential fatty acids can cause bleeding(19).

COVID-19 attacks and thus creates T cells with dysfunctional mitochondria not able to produce ATP properly. T cell metabolic failure results in circulating cytokine accumulation activated by a protein called NFkB, resembling the chronic inflammation of aging (“inflammaging”)(20). Dexamethasone, a steroid that can suppress cytokines, inflammatory enzymes, etc., has been found orally or IV at low dosages to benefit hospitalized adult patients having COVID-19(21). It reduced death rates by 35 percent in patients needing treatment with ventilators, 20 percent in those only needing supplemental oxygen, but no change in those less ill(21). In mice, lower dose dexamethasone increased mitochondrial respiration and new glucose production (gluconeogenesis)(22, 23). However, high longer levels can cause nerve damage and other problems(24), thus precluding its use for general protection and the prevention of COVID-19.

Metformin, a medication that is commonly used to treat type II diabetes, blocks the cellular cytokine activation by NFkB in metformin-treated cells. In a study of activated T cells from the blood of healthy 30 and 60-year-old people, respectively, the older group produced more Th 17 cytokines, a type of t lymphocytes associated with inflammation. Metformin reduced the Th 17 “inflammaging” profile and reversed it toward the profile of 30-year olds, in T cell culture. This has yet to be demonstrated in vivo(25). Antiaging effects have been reported in animal models and anti-inflammatory and anti-cancer effects in diabetic patients on Metformin(25).

Mitochondrial dysfunction with age makes the elderly more vulnerable to many illnesses, including viral infections such as COVID-19(26). However, exercise can also be helpful in improving mitochondrial function and viral resistance. Exercise improves mental status (attention/concentration, higher cognitive functioning, and short-term memory), sleep, and cardiovascular fitness indicators, such as stress test heart rate and oxygen consumption in older adults(27). Similarly, rejection of the sick role improved health outlook(27) and mood, including decreased anxiety and an improved sense of well-being results(28).

All decisions regarding this information should be made with guidance from your professional health care provider and physical trainer.

References

1. Marrs, C.: Micronutrient deficiencies and mitochondrial dysfunction. Chap 7 in Integrative Therapies for Depression 2016, Greenblatt, JM., Brogen, K, editors CRC Press, Boca Raton, FL. Pgs 73 – 95.

2. Rioca, C, Aillon, A., Bergandi, L, et al.: Vitamin D Receptor Is Necessary for Mitochondrial Function and Cell Health. Int J Mol Sci. 5 Jun 2018; 19(6): 1672-84; doi: 10.3390/ijms19061672.

3. Tomez, H., Kalim, S., Thadhani, R. Does Vitamin D Modulate Blood Pressure? Curr Opin Nephrol Hypertens. 2013 Mar; 22(2): 204–209.doi: 10.1097/MNH.0b013e32835d919b

4. Takiishi, T., Gysemans, C., Bouillon, R., et al.: Vitamin D and Diabetes. Endocrinol Metab Clin North Am. 2010 Jun;39(2):419-46. doi: 10.1016/j.ecl.2010.02.013.

5. Wortsman, J., Matsoka, L.Y., Chen, T.C., et al.: Decreased Bioavailability of Vitamin D in Obesity. Am J Clin Nutr. 2000 Sep;72(3):690-3. doi: 10.1093/ajcn/72.3.690.

6. Pourshahidi, L. K.: Vitamin D and Obesity: Current Perspectives and Future Directions. Proc Nutr Soc. 2015 May;74(2):115-24. doi: 10.1017/S0029665114001578. Epub 2014 Oct 31.

7. Norman, P. E., Powell, J. T.: Vitamin D and Cardiovascular Disease. Circ Res. 2014 Jan 17;114(2):379-93. doi: 10.1161/CIRCRESAHA.113.301241.

8. Abbasi, J.: Anthony Fauci, MD, on COVID-19 Vaccines, Schools, and Larry Kramer. JAMA. Published online June 8, 2020. doi:10.1001/jama.2020.9222

9. Lite, J.: Vitamin D deficiency soars in the U.S., study says. Scientific American. March 23, 2009

10. Raman, R.: What Vitamin D Dosage Is Best? Healthline, October 8, 2017

11. mitochondrial death pathway through p38 MAP kinase activation. J Gen Virol. 2008 Aug;89(Pt 8):1960-1969. doi: 10.1099/vir.0.83665-0.

12. Chen, RW., Chuang, DM.: Long term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression. A prominent role in neuroprotection against excitotoxicity. J Biol Chem. 1999 Mar 5;274(10):6039-42.

13. Bachmann, RF., Wang, Y., Yuan, P., et al: Common effects of lithium and valproate on mitochondrial functions: protection against methamphetamine-induced mitochondrial damage. Int J Neuropsychopharmacol. 2009 Jul;12(6):805-22. doi: 10.1017/S1461145708009802.

14. Nowak, JK., Walkowiak, J.: Is lithium a potential treatment for the novel Wuhan (2019-nCoV) coronavirus? A scoping review. F1000.Research 2020, 9-93 Last updated: 03 APR 2020, 9-93. DOI: 10.12688/f1000research.22299.1

15. Khosrojerdi, A., Mashayekhi, K., Marzouni, H. Z., Curcumin (Extracted from Tumeric) and its Therapeutic Effects.  Jorjani Biomed J 2017, 4(2): 1-20. http://goums.ac.ir/jorjanijournal1-471-en.html.

16. Liu, Z., Yu, Y., Li, X., et al: Curcumin protects against A53T alpha-synuclein-induced toxicity in a PC12 inducible cell model for Parkinsonism. Pharmacol Res. 2011 May;63(5):439-44. doi: 10.1016/j.phrs.2011.01.004.

17. Kuo, JJ., Chang, HH., Tsai, TH., Lee, TY.: Positive effect of curcumin on inflammation and mitochondrial dysfunction in obese mice with liver steatosis. Int J Mol Med. 2012 Sep;30(3):673-9. doi: 10.3892/ijmm.2012.1049.

18. Kuo, JJ., Chang, HH., Tsai, TH., Lee, TY.: Curcumin ameliorates mitochondrial dysfunction associated with inhibition of gluconeogenesis in free fatty acid-mediated hepatic lipoapoptosis. Int J Mol Med. 2012 Sep;30(3):643-9. doi: 10.3892/ijmm.2012.1020.

19. Omega-3 Fatty acids, Food and Benefits.my.clevelandclinic.org, accessed 4/26/2020

20. Van den Bossche, J.: A brake on inflammaging. Science Translational Medicine 27 May 2020: Vol. 12, Issue 545, eabb7104. DOI: 10.1126/scitranslmed.abb7104

21. RECOVERY Trial of British National Health Service (NHS). Date to be published, 2020

22. Hernández-Alvarez, M. I., Paz, J. C., Sebastián, D., et al.: Glucocorticoid Modulation of Mitochondrial Function in Hepatoma Cells Requires the Mitochondrial Fission Protein Drp1. Antioxid Redox Signal. 2013 Aug 1; 19(4): 366–378.doi: 10.1089/ars.2011.4269

23. Nakai, A., Shibazaki, Y., Taniuchi, Y., et al.: Effect of dexamethasone on mitochondrial maturation in the fetal rat brain. General Obstetrics and Gynecology: Fetus-Placenta-Newborn. March 2002, 186, 3, 574-578. doi.org/10.1067/mob.2002.121542

24. Suwanjang, W., Wu, K. L. H., Prachayasittikul, S., et al.: Mitochondrial Dynamics Impairment in Dexamethasone-Treated Neuronal Cells. Neurochem Res. 2019 Jul;44(7):1567-1581. doi: 10.1007/s11064-019-02779-4.

25. Moiseeva, O., Deschênes‐Simard, X., St-Germain, E., et al.: Metformin inhibits the senescence‐associated secretory phenotype by interfering with IKK /NF ‐κB activation. 23 March 2013. Aging Cell. doi.org/10.1111/acel.12075

26. Lane, RK., Hilsabeck, T., Rea, SL.: The role of mitochondrial dysfunction in age-related diseases. Biochim Biophys Acta. 2015 Nov;1847(11):1387-400. doi: 10.1016/j.bbabio.2015.05.021.

27. Stevenson, JS., Topp, R.: Effects of moderate and low intensity long-term exercise by older adults. Res Nurs Health. 1990 Aug;13(4):209-18. DOI: 10.1002/nur.4770130403.

28. Dietrich, A., McDaniel, W. F.: Endocannabinoids and exercise. Br. J. Sports Med 2004; 38, 536-41.