Vitamins B1, D, C, NAD+, supplements help prevent COV-19

Thiamine or vitamin B1… is central to mitochondrial and mental health. It was found deficient in 75 and 76% of type 1 and 2 diabetics, respectively and 29% 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 maybe 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 thru 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 is 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 does not 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, they do worse.

Vitamin D deficiency undermines mitochondrial ATP production. Scientific American reports that “three-quarter 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 COV-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). Long term Valproate and lithium treatment, often used for bipolar disorder at therapeutic levels, suppresses P53 and Bax expression but increases BCL-2 expression in rat brains cell cultures ⁽¹²⁾. Lithium and valproate also protected against methamphetamine induced reduction of mitochondrial cytochrome C ⁽¹³⁾. One report suggested that lithium might be a potential treatment for SARS-COV-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 increases 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 intracellular liver fat accumulation damages mitochondria. Curcumin also decreases obesity toxicity-induced mitochondrial dysfunction ⁽¹⁸⁾ which resulted in increased energy production and reduced obesity.

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 suggest 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 which 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% in patients needing treatment with ventilators, 20% 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 (gluconegenesis) ^{(22, 23)}. However, high longer levels can cause nerve damage and other problems (24), thus precluding its use for general protection and prevention of COVID-19.

Metformin, commonly used to treat type II diabetes, blocks the cellular cytokine activation by NFkB (which coordinates the inflammatory response) 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 lymphocyte associated with inflammation. Metformin reduced the Th 17 “inflammaging” profile and reversed it toward the profile of 30-year olds, in T cell culture ⁽²⁵⁾. This resulted from metformin improving in parallel autophagy (the critical recycling of cellular parts from the removal of old and diseased cells) and mitochondrial function ⁽²⁵⁾. Antiaging effects have been reported in animal models and anti-inflammatory and anti-cancer effects in diabetic patients on metformin ⁽²⁵⁾.

NAD+ (nicotinamide adenine dinucleotide) precursors act similarly to metformin in rescuing T. Fam- deficient T cells from causing premature aging in mice ^{(25, 26)} as well as improving mitochondrial regulation over lysosomal autophagia during inflammation ⁽²⁷⁾ (mitochondria have their own specific separate genome which T. Fam regulates and controls). Precursors of NAD+ include niacin or nicotinic acid (NA), nicotinamide (NAM) or vitamin B3, nicotinamide riboside (NR), and nicotinamide adenine dinucleotide phosphate (NADPH). The latter was found to provide necessary biochemicals to mitochondria for the maintenance of cellular energy balance. NAD+, a critical co-enzyme decreases with age, turns nutrients into energy in its role in mitochondrial function, and assists other proteins such as sirtiuns that regulate cellular health, repair, and longevity. NR appears to be the most efficient precursor, used by all cells to make NAD+ which helps repair damaged and stressed cells. It does not cause flushing (e.g. NA), inhibit the reproductive properties of the sirtiuns system (which resveratrol uses), or decline in effectiveness with age (e.g. NAM). One study in mice found that NR was more effective than NAM in reversing glucose, insulin and mitochondrial dysfunction and liver damage ⁽²⁸⁾.

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A cell-based study reveals COVID-19 infection depletes cellular NAD+ thereby impairing the body’s innate immune mitochondrial based ability to fight viral infection. NAD+ boosting compounds decreased replication of SARS-COV protein required for viral “replication in vivo”. In infected cell culture NAM, NR and NA depressed SARS-COV-19 replication by 8.3, 6.4 and 1.9 fold, respectively. The higher the NAD+ status, the more depressed the viral cell culture infection ⁽²⁸⁾. There is no daily recommended dose of NR, but a study demonstrated that consumption of a daily dose of 100, 300, and 1,000 mg daily increased whole blood NAD+ by 22%, 51% and 142%, respectively, within 2 weeks with no adverse effects ⁽²⁹⁾.

Melatonin, which also decreases with age, is an antioxidant not only involved in sleep. It also regulates blood pressure by brain and peripheral mechanisms involving the kidney’s renin-angiotensin system (RAS). Melatonin is also involved in mitochondrial physiology in the heart, brain, kidney, and blood vessels involving RAS and its associated ACE-2 receptors ⁽³⁰⁾ (used by COVID-19 and influenza for infection). The initial dose may be 1 mg or less. “A safe dose will depend on your body weight, age and sensitivity to the supplement”. It should be decreased if you feel groggy the next morning, have vivid dreams or headache ⁽³¹⁾. It is often taken 1 hour before bedtime to maximize absorption.

There are numerous papers documenting that vitamin C, especially intravenously (IV), is helpful in critically ill patients with septicemia (i.e. blood poisoning caused especially by viruses, bacteria and their toxins). A vitamin C deficiency is related to the increased risk and severity of influenza infection suggesting that it may have a protective effect. It is highly concentrated in our cells such as lymphocytes, leucocytes, and macrophages. It influences their phagocytic ability (swallowing and removing bacteria, viruses, etc.), chemotaxis (migration of the right immune cells, to the right place, at the right time), oxidative killing ability, proliferation, and overall function. In deficient vitamin C mice, influenza infection was very lethal and was associated with decreased production of interferon, the anti-viral cytokine and increased inflammatory cells in the lung. This was reversed when Vitamin C was given prior to exposure ⁽³²⁾. Vitamin C has demonstrated activity against numerous viral infections, many of which were found to have low circulating vitamin C levels. This was also found in patients having Herpes Zoster (shingles), whose pain decreased significantly when given vitamin C IV. Mice with pneumonia from the common human H1N1 influenza virus had dose dependent vitamin C reduction in lung injury and mortality. Moreover, vitamin C administration significantly recovered normal mitochondrial membrane potential (difference in electrical charge inside and outside of the cell necessary for proper functioning) and decreased the amount of pro-inflammatory cytokines by reducing their gene expression. Vitamin C enters the mitochondria and gives mitochondrial protection against oxidative injury, which occurs in immune T cells during viral infections ⁽³³⁾, as expressed in COVID-19 with T cell depletion and functional exhaustion ⁽³⁴⁾. Vitamin C is an essential factor in the anti-viral immune response because of its role in healthy mitochondrial function ⁽³³⁾, without which all cellular mechanisms stop working, since all are dependent on mitochondrial ATP, the life source. Mayo clinic suggests that the necessary daily adult dose is 65 to 90 milligrams (mg)/day and the upper limits is 2,000 mg/day. Higher doses may cause heart burn, nausea, diarrhea, vomiting, headache, abdominal cramps, and insomnia. Since it is water soluble, excessive amounts are usually urinated out of the body. My personal preference is to have lime or lemon juice in warm water first thing in the morning (I live in SW FL). The body evolutionarily never knew what a 1,000 mg of vitamin C was or is, and if that dose were to be used, it would seem more appropriate to take 500 mg twice a day with a meal. If infection were to occur, this daily dose may create a reservoir to blunt the large amount initially consumed as apparently reflected in the low circulating levels observed with acute infectious diseases. A large Chinese clinical trial of vitamin C IV in COVID-19 pneumonia is starting.

All decisions regarding this information should be made with guidance from your professional health care provider and physical trainer. PS. On Thursday, September 10, 2020, Dr. Fauci confirmed that he takes vitamins D and C supplements that they can decrease “your susceptibility to infection” ⁽³⁷⁾.