The paper “Be Well: A Potential Role for Vitamin B in COVID-19,” was published in the journal Maturitas (1). The paper is the result of a joint collaboration between researchers at the University of Oxford, United Arab Emirates University and the University of Melbourne, Australia. While no studies using B vitamins have been performed on COVID-19 patients, the researchers stress that, based on B vitamins’ effects on your immune system, immune-competence and red blood cells (which help fight infection), supplementation may be a useful adjunct to other prevention and treatment strategies. They are not suggesting B vitamins might prevent or treat COVID-19 by themselves.
One of the factors that make COVID-19 so dangerous to those with underlying conditions or old age is its ability to overactivate your immune system, triggering cytokine storms.
As explained by Dr. Uma Naidoo, a nutrition expert at Harvard Medical School, who was not involved in the paper:
“You can think of the immune system as an army. Its job is to protect the body. But if the immune system army isn’t well-regulated, it can overreact and actually cause more damage — this overreaction is what often happens in COVID-19 and is referred to as the cytokine storm.
Cytokines are inflammatory molecules released by immune cells. They are like the weapons of the immune system army. So, if immune cells are soldiers, cytokines are guns and grenades.
And in a poorly regulated immune system, the body’s cytokine storm induced by COVID cause lots of inflammation in the body, just as if little grenades were being tossed around. This is what causes the worst outcomes and death in COVID.
It follows that anything that improves immune system function and decreases the chances that an infected person will have a catastrophic cytokine storm may improve the outcome of COVID-19 cases and decrease the overall death rate. Therefore, it’s quite feasible that B-vitamin supplementation could contribute to preventing the worst COVID outcomes.” (2)
As noted by the authors of “Be Well: A Potential Role for Vitamin B in COVID-19”:
“There is a need to highlight the importance of vitamin B because it plays a pivotal role in cell functioning, energy metabolism, and proper immune function. Vitamin B assists in proper activation of both the innate and adaptive immune responses, reduces pro-inflammatory cytokine levels, improves respiratory function, maintains endothelial integrity, prevents hypercoagulability and can reduce the length of stay in hospital.
Therefore, vitamin B status should be assessed in COVID-19 patients and vitamin B could be used as a non-pharmaceutical adjunct to current treatments …Vitamin B not only helps to build and maintain a healthy immune system, but it could potentially prevent or reduce COVID-19 symptoms or treat SARS-CoV-2 infection. Poor nutritional status predisposes people to infections more easily; therefore, a balanced diet is necessary for immuno-competence.”
The graphic below illustrates the roles various B vitamins play in the COVID-19 disease process. As you can see, B vitamins are involved in several disease aspects, including viral replication and invasion, cytokine storm induction, adaptive immunity and hypercoagulability.
Let’s see how each B-complex vitamin may help treat COVID-19, according to a study published in Maturitas.
Vitamin B1 (Thiamine)
Thiamine is able to improve immune system function and has been shown to reduce the risk of type-2 diabetes, cardiovascular disease, aging-related disorders, kidney disease, cancer, mental disorders and neurodegenerative disorders. Thiamine deficiency affects the cardiovascular system, causes neuroinflammation, increases inflammation and leads to aberrant antibody responses. As antibodies, and importantly T-cells, are required to eliminate the SARS-CoV-2 virus, thiamine deficiency can potentially result in inadequate antibody responses, and subsequently more severe symptoms. Hence, adequate thiamine levels are likely to aid in the proper immune responses during SARS-CoV-2 infection. In addition, the symptoms of COVID-19 are very similar to altitude sickness and high-altitude pulmonary edema. Acetazolamide is commonly prescribed to prevent high-altitude sickness and pulmonary edema through inhibition of the carbonic anhydrase isoenzymes and subsequently increases oxygen levels. Thiamine also functions as a carbonic anhydrase isoenzyme inhibitor; hence, high-doses of thiamine given to people at early stages of COVID-19 could potentially limit hypoxia and decrease hospitalization. Further research is required to determine whether administration of high thiamine doses could contribute to the treatment of patients with COVID-19.
Vitamin B2 (Riboflavin)
Riboflavin together with UV light cause irreversible damage to nucleic acids such as DNA and RNA, rendering microbial pathogens unable to replicate. Riboflavin and UV light has been shown to be effective against the MERS-CoV virus, suggesting that it could also be helpful against SARS-CoV-2. In fact, riboflavin-UV decreased the infectious titer of SARS-CoV-2 below the limit of detection in human blood and in plasma and platelet products. This could alleviate some of the risk of transfusion transmission of COVID-19 and as well as reducing other pathogens in blood products for critically ill COVID-19 patients.
Vitamin B3 (Nicotinamide, Niacin)
Niacin acts as a building block of NAD and NADP, both vital during chronic systemic inflammation. NAD+ acts as a coenzyme in various metabolic pathways and its increased levels are essential to treat a wide range of pathophysiological conditions. NAD+ is released during the early stages of inflammation and has immunomodulatory properties, known to decrease the pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α. Recent evidence indicates that targeting IL-6 could help control the inflammatory storm in patients with COVID-19. Moreover, niacin reduces neutrophil infiltration and exhibits an anti-inflammatory effect in patients with ventilator-induced lung injury. In hamsters, niacin and nicotinamide prevents lung tissue damage. In addition, nicotinamide reduces viral replication (vaccinia virus, human immunodeficiency virus, enteroviruses, hepatitis B virus) and strengthens the body’s defense mechanisms. Taking into account the lung protective and immune strengthening roles of niacin, it could be used as an adjunct treatment for COVID-19 patients.
Vitamin B5 (Pantothenic acid)
Pantothenic acid has a number of functions, including cholesterol- and triglyceride-lowering properties, improves wound healing, decreases inflammation and improves mental health. Even though there are limited studies demonstrating the effects of pantothenic acid on the immune system, it is a viable vitamin for future investigation.
Vitamin B6 (Pyridoxal 5′-phosphate, Pyridoxine)
Pyridoxal 5′-phosphate (PLP) is an active form of pyridoxine, and is an essential cofactor in various inflammatory pathways with deficiency leading to immune dysregulation. PLP has an inverse relationship with plasma IL-6 and TNF-α in chronic inflammatory conditions. During inflammation, the utilization of PLP increases results in its depletion, suggesting that COVID-19 patients with high inflammation may have deficiency. Low PLP levels have been noted in patients with type-2 diabetes, cardiovascular disease and in the elderly, groups who are at higher risk of poorer COVID-19 outcomes. Dysregulation of immune responses and increased risk of coagulopathy have also been noted among COVID-19 patients. In a recent preprint it is suggested that PLP supplementation mitigates COVID-19 symptoms by regulating immune responses, decreasing pro-inflammatory cytokines, maintaining endothelial integrity and preventing hypercoagulability. In fact, it was shown three decades ago that PLP levels reduce abnormalities in platelet aggregation and blood clot formation. Recently researchers at Victoria University reported that vitamin B6 (as well as B2 and B9) upregulated IL-10, a powerful anti-inflammatory and immunosuppressive cytokine which can deactivate macrophages and monocytes and inhibit antigen-presenting cells and T cells. COVID-19 patients often respond to the virus by mounting an excessive T cell response and secretion of pro-inflammatory cytokines. It may be that PLP is able to contribute to dampening the cytokine storm and inflammation suffered by some COVID-19 patients.
Vitamin B9 (folic acid, folate)
Folate is an essential vitamin for DNA and protein synthesis and in the adaptive immune response. Furin is an enzyme associated with bacterial and viral infections and is a promising target for treatment of infections. Recently, it was noted that folic acid was able to inhibit furin, preventing binding by the SARS-CoV-2 spike protein, preventing cell entry and virus turnover. Therefore it was suggested that folic acid could be beneficial for the management of COVID-19-associated respiratory disease in the early stages. A recent preprint report that folic acid and its derivatives tetrahydrofolic acid and 5-methyl tetrahydrofolic acid have strong and stable binding affinities against the SARS-CoV-2, through structure-based molecular docking. Therefore, folic acid may be used as a therapeutic approach for the management of COVID-19.
Vitamin B12 (cobalamin)
Vitamin B12 is essential for red blood cell synthesis, nervous system health, myelin synthesis, cellular growth and the rapid synthesis of DNA. The active forms of vitamin B12 are hydroxo-, adenosyl- and methyl-cobalamin. Vitamin B12 acts as a modulator of gut microbiota and low levels of B12 elevate methylmalonic acid and homocysteine, resulting in increased inflammation, reactive oxygen species and oxidative stress. Hyperhomocysteinemia causes endothelial dysfunction, activation of platelet and coagulation cascades, megaloblastic anemia, disruption of myelin sheath integrity and decreased immune responses. However, SARS-CoV-2 could interfere with vitamin B12 metabolism, thus impairing intestinal microbial proliferation. Given that, it is plausible that symptoms of vitamin B12 deficiency are close to COVID-19 infection such as elevated oxidative stress and lactate dehydrogenase, hyperhomocysteinemia, coagulation cascade activation, vasoconstriction and renal and pulmonary vasculopathy. In addition, B12 deficiency can result in disorders of the respiratory, gastrointestinal and central nervous systems. Surprisingly, a recent study showed that methylcobalamin supplements have the potential to reduce COVID-19-related organ damage and symptoms. A clinical study conducted in Singapore showed that COVID-19 patients who were given vitamin B12 supplements (500 μg), vitamin D (1000 IU) and magnesium had reduced COVID-19 symptom severity and supplements significantly reduced the need for oxygen and intensive care support.
REFERENCES
- Shakoor H, Feehan J, Mikkelsen K, et al. Be well: A potential role for vitamin B in COVID-19. Maturitas. 2021;144:108-111. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428453/
- Haglage A. Vitamin B could help prevent the ‘worst outcomes’ in COVID-19 cases, experts say. August 27, 2020. https://www.yahoo.com/lifestyle/vitamin-b-could-help-prevent-the-worst-outcomes-in-covid-19-cases-experts-say-163709320.html
Marios Dimopoulos
Doctor of Naturopathy-Nutritionist-Author
PhD candidate in Integrative Medicine
Member of American Naturopathic Medical Association
Fellow of the American Council of Applied Clinical Nutrition
Member of the American Association of Drugless Practitioners
Member of the American Association of Nutritional Consultants
Member of the Canadian Association of Natural Nutritional Practitioners
Member of the Association for Natural Medicine in Europe
Member of the Society of Complementary Alternative and Holistic Practitioners
Member of the Pancyprian Association of Nutritionists
Member of the Professional Association of Complementary Medicine and Humanities
