Even More Reasons to Like Vitamin D

As Ben Franklin famously wrote in 1817, “…nothing is certain except death and taxes.” While in modern times we could perhaps add to this short-list of life’s certainties, there is, nonetheless, a measure of wisdom in those words made famous by Franklin. In fact, I would suggest that though our knowledge of the human body is vast, there still exists great uncertainty in many matters of biological function and disease states.

However, most scientists and doctors would agree that the importance of vitamins in biological pathways remains one area of certainty. Myriad functions of vitamins have been elucidated over decades of research, with new discoveries proceeding apace. Of the many vitamins identified and for which important functions have been described, vitamin D is in the mix for most important. Aside from its well-known role in maintaining bone health, ongoing research has increased our knowledge on this important micronutrient and uncovered evidence of even more roles in physiological function.       

Sources of Vitamin D

The most well-known source of vitamin D is sunshine. Of course, the “vitamin-D-from-the-sun” process is more complicated than might be thought. To produce vitamin D from the sun, the precursor 7-dehydrocholesterol in the skin absorbs UV B from the sun, converting it to the precursor vitamin D3 which is then isomerized to create vitamin D3. The vitamin D produced in this manner is not biologically active and must undergo hydroxylation in the liver to 25 hydroxy vitamin D [25(OH)D], then undergo a second hydroxylation, primarily in the kidneys, to 1,25 hydroxy vitamin D [1,25(OH)D], the physiologically active form.

In addition to production of vitamin D from sunlight, some foods can provide this important molecule, though typically at fairly low levels. The flesh of fish such as trout, salmon and tuna are good sources, as are fish oils. Interestingly, such sources may not only provide vitamin D, but also the 25(OH)D mentioned above. In addition, some foods are fortified with vitamin D, such as milk and many breakfast cereals.   

With most foods providing small amounts of vitamin D, or none at all, supplementation may offer an effective way to ensure that our levels are adequate. Many people are deficient in vitamin D due to lack of sunshine and poor diet. The impact of deficiency was evidenced in outcomes of those with low levels of vitamin D during the recent Covid-19 pandemic (see below). 

SARs CoV-2 (COVID-19)

Fairly early during the recent Covid-19 pandemic it was recognized that many patients with severe illness and many who died, were deficient in vitamin D levels, or more specifically, they had low plasma levels of 25(OH)D. Since that time several meta-analyses have been conducted, some with many thousands of patients. These analyses showed that 25(OH)D plasma-level deficiency is associated with an increased risk of severe illness and mortality in adults, as well as with increased risk of severe illness in children.

It may be that vitamin D lowers risk of severe illness and mortality through enhancement of the innate antiviral immune response, specifically by reducing the cytokine storm so often discussed during the pandemic. The role of vitamin D in immune function is well known, as it enhances the killing capacity of macrophages, as well as modulating production of inflammatory cytokines.

In addition to risk reduction associated with Covid-19, a large meta-analysis of over 10,000 patients, published in the British Medical Journal, showed that vitamin D supplementation significantly reduced the risk of acute respiratory tract infection.

Depression/Suicide

Recent studies have found that low vitamin D levels increase the risk of depression, as well as risk of suicide. In addition, a recent study in veterans showed that vitamin D supplementation is associated with a 45 – 48% reduction in suicide attempt and self-harm ideation.

One theory considered in the association of vitamin D and suicidal tendencies is the effect that vitamin D has on serotonin levels. The active form of vitamin D has been shown to activate transcription of the gene that synthesizes serotonin in the brain.

It should be noted that patients with suicidal behaviors have also been shown to have increased C-Reactive Protein (CRP) levels. CRP is a marker for inflammation and can be an indication of heart attack risk. There is evidence that Omega-3 supplementation may reduce systemic inflammation by reducing CRP levels, so Omega-3 supplementation may provide benefits.

Alzheimer’s

It has been known that vitamin D is involved in clearance of amyloid beta aggregates, the plaque substance present in patients with Alzheimer’s disease. Therefore, as one would expect, low serum levels of vitamin D have been associated with a greater risk of dementia and Alzheimer’s disease. Further, there is plentiful evidence that cholecalciferol (vitamin D3) more readily maintains higher serum levels than ergocalciferol (vitamin D2).

A recent study that looked at more than 12,000 persons showed that exposure to vitamin D was associated with greater dementia-free survival and lower dementia rates over a 10-year period. Interestingly, the effect of exposure to vitamin D was greater in females. This may be due to declining estrogen levels in peri and post-menopausal women. It is believed that estrogen increases the activity of enzymes involved in activating vitamin D.

Inflammation

We will delve more deeply into inflammation and supplements in a future article, but a short discussion on inflammation and vitamin D should be explored briefly here.

As mentioned above, vitamin D deficiency has been associated with increased levels of pro-inflammatory cytokines, a major factor in poor outcomes in Covid-19 infection, as well as CNS inflammation.  Vitamin D is known as an immune modulator that works through regulation of prostaglandins and leukotrienes. In addition, there is evidence that higher vitamin D levels are associated with lower levels of CRP (see above). Further, evidence suggests that Omega-3 supplementation may be beneficial for lowering CRP as well.

Summary

Evidence continues to grow concerning the many potential benefits of vitamin D. For many people, however, getting the appropriate amount of nutrients such as vitamin D in their diet is a challenge. Supplementing a healthy diet with a vitamin D supplement can help fill in nutritional gaps. In addition, with evidence that Omega-3 has shown promise in decreasing inflammation and has potential benefits for COVID-19 (as does vitamin D), it would be wise to add a high quality Omega-3 supplement to ones diet.     

References

Amira Mohamed Taha, Ahmad Shehata Shaarawy, Mohamed Mosad Omar, Khaled Abouelmagd, Noran Magdy Shalma, Mais Alhashemi, Hala Mahmoud Ahmed, Ahmed Hafez Allam, Mohamed Abd-ElGawad (2022) Effects of Omega-3 fatty acids supplementation on serum level of C-reactive protein in patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials, Journal of Translational Medicine

Office of Dietary Supplements NIoH. Vitamin D Fact Sheet for Health Professionals. (2021) National Institutes of Health. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/?print=1.

Arrigo F. G. Cicero, Federica Fogacci, Claudio Borghi, (2022) Vitamin D Supplementation and COVID-19 Outcomes: Mounting Evidence and Fewer Doubts, Nutrients

Yagci I, Avci S., (2021) Biochemical predictors in presentations to the emergency department after a suicide attempt, Bratislava Medical Journal

Philip C. Calder, Aintra C. Carr, Adrian F. Gombart, Manfred Eggersdorfer, (2020) Optimal Nutrition Status for a Well-Functioning Immune System Is and Important Factor to Protect against Viral Infection, Nutrients

Jill E. Livigne, Jason B. Gibbons, (2023)  The association between vitamin D serum levels, supplementation, and suicide attempts and intentional self-harm, PLOS ONE

Ghahremani M, Smith EE, Chen H-Y, Creese B, Goodarzi Z, Ismail Z. Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status. Alzheimer’s Dement. 2023;15:e12404. https://doi.org/10.1002/dad2.1240