All About Vitamin D

Vitamin D is a steroid hormone and micronutrient that has many biological functions. It occurs mainly in two forms, D3 (cholecalciferol) and D2 (ergocalciferol), but also as the vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) [1].

Aside from its well-known role in bone health, vitamin D supports a wide range of cellular processes, and is linked to immune health, inflammation, muscle function, and brain and nervous system activity. Vitamin D allows the absorption of calcium from the gut and maintains the levels of calcium and phosphorous in the blood, both of which are essential minerals for building bone tissue [2]. It is also indispensable for remodeling bone, a constant process that involves the removal of "old" bone and replacing it with "new" bone tissue.

The Recommended Daily Allowance (RDA) for vitamin D is 400 international units (IU) for children up to 12 months, 600 IU for those aged 1 to 70 years of age, and 800 IU for people over 70 years of age [3,4]. With that said, vitamin D is generally difficult to obtain from food that we eat, as only a limited number of foods contain appreciable amounts, such as fortified milk and cereals, as well as fatty fish (e.g., salmon, mackerel, sardines). Rather, the main source of vitamin D is the sun.

When we are exposed to direct sunlight, specifically ultraviolet B (UVB) radiation, a chemical in our skin is converted into an active form of vitamin D called calciferol. The amount of vitamin D produced by this process is affected by the time of day, season, location, and skin pigmentation. 

In this article, we will look at the role of vitamin D, its evolution, and also explore the effects of deficiency in this important micronutrient. In addition, we will consider the rationale for vitamin D supplementation in the general population. 

Vitamin D in the Context of Evolution 

For at least 1.2 billion years, eukaryotes (organisms whose cells contain a nucleus and other membrane-bound organelles – this includes humans!) have been able to synthesize sterols and produce vitamin D when exposed to UVB rays [5,6].

The endocrinology of vitamin D was established some 550 million years ago, when the high-affinity nuclear vitamin D receptor evolved, as well as its associated transport proteins and enzymes [5,7].

More recently, the impact of vitamin D on human health is evidenced by the fact that the need for its efficient synthesis served European hunters and gatherers as an evolutionary driver for increased 7-dehydrocholesterol levels, whereas light skin was established far later via populations from Anatolia and the northern Caucasus entering Europe 9,000 and 5,000 years ago, respectively. The later population settled in northern Europe and it has been hypothesized that the introduction of high vitamin D responsiveness was an essential attribute for surviving dark winters without enduring the detrimental consequences of vitamin D deficiency [8].

How Does Vitamin D Work? 

Vitamin D is well-known for its role in the development of a healthy calcified skeleton, and has been described as the "sunshine vitamin" [6]. Our understanding of vitamin D has now evolved to include a wide range of biological effects, to the extent that it could be referred to as a hormone [9,10]. In fact, vitamin D has been called a multifunctional hormone or "prohormone" due to this diverse and important contribution to so many functions and processes in the body [11,12]. These effects are found in the immune system, cardiovascular system, endocrine system, and other metabolic pathways. It may also play a role in depression, cancer, and pain management.

Most cells in the body have a vitamin D receptor, a nuclear receptor which binds nutritionally-derived ligands and exerts effects on bone mineral balance, detoxification of compounds from within and outside the body, cancer prevention, and hair cycling in mammals [13].

When we are exposed to sunlight, UVB radiation converts 7-dehydrocholesterol to previtamin D3 which in turn rapidly isomerizes to vitamin D3. Once formed, vitamin D3 is metabolized in the liver to 25-hydroxyvitamin D3 and in the kidneys to its active form 1,25-dihydroxyvitamin D3. 1,25-dihydroxyvitamin D3 then interacts with its vitamin D receptor in calcium-regulating tissues to exert its influence on calcium metabolism and bone health [6]. 

The Impact of Vitamin D Deficiency 

Over 1 billion people around the world are deficient or insufficient in vitamin D to some degree [6]. Although there are various definitions of vitamin D deficiency, there is general acknowledgement that deficiency is present in both low and high income countries. A blood serum 25-hydroxyvitamin D (25(OH)D) threshold of <25/30 nmol/L is broadly used to detect deficiency, but this can be rather conservative and optimal levels are likely between 50 and 70 nmol/L [14]. These serum concentrations are used to measure the adequacy of vitamin D stores in the body.

As discussed above, UVB-rich sunlight stimulates the production of vitamin D in the skin. However, there are personal and environmental factors that can prevent or impede this process. For example, people tend to work for extended periods indoors, and there are complexities associated with advocating sun exposure to address this important health issue. 

Obtaining vitamin D through dietary means is also a challenge, as vitamin D-rich sources (>4 micrograms per 100 g of food) are limited and rarely consumed. These sources comprise some fish and fish liver oils, cheese, beef liver, and eggs, as well as fortified foods such as cereals, milk, and yoghurt [1].

Is There a Need for Vitamin D Supplements? 

An adequate daily intake of vitamin D, according to the European Food Safety Authority, of 15 micrograms is difficult to achieve through diet alone, and therefore supplements are often advised if this is the case [1]. What’s more, the recommended intake appears to be insufficient when sunlight exposure is limited [15]. It is even more difficult to achieve in populations with darker skin tones that require much more sunlight to achieve the same blood levels.

In North America, most people obtain sufficient vitamin D from their diet and sun exposure, however, daily supplementation with doses of 2,000 IU or lower is not likely to cause harm [4]. In people with a documented deficiency in vitamin D, however, supplementation with a cumulative dose of at least 600,000 IU (administered over several weeks) may be necessary to replenish vitamin D stores [4].

Several meta-analyses (a meta-analysis is a pooled statistical analysis of available and relevant research) have noted that vitamin D supplementation might benefit specific populations of interest. For example, postmenopausal women can potentially experience improvements in muscle strength after vitamin D supplementation [16].

In a separate meta-analysis in people over 60 years of age, a population known to exhibit losses in muscle strength and function [17], vitamin D supplementation (daily doses of 800-1,000 IU) was found to improve postural sway and balance as well as muscle strength [18].

In light of the recent COVID-19 global pandemic, vitamin D supplementation has also been proposed to offer a protective role against ICU hospitalization and a decreased risk of death, although further studies are needed to strengthen this claim [19].

Conclusion

Vitamin D evolved millions of years ago and is absolutely essential to thousands of enzymatic processes. Sunlight is the most efficient way of getting your vitamin D but supplementation may be helpful if exposure to natural light is limited or in the winter months when the angle of sun prevents as much vitamin D absorption. In addition, there are various sunlamps and devices that can also help raise vitamin D levels if you live in a cold, dark locale. 

And while you are getting your vitamin D via sunlight, do you know what also goes well with sun? Methylene blue! Methylene blue + near infrared wavelengths in sunlight (660 nm) synergize and power up your mitochondria. Buy some Just Blue here and feel the difference!

References 

[1]        E. Benedik, Sources of vitamin D for humans, Int J Vitam Nutr Res. 92 (2022) 118–125. https://doi.org/10.1024/0300-9831/a000733. 

[2]        L.A. Plum, H.F. DeLuca, The Functional Metabolism and Molecular Biology of Vitamin D Action, Clinic Rev Bone Miner Metab. 7 (2009) 20–41. https://doi.org/10.1007/s12018-009-9040-z. 

[3]        M.G.J. Balvers, E.M. Brouwer-Brolsma, S. Endenburg, L.C.P.G.M. de Groot, F.J. Kok, J.K. Gunnewiek, Recommended intakes of vitamin D to optimise health, associated circulating 25-hydroxyvitamin D concentrations, and dosing regimens to treat deficiency: workshop report and overview of current literature, J Nutr Sci. 4 (2015) e23. https://doi.org/10.1017/jns.2015.10. 

[4]        S.T. Haines, S.K. Park, Vitamin D supplementation: what’s known, what to do, and what’s needed, Pharmacotherapy. 32 (2012) 354–382. https://doi.org/10.1002/phar.1037. 

[5]        C. Carlberg, Vitamin D in the Context of Evolution, Nutrients. 14 (2022) 3018. https://doi.org/10.3390/nu14153018. 

[6]        M.F. Holick, Vitamin D: evolutionary, physiological and health perspectives, Curr Drug Targets. 12 (2011) 4–18. https://doi.org/10.2174/138945011793591635. 

[7]        D.D. Bikle, Vitamin D: an ancient hormone, Exp Dermatol. 20 (2011) 7–13. https://doi.org/10.1111/j.1600-0625.2010.01202.x. 

[8]        A. Hanel, C. Carlberg, Vitamin D and evolution: Pharmacologic implications, Biochem Pharmacol. 173 (2020) 113595. https://doi.org/10.1016/j.bcp.2019.07.024. 

[9]        J.W. Pike, S. Christakos, Biology and Mechanisms of Action of the Vitamin D Hormone, Endocrinol Metab Clin North Am. 46 (2017) 815–843. https://doi.org/10.1016/j.ecl.2017.07.001. 

[10]      R.S. Mason, Vitamin D: a hormone for all seasons, Climacteric. 14 (2011) 197–203. https://doi.org/10.3109/13697137.2010.514366. 

[11]      D.L. Ellison, H.R. Moran, Vitamin D: Vitamin or Hormone?, Nurs Clin North Am. 56 (2021) 47–57. https://doi.org/10.1016/j.cnur.2020.10.004. 

[12]      F. Sassi, C. Tamone, P. D’Amelio, Vitamin D: Nutrient, Hormone, and Immunomodulator, Nutrients. 10 (2018) 1656. https://doi.org/10.3390/nu10111656. 

[13]      M.R. Haussler, C.A. Haussler, L. Bartik, G.K. Whitfield, J.-C. Hsieh, S. Slater, P.W. Jurutka, Vitamin D receptor: molecular signaling and actions of nutritional ligands in disease prevention, Nutr Rev. 66 (2008) S98-112. https://doi.org/10.1111/j.1753-4887.2008.00093.x. 

[14]      K.D. Cashman, Vitamin D Deficiency: Defining, Prevalence, Causes, and Strategies of Addressing, Calcif Tissue Int. 106 (2020) 14–29. https://doi.org/10.1007/s00223-019-00559-4. 

[15]      H. Glerup, K. Mikkelsen, L. Poulsen, E. Hass, S. Overbeck, J. Thomsen, P. Charles, E.F. Eriksen, Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited, J Intern Med. 247 (2000) 260–268. https://doi.org/10.1046/j.1365-2796.2000.00595.x. 

[16]      J.-L. Zhang, C.C.-W. Poon, M.-S. Wong, W.-X. Li, Y.-X. Guo, Y. Zhang, Vitamin D Supplementation Improves Handgrip Strength in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, Front Endocrinol (Lausanne). 13 (2022) 863448. https://doi.org/10.3389/fendo.2022.863448. 

[17]      A.J. Cruz-Jentoft, G. Bahat, J. Bauer, Y. Boirie, O. Bruyère, T. Cederholm, C. Cooper, F. Landi, Y. Rolland, A.A. Sayer, S.M. Schneider, C.C. Sieber, E. Topinkova, M. Vandewoude, M. Visser, M. Zamboni, Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2, Sarcopenia: revised European consensus on definition and diagnosis, Age Ageing. 48 (2019) 16–31. https://doi.org/10.1093/ageing/afy169. 

[18]      S.W. Muir, M. Montero-Odasso, Effect of vitamin D supplementation on muscle strength, gait and balance in older adults: a systematic review and meta-analysis, J Am Geriatr Soc. 59 (2011) 2291–2300. https://doi.org/10.1111/j.1532-5415.2011.03733.x. 

[19]      C. Argano, R. Mallaci Bocchio, G. Natoli, S. Scibetta, M. Lo Monaco, S. Corrao, Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis, Pharmaceuticals (Basel). 16 (2023) 130. https://doi.org/10.3390/ph16010130.