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What is Vitamin D and Why is it Important?

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What is Vitamin D and Why is it Important?

What is Vitamin D and Why is it Important?

We start this blog post with a highly shocking truth: vitamin D deficiency and insufficiency is a current epidemic in our society affecting more than one billion children and adults worldwide!  According to Dr. Michael Holick, a researcher and considered a specialist in Vitamin D, it is estimated “that vitamin D deficiency is the most common medical condition in the world.”

Now, you might be asking, why is this so shocking?

Because Vitamin D is VITAL to health!

Vitamin D is an ancient vitamin hormone that has been produced on this earth for more than 500 million years. If it was “conserved” throughout the evolution of different animal species it must be truly important, because nature does not act randomly.

In humans, it plays an essential role in regulating calcium and phosphate metabolism. It is vital for growth and necessary for developing and maintaining a healthy mineralized skeleton. Relating to cancer, one of the most important effects is that it causes redifferentiation of cancer cells, which means it causes them to return to being normal cells.

Other significant benefits of Vitamin D include:

  • protects against inflammation.
  • may help lower high blood pressure.
  • helps muscles and bone development and maintenance.
  • improves brain function.
  • Has been shown to be protective against cancer.

This worldwide common vitamin deficiency is considered the one that has the most significant impact on the individual’s quality of life1. Vitamin D deficiency causes rickets in children and will precipitate and exacerbate osteopenia and osteoporosis in adults. It also causes the painful bone disease osteomalacia (softening of the bones) and fractures in adults. Vitamin D deficiency affects not only the bones but other tissues such as the brain, prostate, papilla, colon, immune cells, etc.

Deficiency in this vitamin is also correlated with a myriad of acute and chronic illnesses, including autoimmune disorders like multiple sclerosis (MS), rheumatoid arthritis (RA), osteoarthritis and type 1 diabetes, hypertension, cardiovascular disorders, infectious diseases, deadly cancers, type 2 diabetes, neurological disorders, preeclampsia, childhood dental caries, periodontitis 2.

What is Vitamin D?

Vitamin D, also known as the sunshine vitamin, is actually a hormone. Vitamin D3 is produced in the tissues, then transported in the blood, producing its effects on other tissues. Feedback mechanisms modulate those effects. Therefore, it is considered a steroid-based hormone rather than a vitamin3. Important: Vitamin D is a hormone, not a vitamin!

This vitamin also has two forms – D3 and D2

  • Vitamin D3 (cholecalciferol) – synthesized endogenously in the skin and found naturally in oily fish and cod liver oil.
  • Vitamin D2 (ergocalciferol) – is synthesized from ergosterol and found in yeast and mushrooms.

Vitamin D3 is, however, biologically inert. Once vitamin D3 is formed in the skin or ingested in the diet, it must be hydroxylated in the liver and kidney to form its biologically active hormone 1,25-dihydroxyvitamin D3.

The pressing question is, why is most of the world’s population deficient in Vitamin D?

It is, in fact, very simple: we don’t get enough SUN! It is estimated that the sunlight meets around 90% of the body’s vitamin D demand and only 10% is obtained from foods. This means that the amount of vitamin D obtained from food is almost insignificant.

Sun exposure is the main contributor to Vitamin D production. Or better said, skin exposure to the sun. Most people think they are getting enough sun, but they are covered in clothing or sunscreen, which won’t allow Vitamin D production. Food and supplementation may play an important role when production through sunlight is reduced.

Exposure to sun is crucial, because when sunlight reaches our skin it acts as a stressor to our body – it can be considered an environmental stressor through UV radiation. Most environmental stressors in small amounts are beneficial for the body. This happens with the sunlight, cold water, and movement… and it is called hormesis. The body’s mechanisms of adaptation to external challenges make it more resilient and better apt to protect itself against many different conditions, including diabetes, cardiovascular disease, cancers, and neurodegenerative disorders.

 

How does the skin produce vitamin D3 from sunlight?

Vitamin D3, cholecalciferol, is produced in the skin. During exposure to sunlight, the high-energy UV photons (UVB 290-315 nm) penetrate the epidermis and photolyze cutaneous stores of 7-dehydrocholesterol (provitamin D3) to previtamin D3. Once formed, previtamin D3 undergoes a temperature-dependent isomerization to vitamin D3, cholecalciferol, that takes 2-3 days to reach completion 4.

Schematically

  • High-energy UV photons penetrate the skin
  • Stores of provitamin D3 are photolyzed to previtamin D3
  • Previtamin D3 is isomerized to vitamin D3

Important: the skin is responsible for producing vitamin D3!

However, the vitamin D3 produced by the skin or obtained through diet and the vitamin D2 obtained from plant-based foods (mushrooms and yeast) are both not biologically active. Vitamin D2 can be converted to D3 in hepatic (liver) tissues, and then vitamin D3 activation happens in the liver and kidneys5.

 

The “complex” process of vitamin D activation in the liver and kidneys

Vitamin D3 in circulation is carried to the liver by vitamin D-binding protein. It is then sequentially metabolized in the liver by an enzyme (26-hydroxylase) into calcidiol (25-hydroxy-vitamin D [25(OH)D], the major circulating form of vitamin D. Then it is mainly converted, if not exclusively, in the kidneys by another enzyme (1-alpha hydroxylase) to the final hormone, the biologically active calcitriol (1,25-dihydroxy vitamin D).

Calcidiol, the major circulating form, it is inactive, and its concentrations are almost 1000-fold of calcitriol6. In this sense, the enzyme responsible for the conversion in the kidneys, 1-Alpha-hydroxylase, is the key enzyme for vitamin D synthesis. The activity of this enzyme in the renal tissues is regulated by the parathormone (PTH).

More recent studies found that the 1-alpha hydroxylase enzyme, besides the kidneys, also exists in the intestines, epidermis, prostate, breast, pancreas, and parathyroid glands. This important finding may indicate that sufficient calcidiol (non-active form of vitamin D) levels are also required in non renal tissues to produce calcitriol (active form of vitamin D).

By understanding the process of vitamin D production, we realize that liver and kidney function are essential to forming active Vitamin D3.

References

  1. Michael F. Holick, Neil C. Binkley, Heike A. Bischoff-Ferrari, Catherine M. Gordon, David A. Hanley, Robert P. Heaney, M. Hassan Murad, Connie M. Weaver, Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 96, Issue 7, 1 July 2011, Pages 1911–1930, https://doi.org/10.1210/jc.2011-0385
  2. Holick MF. The vitamin D deficiency pandemic: Approaches for diagnosis, treatment, and prevention. Rev Endocr Metab Disord. 2017 Jun;18(2):153-165. doi: 10.1007/s11154-017-9424-1. PMID: 28516265.
  3. Kulda V. Metabolizmus vitaminu D [Vitamin D metabolism]. Vnitr Lek. 2012 May;58(5):400-4. Czech. PMID: 22716179.
  4. Holick MF, Smith E, Pincus S. Skin as the site of vitamin D synthesis and target tissue for 1,25-dihydroxyvitamin D3. Use of calcitriol (1,25-dihydroxyvitamin D3) for treatment of psoriasis. Arch Dermatol. 1987 Dec;123(12):1677-1683a. PMID: 2825606.
  5. Bikle DD. What is new in vitamin D: 2006-2007. Curr Opin Rheumatol. 2007 Jul;19(4):383-8. doi: 10.1097/BOR.0b013e32818e9d58. PMID: 17551371.

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