Taking skin cells as an example in skin cells-keratinocytes-all three main forms of vitamin D3 activate the HPA axis and the peripheral cellular process where this occurs to produce pro-opiomelanocortin (POMC). 1

To summarize the three main forms of vitamin D3. 

  1. Cholecalciferol- the form of vitamin D3 produced from UV-B in the skin and taken in oral supplements). 
  1. Calcifediol (the vitamin D3 form created in the liver, the blood storage form and form we measure in blood to determine blood plasma levels)
  1. Calciferol (the active form of vitamin D3 produced in the kidneys but also, inside most cells)

One interesting fact is how the body produces POMC. As UV-B exposure of  keratinocytes in the skin dermis results in activation of p53. 2 As a transcription factor, p53 binds directly to the POMC gene promoter which results in the production of POMC. 

More of POMC that is produced then potentially more of its products like beta-endorphins and A- and B-MSH that can be produced and released to act on the body. For example through A-MSH producing pigmentation, the suntan response, to protect from UV-B light.

Additionally skin exposure to ultraviolet light results in the releasing of beta-endorphins. Creating a positive feedback-reward for sun exposure. Besides effecting pain, beta endorphins act directly on the immune system by acting on the T-lymphocyte, B-lymphocyte, and monocytes. To fight infections.

Beta-endorphins also boost natural killer cells  function for example. These cells are part of the immune system and known to be critical in destroying cancer cells. 4 All are part of our immune system. Also, vitamin D binding protein (DBP) as I explained in the previous blog post is involved in the immune system.

As nothing seems to be wasted and none of the substances related to vitamin D3 seem to have only one use. DBP also has been shown to be a significantly slow cancer growth. 5 So, so far, we have UV-A, UV-B, beta-endorphins, DBP and the P53 gene all associated with the immune system and/or cancer.

Now to the CYP24A1 genes function is manipulation by many different types of cancers. That is critical as to why they are so successful in evading the immune system that would otherwise destroy them. As was explained previously part of the immune systems function is to destroy abnormal cells, like cancer cell. 

As I have both blogged and written about before how optimal blood plasma levels of vitamin D3 are critical to a properly functioning immune system. In my experience vitamin D3 most profound and consistent effect is on our immune system. Like how it protects us both from the “flu” and I believe from Covid-19.


  1. Siegel C, Prusty BK, Rudel T, et al. (November 6, 2014) Tumor suppressor p53 alters host cell metabolism to limit chlamydia trachomatis infection. 9(3):918-29.
  2. Oren M, Bartek J. (9 March 2007). The sunny side of p53. Cell. 128(5);826-28.
  3. 3. Cui R, Widlund HR, Feige E, et al. (9 March 2007) Central role of p53 in the suntan response and pathological hyperpigmentation. Cell. 128(5);853-864.
  4. Wu J, Lanier LL. (2003). Natural killer cells and cancer. Adv Cancer Res 90:127-56.
  5. Kalvin JG, Zhao B, Bielenburg DR, et al. (2010). Vitamin D binding protein-macrophage activating factor directly inhibits proliferation, migration, and uPAR expression of prostate cancer cells. PloS One. 5(10): e13428.

*The information posted above is for educational purposes only. Always check with your doctor before initiating any changes in your medical treatment. If you do not, then The Two-Minute Health Fact, Dr. Judson Somerville, nor The Optimal Dose is responsible!


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