The truth about vitamin D synthesis

There are many misconceptions when it comes to vitamin D synthesis.  Most people think that when they take a vitamin D supplement they're taking the active form, and directly changing their body's concentration , when really this isn't quite true. I'd like to expand on vitamin D metabolism in a bit more detail, and explain why I believe vitamin D supplements couldn't possible replace sunlight exposure.

Vitamin D is actually synthesized through a multiple-step reaction, starting in the skin with a cholesterol analog known as 7-dehydro-cholesterol, which is converted to a compound called pre-vitamin D in response to UV-B spectrum light. Pre-vitamin D is then carried to the liver, along the way naturally breaking down to D3 as a result of body temperature. D3 is the form most people take in supplements but it's not the end product of this pathway.

When D3 reaches the liver it's converted into the storage form, known as 25D. From there, 25D is then either sent back out into circulation as needed, or if enough excess builds up, stored in the liver for long periods of time. 25D is then converted into the final active form of this hormone, 1,25D. This conversion occurs primarily in the kidneys, but to a lesser extent in other tissue throughout the body.

Now there are actually several rate-limiting points the body uses to regulate each step in this pathway. Vitamin D production in the liver is limited so that excess storage does not arise, production of active form in the kidneys is even further limited. There is a good reason that this limiting occurs. Vitamin D is one of the 3 primary calcium regulation hormones in the body (the other two being parathyroid hormone and calcitonin), and excess of it causes imbalances of elevated serum calcium. This is a big part of why I believe that most everyone should avoid D3 supplementation.

When you supplement D3 you build up the storage form artificially. The body does its best to limit this, which is why it's extremely difficult to raise low-moderate vitamin D levels in serum, but it is possible. Our current blood testing falls short of giving us an actual picture of what's going on, so in some cases this increase isn't even necessary. When your doctor tests your vitamin D status they look at the level of 25D in serum, as it's the most stable marker. Unfortunately 25D in serum does not accurately reflect the overall level of 25D in different tissues, much less 1,25D levels anywhere in the body. 

Interestingly, the levels of 25D that are considered optimal now are actually far higher than the original "optimal" levels. This change was made by the Endocrine Society and went against the research standards established by the US and Canadian government, yet gained widespread acceptance. Before this change in public opinion,12ng/ml was considered the cutoff for deficiency, compared to 30ng/ml being the cutoff today. Some research, for example this study, indicates no added benefit to levels above 20ng/ml. The levels of the active 1,25D form are generally expected to be 2.5x higher than 25D in serum.

Beyond the issues with blood testing, there are many more benefits to vitamin D production from UV-B light that extend beyond the effects of supplements alone. This includes a number of other compounds produced beyond just 1,25D. In sunlight there's actually a WATER soluble form of vitamin D produced through sulfation, so vitamin D is not just a fat-soluble hormone!

Some pre-vitamin D is also converted to a variety of other compounds through a side reaction before it reaches the liver. Lumisterol and tachysterol are the most well-studied, and while thought to be generally inactive, go on to produce another 5-10 possibly active analogs each.

When we reach 25D production, there is even further divergence in this pathway. There are actually 12 different analogs of 25D produced in the liver as well, using both the sulfated and standard form of D3 as a precursor. This means that at least half of these are only produced by UV-B! Some of these come from an epimerization pathway that creates epi-25D analogs, which play less of a role in calcium regulation. Interestingly, there's some studies suggesting that up to 60% of 25D created in those that supplement vitamin D is actually epi-25D, perhaps as a means to prevent overload from causing calcium imbalance.

If all these different forms of vitamin D aren't enough, there's recently been research confirming that other analogs of different nutrients, specifically vitamin A, are also produced in response to the UV light spectrum (both UV-A and UV-B). Vitamin A is broken down in response to UV light, and from there its byproducts are converted into various analogs, some of which are thought to modulate gene expression by activating different retinoid receptors. This could lead to a wide variety of downstream effects.

There are other compounds created in sunlight, but I think it's evident from the analogs of vitamin D alone that we can't replace sunlight with a supplement. The body is an extremely dynamic system that tightly regulates vitamin D production. I don't believe there's any need to override that.

If you live somewhere where you can't get UV light year round, rather than taking supplements I'd suggest using a UV-B lamp. Sperti is normally the brand I'd recommend, but as they're currently sold out, here's a few cheaper options as well: 6 Best Vitamin D Lights

For those interested in further research on vitamin D levels, and studies showing issues with vitamin D supplementation, I'll link a few below:

Vitamin D, Calcium Supplements, and Implications for Cardiovascular Health: JACC Focus Seminar | Journal of the American College of Cardiology

Vitamin D Status, Supplementation and Cardiovascular Disease | Anticancer Research

Calcium and/or Vitamin D Supplementation for the Prevention of Fragility Fractures: Who Needs It? - PubMed (

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