The older I get, the more experience I have with vitamin D, the more I realize that this stuff starts to decay as soon as you open the bottle. I think it's gone within 6 weeks.
If this is true, it creates a tremendous confounder for all the published vitamin D literature that measures the effects of supplements. All the research, in other words, might have a significant problem. What a pain, if one is trying to be scientific about all this.
What evidence do I have of this? First, according to this chemical database from the NIH, vitamin D3 (cholecalciferol) is "oxidized and inactivated by moist air within a few days."
Second, I have direct observation. When I was working at the Buffalo Psychiatric Center in the early 2000s, I found many patients with vitamin D deficiency. I started supplementing them with what was standard at the time: ergocalciferol (vitamin D2) 50,000 units a week. At first this worked well, but after a few months I found that I couldn't get the vitamin D levels up despite this large-dose supplementation. Could all my patients have malabsorption? I doubted it. So, after seeing the information above about vitamin D degradation, I went down to the pharmacy and asked them how they store it. They had opened a bottle about six months previously and individually packed the pills into blister packs. So essentially the vitamin D had been sitting in air for the past six months.
The makers of Replesta apparently have figured this out. (I have no relationship with the company.) They individually wrap their high-dose vitamin D in little foil packets. I have started using this stuff in my office, the vitamin D levels go up very rapidly, to the point that I have to change my practice patterns. I rarely give 50,000 units a week any more; that turns out to be too much. Now it's 14,000 a week for almost everybody.
So based on this perspective, and considering that I have never seen a research study indicate how vitamin D is stored after it is dispensed to the research subjects, I am being careful about interpreting clinical trials of vitamin D. They may underestimate the true effect of this steroid hormone.