Vitamin D Absorption and Excretion

Vitamin D comes in two forms, Vit D₂ and Vit D₃ . Most of the information being published now refers to Vit D₃ , which is the form made in the skin of humans; Vit D₂ is obtained from plant sources. Vit D₃ is converted to 25-hydroxy Vit D₃ in the liver, and then to 1,25-dihydroxy Vit D₃ (active form) in the kidney and other tissues. Before I go into perhaps too much detail, I should say that vitamin D activity stays in the body for a long time, and that daily dosing with fatty food is probably best.

Vit D₃ is fat soluble and appears to be absorbed best when it is taken with food containing some fat; I take it with peanut butter at breakfast time. Once it has been absorbed it distributes into fat with a half-life of about 1.5 days, and then is removed by metabolism with a half-life reported be three days to almost a month. There is likely to be considerable variability in the both phases in part because of the varying amounts of fat in the bodies of different people. The original study I read was done on a small number of people in 1969 when obesity was less prevalent. The half-life of 25-hydroxy Vit D₃ and 1,25-dihydroxy Vit D₃ appear to be 15 days and 15 hours, respectively. In practical terms, this means that the blood levels take quite a long time to stabilize fully; some authorities suggest 6-8 weeks (see below). For most of us, taking a consistent dose will get us to a steady state level after 4-5 times the half-life of the longest lived molecule in question (Goodman & Gilman, the Pharmacological Basis of Therapeutics, Chap 1). I think (guess?) that we get some vitamin D benefit almost immediately and then continue to get it full benefits over a period of many days. Using the principles of pharmacokinetics, one might predict that a loading dose followed by a maintenance dose would be best, but the observations seem to support just daily dosing. Maybe the modelling, multiple variables and unknown properties of vitamin D₃ and its metabolites are just complex for me to understand.

Another variable that complicates predictions about body content of vitamin D is exposure to sunlight. The rate at which a person’s skin makes vitamin D depends on-

(a) duration of exposure- longer exposure results in more synthesis

(b) skin colour- darker skin contains more melanin and decreases synthesis; tanning reduces synthesis

(c) area of skin exposed- more area results in more synthesis

(d) time of year- summer months produce the most and winter months the least

(e) latitude- closer to the equator is best, all of Canada is in a low synthesis zone

(f) time of day- maximum vitamin D synthesis coincides with the time of maximum sunburn risk

(g) altitude- there is less atmosphere to block UV radiation at higher altitudes

(h) age- older people tend to make less vitamin D

To put this into context, a light skinned person with full body exposure to sunlight at mid-day may start to turn pink in 15-20 minutes and make 10000 IU of vitamin D.

The American Association of Clinical Endocrinologists has a nice set of slides on vitamin D requirements and dosing at https://www.aace.com/sites/default/files/2019-02/Vitamin_D_Deficiency_formatted.pdf

Slide 3 shows how the definitions of deficiency vary in comparison with other academic parties; nevertheless there is a trend toward recommending higher intakes of vitamin D. Slide 10 describes using a loading strategy to address frank vitamin D deficiency; this would be done under medical supervision for individuals whose blood level of 25-hydroxy Vit D₃ has been determined.

I think that the now known properties of vitamin D, where we live and how we live are consistent with a number of health issues facing contemporary Canadian society. For example, we know that the “flu” season occurs in winter; this would be about the time that our bodies become quite depleted in vitamin D. Before the advent of effective drugs, tuberculosis used to be treated by putting patients in the sun. We have seen an unexplained increase in the prevalence of asthma, since about 1970 and this coincides with kids spending less time outdoors, partially because of computer toys and partially because of overprotective parents who are hesitant to chase their kids out to play. Obesity is a stated risk factor for death in COVID-19; is this due to the larger vitamin D sink or the generation of inflammatory cytokines by adipocytes? Too many questions, not enough answers.