Health effects of vitamin D - another epidemiological conundrum

Forget an apple a day keeping the doctor away, current wisdom suggests that a dose of vitamin D a day will keep every imaginable specialist away.  Vitamin D deficiency has been associated with cancer, cardiovascular disease, immune problems like asthma, flu, tuberculosis, autoimmune diseases like multiple sclerosis, low bone density and osteoporosis, and many other diseases.  As with so many epidemiological studies, however, the evidence for most of these is not unequivocal.  Indeed, it's not even clear what "normal" vitamin D levels should be.  Even so, vitamin D supplementation is big, with almost half of adults over 50 in the US currently taking them.

However, as reported in the NYTimes and elsewhere, a new paper in The Lancet ("Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis", Reid et al., Oct 11) concludes that there's essentially no evidence that vitamin D supplementation improves bone density or prevents osteoporosis.

The paper is a report of a meta-analysis of twenty-three studies, with an average duration of about 2 years.  A total of 4082 participants, 92% women, with an average age of 59, were included in the studies in the meta-analysis.  Nineteen of the studies were of predominantly white women.  Baseline vitamin D was generally within normal levels, women were healthy by and large, and were given vitamin D doses between 500 and 800 units per day.  Some were also given calcium.  Bone mineral density was measured at one to five sites (lumbar spine, femoral neck, total hip, trochanter, total body, or forearm).  The analysis showed a small benefit only at one site (femoral neck), though not in all the studies, and no effect was found at any other site.  The authors conclude,

Continuing widespread use of vitamin D for osteoporosis prevention in community-dwelling adults without specific risk factors for vitamin D deficiency seems to be inappropriate.

Vitamin D is available in small amounts in some foods, but most mammals, including humans, make their own, induced by exposure to the sun.  Without a doubt, severe vitamin D deficiency can cause osteomalacia (softening of the bones) or rickets (softening of the bones in children), but other health effects aren't so clear.  And, optimal vitamin D levels haven't been agreed upon, and they may well vary by age, sex and ethnicity.

2-yr old rickets patient; Wikipedia

Indeed, people with darker skin don't synthesize as much vitamin D from sun exposure as lighter- skinned people do, but African American women are less susceptible to osteoporosis and fractures than are European women (much has been written about this paradox, including this).  So, even after decades of intense study, there's a lot that's not yet understood about vitamin D and its contributions to health.

Whether or how vitamin D boasts the immune system, or protects against the many diseases it is said to are still open questions.  Multiple studies have shown that TB patients do have lower serum vitamin D levels than healthy controls, but it's not clear that low vitamin D preceded disease, and vitamin D supplementation doesn't seem to speed recovery.  Thus there is the question of cause vs correlation, statistical association vs confounding by unmeasured correlated causal factors.  The same kinds of equivocal findings are true of other diseases.  Further, clinicians don't agree on optimal levels, and excess vitamin D, too, may be associated with risk of some cancers or atrial fibrillation. Each person is likely to react differently to high or low doses, based on genetic variation or other lifestyle factors.

There's much still to be sorted out about the association between vitamin D and health.  Because results have not been definitive, it's likely that the effects of vitamin D are modest, at best, except for long known effects of severe deficiency.  Because vitamin D doesn't act alone, and the complex diseases it has been associated with are themselves associated with multiple risk factors, teasing out the role of vitamin D won't be straightforward.  Another epidemiological conundrum.