Feb 112014

After a stupefying amount of research on vitamin D -- with 70 vitamin D studies published in PubMed in January 2014 alone -- there is no consistent signal tying vitamin D supplementation to improvement in any health condition. A recent "futility analysis" (a form of meta-analysis) of 40 randomized trials suggests vitamin D does not prevent fractures, cardiovascular disease, cancer, or mortality, and that continued study would be unlikely to discover any benefit. (In 2 randomized trials, vitamin D supplementation did reduce hip fractures in institutionalized patients.)

More than half of people with COPD have vitamin D deficiency. Researchers have explored the relationship between COPD and vitamin D deficiency, but without finding a meaningful connection thus far:

What They Did

In the January 2014 Chest, Milo Puhan et al take their turn in the sun. They report following 356 patients with moderate to severe COPD for 2 years, 77% of whom had vitamin D deficiency. Patients were surveyed every 6 months, and their pharmacy records monitored for steroid/antibiotic prescriptions.

What They Found

Vitamin D levels (mild, moderate, severe deficiency) had no relationship to the frequency or severity of COPD exacerbations. Most patients did have at least one exacerbation.

There were 24 patients with healthy vitamin D levels (>30 ng/dL), and they did have a lower absolute rate of COPD exacerbations (incidence ratio 0.72), but this was not statistically significant. Vitamin D levels had no association with mortality.

What It Means

There's still a glimmer of a chance that supplementing vitamin D in severely deficient people could reduce COPD exacerbations -- see the post hoc signal in Lehouck et al, and the finding here that normal vitamin D levels might have been somehow protective against exacerbations. (Or not, and the healthy vitamin D levels were just a marker of better health and resistance to exacerbation in other unmeasured ways).

Because of the relatively low event rates in COPD (~1 to 2 exacerbations/patient/year), it would have to be a randomized trial enrolling hundreds of patients, and/or restricted to patients with severe COPD with frequent exacerbations. One fitting this bill (n=240) wrapped up last August in the U.K.; no results posted yet on clinicaltrials.gov.

Until we get better information, I lean toward Karl Michaelsson's recent editorial, in which he suggests that much vitamin D deficiency may be another form of overdiagnosis:

Existing evidence does not lend support to the commonly held belief that vitamin D supplementation in general prevents osteoporosis, fractures, and nonskeletal diseases. Consequently, the impression that vitamin D is a sunshine vitamin and that increasing doses lead to improved health is far from clear.

Without stringent indications -- i.e. supplementing those without true insufficiency -- there is a legitimate fear that vitamin D supplementation might actually cause net harm. Until more information is available, it would be prudent to choose a cautious approach to vitamin D supplementation and to put more emphasis on the development of evidence-based cutoff points for vitamin D inadequacy.

42% of the U.S. population is supposedly "deficient" in vitamin D, including 82% of African-Americans. When we're labeling so many people with a health condition, one ought to question the definition itself.

Milo A Puhan et al. No Association of 25-Hydroxyvitamin D With Exacerbations in Primary Care Patients With COPD. Chest. 2014;145(1):37-43. doi:10.1378/chest.13-1296

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Vitamin D: no relationship to COPD exacerbations