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Practice NIHR Signals

Can treating vitamin D deficiency reduce exacerbations of chronic obstructive pulmonary disease?

BMJ 2019; 364 doi: (Published 18 March 2019) Cite this as: BMJ 2019;364:l1025


NIHR’s research signals in The BMJ

Chronic obstructive pulmonary disease and 25(OH)D

The piece in the Practice section promoting vitamin D supplementation for chronic obstructive pulmonary disease with low vitamin D (less than 25 nmol/L) deserves comment.(1)

First, vitamin D supplementation has no effect on exacerbation rates of chronic obstructive pulmonary disease. The 0.55 incidence rate ratio in the subgroup of people with low vitamin D (less than 25 nmol/L) receiving supplementation is only an hypothesis, as with any subgroup post hoc analysis. How to overlook the example from the ISIS-2 trial showing aspirin was ineffective when born under Gemini or Libra astrological signs.(2) Moreover using an arbitrary cut-point to derive subgroups is not appropriate as there is a continuous distribution of the values with no obvious modal values. Moreover, there is no agreement about the cut-point for low vitamin D. Last, assessment of vitamin D level is season dependent and, technically most difficult.(3)

Second, could the hypothesis be relevant for clinical practice? Coincidentally tobacco use, alcohol consumption, obesity, insulin resistance, type 2 diabetes are associated with low vitamin D.(4,5) As a pessimist I feel it is unlikely that vitamin D supplementation could be the magic bullet against the conditions most frequent among patients with chronic obstructive pulmonary disease, being causal or worsening factors. It cannot replace multidisciplinary life-style interventions by trained professionals which are effective.(6)

The prospective survey (NHANES III: n=13,331 adults, from 1988 through 1994, followed for mortality through 2000) showed vitamin D levels cannot predict mortality form either cancer or cardiovascular disease when accounting for age, sex, ethnicity, diabetes, current smoking, body mass index, physical activity, season. This did not preclude an enduring flow of poorly designed research promoting vitamin D supplementation.(8)

1 Cook R, Thomas V, Martin R, NIHR Dissemination Centre. Can treating vitamin D deficiency reduce exacerbations of chronic obstructive pulmonary disease? BMJ 2019;364:l1025.

2 Sleight P. Subgroup analyses in clinical trials: fun to look at – but don’t believe them! Curr Control Trial Cardiovasc Med 2000;1:125–127.

3 Cavalier E, Souberbielle J-C. Vitamin D and its metabolites: from now and beyond. EJIFCC. juill 2018;29(2):105‑10.

4 Wise SA, Tai SS-C, Burdette CQ, Camara JE, Bedner M, Lippa KA, et al. Role of the National Institute of Standards and Technology (NIST) in Support of the Vitamin D Initiative of the National Institutes of Health, Office of Dietary Supplements. J AOAC Int 2017;100:1260‑76.

5 Tønnesen R, Hovind PH, Jensen LT, Schwarz P. Determinants of vitamin D status in young adults: influence of lifestyle, sociodemographic and anthropometric factors. BMC Public Health 2016;16:385.

6 Palaniswamy S, Hyppönen E, Williams D, Jokelainen J, Lowry E, Keinänen-Kiukaanniemi S, Herzig KH, Järvelin MR, Sebert S. Potential determinants of vitamin D in Finnish adults: a cross-sectional study from the Northern Finland birth cohort 1966. BMJ Open 2017;7: e013161.

7 Baumann S, Toft U, Aadahl M, Jørgensen T, Pisinger C. The long-term effect of a population-based life-style intervention on smoking and alcohol consumption. The Inter99 Study--a randomized controlled trial. Addiction 2015;110:1853-60.

8 Braillon A. Vitamin D and breast cancer survival: The good and the bad. JAMA Oncol 2017;3:1138-1139

Competing interests: No competing interests

20 March 2019
alain braillon
senior consultant
University hospital. 80000 Amiens. France