Effect of Monthly, High-Dose, Long-Term Vitamin D on Lung Function: A Randomized Controlled Trial

Abstract

Although observational studies suggest positive vitamin D-lung function associations, randomized trials are inconsistent. We examined effects of vitamin D supplementation on lung function. We recruited 442 adults (50–84 years, 58% male) into a randomized, double-blinded, placebo-controlled trial. Participants received, for 1.1 years (median; range = 0.9–1.5 years), either (1) vitamin D3 200,000 IU, followed by monthly 100,000 IU doses (n = 226); or (2) placebo monthly (n = 216). At baseline and follow-up, spirometry yielded forced expiratory volume in 1 s (FEV1; primary outcome). Mean (standard deviation) 25-hydroxyvitamin D increased from 61 (24) nmol/L at baseline to 119 (45) nmol/L at follow-up in the vitamin D group, but was unchanged in the placebo group. There were no significant lung function improvements (vitamin D versus placebo) in the total sample, vitamin D-deficient participants or asthma/chronic obstructive pulmonary disease (COPD) participants. However, among ever-smokers (n = 217), the mean (95% confidence interval) FEV1 increase in the vitamin D versus placebo was 57 (4, 109) mL (p = 0.03). FEV1 increases were larger among vitamin D-deficient ever-smokers (n = 54): 122 (8, 236) mL (p = 0.04). FEV1 improvements were largest among ever-smokers with asthma/COPD (n = 60): 160 (53, 268) mL (p = 0.004). Thus, vitamin D supplementation did not improve lung function among everyone, but benefited ever-smokers, especially those with vitamin D deficiency or asthma/COPD.

Consensus statement from 2nd International Conference on Controversies in Vitamin D

“…However, beneficial effects from vitamin D supplementation were seen: for persistence with taking statins in participants on long-term statin therapy [228]; and also in bone mineral density [229], and arterial function (central blood pressure) [230], particularly in participants with low serum 25(OH)D concentrations. Beneficial effects were also seen on lung function (forced expiratory volume in 1 second) among ever smokers, and patients with Chronic Obstructive Pulmonary Disease (COPD) or asthma (especially if vitamin D deficient) [231]. The latter findings are consistent with several previous studies.…”

“…The lack of effect could be due to the use of monthly, rather than daily or weekly supplementation, insufficient participants with vitamin D deficiency, lack of co-supplementary calcium or too short a follow-up period for chronic disease outcomes. However, the ViDA study did show that the beneficial effects for some outcomes such as BMD [229], FEV1 [231] and arterial function [230] are more pronounced in subjects with serum 25(OH)D concentrations of <50 nmol/L. These findings are consistent with several previous studies, including VITAL and D2d, which collectively suggest that vitamin D supplementation may only be beneficial in people who are deficient [232].…”

Emerging Evidence of Thresholds for Beneficial Effects from Vitamin D Supplementation

“…The clinical significance of these findings is unclear at the moment until further research quantifies the role of these parameters in predicting cardiovascular disease. In addition, vitamin D supplementation for one year (compared with placebo) increased forced expiratory volume in 1 s (FEV 1 ), measured by spirometry, more in participants who had ever smoked tobacco and had 25(OH)D levels of <50 nmol/L (by 109 mL or 5%) than in those who had ever smoked and had higher vitamin D levels ( P interaction = 0.048) [ 42 ]. Changes in FEV 1 of >100 mL are clinically significant [ 43 ].…”

Vitamin D deficiency is an independent predictor of mortality in patients with chronic heart failure

“…The Vitamin D Assessment study (ViDA) in 5100 healthy subjects, aged > 50 years, recently reported that 100,000 IU oral vitamin D 3 monthly was neutral for the prevention of CV disease [49,50], with a low rate of 25[OH]D deficiency in participants (25%), a lower than expected endpoint rate and monthly doses cited as possible reasons [51]. Metaanalysis and data from ViDA and other studies describe that benefits on clinical outcomes are greatest in the most deficient, and in studies using daily dosing regimens (as in VINDICATE) rather than monthly [52][53][54][55].…”