Vitamin D supplements have unintended lipid consequences

Correcting vitamin D levels in individuals at risk for cardiovascular disease (CVD) may have detrimental effects on their lipid profiles, report researchers.

The findings not only challenge cross-sectional studies supporting a role for vitamin D repletion in ameliorating dyslipidemia, but also raise the possibility that vitamin D supplements may in fact worsen it for some patients, say Jan Breslow (The Rockefeller University, New York, USA) and colleagues.

Of 151 individuals with vitamin D deficiency (25-hydroxyvitamin D [25[OH)D] <20 ng/mL) and at least one risk factor for CVD, those randomly allocated to receive weekly vitamin D supplementation (50,000 IU) had improved 25(OH)D levels after 8 weeks (mean level 43.0 ng/mL), while levels remained unchanged in those who received placebo, at a mean of 14.6 ng/mL.

Compared with the placebo group, there was no improvement in lipid profiles among those who received vitamin D supplementation. On the contrary, levels of total cholesterol, low-density lipoprotein (LDL), and triglycerides increased more in the vitamin D versus placebo group, by 5.8 mg/dL, 3.8 mg/dL, and 7.9 mg/dL, respectively.

"The uncoupling between our randomized clinical trial data and the cross-sectional associations of higher 25(OH)D levels should spark caution towards inferred benefits of vitamin D supplementation on the lipid profile," warns the team.

As reported in Arteriosclerosis, Thrombosis, and Vascular Biology, serum calcium levels increased by 0.12 mg/dL in the vitamin D group relative to placebo while parathyroid hormone (PTH) levels decreased by an average of 18 pg/mL in the vitamin D group and were unchanged in the placebo group.

Vitamin D repletion had a strong effect on the biomarkers calcium and PTH, say the researchers. They went on to explore whether the response was associated with the observed changes in LDL cholesterol.

Indeed, multivariate analysis showed that in the vitamin D group, changes in LDL cholesterol correlated positively with the changes in calcium and inversely correlated with the changes in PTH.

On stratifying the participants by change in serum calcium with vitamin D therapy, Breslow and colleagues found that, compared with individuals with below-median response, those with an above-median response had an increase in LDL cholesterol of 15.4 mg/dL.

"High-dose oral supplementation in an at-risk population may have an adverse effect on cardiovascular risk for those individuals who have the strongest biological response to vitamin D," they remark.

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