Published: Mar 10, 2014
By Charles Bankhead, Staff Writer, MedPage Today
Action Points
- In this randomized trial in postmenopausal women, supplemental CaD significantly increased 25[OH]D3 concentrations and decreased LDL -C.
- Higher concentrations of 25[OH]D3 were also associated with modestly higher HDL-C levels and lower triglyceride levels.
Postmenopausal women had significant improvement in their lipid profile with long-term calcium and vitamin D supplementation, data from the Women’s Health Initiative (WHI) showed.
After 6 years of follow-up, supplementation was associated with a statistically significant 4.46 mg/dL decrease in LDL versus placebo, a numerical decrease in triglycerides, and a numerical increase in HDL.
Estimated serum 25-hydroxyvitamin D3 (25[OH]D3) concentration had significant associations with with LDL, HDL, and triglycerides, as reported in Menopause.
“These results support the hypothesis that higher concentrations of 25OHD3, in response to calcium-vitamin D supplementation, are associated with improved LDL-C,” Peter F. Schnatz, DO, of Reading Hospital in Pennsylvania, and co-authors concluded. “Although further studies are need to determine whether these findings translate into clinically meaningful results, this should be viewed as a reminder that women at higher risk for 25OHD3 deficiency should consider supplementation with calcium and vitamin D.”
Numerous studies have evaluated the effect of calcium supplementation on lipid levels, producing inconsistent results. In contrast, few studies have examined the effects of vitamin D supplementation and 25(OH)D3 concentrations, coronary heart disease (CHD), and CHD risk factors. To assess the relationships, Schnatz and colleagues analyzed data from the WHI randomized, placebo-controlled study of calcium-vitamin D supplementation.
The principal objectives of the analysis were to evaluate relationships among calcium-vitamin D supplementation, serum 25(OH)D3, and plasma cholesterol concentrations. The effects of supplementation on lipids was not the primary objective of the parent trial, which examined the supplements’ effects on fracture risk and colorectal cancer in postmenopausal women.
Participants in the randomized trial received supplements (1,000 mg elemental calcium plus 400 IU vitamin D) or placebo. Of 1,048 participants in the trial, 600 had lipid and 25(OH)D3measurements at baseline and years one, three, and six. Participants’ 25(OH)D3 levels were not measured at baseline or year six, and values for those time points were imputed.
To determine whether supplementation significantly affected LDL and whether 25(OH)D3levels mediated the effect, the authors evaluated four issues:
- Relationship between supplements and 25(OH)D3 concentration
- Effect of supplementation on LDL
- Whether the effect of supplements on LDL was attenuated after adjustment for 25(OH)D3
- Whether 25(OH)D3 was significantly associated with LDL
The final analysis comprised 576 participants with a valid dataset. The women had a mean age of 61.8 at baseline. and they averaged 14.6 years from menopause. The supplementation and placebo groups did not differ significantly with respect to demographic or clinical characteristics at baseline.
The group that received supplements had a significantly higher mean 25(OH)D3concentration by year three (24.3 versus 18.2 ng/mL, P<0.001). The mean postintervention 25(OH)D3 concentration was 1.38 times greater in the supplementation group, representing a 38% increase over the placebo group.
Women in the supplement arm were more than twice as likely to have 25(OH)D3concentrations ≥30 ng/mL as compared with the placebo group: 35.4% versus 15.1% (RR 2.35, P<0.001). Supplementation was associated with almost a 60% increased likelihood of attaining 25(OH)D3 levels ≥20 ng/mL (76.5% versus 47.7%, RR 1.58, P<0.001).
In an unadjusted analysis, the 4.46 mg/dL difference in LDL in favor of the supplement group was statistically significant (P=0.03). Nonsignificant improvement was observed in HDL and triglyceride levels among patients receiving supplements.
In a statistical model that incorporated 25(OH)D3 level, the mean difference in LDL decreased to 3.24 mg/dL and no longer achieved statistical significance. Instead, 25(OH)D3 proved to be the significant predictor of LDL, as every 38% increase in vitamin D level was associated with 1.28 mg/dL decrease in LDL (P=0.04).
The multiple imputation analysis also showed an attenuated effect of calcium-vitamin D supplementation and LDL, which was significantly associated with 25(OH)D3 (P=0.001).
Models of pre- and post-randomization visits showed that higher 25(OH)D3 levels were significantly associated with higher HDL levels (P=0.003) and with lower triglyceride levels (P<0.001). Associations between vitamin D concentration and lipid levels were not affected by visit year or treatment assignment.
The findings provide a measure of reassurance that calcium-vitamin D supplementation did not adversely affect lipids, said Margery Gass, MD, executive director of the North American Menopause Society.
“Oftentimes we find that we get some benefits here but there’s a downside in terms of risk or side effects,” Gass told MedPage Today. “I see these results as something that can be viewed positively and perhaps reinforce the other, stronger reasons for using vitamin D supplementation, mainly bone.”
Critics might argue that the effects on LDL and other lipid parameters are modest and perhaps not clinically relevant because the study did not have so-called “hard endpoints,” such as cardiac events or death, she acknowledged.
“I think the main point is the study is reassuring that there’s no deleterious effect on cholesterol profile, even if we can’t assume that we’ll see sizable clinical benefits,” said Gass.
The Women’s Health Initiative was supported by the National Institutes of Health.
The authors disclosed no relevant relationships.
Primary source: Menopause