Main Content

Supplements May Cut LDL in Older Women


Dr. Chauncey Crandall shares with us weekly top article pick:

Postmenopausal women taking calcium and vitamin D supplements had improved lipid profiles compared with those taking placebo, researchers found.

In an analysis of data from the Women’s Health Initiative (WHI), the level of LDL cholesterol was lower by an average of 4.46 mg/dL in the women on active treatment (P=0.03), according to Peter F. Schnatz, DO, of Reading Hospital in Pennsylvania, and co-authors.

In addition, higher concentrations of 25-hydroxyvitamin D3 (25[OH]D3)were associated with higher levels of HDL cholesterol and lower levels of LDL cholesterol and triglycerides, they reported in Menopause.

“These results support the hypothesis that higher concentrations of 25(OH)D3 in response to calcium-vitamin D supplementation, are associated with improved LDL-C,” they wrote. “Although further studies are needed to determine whether these findings translate into clinically meaningful results, this should be viewed as a reminder that women at higher risk for 25(OH)D3 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 were 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)D3 measurements at baseline and years 1, 3, and 6. Participants’ 25(OH)D3 levels were not measured at baseline or year 6, and values for those time points were imputed.

To determine whether supplementation significantly affected LDL and whether 25(OH)D3 levels 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)D3 concentration by year 3 (24.3 versus 18.2 ng/mL, P<0.001). The mean post-intervention 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)D3 concentrations ≥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 NIH.

The authors disclosed no relevant relationships.

Skip to content