Calcium/vitamin D supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol profiles in the Women's Health Initiative calcium/vitamin D randomized trial.

OBJECTIVE: The objective of this study was to evaluate whether increased serum 25-hydroxyvitamin D3 (25OHD3) concentrations, in response to calcium/vitamin D (CaD) supplementation, are associated with improved lipids in postmenopausal women. METHODS: The parent trial was a double-blind, randomized, placebo-controlled, parallel-group trial designed to test the effects of CaD supplementation (1,000 mg of elemental calcium + 400 IU of vitamin D3 daily) versus placebo in postmenopausal women. Women from the general community, including multiple sites in the United States, were enrolled between 1993 and 1998. This cohort included 300 white, 200 African-American, and 100 Hispanic participants who were randomly selected from the Women's Health Initiative CaD trial. Serum 25OHD3 and lipid (fasting plasma triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], and calculated low-density lipoprotein cholesterol [LDL-C]) levels were assessed before and after CaD randomization. RESULTS: There was a 38% increase in mean serum 25OHD3 concentrations after 2 years (95% CI, 1.29-1.47, P < 0.001) for women randomized to CaD (24.3 ng/mL postrandomization mean) compared with placebo (18.2 ng/mL). Women randomized to CaD had a 4.46-mg/dL mean decrease in LDL-C (P = 0.03). Higher concentrations of 25OHD3 were associated with higher HDL-C levels (P = 0.003), along with lower LDL-C and TG levels (P = 0.02 and P < 0.001, respectively). CONCLUSIONS: Supplemental CaD significantly increases 25OHD3 concentrations and decreases LDL-C. Women with higher 25OHD3 concentrations have more favorable lipid profiles, including increased HDL-C, lower LDL-C, and lower TG. These results support the hypothesis that higher concentrations of 25OHD3, in response to CaD supplementation, are associated with improved LDL-C.

The association between plasma 25-hydroxyvitamin D3 concentrations, C-reactive protein levels, and coronary artery atherosclerosis in postmenopausal monkeys.

OBJECTIVE: The aim of this study was to identify the potential relationships between plasma 25-hydroxyvitamin D(3) (25OHD(3)), C-reactive protein (CRP), coronary artery atherosclerosis (CAA), and coronary artery remodeling in monkeys consuming atherogenic diets. METHODS: Female cynomolgus monkeys (n = 74) were fed a casein-lactalbumin (C/L)-based, moderately atherogenic diet for 12 months. They then consumed either a soy-based (n = 35) or C/L-based (n = 39) diet for 32 months. CRP concentrations were then determined, and monkeys underwent surgical menopause. Each diet group was then rerandomized to receive soy (n = 36) or C/L (n = 38). After 32 postmenopausal months, 25OHD(3), CRP, CAA, and coronary artery remodeling were determined. All monkeys received a woman's equivalent of 1,000 IU/day of vitamin D(3) and 1,200 mg/day of calcium throughout the study. RESULTS: The premenopausal and postmenopausal dietary protein sources had no effect on postmenopausal 25OHD(3) concentrations (P = 0.6). Across treatment groups, there was a statistically significant inverse relationship between 25OHD(3) concentrations and CRP at necropsy (r = -0.35, P = 0.003). A significant inverse correlation between 25OHD(3) concentration and the change in CRP from premenopause to postmenopause was observed (r = -0.32, P = 0.007). The significant associations identified between plasma 25OHD(3) and CRP remained after controlling for postmenopausal diet. Those monkeys with a greater increase in CRP also had significantly more CAA and less ability to maintain normal lumens by remodeling. CONCLUSIONS: Higher plasma concentrations of 25OHD(3) were associated with lower CRP. Lower CRP was associated with less coronary atherosclerosis and improved coronary artery remodeling. These findings suggest that 25OHD(3) concentrations are associated with an anti-inflammatory state and may support an association between oral vitamin D3 and cardioprotection.