Long-term vitamin D3 supplementation may have adverse effects on serum lipids during postmenopausal hormone replacement therapy

Abstract

Objective: The positive short-term effects of postmenopausal hormone replacement therapy (HRT) on serum lipids are well known, but it has been suggested that they vanish with time. Cholecalciferol (vitamin D 3 ) is widely used to prevent postmenopausal osteoporosis but the influence of vitamin D 3 on serum lipids is poorly known. The long-term effects of HRT and vitamin D 3 on the concentrations of serum lipids were studied in a population-based prospective 3-year study. Design and methods: 464 women were randomized into four treatment groups: (i) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), (ii) Vit D 3 (vitamin D 3 300 IU/ day), (iii) HRT+Vit D 3 (both as above), (iv) placebo (calcium lactate 500 mg/day). Results: 320 women completed the study. After three years of treatment, serum concentrations of low density lipoprotein (LDL) cholesterol decreased in the HRT group (10.1%, P<0.001) and the HRT+Vit D 3 group (5.9%, P=0.005), increased in the Vit D 3 group (4.1%, P=0.035) but remained unchanged in the placebo group. The concentrations of total cholesterol decreased by 5.8% in the HRT group (P<0.001) and by 3.3% in the HRT+Vit D 3 group (P=0.023), but did not change in the other two groups. Serum concentrations of high density lipoprotein (HDL) cholesterol decreased in the Vit D 3 group (5.2%, P=0.001), HRT+Vit D 3 group (3.7%, P=0.046), and the placebo group (4.5%, P=0.006) but did not change significantly in the HRT group. The HDL/LDL ratio increased in the HRT group (10.5%, P=0.006) and decreased in the Vit D 3 group (10.5%, P<0.001) whereas no changes occurred in the other two groups. In addition, serum triglycerides increased similarly in all groups (14.0-18.8%, P<0.05-0.001). Conclusions: Our results confirm the positive long-term effect of HRT with sequential estradiol valerate and cyproterone acetate on serum lipid concentrations. In addition, the results suggest that vitamin D 3 supplementation may have unfavorable effects on lipids in postmenopausal women. Pure vitamin D 3 treatment was associated with increased serum LDL cholesterol. Furthermore, the beneficial effects of HRT on serum LDL cholesterol content were reduced when estradiol valerate was combined with vitamin D 3 . However, the relevance of these associations to cardiovascular morbidity remains to be established. [495][496][497][498][499][500][501][502] European Journal of Endocrinology 137

High serum 25-hydroxyvitamin D concentrations are associated with a favorable serum lipid profile

“…So far only a few such intervention studies have been reported. Regarding serum TAG concentrations, which appear to be strongly associated with serum 25(OH)D, we have in our study of overweight and obese subjects found no effect on serum TAG of 20 000-40 000 IU vitamin D per week given for 1 year (Jorde et al, 2009);Heikkinen et al (1997) found no effect by supplementation with 300 IU vitamin D for 3 years in 323 postmenopausal women; Andersen et al (2009) found no change in 173 Pakistani subjects living in Denmark and given vitamin D in daily doses of 400 or 800 IU for 1 year; whereas Zittermann et al (2009) in their study on 200 overweight subjects found a significant 13% decrease in the serum TAG in those given 3320 IU daily for 1 year. These discrepancies could be due to the doses of vitamin D given as well as differences between the study groups.…”

Vitamin D supplementation does not affect serum lipids and lipoproteins in Pakistani immigrants

“…T-C was increased after 2 years, but the effect was nonsignificant after 3 years. TAG was significant increased and HDL/LDL-ratio decreased after both 2 and 3 years of vitamin D intervention (Heikkinen et al, 1997). No effect on blood lipids and lipoproteins were found in a 12-week vitamin D and calcium intervention study (Gannage-Yared et al, 2003) and in a 1-year vitamin D intervention study (Lips et al, 1988) (dosages 10-20 mg/day).…”

“…In a Finnish study investigating the effect of postmenopausal hormone replacement therapy LDL-C was significantly increased by 4.1% and HDL-C decreased by 5.2% after 3-years intervention with 7.5 mg vitamin D per day; LDL-C was also significantly increased after 2 years, but none of them were significant after 1 year (Heikkinen et al, 1997). T-C was increased after 2 years, but the effect was nonsignificant after 3 years.…”

“…In 1997, a Finnish study found significant higher LDL-cholesterol (LDL-C) and lower HDL-cholesterol (HDL-C) after 3 years of vitamin D supplementation (Heikkinen et al, 1997). Shorter intervention studies (6 weeks to 1 year) did not find an effect (Carlson et al, 1970;Lips et al, 1988;Gannage-Yared et al, 2003).…”

Pharmacokinetics and effects of demographic factors on blood 25(OH)D3 levels after a single orally administered high dose of vitamin D3

“…Consistently with the present results, a previous study has found a reduction in triglycerides but not total cholesterol, low-density lipoproteins or high-density lipoproteins 6 months after the administration of 4000 IU/d of vitamin D [26] . Vitamin D and calcium may increase the oxidation of whole body fat and increase lipolysis [27,28] . The present investigation found an increase in free fatty acids in blood at d 84 and 112, thus suggesting increased breakdown of lipids after administration of vitamin D. In the current study, a decrease in total cholesterol at d 84 and 112 was observed, consistently with previous findings that after two doses of 50 000 IU vitamin D3, there is a reduction in the concentration of serum total cholesterol in women with gestational diabetes mellitus [29] .…”