Simvastatin Does Not Affect Vitamin D Status, but Low Vitamin D Levels Are Associated with Dyslipidemia: Results from a Randomised, Controlled Trial

Objectives. Statin drugs act as inhibitors of the 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase enzyme early in the mevalonate pathway, thereby reducing the endogenous cholesterol synthesis. In recent studies, it has been suggested from epidemiological data that statins also may improve vitamin D status, as measured by increased plasma 25-hydroxyvitamin D (25OHD) levels. We now report the results from a randomised controlled trial on effects of simvastatin on plasma 25OHD levels. Design and Methods. We randomised 82 healthy postmenopausal women to one year of treatment with either simvastatin 40 mg/d or placebo and performed measurement at baseline and after 26 and 52 weeks of treatment. The study was completed by 77 subjects. Results. Compared with placebo, plasma levels of cholesterol and low-density lipoproteins decreased in response to treatment with simvastatin, but our study showed no effect of simvastatin on vitamin D status. However, plasma levels of triglycerides were inversely associated with tertiles of plasma 25OHD levels and changes in plasma triglycerides levels correlated inversely with seasonal changes in vitamin D status. Conclusion. Our data do not support a pharmacological effect of statins on vitamin D status, but do suggest that vitamin D may influence plasma lipid profile and thus be of importance to cardiovascular health

Vitamin D Status and Bone and Connective Tissue Turnover in Brown Bears (Ursus arctos) during Hibernation and the Active State

BACKGROUND: Extended physical inactivity causes disuse osteoporosis in humans. In contrast, brown bears (Ursus arctos) are highly immobilised for half of the year during hibernation without signs of bone loss and therefore may serve as a model for prevention of osteoporosis. AIM: To study 25-hydroxy-vitamin D (25OHD) levels and bone turnover markers in brown bears during the hibernating state in winter and during the active state in summer. We measured vitamin D subtypes (D₂ and D₃), calcitropic hormones (parathyroid hormone [PTH], 1,25-dihydroxy-vitamin D [1,25(OH)₂D]) and bone turnover parameters (osteocalcin, ICTP, CTX-I), PTH, serum calcium and PIIINP. MATERIAL AND METHODS: We drew blood from seven immobilised wild brown bears during hibernation in February and in the same bears while active in June. RESULTS: Serum 25-hydroxy-cholecalciferol (25OHD₃) was significantly higher in the summer than in the winter (22.8±4.6 vs. 8.8±2.1 nmol/l, two tailed p-2p = 0.02), whereas 25-hydroxy-ergocalciferol (25OHD₂) was higher in winter (54.2±8.3 vs. 18.7±1.7 nmol/l, 2p<0.01). Total serum calcium and PTH levels did not differ between winter and summer. Activated 1,25(OH)₂D demonstrated a statistically insignificant trend towards higher summer levels. Osteocalcin levels were higher in summer than winter, whereas other markers of bone turnover (ICTP and CTX-I) were unchanged. Serum PIIINP, which is a marker of connective tissue and to some degree muscle turnover, was significantly higher during summer than during winter. CONCLUSIONS: Dramatic changes were documented in the vitamin D₃/D₂ ratio and in markers of bone and connective tissue turnover in brown bears between hibernation and the active state. Because hibernating brown bears do not develop disuse osteoporosis, despite extensive physical inactivity we suggest that they may serve as a model for the prevention of this disease

25(OH)D3 and 1.25(OH)2D3 inhibits TNF-α expression in human monocyte derived macrophages.

PurposeWe wanted to investigate effects of vitamin D3 (25(OH)D3 and 1.25(OH)2D3) on inflammatory cytokine expression in both activated and non-activated Mφ.Materials and methodsMononuclear cells, isolated from healthy donor buffy coats were cultured for a 6-day differentiation-period. Fully differentiated Mφ were pre-treated with either 25(OH)D3 or 1.25(OH)2D3 for (4, 12 or 24 hours) +/-LPS challenge for 4 hours. Gene expression analyses of VDR, Cyp27b1 and pro-inflammatory markers TNF-α, IL-6, NF-κB, MCP-1, was performed using RT-quantitative PCR. TNF-α protein levels from Mφ culture media were analysed by ELISA.ResultsBoth 25(OH)D3 and 1.25(OH)2D3 significantly inhibited TNF-α expression in both LPS-stimulated and unstimulated Mφ. Also, NF-κB, and to a lesser extend IL-6 and MCP-1 were inhibited. LPS up-regulated Cyp27b1 gene expression which was partly reverted by 1.25(OH)2D3.ConclusionThese data show anti-inflammatory effects of vitamin D3 (25(OH)D3 and 1.25(OH)2D3) in human macrophages, and support, that means for targeting high dose vitamin D3 to the immune system may have beneficial clinical effect in inflammatory conditions

Vitamin D status in Greenland is influenced by diet and ethnicity:a population-based survey in an Arctic society in transition

Vitamin D status as measured by plasma 25-hydroxyvitamin D (25(OH)D) is important to human health. Circumpolar people rely on dietary sources and societal changes in the Arctic are having profound dietary effects. The objective of the present study was to determine plasma 25(OH)D status and factors important to plasma 25(OH)D in populations in Greenland. Inuit and non-Inuit aged 50–69 years in the capital in West Greenland (latitude 64°15′N) and in a major town and remote settlements in East Greenland (latitude 65°35′N) were surveyed. Supplement use and lifestyle factors were determined by questionnaires. Inuit food scores were computed from a FFQ of seven traditional Inuit and seven imported food items. 25(OH)D2 and 25(OH)D3 levels were measured in the plasma. We invited 1 % of the population of Greenland, and 95 % participated. 25(OH)D3 contributed 99·7 % of total plasma 25(OH)D. Non-Inuit had the lowest median plasma 25(OH)D of 41 (25th–75th percentile 23–53) nmol/l compared with 64 (25th–75th percentile 51–81) nmol/l in Inuit (P&lt; 0·001). Plasma 25(OH)D was below 20 and 50 nmol/l in 13·8 and 60·1 % of participants, respectively, with Inuit food item scores below 40 % (P&lt; 0·001), and in 0·2 and 25·0 % of participants, respectively, with higher scores (P&lt; 0·001). The Inuit diet was an important determinant of plasma 25(OH)D (P&lt; 0·001) and its effect was modified by ethnicity (P= 0·005). Seal (P= 0·005) and whale (P= 0·015) were major contributors to plasma 25(OH)D. In conclusion, a decrease in the intake of the traditional Inuit diet was associated with a decrease in plasma 25(OH)D levels, which may be influenced by ethnicity. The risk of plasma 25(OH)D deficiency in Arctic populations rises with the dietary transition of societies in Greenland. Vitamin D intake and plasma 25(OH)D status should be monitored.</jats:p