Serum retinol levels and the risk of fracture.

BACKGROUND: Although studies in animals and epidemiologic studies have indicated that a high vitamin A intake is associated with increased bone fragility, no biologic marker of vitamin A status has thus far been used to assess the risk of fractures in humans. METHODS: We enrolled 2322 men, 49 to 51 years of age, in a population-based, longitudinal cohort study. Serum retinol and beta carotene were analyzed in samples obtained at enrollment. Fractures were documented in 266 men during 30 years of follow-up. Cox regression analysis was used to determine the risk of fracture according to the serum retinol level. RESULTS: The risk of fracture was highest among men with the highest levels of serum retinol. Multivariate analysis of the risk of fracture in the highest quintile for serum retinol (>75.62 microg per deciliter [2.64 micromol per liter]) as compared with the middle quintile (62.16 to 67.60 microg per deciliter [2.17 to 2.36 micromol per liter]) showed that the rate ratio was 1.64 (95 percent confidence interval, 1.12 to 2.41) for any fracture and 2.47 (95 percent confidence interval, 1.15 to 5.28) for hip fracture. The risk of fracture was further increased within the highest quintile for serum retinol. Men with retinol levels in the 99th percentile (>103.12 microg per deciliter [3.60 micromol per liter]) had an overall risk of fracture that exceeded the risk among men with lower levels by a factor of seven (P<0.001). The level of serum beta carotene was not associated with the risk of fracture. CONCLUSIONS: Our findings, which are consistent with the results of studies in animals, as well as in vitro and epidemiologic dietary studies, suggest that current levels of vitamin A supplementation and food fortification in many Western countries may need to be reassessed.

Magnesium infusion improves endothelium-dependent vasodilation in the human forearm.

The effect of intra-arterial magnesium infusion on endothelium-dependent vasodilation (EDV) in the forearm was studied in nine young healthy students (four men and five women). The EDV was assessed as forearm blood flow (FBF), measured by venous occlusion plethysmography, during infusion of methacholine (MCh). Endothelium-independent vasodilation (EIDV) was defined as FBF during infusion of sodium nitroprusside (SNP). During magnesium infusion in the brachial artery, 0.066 mmol/min, the concentration of ionized magnesium in venous plasma in the infused arm increased by 114%, from 0.59 (SD 0.04) to 1.26 (0.34) mmol/L (P = .0002). The FBF at baseline (ie, before administration of MCh or SNP) increased from 3.5 (1.1) to 7.3 (3.4) mL/min/100 mL tissue during magnesium infusion (P = .002). During low-dose MCh administration (2 microg/min), FBF increased by 24%, from 15.4 (5.5) to 19.1 (6.8) mL/min/100 mL tissue (P = .04), and during high-dose MCh administration (4 microg/min) FBF increased by 18%, from 20.3 (6.4) to 24.0 (7.2) mL/min/100 mL tissue (P = .04). The EIDV did not change significantly. Systemic blood pressure was not significantly altered by magnesium infusion. No change in FBF either at rest or during infusion of MCh or SNP was observed during the time-control protocol. In conclusion, this in vivo study showed that intraarterial magnesium infusion increased EDV in the infused human forearm, which is in accordance with findings in previous in vitro and animal experiments.