Effects of Long-Term Calcium Supplementation on Rats Bone Mineral Density and Cardiovascular Based on Metabonomics

Calcium supplements were necessary for those people with low calcium intake and high risk of osteoporosis. Recent cohort studies have shown that long-term calcium supplements may raise the risk of cardiovascular disease, but its mechanism is still unclear. In this study, metabonomics were employed to evaluate the changes of metabolism in rats with long-term calcium supplementation and further seek the potential markers of cardiovascular risk. SD rats were divided into two groups including normal control group (calcium intake, 0.50 g/kg bw) and high calcium supplement group (calcium intake, 2.50 g/kg bw). After 6 mo, the cardiovascular system and bone mineral density were observed. UPLC-MS was used to analyze serum metabonomics in rats. The results showed that the contents of total cholesterol and low-density lipoprotein cholesterol in the high calcium group were significantly higher than those in normal control group (p<0.05). The interventricular septum thickness (IVS), left ventricular mass (LVM), left ventricular posterior wall thickness (LVPW) in the high calcium group were higher than those in normal control group (p<0.05). Serum metabonomics analysis showed that there were persistent changes in many metabolites such as sphingosine and its derivatives (p<0.01) in the comparison between the high calcium group and the normal group. These results indicated that long term calcium supplementation can lead to dyslipidemia in rats, such as the rise of cholesterol and low-density lipoprotein, which might induce myocardial hypertrophy. Long-term calcium supplementation can cause the changes of the amount of sphingosine and its derivatives in the body, which many have potential risk to cardiovascular diseases such as myocardial hypertrophy and atherosclerosis.