The calcium supplements contained 1 g or more, and could have been taken in the fasting state. As mentioned by the authors, this Pexidartinib nmr may give rise to transient hypercalcemia for several hours, which—when

repeated every day over several years—might increase the risk of coronary heart disease. Indeed, no increased cardiovascular risks were observed with calcium from food which is absorbed more slowly. Even the administration of a calcium supplement in the form of bone powder does not increase the plasma calcium level above normal [11]. In the same way, calcium supplements increase slightly the risk of renal stones in some studies, whereas calcium from food decreases this risk [2]. It might be assumed, therefore, in the light of the studies of Bolland

et al. [4, 5], that supplements of only 500 mg of calcium taken after a meal are harmless, even when taken twice a day. The question remains if a supplement of 500 mg per day is enough. One could argue that a supplement of 500 mg of calcium does not meet the requirements, which were redefined recently by the Institute of Medicine in the USA (IOM) [1]. The report states that 1,000 mg of calcium is the estimated average requirement for women over 50 years, and 1,200 mg/day is the recommended daily allowance. But these figures are derived from studies in populations whose bone health was not optimal. These studies were not titrated against the blood level of 25-hydroxyvitamin Pembrolizumab cost D. They were performed in populations that probably were—as we now know to be—vitamin D deficient. Vitamin D deficiency is prevalent worldwide [12] and Depsipeptide nmr it is reasonable to assume, therefore, that the recommendations of the IOM are unnecessarily high. If human beings were exposed to sunlight regularly, not only would they have higher 25-hydroxyvitamin D levels, they might also need less calcium for optimal bone health. It is, by the way, surprising, how low the recommendations of the IOM report are for vitamin D. They were considered by experts like R.P. Heaney and M. Holick as to ‘fail on three grounds: logic, science and guidance’ [13]. This

allows us to suppose that calcium supplements of 500 mg are effective, so long as the vitamin D level is optimal. Indeed, high 25-hydroxyvitamin D levels seemed to compensate for the otherwise negative effects of a low calcium intake (<716 mg/day) on BMD [14]. In conclusion, if the reported increased risk of MI induced by calcium supplements of 1,000–1,200 mg were the result of a meta-analysis of studies with MI as primary outcomes, it still would not challenge the clinical practice free of cardiovascular dangers, which favours supplements of 500 mg to be taken after meals, combined with vitamin D when the nutritional intake of calcium does not sum up to 800 mg. References 1. Report on Dietary Reference Intakes (DRIs) for calcium and vitamin D by the Institute of Medicine (IOM) (2011) Dietary reference intakes for calcium and vitamin D.