Decreased magnesium status may mediate the increased cardiovascular risk associated with calcium supplementation

DiNicolantonio JJ, et al. Open Heart 2017;7:e000617. doi:10.1136/openhrt-2017-000617 CAN SUPPLEMENTAL CALCIUM INCREASE CARDIOVASCULAR RISK? A meta-analyses of randomised controlled studies of calcium supplementation (some including concurrent modest intakes of vitamin D) has observed a modest increase in risk for vascular events in the calcium-supplemented subjects. Some recent observational epidemiology in prospective cohorts has also linked supplemental calcium to increased vascular risk. Yet, rather perplexingly, relatively high dietary intakes of calcium have been associated with cardiovascular protection, or a neutral outcome in this regard. 3 5 6 Moreover, there are theoretical grounds for expecting that superior calcium nutrition could be protective for vascular health. High-calcium diets decrease secretion of parathyroid hormone; even mild secondary hyperparathyroidism, common in the elderly, is suspected to increase vascular risk. 8 A high calcium intake also tends to suppress absorption of dietary phosphate by forming an insoluble complex with it; emerging data suggest that high phosphate intakes may increase cardiovascular risk, even in those with normal renal function. High calcium intakes have not been found to correlate with increased risk for vascular calcification. The acute vascular impact of the modest rise in serum calcium following a bolus oral dose of calcium citrate has been studied; relative to placebo, arterial stiffness declined and myocardial perfusion increased in the calcium group. However, the diurnal decline in blood pressure was not as high in calcium-supplemented subjects and a coagulation index (thromboelastography) increased. What could explain the increased risk for vascular events associated specifically with calcium supplementation in some controlled studies? Even if subsequent analyses fail to confirm a net negative impact of calcium supplementation on vascular health—this issue is hotly debated and cannot be considered resolved the fact that calcium could be expected to protect the vasculature for certain reasons suggests that it must be exerting some countervailing negative effect even if its impact on vascular health is neutral. The acute impact of bolus calcium on coagulation mechanisms, as noted above, merits further study. Also, a high calcium intake might increase secretion of renin— which increases cardiovascular risk via the prohypertensive, pro-oxidative effects of angiotensin II—by suppressing renal synthesis of calcitriol. Only a few pertinent clinical studies are currently available in this regard, 19 however, and this prediction requires more verification in clinical studies using realistic supplemental intakes of calcium. Moreover, this explanation leaves unexplained the seeming discrepancy between the apparent cardioprotection of dietary calcium versus the potential cardiotoxicity of supplemental calcium. Consideration should, therefore, be given to the possibility that, in some individuals, high supplemental intakes of calcium may disturb magnesium balance. A great deal of recent epidemiology, including meta-analyses, points to higher dietary magnesium intakes, and/or higher serum magnesium levels, as associated with reduced risk for vascular events, arrhythmias, diabetes, hypertension, metabolic syndrome, vascular calcification and mortality. Although to some degree these observations likely reflect the benefits of consuming nutrient-rich whole foods, rather than just magnesium per se, magnesium still often emerges as protective after multiple regression analyses which try to adjust for this To cite: DiNicolantonio JJ, McCarty MF, O’Keefe JH. Decreased magnesium status may mediate the increased cardiovascular risk associated with calcium supplementation. Open Heart 2017;7:e000617. doi:10.1136/ openhrt-2017-000617