1
Saint Luke’s Mid America Coronary heart Institute, Kansas Metropolis, Missouri, USA,
1
Saint Luke’s Mid America Coronary heart Institute, Kansas Metropolis, Missouri, USA,
Can supplemental calcium enhance cardiovascular danger?
A meta-analyses of randomised managed research of calcium supplementation (some together with concurrent modest intakes of vitamin D) has noticed a modest enhance in danger for vascular occasions within the calcium-supplemented topics.1 Some latest observational epidemiology in potential cohorts has additionally linked supplemental calcium to elevated vascular danger.2–4 But, relatively perplexingly, comparatively excessive dietary intakes of calcium have been related to cardiovascular safety, or a impartial end result on this regard.2 3 5 6 Furthermore, there are theoretical grounds for anticipating that superior calcium diet may very well be protecting for vascular well being. Excessive-calcium diets lower secretion of parathyroid hormone; even gentle secondary hyperparathyroidism, widespread within the aged, is suspected to extend vascular danger.7 8 A excessive calcium consumption additionally tends to suppress absorption of dietary phosphate by forming an insoluble complicated with it; rising information counsel that top phosphate intakes could enhance cardiovascular danger, even in these with regular renal perform.9 Excessive calcium intakes haven’t been discovered to correlate with elevated danger for vascular calcification.10 The acute vascular impression 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 elevated within the calcium group.11 Nonetheless, the diurnal decline in blood strain was not as excessive in calcium-supplemented topics and a coagulation index (thromboelastography) elevated.12
What may clarify the elevated danger for vascular occasions related particularly with calcium supplementation in some managed research? Even when subsequent analyses fail to substantiate a web unfavourable impression of calcium supplementation on vascular well being—this situation is hotly debated and can’t be thought-about resolved5 13–15—the truth that calcium may very well be anticipated to guard the vasculature for sure causes means that it have to be exerting some countervailing unfavourable impact even when its impression on vascular well being is impartial.
The acute impression of bolus calcium on coagulation mechanisms, as famous above, deserves additional research. Additionally, a excessive calcium consumption would possibly enhance secretion of renin—which will increase cardiovascular risk16 by way of the prohypertensive, pro-oxidative results of angiotensin II—by suppressing renal synthesis of calcitriol.17 Just a few pertinent medical research are at the moment accessible on this regard,18 19 nonetheless, and this prediction requires extra verification in medical research utilizing real looking supplemental intakes of calcium. Furthermore, this rationalization leaves unexplained the seeming discrepancy between the obvious cardioprotection of dietary calcium versus the potential cardiotoxicity of supplemental calcium.
Consideration ought to, due to this fact, be given to the chance that, in some people, excessive supplemental intakes of calcium could disturb magnesium steadiness.20 An excessive amount of latest epidemiology, together with meta-analyses, factors to increased dietary magnesium intakes, and/or increased serum magnesium ranges, as related to lowered danger for vascular occasions, arrhythmias, diabetes, hypertension, metabolic syndrome, vascular calcification and mortality.21–41 Though to some extent these observations seemingly mirror the advantages of consuming nutrient-rich complete meals, relatively than simply magnesium per se, magnesium nonetheless usually emerges as protecting after a number of regression analyses which attempt to alter for this impact. Furthermore, short-term research of magnesium supplementation in individuals at excessive cardiovascular danger have usually discovered protecting results, notably in these with low baseline magnesium standing. Notably, in sufferers with coronary illness, magnesium supplementation has been discovered to lower ex vivo platelet-dependent thrombosis, enhance flow-mediated vasodilation of the brachial artery and through train, enhance train tolerance, VO2max and left ventricular ejection fraction.42–46 A meta-analysis of placebo-controlled research evaluating the impression of supplemental magnesium on handled hypertensives with baseline systolic strain >155 mm Hg, discovered a imply discount of 18.7 and 10.9 mm Hg in systolic and diastolic pressures, respectively, with excessive statistical significance.47 The mechanism of the obvious advantages conferred by good magnesium standing requires additional research, however it’s suspected that magnesium antagonises a few of the proinflammatory results of elevated cytoplasmic calcium.20 48–52 Certainly, magnesium has typically been known as ‘nature’s physiological calcium blocker’.53–55 For instance, in physiological intracellular concentrations, magnesium competes with calcium for binding to calmodulin and different ‘EF-hand’ calcium-binding proteins, such that magnesium-bound proteins assume an ‘off’ configuration.50 52 The obvious means of excellent magnesium standing to decrease danger for vascular calcification is intriguing in gentle of latest epidemiology pointing to elevated danger of coronary calcification in folks utilizing calcium dietary supplements.4 40 41 56
Determine 1 depicts the inverse affiliation between complete dietary magnesium consumption and danger for arterial calcification.56
Dietary calcium as a determinant of magnesium steadiness
In a sequence of magnesium steadiness research performed by Seelig about 50 years in the past, she discovered that, in males with advisable dietary allowance (RDA)-level magnesium intakes (6 mg/kg/day or above), rising dietary calcium to excessive ranges didn’t impair magnesium steadiness— in line with more moderen stories.20 57 58 Nonetheless, in males with comparatively low intakes, a excessive calcium consumption did certainly lower magnesium steadiness. Considerably paradoxically, a low calcium consumption additionally impaired magnesium availability on this group. If these observations are confirmed in ladies, they suggest {that a} excessive supplemental consumption of calcium would possibly impair magnesium steadiness within the relatively excessive proportion of the inhabitants who’ve comparatively low magnesium intakes, reflecting excessive intakes of ‘empty calorie’ meals. Nonetheless, an elevated consumption of calcium-rich pure meals wouldn’t essentially have a unfavourable impression on magnesium steadiness as a result of these meals additionally would provide magnesium. A cup of milk can present as much as 10% of the dietary magnesium requirement, for instance.
Additional steadiness research are wanted to substantiate Seelig’s57observation {that a} excessive calcium consumption can lower magnesium steadiness when magnesium intakes are comparatively low. Calcium and magnesium usually are not thought to share widespread transport proteins within the intestinal mucosa or renal tubular epithelium;59 60 it’s, due to this fact, not clear what the mechanistic foundation for such an antagonism is likely to be. Inhibition of magnesium absorption by excessive dietary calcium is a well-established phenomenon in rats.61 Brink and colleagues have offered proof that this phenomenon is contingent on a concurrent sufficiently excessive consumption of phosphate.62 These researchers present in rats that an elevated consumption of calcium can lower the ileal solubility of dietary magnesium by selling the formation of insoluble calcium/magnesium/phosphate complexes. This phenomenon is most significant when the ratio of dietary phosphate to magnesium is comparatively excessive, and Brink et al
62 counsel that the truth that this ratio is increased in rat diets than it tends to be in people could account for the failure of excessive calcium intakes to suppress magnesium steadiness in most medical research. Nonetheless, many individuals who devour over-refined low magnesium diets additionally soak up a excessive quantity of bioavailable phosphate from animal merchandise and phosphate additives63; this may very well be a subset of individuals in whom a excessive supplemental consumption of calcium additional compromises magnesium standing.
Alternatively, it has been recommended that the suppression of parathyroid hormone and/or calcitriol related to excessive intakes of calcium would possibly downregulate the effectivity of magnesium absorption.64 Though intestinal magnesium absorption is primarily paracellular, lively mobile transport by way of TRPM6 is prone to develop into extra physiologically essential as magnesium intakes decline.59 65 A number of research in people, in addition to in rats, conclude that calcitriol administration can improve intestinal absorption of magnesium; jejunal absorption of magnesium was elevated within the human research.61 66–71 The likelihood that vitamin D receptor activation would possibly enhance expression of TRPM6 in epithelial cells derived from jejunal mucosa doesn’t seem to have been studied so far; such a mechanism may rationalise proof that top calcium intakes solely suppress magnesium steadiness when magnesium consumption is low and therefore extra depending on lively mobile transport. Homeostatically, it will make sense that calcitriol, a sign to spice up calcium uptake, would concurrently increase magnesium absorption, as sustaining a steadiness between calcium and magnesium ranges is physiologically acceptable.
Balanced supplemental intakes of calcium and magnesium could also be advisable
If excessive calcium intakes in people can certainly impair magnesium steadiness when magnesium intakes are low, the clear implication is that calcium, when supplemented, ought to be given together with a balanced dose of magnesium; some authorities advocate a 2:1 ratio of calcium to magnesium (by weight) as most acceptable, each for supplementation and the overall each day consumption.72 73 This appears acceptable contemplating that good magnesium standing additionally seems to favourably impression bone construction.74–76 The idea of ‘balancing’ calcium and magnesium in dietary supplements has, in actual fact, been the accepted knowledge in ‘health food’ circles for many years, owing to Seelig’s analysis and its promulgation by standard well being meals pundits. Nonetheless, the calcium dietary supplements featured in pharmacies and supermarkets—the place most individuals store—sometimes characteristic solely calcium and vitamin D. Analysis and promotional efforts sponsored by the dairy business have insured that calcium is extremely valued by most of the people, whereas magnesium, no much less essential to well being, is actually an ‘orphan nutrient’, missing the advocacy of economic pursuits.
It ought to be famous that calcium/magnesium steadiness could reduce each methods. In China, the place the usage of dairy merchandise is low, dietary calcium/magnesium ratios are typically a lot decrease than within the West (1.7 vs 3). A latest evaluation of potential cohort research in Shanghai has noticed that, amongst folks with a calcium/magnesium ratio underneath 1.7, an rising consumption of magnesium correlates with elevated complete mortality, whereas in these with a calcium/magnesium ratio above 1.7, will increase in consumption of magnesium and/or calcium correlated with lowered mortality danger.77 Therefore, a excessive supplemental consumption of magnesium could also be inadvisable when calcium intakes are low.
Thus, extra medical research analyzing the impression of various calcium intakes on magnesium steadiness in topics with low-normal magnesium intakes are clearly wanted, as is a greater understanding of the molecular mechanisms, whereby calcium can each positively and negatively affect magnesium absorption and retention. Future epidemiological research ought to make an effort to distinguish calcium supplementers into those that both do or don’t use supplemental magnesium concurrently, and likewise think about dietary magnesium consumption. For the time being, folks (particularly these consuming a comparatively refined weight loss program) who want to complement with calcium is likely to be effectively suggested to take a complement that additionally contains extremely bioavailable magnesium, focusing on a 2:1 calcium to magnesium ratio within the general weight loss program.
Footnotes
References – “calcium magnesium supplementation”
Codecs:
Share