Health effects associated with serum calcium concentrations: evidence from MR-PheWAS analysis in UK Biobank

Zhou, Ang; Morris, H. A.; Hyppönen, Elina

doi:10.1007/s00198-019-05118-z

Cited by 18 publications

(27 citation statements)

References 24 publications

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“…As for other musculoskeletal diseases, a causal association between higher genetically predicted serum calcium levels and lower risk of osteoarthrosis (odds ratio [OR] 0.67; p = 0.0044) was reported in a phenome‐wide MR analysis. ( 34 ) A two‐sample MR study found that serum calcium levels were also inversely associated with the risk of overall osteoarthritis (OR 0.712; p = 1.84 × 10 −4 ), although this significant association was only detected in women (OR 0.967; p = 0.038). ( 35 ) Similar findings were found in a recent MR where a negative causal effect of higher serum calcium on localized osteoarthritis was reported (OR 0.87, p = 0.021).…”

Section: Introductionmentioning

confidence: 99%

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Health Effects of Calcium: Evidence From Mendelian Randomization Studies

et al. 2021

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Calcium is widely used in conjunction with vitamin D to prevent osteoporosis. The use of calcium supplementation is also promoted for its potential benefits in lowering the risk for metabolic syndromes and cancers. However, the causal link between calcium and various health outcomes remains unclear. This review focuses on the evidence from twenty-four Mendelian randomization studies that were designed to minimize bias from confounding and reverse causation. These MR studies evaluated the effect of lifelong genetically higher serum calcium levels on various health outcomes. Overall, available MR studies found no conclusive effects of serum calcium levels on bone mineral density and fracture, ischemic stroke and heart failure, cancers, type 2 diabetes, Parkinson's disease, and offspring birth weight. However, a higher serum calcium concentration was reported to have estimated causal effects on increased risks for coronary artery disease (especially myocardial infarction), migraine, renal colic, allergy/adverse This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as

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Section: Introductionmentioning

confidence: 99%

“…Finally, using two‐sample MR method, Zhou and colleagues ( 34 ) found high serum calcium concentration has an estimated causal effect on urinary calculus (OR 3.5; p = 0.011), renal colic (OR 9.1; p = 8.82 × 10 −4 ), and allergy/adverse effect of penicillin (OR 2.2; p = 9.36 × 10 −5 ).…”

Section: Introductionmentioning

confidence: 99%

Health Effects of Calcium: Evidence From Mendelian Randomization Studies

et al. 2021

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“…Whilst there is evidence to suggest that increased calcium intake is associated with improved lipid profiles [6] and reduced blood pressure [7], increased serum calcium levels have also been associated with an increase in arterial calcification [8]. Furthermore, several Mendelian randomisation studies have underlined the relationship between increases in serum calcium levels and increased incidence of coronary artery disease [9] and myocardial infarction [9,10], but not ischaemic stroke [11]. Despite several previous systematic reviews and meta-analyses having analysed this relationship, these have yielded conflicting results in terms of both incident cardiovascular disease (CVD) and mortality [12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Calcium intake, calcium supplementation and cardiovascular disease and mortality in the British population: EPIC-norfolk prospective cohort study and meta-analysis

et al. 2020

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The role of dietary calcium in cardiovascular disease prevention is unclear. We aimed to determine the association between calcium intake and incident cardiovascular disease and mortality. Data were extracted from the European Prospective Investigation of Cancer, Norfolk (EPIC-Norfolk). Multivariable Cox regressions analysed associations between calcium intake (dietary and supplemental) and cardiovascular disease (myocardial infarction, stroke, heart failure, aortic stenosis, peripheral vascular disease) and mortality (cardiovascular and all-cause). The results of this study were pooled with those from published prospective cohort studies in a meta-analsyis, stratifying by average calcium intake using a 700 mg/day threshold. A total of 17,968 participants aged 40–79 years were followed up for a median of 20.36 years (20.32–20.38). Compared to the first quintile of calcium intake (< 770 mg/day), intakes between 771 and 926 mg/day (second quintile) and 1074–1254 mg/day (fourth quintile) were associated with reduced all-cause mortality (HR 0.91 (0.83–0.99) and 0.85 (0.77–0.93), respectively) and cardiovascular mortality [HR 0.95 (0.87–1.04) and 0.93 (0.83-1.04)]. Compared to the first quintile of calcium intake, second, third, fourth, but not fifth quintiles were associated with fewer incident strokes: respective HR 0.84 (0.72–0.97), 0.83 (0.71–0.97), 0.78 (0.66–0.92) and 0.95 (0.78–1.15). The meta-analysis results suggest that high levels of calcium intake were associated with decreased all-cause mortality, but not cardiovascular mortality, regardless of average calcium intake. Calcium supplementation was associated with cardiovascular and all-cause mortality amongst women, but not men. Moderate dietary calcium intake may protect against cardiovascular and all-cause mortality and incident stroke. Calcium supplementation may reduce mortality in women.

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“…As noted above, calcium supplementation acutely elevates serum calcium concentration, and higher serum calcium levels have been associated in cohort studies with increased risk of myocardial infarction, stroke, and death [18]. This is complemented by two recent Mendelian randomization studies showing that small increases in circulating calcium concentrations within the normal range are associated with increased risks of vascular disease [19,20]. These findings provide a plausible mechanism for how calcium supplements might increase cardiovascular disease.…”

Section: Safetymentioning

confidence: 81%

Calcium and/or Vitamin D Supplementation for the Prevention of Fragility Fractures: Who Needs It?

Reid

Bolland

2020

Nutrients

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Vitamin D and calcium have different biological functions, so the need for supplementation, and its safety and efficacy, need to be evaluated for each separately. Vitamin D deficiency is usually the result of low sunlight exposure (e.g., in frail older people, those who are veiled, those with dark-skin living at higher latitudes) and is reversible with calciferol 400-800 IU/day. Calcium supplements produce a 1% increase in bone density in the first year of use, without further increases subsequently. Vitamin D supplements do not improve bone density in clinical trials except in analyses of subgroups with baseline levels of 25-hydroxyvitamin D <30 nmol/L. Supplementation with calcium, vitamin D, or their combination does not prevent fractures in community-dwelling adults, but a large study in vitamin D-deficient nursing home residents did demonstrate fracture prevention. When treating osteoporosis, co-administration of calcium with anti-resorptive drugs has not been shown to impact on treatment efficacy. Correction of severe vitamin D deficiency (<25 nmol/L) is necessary before use of potent anti-resorptive drugs to avoid hypocalcemia. Calcium supplements cause gastrointestinal side effects, particularly constipation, and increase the risk of kidney stones and, probably, heart attacks by about 20%. Low-dose vitamin D is safe, but doses >4000 IU/day have been associated with more falls and fractures. Current evidence does not support use of either calcium or vitamin D supplements in healthy community-dwelling adults.

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Health effects associated with serum calcium concentrations: evidence from MR-PheWAS analysis in UK Biobank

Cited by 18 publications

References 24 publications

Health Effects of Calcium: Evidence From Mendelian Randomization Studies

Health Effects of Calcium: Evidence From Mendelian Randomization Studies

Calcium intake, calcium supplementation and cardiovascular disease and mortality in the British population: EPIC-norfolk prospective cohort study and meta-analysis

Calcium and/or Vitamin D Supplementation for the Prevention of Fragility Fractures: Who Needs It?

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