Vitamin D, Calcium Supplements, and Implications for Cardiovascular Health

JACC Focus Seminar

Erin D. Michos, MD, MHS; Miguel Cainzos-Achirica, MD, MPH, PHD; Amir S. Heravi, MD; Lawrence J. Appel, MD, MPH

Disclosures

J Am Coll Cardiol. 2021;77(4):437-449. 

In This Article

Abstract and Introduction

Abstract

Vitamin D and calcium supplements are commonly used, often together, to optimize bone health. Multiple observational studies have linked low serum 25-hydroxyvitamin D concentrations with increased cardiovascular risk. However, subsequent randomized controlled trials (RCTs) failed to demonstrate cardiovascular benefit with vitamin D supplementation. Although vitamin D supplements do not appear to be harmful for cardiovascular health, the lack of benefit in RCTs should discourage their use for this purpose, favoring optimizing vitamin D status through healthy lifestyles such as specific foods and modest sunlight exposure. Furthermore, some (but not all) observational and RCT studies of calcium supplementation have suggested potential for cardiovascular harm. Therefore, calcium supplementation should be used cautiously, striving for recommended intake of calcium predominantly from food sources. In this review, the authors examine the currently available evidence investigating whether vitamin D and calcium supplements are helpful, harmful, or neutral for cardiovascular health.

Introduction

Vitamin D and calcium supplements are commonly used, often together, as means to optimize bone health. In the United States, more than one-third of adults consume these supplements, and among older adults, the prevalence is much higher.[1,2] Given their widespread availability, low cost, and escalating use, the cardiovascular effects of such supplements are of great clinical and public health interest from the standpoints of both cardiovascular safety and cardiovascular health promotion.[3]

Substantial epidemiological observational science has consistently and independently linked low blood concentrations of vitamin D, as measured by serum 25-hydroxyvitamin D (25[OH]D), to elevated cardiovascular disease (CVD) risk.[4–12] However, subsequent large randomized controlled trials (RCTs) of vitamin D supplementation and meta-analyses of these trials did not confirm a cardiovascular benefit, even among subgroups characterized by inadequate or deficient vitamin D status defined by serum 25(OH)D concentrations <20 ng/ml.[13–15] In light of null RCT findings, it is now widely considered that the previously reported associations of higher serum 25(OH)D concentrations with favorable cardiovascular outcomes were likely driven by confounding by other risk and health factors.[16] For example, low 25(OH)D concentrations might be due to obesity or limited physical activity outdoors, which are associated with worse cardiovascular outcomes, or with unknown factors that reduce 25(OH)D and increase cardiovascular risk. Alternatively, exogenous pill-based supplements may not be able to provide the health benefits obtained through other more natural sources of vitamin D. Regardless, the sun may be setting on the use of the "sunshine vitamin" to improve cardiovascular health through oral supplementation.

Further complicating the vitamin D supplementation picture is the fact that calcium supplements, used by more than 40% of adults,[2] are often prescribed concurrently with vitamin D to optimize bone health. Adequate calcium intake is important for the development and maintenance of bone density. However, unlike vitamin D supplements, which are relatively safe except in very high doses, calcium supplements have been associated with an increased risk for CVD events in some studies, but not all,[17] including data from both observational[18–21] and RCT[22–24] studies. This excess cardiovascular harm has not been seen with calcium intake from food sources.[21,24] Calcium supplements, either alone or in combination with vitamin D, have also been linked to other adverse effects, such as kidney stones.[25] Risks related to calcium supplementation may be due to formulation, dosing, and whether used concomitantly with vitamin D.

In this review, we examine the currently available observational and experimental evidence investigating whether vitamin D and calcium supplements are helpful, harmful, or neutral for cardiovascular health (Central Illustration). We provide a critical appraisal of published studies, focusing mostly on RCTs, and make recommendations for clinicians and patients on the basis of currently best available evidence.

Central Illustration.

Vitamin D and Calcium Supplements for Cardiovascular Health: Evidence From Observational and Interventional Studies and Clinical Recommendations
Putting evidence to practice: recommendations for patients and practitioners regarding vitamin D and calcium supplements and implication for cardiovascular health. CV = cardiovascular; CVD = cardiovascular disease; MI = myocardial infarction; RCT = randomized controlled trial.

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