Calcium supplements modestly increase the risk of renal calculi.39 Calcium supplements can also cause abdominal bloating and constipation.39 It has been reported there could be an increased risk of myocardial infarction with calcium supplements,40 but not all studies support this conclusion.41 Calcium and vitamin D supplements do not increase the risk of death and some studies suggest a small reduction in the risk of death.41
Clinical toxicity is uncommon with vitamin D, even at high doses. Single doses of up to 500,000 IU are tolerated without causing hypercalcemia or hypercalciuria. However, the use of higher-dose formulations of vitamin D in older people has been associated with an increased risk of falls. Overall, daily, or at most, weekly vitamin D supplements are preferred.31
Evidence Statement
The benefit of vitamin D and/or calcium supplementation on fracture prevention has been extensively assessed in numerous clinical trials with varying protocols, with a significant number of systematic reviews and meta-analyses reporting different conclusions.29,33–35 A Cochrane review of vitamin D in postmenopausal women and older men,36 as well as several other reviews,29,31,33,34,37 concluded that although vitamin D alone is unlikely to prevent fractures in the doses and formulations tested so far in older people, supplements of vitamin D with calcium may prevent hip or other type of fracture. A 2022 comprehensive umbrella review assessing reasons for the discrepancies among systematic reviews/meta-analyses of trials (generally of less than five years) on vitamin D supplementation concluded that although calcium and vitamin D supplements together reduce the risk of hip and other fractures, this seemed largely due to data from institutionalised individuals, despite there being no significant differences in relation to residency in subgroup analyses.31 Overall, the reductions in fracture risk with vitamin D and calcium from these trials are small in absolute terms with relatively large numbers of people needed to be treated to prevent fractures. Only the Cochrane review37 was deemed by the umbrella review to be of moderate quality.31
A recent ancillary study of the randomised controlled Vitamin D and Omega-3 Trial (VITAL) involving 28,871 participants with mean age of 67 years reported that vitamin D3 supplementation (2000 IU per day) alone did not result in a significantly lower risk of fractures than placebo among generally healthy mid-life and older adults with generally good vitamin D status.38 These recent findings importantly question the health benefits of vitamin D supplements alone in the general population of older adults, although as the authors of the VITAL study state, the study was not designed to investigate people with low vitamin D status and there were not enough participants with low vitamin D to draw any conclusions for them.38 RCTs are necessarily conducted over a few years only and with limited exceptions, such as those involving subjects in aged care facilities, generally enrol people of good enough health and mobility to participate in the trial process. Vitamin D and calcium are both threshold ‘nutrients’, meaning that giving more to people who already have enough, however defined, cannot be expected to have a benefit.28
A recent study regarding improving nutrition in aged care settings that included increasing calcium and protein intake levels in people who were vitamin D replete have shown benefits such as fall and fracture reduction.16
A very large body of evidence, including the 662-page 2011 Institute of Medicine report8 and other reviews,28 points to a causal role of vitamin D and calcium for bone health. Severe vitamin D and/or calcium deficiency is the cause of most cases of rickets and osteomalacia.8,28 Deficiency of either calcium or vitamin D can accelerate bone loss and osteoporosis in older people due to increases in parathyroid hormone and secondary hyperparathyroidism.8,17,28
The safety of calcium and/or vitamin D supplements has also been examined in several meta-analyses.37,39,40 In a Cochrane review, the risk of renal insufficiency or calculi was found to be increased by vitamin D and calcium supplements (RR 1.17; 95% CI: 1.03–1.34).39 That review also found an increased risk of gastrointestinal symptoms with vitamin D and calcium supplements (RR 1.04; 95% CI: 1.00–1.08).39 The risk of cardiac events has also been examined, but despite being based on datasets from the same RCTs, different meta-analyses have drawn different conclusions. One meta-analysis found an increased risk of myocardial infarction (RR 1.24; 95% CI: 1.07–1.45) and stroke (RR 1.15; 95% CI: 1.00–1.32) in people taking calcium supplements with or without vitamin D;40 another meta-analysis found no association with myocardial infarction (RR 1.08; 95% CI: 0.92–1.26) or coronary heart disease in general.37 Meta-analyses generally indicate that calcium supplements with or without vitamin D have no effect on overall mortality, but the combination of calcium and vitamin D has been found to reduce the risk of death in one meta-analysis.41
RCTs have evaluated the effectiveness of higher-dose intermittent vitamin D supplements to reduce the risk of falls in individuals at high risk of falling. The use of high-dose oral vitamin D increased the risk of falls rather than reduced it.42,43 One trial that compared the effect of 24,000 IU vitamin D once per month to 60,000 IU vitamin D once per month found that the higher dose was associated with a significantly increased incidence of falls.43