Decreased risk only observed when vitamins were used together.
When given with calcium, vitamin D supplements appear to be associated with lower mortality in older individuals, a meta-analysis showed.
Patients receiving both calcium and vitamin D had a 9 percent lower mortality rate through 3 years of treatment than those not receiving vitamin D, according to Lars Rejnmark, MD, PhD, of Aarhus University in Aarhus, Denmark, and colleagues.
The absolute risk reduction through 3 years of treatment was 0.66 percent, making 151 the number needed to treat, the researchers reported online in the Journal of Clinical Endocrinology & Metabolism.
A previous meta-analysis showed a 7 percent relative reduction in the all-cause mortality risk with vitamin D supplementation, although three more recent meta-analyses failed to support the finding. Two of them did, h0wever, show a significant reduction in mortality with the combination of calcium and vitamin D.
To further explore the issue, Rejnmark and colleagues performed meta-analyses using both patient-level and trial-level data from randomized controlled trials evaluating the impact of vitamin D supplementation on fracture risk. Supplements included either cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2).
The patient-level analysis included eight trials that had at least 1,000 participants. There were a total of 70,528 individuals. Most were women (86.8 percent).
In those trials, 5.4 percent of the participants died during the 3 years of treatment — 5.3 percent of those receiving vitamin D with or without calcium and 5 percent of the controls.
After adjustment for potential confounders, including incident hip and spine fractures, vitamin D supplementation with or without calcium was associated with a 7 percent lower mortality risk.
A deeper look showed that the reduction was significant for those taking calcium and vitamin D together, but not for those taking vitamin D alone.
A trial-level meta-analysis that included 24 trials — eight from the patient-level analysis and 16 other studies — yielded similar results.
The findings suggest that calcium and not vitamin D might have a beneficial effect on mortality, which might be considered counterintuitive considering the recently identified risks of MI associated with calcium supplementation, according to the researchers.
They noted that the relative increase in MI would likely have a small effect on overall mortality, however.
Also, they speculated, it could be that calcium has other benefits that outweigh the potential MI risks.
"Calcium supplementation could reduce recurrence of colorectal adenomas and thus colorectal cancer and mortality, an effect that may be strengthened if vitamin D is also provided," the authors wrote. "Calcium and vitamin D may reduce the risk of cancer, particularly breast and colorectal cancer."
Or, the effects of calcium and vitamin D combined may be greater than either supplement alone, the authors added.
But, they wrote, the finding of lower mortality with calcium and vitamin D combined but not vitamin D alone could be related to inadequate doses and methods of administration in certain trials or differences between the trials in detecting outcomes.
The researchers acknowledged that the analysis was limited by the lack of information on causes of death, by flaws found in the original studies, and by the lack of consistent information on adherence, self-administered calcium or vitamin D supplements, and baseline dietary calcium and vitamin D intake.
Earlier this week, the U.S. Preventive Services Task Force issued a draft recommendation stating that, for postmenopausal women, there is no value in supplements up to 400 IU of vitamin D and 1,000 mg of calcium.