It is well known that vitamin D is essential for calcium absorption and bone growth, and now, new research is providing evidence that vitamin D deficiency may be linked to autoimmune disease, cancer, cardiovascular disease, depression, dementia and certain infectious diseases. Vitamin D supplementation is increasingly being used in higher doses in randomized controlled trials (RCTs) and recent studies have shown that vitamin D supplementation, by itself or in combination with calcium, increases the risk of hypercalcemia, kidney stones or renal insufficiency.
A recently-published study in the American Journal of Clinical Nutrition aimed to update the findings of previous studies and analyze the side effects related to calcium metabolism, specifically hypercalcemia (too much calcium in the blood), hypercalciuria (too much calcium in the urine), and kidney stones with long-term vitamin D supplementation (>24 week) given by itself or along with calcium. Ovid Medline (Pubmed), EMBASE and Cochrane library database were searched for all of the studies that included adults receiving long-term vitamin D supplements (>24 weeks). Studies with the co-supplementation of calcium with vitamin D were also included provided that the control or placebo arm also received calcium. Studies were excluded if there was no calcium supplement in the placebo group, were conducted in pregnant women, had vitamin D in fortified foods rather than as a supplement, had a duration of supplementation or follow-up <24 weeks, or gave analogs of vitamin D.
The 3 primary outcomes measured were hypercalcemia, hypercalciuria and kidney stones. Data analyses were conducted on 48 studies with 19,833 participants who reported ≥1 of the 3 side effects. The results showed that vitamin D, when given alone or with calcium, significantly increased the risk of hypercalcemia. Also, vitamin D significantly increased risk of hypercalciuria when calcium supplementation was balanced in both groups. Contrary to previous studies, the research did not find increased risk of kidney stones from long-term supplementation of natural vitamin D. However, this study also had some limitations. The outcomes analyzed were not systematically searched for in all participants and as the meta analyses only included studies that provided supplementation for >24 weeks, short-term calcium-related effects from vitamin D supplements may not have been detected.
In conclusion, the results show that long-term vitamin D supplementation results in changes in calcium metabolism with increased risks of hypercalcemia and hypercalciuria not related to the vitamin D dose, with no increase in risk of kidney stones. The clinical significance of these results is unclear because of the asymptomatic side effects that are linked to vitamin D, and for future research, large RCTs of long-term vitamin D supplementation are required to confirm these findings.
Written By: Dr. Shreyasi Sharma, MBBS