Large dose Vitamin D taken in 32 long trials –adverse events were rare
Adverse events from large dose vitamin D supplementation taken for one year or longer: Short running title: Safety of long-term high-dose vitamin D supplementation
The Journal of Steroid Biochemistry and Molecular Biology https://doi.org/10.1016/j.jsbmb.2018.12.002
Zmalihi Zhenqiang Wu Carlene M.M.Lawes Robert Scragg
1. Kidney Stones
* Overview Kidney Stones and vitamin D
* Vitamin D supplementation and fewer kidney stones – meta-analysis of RCT Sept 2016
* Kidney stones (Calcium) associated with lower vitamin D this time – April 2016
* Kidney stone production REDUCED in rats when Vitamin D and Calcium was added – Dec 2013
More adverse events in Placebo groups than Vitamin D groups?
Highlights
There is uncertainty about the safety of long-term high-dose vitamin D supplementation.
This systematic review included clinical trials which gave ≥2800 IU/d vitamin D supplementation for one year or longer.
Long-term high-dose vitamin D supplementation did not increase the risk of total adverse events or kidney stones.
There was borderline increased risk of hypercalcemia, and possibly of hypercalciuria, but the power to detect an effect from vitamin D on the latter outcome was limited.
In recent years, clinical trials increasingly have given large doses of vitamin D supplements to investigate possible health benefits beyond bone at high 25-hydroxyvitamin D levels. However, there are few publications on the safety of high-dose vitamin D given long term. The study objective was to investigate the cumulative relative risk (RR) of total adverse events, kidney stones, hypercalcemia and hypercalciuria from ≥2800 IU/d vitamin D2 or D3 supplementation, followed for one year or more in randomized controlled trials (RCTs). A systematic review was conducted in Medline Ovid, EMBASE and Cochrane in March 2018 to update results of studies published since a previous review in October 2015. RCTs were included if they gave vitamin D2 or D3 at ≥2800 IU/d for at least one year and reported on total adverse events or at least one calcium-related adverse event. There were a total of 32 studies that met the inclusion criteria.
Of these, only 15 studies (3,150 participants) reported one or more event of the outcomes of interest.
Long-term high-dose vitamin D supplementation did not increase total adverse events compared to placebo in 1,731 participants from 10 studies (RR = 1.05; 95% CI = 0.88, 1.24; p = 0.61), nor kidney stones in 1,336 participants from 5 studies (RR = 1.26; 95% CI = 0.35, 4.58; p = 0.72).
However, there was a trend for vitamin D to increase risk of hypercalcemia in 2,598 participants from 10 studies (RR = 1.93; 95% CI = 1.00, 3.73; p = 0.05); while its effect on hypercalciuria in only 276 participants from 3 studies was inconclusive (RR = 1.93; 95% CI = 0.83, 4.46; p = 0.12). In conclusion, one year or longer supplementation with a large daily, weekly or monthly dose of vitamin D2 /D3 did not significantly increase a risk of total adverse events or kidney stones, although there was a trend towards increased hypercalcemia, and possibly for hypercalciuria.