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
Overview Toxicity of vitamin D has the following chart
More adverse events in Placebo groups than Vitamin D groups?
- 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.