Vitamin D clinical trials are conducted with the intent of determining if vitamin D supplementation has a positive effect on health. Very rarely, if ever, will you see an RCT designed to find out if vitamin D supplementation has a negative impact on health outcomes in humans. This is due to the codes of ethical research which states that researchers have the moral responsibility to minimize the risk of harm on consenting participants.
While some studies may consequently discover increased risks of adverse health effects, this is never the primary intention of the study. However, we have much to learn from both the positive and negative consequences that result from any health exposures (such as vitamin D supplementation).
The effect of vitamin D toxicity on calcium levels in the blood is easy to evaluate because this is a scientifically accepted physiologic and metabolic relationship. But what about the non-calcemic adverse effects of vitamin D supplementation on the body? In an effort to better understand this relationship, researchers recently conducted a systematic review and meta-analysis.
This analysis included studies which comprised of a vitamin D2 or D3 supplementation group, a placebo group, ran for at least 24 weeks and measured any adverse effects which occurred during the study. This analysis also reported on subject withdrawals, which is the participant’s decision to leave the study for any given reason (i.e. adverse effects or complications). A total of 128 RCTs with 52,297 participants were included in this analysis; 26,852 of which belonged to a group receiving vitamin D supplementation and 25,445 of which received a placebo.
This is what the researchers found:
- The average dose of vitamin D3 among all studies was 2,167 IU/day (54 mcg/day), while the average dose of D2 was 11,055 IU/day (276 mcg/day).
- The highest dose of vitamin D3 of the studies included was 10,000 IU/day (250 mcg/day), while the highest dose of D2 was 100,000 IU/day (2,500 mcg/day).
- Average baseline vitamin D levels were 18.32 ng/ml (45.8 nmol/l).
- A total of 62 of the studies reported all adverse effects that occurred in the participants, discovering vitamin D supplementation did not increase the risk of these adverse effects (RR= 0.97; 95%CI: 0.92–1.02).
- Adverse effects were not associated with duration of the study, baseline vitamin D status or type of vitamin D administered (p > 0.05).
- A total of 27 studies included gastrointestinal adverse effects that occurred in the participants, but vitamin D supplementation did not increase the risk of these adverse effects (RR= 1.01; 95%CI: 0.87–1.17).
- Adverse gastrointestinal effects were not associated with the duration of the study, baseline vitamin D status or whether or not calcium was administered with the vitamin D supplement (p > 0.05).
- Only 8 studies reported dermatological adverse effects, but vitamin D supplementation did not increase the risk of these adverse effects (RR= 1.33; 95%CI: 0.82–2.15).
- Last, 123 studies reported withdrawals as an outcome, but vitamin D supplementation did not increase the risk of withdrawal (RR= 1.03; 95%CI: 0.96–1.09).
The researchers concluded:
“Supplementation with vitamin D in its natural forms (D2 and D3) did not result in more adverse events, or more withdrawals, compared with placebo treatment. Additionally, supplementation with vitamin D did not increase the risk of GI or dermatological adverse effects.”
There is much to be learned about vitamin D supplementation, but at this time, the research is indicating that vitamin D is safe and extremely beneficial for human health. The Vitamin D Council recommends supplementing with 5,000 IU (125 mcg), up to 10,000 IU (250 mcg), daily in order to attain optimal vitamin D status (40-80 ng/ml; 100-200 nmol/l). It is an inexpensive, safe and easy way to help improve your overall state of health. Email us at [email protected] for any questions or concerns you may have about vitamin D supplementation.
Peterson, R. & Cannell, JJ. Can vitamin D supplementation increase your risk of adverse effects? A recent study suggests otherwise. The Vitamin D Council Blog & Newsletter, 2017.
Malihi, Z. et al. Noncalcemic adverse effects and withdrawals in randomized controlled trials of long-term vitamin D2or D 3 supplementation: a systematic review and meta-analysis. Nutrition Reviews, 2017.