Critical Appraisal of Large Vitamin D Randomized Controlled Trials.

Abstract

As a consequence of epidemiological studies showing significant associations of vitamin D deficiency with a variety of adverse extra-skeletal clinical outcomes including cardiovascular diseases, cancer, and mortality, large vitamin D randomized controlled trials (RCTs) have been designed and conducted over the last few years. The vast majority of these trials did not restrict their study populations to individuals with vitamin D deficiency, and some even allowed moderate vitamin D supplementation in the placebo groups. In these RCTs, there were no significant effects on the primary outcomes, including cancer, cardiovascular events, and mortality, but explorative outcome analyses and meta-analyses revealed indications for potential benefits such as reductions in cancer mortality or acute respiratory infections. Importantly, data from RCTs with relatively high doses of vitamin D supplementation did, by the vast majority, not show significant safety issues, except for trials in critically or severely ill patients or in those using very high intermittent vitamin D doses. The recent large vitamin D RCTs did not challenge the beneficial effects of vitamin D regarding rickets and osteomalacia, that therefore continue to provide the scientific basis for nutritional vitamin D guidelines and recommendations. There remains a great need to evaluate the effects of vitamin D treatment in populations with vitamin D deficiency or certain characteristics suggesting a high sensitivity to treatment. Outcomes and limitations of recently published large vitamin D RCTs must inform the design of future vitamin D or nutrition trials that should use more personalized approaches.

• Authors: Stefan Pilz, Christian Trummer, Verena Theiler-Schwetz, Martin R Grübler, Nicolas D Verheyen, Balazs Odler, Spyridon N Karras, Armin Zittermann, Winfried März
• Journal: Nutrients (Nutrients) Vol. 14 Issue 2 (Jan 12 2022) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 35057483 (Publication Type: Journal Article, Meta-Analysis, Review)

Chemical References

• Vitamins
• Vitamin D

Topics

• Adolescent
• Adult
• Aged
• Child
• Dietary Supplements
• Female
• Humans
• Male
• Middle Aged
• Nutrition Therapy
• Pregnancy
• Randomized Controlled Trials as Topic
• Vitamin D (therapeutic use)
• Vitamin D Deficiency (complications, therapy)
• Vitamins (therapeutic use)
• Young Adult