Vitamin D: A magic bullet or a myth?

Area of Science:

• Endocrinology
• Nutritional Science
• Public Health

Background:

• Vitamin D (Vit D) receptors are found in many cells, suggesting roles beyond bone health.
• Epidemiological studies link low Vit D to various diseases, prompting investigation into supplementation.
• Large randomized controlled trials (RCTs) have yielded inconclusive evidence for Vit D's benefits in major non-bone health conditions.

Purpose of the Study:

• To review the literature on the association between Vitamin D status and various diseases.
• To evaluate the evidence from observational studies and RCTs regarding Vitamin D supplementation.
• To critically assess the validity of plasma Vitamin D levels as a marker of status, especially during illness.

Main Methods:

• Literature search using PubMed for systematic reviews of observational studies on Vit D status and diseases (cancer, cardiovascular, autoimmune, sepsis, mortality).
• Searched for RCTs, focusing on those with positive intervention effects on primary or secondary outcomes.
• Reviewed studies on Vit D metabolism, endogenous production, dietary intake, activation, transport, and the role of Vit D Binding Protein.

Main Results:

• Most large RCTs found no significant positive effects of Vit D supplementation on cancer, cardiovascular, autoimmune, or inflammatory diseases.
• Few studies demonstrated positive intervention effects; the majority showed no significant benefits.
• Altered Vit D Binding Protein concentrations during inflammation can lead to low plasma Vit D without indicating low active Vit D, questioning its status assessment.

Conclusions:

• The presumed high prevalence of Vitamin D deficiency warrants reconsideration.
• Plasma Vitamin D levels may not accurately reflect true Vit D status in disease states due to factors like altered binding protein levels and reversed causality.
• Widespread food fortification and encouragement of supplement use for Vitamin D should be re-evaluated.