Vitamin D, C-Reactive Protein, and Increased Fall Risk: A Genetic Epidemiological Study

Area of Science:

• Nutritional epidemiology
• Genetic epidemiology
• Biomarkers of inflammation

Background:

• Falls represent a significant public health issue.
• Vitamin D supplementation is explored for fall prevention, but high doses may increase fall risk.
• Inflammation may influence vitamin D levels and motor function, impacting fall risk.

Purpose of the Study:

• To investigate the association between vitamin D, inflammation, and fall risk using a genetic epidemiological approach.
• To explore how inflammation modifies the relationship between 25-hydroxyvitamin D [25(OH)D] and fall risk.

Main Methods:

• Utilized UK Biobank data from 307,082 participants.
• Conducted observational and Mendelian randomization (MR) analyses.
• Examined associations between 25(OH)D, C-reactive protein (CRP), and fall risk, focusing on individuals with inflammation (CRP ≥ 5 mg/L).

Main Results:

• Higher CRP levels were associated with increased fall odds; higher 25(OH)D was associated with lower fall odds.
• A U-shaped association between 25(OH)D and falls was observed in participants with inflammation (CRP ≥ 5 mg/L), with elevated risk at both low (<25 nmol/L) and high (≥100 nmol/L) concentrations.
• Genetically predicted higher 25(OH)D showed a suggestive association with increased fall risk in individuals with high inflammation (CRP > 20 mg/L).

Conclusions:

• Inflammation appears to modify the relationship between vitamin D and fall risk.
• Both low and high 25(OH)D levels are linked to increased falls in individuals with chronic inflammation.
• Findings may explain increased fall risk observed with high-dose vitamin D supplementation in trials, warranting further investigation.