A recent genetic epidemiological study suggested that both low and high levels of 25-hydroxyvitamin D are associated with an increased risk of falls in patients with elevated C-reactive protein, indicating that inflammation may modify the relationship between vitamin D status and fall risk.
According to their article published in Nutrients, the researchers utilized data from 307,082 participants in the UK Biobank and employed both observational and Mendelian randomization (MR) analyses to explore these associations.
Observational findings revealed that elevated C-reactive protein (CRP) levels correlated with an increased likelihood of falls, with an odds ratio (OR) of 1.06 per 5 mg/L increase in CRP (95% confidence interval [CI] = 1.05–1.07). Higher 25-hydroxyvitamin D [25(OH)D] concentrations were linked to a decreased risk of falls; however, the relationship was nonlinear (P < .001), which suggested a plateau effect at higher concentrations. An interaction between 25(OH)D and CRP levels was observed (P = .009), indicating that inflammation may modify the effect of vitamin D on fall risk.
In participants with CRP levels of at least 5 mg/L, a U-shaped relationship emerged between 25(OH)D levels and fall risk. Specifically, increased fall risk was noted in patients with 25(OH)D concentrations below 25 nmol/L or 100 nmol/L or more (P < .004). This association was most pronounced in participants with CRP levels of 20 mg/L or more. Those with 25(OH)D concentrations of at least 100 nmol/L had an OR of 2.40 (95% CI = 1.50–3.86) for falls compared with patients with levels between 50 and 74.99 nmol/L.
Mendelian randomization analyses indicated that genetically predicted higher 25(OH)D levels were not associated with fall risk in the overall population. However, a suggestive association was noted in participants who had fallen and had CRP levels greater than 20 mg/L (926 cases; OR = 1.20, 95% CI = 1.00–1.44).
"Both low and high 25(OH)D levels increased fall risk in individuals with chronic inflammation, with supporting evidence for the association between higher 25(OH)D and increased fall risk in those with chronic inflammation provided via MR analysis," wrote Joshua P. Sutherland of the Australian Centre for Precision Health, University of South Australia and colleagues.
The researchers suggested that future research should investigate whether the increased fall risk observed after high-dose vitamin D supplementation in clinical trials is related to the excessive formation of VDR-RXR heterodimers, which may lead to functional retinol deficiency and potentially impact anti-inflammatory and motor function pathways.
The authors declared that they have no competing interests.