Serum vitamin C levels and risk of osteoporosis: results from a cross-sectional study and Mendelian randomization analysis
Authors: Liu Zhiwen , Peng Zijing , Zhong Yelin , Wu Jianjun , Xiong Sicheng , Zhong Wei , Luo Jiehua , Zhang Zhihai , Huang Hongxing 
Published: November 2024

Abstract
Background
The role of vitamin C as an antioxidant in guarding against osteoporosis in adults is still debated. This research employs both a cross-sectional study and a two-sample bidirectional Mendelian randomization (MR) analysis to explore how serum vitamin C levels correlate with the incidence of osteoporosis among adults.

Methods
In this study, we utilized data from the National Health and Nutrition Examination Survey (NHANES) database for the years 2003–2006, and 2017–2018 to conduct both a cross-sectional analysis and MR to investigate the relationship between serum vitamin C levels and the risk of osteoporosis in adults. We adjusted our analyses for essential demographic and lifestyle variables, and applied logistic regression techniques. Genetic determinants of vitamin C levels were analyzed through MR, using methods like inverse-variance weighted (IVW) and MR-Egger to assess causality. Statistical computations were carried out in R, incorporating visual tools such as restricted cubic spline curves (RCS) and forest plots to clarify the dose–response dynamics and variations across different subgroups. This study was approved by the NCHS Ethics Review Board, and informed consent was obtained from all participants.

Results
In our investigation, we analyzed data from 3,940 participants, among whom 291 were diagnosed with osteoporosis. The logistic regression analysis of serum vitamin C quartiles did not indicate a significant trend. The most adjusted model showed a slight, albeit inconsistent, protective effect in the highest quartile (OR = 0.68, 95% CI: 0.47–0.99, P = 0.22). Mendelian randomization, employing methods such as IVW, reinforced the absence of a significant causal relationship between serum vitamin C levels and osteoporosis risk (IVW OR = 1.000, 95% CI: 0.999–1.001, P = 0.601).Subgroup analyses, visualized through forest plots and restricted cubic spline (RCS) curves, supported the primary findings, showing no significant effects or interactions between vitamin C levels and osteoporosis risk across different demographic and lifestyle subgroups. The RCS analysis particularly highlighted a lack of significant non-linear relationships between serum vitamin C concentration and the odds of osteoporosis (P for nonlinear = 0.840).

Conclusions
The cross-sectional study revealed that higher serum vitamin C levels do not consistently correlate with a reduced risk of osteoporosis. Meanwhile, the Mendelian randomization analysis confirmed that there is no genetic evidence to suggest a causal relationship between vitamin C levels and osteoporosis risk. Recent research highlights the polygenic nature of osteoporosis, with genetic predispositions playing a significant role in disease risk. The relationship between serum vitamin C and osteoporosis requires further research. This suggests the need for further investigation into the connection between vitamin C and bone health.