Serum vitamin C levels and risk of osteoporosis: results from a cross-sectional study and Mendelian randomization analysis.

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.