AUTHOR=Wu Hui , Guo Jiang-Long , Yao Jing-Jiong , Yu Jia-Jun , Xia Run-Yu , Huang Wei-Qing , Tang Xuan , He Guang-Ming 

TITLE=Serum vitamin C levels and risk of non-alcoholic fatty liver disease: results from a cross-sectional study and Mendelian randomization analysis

JOURNAL=Frontiers in Nutrition

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1162031

DOI=10.3389/fnut.2023.1162031

ISSN=2296-861X

ABSTRACT=Background & Aims: Vitamin C, as an antioxidant, may play a role in the treatment of NAFLD. This research aimed to investigate the association of serum vitamin C levels with the risk of NAFLD and to further examine the causal relationship by Mendelian randomization (MR) method.
Methods: The cross-sectional study selected 5,578 participants of the National Health and Nutrition Examination Survey (NHANES), 2005–2006 and 2017-2018. The association of serum vitamin C levels with NAFLD risk was evaluated under a multivariable logistic regression model. A two-sample MR study, using genetic data from large-scale genome-wide association studies (GWAS) of serum vitamin C levels (52,014 individuals) and NAFLD (primary analysis: 1,483 cases / 17,781 controls; secondary analysis: 1,908 cases / 340,591 controls), was conducted to infer causality between them. The inverse-variance-weighted (IVW) was applied as the main method of MR analysis. A series of sensitivity analyses were used to evaluate the pleiotropy.
Results: In the cross-sectional study, results showed that Tertile 3 group (Tertile 3:≥1.06 mg/dl) had a significantly lower risk (OR=0.59, 95% CI: 0.48~0.74, p<0.001) of NAFLD than Tertile 1 group (Tertile 1:≤0.69 mg/dl) after full adjustments. In regard to gender, serum vitamin C was protective against NAFLD in both women (OR=0.63, 95% CI: 0.49~0.80, p<0.001) and men (OR=0.73, 95% CI: 0.55~0.97, p=0.029) but was stronger among women. However, In the IVW of MR analyses, no causal relationship between serum vitamin C levels and NAFLD risk was observed in the primary analysis (OR = 0.82, 95% CI: 0.47~1.45, p = 0.502) and secondary analysis (OR = 0.80, 95% CI: 0.53~1.22, p = 0.308). MR sensitivity analyses yielded consistent results.
Conclusions: Our MR study did not support a causal association between serum vitamin C levels and NAFLD risk. Further studies with greater cases are warranted to confirm our findings.