Wu Hui, Guo Jiang-Long, Yao Jing-Jiong, Yu Jia-Jun, Xia Run-Yu, Huang Wei-Qing, Tang Xuan, He Guang-Ming
Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Medical Imaging, The Second Clinical School of Guangzhou Medical University, Guangzhou, China.
Front Nutr. 2023 May 12;10:1162031. doi: 10.3389/fnut.2023.1162031. eCollection 2023.
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.
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 analyzes were used to evaluate the pleiotropy.
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, < 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, < 0.001) and men (OR = 0.73, 95% CI: 0.55 ~ 0.97, = 0.029) but was stronger among women. However, in the IVW of MR analyzes, 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, = 0.502) and secondary analysis (OR = 0.80, 95% CI: 0.53 ~ 1.22, = 0.308). MR sensitivity analyzes yielded consistent results.
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.
维生素C作为一种抗氧化剂，可能在非酒精性脂肪性肝病（NAFLD）的治疗中发挥作用。本研究旨在探讨血清维生素C水平与NAFLD风险之间的关联，并通过孟德尔随机化（MR）方法进一步检验因果关系。
横断面研究选取了2005 - 2006年和2017 - 2018年国家健康与营养检查调查（NHANES）的5578名参与者。在多变量逻辑回归模型下评估血清维生素C水平与NAFLD风险的关联。进行了一项两样本MR研究，使用来自血清维生素C水平（52014人）和NAFLD的大规模全基因组关联研究（GWAS）的遗传数据（主要分析：1483例/17781例对照；次要分析：1908例/340591例对照），以推断它们之间的因果关系。采用逆方差加权（IVW）作为MR分析的主要方法。使用一系列敏感性分析来评估基因多效性。
在横断面研究中，结果显示，在进行全面调整后，第三分位组（第三分位：≥1.06mg/dl）患NAFLD的风险（OR = 0.59，95%CI：0.48 ~ 0.74，P < 0.001）显著低于第一分位组（第一分位：≤0.69mg/dl）。在性别方面，血清维生素C对女性（OR = 0.63，95%CI：0.49 ~ 0.80，P < 0.001）和男性（OR = 0.73，95%CI：0.55 ~ 0.97，P = 0.029）的NAFLD均有保护作用，但在女性中作用更强。然而，在MR分析的IVW中，主要分析（OR = 0.82，95%CI：0.47 ~ 1.45，P = 0.502）和次要分析（OR = 0.80，95%CI：0.53 ~ 1.22，P = 0.308）均未观察到血清维生素C水平与NAFLD风险之间的因果关系。MR敏感性分析得出了一致的结果。
我们的MR研究不支持血清维生素C水平与NAFLD风险之间存在因果关联。需要进一步进行更大样本量的研究来证实我们的发现。
