Xu Yin, Zou Menglong, Fu Jia, Yi Zhan, Zhu Ying
Department of Gastroenterology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.
Hunan University of Chinese Medicine, Changsha, Hunan, China.
Medicine (Baltimore). 2025 Jul 25;104(30):e43380. doi: 10.1097/MD.0000000000043380.
The brain, which contains high levels of catecholamines and unsaturated lipids, is particularly susceptible to oxidative damage. Against this background, increasing antioxidant levels through diet seems to be a potential approach to the prevention of neurodegenerative diseases. A recent innovative study suggests that the shape of the brain itself, rather than just the neural pathways, can have a significant impact on our cognitive processes. Here, we investigated the causal relationship between diet-derived circulating antioxidants and surface area (SA) and thickness (TH) of brain cortical structure using Mendelian randomization (MR). Published studies were used to identify instrumental variables related to absolute levels of circulating antioxidants like lycopene, retinol, ascorbate, and β-carotene, as well as antioxidant metabolites such as ascorbate, retinol, α-tocopherol, and γ-tocopherol. Outcome data on brain cortical structure were obtained from the ENIGMA consortium, which included a total of 51,665 participants. Following the guidelines of the Desikan-Killiany atlas, the cortical structure was divided into 34 regions, resulting in 70 phenotypes covering both the global and regional aspects of SA and TH. Inverse variance weighted or Wald ratio was chosen as the main method for MR analysis based on the number of single nucleotide polymorphisms. Furthermore, we performed sensitivity analyses to confirm the reliability of the findings. At the global level, absolute circulating levels of ascorbate were found to increase SA of the full cortex (β = 2244.536 mm2, 95% CI: 921.172 mm2 to 3567.901 mm2, P = .001) but had no causal relationship with TH of the full cortex (β = -0.008 mm, 95% CI: -0.020 mm to 0.005 mm, P = .228). For the levels of functional parcellation analysis, we found that circulating ascorbate metabolite significantly reduced the SA of the inferior parietal (β = -110.917 mm2; 95% CI: -176.543 mm2 to -45.292 mm2; P = .00092) and absolute circulating retinol significantly reduced the TH of the precuneus (β = -0.045 mm; 95% CI: -0.073 mm to -0.017 mm; P = .00146). No heterogeneity, pleiotropy or outliers were found. MR estimates suggest that absolute circulating levels of ascorbate increase the SA of the whole cortex. There were also 2 significant negative correlations between circulating antioxidants and cortical structure. These results provide important insights into how circulating antioxidants influence structural changes within specific cortical areas and remind us of the potential adverse consequences of supplementation with circulating antioxidants.
大脑中含有高水平的儿茶酚胺和不饱和脂质，特别容易受到氧化损伤。在此背景下，通过饮食提高抗氧化剂水平似乎是预防神经退行性疾病的一种潜在方法。最近一项创新性研究表明，大脑本身的形状，而非仅仅是神经通路，会对我们的认知过程产生重大影响。在此，我们使用孟德尔随机化（MR）方法研究了饮食来源的循环抗氧化剂与脑皮质结构表面积（SA）和厚度（TH）之间的因果关系。利用已发表的研究来确定与循环抗氧化剂（如番茄红素、视黄醇、抗坏血酸和β-胡萝卜素）的绝对水平以及抗氧化代谢物（如抗坏血酸、视黄醇、α-生育酚和γ-生育酚）相关的工具变量。关于脑皮质结构的结果数据来自ENIGMA联盟，该联盟总共包括51665名参与者。按照Desikan-Killiany图谱的指导原则，将皮质结构划分为34个区域，从而产生70种涵盖SA和TH全局及区域方面的表型。基于单核苷酸多态性的数量，选择逆方差加权或Wald比率作为MR分析的主要方法。此外，我们进行了敏感性分析以确认研究结果的可靠性。在全局水平上，发现抗坏血酸的绝对循环水平会增加整个皮质的SA（β = 2244.536 mm²，95% CI：921.172 mm²至3567.901 mm²，P = .001），但与整个皮质的TH没有因果关系（β = -0.008 mm，95% CI：-0.020 mm至0.005 mm，P = .228）。对于功能分区分析水平，我们发现循环抗坏血酸代谢物显著降低了顶下小叶的SA（β = -110.917 mm²；95% CI：-176.543 mm²至-45.292 mm²；P = .00092），并且视黄醇的绝对循环水平显著降低了楔前叶的TH（β = -0.045 mm；95% CI：-0.073 mm至-0.017 mm；P = .00146）。未发现异质性、多效性或异常值。MR估计表明抗坏血酸的绝对循环水平会增加整个皮质的SA。循环抗氧化剂与皮质结构之间也存在2个显著的负相关。这些结果为循环抗氧化剂如何影响特定皮质区域内的结构变化提供了重要见解，并提醒我们补充循环抗氧化剂可能产生的不良后果。
