Shuo Jiang

Background: The impact of dietary fat on dementia risk remains controversial due to conflicting findings on fat subtypes, over-reliance on linear models, and limited attention to fat source balance. Methods: In a large prospective analysis of 97,765 UK Biobank adults, we examined associations between dietary fat composition and incident dementia, integrating genetic susceptibility and metabolomic profiling. Results: Total fat intake, animal fat, and plant fat all showed significant U-shaped associations with dementia risk. Notably, the animal-to-plant fat ratio exhibited a clear U-shaped association ( P _FDR for nonlinearity = 0.011), with the lowest risk observed at a ratio of 0.9. A significant interaction with APOE -ε4 carriage was identified ( P for interaction = 0.041), in which carriers in the lowest quartile of the fat ratio had the highest dementia risk (HR = 3.88, 95% CI: 3.00–5.00). A similar nonlinear pattern was observed for executive function. Mediation analyses implicated very-low-density lipoprotein-related metabolites as key intermediates. Conclusions: These findings highlight the importance of balanced fat sources and support precision nutrition strategies tailored to genetic risk.

Background: Previous studies have reported associations between fatty acids and the risk of pre-eclampsia. However, the causality of these associations remains uncertain. This study postulates a causal relationship between specific plasma fatty acids and pre-eclampsia or other maternal hypertensive disorders (PE-HTPs). To test this hypothesis, two-sample bidirectional Mendelian randomization (MR) analyses were employed to determine the causality effects. Methods: Single-nucleotide polymorphisms associated with PE-HTPs and fatty acids were obtained from a genome-wide association study (GWAS) of European ancestry. Bidirectional MR analyses were conducted using methods such as inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses, including tests for heterogeneity, horizontal pleiotropy, and co-localization, were conducted to assess the robustness of MR results. Results: The analyses revealed causal relationships between PE-HTPs and several fatty acids, including monounsaturated fatty acid (MUFA), omega-6 fatty acid (n-6 FA), linoleic acid (LA), docosahexaenoic acid (DHA), and the PUFA/MUFA ratio. Genetically predicted higher risk of PE-HTPs was significantly associated with lower plasma n-6 FA (OR = 0.96, 95% CI: 0.93–0.99), particularly LA (OR = 0.95, 95% CI: 0.92–0.98). Conversely, increased DHA (OR = 0.86, 95% CI: 0.78–0.96) and a higher PUFA/MUFA ratio (OR = 0.86, 95% CI: 0.76–0.98) were associated with a reduced risk of PE-HTPs. Elevated MUFA levels (OR = 1.12, 95% CI: 1.00–1.25) were related to an increased risk. Conclusions: This study provides robust genetic evidence supporting bidirectional causal relationships between PE-HTPs and specific plasma fatty acids, underscoring the critical role of fatty acid metabolism in maternal hypertensive disorders.

Background: We aimed to comprehensively assess the relationship of specific dietary patterns and various nutrients with chronic kidney disease (CKD) and its progression. Methods: The observational study data were from the NHANES 2005–2020. We calculated four dietary pattern scores (healthy eating index 2020 (HEI-2020), dietary inflammatory index (DII), alternative mediterranean diet (aMed), and dietary approaches to stop hypertension (DASH)) and the intakes of various nutrients and defined CKD, CKD—very high risk, and kidney dialysis. Associations between dietary patterns and nutrients and disease were assessed by means of two logistic regression models. Two-sample MR was performed with various food and nutrients as the exposure and CKD, kidney dialysis as the outcome. Sensitivity analyses were conducted to verify the reliability of the results. Results: A total of 25,167 participants were included in the analyses, of whom 4161 had CKD. HEI-2020, aMed, and DASH were significantly negatively associated with CKD and CKD—very high risk at higher quartiles, while DII was significantly positively associated. A higher intake of vitamins and minerals may reduce the incidence and progression of CKD to varying degrees. The MR results, corrected for false discovery rates, showed that a higher sodium intake was associated with a higher prevalence of CKD (OR: 3.91, 95%CI: 2.55, 5.99). Conclusions: Adhering to the three dietary patterns of HEI-2020, aMed, and DASH and supplementing with vitamins and minerals benefits kidney health.