Associations among dietary 1-carbon metabolism nutrients, genetic risk, and Alzheimer disease: a prospective cohort study

Yongsheng Wang; Ningning Mi; Kun Liao; Yan Li; Yuxuan Sun; Peng Xie; Linmin Hu; Siqing Wu; Zixin Liang; Qiangsheng He; Zijun Li; Mina Ma; Kehu Yang; Jinqiu Yuan; Bin Xia; Xiuxia Li

doi:10.1016/j.ajcnut.2024.08.027

Associations among dietary 1-carbon metabolism nutrients, genetic risk, and Alzheimer disease: a prospective cohort study

Am J Clin Nutr. 2024 Nov;120(5):1009-1018. doi: 10.1016/j.ajcnut.2024.08.027. Epub 2024 Aug 30.

Authors

Yongsheng Wang¹, Ningning Mi², Kun Liao³, Yan Li⁴, Yuxuan Sun⁵, Peng Xie⁶, Linmin Hu⁷, Siqing Wu⁴, Zixin Liang⁵, Qiangsheng He⁵, Zijun Li¹, Mina Ma⁸, Kehu Yang⁹, Jinqiu Yuan¹⁰, Bin Xia¹¹, Xiuxia Li¹²

Affiliations

¹ Health Technology Assessment Center, School of Public Health, Lanzhou University, Lanzhou, Gansu, China; The Cross-innovation Laboratory of Evidence-based Social Sciences, Lanzhou University, Lanzhou, Gansu, China.
² The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu, China.
³ State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
⁴ School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, China.
⁵ Department of Epidemiology and Biostatistics, Clinical Big Data Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China; Chinese Health Risk Management Collaboration (CHRIMAC), Shenzhen, Guangdong, China.
⁶ Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China.
⁷ School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong, China.
⁸ The Cross-innovation Laboratory of Evidence-based Social Sciences, Lanzhou University, Lanzhou, Gansu, China; Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.
⁹ Health Technology Assessment Center, School of Public Health, Lanzhou University, Lanzhou, Gansu, China; The Cross-innovation Laboratory of Evidence-based Social Sciences, Lanzhou University, Lanzhou, Gansu, China; Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.
¹⁰ Department of Epidemiology and Biostatistics, Clinical Big Data Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China; Chinese Health Risk Management Collaboration (CHRIMAC), Shenzhen, Guangdong, China. Electronic address: yuanjq5@mail.sysu.edu.cn.
¹¹ Department of Epidemiology and Biostatistics, Clinical Big Data Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China; Chinese Health Risk Management Collaboration (CHRIMAC), Shenzhen, Guangdong, China. Electronic address: xiab7@mail.sysu.edu.cn.
¹² Health Technology Assessment Center, School of Public Health, Lanzhou University, Lanzhou, Gansu, China; The Cross-innovation Laboratory of Evidence-based Social Sciences, Lanzhou University, Lanzhou, Gansu, China. Electronic address: lixiuxia@lzu.edu.cn.

PMID: 39216592
DOI: 10.1016/j.ajcnut.2024.08.027

Abstract

Background: The associations between 1-carbon metabolism (OCM) nutrients (methionine, folate, vitamin B-6, and vitamin B-12) and Alzheimer disease (AD) remains inconclusive.

Objectives: This study aimed to investigate the association of dietary OCM nutrients with subsequent risk of AD and further assess whether participants with high genetic risk for AD might benefit from dietary OCM nutrients.

Methods: We analyzed data from 192,214 participants who completed at least one 24-h dietary questionnaire and had no previous history of AD based on the UK Biobank. Nutrients intake was calculated using McCance and Widdowson's The Composition of Food and USDA's Food and Nutrient Database for Dietary Studies. Cox proportional models with restricted cubic splines were applied to explore the associations.

Results: Over a median follow-up of 13.35 y, 959 cases of AD (41 early-onset cases and 918 late-onset cases) were identified. Compared with those in the low-intake OCM group (quartile 1), participants in the high-intake OCM group (quartile 4) had reduced risk of developing AD. The corresponding hazard ratios (HRs) and 95% confidence intervals (CIs) for methionine, folate, vitamin B-6, and vitamin B-12 intake were 0.66 (0.54, 0.80), 0.71 (0.58, 0.87), 0.71 (0.59, 0.87), and 0.77 (0.64, 0.93), respectively. Similar associations were observed in late-onset AD. In early-onset AD, high methionine and vitamin B-12 intake were associated with 70% (HR: 0.30; 95% CI: 0.10, 0.86) and 71% (HR: 0.29; 95% CI: 0.09, 0.96) reduction in risk, respectively. Participants with low genetic risk and high OCM nutrients intake had >75% reduced AD risk compared with high-risk, low-intake participants.

Conclusions: In this prospective cohort study, we found that higher intake of OCM nutrients is associated with reduced risk of AD. Participants with high genetic risk of AD are more likely to benefit from dietary OCM nutrients intake.

Keywords: Alzheimer disease; UK Biobank; cohort study; genetic risk; methionine; polygenic risk score; vitamin B complex.

MeSH terms

Aged
Alzheimer Disease* / epidemiology
Alzheimer Disease* / genetics
Alzheimer Disease* / prevention & control
Carbon / metabolism
Diet*
Female
Folic Acid* / administration & dosage
Genetic Predisposition to Disease
Humans
Male
Methionine* / administration & dosage
Middle Aged
Nutrients / administration & dosage
Proportional Hazards Models
Prospective Studies
Risk Factors
Vitamin B 12* / administration & dosage
Vitamin B 6 / administration & dosage

Substances

Methionine
Folic Acid
Vitamin B 12
Vitamin B 6
Carbon