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Effect of glutamate and aspartate on ischemic heart disease, blood pressure, and diabetes: a Mendelian randomization study.
Am J Clin Nutr 2019; 109(4):1197-1206AJ

Abstract

BACKGROUND

Evolutionary biology suggests reproduction trades off against longevity. Genetic selection in favor of fertility and ischemic heart disease (IHD) exists in humans. Observationally, soy protects against IHD. Soy amino acids, glutamate and aspartate, may lower androgens. No large randomized controlled trials testing their health effects exist.

OBJECTIVE

Using Mendelian randomization, we assessed how genetically predicted glutamate and aspartate affected IHD, blood pressure, and diabetes.

METHODS

A separate sample instrumental variable analysis with genetic instruments was used to obtain unconfounded estimates using genetic variants strongly (P < 5 × 10(-8)) and solely associated with glutamate or aspartate applied to an IHD case (n ≤76,014)-control (n ≤ 264,785) study (based on a meta-analysis of CARDIoGRAMplusC4D 1000 Genomes, UK Biobank CAD SOFT GWAS and Myocardial Infarction Genetics and CARDIoGRAM Exome), blood pressure from the UK Biobank (n ≤ 361,194), and the DIAbetes Genetics Replication And Meta-analysis diabetes case (n = 26,676)-control (n = 132,532) study. A weighted median and MR-Egger were used for a sensitivity analysis.

RESULTS

Glutamate was not associated with IHD, blood pressure, or diabetes after correction for multiple comparisons. Aspartate was inversely associated with IHD (odds ratio (OR) 0.92 per log-transformed standard deviation (SD); 95% confidence interval (CI) 0.88, 0.96) and diastolic blood pressure (-0.03; 95% CI -0.04, -0.02) using inverse variance weighting, but not diabetes (OR 1.00; 95% CI 0.91, 1.09). Associations were robust to the sensitivity analysis.

CONCLUSIONS

Our findings suggest aspartate may play a role in IHD and blood pressure, potentially underlying cardiovascular benefits of soy. Clarifying the mechanisms would be valuable for IHD prevention and for defining a healthy diet.

Authors+Show Affiliations

School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. City University of New York, School of Public Health and Health Policy, New York, NY.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30949673

Citation

Zhao, Jie V., et al. "Effect of Glutamate and Aspartate On Ischemic Heart Disease, Blood Pressure, and Diabetes: a Mendelian Randomization Study." The American Journal of Clinical Nutrition, vol. 109, no. 4, 2019, pp. 1197-1206.
Zhao JV, Kwok MK, Schooling CM. Effect of glutamate and aspartate on ischemic heart disease, blood pressure, and diabetes: a Mendelian randomization study. Am J Clin Nutr. 2019;109(4):1197-1206.
Zhao, J. V., Kwok, M. K., & Schooling, C. M. (2019). Effect of glutamate and aspartate on ischemic heart disease, blood pressure, and diabetes: a Mendelian randomization study. The American Journal of Clinical Nutrition, 109(4), pp. 1197-1206. doi:10.1093/ajcn/nqy362.
Zhao JV, Kwok MK, Schooling CM. Effect of Glutamate and Aspartate On Ischemic Heart Disease, Blood Pressure, and Diabetes: a Mendelian Randomization Study. Am J Clin Nutr. 2019 04 1;109(4):1197-1206. PubMed PMID: 30949673.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of glutamate and aspartate on ischemic heart disease, blood pressure, and diabetes: a Mendelian randomization study. AU - Zhao,Jie V, AU - Kwok,M K, AU - Schooling,C Mary, PY - 2018/05/17/received PY - 2018/11/29/accepted PY - 2019/4/6/pubmed PY - 2019/4/6/medline PY - 2019/4/6/entrez KW - Mendelian randomization KW - aspartate KW - blood pressure KW - diabetes KW - ischemic heart disease SP - 1197 EP - 1206 JF - The American journal of clinical nutrition JO - Am. J. Clin. Nutr. VL - 109 IS - 4 N2 - BACKGROUND: Evolutionary biology suggests reproduction trades off against longevity. Genetic selection in favor of fertility and ischemic heart disease (IHD) exists in humans. Observationally, soy protects against IHD. Soy amino acids, glutamate and aspartate, may lower androgens. No large randomized controlled trials testing their health effects exist. OBJECTIVE: Using Mendelian randomization, we assessed how genetically predicted glutamate and aspartate affected IHD, blood pressure, and diabetes. METHODS: A separate sample instrumental variable analysis with genetic instruments was used to obtain unconfounded estimates using genetic variants strongly (P < 5 × 10(-8)) and solely associated with glutamate or aspartate applied to an IHD case (n ≤76,014)-control (n ≤ 264,785) study (based on a meta-analysis of CARDIoGRAMplusC4D 1000 Genomes, UK Biobank CAD SOFT GWAS and Myocardial Infarction Genetics and CARDIoGRAM Exome), blood pressure from the UK Biobank (n ≤ 361,194), and the DIAbetes Genetics Replication And Meta-analysis diabetes case (n = 26,676)-control (n = 132,532) study. A weighted median and MR-Egger were used for a sensitivity analysis. RESULTS: Glutamate was not associated with IHD, blood pressure, or diabetes after correction for multiple comparisons. Aspartate was inversely associated with IHD (odds ratio (OR) 0.92 per log-transformed standard deviation (SD); 95% confidence interval (CI) 0.88, 0.96) and diastolic blood pressure (-0.03; 95% CI -0.04, -0.02) using inverse variance weighting, but not diabetes (OR 1.00; 95% CI 0.91, 1.09). Associations were robust to the sensitivity analysis. CONCLUSIONS: Our findings suggest aspartate may play a role in IHD and blood pressure, potentially underlying cardiovascular benefits of soy. Clarifying the mechanisms would be valuable for IHD prevention and for defining a healthy diet. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/30949673/Effect_of_glutamate_and_aspartate_on_ischemic_heart_disease_blood_pressure_and_diabetes:_a_Mendelian_randomization_study_ L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.1093/ajcn/nqy362 DB - PRIME DP - Unbound Medicine ER -