Body mass index determines the response of plasma sulfur amino acids to methionine loading

Elshorbagy, Amany K.; Graham, Ian; Refsum, Helga

doi:10.1016/j.biochi.2020.03.001

Cited by 7 publications

(2 citation statements)

References 35 publications

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“…Several mechanisms have been established to clarify the relationships between Hcy concentrations and the pathogenesis of obesity and musculoskeletal metabolism. A changed cysteine and Hcy have a corresponding reaction to the ingested methionine in obesity, in which case both could elevate in response to dietary methionine ( 73 ). This may help explain why human obesity consistently impacts the increased concentrations of Hcy and cysteine, as already explored in the existing studies ( 74 – 76 ).…”

Section: Discussionmentioning

confidence: 99%

Causal effects of B vitamins and homocysteine on obesity and musculoskeletal diseases: A Mendelian randomization study

Wang²,

Hu³

2022

Front. Nutr.

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ObjectivesAlthough homocysteine (Hcy) increases the risk of cardiovascular diseases, its effects on obesity and musculoskeletal diseases remain unclear. We performed a Mendelian randomization study to estimate the associations between Hcy and B vitamin concentrations and their effects on obesity and musculoskeletal-relevant diseases in the general population.MethodsWe selected independent single nucleotide polymorphisms of Hcy (n = 44,147), vitamin B12 (n = 45,576), vitamin B6 (n = 1864), and folate (n = 37,465) at the genome-wide significance level as instruments and applied them to the studies of summary-level data for fat and musculoskeletal phenotypes from the UK Biobank study (n = 331,117), the FinnGen consortium (n = 218,792), and other consortia. Two-sample Mendelian randomization (MR) approaches were utilized in this study. The inverse variance weighting (IVW) was adopted as the main analysis. MR-PRESSO, MR-Egger, the weighted median estimate, bidirectional MR, and multivariable MR were performed as sensitivity methods.ResultsHigher Hcy concentrations were robustly associated with an increased risk of knee osteoarthritis [odds ratio (OR) 1.119; 95% confidence interval (CI) 1.032–1.214; P = 0.007], hospital-diagnosed osteoarthritis (OR 1.178; 95% CI 1.012–1.37; P = 0.034), osteoporosis with pathological fracture (OR 1.597; 95% CI 1.036–2.46; P = 0.034), and soft tissue disorder (OR 1.069; 95% CI 1.001–1.141; P = 0.045) via an inverse variance weighting method and other MR approaches. Higher vitamin B12 levels were robustly associated with decreased body fat percentage and its subtypes (all P < 0.05). Bidirectional analyses showed no reverse causation. Multivariable MR analyses and other sensitivity analyses showed directionally similar results.ConclusionsThere exist significant causal effects of vitamin B12 in the serum and Hcy in the blood on fat and musculoskeletal diseases, respectively. These findings may have an important insight into the pathogenesis of obesity and musculoskeletal diseases and other possible future therapies.

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Section: Discussionmentioning

confidence: 99%

Causal effects of B vitamins and homocysteine on obesity and musculoskeletal diseases: A Mendelian randomization study

Wang²,

Hu³

2022

Front. Nutr.

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“…45 Such conserved nutrient and stress response pathways might be regulating a physiological adaptation to overfeeding on a modern standard US diet, which includes elevated methionine intakes. 46,47 Much of the research on methionine and human health has been generated within the framework of nutritional deficiency. Over the past decade, research focus is turning to the potential health risks arising from methionine intake that is chronically above what is required.…”

Section: How Methionine Availability Connects To Human Healthmentioning

confidence: 99%

A planetary health perspective on synthetic methionine

Neubauer

Landecker

2021

The Lancet Planetary Health

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Methionine is an amino acid that humans and farm animals must derive from food. This metabolite, a tightly regulated resource in ecosystems, has become a mass commodity in the global economy, with well over 1 million tons being produced annually from petroleum to fortify livestock feed. Viewed from the standpoint of planetary health, anthropogenic methionine synthesis is an important enabler of low-cost animal protein production, with interdependent but unexamined effects on human health and ecosystems. At a time when agrochemical engineering is shifting the way sulphur is assimilated and moves up our food chain, research suggests that dietary methionine restriction alone captures many healthspan benefits noted with calorie restriction. As such, methionine synthesis is an excellent exemplar of planetary scale anthropogenic activity that manifests at the molecular scale of cellular metabolism, with potential systemic effects on human health. In this Personal View we establish the scale and historical trajectory of the methionine industry and provide a preliminary model for tracing this amino acid through the food supply into the human body. We draw together insights across disparate publications of applied animal agriculture, human nutrition, and biomedical research to call for cross-disciplinary dialogue on responsible use of methionine-augmentation technologies.

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Differential expression of cystathionine beta synthase in adolescents with Down syndrome: impact on adiposity

Meguid

Hemimi

Ghozlan

et al. 2022

J Diabetes Metab Disord

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Body mass index determines the response of plasma sulfur amino acids to methionine loading

Cited by 7 publications

References 35 publications

Causal effects of B vitamins and homocysteine on obesity and musculoskeletal diseases: A Mendelian randomization study

Causal effects of B vitamins and homocysteine on obesity and musculoskeletal diseases: A Mendelian randomization study

A planetary health perspective on synthetic methionine

Differential expression of cystathionine beta synthase in adolescents with Down syndrome: impact on adiposity

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