Cumulative Consumption of Sulfur Amino Acids and Risk of Diabetes: A Prospective Cohort Study

Abstract

Background Cross-sectional studies suggested that consumption of sulfur amino acids (SAAs) including methionine and cysteine is associated with a higher risk of type 2 diabetes (T2D) in humans and T2D-related biomarkers in animals. But, whether higher long-term SAA intake increases the risk of T2D in humans remains unknown. Objectives We aimed to investigate the association between long-term dietary SAA intake and risk of T2D. Methods We analyzed data collected from two different cohorts of the Framingham Heart Study, a long-term, prospective, and ongoing study. The Offspring cohort (1991–2014) included participants from fifth through ninth exam, and Third-Generation cohort (2002–2011) included participants from first and second exam. After excluding participants with a clinical history of diabetes, missing dietary data or implausible total energy intake, 3,222 participants in the Offspring and 3,205 participants in the Third-Generation cohort were included. Dietary intake was assessed using a validated food frequency questionnaire. The relations between energy-adjusted total SAA (methionine and cysteine) intake or individual SAA intake (in quintiles) and risk of incident T2D were estimated via Cox proportional hazards models after adjusting for dietary and non-dietary risk factors. Associations across the two cohorts were determined by direct combination and meta-analysis. Results During the 23 years follow-up, 472 participants reported a new diagnosis of T2D in the two cohorts. In the meta-analysis, the Hazard Ratios (95% Confidence Interval) of T2D comparing the highest with the lowest intake of total SAAs, methionine, and cysteine were 1.8 (1.3, 2.5), 1.7 (1.2, 2.3), and 1.4 (1.0, 2.1), respectively. The association of SAA intake with T2D was attenuated after adjusting animal protein intake in sensitivity analyses. Conclusions Our findings show that excess intake of SAA is associated with higher risk of T2D. Dietary patterns that are low in SAA diet may help in preventing T2D.

Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial

“…An additional limitation with the present study includes the relatively short study duration of 8 weeks. Lastly, the intake of SAA in the control group may be higher than a typical Western diet, however, relative to body weight the content it is in line with reported intake in upper quantile groups in large population studies including NHANES and the Framingham cohort studies 6–8 .…”

“…Methionine and cysteine are essential and semi-essential sulfur amino acids (SAA) with a FAO/WHO minimum (recommended) intake of 15 (19) mg/kg/d in adults 1 . High dietary intake and plasma concentrations of SAA are strongly and linearly related to increased risk of metabolic disease and development of obesity [2][3][4][5][6][7][8][9] . In a large population-based cohort study of men and women (n = 5179), the difference in fat mass between lower and upper percentiles of plasma total cysteine (tCys) was 11 kg 3 .…”

“…Moreover, in two independent Dutch cohorts of men and women aged 40-74 y, plasma methionine was associated with liver fat, whereas tCys was associated with overall obesity 9 . Recent prospective cohort studies showed that plasma tCys was associated with diabetes risk 10 , whereas dietary intake of SAA was associated with increased cardiovascular risk scores, diabetes risk and diabetes-related mortality [6][7][8] .…”

Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial

“…In two independent Dutch cohorts of men and women aged 40–74 y, plasma methionine was associated with liver fat, whereas tCys was associated with overall obesity [ 10 ]. Recent prospective cohort studies showed that plasma tCys was associated with diabetes risk [ 11 ], whereas an increased dietary intake of SAA was associated with increased cardiovascular risk scores, diabetes risk and diabetes-related mortality [ 7 – 9 ].…”

Dietary Amino Acid Composition and Glycemic Biomarkers in Japanese Adolescents

“…Amino acids other than BCAAs are also involved in glucose metabolism. Excess intake of sulfur amino acids (methionine and cysteine) is associated with a higher risk of diabetes in the US population [ 15 ], and histidine is negatively associated with glucose and insulin resistance in the Chinese population [ 16 ]. In diabetic rats, alanine and glutamine supplementation reduces and improves blood glucose levels [ 17 ].…”