Disease prevention and delayed aging by dietary sulfur amino acid restriction: translational implications

Abstract

Sulfur amino acids (SAAs) play numerous critical roles in metabolism and overall health maintenance. Preclinical studies have demonstrated that SAA-restricted diets have many beneficial effects, including extending life span and preventing the development of a variety of diseases. Dietary sulfur amino acid restriction (SAAR) is characterized by chronic restrictions of methionine and cysteine but not calories and is associated with reductions in body weight, adiposity and oxidative stress, and metabolic changes in adipose tissue and liver resulting in enhanced insulin sensitivity and energy expenditure. SAAR-induced changes in blood biomarkers include reductions in insulin, insulin-like growth factor-1, glucose, and leptin and increases in adiponectin and fibroblast growth factor 21. On the basis of these preclinical data, SAAR may also have similar benefits in humans. While little is known of the translational significance of SAAR, its potential feasibility in humans is supported by findings of its effectiveness in rodents, even when initiated in adult animals. To date, there have been no controlled feeding studies of SAAR in humans; however, there have been numerous relevant epidemiologic and disease-based clinical investigations reported. Here, we summarize observations from these clinical investigations to provide insight into the potential effectiveness of SAAR for humans.

Sex differences in the response to dietary restriction in rodents

“…More than 20 years ago, Orentreich and colleagues reported that a reduction in the concentration of a single dietary essential amino acid, methionine (from 0.86% to 0.17% w/w), resulted in a 30% longer lifespan of male Fisher-344 rats [30]. While perhaps more aptly referred to as sulfur amino acid restriction (SAAR) due to the fact that the nonessential sulfur amino acid cysteine is absent in MetR diets, the phenomenon has been replicated in different rodent models [31]. Additional benefits of MetR that overlap with CR despite ad libitum access to food include reductions in bodyweight, fat mass and oxidative stress coupled with improvements in insulin sensitivity as well as changes in circulating insulin, glucose, leptin, adiponectin, IGF-1 and FGF-21 [31,32].…”

Effects of dietary methionine and cysteine restriction on plasma biomarkers, serum fibroblast growth factor 21, and adipose tissue gene expression in women with overweight or obesity: a double-blind randomized controlled pilot study

“…Dietary intervention is a common strategy in obesity management; however, whether specific dietary interventions are more efficient than others for weight control is still debated. Dietary restriction of the sulfur amino acids methionine and cysteine has the past decades become increasingly recognized as a research model to promote leanness and longevity in animals [3][4][5][6].…”

Effects of High- and Low-proteindiets on Inflammatory Profiles in People With Morbid Obesity: A 3-week Intervention Study

“…In a large cross-sectional study of US adults, methionine-rich diets were associated with a higher prevalence of cardiometabolic disease risk factors, i.e. higher levels of cholesterol, glucose, glycated hemoglobin, uric acid and insulin (33). The concentrations of CRP also showed to be higher with higher intake of methionine-rich diet, albeit the trend did not reach statistical signi cance.…”

“…Compared to calorie restriction, responses to methionine restriction were found to be more robust over the long-run (27). Dietary methionine restriction has been especially associated with metabolic changes in adipose tissue and liver resulting in enhanced insulin sensitivity and energy expenditure (33). In animal studies, methionine restriction was shown to reduce concentrations of insulin, insulin-like growth factor-1, glucose, and leptin and increased adiponectin (33).…”

“…Dietary methionine restriction has been especially associated with metabolic changes in adipose tissue and liver resulting in enhanced insulin sensitivity and energy expenditure (33). In animal studies, methionine restriction was shown to reduce concentrations of insulin, insulin-like growth factor-1, glucose, and leptin and increased adiponectin (33). However, evidence from human research has been sparse.…”