It has been suggested in the literature that consumption in the diet of methionine – an amino acid such as in animal protein may have a negative effect on healthspan and potentially lifespan.

It has also been suggested that dietary restriction (DR) of methionine is a good lifestyle choice for healthy aging.

This presents a problem for those of us that are omnivores and include quality animal protein in our diets.

A suggested solution to this quandary is to consume supplemental glycine, a readily available and inexpensive amino acid.

Following are representative abstracts on these topics.

It is worth noting that with respect to cancer that glycine may stimulate growth so dietary glycine restriction may be of benefit.

Prog Mol Biol Transl Sci. 2014;121:351-76. doi: 10.1016/B978-0-12-800101-1.00011-9.

The impact of dietary methionine restriction on biomarkers of metabolic health.

Orgeron ML¹, Stone KP¹, Wanders D¹, Cortez CC¹, Van NT¹, Gettys TW¹.  

Abstract

Calorie restriction without malnutrition, commonly referred to as dietary restriction (DR), results in a well-documented extension of life span. DR also produces significant, long-lasting improvements in biomarkers of metabolic health that begin to accrue soon after its introduction. The improvements are attributable in part to the effects of DR on energy balance, which limit fat accumulation through reduction in energy intake.

Accumulation of excess body fat occurs when energy intake chronically exceeds the energy costs for growth and maintenance of existing tissue. The resulting obesity promotes the development of insulin resistance, disordered lipid metabolism, and increased expression of inflammatory markers in peripheral tissues. The link between the life-extending effects of DR and adiposity is the subject of an ongoing debate, but it is clear that decreased fat accumulation improves insulin sensitivity and produces beneficial effects on overall metabolic health. Over the last 20 years, dietary methionine restriction (MR) has emerged as a promising DR mimetic because it produces a comparable extension in life span, but surprisingly, does not require food restriction.

Dietary MR also reduces adiposity but does so through a paradoxical increase in both energy intake and expenditure. The increase in energy expenditure fully compensates for increased energy intake and effectively limits fat deposition. Perhaps more importantly, the diet increases metabolic flexibility and overall insulin sensitivity and improves lipid metabolism while decreasing systemic inflammation. In this chapter, we describe recent advances in our understanding of the mechanisms and effects of dietary MR and discuss the remaining obstacles to implementing MR as a treatment for metabolic disease.

KEYWORDS:

Amino acid sensing; Animal models; Dietary protein; Insulin sensitivity; Obesity

Biochemistry/Molecular Biology

Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats

Joel Brind,Virginia Malloy,Ines Augie,Nicholas Caliendo,Joseph H Vogelman,Jay A. Zimmerman, and Norman Orentreich
Abstract

Dietary methionine (Met) restriction (MR) extends lifespan in rodents by 30–40% and inhibits growth. Since glycine is the vehicle for hepatic clearance of excess Met via glycine N-methyltransferase (GNMT), we hypothesized that dietary glycine supplementation (GS) might produce biochemical and endocrine changes similar to MR and also extend lifespan. Seven-week-old male Fisher 344 rats were fed diets containing 0.43% Met/2.3% glycine (control fed; CF) or 0.43% Met/4%, 8% or 12% glycine until natural death.

In 8% or 12% GS rats, median lifespan increased from 88 weeks (w) to 113 w, and maximum lifespan increased from 91 w to 119 w v CF. Body growth reduction was less dramatic, and not even significant in the 8% GS group. Dose-dependent reductions in several serum markers were also observed. Long-term (50 w) 12% GS resulted in reductions in mean (±SD) fasting glucose (158 ± 13 v 179 ± 46 mg/dL), insulin (0.7 ± 0.4 v 0.8 ± 0.3 ng/mL), IGF-1 (1082 ± 128 v 1407 ± 142 ng/mL) and triglyceride (113 ± 31 v 221 ± 56 mg/dL) levels compared to CF.

Adiponectin, which increases with MR, did not change in GS after 12 w on diet. We propose that more efficient Met clearance via GNMT with GS could be reducing chronic Met toxicity due to rogue methylations from chronic excess methylation capacity or oxidative stress from generation of toxic by-products such as formaldehyde. This project received no outside funding.