Methionine restriction (MR) prevents obesity because of a futile lipid cycle in which two metabolic pathways run simultaneously in opposite directions and have no overall effect other than to dissipate energy in the form of heat. In this study, we show that MR promotes weight loss not just by this futile lipid cycle, but also by a coordinated response that involves apoptosis (normal cell death) and autophagy (a metabolic process by which the body consumes its own tissue) to maintain physiological equilibrium.
It has been observed that the hormones adiponectin and fibroblast growth factor 21 are consistently elevated during MR. To clearly define the roles of ADIPOQ and FGF21 during MR, we used mice that lacked either or both hormones. The obese mice, once placed on an MR diet, lost weight regardless of the presence of these hormones, demonstrating that neither is essential to reduce fat during MR.
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Cooke, D., Mattocks, D., Nichenametla, S. N., Anunciado‐Koza, R. P., Koza, R. A., & Ables, G. P. (2020). Weight Loss and Concomitant Adipose Autophagy in Methionine‐Restricted Obese Mice is Not Dependent on Adiponectin or FGF21. Obesity.
A new epidemiological study published in The BMJ explores the association between eating red meat and the risk of death, specifically how risk of death can be lessened through dietary change—decreasing red meat consumption while increasing intake of healthier animal and plant-based foods. This correlates with OFAS research in rodents demonstrating that a sulfur amino acid-restricted (SAAR) diet can increase lifespan and delay onset of age-related diseases. In general, meat and other animal-based food sources have high SAA while plant-based food sources such as vegetables, legumes, whole grains, and fruits have low SAA.
The study looked to produce evidence backing previous studies showing “that higher red meat consumption, especially processed red meat, is associated with an increased risk of type 2 diabetes, cardiovascular disease, certain types of cancer, including colorectal cancer, and mortality.” Analyzing data from a cohort of 81,469 US health professionals (male and female) from a 16-year period, this study found 1) increases in red meat consumption, especially processed meat, are associated with a higher risk of death and 2) decreases in red meat consumption and simultaneous increases in healthy alternative food choices over time are associated with a lower mortality risk, further supporting the health benefits of replacing red and processed meat with healthy protein sources, whole grains, or vegetables.
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Zheng Yan, Li Yanping, Satija Ambika, Pan An, Sotos Prieto Mercedes, Rimm Eric et al. Association of changes in red meat consumption with total and cause specific mortality among US women and men: two prospective cohort studiesBMJ 2019; 365 :l2110
Human health, diet, and environmental sustainability are prevailing concerns that share many common uncertainties. Fulfilling the nutritional needs of a growing population while limiting environmental degradation is a critical challenge that requires global collaboration and commitment. Current food systems, in addition to supporting unhealthy diets and practices, greatly impact the environment, leading to climate change, biodiversity loss, freshwater misuse, interference with the global nitrogen and phosphorus cycles, and land-system change. Current global food systems are simply unable to provide the population of ~7.7 billion with healthy diets while also achieving environmental sustainability.
The EAT-Lancet Commission brings together scientists and experts from the diverse fields of human health, agriculture, political sciences, and environmental sustainability in an effort to establish global targets for healthy diets and sustainable food production. Using the best scientific evidence available, the Commission seeks a global transformation of food systemsthat will help to achieve the goals set forth in the UN Sustainable Development Goals (SDGs) and the Paris Agreement. The SDGs are global goals reduce hunger and improve nutrition. The Paris Agreement sets a budget on greenhouse gas emissions to keep the global mean temperature increase to less than 2°C.
The EAT-Lancet Commission has quantitatively characterized a universal healthy reference diet that will positively impact both human health and the environment. This healthy reference diet consists predominantly of vegetables, fruits, whole grains, legumes, and unsaturated oils; includes a low to moderate amount of seafood and poultry; and includes no or little red meat, processed meat, added sugar, refined grains, and starchy vegetables. The commission has also rendered scientific boundaries that will aid in the reduction of environmental degradation caused by food production at all scales.
At OFAS, we have spent over 25 years studying how a low-methionine diet improves lifespan and healthspan. This diet consists primarily of vegetables, fruits, whole grains, and legumes and contains limited quantities of meats, seafood, and poultry—much like the the EAT-Lancet Commission’s healthy reference diet. Thus, a low methionine diet not only provides benefit to an individual’s health but also promotes a sustainable environment.
The EAT-Lancet Commission proposes five strategies to achieve the “Great Food Transformation”.
1. Seek international and national commitment to shift towards healthy diets
2. Reorient agricultural priorities from producing large quantities of food to producing healthy food
3. Sustainably intensify food production, generating high-quality output
4. Strong and coordinated governance of land and oceans
5. At least halve food loss and waste, in line with global SDGs
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Willett, W., Rockström, J., Loken, B., Springmann, M., et.al. 2019. Food in the Anthropocene: the EAT–Lancet Commission on healthy diets from sustainable food systems. EAT-Lancet EAT–Lancet Commission on healthy diets from sustainable food systems DOI: 10.1016/S0140-6736(18)31788-4
Ables, G.P., and Johnson, J.E. (2017). Pleiotropic responses to methionine restriction. Exp Gerontol 94, 83-88.
Did you know that kidney disease is one of the major causes of early mortality, morbidity, and rising medical costs in the United States? Now, more than ever, it is crucial to find a way to delay or avoid this devastating disease. OFAS and other researchers have proven that methionine restriction extends the lifespan of several species, and although studies have been conducted on various rodent organs, the effects of MR on kidneys are not well known. A study conducted by the Orentreich Foundation’s Associate Science Director, Dr. Gene Ables, has shown that MR reduced the effects of kidney injury by suppressing inflammation and fibrosis mechanisms. This, in turn, delays the progression of kidney disease.
When protein is ingested, protein waste products are created. Healthy kidneys have millions of nephrons that filter this waste, which then leaves the body in urine. Unhealthy kidneys lose the ability to remove protein waste, and it starts to build up in the blood. One way to prevent this is by putting patients with chronic kidney disease on low-protein diets. Methionine restrictive diets offer the alternative of simulating a low-protein diet without actually reducing overall protein intake, which is done through the increased consumption of plant-based foods instead of animal-based foods. It is recommended that future studies that investigate the effects of MR on kidney function should be done with older mice in order to include the effects of age and provide more insight.
FASEB J. 2017 Oct.
Methionine restriction (MR) extends the lifespan across several species, such as rodents, fruit flies, roundworms, and yeast. MR studies have been conducted on various rodent organs, such as liver, adipose tissue, heart, bones, and skeletal muscle, to elucidate its benefits to the healthspan; however, studies of the direct effect of MR on kidneys are lacking. To investigate the renal effects of MR, we used young and aged unilateral nephrectomized and 5/6 nephrectomized (5/6Nx) mice. Our studies indicated that MR mice experienced polydipsia and polyuria compared with control-fed counterparts. Urine albumin, creatinine, albumin-to-creatinine ratio, sulfur amino acids, and electrolytes were reduced in MR mice. Kidneys of MR mice up-regulated genes that are involved in ion transport, such as Aqp2, Scnn1a, and Slc6a19, which indicated a response to maintain osmotic balance. In addition, we identified renoprotective biomarkers that are affected by MR, such as clusterin and cystatin C. Of importance, MR attenuated kidney injury in 5/6Nx mice by down-regulating inflammation and fibrosis mechanisms. Thus, our studies in mice show the important role of kidneys during MR in maintaining osmotic homeostasis. Moreover, our studies also show that the MR diet delays the progression of kidney disease.—Cooke, D., Ouattara, A., Ables, G. P. Dietary methionine restriction modulates renal response and attenuates kidney injury in mice.