Calorie restriction is well documented as the gold standard in terms of minimizing disease risk and maximizing longevity in almost every organism tested-worms, flies, mice, rats, dogs and monkeys. However, eating 10-30% less calories than usual is a difficult task for most people, as evidenced by the continuous rise in global obesity. But, there may be a way to reap the benefits of a calorie restricted diet without actually eating less calories, one that involves eating less methionine.
Methionine is one of the 20 essential amino acids, meaning that the human body cannot synthesize it, and therefore, it must be supplied by the diet. As shown below, a 5.5-fold restriction in dietary methionine (0.17% of total calories compared with 0.86%) without any other dietary changes (in rats) has been shown to increase average lifespan by ~20%, and maximal lifespan by 12% (Orentreich et al. 1993). Translated into human lifespan, a 20% increase would equate to an average lifespan from 75 to 90 years and a maximal lifespan from 122 to 134 years!
More importantly, food intake when normalized to body weight was greater in methionine-restricted animals, evidence that indicates that the lifespan extending effect was not due to a reduction in calories.
In other words, the methionine-restricted rats ate more than rats on the normal diet, but, these calories were not deposited as fat (or muscle), but burned as heat. This concept, of an increase in heat production (as opposed to energy production) is known as uncoupling, and has also been shown to be associated with an increased lifespan (Speakman et al. 2004). Furthermore, dietary methionine restriction has been shown to increase uncoupling (Hasek et al. 2010), and may be playing a part in the observed extended lifespan shown by Orentreich et al. (1993).
So how can we incorporate methionine restriction into our every day diet? The easy answer would be to reduce overall protein intake. For example, a diet that included a 4-egg white omelet for breakfast, a tuna sandwich for lunch, and a relatively lean (85-15, protein-fat) burger for dinner would contain a total of ~75 grams of protein and ~2.1 grams of methionine (based on the methionine content list as reported by McCarty et al. 2009) . Replacing these protein (and methionine) rich sources with an equivalent amount of calories (80 calories, egg whites; 170 calories, tuna; 250 calories beef) with whole wheat pasta (500 calories, or any other grain) reduces the overall protein intake to 24 grams, with ~300 mg (0.3 grams) of methionine. As you can see, elimination of egg/fish/meat reduces the methionine content by 7-fold, and, may be feasible in humans as a means for increasing lifespan.
My 7-day average protein intake is shown below. Within that, my average methionine intake is 0.8g/day. However, it is important to note that the nutrient-tracking software that I use (cronometer.com) for some reason doesn’t have the amino acid breakdown for my daily can of sardines, which adds 0.6 g of methionine. In total, I consume on average, 0.8 g + 0.6 g = 1.4 daily grams of methionine. Each gram of protein contains 4 calories. Therefore, my daily methionine intake =1.4*4 = 5.6 calories. My average calorie intake during that 7-day period was 2241 calories. 5.6/2241 *100 = 0.25%, which puts me closer to the 0.17% long-lived diet than to the shorter-lived 0.86% of Orentreich et al. 1993.
Hasek BE, Stewart LK, Henagan TM, Boudreau A, Lenard NR, Black C, Shin J, Huypens P, Malloy VL, Plaisance EP, Krajcik RA, Orentreich N, Gettys TW. Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states. Am J Physiol Regul Integr Comp Physiol. 2010 Sep;299(3):R728-39.
McCarty MF, Barroso-Aranda J, Contreras F. The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. Med Hypotheses. 2009 Feb;72(2):125-8.
Orentreich N, Matias JR, DeFelice A, Zimmerman JA. Low methionine ingestion by rats extends life span. J Nutr. 1993 Feb;123(2):269-74.