Methionine: Good or Bad? Implications for Future Research on Longevity, Oxidative Stress

Methionine is an amino acid that is essential for many metabolic processes in the body. Typically, you get methionine for protein sources of food, so most people eating balanced diets get enough of it. However, there has been some previous debate about whether or not restricting your methionine levels in the body will be beneficial for longevity. What's the best way to balance this? Are there optimal levels? What should people who generally eat a lot of protein do?

As a brief introduction, methionine is involved in several physiological processes:

  • S-adenosylmethionine (SAM), which is a methionine carrier, is involved in the immune system, in structural components of the cell membranes, and in metabolism, especially metabolism of neurotransmitters including serotonin, dopamine and melatonin. SAM is heavily involved in DNA methylation, which is important for normal development with respect to DNA imprinting, X-chromosome inactivation, and healthy regulation of DNA transcription.

  • antioxidant: L-methionine can act as an antioxidant, for example, in the prevention of urinary tract infections, by acidifying urine so that bacteria including E. coli cannot survive.1

However, there has been a growing amount of interest and science suggesting that restricting methionine levels in the body may lead to increased longevity. Below, we review current research on methionine sources, benefits of methionine restriction, and dietary balances regarding methionine.

Sources of Methionine

Methionine is an amino acid, and you would get it from foods that have protein. Regarding specific foods, the most prominent metionine sources are cheese, milk and tuna.

methionine_protein

Amount of methionine (mg methionine per 100 g of food) in various sources.

If you're a bodybuilder or athlete, you may consume protein supplements in your diet, and thus be interested in methionine content in these protein supplements. Unfortunately very little data is out there measuring specific amounts of methionine in protein supplements. In general, casein protein supplements contain about 25g methionine per kg of caseine, and whey protein supplements contain about 19 g methionine per kg of whey.2

Benefits of Methionine Restriction

Previously, it has been suggested that restricting methionine in the diet may lead to an improved metabolic profile.3

One study showed that a 40% decrease in methionine intake led to a decrease in production of reactive oxygen species in the liver.4IN the study, there was nearly a 60% reduction in various markers of protein lipoxidation (the process of breaking down key proteins) in the liver, in animals undergoing 80% decrease in methionine intake.

methionine_restrict_40pct_80pct It seems that restriction of methionine by up to 80% is beneficial for decreasing levels of oxidative, glycoxidative and lipoxidative damage in liver mitochondria. GSA: glutamic semialdehyde; AASA: aminoadipic semialdehyde, CEL: carboxyethyl-lysine, CML: carboxymethyl-lysine, MDAL: malondialdehyde-lysine.

Since the generation of free radicals by mitochondria is generally believed to be a major contributor to aging (and associated cell damage), it is promising to see studies demonstrating an effect of methionine restriction on longevity. A study in mice showed that there was a 7% increase in lifespan associated with a methionine-restricted diet.5

methionine_restrict_7pct_increase_longevity A methionine-restricted diet was shown to result in roughly a 7% increase in lifespan in mice.

One of the reasons excess methionine may be undesired for humans is that it may lead to increased levels of homocysteine, which may lead to liver toxicity.6,7,8One study found that in rats, either composing a diet mostly of whey protein, or supplementing a diet with whey protein, would lead to increased S-adenosylmethionine (SAM) levels but would not lead to significantly increased levels homocysteine (P>0.05). ^deminice-2014-whey-protein-increase-methionine-no-increase-homocysteine]

Warning: Evidence Not Well Substantiated in Humans

Despite the growing (but small) amount of evidence in animals, this postulation of methionine restriction being beneficial for humans, has not been rigorously tested in human studies. While there are studies on general protein restriction, there has not been a great amount of dedicated research on methionine restriction in humans. Future research should make greater efforts to understand this topic more, as the research in animals is promising.

Editorial Opinion

Most of the studies involving methionine reduction for decreases in oxidative damage / improvements in longevity, are done in animals. While the results are promising, there definitely needs to be more work done in humans, in order to fully round out the thesis that decreasing methionine is beneficial for long-term effects. While we don't recommend methionine-restricted diets at this time, this area of research is definitely worth paying attention to, going into the future.

  1. Luo, S., & Levine, R. L. (2009). Methionine in proteins defends against oxidative stress. The FASEB Journal, 23(2), 464-472.

  2. Wakfer, P. Methionine content of foods. [Online, accessed Nov 13, 2016]: http://morelife.org/food/methioninecomparison.html

  3. Sanchez-Roman, I., & Barja, G. (2013). Regulation of longevity and oxidative stress by nutritional interventions: role of methionine restriction. Experimental gerontology, 48(10), 1030-1042.

  4. Caro, P., Gómez, J., López-Torres, M., Sánchez, I., Naudí, A., Jove, M., ... & Barja, G. (2008). Forty percent and eighty percent methionine restriction decrease mitochondrial ROS generation and oxidative stress in rat liver. Biogerontology, 9(3), 183-196.

  5. Sun, L., Akha, A. A. S., Miller, R. A., & Harper, J. M. (2009). Life-span extension in mice by preweaning food restriction and by methionine restriction in middle age. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, glp051. Chicago

  6. Deminice, R., Comparotto, H., & Jordao, A. A. (2014). Whey protein supplementation increases methionine intake but not homocysteine plasma concentration in rats. Applied Physiology, Nutrition, and Metabolism, 40(1), 46-50.

  7. Holstein, J. H., Schmalenbach, J., Herrmann, M., Ölkü, I., Garcia, P., Histing, T., ... & Claes, L. (2012). Excess dietary methionine does not affect fracture healing in mice. Medical science monitor: international medical journal of experimental and clinical research, 18(12), BR469.

  8. Meng, B., Gao, W., Wei, J., Yang, J., Wu, J., Pu, L., & Guo, C. (2013). Quercetin reduces serum homocysteine level in rats fed a methionine-enriched diet. Nutrition, 29(4), 661-666.

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