The Low-Methionine Theory

"He who does not know food, how can he understand the diseases of man?" ~Hippocrates

Caloric restriction has been a hot topic in my course on “Aging” this past week, as it is a scientifically-proven method for prolonging life.

I also learned about another method for increasing longevity, and it has to do with the amino acid methionine. Here is a summary of the presentation I gave on it today:

**Note: I apologize for the technical nature of this post... if not interested in minutiae, please jump to the end for the short summary!**

 Food with a high methionine content

 Food with a low methionine content

What is methionine? 

• An essential amino acid
• One of two sulfur containing amino acids
• In the metabolic pathway of S-adenosyl methionine (SAM) and homocysteine
• An intermediate in the biosynthesis of cysteine, carnitine, taurine, lecithin, phosphatidylcholine, and other phospohlipids
• Most fruits, vegetables, and legumes contain very little methionine
• Meats, fish, eggs, and some plant seeds have high levels of methionine

Methionine-restriction and longevity:
This study from 1993 showed that cutting dietary methionine by 80% in rats increased longevity by greater than 40% in both mean and maximal lifespan. The rats had free access to food and ended up eating more calories per gram of body weight. They were not calorie-restricted.

More recently, other researchers have confirmed these results and found that methionine-restricted mice (with normal calorie intake) had:

• Lower levels of IGF-1, insulin, glucose, and thyroid hormones (these changes are also found in calorically restricted animals)
• Delayed onset of clouding of the lens in the eye (cataracts)
• Delayed immune system changes (changes in T cell subsets)
• Livers more resistant to oxidative stress
• Decreased levels of mitochondrial oxidative damage

Potential mechanisms:
The following mechanisms have been suggested to explain these longevity findings from low-methionine diets:

1. Endocrine changes including decreased IGF-1, T4, glucose, and insulin (all of which are important in the aging process)
2. Hormesis (chronic low levels of stress builds “immunity” against bigger stressors)
3. Changes in levels of s-adenosyl methionine (SAM) and homocysteine (thought to play a role in neoplastic, cardiovascular, and other aging-related diseases)
4. Changes in glutathione (glutathione is protective against oxidative damage) 
5. General decline in protein synthesis (may be protective against age-related decline)

What I really want to know is, what happens to caloric-restricted animals when you supplement methionine levels? Does that diminish any of the longevity benefits? Calorie-restrictors cut their methionine intake simply by eating fewer calories...  what if the longevity benefit is coming from the methionine-restriction rather than calorie-restriction?

What might this mean for humans?
The vegan diet (which includes no animal products) is low in methionine. Here is why:

• The methionine content of plant proteins, legumes, soy, and nuts is lower than in animal proteins
• The overall protein content of plant-derived foods is lower than animal-derived foods
• Plant proteins are digested less efficiently than animal proteins

Studies on vegans provide some evidence for increased longevity:

• Vegans have lower IGF-1 levels (suggested to be a “pacesetter” in the aging process”)
• Vegans have lower insulin levels (lower insulin levels leads to lower levels of IGF-1)
• Vegans have lower rates of diseases of aging, including cancer, diabetes, and cardiovascular disease

Summary:

• A low-methionine diet in animal models has been proven to delay the aging process
• Vegan diets are low in methionine, and human studies on vegans provide some evidence for increased longevity in this population
• There are many remaining questions, and some of mine include: Calorie-restriction versus methionine-restriction – are they additive? What is the impact of methionine-restriction on fertility? How does methionine-restriction impact telomere length/telomerase activity? 

This longevity theory makes the vegan diet even more attractive... adding to the ethical, environmental, and health benefits that are already known.

I am curious about what the Calorie Restriction Society would think about this. Are there any Methionine-Restriction Societies? This idea of methionine-restriction might be something The Vegan Society could discuss/advertise.