Chapter 187
Lower Methionine Intake
Restricting just this one amino acid can increase the maximum lifespan of rats by up to 44 percent, which is more than what is typically achieved with calorie restriction. Methionine restriction also extends the maximum lifespan of mice, increases stress resistance, reduces visceral fat, and slows the aging of the eyes and the immune system. The exact mechanisms by which lowering the methionine content of the diet leads to a slowing of the aging process are not known, but methionine restriction drives FGF21 up, initiates autophagy, and reduces inflammation and IGF-1. The IGF-1 pathway could be decisive, because mice with defects in growth hormone signaling do not respond to methionine restriction, but there are other possibilities as well.
In studies in which animals were fed excessive amounts of various amino acids, methionine was always the most toxic. Perhaps because methionine has a pro-oxidative effect. When rodents are given additional methionine, that leads to an increase in markers of oxidative stress in the blood and a depletion of antioxidants in the tissue. Conversely, reducing methionine intake leads to a marked reduction in the formation of free radicals in the mitochondria and oxidative damage to mitochondrial DNA, which is consistent with the mitochondrial theory of aging. This is the only amino acid for which this effect has ever been demonstrated. You can reduce any other amino acid, but with the exception of methionine, this effect cannot be replicated with any of them.
Among amino acids, methionine is also one of those most susceptible to oxidation. When it oxidizes while embedded in a protein, that can lead to loss of protein function. Fortunately, there is an enzyme—methionine sulfoxide reductase—that repairs this damage and protects cells from methionine-related oxidative damage. Animals that were genetically modified to overexpress this methionine detoxification enzyme lived especially long.
A slight restriction of protein synthesis rejuvenated senescent cells and enabled “zombie cells” to grow again. This was demonstrated in vitro with a drug called cycloheximide, which blocks a final translation step in protein formation. The researchers conclude: “It is desirable to find a substitute for cycloheximide … to bring about a holistic health-promoting effect and reduce excessive or unnecessary synthesizing of protein … ” The same effect is achieved through methionine restriction, because methionine serves as the start codon for the translation of most proteins. In fact, reducing the methionine concentration in a cell culture can lead to an extension of the replicative lifespan of human cells by 60 to 75 percent, the Hayflick limit, the number of cell divisions a cell can undergo before it becomes senescent. In addition, cells under methionine restriction are far more resistant to various stressors, such as heat, radiation, carcinogens, and free radicals.
Lower Methionine Intake
Pharmaceutical companies are competing to be the first to bring a drug to market that lowers methionine levels—for example, methionine-munching enzymes for patients with advanced cancer. But because methionine mainly comes from the diet, the better strategy would be to lower methionine levels by reducing intake. There are three ways to achieve that. The first is calorie restriction—if you eat less overall, you also reduce your methionine intake. For example, the purported life-extending effect of alternate-day fasting has been attributed to the periodic drop in the “pro-aging amino acid methionine.” The second way: Since methionine is contained in protein, instead of eating less overall, one could simply consume less protein. If you simply dial back protein intake from today’s customary excessive amounts to the recommended level, major improvements in health are likely to occur. The third way: Even if you change nothing about the amount of food and protein, you can achieve methionine restriction by switching from animal protein sources to plant-based ones, which usually contain relatively little methionine. A review of the impact of protein intake on health and longevity concluded that in order to reduce methionine, one probably should “eat fewer animal foods.”
One of the universal hallmarks of cancer is the so-called Hoffman effect, “methionine addiction.” The dependence of cancer cells on methionine led to attempts to feed cancer patients a methionine-free “amino acid-modified medical food powder.” It consists mainly of corn syrup, oil, and all the other amino acids and is intended to displace methionine sources in normal daily food. The problem, however, is that it “doesn’t taste good,” so hardly anyone sticks with it. The unpopularity of such mixtures stirred together from oil and corn syrup has led some researchers to conclude that it is “necessary to develop palatable foods from which methionine has been selectively removed.” We already have something like that. It’s called fruits and vegetables.
Where Is Methionine Found?
Plant-based eating could “make methionine restriction practical as a strategy for life extension.” The graphic compares the bioavailable methionine content in some selected common plant and animal foods:
As you can see, fish and poultry tend to have the highest methionine content. I used canned tuna as a stand-in, but 100 calories of haddock, halibut, or orange roughy can yield even nastier numbers, namely up to 709 milligrams. The lowest methionine content among seafood is found in oysters, with lows of only 92 milligrams. For the “poultry” bar, I depicted grilled chicken breast, but fried chicken breast can also reach up to 587 milligrams.
Dairy, red meat, and eggs contain less methionine. I used hard-boiled eggs, but an egg-white-only omelet could land at the very top of the rankings with 714 milligrams. As a representative for red meat, I used ground beef, but pork and lamb can reach 509 and 564 milligrams, respectively (though blood sausage ranks low at 49). For the “dairy” bar I used milk, even though a dairy product like butter contains almost no methionine, since it is nearly pure fat. In contrast, a protein-rich dairy product like low-fat cottage cheese can reach 482 milligrams.
The foods with the least methionine are mostly fruits, nuts, vegetables, grains, and beans. Here I used canned chickpeas, but all other beans have similar values; even the “methionine-rich” legume, the kidney bean, comes in at 65. Only when plant protein is concentrated in a food like tofu can it rise to 114. For grains I used whole-wheat bread, but proso millet, the most methionine-rich grain, has 99, followed by quinoa with 64. For the “nuts” bar I used mixed nuts. There are no major differences, with the exception of the Brazil nut, which has 136 milligrams. Hemp seeds are also quite high, at 135. For vegetables I used carrots. Spinach is surprisingly high at 184 milligrams, but it has so few calories that you have to eat about 15 cups of it to get to 100 calories. Kale is lower, with 66 milligrams of methionine at 14 cups. For fruit I used bananas, but even oranges, the common fruit with the highest methionine content, contains on average only 34 milligrams.
Achievable Methionine Restriction
Bottom line: A review of methionine restriction for life extension concluded: “In humans, methionine restriction can be achieved through a predominantly vegan diet.” Even with the same protein intake, vegetarians consume up to 36 percent less methionine. But because of the methionine content of eggs and dairy products, only vegans have significantly lower methionine levels in the blood.