methionine restriction and longevity
This is a continuation from the previous post in which one of my readers asked about methionine restriction as it relates to longevity and methionine content in eggs. I never claim to be “the knower of the answer” but I like to provide enough information for people to form their own, and perhaps new, ideas.
As I mentioned last time an increase in metabolism will always result in an elevation of all ROS in cells. This, by default, speeds cell turnover and aging. Inversely, reduced metabolism reduces turnover and aging of cells. This is the same mechanism through which caloric restriction is theorized to promote longevity.
Restriction of any substance that is severe enough to slow down metabolism causes the mind and body to go into a torpor-like state. If it doesn’t, damage is incurred. I see this regularly in my practice as a condition that I have termed “Boulder Syndrome” which I’ve talked about in previous posts.
It seems that in order to live longer though means of dietary restriction, you have stop fully living or suffer health consequences. Take SAMe as an example. SAMe is made from methionine in the liver and acts as the rate limiting step in the production of several neurotransmitters. These include dopamine, serotonin, norepinephrine and its conversion in the brain to epinephrine. Low levels of these neurotransmitters tend to reduce mental clarity, motivation, drive and overall energy. This is likely part of the whole conservation mechanism that would naturally slow down the body in times of protein scarcity.
Eggs are so interesting because they contain all the essential nutrients to carry out Phase 1 detoxification and methylation in the liver (choline, methionine, magnesium, B12, B6 and folate). It happens that a deficiency of any one or more of these essential nutrients has a documented effect on reducing fertility. (Sorry, I just didn’t have time to find that many references for one statement but I can assure you it is a fact). As I mentioned in the previous post, this could be from some type of signaling from Phase 1 that would indicate the presence of sufficient nutients available for reproduction. I suspect that if the above nutrients are scarce, Phase 1 probably slows for the purpose of conserving them to maintain other bodily functions more consistent with survival and not reproduction.
Consider how we evolved eating eggs. In non-tropical zones, eggs are in abundance mainly in the spring and early summer. As the weather warms the insects hatch providing a sustainable protein source for birds. The increase in dietary protein, and thus methionine, in birds’ diets would signal the appropriate anabolic processes for them to become fertile and produce eggs. A few weeks later, early humans would have access to these eggs which would provide the appropriate nutrients for signaling anabolic processes to start preparing them for reproduction. Methionine moves like a wave through the food chain, from sulfur in soil to plants to insects to birds to humans, signaling the anabolic processes that enable reproduction.
In tropical zones, eggs would have been available most of the time as would an abundance of nutrients that would support reproduction. This scenario applies more to the people of the developed world.
I don’t think simple reduction of dietary methionine intake is sufficient enough to slow aging. I think it has to be fairly extreme. Alternatively, I do think that excess amounts of methionine, which would imply excess amounts of protein could be damaging especially if intake of magnesium, folic acid, B12 and B6 is insufficient. We also have to consider that if we reduce methionine enough to slow down metabolism, caloric consumption must be reduced as well or the slower metabolism will lead to weight gain.
That said, if you would still like to try to reduce your dietary methionine here are some things to consider. With regards to dietary intake, you have to look at absorption rates. This is influenced by the ratio of methionine to the other amino acids in the protein source. As a general rule, amino acids will compete with one another for absorption. For example, if you have low levels of threonine, high valine levels inhibit the absorption of methionine (Anyone want to research which protein sources have these ratios? Good data at http://www.nutritiondata.com/ ) The higher the ratios of other amino acids the lower the absorption will be of methionine. Animal proteins contain high levels of methionine but much higher ratios of the various other amino acids so ultimately methionine absorption is diminished. I checked some methionine levels in various protein sources and unfortunately got varying results. It turns out that methionine content of food is related to sulfur content in the soil so there will be significant variability depending on the geography of the food source. However as a general rule, cottage cheese, eggs and fish were all similar in methionine content. Pork and poultry were a bit higher. Beef was high but had really high levels of competing amino acids. Legumes and seeds were much lower. NOW FOR THE INTERESTING PART. It has been suggested that a vegan diet offers less methionine and would contribute to longevity through methionine restriction. However, I found a study done on amino acid absorption in rats. It turns out that pinto beans, one of the least rich protein sources of methionine, had the highest absorption rate the amino acid. I’m sure absorption of methionine from soy is low as well because some of the chemicals in soy interfere with overall amino acid absorption.
However, soy introduces an extremely important consideration that might make it impossible for humans to benefit from methionine restriction. Soy contains estrogen-mimicking phytochemicals which will have some effect on producing anabolic processes. (the exact thing we’re trying to prevent to extend longevity) These chemicals must be detoxified by Phase 1 enzymes in the liver. If this pathway is not working because of a deficiency of methionine, folic acid etc then there will be accumulation of these chemicals in the fat tissues possibly increasing incidence of hormone-sensitive cancers. There are hundreds of anabolic hormone-mimicking chemicals that are now ubiquitous in our environment including BPA, several pesticides and hormones from pharmaceutical use. Any steps taken to reduce methionine will slow detoxification of these chemicals to a trickle.
If you want to continue to think creatively, be active, fully participate in life and be able to detoxify various environmental chemicals, you have no choice but to consume foods that allow your body to do this. If you want to attempt to extend your life through the means of caloric and methionine restriction then you will spend your life existing, not fully living and you might still get cancer. Perhaps one way of using the current knowledge of caloric and methionine restriction to extend life is to follow what would naturally happen with the seasons. For example, reduce your activity in the winter and practice caloric and methionine restriction. Personally, I love skiing too much and need lots of protein to be able to do it. That said, I’m going to continue to eat 8-10 eggs per week along with lots of kale.by
One of my readers questioned my recipe from “If Popeye Was a Real Man He Would Have Eaten Kale” and asked what I thought about the research linking longevity and methionine restriction. Eggs are a significant source of methionine and so perhaps could lead to faster aging. In order to answer this question, it’s important to consider the mechanisms involved and the evolutionary advantages. This question enters one of the world’s biggest rabbit holes and is too much for one posting so watch for posts related to methionine restriction and longevity in the future.
To review, several research studies have shown that dietary restriction of the essential amino acid, methionine, results in 42-44% increase in average life span of rats, mice and fruit flies. There are two major mechanisms that have been identified that contribute to this. One is lowered production of mitochondrial reactive oxygen species (mROS). These are basically free radicals produced in the mitochondria where our cells make energy or ATP. mROS speed up degeneration of mitochondrial DNA, ultimately leading to faster cell turnover and aging. Glutathione (GSH), is one of the most powerful reducers of mROS. GSH is made from methionine. However, restricting methionine intake results in elevated levels of GSH in all tissues except for the kidneys. How is it that restricting methionine, the one essential amino acid that is a precursor to glutathione, results in higher levels of glutathione? It’s going to be very interesting when researchers figure out the answer to the dichotomy.
With regards to longevity, I think methionine restriction has two contributing factors. I’ll discuss one of them here and leave the second for another time. Here is the first:
Since methionine is an essential amino acid and is present in all naturally-occurring protein sources, it likely acts as a signal for protein abundance or scarcity. Cellular signaling mechanisms are too involved for this discussion. To simplify I’ll just say signaling may directly due to the presence or absence of methionine or may be through a secondary metabolite like homocysteine. If its presence signals abundance, then the body would increase metabolism as it goes into an anabolic state preparing for reproduction. An increase in metabolism will always result in an elevation of all ROS in cells. This, by default, speeds cell turnover and aging. On the other hand, if protein intake, and thus methionine, is scarce then the body likely creates different signals that reduce metabolism. Reduced metabolism reduces turnover and aging of cells. This is the same mechanism through which caloric restriction is theorized to promote longevity.
With methionine, this control mechanism would incur an ultimate evolutionary survival advantage. We know that methionine restriction reduces fecundity (reproductive ability). During times of protein scarcity reduced metabolism via this signaling mechanism would minimize ongoing damage to mitochondrial and cellular DNA. This would help to preserve the potential for successful reproduction (passing on of genes) and to prolong existence in anticipation for a more abundant and auspicious time. As mentioned, in times of protein abundance, methionine would signal anabolism and preparation for reproduction. If an individual is past reproductive age, metabolism will still increase. In a community setting the increased vitality of older individuals would allow them to contribute more in the short term. In this situation, survival advantage would be incurred throught The Grandmother Hypothesis . It would also speed its ultimate demise, freeing up resources for the younger individuals who can still reproduce.
Since we, in the first world, live in a state of perpetual abundance we have time to figure out how we can live longer. Restricting dietary methionine may likely contribute to this. It seems logical that you would simply restrict foods that contain high amounts of methionine. However, it isn’t that straight forward. Next time I will discuss the glutathione dichotomy and methionine’s role in the alternation between Phase 1 and Phase 2 liver detoxification, the intricacies of dietary amino acid absorption, and research that contradicts the hypothesis that a vegan diet reduces methionine intake. Yes, the egg question will finally be answered.by