The methionine restriction showing 7% median male lifespan increase was done at U Michigan and co-authored by Richard Miller, while the isoleucine restriction study showing 33% median increase in males was done by the Lamming lab and used the same stock of mice that the ITP uses, making these lifespan results only slightly less robust than those of the ITP and its three replicates.

If you take the ITP results seriously (as most of us in this space do) the implication of these studies is clear: even normal levels of protein accelerate aging. Attia clearly takes the ITP results seriously, so his reasoning is inconsistent when he recommends high protein diets.

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I guess mixing rice protein and collagen could be an option for younger or middle age persons, if I want to restrict methionine as well as isoleucine. Later in life, there is an issue of preventing loss of muscle.

How much does glycine supplementation help to counter the detrimental effects of methionine? Is this somewhere quantified so that a comparison with methionine restriction can be made?

I can’t put words in his mouth, but I think that’s because mice are not humans, and most humans don’t really want to be extremely frail and sarcopenic from calorie restriction. Plus, all the other benefits of having extra skeletal muscle. I also can’t imagine any practical way in which a functional, aging, human being can restrict single amino acids from their diet without significant compromises in other areas.

IMO, a key factor is going to be why and where mTOR is stimulated. If mTOR activity is periodically/temporarily high in your quads and glutes because you did some squats, or went for a run, and you supplied protein for recovery, I really find it hard to believe that is detrimental for lifespan. But if mTOR is high because you’re in a chronic calorie surplus, I find it very easy to believe that is detrimental for lifespan.

So for me, I try to eat around maintenance calories, with reasonably high protein, combined with strength training. Based on my logic, that shuttles the calories and protein into muscle tissue. I take the Rapamycin weekly, along with a ~24h water-only fast. I am imagining that this will have the effects of autophagy etc as a longer fast, without the muscle loss.

Supposedly soon we have a study from Brad Stanfield about whether Rapamycin in humans actually affects muscle growth, so we shall see!

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For methionine restriction extending lifespan in mice:

Miller et al. (2005) published in Aging Cell showing that methionine restriction (reducing dietary methionine to ~20% of normal) extended median and maximum lifespan in mice by approximately 30%. This pioneering study established methionine restriction as a powerful dietary intervention.

Methionine‐deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF‐I and insulin levels, and increases hepatocyte MIF levels and stress resistance - PMC

For glycine supplementation extending lifespan:

Miller et al. (2019) in Aging Cell reported that within the ITP: 8% glycine supplementation in mice extended median lifespan by 5.8% and maximum lifespan by 4.4% - while this is less than the ~30% I mentioned earlier, it’s significant for a single amino acid supplement.

Methionine restriction has consistently shown 20-40% lifespan extension across multiple studies, the glycine supplementation data is still emerging. The strongest evidence for glycine’s benefits seems to come from its ability to restore normal lifespan in mice fed high-methionine diets and its consistent improvement in healthspan markers.

Glycine supplementation operates through complementary mechanisms to methionine restriction by improving the clearance of methionine metabolites, leading to similar metabolic benefits. However, the magnitude of lifespan extension with glycine alone appears to be more modest than with methionine restriction based on current evidence.

Restricting methionine over many years is not something I can consider. Adding glycine is easier but might be less rewarding. But I already add glycine to my diet. Converting the human dose of glycine at in a diet of 6% glycine for a 75 kg human can be calculated as (Using AI):

  1. Determine total daily caloric intake for a 75 kg human,.

For moderate activity: 30-35 calories per kg body weight

For a 75 kg person: 75 × 30-35 = 2,250-2,625 calories per day

Let’s use 2,400 calories as our working value

  1. Calculate 6% of total calories

6% of 2,400 calories = 0.06 × 2,400 = 144 calories from glycine

  1. Convert calories to grams of glycine

Glycine provides 4 calories per gram (like all amino acids)

Therefore: 144 calories ÷ 4 calories/gram = 36 grams of glycine per day

Compare to other dosing approaches

This calculation gives us 36 grams of glycine per day for a 75 kg human to match 6% of caloric intake used in animal studies. This is notably higher than what’s typically used in human research.

Why the discrepancy? There are several key considerations:

  • Caloric density differences: Mice typically consume relatively more calories per unit of body weight than humans (they have higher metabolic rates)

  • Bioavailability: Glycine absorption efficiency may differ between species

  • Metabolic scaling: the body surface area scaling factor means that doses don’t translate directly

Our calculation showing 36 grams, but human studies have shown benefits with much lower doses:

Clinical studies: 3-15 grams per day

Metabolic benefits: Often seen at 10-12 grams per day

Upper practical limit: Most researchers don’t go above 20 grams per day

The calculation suggests 36 grams to precisely match the animal study proportion, the practical human dose would be less:

5-10 grams per day, if that is ok then maybe increase to 15-20 grams per day if desired and well-tolerated. Maybe split into 2-3 doses throughout the day.

This discrepancy highlights why direct translation from animal studies to human doses often requires adjustment. The key principle is that glycine appears to work by correcting the methionine ratio in the diet, and humans typically need less supplementation to achieve this balance than would be predicted by direct caloric percentage conversion.

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Efficacy of High-Dose Glycine in the Treatment of Enduring Negative Symptoms of Schizophrenia | Psychiatry and Behavioral Health | JAMA Psychiatry | JAMA Network

  • Doses ranged from 30-60 grams per day
  • Established safety profile for high doses
  • While this was for psychiatric purposes, it demonstrates glycine’s safety at very high doses
  • Published in Archives of General Psychiatry

This study was only ongoing for 6 weeks but it signals that massive doses of Glycine is absorbed well without actute negative effects.

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My comment was about restricting or at the very least not consuming excessive methionine and/or isoleucine (which can be done without restricting other amino acids). I’m not sure why you’re bringing up the point about CR, as that’s something else entirely.

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yes, there is Met restriction and then Gly on a high (!) Met diet, and Met triggers mTOR quite directly while Gly removes the also detrimental Met metabolites, which is why these studies are not so informative for us, moreover since the mice are just fed certain constant diets, while I personally, and many here via Rapamycin, cycle mTOR versus AMPK days, i.e., for example, I add additional Gly after eating red meat, but on average do not have a hight Met diet. So for me for example, it is not clear that further Met restriction is going to be that much better.

Maybe I’m misunderstanding, but when you said “Attia clearly takes the ITP results seriously, so his reasoning is inconsistent when he recommends high protein diets” I assumed your comment was about high protein intake?

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