27 replies to this topic

[InquilineKea]

So now it appears that leucine is bad too. And... almost ALL the legumes (black beans, lentils, soybeans, etc) are VERY high in leucine (the leucine content is higher than the content for most of the other amino acids). Even quinoa is comparatively high in leucine.

So now what? Am I screwed?

Ugh, even oatmeal. http://nutritiondata...-cereals/1598/2

From the CR Society Mailing List:

The below paper is not pdf-availed (free full-text?) for 3 months.


Leucine Deprivation Increases Hepatic Insulin Sensitivity via GCN2/mTOR/S6K1 and AMPK Pathways.
Xiao F, Huang Z, Li H, Yu J, Wang C, Chen S, Meng Q, Cheng Y, Gao X, Li J, Liu Y, Guo F.
Diabetes. 2011 Mar;60(3):746-56. Epub 2011 Jan 31.
PMID: 21282364

Abstract

OBJECTIVE

We have previously shown that serum insulin levels decrease threefold and blood glucose levels remain normal in mice fed a leucine-deficient diet, suggesting increased insulin sensitivity. The goal of the current study is to investigate this possibility and elucidate the underlying cellular mechanisms.

RESEARCH DESIGN AND METHODS

Changes in metabolic parameters and expression of genes and proteins involved in regulation of insulin sensitivity were analyzed in mice, human HepG2 cells, and mouse primary hepatocytes under leucine deprivation.

RESULTS

We show that leucine deprivation improves hepatic insulin sensitivity by sequentially activating general control nonderepressible (GCN)2 and decreasing mammalian target of rapamycin/S6K1 signaling. In addition, we show that activation of AMP-activated protein kinase also contributes to leucine deprivation-increased hepatic insulin sensitivity. Finally, we show that leucine deprivation improves insulin sensitivity under insulin-resistant conditions.

CONCLUSIONS

This study describes mechanisms underlying increased hepatic insulin sensitivity under leucine deprivation. Furthermore, we demonstrate a novel function for GCN2 in the regulation of insulin sensitivity. These observations provide a rationale for short-term dietary restriction of leucine for the treatment of insulin resistance and associated metabolic diseases.

-- Al Pater, alpater@SHAW.ca

Thanks for this important reminder, Al, about how leucine stimulates mTOR.
Although this has been discussed in the past, I imagine there are a fair
number of new Society members who haven't seen research on the mTOR-leucine
theme and make want to rethink their intake of foods like whey that are high
in leucine.

http://www.crsociety...8508#msg-198508

Edited by InquilineKea, 08 March 2011 - 08:02 PM.

[Skötkonung]

Go ahead and try and restrict your protein some more.. guess what will happen? Increased age related muscle wasting. No thanks!

Potential Importance of Leucine in Treatment of Obesity and the Metabolic Syndrome
"Leucine is known to interact with the insulin signaling pathway to stimulate downstream signal control of protein synthesis, resulting in maintenance of muscle protein during periods of restricted energy intake. Leucine also appears to modulate insulin signaling and glucose use by skeletal muscle. Whereas total protein is important in providing substrates for gluconeogenesis, leucine appears to regulate oxidative use of glucose by skeletal muscle through stimulation of glucose recycling via the glucose-alanine cycle. These mechanisms produce protein sparing and provide a stable glucose environment with low insulin responses during energy-restricted periods."

A leucine-supplemented diet restores the defective postprandial inhibition of proteasome-dependent proteolysis in aged rat skeletal muscle

Increasing Dietary Leucine Intake Reduces Diet-Induced Obesity and Improves Glucose and Cholesterol Metabolism in Mice via Multimechanisms
"Leucine supplementation decreases diet-induced obesity by increasing resting energy expenditure associated with increased UCP3 expression in thermogenic tissues. Leucine supplementation improves glucose metabolism, reduces diet-induced insulin resistance, and lowers plasma glucagon levels and hepatic glucose-6-phosphatase expression. Leucine supplementation reduces diet-induced hypercholesterolemia independent of adiposity."

Getting adequate amounts of essential amino acids is very important. Without adequate complete protein, glutathione falls (an endogenous antioxidant) and oxidative stress increases. Instead of trying to starve yourself of an amino acid essential to proper function of your body, why not simply try and keep your protein intake at a normal level for your bodyweight (1g/kg)? If you're already calorically restricted, it is likely that your protein intake respective to your bodyweight is already quite low. Lowering it further presents a danger.

[platypus]

Isn't leucine the most anabolic (muscle building) of all amino-acids? Just adding it to the standard diet can build more muscle.

[yoyo]

does anyone know what "glucose recycling via the glucose-alanine cycle" is?

[sthira]

Paul McGlothin in that thread you posted writes: "...the promotion of whey as an anabolic stimulant is what I call “The strong today, gone tomorrow diet.”.

He expands that theme with: "Some here think it is a good idea to stimulate IGF-I secretion with extra protein (which likely also means activating mTOR). They hope for bone growth and maintenance of muscle strength. If such a strategy could magically direct growth activities to specific areas like bone and muscle, that might be a viable idea. It’s too bad, but increasing whole body IGF-I probably hits the IGF-I hot spots the most – prostate, breast, ovaries, etc, where IGF-I receptors are in high concentration."

FWIW, I eat lentils - they seem lower on the leucine list than, say, watercress - which I gobble with abandon. The highest overall leucine foods seem to be meat, dairy, fish, soy products. Egg whites are highest off all, as I'm sure you know. I share Skot's opinion to keep overall protein intake at RDAish levels on CR. Although for me, that's a challenge since I eat a veg diet naturally low. Oddly, in my blood test protein levels appear normal - smack in the middle of the range, actually. Anecdotes-schmanicdotes.

[InquilineKea]

FWIW, I eat lentils - they seem lower on the leucine list than, say, watercress - which I gobble with abandon. The highest overall leucine foods seem to be meat, dairy, fish, soy products. Egg whites are highest off all, as I'm sure you know. I share Skot's opinion to keep overall protein intake at RDAish levels on CR. Although for me, that's a challenge since I eat a veg diet naturally low. Oddly, in my blood test protein levels appear normal - smack in the middle of the range, actually. Anecdotes-schmanicdotes.

Hm interesting - I went to that nutritiondata site and saw the data for lentils. It was quite frightening. Lentils contain more leucine than any other amino acid (other than the super-common glutamatic acid IIRC) - at least 500 mg leucine per serving.

Wow, which proteins did you get tested on?

==

PS: does anyone know if creatine also stimulates IGF-1? It seems to be anabolic, and I take it because it supposedly boosts IQ in vegans.

Edited by InquilineKea, 09 March 2011 - 03:56 AM.

[sthira]

Well, we gotta eat something. I mean, all foods have up and downside risk. I guess part of what all of us are doing here is attempting to minimize risk - to do what's best to the best of our incoming knowledge and as often as possible.

From a low leucine/methionine perspective, lentils look quite good to me. I eat them with quinoa, barley, fava beans - I hope for the best. If you were swallowing egg whites with every meal, then you might worry. Or protein isolates...

My blood test for protein was "Total protein: 7.4 g/dL (range 6.1-7.9)". Weird to me that result. Clearly my body is working something out.

[InquilineKea]

That's true. We do have to eat something. We just have to eat whatever happens to be least evil.

Hm, as for lentils, you get this: http://nutritiondata...roducts/4338/2. Wow, actually 1295 mg/serving, which is quite high. Hm I should look up the other grains you eat. Barley has 1055 mg/serving (ugh). Quinoa has 483 mg/serving, which is better though. What's the GI of Quinoa?

Fava beans has ~1000 mg/serving.

Oh I see. Hm, doesn't the body always find a way to compensate if your levels are too low or to high? Is it sort of like sodium or potassium, in which case the body does a REALLY good job at keeping the levels at a narrow range?

[sthira]

One thing I'm learning here is to not get too married to any one study or set of studies. Just when I get confident X is evil, don't do X, along comes contrary evidence. Not in every case, of course: trans fats, excess sodium, excess protein/carbs/fats. Hell, excess kale I'm sure is evil.

So it goes with leucine restriction. Recent evidence seems to suggest lowering intake of the stuff may be less evil. But damn, leucine is ubiquitous in protein, so the best method to lower it is to just cut your protein intake. But that has problems, too. And, the next study may point in the opposite leucinic way.

[Lufega]

Sure, Leucine is very insulinogenic. In fact, this is why milk raises insulin levels so much. It doesn't make it bad though. This is not a real problem is you adjust for other insulin elevating foods. Leucine IS the amino acid in food that triggers muscle synthesis and it's important for a bunch of other stuff. I added 20 grams a day a couple of weeks ago with additional BCAA's and I'm seeing impressive results at the gym where before I saw none.

[capsun]

Don't restrict leucine. It (along with the other BCAA's) increased mean lifespan in mice. The result was likely due to increased mitochondrial biogenesis. So you see, it is a two-way street. Leucine provides positive benefits. So what if it activates mTOR? Forget about it. There are other methods to inhibit it again.

Methionine restriction is more effective and also probably easier. But the idea is that you only restrict *one* amino acid (and not too much) while supplying plenty (even more than normal) amounts of the other amino acids. And don't ever restrict anything to the point where your erythrocyte glutathione levels start dropping (they should actually increase).

[Michael]

So now it appears that leucine is bad too. And... almost ALL the legumes (black beans, lentils, soybeans, etc) are VERY high in leucine (the leucine content is higher than the content for most of the other amino acids). Even quinoa is comparatively high in leucine.

As already posted on CR Society, You seem to have missed or misunderstood the import of the links provided previously by Al Pater and me. Lists that describe a food as "high in nutrient X" have to be taken with extreme caution. The issue is, "high by what standard?" As you note, nearly all protein-rich foods (itself a relative term) contain large amounts of leucine, which is exactly why the molecular machinery of the cell uses it as the primary sensor to activate mRNA translation via mTOR and initiate protein synthesis: if there's leucine coming down the pipes, it's a sign that there's protein available. Obviously, crystalline fructose is low in leucine, because it contains no protein, but that isn't a relevant test. The relevant standard here is to derive your protein from foods that are low in leucine (and, I would add, methionine and cysteine) per unit of protein. By that standard, as previously discussed, all legumes do well, and lentils and fava beans do quite well indeed, whereas as sthira notes, animal proteins (and esp. egg whites) do poorly on both counts.

Go ahead and try and restrict your protein some more.. guess what will happen? Increased age related muscle wasting. No thanks!

All of the loose talk of 'protein restriction' completely mischaracterizes the issue. The goal is to avoid overriding the reduction of IGF-1 induced by CR by engaging in protein moderation -- ie, keep your protein to around the RDA (and it evidently need not be much lower than your suggested 1 g/kg). There are additional reasons to maintain low (but still ballpark-RDA) intake of these 3 amino acids, above and beyond protein moderation.

FWIW, I eat lentils - they seem lower on the leucine list than, say, watercress - which I gobble with abandon.

See above . It's important to take into account both how much leucine is there per gram of protein in the 2 foods, and how much protein is in the 2 foods, period. You should be quite fine with both.

Oddly, in my blood test protein levels appear normal - smack in the middle of the range, actually. Anecdotes-schmanicdotes.

Serum protein doesn't actually tell you anything beyond that you aren't badly malnourished or ill; I'd ignore it, unless of course it really is below the reference range.

Anecdotes-schmanicdotes.

Indeed

PS: does anyone know if creatine also stimulates IGF-1? It seems to be anabolic, and I take it because it supposedly boosts IQ in vegans.

It does not: I just confirmed this a couple of weeks ago, tho' I didn't save the refs. And you do realize that you only need 3 g or so to get the cognitive "correction," yes?

Don't restrict leucine. It (along with the other BCAA's) increased mean lifespan in mice. The result was likely due to increased mitochondrial biogenesis.

No, the BCAA/lifespan "result" was likely due to the researchers not being able to raise healthy mice .

Methionine restriction is more effective and also probably easier.

Methionine restriction is impossible,^* unless you're going to stop eating actual food. However, Met moderation is entirely doable, and happily largely via the same strategy as leucine moderation. "More effective" doesn't play into it: the pathways involved are completely unrelated, and the benefits of moderation (and, in mice on a synthetic diet, of actual restriction of Met + Cys) distinct.

^* Note that this post was heavy on emphasizing the limitations of the MetR research at that time; today, I find it pretty convincing -- just irrelevant for human application.

[capsun]

Don't restrict leucine. It (along with the other BCAA's) increased mean lifespan in mice. The result was likely due to increased mitochondrial biogenesis.

No, the BCAA/lifespan "result" was likely due to the researchers not being able to raise healthy mice .

I posted in that thread. I think the issue is inconclusive.

Methionine restriction is more effective and also probably easier.

Methionine restriction is impossible,^* unless you're going to stop eating actual food. However, Met moderation is entirely doable, and happily largely via the same strategy as leucine moderation. "More effective" doesn't play into it: the pathways involved are completely unrelated, and the benefits of moderation (and, in mice on a synthetic diet, of actual restriction of Met + Cys) distinct.

^* Note that this post was heavy on emphasizing the limitations of the MetR research at that time; today, I find it pretty convincing -- just irrelevant for human application.

No, methionine restriction is not impossible. Please calculate the mg's of MET+CYS again based on the MetR studies conducted thus far. I want to see your new calculation.

[Michael]

 

 

Don't restrict leucine. It (along with the other BCAA's) increased mean lifespan in mice. The result was likely due to increased mitochondrial biogenesis.

No, the BCAA/lifespan "result" was likely due to the researchers not being able to raise healthy mice .

 

I posted in that thread. I think the issue is inconclusive.

 

They haven't shown a life extension effect. In that sense, I s'pose it's "inconclusive," rather like the putative existence of an unicorn which has not yet been presented for examination .
 

 

 

Methionine restriction is more effective and also probably easier.

Methionine restriction is impossible, unless you're going to stop eating actual food. However, Met moderation is entirely doable, and happily largely via the same strategy as leucine moderation. "More effective" doesn't play into it: the pathways involved are completely unrelated, and the benefits of moderation (and, in mice on a synthetic diet, of actual restriction of Met + Cys) distinct.

 

No, methionine restriction is not impossible. Please calculate the mg's of MET+CYS again based on the MetR studies conducted thus far. I want to see your new calculation.

 

"No, it is not impossible. Prove me right."

But, OK: Human RDA for Met + Cys is 19 mg/kg/d. For eg. an once-average adult American of 70 kg, this is 1330 mg of the 2 aminos combined.

Life-extending methionine restriction is done at a 0.17% or 0.12% Met, zero-cysteine diet, vs. a 0.86% Met diet in standard AIN diets for rats or mice. Restricting from 1330 mg Met+Cys would then give 1330 x [0.17/0.86] = 263 mg. Even (say) 3 kg of russet potatoes (2370 Calories, a shade more than that once-average American adult needs for Calorie requirements) yields 900 mg; something as radical as broccoli for the same energy contains 2600 mg. You gonna get most of your Calories from the sugar bowl, or gelatin, or what?

Edited by Michael, 26 September 2014 - 07:04 PM.

[InquilineKea]

Wow seriously, and now here's an article that argues otherwise...

http://www.plosone.o...al.pone.0021187

Doubling dietary leucine reversed many of the metabolite abnormalities and caused a marked improvement in glucose tolerance and insulin signaling without altering food intake or weight gain. Increased dietary leucine was also associated with a decrease in hepatic steatosis and a decrease in inflammation in adipose tissue. These changes occurred despite an increase in insulin-stimulated phosphorylation of p70S6 kinase indicating enhanced activation of mTOR, a phenomenon normally associated with insulin resistance. These data indicate that modest changes in a single environmental/nutrient factor can modify multiple metabolic and signaling pathways and modify HFD induced metabolic syndrome by acting at a systemic level on multiple tissues. These data also suggest that increasing dietary leucine may provide an adjunct in the management of obesity-related insulin resistance.

That being said, it's only for obesity-related insulin resistance, so it doesn't apply to CRONites. But still, it sort of does make me a bit more skeptical of the original finding I posted in the OP.

[Donnie]

The goal is to avoid overriding the reduction of IGF-1 induced by CR by engaging in protein moderation -- ie, keep your protein to around the RDA (and it evidently need not be much lower than your suggested 1 g/kg).

Does that mean there's no benefit in keeping leucine/methionine low for non-CRONies?

I was convinced that more protein would equal increase IGF-1 regardless of a normal diet or CRON. Is that only true to some extent i.e. a certain protein level threshold?

[Michael]

Wow seriously, and now here's an article that argues otherwise...

http://www.plosone.o...al.pone.0021187

Doubling dietary leucine reversed many of the metabolite abnormalities and caused a marked improvement in glucose tolerance and insulin signaling [in obese, insulin-resistantn mice] despite an increase in insulin-stimulated phosphorylation of p70S6 kinase indicating enhanced activation of mTOR, a phenomenon normally associated with insulin resistance.

That being said, it's only for obesity-related insulin resistance, so it doesn't apply to CRONites. But still, it sort of does make me a bit more skeptical of the original finding I posted in the OP.

Now, wait a minute. You've got one study that shows that decreasing the amount of leucine in normal rodent chow improves insulin sensitivity in normal, healthy, nonobese, nondiabetic mice. And then a second study comes along that shows that doubling leucine intake in obese, insulin-resistant mice improves glucose tolerance, despite the absence of improved insulin sensitivity and an increase activation of mTOR, which latter is very likely bad from a life extension point of view; this study also shows (and maybe you missed this) that doubling leucine intake in normal, healthy, nonobese, nondiabetic mice either has no effect upon, or possibly WORSENS, glucose tolerance, while (again) increasing activation of mTOR -- which (again) good evidence suggests we should be avoiding as much as possible, and is certainly contrary to the effects of CR.

Why, exactly, does this make you more skeptical of the original finding?? The new finding either has no effect on, or REINFORCES, the finding of the original study if you're a CR practitioner, and likely if you're anything other than an overweight, insulin-resistant person.

[InquilineKea]

Oh okay, good point! Unfortunately, I didn't have the time to read the new finding - only to post it. But I'm glad that you pointed it out! I just said "a bit more skeptical". But now I'm just as convinced of the original finding.

[JLL]

What is the point of eating foods with protein if you specifically limit the intake of essential amino acids at the same time? Why not just eat less protein in general?

[Michael]

The goal is to avoid overriding the reduction of IGF-1 induced by CR by engaging in protein moderation -- ie, keep your protein to around the RDA (and it evidently need not be much lower than your suggested 1 g/kg).

Does that mean there's no benefit in keeping leucine/methionine low for non-CRONies?

I was convinced that more protein would equal increase IGF-1 regardless of a normal diet or CRON. Is that only true to some extent i.e. a certain protein level threshold?

Fist, let me emphasize again: the issues of IGF-1 in CR -- which is primarily an effect of dietary protein -- separate from the question of specific amino acids, which we're moderating for independent reasons (in leucine's case, to avoid stimulating mTOR).

Second, I don't honestly know either the degree to which lowering protein intake affects IGF-1 levels in AL folks (I have seen studies showing some effect -- I just can't quantify it). More importantly, I don't know how much benefit it would be to lower IGF-1 in AL folks, since you aren't simultaneously benefiting from the many other age-retarding aspects of CR, but are instead aging "normally."

What is the point of eating foods with protein if you specifically limit the intake of essential amino acids at the same time? Why not just eat less protein in general?

First, again, the effects are separate: in the 2 studies in this thread, eg, they lowered and boosted (respectively) leucine without altering the total protein intake. See a similar effect on methionine in both rodent MetR studies and in human epidemiology as documented in the post I linked that you apparently didn't read .

Second: it seems to me to be possibly risky to lower one's protein intake below the RDA, and yet even at RDA levels one can easily be substantially aabove the RDA for Leu, and above the threshold for heart problems documented in the twice-aforementioned post for Met+Cys, depending on your choice of specific protein foods.

Finally: in my own case, at least, I've found that even at quite substantial CR, once you cut sugar and grains almost entirely out of your diet, it's diffiicult to actually get one's protein down to RDA levels: meals composed even entirely of vegetables and fat are sometimes still well above the RDA for protein (plug, eg, a 1800 Cal dietf composed of 40% fat from your pref'd source plus broccoli into COM).* And even if you are only getting RDAish protein, you could still wind up too high on Leu and/or Met+Cys if you are eating any meat, eggs/egg white, or whey protein.

-Michael

*I'm OK with that still-"high" total protein (~2 x RDA), because my IGF-1 has come down and my IGF-BP3 has risen, but you've gotta look at both, to some degree.

[Donnie]

Second, I don't honestly know either the degree to which lowering protein intake affects IGF-1 levels in AL folks (I have seen studies showing some effect -- I just can't quantify it). More importantly, I don't know how much benefit it would be to lower IGF-1 in AL folks, since you aren't simultaneously benefiting from the many other age-retarding aspects of CR, but are instead aging "normally."

Slightly depressing, but thank you nonetheless

[madanthony]

There is a lot of discussion here about avoiding leucine because it raises insulin to do so. But why would you then want to avoid leucine? It is my understanding that raising insulin makes you EAT MORE and this GAIN WEIGHT. And anyway you do not need to avoid leucine to affect your insulin --- for instance, NETTLE raises insulin and guggul LOWERS insulin. I had to take nettle in a high dose for my allergies since it blocks all 4 histamine receptors but it also raised my insulin and lowered my blood pressure, so after hayfever season (when I figured out what happened) I am now taking guggul because it lowers insulin. There are about a bazillion herbals that raise and lower your insulin - whatever you want. So I would not worry about proteins you need for health. Almost every herbal you run across lowers lack of insulin sensitivity. It's a crime that most restaurant and prepared foods limit the spices used to salt and pepper because there are so many many benefits in herbs and spices and they tatse good too.

[LexLux]

Sorry for reviving such an old thread but can anyone tell me if a vegan diet, incorporating legumes into meals about 4 times a week would result in any meaningful (for L.E) decrease in methionine or leucine? Has there been any important new research in this area?

[LexLux]

I found this 2013 article which states that 40% (as opposed to 80%) MetR decreases mtROSp.

 

 

Regulation of longevity and oxidative stress by nutritional interventions: Role of methionine restriction

Ines Sanchez-Roman, Gustavo Barja

• http://www.sciencedi...531556513000612

 

Abstract

 

"Comparative studies indicate that long-lived mammals have low rates of mitochondrial reactive oxygen species production (mtROSp) and oxidative damage in their mitochondrial DNA (mtDNA). Dietary restriction (DR), around 40%, extends the mean and maximum life span of a wide range of species and lowers mtROSp and oxidative damage to mtDNA, which supports the mitochondrial free radical theory of aging (MFRTA). Regarding the dietary factor responsible for the life extension effect of DR, neither carbohydrate nor lipid restriction seems to modify maximum longevity. However protein restriction (PR) and methionine restriction (at least 80% MetR) increase maximum lifespan in rats and mice. Interestingly, only 7 weeks of 40% PR (at least in liver) or 40% MetR (in all the studied organs, heart, brain, liver or kidney) is enough to decrease mtROSp and oxidative damage to mtDNA in rats, whereas neither carbohydrate nor lipid restriction changes these parameters. In addition, old rats also conserve the capacity to respond to 7 weeks of 40% MetR with these beneficial changes. Most importantly, 40% MetR, differing from what happens during both 40% DR and 80% MetR, does not decrease growth rate and body size of rats. All the available studies suggest that the decrease in methionine ingestion that occurs during DR is responsible for part of the aging-delaying effect of this intervention likely through the decrease of mtROSp and ensuing DNA damage that it exerts. We conclude that lowering mtROS generation is a conserved mechanism, shared by long-lived species and dietary, protein, and methionine restricted animals, that decreases damage to macromolecules situated near the complex I mtROS generator, especially mtDNA. This would decrease the accumulation rate of somatic mutations in mtDNA and maybe finally also in nuclear DNA."

Edited by LexLux, 10 April 2014 - 06:55 PM.

[LaViidaLocaa]

I found this 2013 article which states that 40% (as opposed to 80%) MetR decreases mtROSp.

 

 

Regulation of longevity and oxidative stress by nutritional interventions: Role of methionine restriction

Ines Sanchez-Roman, Gustavo Barja

• http://www.sciencedi...531556513000612

 

Abstract

 

"Comparative studies indicate that long-lived mammals have low rates of mitochondrial reactive oxygen species production (mtROSp) and oxidative damage in their mitochondrial DNA (mtDNA). Dietary restriction (DR), around 40%, extends the mean and maximum life span of a wide range of species and lowers mtROSp and oxidative damage to mtDNA, which supports the mitochondrial free radical theory of aging (MFRTA). Regarding the dietary factor responsible for the life extension effect of DR, neither carbohydrate nor lipid restriction seems to modify maximum longevity. However protein restriction (PR) and methionine restriction (at least 80% MetR) increase maximum lifespan in rats and mice. Interestingly, only 7 weeks of 40% PR (at least in liver) or 40% MetR (in all the studied organs, heart, brain, liver or kidney) is enough to decrease mtROSp and oxidative damage to mtDNA in rats, whereas neither carbohydrate nor lipid restriction changes these parameters. In addition, old rats also conserve the capacity to respond to 7 weeks of 40% MetR with these beneficial changes. Most importantly, 40% MetR, differing from what happens during both 40% DR and 80% MetR, does not decrease growth rate and body size of rats. All the available studies suggest that the decrease in methionine ingestion that occurs during DR is responsible for part of the aging-delaying effect of this intervention likely through the decrease of mtROSp and ensuing DNA damage that it exerts. We conclude that lowering mtROS generation is a conserved mechanism, shared by long-lived species and dietary, protein, and methionine restricted animals, that decreases damage to macromolecules situated near the complex I mtROS generator, especially mtDNA. This would decrease the accumulation rate of somatic mutations in mtDNA and maybe finally also in nuclear DNA."

See brown: I wonder if this has the same implications in humans, i.e. if it's possible to delay aging and onset of diseases by only restricting methionine instead of overall calories.

As I lift weights, to build muscle I have to eat in a surplus (completely opposed to CR), but I wonder if it's possible to build (almost) the same amount of muscle while following an MetR diet?

[Darryl]

Moderation, not restriction indeed. The World Heath Organization's leucine requirement is 39 mg/kg/day, with a considerable safety margin. That's 2.34 g for a 60 kg person, 2.73 g for a 70 kg person etc.

 

So how much leucine do Americans get?

 

percentile  leucine (g)

1st         2.3

5th         3.1

10th        3.6

25th        4.5

50th        5.8

75th        7.3

90th        8.9

95th       10.1 

99th       12.6 

mean        6.1

 

Most are getting mTOR signalling from 2-500% of their lean tissue leucine requirements, and this was before the low-carb craze.

 

The recent study indicating a biphasic response of mortality to dietary protein suggests low-protein till 65-70, followed by higher levels to prevent frailty, sarcopenia, thereafter. Perhaps a diet sufficent to keep one in the 19-22 optimum BMI.

 

Practically for those under 65, it just means sating hunger with fiber rather than hypothalamic mTOR signalling, I hope when I reach that threshold in 25 years we'll have effective myostatin inhibitors and other means to prevent the downside of mTOR moderation. 

Edited by Darryl, 10 April 2014 - 08:30 PM.

[Adaptogen]

It is a shame that leucine is so anabolic, yet also detrimental. Would HMB likely have the same negative implications as leucine?

It seems more and more that hypertrophy and health cannot go hand in hand

[LexLux]

 

I found this 2013 article which states that 40% (as opposed to 80%) MetR decreases mtROSp.

 

 

Regulation of longevity and oxidative stress by nutritional interventions: Role of methionine restriction

Ines Sanchez-Roman, Gustavo Barja

• http://www.sciencedi...531556513000612

 

Abstract

 

"Comparative studies indicate that long-lived mammals have low rates of mitochondrial reactive oxygen species production (mtROSp) and oxidative damage in their mitochondrial DNA (mtDNA). Dietary restriction (DR), around 40%, extends the mean and maximum life span of a wide range of species and lowers mtROSp and oxidative damage to mtDNA, which supports the mitochondrial free radical theory of aging (MFRTA). Regarding the dietary factor responsible for the life extension effect of DR, neither carbohydrate nor lipid restriction seems to modify maximum longevity. However protein restriction (PR) and methionine restriction (at least 80% MetR) increase maximum lifespan in rats and mice. Interestingly, only 7 weeks of 40% PR (at least in liver) or 40% MetR (in all the studied organs, heart, brain, liver or kidney) is enough to decrease mtROSp and oxidative damage to mtDNA in rats, whereas neither carbohydrate nor lipid restriction changes these parameters. In addition, old rats also conserve the capacity to respond to 7 weeks of 40% MetR with these beneficial changes. Most importantly, 40% MetR, differing from what happens during both 40% DR and 80% MetR, does not decrease growth rate and body size of rats. All the available studies suggest that the decrease in methionine ingestion that occurs during DR is responsible for part of the aging-delaying effect of this intervention likely through the decrease of mtROSp and ensuing DNA damage that it exerts. We conclude that lowering mtROS generation is a conserved mechanism, shared by long-lived species and dietary, protein, and methionine restricted animals, that decreases damage to macromolecules situated near the complex I mtROS generator, especially mtDNA. This would decrease the accumulation rate of somatic mutations in mtDNA and maybe finally also in nuclear DNA."

See brown: I wonder if this has the same implications in humans, i.e. if it's possible to delay aging and onset of diseases by only restricting methionine instead of overall calories.

As I lift weights, to build muscle I have to eat in a surplus (completely opposed to CR), but I wonder if it's possible to build (almost) the same amount of muscle while following an MetR diet?

 

I just posted a new thread about body size and MetR so as not to derail this thread too much from leucine.

 http://www.longecity...y-size-of-rats/

Edited by LexLux, 10 April 2014 - 09:17 PM.