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Ron Put

Relationship of Intake of Plant and Animal Protein, and Longevity

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Lazy day, so I've been reading a bit more on the relationship of higher protein intake to increased all cause mortality, until one reaches about 70 years of age, after which a slight increase (Longo suggests about an increase of about 1.5g per kg, although his study was based on kind of fuzzy 24 hour recall and didn't seem to find a difference between animal and plant protein, which may be attributed to the methodology).

I am essentially a vegan (occasionally eat cheese or eggs), so I obviously have my biases. Nevertheless, I have been trying to keep my protein intake lower and it's not easy: legumes have significant amounts of protein, as well as nuts and nutritional/brewer's yeasts. I hover about 1.12g per kg.

I knew from a couple of studies postulating that higher intake of plant protein doesn't show the significant correlation with mortality that animal protein does, so today I spent a bit of time reading up on it. And to me, it seems to hold water, based on amino acid content differrences:

"Plant proteins have a reduced content of essential amino acids in comparison to animal proteins. A significant reduction of limiting amino acids (methionine, lysine, tryptophan) means lower protein synthesis. In subjects with predominant or exclusive consumption of plant food a higher incidence of hypoproteinemia due to significant reduction of methionine and lysine intakes was observed. On the other hand, lower intake of these amino acids provides a preventive effect against cardiovascular disease via cholesterol regulation by an inhibited hepatic phospholipid metabolism. Vegetarians have a significantly higher intake of non-essential amino acids arginine and pyruvigenic amino acids glycine, alanine, serine. When plant protein is high in non-essential amino acids, down-regulation of insulin and up-regulation of glucagon is a logical consequence. The action of glucagon in the liver is mediated by stimulation of adenyl cyclase that raises cyclic-AMP (adenosine-3,5-monophosphate) concentrations. Cyclic-AMP down-regulates the synthesis of a number of enzymes required for de novo lipogenesis and cholesterol synthesis, up-regulates key gluconeogenic enzymes and the LDL receptors and decreases the IGF-1 activity (insulin-like growth factor). Cyclic-AMP thus provides a reduction of atherosclerosis risk factors as well as a retardation of cancer development. A sufficient consumption of plant proteins has the protective effects against chronic degenerative diseases...."
https://www.ncbi.nlm.nih.gov/pubmed/16201743/
 

"Lifespan and metabolic health are influenced by dietary nutrients. Recent studies show that a reduced protein intake or low-protein/high-carbohydrate diet plays a critical role in longevity/metabolic health. Additionally, specific amino acids (AAs), including methionine or branched-chain AAs (BCAAs), are associated with the regulation of lifespan/ageing and metabolism through multiple mechanisms. Therefore, methionine or BCAAs restriction may lead to the benefits on longevity/metabolic health. Moreover, epidemiological studies show that a high intake of animal protein, particularly red meat, which contains high levels of methionine and BCAAs, may be related to the promotion of age-related diseases. Therefore, a low animal protein diet, particularly a diet low in red meat, may provide health benefits. However, malnutrition, including sarcopenia/frailty due to inadequate protein intake, is harmful to longevity/metabolic health."
https://www.sciencedirect.com/science/article/pii/S2352396419302397

"Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving "aging retardant" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents."
https://www.greenmedinfo.com/article/low-methionine-content-vegan-diet-may-result-increased-longevity

 

"Replacing animal protein of various origins with plant protein was associated with lower mortality. In particular, the HRs for all-cause mortality were 0.66 (95% CI, 0.59-0.75) when 3% of energy from plant protein was substituted for an equivalent amount of protein from processed red meat, 0.88 (95% CI, 0.84-0.92) from unprocessed red meat, and 0.81 (95% CI, 0.75-0.88) from egg.

Conclusions:

High animal protein intake was positively associated with mortality and high plant protein intake was inversely associated with mortality, especially among individuals with at least one lifestyle risk factor. Substitution of plant protein for animal protein, especially that from processed red meat, was associated with lower mortality, suggesting the importance of protein source."
https://www.acc.org/latest-in-cardiology/journal-scans/2016/08/02/11/53/association-of-animal-and-plant-protein-intake

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I looked into methionine moderation (restriction sounds unrealistically ambitious) awhile ago and found it very difficult to achieve on almost any diet that’s heathy, and pretty much impossible on the pescatarian diet I favor. It’s surprisingly hard to avoid methionine, as it’s almost everywhere, including massive quantities in stuff you’d never suspect, like garlic. I wish it were easier to accomplish without resorting to food that comes out of a lab.

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Quote

 methionine ... in stuff you’d never suspect, like garlic

Methionine is one of a few sulfur containing amino acids; garlic's unique flavor comes from sulfur compounds  (from sulfate in the soil  which is  incorporated into amino acids and sulfur storage molecules.)

Vegan diets are known to be relatively low in methionine.
 

Quote

High levels of methionine can be found in eggs, meat, and fish; sesame seeds, Brazil nuts, and some other plant seeds; and cereal grains. Most fruits and vegetables contain very little. Most legumes, though protein dense, are low in methionine.

 

If you sharply limit fish, eggs, meat and dairy products, moderate intake of  certain nuts, seeds and grains ("though it's hard to get a meaningful increase in % dietary protein from grains"--Michael Rae), and make legumes and pulses your primary sources of protein in a relatively low-protein diet,  then you can achieve methionine moderation. 

Cf.Methionine Restriction is Not Viable in Humans  by Michael R.

https://www.crsociety.org/topic/13120-methionine-restriction-is-not-viable-in-humans/

 

Edited by Sibiriak

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7 hours ago, TomBAvoider said:

including massive quantities [of methionine] in stuff you’d never suspect, like garlic.

"massive quantities" Tom? I thought you were Mr. "the dose makes the poison"?

The USDA nutrition database entry for raw garlic says 100g contains 76mg of methionine. Two cloves of raw garlic (my daily dose) weigh ~6g, which translates to 4.5mg of methionine. In contast, a single serving of beef or fish contains nearly 200x more methionine - 100g of lean beef contains 930mg and 100g of salmon contains 810mg. 

It isn't that hard to keep methionine intake relatively low on a vegan diet, although as Michael points out, this does not equate to methionine restriction as studied in rodents.

--Dean

 

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Does anyone have good information on studies specifying human values for leucine and valine?

As to metnionine, I am basically trying to keep my intake as close to 1g (0.8g minimum RDA) as I can, but definitely below 1.5g (1.7g is the cut off number I seem to recall from human studies).

Here is my Cronometer 4-week data, most of the metionine is from flax, chia, yeast and caco nibs.

I am trying to be meticulous, but even though it says 20 kcal surplus, I've lost about 1.2 kg, which puts me a bit too low for my taste (9.5% fat mass; 4.6% bone mass and 85.9% muscle mass). So I must be screwing up someplace, or Fitbit and Cronometer are. I'll eat a whole pizza tonight 😄

 

1645612821_ScreenShot2019-08-04at16_34_25.thumb.png.97eefed8173b0daf1ffe0b3674567137.png
 

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14 hours ago, Ron Put said:

I am trying to be meticulous, but even though it says 20 kcal surplus, I've lost about 1.2 kg, which puts me a bit too low for my taste (9.5% fat mass; 4.6% bone mass and 85.9% muscle mass). So I must be screwing up someplace, or Fitbit and Cronometer are. I'll eat a whole pizza tonight 😄

Ron, as I've recently verified, on a 2200 kCals diet I'm going to loose weight, even though I'm just 5'7" and it was with high leucine, methionine and triptophane (from abundant yogurt products).

I'm not surprised that you being well over 6' and with little of those AAs, you are loosing bodyweight. As I have observed, probably calorically and proteically restricted vegan diets work well with obese individuals, who have a genetic makeup favourable to bodyweight gain or manteinance. I've gained some weight on a vegan diet, but I had to eat over 3000 kcals daily and abundant soy products.

Edited by mccoy

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mccoy, you might be on to something:

Direct comparison of methionine restriction with leucine restriction on the metabolic health of C57BL/6J mice

"Control-fed mice maintained a stable body mass throughout the course of the study, which only increased slightly by 2.3 g (Fig. 1a). However, MR- and LR-fed mice both significantly decreased their body mass over the course of the study, compared to control-fed mice (Fig. 1a). MR-fed mice decreased body mass by 8.6 g and LR-fed mice reduced body mass by 4.9 g during the 8 week treatment, the overall effect of the diets was not significant; however, MR and LR produced a significantly different effect on body mass over time (Fig. 1a). After approximately 3 weeks on diet, MR produces a greater decline in body mass than LR (Fig. 1a). MR and LR diet-fed mice had significantly higher levels of food intake (adjusted for body mass) during the course of the study compared to control-fed mice, whereas there were no measurable differences between LR and MR (Fig. 1b). Both MR and LR significantly decreased levels of fat mass compared to control diet in terms of both total amount (g) and as a proportion of body mass (%) (Fig. 1c,d). LR and MR diets did not differ for levels of fat mass (Fig. 1c,d). Similarly, the two dietary treatments also significantly decreased total amount of lean mass (g) compared to control diet and MR significantly reduced lean mass (g) compared to LR diet; however, this was a result of losing both, fat and lean mass, but predominantly fat mass...

In conclusion, this study suggests that 80% LR is an effective dietary regime for improving metabolic health; however, 80% MR has stronger beneficial metabolic effects on body mass reduction and improvement in glucose homeostasis than 80% LR. Pathways unique to a specific EAA may cause the discrepancy in the magnitude of the effects between MR and LR, including the mechanisms by which FGF21 is induced and Akt is activated in the liver."


https://www.nature.com/articles/s41598-017-10381-3

 

I am going to adjust my caloric intake to keep stable, but will still try and maintain sufficient, but relatively low methionine, leucine and valine. Especially for methionine, I aiming for less than 1.5g for my weight. Also will be trying to keep my overall protein intake to less than 1.2g per kg.

Now trying to figure out if my current leucine and valine levels are OK or if they need much optimization.

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In my case, even by abundant Met and Leu, I lost weight. Evidently, calories still govern bodyweight regulation, in an hypocaloric state probably muscle mass is better conserved with abundant EAAs.

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20 hours ago, mikeccolella said:

just published and me thinks a good study

And super relevant here because they were practicing severe CR with median daily caloric intake by quintiles ranging from 1567 to 1739!  And considering they found such a profound mortality benefit from dropping animal protein from 15.2% to 11.9% of energy you Mike at nearly 0% should be well on your way to immortality!

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Todd,

Your sarcasm sounds like you may be a bit sensitive on the subject.

In fact there were quite large differences between top and bottom quintiles of the healthy plant-based score when it comes to foods that most impact health. See the highlighted differences servings per day between bottom (left) ant top (right) quintiles:

Screenshot_20190822-155704_Chrome.jpg

The top quintile of healthy plant-based eaters ate two servings of less animal foods overall and about half as many servings of red/processed meat in particular, substituting them with more healthy plant-based foods (almost four servings more per day). 

1 hour ago, Todd Allen said:

daily caloric intake by quintiles ranging from 1567 to 1739!

It is well known that people across the board under-report how much they eat on food frequency questionaires. Unless you somehow have evidence this phenomena skews results in favor of plants, it seems irrelevant to the results of this study which found ~16% reduced mortality in those who ate the most healthy plants and the least animal products.

--Dean

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I too tend to be skeptic about food questionnaires, but I found the following plot very eloquent. Even the upper bound of the CI after the value of 44 plant score underlines a significant drop in HR, proportional to theincrease of plant based foods.

image.png.5e573893df374e99d1eb09b7401dde65.png

 

Edited by mccoy

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18 hours ago, Dean Pomerleau said:

Your sarcasm sounds like you may be a bit sensitive on the subject.

No, not sensitive.  Contemptuous.

I see no value in the hypothesis and even if the data wasn't blatantly poor it could not test the hypothesis in a meaningful way.  It was a pointless waste of effort to produce the study and it was a waste of my time to look at it even superficially.  We have decades of data collected and analyzed in similar fashion which at a societal level has failed to result in dietary changes producing noticeable improvements in public health or the top causes of mortality such as heart disease, cancer and dementia.

Even if the question of whether plant or animal foods are healthier is answerable at a statistical level as an individual having the answer would be no better than having the answer to whether it is statistically better to invest in large or small cap stocks.  As an individual investor one should evaluate how a particular investment fits their goals.  Placing undue emphasis on a single aspect such as small or large cap is a poor strategy for personal wealth and the simple minded approach to food of plant or animal is a poor strategy for personal health.

This study's superficial look at food quality would suggest that an industrial ag chicken breast from KFC rolled in white flour and deep fried in rancid corn oil being neither red or processed is healthier than my daily ounce of organic pastured raw beef liver.

Edited by Todd Allen

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Guys, is it necessary to argue? I couldn't read the original article since here sci-hub is no more reachable. Questionnaires have their known drawbacks and 16 % less HR in view of the uncertainties may not in reality be such a large advantage, although form a purely chemical and functional point of view it's very hard to negate the health advantages of plant based foods (fibers, specific micronutrients, phenolic compounds and other phytonutrients).

Todd, the very authoritative IARC issued a verdict of possible carcinogen for mammalians' meat (so called red meats). The paleo raised so many objections, but IARC is the leading authority on cancer and to me it remains the most credible source. Your amounts are very small, but it makes sense that higher amounts could be potentially very deleterious to health. 

 

 

Edited by mccoy

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46 minutes ago, mccoy said:

the very authoritative IARC issued a verdict of possible carcinogen for mammalians' meat (so called red meats).

And red meat is high in bioavailable heme iron.  Those prone to hemochromatosis would be wise to minimize intake while those prone to iron deficiency anemia could find the iron a desirable attribute.  Red meat tends to be high in numerous other things such as carnosine, carnitine, choline, creatine, methionine, etc.  One can make an effort to evaluate the various known properties and weigh their desirability/undesirability to make the decision on how much if any red meat one wants in their diet. 

Pretty much every food has trade offs good and bad.  I eat cacao nearly daily.  Most cacao contains measurable amounts of cadmium which is quite toxic in addition to being a carcinogen and some cacao is considered dangerously high in it.  I try to source mine carefully but haven't the ability to test it and my decision is at best a calculated guess that my exposure risk does not outweigh my other reasons for choosing this food.  Arsenic is a known carcinogen and it is commonly found in high levels in rice.  Is that sufficient reason to stop consuming rice?  I have additional reasons not to eat it and no compelling reasons to do so.  But I recognize it is a common food and I'm ok with others making their own informed decisions to eat it or not.

 

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Todd - I’m sure you mentioned this previously, but what are you showing in your photo (exactly) - thanks,

Clinton

btw

one of my (personal) regrets was following Vince Giuliano’s blog for a while, when as an engineer (by day) and a guy that didn’t study biology- led me to assume dark chocolate (cacao) (among many other poor influences) was a good thing. 

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2 hours ago, Todd Allen said:

red meat is high in bioavailable heme iron

Also, the "Impossible Burger" -- a vegan burger substitute -- has high heme iron.

2 hours ago, Todd Allen said:

cadmium which is quite toxic

Cd, and other heavy metals, is poorly metabolized by older adults.

2 hours ago, Todd Allen said:

Arsenic is a known carcinogen and it is commonly found in high levels in rice

Inorganic arsenic is very toxic.  But organically bound arsenic in vegetables is not believed to be toxic.

Interestingly, I have my bloodwork tested for heavy metals regularly -- this is because I eat fish, and was concerned about Hg.  Interstingly, all tests show essentially zero for all heavy metals -- with one exception:  Arsenic.  My CR friendly nephrologist did more careful tests -- all of my measurable arsenic was organic.

I don't know which plant source provides my organic arsenic -- but I'm not worried.

  --  Saul

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4 hours ago, Clinton said:

... one of my (personal) regrets was following Vince Giuliano’s blog for a while, when as an engineer (by day) and a guy that didn’t study biology- led me to assume dark chocolate (cacao) (among many other poor influences) was a good thing. 

Why? I have been eating cacao nibs for years, usually between 20-40g per day. I have tested for heavy metal levels several times, and all are zilch. Cadmium results are "None detected."

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4 hours ago, Clinton said:

Todd - I’m sure you mentioned this previously, but what are you showing in your photo (exactly) - thanks

It's my forearm just below the elbow.  I posted it after mccoy's pumped upper body avatar.  Despite my resistance training efforts I haven't much of bulging muscles to display due to Kennedy's disease but as my subcutaneous fat thins out my veins have been reappearing and look disproportionately large over my undersized muscles.  My phlebotomist has been pleased with the new me.  Before I started CR there were days when she would try half a dozen times to hit a vein and give up.

Edited by Todd Allen

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38 minutes ago, Ron Put said:

Why? I have been eating cacao nibs for years, usually between 20-40g per day. I have tested for heavy metal levels several times, and all are zilch. Cadmium results are "None detected."

Hopefully you got the right test.  I think blood is for acute exposure but urine is needed to see chronic low dose exposure.

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2 hours ago, Todd Allen said:

Hopefully you got the right test.  I think blood is for acute exposure but urine is needed to see chronic low dose exposure.

They use a blood test to check cadmium levels in smokers, so my guess it should work similarly for cacao. Both are long-term accumulations (the tobacco plant gets it from the soil too).

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10 hours ago, Clinton said:

one of my (personal) regrets was following Vince Giuliano’s blog for a while, when as an engineer (by day) and a guy that didn’t study biology- led me to assume dark chocolate (cacao) (among many other poor influences) was a good thing. 

Clinton,

we've been discussing at length on cacao products and if you search the forum there are many interesting threads on it. Cacao products, cacao powder and derivatives, like cacao-rich dark chocolate, are rich in phenolic compounds, particularly in (-)-epicatechin, which among other things seems to exhibit a protective action on the endothelium of arteries and against cancer proliferation (anti-angiogenetic?).

The Kuna Indians display an exceptionally low CVD and cancer mortality, presumably because of their very high consumption of coca. I myself am a huge consumer of unprocessed (undutched) cacao powder, which contains on the average thrice as many phenolic compounds and (-)-epicatechin as processed cacao powder. Soem products are even partly defatted, like my choice, El Ceibo cacao, so you can limit the intake of saturated fats, one of the few drawbacks of cacao.

Raw organic cacao powder is the best choice, since raw is unprocessed, but undutched is also unprocessed so it's good just the same anf probably cheaper. In previosu posts there are discussiosn on the cadmium content of some products sold in America.

This thread reminds me that I should write to El Ceibo producers and ask if they tested cadmium. Or I should have some analyses doen on myself. Some heavy consumers of cacao in the longecity forum did not find anomalies in their hair Cd content. 

In the industrial hygiene field, where some of my work is carried out, urinary metabolites are often measured to assess the individual exposure. Maybe that's one of the ways, I just quicly googled the subject and this article popped up.

 

J Toxicol Sci. 2018;43(2):89-100. doi: 10.2131/jts.43.89.

Effects of long-term cadmium exposure on urinary metabolite profiles in mice.

Author information

1
Department of Biology, University of Ottawa, Canada.
2
Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University.
3
Laboratory of Molecular Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University.

Abstract

Cadmium (Cd) is a common environmental pollutant with known toxic effects on the kidney. Urinary metabolomics is a promising approach to study mechanism by which Cd-induced nephrotoxicity. The aim of this study was to elucidate the mechanism of Cd toxicity and to develop specific biomarkers by identifying urinary metabolic changes after a long-term of Cd exposure and with the critical concentration of Cd in the kidney. Urine samples were collected from wild-type 129/Sv mice after 67 weeks of 300 ppm Cd exposure and analyzed by ultra performance liquid chromatography connected with quadrupole time of flight mass spectrometer (UPLC-QTOF-MS) based metabolomics approach. A total of 40 most differentiated metabolites (9 down-regulated and 31 up-regulated) between the control and Cd-exposed group were identified. The majority of the regulated metabolites are amino acids (glutamine, L-aspartic acid, phenylalanine, tryptophan, and D-proline) indicating that amino acid metabolism pathways are affected by long-term exposure of Cd. However, there are also some nucleotides (guanosine, guanosine monophosphate, cyclic AMP, uridine), amino acid derivatives (homoserine, N-acetyl-L-aspartate, N-acetylglutamine, acetyl-phenylalanine, carboxymethyllysine), and peptides. Results of pathway analysis showed that the arginine and proline metabolism, purine metabolism, alanine, aspartate and glutamate metabolism, and aminoacyl-tRNA biosynthesis were affected compared to the control. This study demonstrates that metabolomics is useful to elucidate the metabolic responses and biological effects induced by Cd-exposure.

 

 

Edited by mccoy

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3 hours ago, Ron Put said:

They use a blood test to check cadmium levels in smokers, so my guess it should work similarly for cacao. Both are long-term accumulations (the tobacco plant gets it from the soil too).

Ron, I'm going to ask the lab guys here about the SOP for Cadmium, it is not a routine analysis in my place. Whatever the reports, I think I should go on with that. I eat amounts of cacao powder comparable to those of the Kuna Indians.

Edited by mccoy

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22 hours ago, Ron Put said:

Why? I have been eating cacao nibs for years, usually between 20-40g per day. I have tested for heavy metal levels several times, and all are zilch. Cadmium results are "None detected."

Yes - I was concerned about the cadmium.  I was eating Lindt chocolate 85% cacao.

Edited by Clinton

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