149 replies to this topic

[JLL]

Yes, but the issue here is whether lowering IGF-1 might extend lifespan, and if yes, how to lower IGF-1. It's not clear to me that a vegetarian diet would automatically reduce IGF-1 in humans.

[Blue]

It looks like in humans CR is not enough. You must also do mild PR.
http://www.ncbi.nlm....pubmed/18843793

[TheFountain]

Take a look at Aubrey deGrey or any other vegetarian, they look like a walking viral infection. All one has to do is look at human teeth to figure out what our diet should be composed of. Vegetarianism is more of an "ism" than a health strategy.

Yea take a look at this walking 38 year old virus...

he looks so sickly and infected..

[TheFountain]

It's not clear to me that a vegetarian diet would automatically reduce IGF-1 in humans.

Then the studies brought up earlier that show a strong correlation between healthy vegetarian dieting and lowered IGF-1 completely went over your head.

[JLL]

It's not clear to me that a vegetarian diet would automatically reduce IGF-1 in humans.

Then the studies brought up earlier that show a strong correlation between healthy vegetarian dieting and lowered IGF-1 completely went over your head.

And apparently the ones I just posted went over yours.

Edited by JLL, 11 October 2009 - 10:58 AM.

[TheFountain]

Insulin-Like Growth Factor I, Insulin-Like Growth Factor I Binding Protein 1, Insulin, Glucose, and Leptin Serum Levels Are Not Influenced by a Reduced-Fat, High-Fiber Diet Intervention

But ARE influenced by reduced animal protein intake.

[JLL]

I just went through the thread again and I'm not sure which studies you're referring to. This one? I assume not because it didn't actually measure IGF-1 levels.

There are all kinds of "vegetarian" diets. Clearly not all of them lower IGF-1. You seem to be saying that they do, so please show us the evidence.

[JLL]

Insulin-Like Growth Factor I, Insulin-Like Growth Factor I Binding Protein 1, Insulin, Glucose, and Leptin Serum Levels Are Not Influenced by a Reduced-Fat, High-Fiber Diet Intervention

But ARE influenced by reduced animal protein intake.

Animal protein or just protein? What about a vegan diet with a lot of soy and beans?

[TheFountain]

There are all kinds of "vegetarian" diets. Clearly not all of them lower IGF-1. You seem to be saying that they do, so please show us the evidence.

I didn't say that. I said healthy vegetarian diets not ones that call themselves vegetarian and eat junk food and lots of sugar and refined carbs. In terms of citing studies there's this one and I am sure a few other's for you to digest.

'The mean serum C-reactive protein (P = .03), *insulin-like growth factor* 1 (P = .002), and leptin (P = .005) were lower in the RF group.'

Of course you'll have some contrived critique of this but so be it..

Edited by TheFountain, 11 October 2009 - 12:18 PM.

[TheFountain]

Insulin-Like Growth Factor I, Insulin-Like Growth Factor I Binding Protein 1, Insulin, Glucose, and Leptin Serum Levels Are Not Influenced by a Reduced-Fat, High-Fiber Diet Intervention

But ARE influenced by reduced animal protein intake.

Animal protein or just protein? What about a vegan diet with a lot of soy and beans?

I think it is the enzymes in meat that make it pro-IGF-1 because there are some studies that show other animal products may be secretegogues of IGF-1 as well, such as casein for example.

[JLL]

There are all kinds of "vegetarian" diets. Clearly not all of them lower IGF-1. You seem to be saying that they do, so please show us the evidence.

I didn't say that. I said healthy vegetarian diets not ones that call themselves vegetarian and eat junk food and lots of sugar and refined carbs. In terms of citing studies there's this one and I am sure a few other's for you to digest.

'The mean serum C-reactive protein (P = .03), *insulin-like growth factor* 1 (P = .002), and leptin (P = .005) were lower in the RF group.'

Of course you'll have some contrived critique of this but so be it..

Do you have access to the full paper? Were they vegans or did they eat eggs and dairy as well?

It'd be interesting to see a comparison of IGF-1 levels in omnivores and vegans with equal protein intakes. Even more interesting would be to see the same thing with non-milk drinking omnivores to see if dairy, protein or meat is the culprit.

[TheFountain]

There are all kinds of "vegetarian" diets. Clearly not all of them lower IGF-1. You seem to be saying that they do, so please show us the evidence.

I didn't say that. I said healthy vegetarian diets not ones that call themselves vegetarian and eat junk food and lots of sugar and refined carbs. In terms of citing studies there's this one and I am sure a few other's for you to digest.

'The mean serum C-reactive protein (P = .03), *insulin-like growth factor* 1 (P = .002), and leptin (P = .005) were lower in the RF group.'

Of course you'll have some contrived critique of this but so be it..

Do you have access to the full paper? Were they vegans or did they eat eggs and dairy as well?

It'd be interesting to see a comparison of IGF-1 levels in omnivores and vegans with equal protein intakes. Even more interesting would be to see the same thing with non-milk drinking omnivores to see if dairy, protein or meat is the culprit.

I gather it is animal protein generally. Some sort of enzyme metabolism co-variant. I am sure the vegetarian raw foodists consumed some form of protein be it soy or some other plant based source. Either way the studies are pointing to animal protein as the mechanism. Although eating alot of dairy (as I do when attempting to gain weight) surely cannot help matters it seems better than eating dairy+meat.

[JLL]

I've yet to see the evidence for this enzyme being the key. I mean, how can you tell whether it's protein restriction in vegans or excess animal protein in omnivores that is the key here? Vegans often have lower protein intakes, and even more importantly, while omnivores will get all the amino acids from meat and thus complete protein synthesis, plant sources (except for soy) don't have all the necessary amino acids. So even if you have a vegan eating 100 grams of protein per day, it may not be the same as an omnivore eating 100 grams of protein per day.

We already know that protein restriction is needed to lower IGF-1 in CR people. I take it they don't eat huge quantities of meat (but rather protein powders etc. with less calories), and yet their IGF-1 stays the same -- just like their protein intake. How do we account for this?

It wouldn't surprise me if it was something in meat itself that is increasing IGF-1, but so far, the proof that this is the case is lacking.

[TheFountain]

I've yet to see the evidence for this enzyme being the key. I mean, how can you tell whether it's protein restriction in vegans or excess animal protein in omnivores that is the key here? Vegans often have lower protein intakes, and even more importantly, while omnivores will get all the amino acids from meat and thus complete protein synthesis, plant sources (except for soy) don't have all the necessary amino acids. So even if you have a vegan eating 100 grams of protein per day, it may not be the same as an omnivore eating 100 grams of protein per day.

We already know that protein restriction is needed to lower IGF-1 in CR people. I take it they don't eat huge quantities of meat (but rather protein powders etc. with less calories), and yet their IGF-1 stays the same -- just like their protein intake. How do we account for this?

It wouldn't surprise me if it was something in meat itself that is increasing IGF-1, but so far, the proof that this is the case is lacking.

No matter how we break this down the studies show that vegetarian diets are lowering IGF-1 regardless of the mechanism behind it, be it protein restriction or what not. Remember a single serving of animal protein has, on average, 3-4 times the amount of protein as a single serving of plant protein. So even if it was protein restriction that did it it would seem fairly obvious that protein restriction is impossible on a meat based diet.

[Skötkonung]

Here are interesting studies on soy and IGF-1. They basically indicate that isoflavones have little to no effect on IGF-1 levels.

Study: Dietary soy and fats in relation to sere insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels in premenopausal Japanese women

"There was no significant correlation between soy product as well as soy isoflavone intake and serum IGF-1 or IGFBP-3 levels after controlling for age, total energy, percent body fat, and education level."

Study: Soy isoflavones in the treatment of prostate cancer.

"No significant changes were observed in serum levels of testosterone, IGF-1, IGFBP-3, or 5-OHmdU."

Study: Effect of red clover-derived isoflavone supplementation on insulin-like growth factor, lipid and antioxidant status in healthy female volunteers: a pilot study

"This study shows that 1-month supplementation with red clover isoflavones has a positive effect on HDL cholesterol, but at most a small effect on IGF status in premenopausal and no effect in postmenopausal subjects."

[Skötkonung]

I think it is the enzymes in meat that make it pro-IGF-1 because there are some studies that show other animal products may be secretegogues of IGF-1 as well, such as casein for example.

Be careful how much casein you are consuming. T. Colin Campbell (one of the proponents of protein restriction) found that when casein consumption exceeds 10% of daily protein intake, that the risk for certain cancers markedly increased (at least in the context of his studies). I don't know if this was directly linked to stimulation of IGF-1. A critique of the study can be found below:

"Aflatoxins are naturally occurring toxins that are produced by a variety of fungi, most notably Aspergillus flavus and Aspergillus parasiticus. These fungi normally reside in soil, but can invade food crops under conditions of high humidity or other stress.

Food crops most frequently affected are cereals, nuts and legumes (which represent the mainstays of plant
based, vegetarian diets). The toxin is also found in the milk of animals fed contaminated feed. Aflatoxins
are metabolized in the liver to become potent liver carcinogens for all mammals including humans (157).
High-level aflatoxin exposure causes liver cancer, whereas chronic, low level exposure to aflatoxin does not necessarily lead to cancer (157).

Colin's research group developed a rodent model of liver cancer in which they dosed the animals with
high concentrations (typically 200-350 microgram/kg per day for 10 days) of aflatoxin and then fed them diets containing varying amounts (typically 20, 16, 12, 8, 4 % of total energy) of casein (158-161). Regardless
of the casein dose, all animals developed cancerous or pre-cancerous liver lesions (161), however the animals fed the higher amounts of casein developed more cancerous lesions, particularly when a level of approximately 12 % casein was reached (160). From these experiments Colin concluded that, "low protein intake inhibits lesion development" and that "AFB1 (aflatoxin) induced preneoplastic foci (precancerous lesions) depends upon a high protein intake" (161).

Although Colin has inferred from his experiments with rodents that high protein diets promote cancer and
low protein diets repress it following cancer initiation by a carcinogen, this interpretation is incorrect. The
only logical conclusion that can be reached from his series of experiments is that only the milk protein,
casein, when consumed at more than 10% of energy, promotes liver cancer in rodents exposed to high
concentrations of aflatoxin. His experiments cannot be generalized to other animal proteins, such as those
found in lean meats. In the typical U.S. diet, dairy food consumption represents 10.6 % of the total energy (13)
and is distributed in the following manner: whole milk (1.6 %), low fat milk (2.1%), cheese (3.2 %), butter (1.1
%), and other 2.6 % (13). The total protein content by energy for milk is 21 % , low fat milk ~29 % , cheese ~25
% , butter 0 %, and other ~27 %. Casein represents ~80 % of all milk proteins, so the average total casein
content in the U.S diet is ~2.0 % energy. Accordingly, current consumption of casein in the U.S. diet would have little or no bearing on cancer incidence rates if we assume Colin's rodent model of cancer is correct
and applicable to humans.

In the typical U.S. diet ~75 % of the protein comes from animal products other than dairy (20). In the
U.S. diet muscle meats from birds, mammals, fish and invertebrates represent far and away the greatest
protein source, as organ meats are infrequently consumed. The primary proteins in muscle tissues
are actin and myosin. Consequently, Colin's rodent experiments using casein as a generalized surrogate
for protein in the typical U.S. diet has little or no relevance to human cancers for two reasons. First,
as I have previously shown, in the U.S. population it would be virtually impossible to ingest 10 % of the daily
caloric intake as casein, and secondly the primary animal proteins (actin and myosin) in the typical U.S.
diet were never tested in Colin's animal experiments. Hence Colin's conclusions that high dietary protein
from all animal sources promotes cancer and lower dietary protein prevents it cannot be inferred from his
rodent experiments."

Edited by Skotkonung, 14 October 2009 - 01:16 AM.

[Skötkonung]

I've yet to see the evidence for this enzyme being the key. I mean, how can you tell whether it's protein restriction in vegans or excess animal protein in omnivores that is the key here? Vegans often have lower protein intakes, and even more importantly, while omnivores will get all the amino acids from meat and thus complete protein synthesis, plant sources (except for soy) don't have all the necessary amino acids. So even if you have a vegan eating 100 grams of protein per day, it may not be the same as an omnivore eating 100 grams of protein per day.

We already know that protein restriction is needed to lower IGF-1 in CR people. I take it they don't eat huge quantities of meat (but rather protein powders etc. with less calories), and yet their IGF-1 stays the same -- just like their protein intake. How do we account for this?

It wouldn't surprise me if it was something in meat itself that is increasing IGF-1, but so far, the proof that this is the case is lacking.

No matter how we break this down the studies show that vegetarian diets are lowering IGF-1 regardless of the mechanism behind it, be it protein restriction or what not. Remember a single serving of animal protein has, on average, 3-4 times the amount of protein as a single serving of plant protein. So even if it was protein restriction that did it it would seem fairly obvious that protein restriction is impossible on a meat based diet.

I think that both quality and quantity of protein is important when discussing IGF-1. This likely explains why vegetarians have lower IGF1 - plant proteins are of lower quality and in lower quantity.

Study: Effect of dietary proteins on insulin-like growth factor-1 (IGF-1) messenger ribonucleic acid content in rat liver

"Effects of quantity and quality of dietary proteins on plasma immunoreactive insulin-like growth factor-1 (IGF-1) concentration, and content of IGF-1 mRNA in rat liver were investigated in rats. Plasma immunoreactive IGF-1 concentration in rats given a casein diet was higher than that in rats given a soya-bean-protein or protein-free diet. The IGF-1 mRNA content in liver was estimated by the Northern blot hybridization technique employing ³²P-labelled rat IGF-1 complementary DNA (cDNA). At least four molecular species of IGF-1 mRNA of different molecular weight were found in rat liver. The sizes were 0·8–1·2, 2·0, 3·6–4·0 and 7·4 kb. Most of the mRNA species decreased in the livers of rats given a gluten diet (120 g gluten/kg diet) compared with rats given the casein diet. In particular, mRNA of 7·4 kb decreased markedly. When rats were fed on the protein-free diet, mRNA of all species decreased significantly. The estimated IGF-1 mRNA in the livers of rats fed on the gluten or protein-free diet was almost 0·4 of that of the rats given the casein diet. Feeding the soya-bean-protein diet did not result in a marked effect on the hepatic content of mRNA species of IGF-1. The results showed that liver IGF-1 mRNA content is sensitively regulated by quantity and nutritional quality of dietary proteins."

[Blue]

MR has been discussed in lots of other threads. All the lab studies have also used 0% cysteine diets which is impossible to achieve on a normal diet.

[TheFountain]

Protein restriction would not be a great solution for people doing sports especially bodybuilding etc.

Yea well anyone truly interested in life extension would sacrifice momentary performance for long term benefits. Otherwise I would question how truly interested they are in it all. Especially those who have read the data. It's not like we're saying the trade off is paraplegia for life extension. More like a bit of reduction in sports performance for a longer, healthier overall life. And when you think about it health-span really would be increased too, especially as you get into old age, which, theoretically, it should take longer to get to on protein/methionine restriction diets.

Edited by TheFountain, 14 October 2009 - 01:06 PM.

[Blue]

Regading the raw food vegetarian diet study:
http://www.ncbi.nlm....6?dopt=Abstract

Does not prove that it is the meat that was the cause of the difference. Could be the lack of heating and advanced glycation end products.

[Blue]

I think that both quality and quantity of protein is important when discussing IGF-1. This likely explains why vegetarians have lower IGF1 - plant proteins are of lower quality and in lower quantity.

Study: Effect of dietary proteins on insulin-like growth factor-1 (IGF-1) messenger ribonucleic acid content in rat liver

"Effects of quantity and quality of dietary proteins on plasma immunoreactive insulin-like growth factor-1 (IGF-1) concentration, and content of IGF-1 mRNA in rat liver were investigated in rats. Plasma immunoreactive IGF-1 concentration in rats given a casein diet was higher than that in rats given a soya-bean-protein or protein-free diet. The IGF-1 mRNA content in liver was estimated by the Northern blot hybridization technique employing ³²P-labelled rat IGF-1 complementary DNA (cDNA). At least four molecular species of IGF-1 mRNA of different molecular weight were found in rat liver. The sizes were 0·8–1·2, 2·0, 3·6–4·0 and 7·4 kb. Most of the mRNA species decreased in the livers of rats given a gluten diet (120 g gluten/kg diet) compared with rats given the casein diet. In particular, mRNA of 7·4 kb decreased markedly. When rats were fed on the protein-free diet, mRNA of all species decreased significantly. The estimated IGF-1 mRNA in the livers of rats fed on the gluten or protein-free diet was almost 0·4 of that of the rats given the casein diet. Feeding the soya-bean-protein diet did not result in a marked effect on the hepatic content of mRNA species of IGF-1. The results showed that liver IGF-1 mRNA content is sensitively regulated by quantity and nutritional quality of dietary proteins."

If the high-gluten diet was lysine deficient then that is the same as protein restriction. I interpret this study as that IGF-1 mRNA was equal between a soybean and casein diet?

[Skötkonung]

Yea well anyone truly interested in life extension would sacrifice momentary performance for long term benefits. Otherwise I would question how truly interested they are in it all. Especially those who have read the data. It's not like we're saying the trade off is paraplegia for life extension. More like a bit of reduction in sports performance for a longer, healthier overall life. And when you think about it health-span really would be increased too, especially as you get into old age, which, theoretically, it should take longer to get to on protein/methionine restriction diets.

MR is controversial as it has only been tested in rodents and to achieve the results from the rodent trials it would require a diet that is un-achievable for most humans (as Blue noted, all the lab studies have also used 0% cysteine diets). I find it interesting that people would be willing to commit to such a dietary regimen with potentially harmful consequences without first even reading the entire published document (and not just the abstract) of all studies involved. I also find it interesting how such individuals would also attempt MR without first quantifying the exact methionine content of their own diet and developing an analogue maximum threshold similar to those used in the aformentioned rodent studies. Until MR is more thouroughly examined in the context of human metabolism, it is nothing more than an interesting idea that merits further research. It could be that any reasonable reduction in methionine may not be adequate to induce the life extending benefits seen in lower tier organisms. It could also be that the benefits of MR are not scalable to larger organisms. Such is the case with Resveratrol.

At any rate, any meaningful life extension will only occur through SENS.

[Skötkonung]

Did the Inuits have ketosis? That should settle if an almost exclusively animal and high-protein, high-fat diet can cause ketosis.

This study indicates that they did, and that it did not impair their physical performance.

Ketogenic diets and physical performance
"Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis."

[Skötkonung]

Did the Inuits have ketosis? That should settle if an almost exclusively animal and high-protein, high-fat diet can cause ketosis.

This study indicates that they did, and that it did not impair their physical performance.

Ketogenic diets and physical performance
"Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis."

Interesting blog post analyzing mortality and lifespan of the Inuit during the early 1800s:
http://wholehealthso...n-of-inuit.html

[Blue]

Did the Inuits have ketosis? That should settle if an almost exclusively animal and high-protein, high-fat diet can cause ketosis.

This study indicates that they did, and that it did not impair their physical performance.

Ketogenic diets and physical performance
"Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis."

"It is interesting to note from the careful observations published from the Bellevue study that Stafansson ate relatively modestly of protein, deriving between 80–85% of his dietary energy from fat and only 15–20% from protein [9]. This was, and still remains, at odds with the popular conception that the Inuit ate a high protein diet, whereas in reality it appears to have been a high fat diet with a moderate intake of protein. In his writings, Stefansson notes that the Inuit were careful to limit their intake of lean meat, giving excess lean meat to their dogs and reserving the higher fat portions for human consumption."

While this looks to be more protein than the ketogenic diet for children I would not call it a high-protein diet.

Edited by Blue, 14 October 2009 - 08:25 PM.

[Blue]

Interesting blog post analyzing mortality and lifespan of the Inuit during the early 1800s:
http://wholehealthso...n-of-inuit.html

Have we not already discussed this blogpost in another thread? Average lifespan was short.

Edited by Blue, 14 October 2009 - 08:32 PM.

[Skötkonung]

Interesting blog post analyzing mortality and lifespan of the Inuit during the early 1800s:
http://wholehealthso...n-of-inuit.html

Have we not already discussed this blogpost in another thread? Average lifespan was short.

25% of the population living past 60 during the 1830s in a hunter-gatherer culture living in arctic conditions is considered short? Maybe by contemporary standards. But you have to remember that most of these cultures, European and Asian included, had very few people living past 60 in the early 19th century. By comparison, centarians were absent from Okinawan culture until 20th century medical advances acted synergistically with their culture and diet. As recently as 1960, the average life expectancy in Okinawa was barely over 70 years of age [source]. I think this clearly indicates that normal life expectancy is the probable outcome of a prolonged and well organized ketogenic diet. Pending further study, it could be possible that ketogenic diets may have some life extending benefits, if one was able to maintain it consistently.

[Skötkonung]

While this looks to be more protein than the ketogenic diet for children I would not call it a high-protein diet.

Again, you seem to be consistently restating your misconception that hunter-gatherer cultures (or paleolithic cultures) are eating only lean meats (or more precisely, strictly high protein diets in the absence of fat and carbohydrate) when this obviously is not the case. As I demonstrated earlier with my discussion on Stefansson's "rabbit starvation", extremely high protein ketogenic diets are not sustainable for any duration of time. Ketogenic diets with less than 60% fat content by caloric volume result in this affliction. Furthermore, in such situations, there would not be enough energy from dietary fat to break down the protein via gluconeogenesis and make this process sustainable.

Lets look how gluconeogenesis works:
The liver requires energy to convert the protein to glucose. The energy comes from fat. As the liver breaks down the fat to release its energy to power gluconeogenesis, the conversion of protein to sugar, it produces ketones as a byproduct. When this occurs, you are in "ketosis." If insufficient dietary fat is provided for gluconeogenesis, the body relies on triglycerides (remember that although glucose can be converted to fat, the reaction can't go the other way. Fat is stored as a triglyceride, which is three fatty acids hooked on to a glycerol molecule). With the body depending on fat to enable gluconeogenesis, a person living in a ketogenic state with little dietary fat would quickly eat through their body-fat and encounter health problems almost immediately.

But there are also other problems...
When ketones (essentially a water soluble fat) begin being produced in large quantities as a result of gluconeogenesis, the body's tissues adapt by reducing glucose dependence and utilizing the available ketone supply. Since the ketosis process is providing energy for the brain and other tissues, the requirement for glucose drops to about 120-130g per day. This is much lower than 200g of sugar per day usually needed to meet all the needs of the glucose-dependent tissues. The implication of this conversion to ketones for energy is that body will increase its dependence of body-fat to power gluconeogenesis.

This is why I do not believe early modern humans (or the Inuit for discussion purposes) could successfully thrive on such a very high protein ketogenic diet. Such a diet would make these people sick and eventually die from loss of body-fat and other complications. These people would have only lived on exclusively very high protein diets for short durations of time, when food supplies were limited (such as reliance on stored pemmican by the Inuit).

At any rate, this is why you will find little to no modern nutrition studies involving humans on a high protein, fat deficient ketogenic diet.

Edited by Skotkonung, 14 October 2009 - 09:56 PM.

[Sillewater]

I can't find the thread where niner, kismet, and me where having a discussion on Fructose serum concentrations but I found an interesting study and I'll post it here:

Laboratory Investigation advance online publication 8 March 2010; doi: 10.1038/labinvest.2010.62
Immunological detection of fructose-derived advanced glycation end-products
Masayoshi Takeuchi1, Mina Iwaki2, Jun-ichi Takino1, Hikari Shirai1, Mihoko Kawakami1, Richard Bucala3 and Sho-ichi Yamagishi4

...The assay of Fru-AGE was established using the immunoaffinity-purified-specific antibody, and the presence of Fru-AGE in healthy and diabetic serum was shown (7.04±4.47 vs 29.13±18.08 U/ml).