Low Protein / High Carb Diet - Healthier Than Caloric Restriction

haidut

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Ray has written about this before, several times across his many articles. He criticizes the caloric restriction (CR) studies due to the fact that the studies used toxic food ingredients, including PUFA. So, lowering those toxic food ingredients in the CR diets would produce a positive effect even though it is the restriction of toxins that is beneficial and not total calories.
Well, as we have becomes accustomed lately, Ray seems to be right again, at least when it comes to the health benefits of CR. The study did not test effects on lifespan but the authors plan on doing it soon.
This study shows that when mice were fed a low protein / high carb (LPHC) diet they enjoyed the same health benefits as CR animals, despite a much higher caloric ingestion. In other words, despite the much higher caloric intake the mice did not get fat. On the contrary, the CR mice had worse body composition than the LPHC mice, but it was still better than the HPLC mice. The LPHC mice had the highest metabolism and the healthiest metabolic profile as well.
Finally, keep in mind that the LPHC and HPLC mice were fed ad libitum, so the LPHC group had every opportunity to get fat but it didn't.

http://www.cell.com/cell-reports/abstra ... %2900505-7

Here are the highlights of the study, according to the authors.

  • Ad libitum low-protein, high-carbohydrate diets (LPHC) improve metabolic health
    Caloric restriction combined with LPHC diet does not provide added health benefits
    Energy intake and energy expenditure are increased on LPHC diets

Here is an screenshot of the mouse diets and their composition. You can see that the LPHC mice enjoyed great health despite eating soybean oil as the majority of their fat intake.


Here are some additional excerpts from the study, which I thought were notable:

"...More recently, it has been demonstrated in studies using nutritional geometry that the balance of macronutrients has a profound impact on healthspan and lifespan in animals with ad libitum (AL) access to food (Lee et al., 2008, Piper et al., 2011, Solon-Biet et al., 2014). In these studies, CR induced by dietary dilution did not increase lifespan (Solon-Biet et al., 2014). In AL-fed mice and Drosophila melanogaster, diets low in protein and high in carbohydrates (LPHC) maximized lifespan, while a reduction of total energy intake had no positive impact on longevity (Lee et al., 2008, Solon-Biet et al., 2014). Moreover in mice, LPHC diets were associated with improved late-life cardiometabolic health (Solon-Biet et al., 2014) and a younger immune profile (Le Couteur et al., 2014). Low protein intake has also been associated with better health and reduced mortality in observational studies of humans (Levine et al., 2014), while high-protein, low-carbohydrate (HPLC) diets are associated with higher mortality, cardiovascular disease, and diabetes mellitus (Fontana and Partridge, 2015, Fung et al., 2010, Lagiou et al., 2012, Simpson et al., 2015)."

"...The question arises as to which dietary intervention is more effective at improving metabolic health and whether there is any synergy between these dietary regimens. In this study, we directly compared CR with diets differing in protein to carbohydrate ratio and evaluated several metabolic and hepatic outcomes. The results indicate that LPHC diets under AL-feeding conditions achieve the metabolic gains seen with CR. As expected, LPHC was associated with increased energy intake, but over a period of 8 weeks this was counterbalanced by increased energy expenditure and did not lead to a significant increase in body adiposity or fatty liver. Additional health improvements were not achieved by combining CR with LPHC diets, although CR prevented the negative metabolic consequences of a HPLC diet in AL-fed mice."

"...Energy expenditure was significantly higher in the AL LPHC animals compared to all of the CR animals. The respiratory exchange ratio (RER) approached 1 in the AL LPHC animals, indicating carbohydrate was the primary source of energy, compared to the other groups, where the value approached 0.7, indicating utilization of fat (Figure 4A; Table S2). There were discernible effects of dietary interventions on body composition. Body mass was lower in the CR animals (Figure 1C) while, interestingly, percentage body fat showed opposing patterns, with animals in CR groups tending to have increased adiposity (relative to lean mass) (Figure 4C)."

"...Our results provide a direct comparison of CR to AL LPHC diets, to determine whether it is possible to generate similar metabolic outcomes achieved with CR using AL diets. Our results show that, after 8 weeks, AL-fed LPHC mice had similar metabolic improvements as seen under CR, despite increased energy intake, but without the development of increased body adiposity and fatty liver that is observed in longer-term chronic LPHC feeding. Manipulating dietary P:C ratios in animals under CR conditions did not generate any additional benefits in terms of these outcomes, nor did it cause any detrimental effects to the mice."

"...Mice, like humans and various other species, demonstrate “protein leverage,” where protein intake is prioritized over fat and carbohydrates (Gosby et al., 2011, Raubenheimer et al., 2015, Simpson and Raubenheimer, 2005). Such an effect was evident in the present study, with the AL LPHC diet resulting in increased food and energy intake of about 25%–30% compared to the AL HPLC diet. Despite this elevated intake, we did not observe increased adiposity, body weight, or diet-induced fatty liver in AL LPHC mice. They did, however, show increased energy expenditure, which is consistent with increased diet-induced thermogenesis (DIT) serving to dissipate excess ingested energy and slow development of adiposity (Huang et al., 2013, Stock, 1999)."

"...AL HPLC diets were associated with decreased insulin sensitivity, indicated by elevated circulating insulin, HOMA, and pancreatic glucagon. This metabolic dysregulation may be attributed to the upregulation of gluconeogenesis, subsequently increasing glycogen turnover and total hepatic glucose output (Eisenstein et al., 1974, Linn et al., 2000). Whereas HPLC diets do not sustain optimal late-life cardiometabolic health, it is important to note that nutritional requirements change with age, and higher P:C diets are required to support reproduction rather than sustain maximal lifespan (Simpson et al., 2015, Solon-Biet et al., 2014, Solon-Biet et al., 2015)."

Haidut's note: The negative effects seen with the HPLC diet were probably due to a large part to increased cortisol, which is a known side effect of HPLC diets.

"...Here, we have compared the metabolic effects of short-term CR and AL LPHC diets in mice. The results of this study suggest that it may be possible to titrate the balance of macronutrients to gain some of the metabolic benefits of CR, without the challenge of a 40% reduction in caloric intake. A central priority is to further investigate and compare the long-term effects of traditional CR and AL LPHC diets on metabolic health and lifespan in mice and other model organisms, as well as to begin to consider the effects of the type and quality of proteins and carbohydrates."
 

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jyb

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A problem is the methionine as confounding factor, Ray seems to think it is a big deal lifespan problem in those studies. The high protein ones had 10g/kg of methionine. Seems like huge but I'm not sure what's the human equivalent so can't tell if that's a lot. But either way, the low protein mice can be seen as methionine restricted compared to others.
 
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haidut

haidut

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jyb said:
A problem is the methionine as confounding factor, Ray seems to think it is a big deal lifespan problem in those studies. The high protein ones had 10g/kg of methionine. Seems like huge but I'm not sure what's the human equivalent so can't tell if that's a lot. But either way, the low protein mice can be seen as methionine restricted compared to others.

That's a good point. The 9.8g/kg methionine for a mouse is about 700mg/kg for a human. So, for a 75kg human that would be about 52g per day. This is huge, and quite unrealistic for a human on any diet. I wonder why that added so much methionine to the high protein diet...
On the other hand, I think the findings for the LPHC diet are still valid compared to the CR diet. The mice on LPHC diet got normal casein, which contains methionine and then got some extra methionine on top of that. So, it seems the CR and LPHC diet are realistic and comparable in benefits.
The HPLC diet would be toxic for a human with all that extra methionine added and I am not sure exactly what human diet it mimics.
 

sweetpeat

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haidut said:
You can see that the LPHC mice enjoyed great health despite eating soybean oil as the majority of their fat intake.

And massive amounts of starch. Interesting.
 

Dean

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So I guess the refeeder crowd here can do a victory lap? To get the Peat minimum 80g protein, you'd need upwards of 6k calories to keep protein intake % at 5. I still think it's important to point out that this isn't in line with what Peat recommends to people (not that it's wrong, per se--nor do I want to restart that argument here). I've always heard him come down on the side of a fairly even distribution between the macros.

Also wondering how this study can be squared with previous ones posted about a 35% protein diet reversing fatty liver?

I've also seen info. that diets with high carb % (60-70+) causes fatty liver. So, is it possible that the metabolism boost with high carb, low protein without fattening of the liver is temporary? The study was for only 8 weeks. Is it possible long term use of that high of a percentage of carbs in diet could have different results/effects?
 
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haidut

haidut

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Dean said:
So I guess the refeeder crowd here can do a victory lap? To get the Peat minimum 80g protein, you'd need upwards of 6k calories to keep protein intake % at 5. I still think it's important to point out that this isn't in line with what Peat recommends to people (not that it's wrong, per se--nor do I want to restart that argument here). I've always heard him come down on the side of a fairly even distribution between the macros.

Also wondering how this study can be squared with previous ones posted about a 35% protein diet reversing fatty liver?

I've also seen info. that diets with high carb % (60-70+) causes fatty liver. So, is it possible that the metabolism boost with high carb, low protein without fattening of the liver is temporary? The study was for only 8 weeks. Is it possible long term use of that high of a percentage of carbs in diet could have different results/effects?

Those are good point, especially the long term effects of such a diet. The study talks about these issues in the Discussion section.
Overall, Peat seems to give various guidelines in terms of macros. I have also heard him say that "about equal" distribution of calories is probably optimal. However, that would mean 33% protein, which means 150g+ of protein. He says several times that protein crab ratio should be at least 1:2. He also says 80g-100g of protein is optimal. Not sure how all of these recommendations reconcile, but I think his point that carbs are not fattening, especially ones that do not trigger so much insulin as starch, seems more or less confirmed by the studies. All the high-carb fattening studies I have seen were essentially high fat diets as well.
 
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The point of Ray Peat is restricting certain amino acids is what's behind caloric restriction. Which is probably what happened here. You don't really see Ray Peat eating eighty grams of just any protein.
 
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haidut

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Such_Saturation said:
The point of Ray Peat is restricting certain amino acids is what's behind caloric restriction. Which is probably what happened here. You don't really see Ray Peat eating eighty grams of just any protein.

I think it's actually lowering PUFA accumulation that Ray thinks is behind most benefits of CR.

http://raypeat.com/articles/articles/iron-dangers.shtml
"...A nutrition researcher in San Diego suspected that the life-extending effects of calorie restriction might be the result of a decreased intake of toxins. He removed the toxic heavy metals from foods, and found that the animals which ate a normal amount of food lived as long as the semi-starved animals. Recently, the iron content of food has been identified as the major life-shortening factor, rather than the calories."

http://raypeat.com/articles/articles/fa ... ion3.shtml
"...Several studies suggest that a high degree of unsaturation in the fats is fundamentally related to the aging process, since long lived species have a lower degree of unsaturation in their fats. Caloric restriction decreases the age-related accumulation of the fatty acids with 4 and 5 double bonds."

http://raypeat.com/articles/articles/vitamin-e.shtml
"...The carcinogenic properties of the polyunsaturated fats have been known for more than 50 years, as has the principle of extending the life span by restricted feeding. More recently several studies have demonstrated that the long lived species contain fewer highly unsaturated fats than the short lived species. Restriction of calories prevents the lipids in the brain, heart, and liver from becoming more unsaturated with aging. (Lee, et al., 1999; Laganiere, et al., 1993; Tacconi, et al., 1991; R. Patzelt-Wenczler, 1981.)"

http://raypeat.com/articles/articles/un ... fats.shtml
"...With aging, the highly peroxidizable fatty acids, arachidonic and docosahexaenoic acid, increase greatly in a variety of tissues, and lipid peroxidation increases with aging. Peroxidation slows mitochondrial respiration, lowering the metabolic rate. Caloric restriction slows the accumulation of the highly unsaturated fatty acids in mitochondria, and reduces peroxidation."

And of course this quote, in which it seems it is both the effects of restricting certain amino acids as well as the lower rate of PUFA accumulation that Peat favors.
http://raypeat.com/articles/articles/gelatin.shtml
"...Although Clive McKay's studies of life extension through caloric restriction were done in the 1930s, only a few studies have been done to find out which nutrients' restriction contributes most to extending the life span. Restricting toxic heavy metals, without restricting calories, produces about the same life-extending effect as caloric restriction. Restricting only tryptophan, or only cysteine, produces a greater extension of the life span than achieved in most of the studies of caloric restriction. How great would be the life-span extension if both tryptophan and cysteine were restricted at the same time? "
 

Dean

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Well, I am at around 150g. of protein right now, 30% of calories. I am keeping my carbs at twice the protein, with my fat very low. I was under the impression though that if I added more fat (i.e.- even macro distribution) I could reduce the carbs and not worry about keeping carbs to protein at 2:1. I mean, as long as your giving your body carbs or fat as fuel, right? Or, is this mistaken?

I know most here seem to thrive on ultra high carb; and I know Peat says that hypothyroid people should limit protein to 80-100g, but since upping my protein I am finally getting a boost in appetite. With a higher percentage of carbs and staying in Peat's range on protein, I experienced energy crashes and felt less well. The best periods of health in my past have also been on higher protein regimes. I don't know which would be making the difference in terms of metabolism and feeling of wellness, the higher total intake of protein or the higher percentage of calories taken as protein?
 
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haidut said:
And of course this quote, in which it seems it is both the effects of restricting certain amino acids as well as the lower rate of PUFA accumulation that Peat favors.
http://raypeat.com/articles/articles/gelatin.shtml
"...Although Clive McKay's studies of life extension through caloric restriction were done in the 1930s, only a few studies have been done to find out which nutrients' restriction contributes most to extending the life span. Restricting toxic heavy metals, without restricting calories, produces about the same life-extending effect as caloric restriction. Restricting only tryptophan, or only cysteine, produces a greater extension of the life span than achieved in most of the studies of caloric restriction. How great would be the life-span extension if both tryptophan and cysteine were restricted at the same time? "

Yes! That is the one I remember.
 

Gl;itch.e

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I wonder why they chose to use the cornstarch as the only carbohydrate variable and not sucrose as well.
 

jyb

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haidut said:
That's a good point. The 9.8g/kg methionine for a mouse is about 700mg/kg for a human. So, for a 75kg human that would be about 52g per day. This is huge, and quite unrealistic for a human on any diet. I wonder why that added so much methionine to the high protein diet...
On the other hand, I think the findings for the LPHC diet are still valid compared to the CR diet. The mice on LPHC diet got normal casein, which contains methionine and then got some extra methionine on top of that. So, it seems the CR and LPHC diet are realistic and comparable in benefits.
The HPLC diet would be toxic for a human with all that extra methionine added and I am not sure exactly what human diet it mimics.

Actually the whole protein load seems insane, not just methionine. I mean, there's 10 times more protein in the HPLC, which is nonsense. In humans, that's like comparing a poor diet, let's say 30g/d, to a whopping 300g/d... But exaggerating on protein is already known to do bad things, for example increased cortisol.
 
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jyb said:
Hyperlipid thinks this study is indeed junk: http://high-fat-nutrition.blogspot.co.u ... 0casein%3F

That's not the same study. The one he is talking about is from 2014 and the one I posted is from 2015. The titles are also different, even though they tested similar concepts. The methionine overload is still there though. I doubt the scientist would just add that insane amount of methionine without reason. Maybe I will write to them and ask for clarification.
 

jyb

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haidut said:
jyb said:
Hyperlipid thinks this study is indeed junk: http://high-fat-nutrition.blogspot.co.u ... 0casein%3F

That's not the same study. The one he is talking about is from 2014 and the one I posted is from 2015. The titles are also different, even though they tested similar concepts. The methionine overload is still there though. I doubt the scientist would just add that insane amount of methionine without reason. Maybe I will write to them and ask for clarification.

Hyperlipid thinks he knows why...

Methionine restriction has been shown to prevent metabolic syndrome and possibly to extend lifespan. If you wanted to show protein was bad, might you spike casein by adding extra methionine?
 
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haidut

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jyb said:
haidut said:
jyb said:
Hyperlipid thinks this study is indeed junk: http://high-fat-nutrition.blogspot.co.u ... 0casein%3F

That's not the same study. The one he is talking about is from 2014 and the one I posted is from 2015. The titles are also different, even though they tested similar concepts. The methionine overload is still there though. I doubt the scientist would just add that insane amount of methionine without reason. Maybe I will write to them and ask for clarification.

Hyperlipid thinks he knows why...

Methionine restriction has been shown to prevent metabolic syndrome and possibly to extend lifespan. If you wanted to show protein was bad, might you spike casein by adding extra methionine?

But why would they want to show protein is bad? The way I read both of their studies was they wanted to show that with the right macronutrient ratio you don't need CR, and in fact CR has some negative effects of its own.
Btw, the mice in the LPHC group had the human equivalent of 5g - 6g of extra methionine, which is also not low and certainly not close to restricting it. If they wanted to skew the results I would have expected to see much less extra methionine in the LPHC group...
 

jyb

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haidut said:
If they wanted to skew the results I would have expected to see much less extra methionine in the LPHC group...

Well, they have to put at least some to make things comparable so can't go much below 1g... Which is amplified by factor of 10 between groups for an amino acid with bad reputation for those kind of lifespan studies.

If you look at that plus the high PUFA poison...I find it not difficult to hate this study.
 

Waremu

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Dean said:
So I guess the refeeder crowd here can do a victory lap? To get the Peat minimum 80g protein, you'd need upwards of 6k calories to keep protein intake % at 5. I still think it's important to point out that this isn't in line with what Peat recommends to people (not that it's wrong, per se--nor do I want to restart that argument here). I've always heard him come down on the side of a fairly even distribution between the macros.

Also wondering how this study can be squared with previous ones posted about a 35% protein diet reversing fatty liver?

I've also seen info. that diets with high carb % (60-70+) causes fatty liver. So, is it possible that the metabolism boost with high carb, low protein without fattening of the liver is temporary? The study was for only 8 weeks. Is it possible long term use of that high of a percentage of carbs in diet could have different results/effects?

Keep in mind that Ray Peat did somewhat change his position on macronutrient ratios from his previous position a number of years ago. Years ago, Ray Peat said he ate a higher fat (saturated over PUFA, of course) diet until a number of years ago, when he realized that his PUFA consumption should ideally be lower and also because even many animal foods that are high in saturated fat can still add a decent amount of PUFA if consumed in large amounts.

Ever since he changed his position, Ray Peat has really been advocating a relitively low fat, moderate protein (80g-100g is moderate by today's standards, whereas 1g per pound is higher), high carb diet. Of course, Ray Peat didn't specifically tell people what ratios to consume, but when his latest work is compiled and what he does himself and says is ideal is all put together, we can really see that Ray Peat advocates a low fat, high carb, moderate protein diet. He says many people can get away with a higher amount of protein of they are athletic (like 1 gram per pound), but if one factors in the typical caloric increase (because of being an athlete and for recovery) that goes along with that larger protein increase then it would still balance to be a moderate and not high protein intake.
 

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