High vs Low Protein

P. D. Mangan Tweeted a quote from a research paper, Reversal of epigenetic aging and immunosenescent trends in humans by Gregory M. Fahy et al. He stated that  the “Most important sentence in aging reversal study” is the following: “Human longevity seems more consistently linked to insulin sensitivity than to IGF‐1 levels, and the effects of IGF‐1 on human longevity are confounded by its inverse proportionality to insulin sensitivity.” Mangan added that “This line agrees with what I wrote a while back” (How Carbohydrates and Not Protein Promote Aging); and in the comments section of that article, someone pointed to a supporting video by Dr. Benjamin Bikman (‘Insulin vs. Glucagon: The relevance of dietary protein’). Here is the context of the entire paragraph from the discussion section of the research paper:

“In this regard, it must be pointed out that GH and IGF‐1 can also have pro‐aging effects and that most gerontologists therefore favor reducing rather than increasing the levels of these factors (Longo et al., 2015). However, most past studies of aging and GH/IGF‐1 are confounded by the use of mutations that affect the developmental programming of aging, which is not necessarily relevant to nonmutant adults. For example, such mutations in mice alter the normal innervation of the hypothalamus during brain development and prevent the hypothalamic inflammation in the adult (Sadagurski et al., 2015). Hypothalamic inflammation may program adult body‐wide aging in nonmutants (Zhang et al., 2017), but it seems unlikely that lowering IGF‐1 in normal non‐mutant adults can provide the same protection. A second problem with past studies is a general failure to uncouple GH/IGF‐1 signaling from lifelong changes in insulin signaling. Human longevity seems more consistently linked to insulin sensitivity than to IGF‐1 levels, and the effects of IGF‐1 on human longevity are confounded by its inverse proportionality to insulin sensitivity (Vitale, Pellegrino, Vollery, & Hofland, 2019). We therefore believe our approach of increasing GH/IGF‐1 for a limited time in the more natural context of elevated DHEA while maximizing insulin sensitivity is justified, particularly in view of the positive role of GH and IGF‐1 in immune maintenance, the role of immune maintenance in the retardation of aging (Fabris et al., 1988), and our present results.”

In the Twitter thread, Командир Гиперкуба said, “So it is insulin [in]sensitivity than drives ageing rather than IGF‐1/GH. Huge if true.” And GuruAnaerobic added that, “I assume this isn’t IR per se, but IR in the presence of carbohydrate/excess food. IOW, the driver is environment.” Mangan then went onto point out that, “It explains the dichotomy of growth vs longevity, and why calorie restriction increases lifespan.” Mick Keith asked, “So drop carbs and sugar?go paleo style?” And Mangan answered, “There are other aspects to insulin sensitivity, but yes.” All of this cuts to the heart of a major issue in the low-carb community, an issue that I only partly and imperfectly understand. What I do get is this has to do with the conclusions various experts come to about protein, whether higher amounts are fine or intake should be very limited. Some see insulin sensitivity as key while others prioritize IGF-1. The confounding requires careful understanding. In the comments section of Mangan’s above linked article, Rob H. summed it up well:

“Great post, very timely too as I believe this is an issue that seems to be polarising the science-based nutrition space at the moment. Personally I fall down on the same side as you Dennis – as per Ben Bikman’s video which has also been posted here, as well as the views of all the main protein researchers including Stuart Philips, Jose Antonio, Donald Layman, Gabrielle Lyon, Ted Naiman, Chris Masterjohn etc who all believe the science clearly supports a high protein intake eg 1.6 -2.2g/kilo of bodyweight – with no upper limit which has yet been observed. At the same time, I have just been reading the new book by Dr Steven Gundry ‘The Longevity Paradox’. Has anyone read this one yet? Whilst about 90% of the content is fairly solid stuff (although nothing that hasn’t already been written about here) he aggressively supports Longo’s view that we should only consume 0.37g protein/ kilo of bodyweight, eg around 25g of protein/ day for most males. Also that animal protein should be avoided wherever possible. Personally I consume double that amount of protein at each meal! It appears that Longo, Gundry, Dr Ron Rosedale and Dr Mercola are all aligned in a very anti-animal protein stance, but also believe their view is backed by science – although the science quoted in Gundry’s book seems to be largely based on epidemiology. Both sides can’t be right here, so I hope more research is done in this field to shut this debate down – personally I feel that advising ageing males to consume only 25g of protein a day is extremely irresponsible.”

In response, Mangan wrote, “I agree that is irresponsible. Recently Jason Fung and James DiNicolantonio jumped on the anti animal protein bandwagon. My article above is my attempt (successful, I hope) to show why that’s wrong.” Following that, Rob added, “Humans have been consuming animal proteins for most or all of our evolutionary history. And certainly, large quantities of animal protein were consumed at times (as when a kill of a large animal was made). So, I cannot imagine that the “evidence” supporting an anti-animal protein stance can be solid or even science-based. This sounds like a case of certain researchers trying their best to find support for their pre-determined dietary beliefs (vegan proponents do this all the time). I’m not buying it.” It’s very much an ongoing debate.

I have suspicions about the point of confusion that originated this disagreement. Fear of promoting too much growth through protein is basically the old Galenic argument based on humoral physiology. The belief is that too much meat as a stimulating/nurturing substance built up the ‘blood’ with too much heat and dryness which would burn up the body and cause a shortened lifespan. This culturally inherited bias about meat has since been fancied up with scientific language. But ancient philosophy is not the best source for formulating modern scientific theory. Let me bring this back to insulin sensitivity and insulin resistance that appears to play the determining role. Insulin is a hormone and so we must understand this from an endicrinological approach, quite different than Galenic-style fears about meat that was filtered through the Christian theology of the Middle Ages.

Hormones are part of a complex hormonal system going far beyond macronutrients in the diet, although it does appear that the macronutrient profile is a major factor. Harry Serpano, in a discussion with Bart Kay, said that: “In a low insulin state, when you’re heavy meat and fat and your insulin is at 1.3, as Dr. Paul Mangan has actually shown in one of his videos, it’s quite clear; and in what I’m showing in one of the studies, it’s quite clear. It’s so close to basically fasting which is 0.8 — it’s very low. You’re not going to be pushing up these growth pathways like mTOR or IGF-1 in any significant way.” Like with so much else, there is strong evidence that what we need to be worrying about is insulin, specifically on a high-carb diet that causes insulin resistance and metabolic syndrome. That is what is guaranteed to severely decrease longevity.

This question about too much protein recently came up in my own thoughts while reading Dr. Stephen Gundry’s new book, The Longevity Paradox. As mentioned above, he makes a case against too much animal protein. But it sounds like there is more information to be considered in the affect on health, growth, and longevity. In a dialogue with Gundry, Dr. Paul Saladino defended meat consumption (Gundry’s Plant Paradox and Saladino’s Carnivory). What Mangan has added to this debate strengthens this position.

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In one of the above quoted comments, Robert H. mentions that Dr. Joseph Mercola is one of those “aligned in a very anti-animal protein stance, but also believe their view is backed by science.” It’s interesting that I’m just now listening to a discussion between Mercola and Siim Land. They met at a conference and got to talking. Mercola then read Land’s book, Metabolic Autophagy. Land is more in the camp supporting the value of protein. His view is nuanced and the debate isn’t entirely polarized. The role protein plays in health depends on the health outcomes being sought and the health conditions under which protein is being eaten: amounts, regularity of meals, assimilation, etc. It’s about how one’s body is able to use protein and to what end.

Right at the beginning of their talk, Mercola states that he is impressed by Land’s knowledge and persuaded by his view on protein. Land makes the simple point that one doesn’t want to be in autophagy all the time but to cycle between periods of growth and not. Too much protein restriction, especially all the time, is not a good thing. Mercola seems to have come around to this view. So, it’s a shifting debate. There is a lot of research and new studies are coming out all the time. But obviously, context is important in making any statement about protein in the diet. Maybe Saladino will similarly bring Gundry on board with greater protein being a good thing for certain purposes or maybe come to a middle ground. These dialogues are helpful, in particular for an outsider like me who is listening in.

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On a personal note, I’m not sure I take a strong position either way. But I’ve long been persuaded by Siim Land’s view. It feels more moderate and balanced. The opposite side can sound too fear-mongering about protein, not seeming to allow as much differences in contexts and conditions. From a low-carb perspective, one has to replace carbs with something and that means either protein or fat, and one can only consume so much fat. Besides, proteins really are important for anabolism and activating mTOR, for building of the body. Maybe if you’re trying to lose weight or simply maintaining where you’re at with no concern for healing or developing muscle then protein would play less of a role. I don’t know.

Traditional societies don’t seem to worry about protein amounts. When they have access to it, they eat it, at times even to the point of their bellies distending. And when not, they don’t. Those populations with greater access don’t appear to suffer any harm from greater protein intake. Then again, these traditional societies tend to do a lot of strenuous physical activity. They also usually mix it up with regular fasting, intermittent and extended. I’m not sure how optimal protein levels may differ depending on lifestyle. Still, I’d think that the same basic biological truths would apply to all populations. For most people in most situations, increased protein will be helpful at least some of the time and maybe most of the time. Other than fasting, I’m not sure why one needs to worry about it. And with fasting, protein restriction happens naturally.

So, maybe eat protein to satiation. Then throw in some fasting. You’ll probably be fine. There doesn’t seem to be anything to be overly concerned about, based on what evidence I’ve seen so far.

Gundry’s Plant Paradox and Saladino’s Carnivory

There is a great discussion between Dr. Steven Gundry and Dr. Paul Saladino. It’s an uncommon dialogue. Even though Gundry is known for warning against the harmful substances in plant foods, he has shifted toward a plant-based diet in also warning against too much animal foods or at least too much protein. As for Saladino, he is a carnivore and so takes Gundry’s argument against plants to a whole other level. Saladino sees no problem with meat, of course. And this leads to one point of potential conflict. His view contradicts what Gundry writes about in his most recent book, The Longevity Paradox.

A major argument in Gundry’s book is that too much protein leads to elevated IGF-1. That has to do with the concern that it is unhealthy for the body to be permanently in growth mode. This partly misses the point that many people on animal-based diets tend toward fasting, ketosis, and autophagy, sometimes caloric restriction as well. This happens because, as starchy and sugary plant foods are eliminated, hunger and cravings lessen. It becomes easier for people to eat less or go for long periods without food, sometimes without intentionally trying to do so.

So, contrary to Gundry’s fear, one would actually expect a carnivore diet to be low in IGF-1. That is exactly what Saladino has found, in himself and in his patients. That goes against a key argument in The Longevity Paradox. The fact of the matter is that a plant-based diet is more likely to drive up IGF-1. “So most of the carnivores I test for IGF-1 are around 120,” said Saladino, “which is significantly lower than people on mixed diets who are not even carnivores. So I think this brings back the idea of context. And the context that I’m talking about here is that IGF-1 can be triggered by a lot of things. But I think that the response of the body to protein is very different when we are in ketosis, than it is on a mixed diet. And we see this with insulin as well.”

Also, they got onto the topic of TMAO. Saladino points out that fish has more fully formed TMAO than red meat produces in combination with grain-loving Prevotella. Even vegetables produce TMAO. So, why is beef being scapegoated? It’s pure ignorant idiocy. To further this point, Saladino explained that he has tested the microbiome of patients of his on the carnivore diet and it comes up low on the Prevotella bacteria. He doesn’t think TMAO is the danger people claim it is. But even if it were, the single safest diet might be the carnivore diet.

Gundry didn’t even disagree. He pointed out that he did testing on patients of his who are long-term vegans and now in their 70s. They had extremely high levels of TMAO. He sent their lab results to the Cleveland Clinic for an opinion. The experts there refused to believe that it was possible and so dismissed the evidence. That is the power of dietary ideology when it forms a self-enclosed reality tunnel. Red meat is bad and vegetables are good. The story changes over time. It’s the saturated fat. No, it’s the TMAO. Then it will be something else. Always looking for a rationalization to uphold the preferred dogma.

Related points are made about advanced glycation end products (AGEs). Gundry asked if Saladino was worried about these. He did say they were a concern, but not for carnivores more than for anyone else on other diets. Everything we cook is going to have AGEs, but we can we lessen them by how we cook (e.g., avoid cooking with olive oil). This problem is far from being limited to cooking meat. And no matter what one is eating, there are ways of avoiding AGEs, such as using a pressure cooker.

Point by point, Saladino knocked down all possible criticisms of eating meat. And, surprisingly, there seemed to be little push back from Gundry. They both understood the science and there really was no difference of opinion based on the facts themselves. It was more about what each preferred to emphasize and the strategies they advocated, but nonetheless both appeared to understand the scientific-based reasoning of the other. It was rather refreshing. In the end, Gundry seemed to be more in line with Saladino than I thought he would be from having read The Longevity Paradox. He even threw out some evidence for how animal or insect protein is important even for other primates. Here are Gundry’s concluding thoughts:

“And in fact, one of the things that got me interested in bugs is that a very famous observation was made at the Washington Zoo back in the 1920s. And I wrote about this in my first book, Dr. Gundry’s Diet Evolution. They brought a bunch of marmoset monkeys from South America who are obligate frugivorous, all they eat is fruit. And they fed them fruit and these monkeys did not do well. They didn’t reproduce. And a young zoologist at the zoo said, “You know, we’re going giving them fruit that basically we buy at the grocery store. And the fruit that these guys are eating out in the jungle is full of bugs.”

“In fact, chimpanzees have been observed by Jane Goodall to take a bite of fruit and look at it, and then throw it on the ground. And she found that the ones that were thrown on the ground didn’t have any bugs in it. And so they introduced 6% animal protein into the diet of the marmoset monkeys to make up for these insects that they weren’t getting in their diet. And lo and behold, they thrived, and they actually began to reproduce. And it was one of the things that really compelled my argument that we’re a great ape, and even great apes have to have some animal protein in their diet.

“So that’s a great question. And chimpanzees will take little sticks and go into termite mounds and get the termites. And believe it or not, even hummingbirds who all they do is drink sugar water will actually go after gnats and little bugs growing or crawling on leaves, because they have to have a source of animal protein.”

We are coming to realize how important are these kinds of foods. Primates don’t only eat insects for observations of hunting have also been made. Even many herbivores will eat some occasional meat when it’s available. There are hundreds of videos of deers, rabbits, etc eating meat, maybe usually what they find dead but sometimes another living animal. We can argue about the carnivore diet, but meat consumption sure is a lot more common than previously thought.

This is true among humans as well. When the so-called Blue Zones are looked at more closely, they include more animal foods than had been acknowledged. Some of the longest living populations are in Asia where research, opposite of that in the West, correlates meat with greater health and longer life. Saladino brought up the example of Hong Kong, the residents of which have a long lifespan averaging 85 years old while also on average eating a pound and a half of meat on a daily basis. Whether or not one wants to be on a carnivore diet, there is no scientific reason to live in fear of animal foods. As Saladino makes clear, humans have been eating large amounts of meat for hundreds of thousands of years. This is what we were evolved to eat.

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Transcript

Carnivore Diet: Crazy delicious, or just plain crazy?

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Like water fasts, meat fasts are good for health.
Carnivore Is Vegan
Too Much Protein?
Vitamin D3 and Autophagy
Fasting, Calorie Restriction, and Ketosis
Ketogenic Diet and Neurocognitive Health
Spartan Diet
Carcinogenic Grains
The Agricultural Mind
Blue Zones Dietary Myth
Low-Carb Diets On The Rise
Does a Healthy LCHF Diet Protect Against Sunburns?
Obese Military?
Official Guidelines For Low-Carb Diet
Slow, Quiet, and Reluctant Changes to Official Dietary Guidelines
American Diabetes Association Changes Its Tune
Dietary Dogma: Tested and Failed
Dietary Dictocrats of EAT-Lancet
The Fad of Warning About Fad Diets