Protein problem
In my odyssey of reading and writing about fat science I have stumbled on the new idea that the epidemic of obesity may be caused by eating to much protein. The low fat fiasco is well known and there are still a lot of experts on the it's-the-carbs-stupid bandwagon. But what if it's been the proteins all along? Wouldn't that be a kicker.
That's all there are just those three possible food suspects in the crime of obesity - protein, fat, and carbohydrates. However only protein is necessary to prevent you from dying. You will die if you don't eat anything. But you could probably survive if you don't eat any fats or carbohydrates. Maybe that's why it has been flying under the radar.
In this essay I try to cobble together and organize multiple of my substack articles about this idea.
Feeding muscles protein
“If you keep muscle healthy, you’ve got a good shot at avoiding obesity, avoiding diabetes, avoiding cancer, etc.” —Don Layman
Don Layman is an illustrious Food Science and Human Nutrition maven at the University of Illinois Urbana-Champaign. He sees the world of human welfare through the proteins in our bodies and diets. I recently listened to a Peter Attia podcast that interviewed him.
Firstly there are some nifty basic science things this podcast added to the background about protein nutrition.
How much protein you need to eat is apparently very hard to figure out and the recommended dietary allowances (RDAs) are based on gross approximations and then doubled just to be safe. Professor Laymen says that the building blocks of proteins in the body, the 21 amino acids, 9 of which are essential and have to be eaten because they can't be made by our metabolic chemistry, should be thought of as like vitamins. It's not just a matter of total protein. The body needs to have available every amino acid building block for a necessary protein or the body doesn't make that protein. He argues we probably need to eat more and better proteins than recommended. But I would quibble that since the RDA of protein is so sloppy and mysterious it could be that the converse is also true.
He points out that all the proteins in the body are in a constant flux and turnover. Why are proteins so fragile that we have to keep throwing them out and making new ones? Part of it is the fine tuning of reacting and adjusting to life's vicissitudes. He does not mention any estimates of the proportion of amino acids that derive from recycled proteins and how many have to be eaten because they are lost. That may also be a flux that is mostly unknowable but that would affect how much protein we need to be eating, in the absence of growing or being pregnant or losing blood etc..
Professor Layman informed me that all amino acids are originally made by bacteria. Some are made in the soil and are used by plants. But plant proteins may be deficient in some of the amino acids that animals are made more of. Animals either have to eat a wider variety of plants, that is inefficient and requires a lot of eating and disposing of the unnecessary redundant incomplete proteins or they have to eat other animals. Or coolest of all, they can brew the plants they eat in a bacterial soup in their stomachs, like cows do, to fortify the amino acid mix. This is called up-cycling. Ruminants are animals, mostly cows, that have this magical chemical factory in their stomachs which they also help by contemplatively regurgitating and chewing more. Turns out steaks and milk are highly processed foods. If bacteria were lost from God's earth so would be the rest of life.
Some amino acids, like leucine, are also signals, like hormones, like insulin, that tell muscle cells when to take advantage of what we just ate.
Muscles are the biggest and most changeable reserve of protein in your body. Muscles like bone and brains and fat are built at an early age that can effect the rest of our lives. Even though the number of muscle cells don't change, their size can change through life. Exercise is the signal to make bigger muscles. If muscle mass is so important then not exercising is deadly. That's why little kids are always exercising insanely. Layman's bottom line is that if we take proper care of our muscles we'll be healthy.
So Layman's group has done multiple good studies demonstrating his dietary prescription of increased dietary protein in weight loss diets. (2,3,4) They consistently demonstrated that while high protein/low carb vs. high carb/low protein diets caused the same weight loss. But more importantly to his way of thinking higher protein relative intake caused more fat loss and less muscle loss. Furthermore they showed that satiety was better with the high protein calorie restricted eaters. That would be expected to improve compliance and maintenance. One of their studies that added exercise to the mix showed that the exercise was additive for improving body composition.
How does this jibe with the protein-is-the-new-culprit idea? Well,.... I'm not sure. All of Layman et als. subjects were calorie restricted. What would happen if you ate too many calories at different protein/carb/fat ratios?
1. https://peterattiamd.com/donlayman/
2. Layman DK et al. A Moderate-Protein Diet Produces Sustained Weight Loss and Long-Term Changes in Body Composition and Blood Lipids in Obese Adults. The Journal of Nutrition, Volume 139, Issue 3, March 2009, Pages 514–521, https://doi.org/10.3945/jn.108.099440
3.Layman DK et al. A moderate-protein diet produces sustained weight loss and long-term changes in body composition and blood lipids in obese adults
J Nutr. 2009 Mar;139(3):514-21. doi: 10.3945/jn.108.099440. Epub 2009 Jan 21. PMID: 19158228 DOI: 10.3945/jn.108.099440
4. Layman DK et al.Dietary protein and exercise have additive effects on body composition during weight loss in adult women. J Nutr. 2005 Aug;135(8):1903-10. doi: 10.1093/jn/135.8.1903. PMID: 16046715 DOI: 10.1093/jn/135.8.1903
5. Ferraz-Bannitz R. Dietary Protein Restriction Improves Metabolic Dysfunction in Patients with Metabolic Syndrome in a Randomized, Controlled Trial.
Nutrients 2022, 14(13), 2670; https://doi.org/10.3390/nu14132670
Extra calories increase fat while extra proteins increase lean body tissue
In this study from 2012, head-authored by Dr. George Bray, a heavyweight in fat science, looked at the effect of overeating a diet containing 3 levels of protein content in a group of 25 normal weight volunteers who were brought into a controlled hospital setting for 10 weeks.(1) I pulled this article from the archives because I was trying to remember where I saw it and I remembered that it was kind of momentous.
First they established how many calories the volunteers were eating while their weight was stable for 2 weeks. That was about 2000 Calories. Then they were overfed by 40% which was about 1000 extra Calories per day for 8 weeks. There were 3 groups during this overfeeding phase. One group got 6% of their calories as protein, the low protein group. Group two got 15%, the normal protein group, and the third group got 26% of their intake as protein, the high protein group. The rest of their diets were fats and carbohydrates to make up the differences calorie-wise. So the low protein group got more, and the high protein group got less, as carbohydrates and fats.
The low protein group gained only half as much weight as the other two groups, 6 1/2 lbs. vs 13 lbs., but all 3 groups gained the same amount of extra fat, 9 pounds. So the normal and high protein groups gained more weight as lean body tissue and the low protein group lost some lean body tissue. This group also had no increase in resting energy expenditure or total energy expenditure, while the normal protein and high protein groups increased their energy expenditure significantly. This part of the project was the stated finding of the study although the weight gain was the more amazing result to me.
What does all this mean? It means that extra calories as protein are different from those calories as carbs or fat. They increase your weight, your lean body tissue, and your energy expenditure. This also means that BMI is not very useful as a measure of what's going on.
As usual, this study raises more questions than it answers. I wonder how long they would have kept gaining weight. The fat weight gain was still steeply upward while the lean body mass was plateauing for all all protein intakes by the end of the 8 weeks. So would they have gained even more weight with more time. Or would they have just gotten sick and refused to eat any more? Since they adjusted the carbs and fats to make up the difference between the 3 different protein groups to maintain the Calorie intakes the same, maybe that's all that matters rather than the proteins. But eating more carbohydrates and fats didn't cause any more fat gain. These authors extrapolate that we're all eating too much because there's this obesity epidemic thing. But in the real world our weights are stable for long periods. So maybe not.
In an editorial (2) two experts from Los Angeles, California seem to be missing the evidence here. They say standard things like,
"This study demonstrates how low protein foods with hidden sugars or fats may be contributing to the obesity epidemic. Sugars such as sucrose, fructose, and high fructose corn syrup are converted efficiently to fat with calorie excess. Carbohydrates and protein elicit different signaling pathways for muscle and fat cells. Therefore, when individuals consume excess carbohydrates out of proportion to protein, the body may gain less weight than when protein is consumed in adequate amounts. The study by Bray et al demonstrated that the lesser added weight consists largely of fat mass rather than lean body mass when excess calories were the same. Moreover, added fat calories (including hidden fat in processed foods) consumed in excess will also lead to weight gain contributing to the obesity epidemic."
Ok the high protein group gained less relative fat since they also made more lean body mass but they put on just as much fat. Eating more protein also increased energy metabolism so they were burning up calories faster. But they put on just as much fat. Maybe the fat distribution was better - smaller bellies - but that was not looked at.
I think the message might be different. We should eat less protein. Sugar and fat are not to blame here. That didn't make any more fat.
These guys did make a more valid point, and another report and editorial in this same issue of JAMA (3,4) also shows, that BMI is not telling you what is going on in terms of weight and fat gain.
1.Bray GA, et al. Effect of dietary protein content on weight gain, energy expenditure, and body composition during overeating. JAMA 2012;307(1):47-55
2. Li Z,Heber D. Overeating and Overweight. Extra Calories Increase Fat Mass While Protein Increases Lean Mass and Overweight. JAMA. 2012;307(1):86-87. doi:10.1001/jama.2011.1959
3. Sjöström L et al. Bariatric Surgery and Long-term Cardiovascular Events. JAMA. 2012;307(1):56-65. doi:10.1001/jama.2011.1914
4. Livingston EH. Inadequacy of BMI as an Indicator for Bariatric Surgery. JAMA. 2012;307(1):88-89. doi:10.1001/jama.2011.1950
Methionine restriction causes weight loss in mice
We and everybody have talked about the new fad of intermittent fasting that might have some of the benefits of calorie restriction on longevity and good health without the pain of being hungry all the time, just part of the time and that part of the time is still hard. Could there be an even better way? How does this form of torture work? Methionine restriction might be at least part of the answer to these questions.
Methionine is almost always the first amino acid in the chain of amnino acids that make up all the proteins in your body. The protein making machinery does not begin anything if there is no methionine available. It is one of the essential amino acids that you can't make from scratch. So it has to come from what you eat. That means you can't remove methionine totally from your diet or you will eventually die. Methionine is also one of the two amino acids, together with cysteine (cysteine is not an essentially amino acid), that contains sulfur. It has been observed, in the short term at least, that removal of only methionine from the diet can reverse diet-induced obesity and promote insulin sensitivity in mice. Methionine restriction also protects a mouse model from spontaneous, polygenic obesity and diabetes.
A recent report shows some of how this works and some of how it probably doesn't work in mice. (1) The data shows that wild type male mice who are induced to be obese by a high fat diet and who are then fed a methionine restricted diet lost 45% of their body weight. Otherwise similar mice continued without methionine restriction gained 8% at 8 weeks after stopping the high fat diet. They also repeated the experiment with the same results in mice with genetic manipulations that prevented the rise of adiponectin and fibroblast growth factor 21 that was seen during methionine restriction. So these were two things that were not causal factors in this process.
It was also seen that methionine restriction promotes a futile lipid cycle and apoptosis and autophagy in fat and other body tissues.
-Futile lipid cycle means that calories are burned without making energy that can be used in the body other than heat production. This happens in brown fat. This is a way for animals to stay warm.
-Apoptosis is the programmed death of cells.
-Autophagy is the process of getting rid of some of a cell's internal structures to conserve energy and to rebuild.
Methionine restriction extends lifespan and healthspan across different species. The same benefits we saw with calorie restriction and intermittent fasting.
If you kids want to try this at home most fruits and vegetables contain very little methionine. Beef has the highest content of methionine at 0.680 g/100 g. Poultry, lamb, veal, game, finfish, shellfish, pork, dairy and egg all contained more than 0.4 g/100 g. Most legumes, though protein dense, are lower in methionine. (2) Maybe those vegan diet eaters are on to something. But in practice it is very hard to deeply restrict methionine by itself without restricting all protein because it is everywhere.
1. Cooke D. et al. Weight Loss and Concomitant Adipose Autophagy in Methionine‐Restricted Obese Mice is Not Dependent on Adiponectin or FGF21. Obesity April 20,2020. https://doi.org/10.1002/oby.22763
2. Ables GP, Johnson JE. Pleiotropic responses to methionine restriction. Experimental Gerontology 2017;94:83-8. https://doi.org/10.1016/j.exger.2017.01.012
Rabbit starvation
At the meeting of the American Society of Bariatric Physicians (ASBP) in 2006 there was a lot of talk about the low or no carbohydrate diet. There is a group of evangelists dedicated to this proposition and they have a professional organization called the Nutrition and Metabolism Society that is somehow affiliated with the ASBP or at least their symposium is coordinated with the annual ASBP symposium and there are a lot of mutual members. Their point of view, made famous by Atkins, says that carbohydrates are poison and the root of all evil in our diets and responsible for the epidemic of obesity that we are having. There is actually some merit in what they are preaching and we've talked about the pros and cons of this idea in many previous columns but one thing that they have shown definitively is that you can survive and do just fine eating no or very little carbohydrate (aside from craving carbs if you lose weight). They've also convinced us that a low fat diet is not so great, especially if you eat more carbohydrates instead.
There are certain fatty acids called essential fatty acids that cannot be made in the human body and so these fatty acids are like vitamins. Essential fatty acid deficiency can cause rashes and there have been a lot of other things attributed to essential fatty acid deficiency but it is not really clear how dangerous it would be to eat no fat forever. Anyway you could survive eating just a little of the essential fatty acids, like taking a vitamin that represents a tiny portion of your total calorie intake.
We also know you cannot survive without eating any protein. That's called kwashiorkor. It is deadly. Even if you're not a growing child or recovering from surgery, there is a certain amount of indispensable turnover and repair that goes on and requires a surprisingly little bit of protein in the diet.
What about staying away from that whole hornet's nest of carbohydrates and fat and eating just protein? There are some weight loss diets and there were some speakers who were pushing diets that have way more protein. People with bad kidneys have to eat a low protein diet because it strains their kidneys further and we know that if you have normal kidneys they will swell to accommodate a high protein diet but you remain otherwise healthy.
Then there is a thing called rabbit starvation that is said to arise if you eat nothing but rabbits which have hardly any fat in their bodies. This disease comes from hoary tales of wilderness expeditions where people had nothing but rabbits or other lean meat to eat for prolonged periods and apparently got sick and died of it. Some authorities say that you should not eat more than 35% of your calories as protein. (1) Other authorities do not mention an upper limit of protein proportion in the diet or a maximal load of protein that can be tolerated. The issue remains unclear but I would not recommend eating only protein.
1. Bilsborough, Shane; Neil Mann (2006). "A Review of Issues of Dietary Protein Intake in Humans". International Journal of Sport Nutrition and Exercise Metabolism (16): 129-152.
Eureka
Not my eureka, somebody else's. I gleaned it from David Allison's ObesityandEnergetics.org listserv (July 29, 2022). I plagarize it for you in the brute form of cut and paste of the reference and abstract. You should read the entire article which I have cast in bronze and put on my mantel.
"Dietary Protein Restriction Improves Metabolic Dysfunction in Patients with Metabolic Syndrome in a Randomized, Controlled Trial
by Rafael Ferraz-Bannitz
Nutrients 2022, 14(13), 2670; https://doi.org/10.3390/nu14132670
Abstract
Dietary restriction (DR) reduces adiposity and improves metabolism in patients with one or more symptoms of metabolic syndrome. Nonetheless, it remains elusive whether the benefits of DR in humans are mediated by calorie or nutrient restriction. This study was conducted to determine whether isocaloric dietary protein restriction is sufficient to confer the beneficial effects of dietary restriction in patients with metabolic syndrome. We performed a prospective, randomized controlled dietary intervention under constant nutritional and medical supervision. Twenty-one individuals diagnosed with metabolic syndrome were randomly assigned for caloric restriction (CR; n = 11, diet of 5941 ± 686 KJ per day)* or isocaloric dietary protein restriction (PR; n = 10, diet of 8409 ± 2360 KJ per day)+ and followed for 27 days. Like CR, PR promoted weight loss due to a reduction in adiposity, which was associated with reductions in blood glucose, lipid levels, and blood pressure. More strikingly, both CR and PR improved insulin sensitivity by 62.3% and 93.2%, respectively, after treatment. Fecal microbiome diversity was not affected by the interventions. Adipose tissue bulk RNA-Seq data revealed minor changes elicited by the interventions. After PR, terms related to leukocyte proliferation were enriched among the upregulated genes. Protein restriction is sufficient to confer almost the same clinical outcomes as calorie restriction without the need for a reduction in calorie intake. The isocaloric characteristic of the PR intervention makes this approach a more attractive and less drastic dietary strategy in clinical settings and has more significant potential to be used as adjuvant therapy for people with metabolic syndrome."
Professor Allison, me, some Brazilians, and now you are among the first to know about this. So far I haven't seen breaking headlines on CNN or in the New York Times that say, "Stop eating so much protein!" and "Excess protein eating is the cause of obesity!" and "New weight loss miracle without starvation!."
* don't worry about this kilojoule (KJ) business. one kilojoule equals .24 Calories. (kilocalories) just math.
Obesity Risk of infant formula
The nefarious operation on our shape of eating too much protein might start early in life. Could lower protein intake possibly prevent childhood obesity? That is the contention of some authors from Amsterdam. (Why do they have to write in English. They must hate that.) Their recent report (1) finds that the increased protein in baby formula compared to breast milk may be a smoking gun.
It is widely acclaimed that breast milk is the best way to feed babies. But I thought that among the benefits of breast milk cited by these authors, prevention of obesity was a largely discredited idea. I'll have to go back and rehash that argument again later. But the observation that cow's milk based formulas have higher protein, and so proportionally less fat and sugar, and the fact that the protein concentration in breast milk decreases over the weeks of lactation, while the protein concentration of infant formulas obviously remains constant, make you wonder what God intended. It has been shown that protein intake during the first 6 months of life is up to 66–70% higher in formula-fed infants compared to breastfed infants.
It has also been reported that premature babies fed fortified formula, fortified with both protein and calories, does result in faster weight and head circumference gains during the first and second year of life. Premature babies are the ones we want to gain the most weight. However there is evidence that even though they grow faster on fortified formulas they eat less of it and so they don't actually eat more calories, just more protein. Or it could be that eating more concentrated calories saves on the energy of eating.
Whether or not breast feeding really prevents obesity this contention about protein remains contentious. Among the problems are the fact that the studies are short term. Will it lower the rates of obesity in adults to feed them lower protein as infants? Exclusive breast or formula feeding mostly only happens before 6 months of age. After that the diets of kids get way more complicated and uncontrollable. Will this tiny window of opportunity really make that much difference? We really have to be careful manipulating the diets if innocent tiny babies, as opposed to the huge uncontrolled experiment foisted on us all since baby formula feeding became popular in the 1950s. Back in the really olden days if you couldn't breast feed or if you were rich, you got a wet nurse for your baby. That must have been some kind of slavery to be a wet nurse.
In 1988 The American Academy of Pediatrics (AAP), being American, had promulgated that the weight gain rate is the single most valuable component of the clinical evaluation of infant formula. We have traditionally esteemed weight gain in babies. However, the higher weight gain rate in formula-fed infants during the first months of life compared to breastfed infants might be the cause of higher weight-for-length, BMI, and obesity risk in later life. Therefore, it might be desirable to lower the weight gain rate of formula-fed infants. And there is movement afoot in Europe to recommend lower protein in formula to do that.
Or you might just avoid all this sticky wicket and breast feed your babies. They discuss lots more intriguing aspects of these questions in this very readable article. Find it and read it.
1. Kouwenhoven SMP, Muts J, Finken MJJ, Goudoever JBV. Low-Protein Infant Formula and Obesity Risk. Nutrients. 2022 Jun 30;14(13):2728. doi: 10.3390/nu14132728. PMID: 35807908; PMCID: PMC9268498.
Protein leverage
There is this thing, called the protein leverage hypothesis, that is being studied as a possible contributor to our obesity epidemic. Protein leverage is the innate drive to eat more if you are not getting enough protein. Your body needs protein to grow and repair. So if the diet is lacking in good protein, that is a complete protein with all the essential amino acids that are the building blocks of protein, then you are driven to keep eating more stuff and more total calories. It is protein hunger, like hunger in general and thirst. An example of the understanding of this sort of thing is the folklore about how pregnant women want to eat strange things, even dirt, in order to get certain vitamins and minerals that they must be lacking in order to feed the cookie monster in their uterus.
The terms “protein leverage” (PL) and the “protein leverage hypothesis” (PLH) were invented in 2005 and these ideas were reviewed by the inventors of those terms in the journal Obesity in August of 2019. (2) They explored some of the implications of this thing as a possible cause of the obesity epidemic. It has been shown that all kinds of animals have a drive to keep eating whatever is available to them in order to get enough protein. Part and parcel of this idea is that they may wind up over eating certain things that they will need to get rid of or waste.
It has indeed been shown that free range humans eat more calories when they eat less protein. From 1961 through 2013 as we were experiencing the obesity epidemic we were eating more calories but about the same amount of protein. But since we need only very little dietary protein, unless we are growing or pregnant or recuperating from surgery and accidents, why would we be so hungry for protein? But if the protein as a percentage of total calorie intake goes down, maybe that hunger of protein leverage still drives. But if you do more math it still can't explain all of the increase in obesity. It's complicated. For more analysis using differential equations and further commentary and further discussion see 3,4,5.
It would seem that the best candidates for examining the protein leverage hypothesis would be in children who are growing and need the most protein. An investigation of the protein hypothesis was done and published in February, 2023, by Christoph Saner and colleagues examining kids in Finland. They carefully found that their kids did eat ate more calories if they ate less protein as a proportion of their total calorie intake, but those extra calories did not correlate at all with their shape. "Increased energy intake on diets with lower protein content was counterbalanced by increased energy expenditure and therefore did not translate into increased adiposity."
They forgot or neglected to conjecture about that amazing fact. Why or how do they think that eating more calories but less protein makes them burn more calories? But that won't inhibit me from wildly surmising. Maybe it has to do with the autophagy thing whereby you recycle your own proteins if you eat less proteins and that costs more energy. Furthermore that contradicts Layman. Remember he said more protein causes more energy expenditure. Maybe it's a different thing in kids.
They did conjecture however, contrary to their own evidence, that children and adolescents who are chronically exposed to a diet containing high quantities of ultra-processed foods could still be more adipose by the protein leverage thing. I think they say that because Finns are not as obese as the rest of the world and eat a more healthy diet, perhaps they are not the best ones to test the ultra-processed food liability on. Hmmm.
1. https://conscienhealth.org/2019/07/protein-leverage-coming-at-us/
2. Raubenheimer D, Simpson SJ. Protein Leverage: Theoretical Foundations and Ten Points of Clarification. Obesity. 2019;27(8):1225-38.
3. 4. Hall K D. The Potential Role of Protein Leverage in the US Obesity Epidemic Obesity 2019;27(8):1222-4.
4. Hill CM, Morrison CD. The Protein Leverage Hypothesis: A 2019 Update for Obesity Obesity. 2019;27(8):1221.
5. https://qz.com/1669418/the-problem-with-americas-protein-diet-obsession/
6. Saner, C. et al. Evidence for protein leverage in a general population sample of children and adolescents. Eur J Clin Nutr (2023). https://doi.org/10.1038/s41430-023-01276-w