Explaining the protein paradox based on science and personal experience
What is new?
High protein (HP) diets are popular for losing weight, gaining muscle, and improving health. These claims are true, BUT not because of the protein and not for most of the diets’ followers.
Why it matters
It is the combination with exercise that makes athletes thrive on a HP diet while couch potatoes suffer on it. And at older age the effects of LP vs HP diets may reverse.
What you should do
If you still can’t bring yourself to exercise sufficiently, take heed of the findings about right protein intake at the right age.
Contrary to what some diet experts want you to believe, it’s the LOW-protein (LP) diets that protect against fat gain, prevent insulin resistance (a precursor of diabetes), and slow down the aging process [1]. High-protein (HP) diets do just the opposite [2]. The paradoxical exception to this rule is that the fittest and healthiest people of all also have the highest protein intake of all — athletes.
Interestingly, it is not protein restriction per se but the restriction of three amino acids that convey the health benefits — the branched-chain amino acids (BCAA) [3]. Again, paradoxically, those three BCAAs are athletes’ top protein supplements.
Which is why I’ll answer three questions based on my research:
- Why are athletes, but not sedentary people, healthy on an HP diet?
- What is it about protein restriction that promotes health and longevity?
- What are YOU supposed to eat? (for a healthy, long lifespan)
Before we answer them, I’d like to very briefly
- Recap the basics of proteins and amino acids
- Caution you about mice
The basics of proteins and amino acids
Amino acids are the building blocks of proteins. Proteins are very large molecules that show up in almost every metabolic reaction. They also provide structure, from the body’s cellular to its organismal level. Different proteins have different sequences of amino acids. These sequences are encoded in our genes.
When a gene is activated to string amino acids together into a specific protein, that process is called translation. There are 20 different amino acids which the body uses to translate genetic instructions into proteins. Of those 20 nine are essential, that is, we need to get them from our food. The 3 BCAAs are part of those 9. The remaining 11 we need not worry about, the body can produce them without our help.
Evolution has relied on these 20 amino acids since long before humans appeared. Mice, for example, not only share exactly the same 20 amino acids with us, but all those that are essential for us are essential for them, too.
That’s why researchers love to experiment with mice, particularly when it comes to investigating metabolism. And that’s why I need to caution you about the results of mouse experiments.
A cautionary note about mice
Answering the three questions, I will dive into recent research on mice and humans. Usually, I am skeptical about translating pre-clinical studies (those done on rodents) to humans. In nine out of 10 cases, drugs and interventions that show promise in mice fail to deliver in people [4]. Man just isn’t a large, 2-legged mouse.
While we share most genes, the genes’ networks are vastly different [5]. Mouse metabolism differs in key aspects from human metabolism, so exercise interventions that show a specific effect in mice may not replicate in humans [6].
On the other hand, controlling mouse experiments for the known differences between them and us can yield valuable insights into the lifestyle causes of human (ill) health [6].
There are certain unique advantages of studying diets in mice.
- Adherence: mice eat what researchers feed them. In human diet studies, adherence and controlling for adherence is always a problem [7].
- Accuracy: Researchers can measure exactly how much mice eat. Try to do that with people.
- Control: Researchers can control diet composition precisely (you can change just one food component at a time). Impossible with human diets.
- Testing: Researchers can do a lot more testing. That includes euthanizing the mice after the experiment, which is generally frowned upon when dealing with human subjects.
For all the mouse studies that I mention, I’ll explain whether and why the results apply to humans.
Why are athletes, but not sedentary people, healthy on an HP diet?
The obvious answer is because of their exercise.
Dudley Lamming and his team at the University of Wisconsin-Madison wanted to dig a little deeper into the effects of exercise on metabolism. They mainly use mice as their subjects.
To separate them into the rodent equivalents of athletes and sedentary people, the researchers made the “athlete” mice pull loaded little carts along a trail daily for several months. The couch potato mice (the experimental control subjects) pulled the same but unloaded carts.
The researchers divided each group further by protein intake: high-protein = 36% of total calories; low-protein = 7% of total calories.
Here is a summary of the results after five months of intervention [8]:
- Total food intake is higher in the LP conditions (figure 1)
- Body fat is higher in the HP
- Insulin sensitivity is generally better in LP, regardless of exercise
Food intake and fat gain
The non-exercising mice on HP diets ate significantly less than those on LP diets. That sounds good but wait: they gained three times more body fat. Exercise, on the other hand, largely prevented the HP-diet-induced fat gain.
Since the percentage of body fat strongly correlates with the risk for cardiometabolic disease (diabetes, heart disease, etc.), strength exercise might be your best option to avoid the fattening effects of a high-protein diet, with the added benefit of significantly gaining muscle mass and size, which the exercising mice did.
Lamming and his team concluded that:
“ resistance exercise protects from HP-induced increases in adiposity … and suggests that metabolically unhealthy sedentary individuals consuming an HP diet or protein supplements might benefit from either reducing their protein intake or beginning a resistance exercise program.”
A couple of years ago, scientists said pretty much the same thing about calorie restriction (CR). CR extends life and health spans, not just in mice but in monkeys (primates that are closer to us than mice).
A study that began in 1989 using rhesus monkeys showed that CR extended health and life span by about 15% [9]. That’s about half of what is achievable for mice. So, in humans, the effects would probably scale down further.
But anyway, the question arose: what is it about CR that leads to lifespan extension?
The first discovery was that it’s protein restriction, as illustrated above. Today, we have ample evidence that protein restriction (PR) alone drives the CR benefits [1].
“Protein restriction is sufficient to confer almost the same clinical outcomes as calorie restriction without the need for a reduction in calorie intake.”
Now, we want to dig even deeper.
What is it about protein restriction that promotes health and longevity?
Dudley Lamming and his team have been diving into this subject for the past ten years or so. Their fascinating discovery: It’s the BCAAs — leucine, isoleucine, and valine [10].
In fact, the chief culprit behind the negative metabolic effects of HP diets is isoleucine, with valine coming in a close second [11].
Reducing those two in your diet:
- Improves insulin sensitivity of the liver
- Improves systemic glucose tolerance
- Reduces adiposity
So, is the reduction of proteins, or BCAAs, generally the right way to health? If it were only that simple.
BCAA reduction may become counter-productive
The entire story of BCAA-reduced diets (or LP diets in general) turns on its head in the elderly. Low circulating BCAA in the blood correlates with frailty and worsening of dementia [12]. Supplementing those elderly folks improves frailty, but with one caveat: only if accompanied by exercise, whereas exercise alone produces nearly the same effects [13].
Age is not the only parameter that can put a different spin on the protein story. Gender and genetics probably play a role, too. At least, this is what Lamming’s mouse experiments suggest.
Male mice saw a significantly larger gain in BCAA-driven life expectancy than females. And the same experiments can show different results in different mouse strains. Since the latter are bred to closely resemble specific human variants of metabolism (obesity, diabetes, etc.), it is reasonable to expect different effects in different people.
So, the answer to this section’s question, “What is it about protein restriction…?” is:
It is NOT about protein restriction. It is all about exercise.
Do all these insights help you design your personal diet? Let’s tackle that in the next section.
Which protein diet are YOU supposed to eat? (for a healthy, long lifespan)
In short, the optimal diet is the one that gets you out of breath and sweating. Its name is Exercise.
Think about it. The answer to the first question, “What keeps athletes healthy despite an HP diet?” was “exercise”. The answer to the second question, “What is it about protein restriction…?” was “exercise”.
At every age, exercise drives your life and, more importantly, your health span. With the right amount and type of exercise, you can thrive on any diet while you are young, middle-aged, or elderly, particularly when you don’t want to screw up your life beyond 65.
The discussion about LP vs. HP diets has crept into our lives only because most of us don’t get enough exercise.
The primacy of exercise over the protein content of our food has an evolutionary reason:
“Nothing in Biology Makes Sense Except in the Light of Evolution” Theodosius Dobzhansky
Physical activity (exercise) has been a driver in the evolution of our species. Our inevitably active ancestors thrived on any diet that their environment provided. Lack of physical activity was never an issue.
If any of our stone-age ancestors had gotten up at the campfire and told his tribe not to eat the boar they just hunted because it is high in protein, they would have clobbered him. Today, the same guy is a guru.
To sum it up:
As much as I hate to quote a corporate tagline, Nike nails it for exercise as a diet: “Just Do It!” If you still loathe it, here is what the researchers say:
“If I was under the age of 65, I’d probably think about ways to decrease my protein intake a bit. Pretty much everyone is eating too much protein.” Dudley Lamming
“Based on the current evidence, protein intakes that far exceed the RDA may promote additional gains in lean body mass and a decrement in fat mass. However, to best achieve a gain in lean body mass or loss of fat mass, this is best achieved when complimented with a rigorous resistance training program.” [14]
My Approach to Nutrition
I eat a meat-leaning diet, which complements my 5-days-per-week exercise regimen (30 minutes of split routine strength training and 60 minutes of cardio). In fact, I would rather live with no carbs than no meat.
To get sufficient nutrients from fruits and veggies, I have developed my breakfast into an “anchor meal” smoothie that eliminates having to worry about getting enough micronutrients (vitamins, minerals, flavonoids, etc.).
I take issue with the statement that LP diets make you less fat than HP diets (if you don’t exercise). It probably depends very much on the type of carbs that you use to displace the protein calories.
When those carbs come from veggies and fruits, OK, but when they come from bread, pasta, or rice, then you’ll probably gain a lot more fat. At least, that’s what I observe in my clients.
Cited References
[1] Ferraz-Bannitz R, Beraldo RA, Peluso A, Dall M, Babaei P, Foglietti RC, et al. Dietary Protein Restriction Improves Metabolic Dysfunction in Patients with Metabolic Syndrome in a Randomized, Controlled Trial. Nutrients 2022;14. doi:10.3390/nu14132670.
[2] Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F, et al. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab 2014;19:407–17. doi:10.1016/j.cmet.2014.02.006.
[3] Newgard CB. Interplay between lipids and branched-chain amino acids in development of insulin resistance. Cell Metab 2012;15:606–14. doi:10.1016/j.cmet.2012.01.024.
[4] Sun D, Gao W, Hu H, Zhou S. Why 90% of clinical drug development fails and how to improve it? Acta Pharm Sin B 2022;12:3049–62. doi:10.1016/j.apsb.2022.02.002.
[5] Perlman RL. Mouse Models of Human Disease: An Evolutionary Perspective. Evol Med Public Heal 2016:eow014. doi:10.1093/emph/eow014.
[6] Fuller KNZ, Thyfault JP. Barriers in translating preclinical rodent exercise metabolism findings to human health. J Appl Physiol 2021;130:182–92. doi:10.1152/JAPPLPHYSIOL.00683.2020.
[7] Schwingshackl L, Stadelmaier J, Lay R, Griebler U, De Santis KK, Zeeb H, et al. In Cochrane nutrition reviews assessment of dietary adherence varied considerably. J Clin Epidemiol 2023;158:1–9. doi:https://doi.org/10.1016/j.jclinepi.2023.03.016.
[8] Trautman ME, Braucher LN, Elliehausen C, Zhu WG, Zelenovskiy E, Green M, et al. Resistance exercise protects mice from protein-induced fat accretion. BioRxiv 2023. doi:10.1101/2022.10.18.512689.
[9] Colman RJ, Beasley TM, Kemnitz JW, Johnson SC, Weindruch R, Anderson RM. Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun 2014;5:1–5. doi:10.1038/ncomms4557.
[10] Trautman ME, Richardson NE, Lamming DW. Protein restriction and branched-chain amino acid restriction promote geroprotective shifts in metabolism. Aging Cell 2022;21:1–19. doi:10.1111/acel.13626.
[11] Yu D, Richardson NE, Green CL, Spicer AB, Murphy ME, Flores V, et al. The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. Cell Metab 2021;33:905–922.e6. doi:10.1016/j.cmet.2021.03.025.
[12] Ikeuchi T, Kanda M, Kitamura H, Morikawa F, Toru S, Nishimura C, et al. Decreased circulating branched-chain amino acids are associated with development of Alzheimer’s disease in elderly individuals with mild cognitive impairment. Front Nutr 2022;9:1–13. doi:10.3389/fnut.2022.1040476.
[13] Chen L-F, Chang H-C, Cai Z-C, Chen Y-J, Hsu W-L, Chuang Y-H, et al. Community-based exercise and nutritional interventions to improve frailty syndrome among older adults: A quasi-experimental study. Geriatr Nurs (Minneap) 2023;51:222–31. doi:https://doi.org/10.1016/j.gerinurse.2023.03.016.
[14] Antonio J, Candow DG, Forbes SC, Ormsbee MJ, Saracino PG, Roberts J. Effects of dietary protein on body composition in exercising individuals. Nutrients 2020;12:1–11. doi:10.3390/nu12061890.
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