It started with an experiment on locusts in 1991. David Raubenheimer and Stephen Simpson, two zoologists who were at the time doing research at Oxford University, wanted to know what would happen to locusts if they varied the relative proportions of protein and carbohydrate in their diets. They therefore conducted an experiment in which they fed locusts pellets containing varying proportions of protein and carbohydrate, and the results astounded them so much that they ended up determining the course of their research over the next thirty years, which they’ve chronicled in their book, Eat like the animals.
What Raubenheimer and Simpson found was that the locusts were not eating until they’d satisfied their overall need for calories. Rather they ate until they’d satisfied their need for protein, so that overall, all the locusts were consuming the same total amount of protein. This meant that the locusts on the high protein diet were consuming much less food overall than the locusts on the low protein diet. Consequently, the locusts on the high protein diet became extremely lean, while the locusts on the low protein diet became fat (which they describe in their book as equivalent to an overweight knight squeezing in to a suit of armour that is a few sizes too small).
This led Raubenheimer and Simpson to conclude that protein is the dominant macronutrient in terms of determining how much we eat – At least if we’re locusts. They wanted to see if the same pattern would be seen in other species. They started off with flies, and the results were similar, which was encouraging. But flies and locusts are relatively closely related, at least in the sense that they’re both insects. What Raubenheimer and Simpson really wanted to know was whether they’d stumbled on a general dietary principle, that could be applied to all animals.
For reasons of practicality, they next chose mice. Unlike locusts and flies, which subsist pretty much entirely on protein and carbs, mice also eat fat, so in order to get a full understanding of how macronutrients impact body composition, this variable also needed to be part of the experiment. Additionally, Raubenheimer and Simpson wanted to increase the scope of their research, to look not just at the effect of various macronutrient combinations on body composition, but also on longevity. They were also curious to see what effect differing levels of dietary fibre would have on the mice.
The experiment took five years to carry out. 856 mice were sorted in to 25 different groups, that were fed identical pellets but with varying compositions of protein, fat, carbs, and fibre. They were followed from birth to death. In terms of body composition, the results were largely as expected. The mice fed a high protein diet all became lean and muscular. When it came to the mice fed a high carb diet, however, there was more variation. Those on a high carb diet that was low in fibre grew fat, while those on a high carb diet that was high in fibre remained slim.
The fact that fibre mattered so much to the body composition of the mice on a high carb diet is interesting. It provides a reasonable explanation for why people in traditional agrarian societies usually aren’t fat, even though their diets are very high in carbohydrates, and for why the current obesity epidemic coincided with a massive increase in intake of processed foods that were rich in carbs but lacking in fibre. It also provides an explanation for why people are able to lose weight both on a paleo/carnivore/keto diet that is low in carbs, and on a vegan diet that is high in carbs but also high in fibre. Fibre appears to provide a kind of “get out of jail free” card that lets you consume lots of carbs without becoming fat.
What about fat? Fat was found to be neutral in terms of it’s effect on how much the mice ate. In other words, fat intake didn’t have any limiting effect on appetite, so the mice on a high fat low protein diet grew fat, just like the mice on a high carb low protein diet that was low in fibre. If this result were to apply also to humans (which is, of course, not necessarily the case), it would suggest that LCHF/keto diets don’t work because people are replacing carbs with fat, but rather because they’re replacing carbs with protein.
Ok, so we know how the various macronutrient combinations affected body composition. What about the effect on life span? Here, the results as presented in Eat like the animals surprised me. Alot. The longest lived mice, according to Raubenheimer and Simpson, were the ones following a high carb low protein diet. Whether they ate a high or low fibre diet didn’t seem to matter. So the fat high carb mice were actually living longer than the lean, muscular high protein mice!
Baffled by these results, I decided to go and take a look at the data, to confirm that they weren’t just trying to pull a fast one, as nutrition researchers so often do when presenting their research. Hidden away in the supplement to the published study, is this table:
Two things immediately jump out at me. The first is that the group with the longest median lifespan was on a 42% protein diet. Hardly low protein!
If instead of looking at the median lifespan, we look at the maximum, we get a different picture. We see that the extremely low protein mice did best. But their median lifespans were far more average. The authors have obviously based the claims in their book, and in their published research article, on the maximum lifespan, rather than the median. That is something I find very odd.
Personally, I assume I’m going to live an average amount of time for people like me, following my type of lifestyle. I don’t assume I’m going to be the outlier who lives to 120! The median provides a much better picture of the effect of a diet on a group than the maximum lifespan seen in a few individuals.
Apart from that, they’ve chosen an odd definition of maximum life span. They’ve defined it as the top 10% with the longest life span in each group. Which is suspicious. Why the top 10% rather than just the top individual, which would be the more common way to define “maximum”? And why not the top 20%? Or top 30%? The definition really seems to have been chosen specifically because it gave the desired result, which is what is usually referred to as “torturing the data”.
I can only imagine that they chose to base their claims on their odd definition of the maximum rather than on the more appropriate median because the maximum showed a picture more in line with their own biases, possibly shaped by an environmental or animal rights agenda, or by the fact that it’s easier to get research published if it feeds in to the dominant dogmas.
The second thing that jumps out from the table is that the mice eating a high fibre diet (i.e. with a low energy density) lived much shorter lives than the other mice. That is by far the biggest difference, much bigger than any difference induced by varying protein or carb concentrations. Does this mean fibre is deadly and should be avoided it like the plague?
Well, no. The pellets that the mice were fed only contained one fibre, cellulose, which is hardly representative of the full spectrum of fibres that exist in real food. So it’s impossible to draw any conclusions from this about the effects of fibre on longevity. What we can say is that cellulose appears to be toxic to mice.
Next, I took the data from the table and re-tabulated it in a form that would allow for easier analysis of the data, which you can see here:
So what we see is that the low protein mice do appear to live the longest, but the differences between the groups are small and hardly linear. The difference between the 5% protein mice and the 42% protein mice is only 2 weeks, equivalent to about a year and a half if translated to a human lifetime. Since there’s no evidence of a linear relationship between protein intake and life expectancy, it’s hard to say that that result isn’t just caused by chance.
If we move on to carbs, then it again isn’t clear that the high carb diet leads to a longer life. The longest lived group is actually the one consuming a moderate 29% carbs, and again, there is no evidence of a linear relationship. The same is also true for fats.
So overall, the claims the authors make about a high carb low protein diet resulting in the longest life expectancy don’t hold up to close inspection. They’ve tortured the data until they’ve gotten the result they want.
What can we conclude?
If you want to be lean, muscular, and beautiful, then you should eat a high protein diet. If you just want to lose weight and be slim, then you can either go high protein or high fiber, or do a combination of both.
Well, as long as you’re a lab mouse, that is. Whether all of this also applies to humans is harder to say for certain. The results from the experiments mentioned here and others have led Raubenheimer and Simpson to develop the “protein leverage hypothesis” of obesity, which basically states that the modern obesity epidemic is due to the fact that modern diets are lacking in protein and fibre. This has come to be one of three main hypotheses that try to explain the rise in obesity. The other two are the “carbohydrate-insulin model”, which argues that the rise in obesity is due to the high consumption of carbohydrates and their downstream effects on insulin levels and thus body fat storage, and the traditional “calories in vs calories out model”, which argues that the rise of obesity is due to the fact that modern foods taste too good and are too readily available while our lifestyles have become too sedentary. From my perspective, Raubenheimers and Simpson’s hypothesis is the one of the three that fits the known facts the best. Their book, Eat like the animals, is therefore well worth a read, even though the claims they make about diet and longevity are unsupported by the evidence they present.
Just macros? No differentiation between types of carbs and fats?
Lots been said about what we eat. With some similar dynamics to the covid errors. Hope you can synthesize all this experience into your analysis. I think you will find more.
Thank you, Dr. Rushworth. Fascinating work. I would suggest one crucial factor driving the obesity epidemic is the amount of linoleic acid in the modern diet.
That was also my thought, and quite often rat/mouse chow is full of PUFA oils. I could not find the original text but I suspect the result would be quite different if the fat was stearic acid etc.
There are studies comparing mouse diets with low and high percentage of linoleic acid and the difference is huge. Mice fed high LA diets get fat.
Perhaps a significant factor in the human obesity epidemic is that people aren’t fed pellets. I quite understand the reluctance in choosing this form of nutrition because they are like eating cardboard. No mouse in his right mind would eat pellets from choice but in the laboratory situation it either them or starvation. Quite why humans spend years feeding pellets to mice is beyond me but, if you insist on keeping us in laboratories I think you could have the decency to give us a modicum of decent food every once in a while. Yours etc. Mouse Overlord Squeeker.
From my point of view, this study with mice is utterly useless to humans, as we have a totally different intestine, bacteria, etc than mice.
We need to look at evolution, and evolution says that a keto/paleo approach with very few carbs or no carbs at all is the best option for humans.
Frank: Read “Nutrition and Physical Degeneration.” While I’m personally sold on the carnivore diet, sixteen months now with many positive changes in health, I discovered about four months in that I had to add back so carb-rich foods. These are dates, figs, prunes, and honey, and garden friuts. What Dr. Price discovered is that there were a wide variety of healthful traditional diets, including those with high percentages of carbohydrates, but the tallest, most robust, and healthiest were those who ate the highest percentage of animal foods.
Hey Gary, I have had a similar experience and have started reading into WAP. Went carnivore for 10 months (due to worsening intolerances of plant food intolerances) but have reintroduced dates and honey. What garden fruits are you eating?
Gene: We have a navel orange (delicious!), a pineapple guava, and an occasional strawberry.
A good follow-up study would be with People who only ate rat food pellets.
Thank you for your well presented article. It won’t however change the way I eat, just eating real food on the lower carb side and avoiding 90% of the supermarket aisles.
Something may be wrong with the study. Isn’t it well accepted that caloric restriction (a low energy diet) extends life significantly (maybe 25%?) in all species looked at?
What their data unequivocally says is a low energy/low calorie diet shortens life span whether considering median lifespan or maximum lifespan. The study doesn’t seem to say much else other than that, for rats eating rat pellets.
Or rats who ate human food?
Wasn’t it mice eating mice pellets?
Low energy here doesn’t mean low calorie. It means low energy density, i.e. high dilution with fibre.
Simpson and Raubenstein argue that it’s protein restriction that prolongs life, not calorie restriction per se.
But you’ve pointed out that the data they present doesn’t support their theory relating to lifespan.
Humans have 23 pairs of chromosomes, while rats have 21 and mice have 20. We are closer to rats.
There are too many factors in diet for just one study – you need two or three studies at least 😉 But seriously carbs ain’t carbs. The work of Robert Lustig on sugar, and before,him John Yudkin basically demonstrates the link between sugar/fructose and obesity.
Then there are studies showing that caloric restriction and fasting are strongly linked to longevity. So it’s not just what you eat but when, and how much. There is also a role for genetics, in particular epigenetics which allows populations to adapt rapidly to changing diets, such as the Inuit and the Maasai whose traditional diet has hardly any vegetables or fruit.
I’ve been vegetarian since the late 20th century because I was sickened by modern livestock farming, where animals have a short and horrible life. This is not 100% true. I know of a beef farm in Derbyshire, England, where the animals live outdoors as far as is practical.
But since I cannot buy directly from the farmer(s), I really couldn’t face the thought of eating meat.
Free range eggs, O.K.
Cheese I do eat though modern dairy is highly suspect.
Wish I could consume more fat, but how and what? Bear in mind I am elderly and very loath to expand my cookery skills!
Added to which I AM UNDERWEIGHT not overweight.
I am a low-income 72 y/o who has become mostly carnivore and an intermittent faster. Still working on solving some constipation issues from my former omnivore diet and sweet sins. [If I stopped spending so much time on my ass, it would probably work better.] My two most accessible fats are pasture-raised butter, butter, butter. One of my favorites is the Irish Kerry Gold brand. And small farm bacon from humanely raised / non-industrial pigs that I find at the local food co-op.
Thank you Michael Burgwin for your helpful and sensible suggestions.
I suspect half our problems are caused by most of our food being over processed and even adulterated with synthetic flavourings.
I’ve been plagued by constipation all my life whatever diet I’ve followed. ‘Remedies’ tend to have the same problems as our foods!
For example ‘Fibogel’. So loaded with synthetic flavouring I have difficulty getting it down me.
Lactulose I can swallow but it being a muscle relaxant, it triggers my haemorrhoids .
Swallowing a tablet is quick and easy but Senokot may be addictive.
Psyllium husk capsules usually work for me but sometimes backed up by a Senokot.
Chocolate, particularly dark chocolate contains a natural anti depressant from the cacao bean. It is much better than serotonin but of course, drinks like cocoa are again, processed.
You may not have to completely resist your sweet tooth! I eat McVitie’s Club Wafers Orange.
In moderation of course. If the ‘orange’ is synthetic I don’t notice it.
Of course you are right about getting up off our backside and taking exercise. My weak ligaments and fear of falling are my excuse!
Information about constipation as a downstream effect of fatty liver and/or IBS has recently found its way into my reality. A real ahah. I don’t use any medications as they tend to require medications to ameliorate the effects of the medications and very very few processed foods. Nothing with seed oils. Am inclined to view all body phenom as psychological first. When younger and more active, when on a backpack trip, even eating processed dehydrated foods, walking constantly for 8-10 hours a day, absolutely no constipation. Full body movement, fresh air, abundance of sunlight, stress-free, best BMs. I know this and yet that does not move me to move regularly. Go figure.
You have shown that the importance of the composition of diet for mice is not clearly established, especially in the light of some of the comments demanding a more detailed classification of fats and so on.
What, then, are the chances that “best” diets for humans are well understood? About nil, I’d say.
Just follow my mother’s advice and eat a mixed diet, bearing in mind the advice of Jeeves that it should contain plenty of fish.
Low carb keeps blood glucose levels even which lets hormones like leptin and ghrelin control appetite and fat storage. Fasting lets the body go into repair mode. Dr Jason Fung covers this on his website at thefastingmethod.com . The modern diet swamps us with glucose; blood glucose goes up; insulin knocks it down; low blood glucose puts the brain into panic mode; brain demands more glucose NOW; individual eats/drinks more glucose; brain relaxes; cycle repeats. Humans are biological machines running on biochemistry which in turn runs on nutrients. The big picture is to increase the good things (vitamins, minerals, fatty acids especially omega 3s, etc.) and to decrease the bad things (pesticides, heavy metals, glucose, etc.).
Sebastian, The problem with most of these studies is that, as you suggest, they are tailored to the biases of the authors. So, inevitably certain variables get included, and certain other ones are excluded.
Here are a few items which I think contribute to weight control, good health, and longevity.
Intermittent fasting to give the system periodic/ regular rest.
Raw foods to conserve the body’s finite supply of enzymes.
Regular moderate – as opposed to vigorous – exercise. (Greta Waitze died at 57.)
One question I haven’t yet seen posed is how insects, or mice, or even humans, actually measure the amount of protein they eat in order to decide when they’ve had enough? I can easily see how creatures might roughly measure the total quantity of food they eat by the weight in their stomach, or its distension or even just by how long they spent eating. But how does a creature set about measuring how much protein they ate to be able to say “I’m full now”?
There are some Youtube videos by Giles Yeo discussing this kind of thing.
(A geneticist working on obesity at Cambridge.)
Thanks. I tend not to use videos for reference. His papers all seem fairly abstract so I’ve ordered a copy of his book Gene Eating and will see if that answers the question. I see he did an episode of Horizon back in 2016 but it isn’t available now.
“I eat what I like and stop eating when I’m full” was my lifelong motto for my personal diet (except the years during and after WW2). Following this motto I kept the same BMI (21) from the age of 18 until the age of 82. This is how all of us are born (DAVIS CM: Am. J. Dis. Child. 36, 651-679 (1928).
Needless to say that I don’t need any drugs in my age. I don’t care about longevity, but about quality of life.
Does anyone know what happened to the blog of M. K., M.D.? Has he been censored?
theasdgamer: I’m concerned, too. The last comments came into my inbox on August 6th, more than three weeks ago.
My long-lived mediterranean relatives are lean, muscular, and beautiful but eat lots of carbs(PASTA) and much less protein. BUT they eat much less of everything than the average American. Eating less in general seems to be the key. Less sugar, less salt, less everything. The American grocery stores are stock with 90% unhealthy foods. We all see it. Seems to me the Blue zones lifestyle and diet might be a better thing to study. https://www.bluezones.com/2019/12/these-people-tried-the-blue-zones-diet-for-3-months-see-what-happened/
MarkP’s comment re protein restriction.
I’ve a theory that for good health growing children require a high proportion of protein in their diet. After all they are building their future bodies and the stronger that is the better it will last surely.
I also suspect that animal protein is ‘higher quality’ than vegetable protein for growing children.
After that it is a case of what sort of body is optimal. Obviously we need muscle not fat surrounding the skeleton.
There is more to that than simply balancing calories in to calories out. While exercise builds muscle I suspect the quality of the muscle will be improved by a high protein diet.
In old age (where I am) things change again.
Longevity may be more to do with genetic inheritance than optimal diet throughout life.
There is also the matter of what bad habits we may have over indulged, quite apart from diet and exercise regimes.
Hi Dr Rushworth,
What do you think of this BMJ article saying plant based diet improves covid outcomes whereas keto based-meat diets worsens outcomes?
https://nutrition.bmj.com/content/early/2021/05/18/bmjnph-2021-000272
It’s a case-control study, i.e. a very low quality form of evidence that is heavily affected by confounders. It cannot say anything about cause and effect.