We all know that the less we eat, the longer we live, and that periods of fasting, long and short, can also trigger a longevity dividend. What about macronutrient proportions—protein, carbohydrates, and fat? The argument for carb restriction is that it helps keep insulin signaling down, and slows the inevitable advance of metabolic syndrome. The argument for protein restriction is that animals on protein restricted diets have sometimes been found to live longer, independent of total calorie intake. The argument for fat restriction is that mice on a high-fat diet have shortened lifespans compared to either high-carb or high-protein. So, what macronutrient proportions are best for people, or does it matter at all? I have advocated the carb restriction diet in the past, but today I’m considering the evidence for protein restriction, and speculating on the possibility we might be able to do both.
Nutritional Geometry is a 9-year-old Australian approach to macronutrient proportions which has been honing its message more recently [ref, ref, ref]. The topic has provided fodder for research grants (and for bloggers) because it is rich with nuance and resists generalization.
If you are looking for bottom-line advice, I’d say:
- High-fluid, high fiber content are consistent recommendations—no tradeoffs, no qualifications. Leafy greens rule!
- Low-protein when you’re young, higher protein when you’re old
- Vegetable protein is preferable to meat or dairy
- If you’re game to try something new, a high-fat ketogenic diet may offer advantages.
But the subtleties are interesting and worth exploring, and (as always) the best diet for you is the one you can live with.
Last year, the Australian group published a study in which they fed mice on 25 different diets, differing in protein, fat, carbohydrate, and energy density. The main result from this study is that mice fed a low protein, high carb diet lived longest, though they ate more food—presumably because they sensed that they were not getting enough protein. At the lowest protein concentrations, their total protein was still low, even though they ate more food, and they lived longer, even though they ate more food. For mice, a low-protein chow led to more eating and a longer life. The trick worked for low protein, high carb diets but not for low protein, high fat diets. In this case, the mice ate so much more food that they became obese and their lifespans were shorter. The optimum diet for female mice had an 11:1 ratio of carbohydrate to protein, and for male mice, 13:1.
If we extrapolate to humans, the message would be that for people who prefer not to restrict their portions, a very low protein diet provides a path to a longer life. But this is a dubious extrapolation. The mice were given no choice of chow. (There were 25 different formulations, but only one available to each cage of mice.) People, in contrast, have a dizzying choice of foods. I know the feeling of having had my fill of fruit, and though not feeling really hungry, craving protein nevertheless. Humans are not at all comparable to lab mice in this regard.
Conclusion: To get the low protein diet of the mouse experiment, you’d probably have to be a fructarian.
I was surprised to see that the study reported no benefit from a high-fiber diet.
Reduction in calorie intake was achieved by diluting the food with nondigestible cellulose, which allows ad libitum feeding but restricts total energy intake when compensation for dilution by increasing food intake is incomplete. Mice fed experimental diets containing 50% nondigestible cellulose ate a greater bulk of food (3.6 vs 2.5 g/day) but ingested about 30% less total energy than mice provided with food containing higher energy content (30 vs 42 kJ/day). Therefore, these mice had a reduction in energy intake similar to those reported in nearly all other studies of calorie restriction in which access to food was restricted… When corrected for lean body mass, the hazard ratio for death was not influenced by calorie intake, except at the highest energy intakes, which were achieved only by low-protein, high-fat diets.
Fiber in the chow filled the mice up, causing them to eat less calories (though more bulk) than they would have otherwise. But did they live longer? Yes, they did, though you might not get it from the language used here. Lifespan was not increased by lower calories “when corrected for lean body mass”, but whem mice are on a lifelong low-calorie diet, they don’t grow as large, so their lean body mass is smaller. Correction “for lean body mass” is generally not the way data is reported in these experiments. So the result here is not necessarily inconsistent with the great body of experimental results that say lifelong caloric restriction leads to longer lifespan.
Most interesting is the last caveat: The problem with high fat diets is that mice overeat, become obese and have shortened lifespans. But with both high fiber and high fat, the mice tended not to overeat, and their lifespans were enhanced.
This may suggest a practical diet strategy for humans. Mice on a high-fat diet ate a lot more calories, and similarly some people find deep fried foods and milk shakes tempt them to eat too much. But for those with the willpower to interrupt a high-fat meal, they may find that they don’t get hungry for several hours afterward. This is because fat is slower to be digested than either protein or (especially) carb. High-carb meals lead to a fast rise in blood sugar, then an insulin spike that makes blood sugar plummet, triggering hunger. After a high-fat meal, hunger is much slower to return.
High-fat meals lead mice to obesity and short lifespans because they overeat. Extra fiber in the food helps them to regulate their intake. If this works for humans, there is the possibility that a high-fat, high-fiber diet can offer the advantages of both protein restriction and low insulin. I’ll go into this option in depth next week.
Protein: How low can you go?
The biggest issue is maintaining muscle mass, which is crucial to vitality and wellbeing, and becomes a protective factor from mortality as we get older. We have all seen pictures of starving African children with bloated bellies. They are not actually suffering from insufficient calories, but insufficient protein. Their largest muscle, in the abdomen, has beeen deprived of protein so long it has lost all its tone.
Both Pederson and Rand (2013) recommend about 0.85g protein for each Kg of body weight. For a 160-pound man that’s 61g, and for a 125-pound woman, 47g of protein daily. Pederson found that all the diseases of old age are statistically associated with higher protein intake. More general sources quote a slightly lower 0.8g/Kg.
These numbers are only an average over many populations in many studies. Your body might need a lot more or a lot less protein than this, and your best indication is to monitor your energy level, your weight, your muscle mass, and blood analysis as you experiment with different diets.
In this study  of Swedish women 30-49, those in the highest decile of protein consumption died at a rate 20% higher than those with the lowest decile. But mortality rates are low through that age range, and what is more important is the effect on health and mortality in the long term.
Animal vs vegetable protein
In a literature review, Pederson (2013) found links between animal protein intake and various mortality factors, but vegetable protein was either beneficial or neutral. Surprisingly, it is the high-protein diets that are associated with type-2 diabetes, not the high-carb diets. But this conclusion seems limited to animal sources.
This study  from Harvard School of Public Health found a 13% increase in mortality for every daily meal at which red meat was consumed, rising to 20% for processed meats, corresponding to 2 to 3 years of extra life.
Seventh Day Adventists are, as a group, health- and diet-conscious, and they live longer. Their religion tells them not to eat meat, but many do anyway. Seventh Day Adventists who are vegetarian live 3 years longer than Seventh Day Adventists who eat meat.
How does the body know animal from vegetable protein? I have seen no theories on this. Animal protein is generally higher in methionine, but methionine restriction only lowers mortality when methionine intake is very low–probably not the case generally in any of these studies. It could be the saturated fat that accompanies the protein; or it could be hormones that are present in all animals, with higher levels in commercial meat; or it could be an effect mediated through the effect on intestinal flora. But my best guess is that it has to do with heightened inflammation from a low-level immune response to chronic exposure to alien animal proteins.
More protein as you get older
My favorite authority on this and other questions of diet is Valter Longo and his group at University of Southern California. In their 2014 review, they found a dividing line at age 65. Younger than 65, higher protein intake was associated with higher mortality, and older than 65, higher protein intake was associated with lower mortality. As in other studies, the damage was only visible for animal protein, and disappeared into the noise for vegetable protein.
Frailty is an issue in older adults., and greater muscle mass can support a more vigorous exercise regimen. This is a plausible reason for the increased protein need with advanced age. Longo also talks about IGF-1 signaling. IGF stands for “insulin-like growth factor”, and it is a hormone we need when we are young, but which increases mortality when we are older. Lower protein is associated with lower IGF-1, though the statistical association falls short of suggesting that this is the reason that low protein is beneficial.
This is the best article I have found on the subject of increasing protein need with age, but still it is not really what I’d like to see. Mortality in young people is not the best measure of whether a low protein diet is beneficial, because mortality in young people is still low, and even a temporary doubling of mortality make little difference. What we really want to know is how protein in the diet of young people affects their life expectancy when they get older. This is a study that has not yet been done, probably because it involves following a large population for a long period of time (like the Framingham Heart Study and the Whitehall Study in Britain, but these did not address protein.)
Roughage = Dietary Fiber
Everyone agrees that fiber in the diet has a large benefit for gut health and especially for preventing colorectal cancer. I have speculated that the benefit goes beyond this. A high-fiber diet is a calorie restriction program in itself. Fill your belly with fiber, and it you feel full with fewer calories. An ultra-high fiber diet pushes food through your digestive tract faster, so you absorb less of it. Fat is adsorbed on the fiber, and less of it makes it into your metabolism. High fiber in the gut encourages a microbial ecology that affords you less calories.
I speculate based on personal experience, but there is also some literature touching on the subject [ref, ref, ref]. “There was a considerable variability in digestibility of fiber components between individuals.”
Does fiber prevent the absorption of vitamins and other micronutrients as well? Maybe. I haven’t seen literature on the topic, but it makes sense that cellulose adsorbs a variety of molecules that are carried through the intestine undigested. Best to take your supplements separate from your fiber.
I am out on a limb recommending an ultra-high-fiber diet, and I suspect that results will vary widely among individuals. But what is not controversial is the health value of leafy green vegetables—the more the merrier.
Conclusions so far:
This much is clear: Green vegetables are good. Animal protein is bad.
Beyond that, we might be tempted to interpret the Nutritional Geometry literature to say that “carbs are ok”. I am wary of this conclusion, however. It’s not just the standard warning that “mice are not people”. The benefits of a high-carb diet have only been shown in the context of severe protein restriction that I think is unrealistic for most of us. To be continued…
Next week: Metabolic Syndrome, Glycemic Load and The ketogenic Diet