Animal and Plant Protein

The protein-to-carbohydrate ratio that seems optimal for a long life appears to be about one to ten across species, which is strikingly similar to that on Okinawa. The traditional Okinawan diet contained 9 percent protein and 85 percent carbohydrates (mainly from sweet potatoes, as you may remember). Before people there westernized their diet, they were among the regions of the world with the most centenarians and had 80 percent less common cancer as well as a fivefold lower mortality rate from a variety of age-related diseases. This longevity was thought to be due to relative calorie restriction, since people ate about 20 percent fewer net calories than Americans, but they also consumed about 50 percent less protein.

In animal experiments, the animals that received high-protein feed had the shortest life expectancy. This aligns with a meta-analysis of prospective cohort studies in humans showing that higher total protein intake is associated with higher all-cause mortality. However, that is because in the Western world most protein comes from animal sources. The more animal protein is consumed, the higher the mortality rate, whereas it is lower the higher the consumption of plant protein is.

There is some evidence that a somewhat higher protein intake might benefit those over 65—perhaps 1.0 grams per kilo of body weight instead of 0.8 grams, which is still less than what most older Americans get. In any case, gerontologists recommend that it should come from plant sources to avoid excessive IGF-1 activation. As already mentioned, the National Institutes of Health (NIH) AARP study, based on more than six million observed person-years, found that in men and women, overall mortality fell by 10 percent when just 3 percent of caloric intake from animal protein was replaced by plant protein. Not all relevant studies showed this effect, but a meta-analysis of 32 prospective cohort studies in which participants were followed for up to 32 years found that overall, increasing the share of plant protein by 3 percent was associated with a significantly lower risk of death from all causes.

Substantial improvements in lifespan seem achievable even by replacing one percent of animal protein with plant protein. In a study on unhealthy aging, an “index of accumulated deficits” was used that captured more than 50 different functional impairments, self-rated health and vitality values, indicators of mental health, chronic diseases, and the use of health services. People who increased their share of plant protein by just one percent by correspondingly reducing animal protein (a swap of only about 5 grams per day) accumulated significantly fewer deficits over a period of eight years. In the Women’s Health Initiative, which followed 100,000 older women for 18 years, replacing 5 percent of animal protein with plant protein was associated with about a 20-percent reduction in the risk of dying from perhaps the greatest of all deficits, dementia. One study even found that theoretically, replacing just a single serving per week of unhealthy protein sources like egg with a healthy source like nuts or whole grains would extend life expectancy. A meta-analysis published in 2022 on substituting animal proteins with plant proteins recommended “introducing plant protein sources as a substitute for animal proteins in order to prevent age-related diseases and promote long life and healthy aging.”

Among the Japanese residents of Okinawa, the emphasis on plant protein sources was even more pronounced than calorie and protein restriction. Animal products made up less than one percent of their traditional diet: that would be fish once a week, other meat once a month, an egg about every two months, and virtually no dairy. As mentioned, the only formally studied population group with a higher life expectancy, the vegetarian Adventists living in California, did not eat 99 percent meat-free but 100 percent meat-free, even if they ate 30 percent more protein than the recommended daily allowance. An article on the influence of protein intake on longevity concluded that the protein source may be more important than the total amount of protein consumed, although at a sufficiently high protein intake the IGF-1 level likely would no longer fall even with a shift to predominantly plant sources.

What happens when you randomize people to switch from animal protein sources to plant sources while also reducing total protein intake? After 16 weeks, the reduced-protein plant-based diet group had lost about five kilos of pure body fat, including several hundred cubic centimeters of visceral fat—the dangerous internal belly fat—and recorded a significant reduction in insulin resistance. In the journal Ageing Research Reviews, this study was described as suggesting that a reduction in animal protein could be “crucial to improving metabolism and the aging process,” but given the corresponding elimination of animal fat, it is difficult to identify the primary trigger for the metabolic improvements.

Less Cancer Through Less Protein

Almost 50 years ago, T. Colin Campbell and colleagues showed that rats fed 5 percent casein (milk protein) in the diet developed 75 percent fewer precancerous lesions in response to a carcinogen than rats fed a 20-percent casein diet. Protein restriction can extend the lifespan of mice by about 30 percent, but common inbred strains of laboratory mice die 90 percent of the time from cancer. Given the enormous effect of protein reduction on cancer, one would not expect the same life extension in humans because they mainly die of heart disease.

Human cancer responds similarly when it is transplanted into mice that are fed different dietary regimens. In mice that are shifted from 21 percent of caloric intake from protein to 7 percent, human breast and prostate cancer tumors reduce their growth by 56 to 70 percent. Even at the higher protein intake, simply switching from animal protein to plant protein can reduce tumor weight by 37 percent, whereas at the low protein intake the source of the protein did not seem to matter.

It is assumed that the reduction in tumor size from protein reduction is due to reducing cancer growth fueled by IGF-1, but low-protein diets also stimulate the targeted killing of cancer cells by the immune system, since more lymphocytes infiltrated the tumors and the “tumor-killing capacity” of macrophages was increased. Even in immunodeficient mice, low-protein diets can cause their tumors to shrink, suggesting a combination of factors. Restricting just a single amino acid, methionine, can slow the growth of cancer tumors.

Methionine Restriction

Just as many of the beneficial effects of dietary restriction can be replicated simply through protein restriction, most of the beneficial effects of protein restriction may be due to restricting a small number of amino acids—the building blocks of proteins—such as methionine. Methionine is the only amino acid whose levels across all mammals strongly correlate with maximum lifespan—that is, the more methionine in body tissues, the shorter the animal lives (for the statistics nerds: r = –0.96). Guinea pigs have about 40 percent more methionine in the heart than rabbits, whose life expectancy is about 40 percent higher. Mice have a threefold higher methionine level than naked mole rats, which can live seven times as long. To prove what is cause and what is effect, one would have to show that lowering methionine levels actually extends lifespan, and methionine restriction does indeed do that.