Bread, grains, fruits, and vegetables arranged in a circular pattern around a shrimp at the center. – Knowable Magazine
The Curious Case of Low-Protein Diets
In today’s health landscape, protein seemingly dominates grocery aisles with offerings like protein chips, protein cookies, and protein water. Recent headlines reflect a shift in dietary guidelines that have increased the recommended intake from 0.8 grams per kilogram of body weight to a range of 1.2 to 1.6 grams.
However, an intriguing group of researchers is investigating a different concept: the potential longevity benefits of low-protein diets. Studies on various organisms—ranging from single-celled yeast to rodents—indicate that drastically reducing protein intake can actually extend lifespan.
While it’s essential to acknowledge that protein is crucial for constructing and repairing body tissues, a diet where protein comprises less than 7% of total caloric intake may lead to malnutrition rather than increased lifespan. Nevertheless, this line of research on protein restriction in laboratory creatures helps scientists unravel how organisms sense nutritional environments and adapt metabolically, which has implications for their overall health and, ultimately, longevity. As noted by Knowable Magazine, these findings could hold valuable lessons for human health.
“There’s a lot to be learned from the principles of protein restriction about how we would manage aging, and aging well,” asserts Stuart Phillips, a physiologist at McMaster University in Canada.
The Mouse Food Diaries
According to Phillips, protein restriction can be seen as a milder version of the well-known longevity strategy of caloric restriction, which involves reducing overall calorie intake by 20% to 50% to promote longer lifespans in lab animals—a trend observed for over a century.
Studies on lab animals demonstrate that dietary manipulation can lead to impressive longevity. For example, one investigation found that mice allowed to consume an unrestricted amount of regular food lived an average of 1,008 days. In contrast, those whose calorie intake was restricted to 80% of what they desired lived up to 1,179 days. A third group of mice consuming the same amount of food but with only 6% of their calories derived from protein survived up to 1,115 days—an impressive figure.
Importantly, the benefits of such restricted diets extended beyond mere longevity; they also contributed to improved health. Mice on either caloric or protein-restricted diets displayed lower blood sugar and insulin levels, demonstrating better metabolic health. These indicators of good health persisted even as the mice aged, while those consuming a typical diet deteriorated. Furthermore, mice on restricted diets also exhibited lower body fat, weighing only two-thirds of their counterparts at one-year benchmarks.
Researchers fed 30 male mice a standard diet with 20 percent protein, and 30 additional mice a diet with only 5 percent protein. Those that got less protein lived longer. – Knowable Magazine
In another recent study, researchers focused on the molecular manifestations of aging. Aging in animals is accompanied by tissue damage from unstable free radicals. Mice on low-protein diets showed increased levels of protective antioxidant enzymes across multiple organs, indicating an array of anti-aging features. These benefits were particularly prominent in middle-aged mice, which suggests that the advantages of a low-protein lifestyle are not uniform throughout the lifespan.
Making Hay or Hunkering Down?
The underlying biological mechanisms that enable mice to thrive on restricted diets remain unclear. One possible reason for their lean yet healthy physiques may be their limited access to nutrients required for growth; however, Christopher Morrison, a physiologist from Pennington Biomedical Research Center, implies that this is only part of the equation. There’s likely more going on in terms of metabolic health and longevity.
Morrison draws an analogy to a car: driving fast utilizes more fuel, leading to more wear and tear, whereas driving slowly extends the vehicle’s lifespan. A high-protein or high-calorie lifestyle might accelerate the production of damaging free radicals, while reducing intake could minimize this oxidative stress. Additionally, protein tends to activate growth-promoting systems, which also lead to aging. A more restrained diet might help the body maintain its functionality over longer periods.
Alternatively, Phillips proposes that a body operating under nutrient scarcity may enter a high-efficiency mode, optimizing the recycling of amino acids, which could result in improved age-related processes and functionalities.
Moreover, it’s becoming increasingly evident that the advantages seen with low-protein diets extend beyond mere starvation. Morrison’s team is examining a hormone known as FGF21, produced in the liver, which seems to communicate with the brain during nutrient scarcity. Mice genetically engineered to lack FGF21 don’t show the same life-extending benefits from low-protein diets—indicative that the brain’s response is crucial in this regard.
“The reduction in growth is a ‘choice,’ if you will,” concludes Morrison, noting that this decision-making process occurs before the body enters a state of deficiency.
A graphic illustrates the response to protein restriction in a lab mouse: The hormone FGF21, produced by the liver, signals the brain to make a number of changes, including increased protein intake and slowed growth. – Knowable Magazine
If longevity in the face of protein scarcity represents an unconscious choice, then the default quicker life with plenty of protein could be another form of choice. Evolutionarily, it appears sensible for animals to invest in reproduction and growth when protein-rich foods are plentiful, even if it means neglecting tissue repair amid oxidative stress. The trade-off might be justified from a survival standpoint, leading to more offspring.
Conversely, during lean times, organisms may initiate protective and repair mechanisms against aging in hopes of enduring until resources become bountiful once again, even if it means compromising their growth. Morrison’s research supports this, indicating that reproductive metrics, such as sperm counts and ovarian follicle numbers, are diminished in mice adhering to low-protein diets compared to their high-protein counterparts.
Researchers are gradually uncovering the biological underpinnings of these divergent strategies, and the insights derived may inspire new treatments aimed at promoting healthy aging in humans. For instance, an enzyme called mTOR, which governs growth, reproduction, and aging, is inhibited by low-protein diets—a mechanism similar to the effects produced by a drug called rapamycin, which has attracted attention for its potential anti-aging properties.
Protein for the People
Despite these compelling findings, most research has been conducted on nonhuman lab animals. “I don’t think we really know what long-term protein restriction will do in humans,” warns Morrison.
Longitudinal studies involving large groups of people following strict low-protein diets are challenging to conduct ethically. However, observational studies often correlate dietary habits reported in questionnaires with disease and longevity outcomes. While results vary, an overall trend suggests that high protein intake may be associated with a slightly increased risk of conditions like cardiovascular disease and type 2 diabetes. Phillips highlights that those consuming animal protein often ingest saturated fats, complicating health outcomes. Notably, diets rich in plant protein do not correlate with similar health risks.
Age also introduces variables into protein needs. One study indicated that individuals aged 50 to 65 adhering to low-protein diets exhibited lower mortality rates associated with cancer and other causes than their high-protein counterparts. Yet, for individuals over 65, the pattern reverses, showing that low protein intake could correlate with higher rates of cancer deaths and overall mortality. Thus, maintaining moderate protein intake during middle age, while increasing it after 65, might offer health benefits.
Graphic showing how protein needs vary with age, as do the effects of low-protein diets, according to observational studies of people. In adults aged 50 to 65, a lower-protein diet correlates with a reduction in deaths due to cancer, diabetes or any other cause. But in people 66 or older, the pattern changes: A low-protein diet is still linked with lower risk of death from diabetes but is associated with a higher risk of death from cancer or other causes. – Knowable Magazine
The practical aspect of adhering to a long-term low-protein diet may present challenges. Simpson suggests that it could feel easier to follow than a strict caloric restriction, even though protein is known to help suppress hunger. His research indicates that individuals deprived of protein tend to crave it. In a controlled study, participants who could choose from a menu with only 10% protein indulged heavily in savory snacks, resulting in increased overall calorie intake—hardly an ideal situation for dietary success.
Interestingly, none of the researchers consulted for this article were currently engaging in low-protein diets. “I’m not a fruit fly or a mouse,” Morrison remarked, noting his balance of protein intake for health while also hesitating to adopt a restrictive diet. “I don’t want to be real scrawny,” he added.
This story was produced by Knowable Magazine and reviewed and distributed by Stacker.
