Abstract
Lifespan and metabolic health are influenced by dietary nutrients. Recent studies show that a reduced protein intake or low-protein/high-carbohydrate diet plays a critical role in longevity/metabolic health. Additionally, specific amino acids (AAs), including methionine or branched-chain AAs (BCAAs), are associated with the regulation of lifespan/ageing and metabolism through multiple mechanisms. Therefore, methionine or BCAAs restriction may lead to the benefits on longevity/metabolic health. Moreover, epidemiological studies show that a high intake of animal protein, particularly red meat, which contains high levels of methionine and BCAAs, may be related to the promotion of age-related diseases. Therefore, a low animal protein diet, particularly a diet low in red meat, may provide health benefits. However, malnutrition, including sarcopenia/frailty due to inadequate protein intake, is harmful to longevity/metabolic health. Therefore, further study is necessary to elucidate the specific restriction levels of individual AAs that are most effective for longevity/metabolic health in humans. © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Generated Summary
This review article examines the impact of dietary protein intake on longevity and metabolic health, exploring the mechanisms through which amino acids (AAs) influence aging and metabolism. It focuses on the roles of low protein intake, specific AAs like methionine and branched-chain AAs (BCAAs), and different protein sources (animal vs. plant) in the context of lifespan and metabolic health. The study also investigates the impact of reduced dietary protein intake on various factors, including mechanistic target of rapamycin complex 1 (mTORC1) activation, autophagy, fibroblast growth factor 21 (FGF21) signaling, and hydrogen sulfide (H2S) production. The review synthesizes findings from both basic and human studies to provide a comprehensive understanding of the relationship between protein intake, longevity, and metabolic health.
Key Findings & Statistics
- The study cites research indicating that a reduced protein intake or low-protein/high-carbohydrate diet plays a critical role in longevity and metabolic health.
- Epidemiological studies show that a high intake of animal protein, particularly red meat, may be related to the promotion of age-related diseases.
- The Geometric Framework for Nutrition shows the macronutrient balance and single nutrients, such as protein, play a more crucial role in longevity and metabolic health than total calorie intake.
- In Drosophila melanogaster, LPHC diets result in lifespan extension.
- In mice, LPHC diets, but not high-protein diets, are associated with longevity and metabolic health.
- In mice, the maximum lifespan was observed in mice fed medium calorie food with 5% protein/75% carbohydrate.
- Mice fed a short-term (8 weeks) LPHC (5%protein) diet exhibited benefits in glucose/lipid metabolism.
- A major study of nutrition involving a United States population (6381 individuals aged 50 years and over) found that both the moderate protein (MP; 10-19% of calories from protein) and high protein (HP; ≥20% of calories from protein) intake groups had higher risks of diabetes-related mortality than the participants in the low protein (LP; <10% of calories from protein) group.
- Among those aged 50-65 years, higher protein levels were linked to significantly increased risks of all-cause and cancer-related mortality.
- In this age range, the HP intake group exhibited a 74% increase in their relative risk of all-cause mortality and were >4-fold likely to die of cancer than those in the LP group.
- Among those aged 66 years and older, the HP diet was associated with the opposite effect on all-cause and cancer-related mortality, with the HP and MP groups exhibiting a 28% and 21% reduction in all-cause mortality, respectively.
- In Okinawa, Japan, the CVD and cancer death rates were found to be only 60-70% of those in other regions of Japan on average, and the all-cause mortality rate among 60- to 64-year-olds was only half that of other Japanese populations.
- The Okinawan diet is derived from 9%protein and 85%carbohydrates.
- Animal protein intake was related to a higher risk of mortality, particularly CVD mortality, while higher plant protein intake was associated with lower all-cause mortality.
- After controlling for the percent of calories from animal protein, the association between the level of protein intake and all-cause and cancer-related mortality was eliminated or significantly reduced.
- Increased circulating BCAA levels or excess BCAAs may be harmful for longevity and metabolic health.
- Dietary MetR has been demonstrated to extend the lifespan of organisms ranging from yeast to rodents.
- In humans, a moderate PR (7-9%protein) diet improved markers of metabolic health.
- In a prospective cohort study, the relative risk of an acute coronary event in individuals with a high methionine intake (>2.2 g methionine/day) was higher than that of individuals with a low methionine intake (<1.7 g methionine/day).
Other Important Findings
- Specific amino acids (AAs), including methionine or branched-chain AAs (BCAAs), are associated with the regulation of lifespan/ageing and metabolism through multiple mechanisms.
- Methionine or BCAAs restriction may lead to benefits on longevity/metabolic health.
- LPD exerts a reno-protective effect by inducing autophagy via the suppression of mTORC1.
- The restriction of dietary sulfur-containing AAs (SAAs), including methionine, leads to stress resistance and longevity.
- The high intake of red meat and processed meat results in an increased intake of saturated fat, cholesterol, iron, salt, and phosphate; oxidative stress/inflammation; elevation of by-products of protein or AA digestion by the gut microbiota, such as trimethylamine n-oxide or indoxyl sulfate; acid load; and protein/AA load, which are possibly associated with increased risks of CVD mortality and CKD.
- Reduced GH/IGF-1 signalling is linked to survival duration and decreased incidence of cancer and T2DM in humans.
- The supplementation of BCAAs abolishes the effect of PR on glucose metabolism and induces inflammation in visceral adipose tissue in mice.
- Methionine restriction decreases visceral fat mass and preserves insulin action in aging male Fischer 344 rats independent of energy restriction.
Limitations Noted in the Document
- The article notes that malnutrition, particularly sarcopenia/frailty due to inadequate protein intake, is harmful to longevity/metabolic health, highlighting a potential limitation of overly restrictive protein diets.
- The review focuses on the detrimental effects of proteins; however, it notes that reduced protein intake does not decrease the potentially negative effects of certain types of carbohydrates and fats, suggesting a limitation in scope.
- Clinical studies comparing lifespan, mortality, and metabolic health between groups randomly assigned to either LP or HP diets or specific AA restriction diets are necessary to identify optimal diets.
- Performing randomized clinical trials to evaluate the effects of protein or specific AA restriction on longevity and metabolic health is difficult, posing a limitation in the research.
Conclusion
The study emphasizes that the quantity, source, and amino acid composition of proteins significantly impact longevity and metabolic health. Dietary interventions, particularly those restricting specific amino acids like methionine and BCAAs, show promise in extending lifespan and improving metabolic outcomes. The review suggests that a low animal protein diet, especially one that limits red meat consumption, may offer health benefits. However, the study also underscores the importance of avoiding malnutrition, including sarcopenia, which can result from inadequate protein intake. The findings emphasize the complex interplay between protein intake, specific amino acids, and metabolic health, particularly in the context of aging and age-related diseases. The potential benefits of reducing animal protein intake and focusing on plant-based protein sources are highlighted, along with the need for further research to determine optimal levels of specific amino acid restriction for human longevity and metabolic health. The review’s emphasis on protein sources and AA composition provides a nuanced perspective that goes beyond simple calorie restriction. The impact of specific AAs on longevity and metabolic health is emphasized, especially the role of BCAAs and methionine. Increased circulating BCAA levels or excess BCAAs may be harmful for longevity and metabolic health. The high intake of BCAAs due to excessive food intake in obese people is harmful in terms of insulin resistance and T2DM. However, a low level of BCAA intake in elderly people is also harmful in terms of sarcopenia. The appropriate intake of BCAAs for individuals is necessary to maintain longevity and metabolic health. Dietary MetR has been demonstrated to extend the lifespan of organisms. The study’s final thoughts suggest that a Mediterranean diet or the DASH diet may be useful for reducing the consumption of animal protein. However, red meat is an important dietary source of micronutrients, including vitamins, iron, and zinc; therefore, an appropriate intake is necessary to avoid malnutrition.