Low protein diets for longevity

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By Kellie Blake, RDN, LD, IFNCP

While the average life expectancy has increased overall throughout the past 70 years, there still exists a significant divide when it comes to maintaining quality of life and excellent health throughout the aging process. According to the National Institute on Aging, 85 percent of Americans over the age of 65, have at least one chronic disease with 60 percent having two or more.

Advances in medicine have increased the average life span from 68 years in 1950 to 78.9 years in 2014, but a 2019 JAMA report described a decline to 78.6 years starting in 2017 related to chronic diseases like obesity, as well as suicide and drug overdose. The number of Americans age 65 and up is projected to almost double to 95 million by the year 2060, so investigating ways to address both chronic disease and longevity simultaneously will be required to enhance individual and economic outcomes.  

As a registered dietitian, I am often called upon to provide meal plans and lifestyle strategies for specific disease conditions, but rarely am I asked to provide a meal plan specifically for longevity. Most of my patients have struggled for years with chronic disease symptoms and seek nutrition therapy to find immediate relief. The popular low carbohydrate, high protein diet is often requested, but while this type of diet initially improves weight and many of the hallmarks of metabolic dysfunction, long-term use of high animal protein diets is associated with negative health outcomes.

According to a report in the journal Cell Metabolism, study participants with self-reported high animal protein intakes, defined as greater than 22 percent of calories, had a 75 percent increase in overall mortality with a four-fold increase in cancer and diabetes mortality. On the other hand, those following a plant-based, lower protein diet experienced reduced chronic disease and mortality risk.

In addition, as reported in Advances in Nutrition, low protein diets have been shown to improve metabolic health, lower blood glucose, and reduce diabetes risk while improving lean body mass, possibly making this an important option for preventing chronic disease and increasing lifespan.

While there are many genetic and lifestyle factors involved in longevity and chronic disease, the growth hormone/insulin growth factor 1 (GH/IGF-1) pathway, its’ downstream effectors, and inflammation are considered to be the driving forces in chronic disease and aging. For example, in yeast and mouse models, the upregulation of GH/IGF-1 and the cascade of events that follow leads to chronic disease and decreased longevity. But, when GH or GH receptors are absent in mice, more anti-inflammatory and less pro-inflammatory byproducts are produced by adipose tissue decreasing diseases of aging and increasing longevity.

Upregulation of the GH/IGF-1 pathways are suspected to lead to similar effects in humans. As reported in Critical Reviews in Oncology/Hematology, humans with conditions of GH excess and increased IGF-1 have a higher risk of age-related diseases, experience accelerated aging, and have shorter life expectancy. In addition, aging itself brings about changes in body composition that increase inflammation. This increased inflammation coupled with the lifetime inflammatory load accelerates the aging process, leads to increased risk for chronic disease, and negatively affects longevity. Healthy centenarians, on the other hand, exhibit lower levels of insulin resistance, oxidative stress, insulin, and glucose.

Preventing chronic disease and extending healthspan and lifespan can be achieved in part with nutrition and lifestyle-related strategies that regulate the secretion of IGF-1 and insulin, as well as enhance insulin sensitivity. Caloric restriction (CR) has been shown to decrease the GH/IGF-1 pathway, enhance longevity and provide protection against chronic disease; however, it is difficult to follow long-term and can lead to the loss of lean body mass, especially in those over age 65. A low animal protein diet though, has also been shown in numerous single-cell to mammal studies to down-regulate the GH/IGF-1 pathways and provide protection against aging and age-related diseases while maintaining muscle mass.

The fasting mimicking diet (FMD) is one low protein option that has been shown in human trials to decrease body weight, abdominal fat, blood pressure, and IGF-1, as well as other aging and disease-related risk factors. In the FMD trials, a very low calorie, low protein meal plan was administered for five consecutive days per month and repeated for a total of three months. All study participants demonstrated significant improvement, with at-risk study participants benefitting most regarding body mass index, fasting blood sugar, IGF-1, triglylcerides, total and LDL cholesterol, and C-reactive protein levels. The authors concluded that the FMD is safe and effective at reducing risk factors for aging and age-related diseases. In addition, the significant reduction in IGF-1 following the FMD trials is likely related to the low protein and amino acid content of the FMD as opposed to caloric restriction.

As reported in the EBioMedicine, protein restriction and the restriction of specific amino acids like methionine decrease IGF-1 levels, enhance longevity, and reduce mitochondrial reactive oxygen species independent of calorie intake in model organisms. In addition, when compared to strict calorie restriction, reducing protein intake and altering the protein source may be a more appealing strategies for patients of middle age.

While a lower animal protein meal plan during middle age seems to optimize health span and longevity, the effects can be detrimental for those over the age of 65. A moderate protein intake becomes important later in life in part as a way to preserve lean body mass. In addition, there seems to be a reduction in mortality in those over the age of 65 with a higher protein intake. Personalizing the meal plan for each patient based on genetics, lifestyle, and lifecycle stage will provide the most benefit when it comes to reducing chronic disease risk and increasing longevity.

Resources

Anisimov, V. and Bartke, A. (2013) The key role of growth hormone-insulin-IGF-1 signaling in aging and cancer. Critical Reviews in Oncology/Hematology. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4095988/

Brandhorst, S. and Longo, V. (2019) Protein Quantity and Source, Fasting-Mimicking Diets, and Longevity. Advances in Nutrition. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855936/

Kitada, M., Ogura, Y., Monno, I., and Koya, D. (2019). The impact of dietary protein intake on longevity and metabolic health. EBioMedicine. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562018/

United States Department of Health and Human Resources. Supporting Older Patients with Chronic Conditions. Retrieved from:  https://www.nia.nih.gov/health/supporting-older-patients-chronic-conditions

United States Census Bureau. Older People Projected to Outnumber Children for the First Time in US History. Retrieved from: https://www.census.gov/newsroom/press-releases/2018/cb18-41-population-projections.html

Woolf, S. and Schoomaker, H. (2019) Life Expectancy and Mortality Rates in the United States, 1959-2017. JAMA. Retrieved from: https://jamanetwork.com/journals/jama/article-abstract/2756187