Protein, Fasting, and the mTOR Pathway

Is there such a thing as too much protein? Nowadays, with so many dieters focused on this macronutrient’s importance—from proponents of the “carnivore” diet to keto believers—it’s worth evaluating appropriate protein needs from an evolutionary point of view.

While replacing processed foods, empty-calorie carbs, sugars, and seed oils typical of the Western diet with organic or sustainably sourced whole foods is a great start to a healthier lifestyle, it says nothing of the ideal protein contribution.

Furthermore, with plentiful food, including protein sources, now so easy to come by—consumed at will, morning, noon, and night—it raises concern about a little known but highly important metabolic sensing mechanism in our cells. This over-feeding chronically activates the mTOR pathway, and some researchers associate this with increased cancer risk and shortened lifespan.

What Is the mTOR Pathway?

mTOR stands for mammalian (most researchers now substitute “mechanistic”) target of rapamycin. Isolated and named in the early 1990s, mTOR was discovered through experiments with rapamycin, a natural antifungal that was found to inhibit cancer cell growth. [1] Researchers found that rapamycin did so by targeting a then-unknown mechanism that controlled cell growth: mTOR.

In simple terms, mTOR exists in almost every cell, where it controls a host of metabolic functions. It monitors numerous environmental cues, including carbohydrate and amino acid concentrations and several growth factor hormones. It constantly balances all these against current needs, surpluses, and deficits.

Depending on system needs (or stress), mTOR may promote cell growth and proliferation, or simply maintain homeostasis. Its role in maintenance and repair includes the vital cellular “house-cleaning” function of autophagy. In this process, dead cells and cellular debris are consumed and recycled by the body.

When the mTOR pathway is activated, it suppresses this important autophagy function, since cells stay in growth mode. Therefore, this also leads to an accumulation of cellular “trash” that further erodes health.

Thus, the more we eat, and the more often we eat, the more we risk “unwanted” or excessive mTOR activation. This includes all macronutrients—even fat, which at least in the laboratory has also been shown to activate mTOR [2].

Balancing Protein Needs with mTOR Activation

Striking the right balance of macronutrients can be tricky. Science suggests we should be “low carb” for its health benefits (compared to standard Western fare), which necessarily increases the protein/fat percentages. Keto dieters may reduce their contribution of calories from protein to 10 to 15%, while most Paleo devotees shoot for the recommended 19 to 35%. [3] (Bear in mind, that The Paleo Diet have taken a strong stance that a healthy diet is about the foods we eat, not the particular macronutrient ratios.)

General nutrition guidelines suggest we consume around 0.6 to 0.8 grams of protein per kilogram of bodyweight. Some nutritionists allow a higher amount for elite athletes, body building, and vigorous resistance training, but this tends to vary with each nutritionist’s background. Furthermore, these figures may not reflect common ancestral calorie percentages.

Complicating the protein question further, older individuals are often told that increased protein is “protective” against all-cause mortality, [4] and that up to 1 or 1.1 grams per kilo of bodyweight is ideal (even 1.2 grams for senior athletes.) [5] A recent study published in The Journal of Nutrition, Health & Aging found increased all-cause mortality in older community-dwelling men as protein consumption decreased (irrespective of protein source.) [6]

A 2014 study published in Cell Metabolism drew similar conclusions: the authors suggested that moderate to high protein consumption increased the activation of mTOR (via IGF-1, an “upstream signaler” [7]) and the likelihood of cancer for individuals aged 50-65. However, it also stated that this finding changes at age 66. Above that age, the authors noted a 28% reduction in all-cause mortality, and a 60% reduction in cancer mortality, also irrespective of protein source, in the high-protein cohort.

Using Fasting to Keep mTOR Activation in Check

Since ideal protein targets vary by age group, and even by individual, strategies to deactivate or suppress mTOR (periodically) appear important. Balance, as always, is everything.

Calorie restriction (CR), including several types of fasting, are often mentioned in discussions of mTOR and longevity. “Dietary” restriction (DR)—for example, periodically reducing protein while maintaining moderate calories—is another approach.

CR and DR could be combined in the “fasting mimicking diet”—which reduces overall calories, typically carbohydrates but it could also include protein—and relies on modest amounts of fat for limited satiety. This diet, not intended for long-term or everyday use, can be used every few weeks or months. A few consecutive days on this regimen allows the housecleaning and maintenance function of autophagy, through downregulated mTOR, to overhaul cellular health, promote stem-cell growth, and de-stress the immune system. [8]

A less drastic approach might be casual intermittent fasting—reducing the daily “eating window,” for example, from a more traditional 7 a.m. to 10 p.m. and instead to 10 a.m. to 7 p.m. This gives autophagy a chance to kick in overnight.

Our ancestors were forced by unsuccessful hunts, bad weather, spoilage, drought, and many other events to go without food, or with very little food, sometimes for days at a time, if not longer. Their bodies, and ours, evolved over time to take advantage of these lean times as mTOR kept cell growth suppressed, “cleaning house” while waiting for new fuel.

All told, a low-glycemic ancestral diet, comprising moderate- to high-protein intake in accordance with activity level—the more activity, the more protein needed—supplemented by intermittent fasting and occasional “fasting mimicking” dieting, seems the most intuitive way to “partner” with the mTOR pathway for health and longevity. A great example of this is Dr. Terry Wahls’ personal approach. [9]

References

1. Sabatini, David. “(PDF) Twenty-Five Years of MTOR: Uncovering the Link from Nutrients to Growth.” ResearchGate, doi:http://dx.doi.org/10.1073/pnas.1716173114. Accessed 8 Aug. 2020.

2. Rivas, Donato A., et al. “Lipid-Induced MTOR Activation in Rat Skeletal Muscle Reversed by Exercise and 5’-Aminoimidazole-4-Carboxamide-1-Beta-D-Ribofuranoside.” The Journal of Endocrinology, vol. 202, no. 3, Sept. 2009, pp. 441–51. PubMed, doi:10.1677/JOE-09-0202.

3. Cordain, Loren. The Paleo Diet: Lose Weight and Get Healthy by Eating the Foods You Were Designed to Eat. Revised edition, John Wiley & Sons, 2010.

4. Baum, Jamie I., et al. “Protein Consumption and the Elderly: What Is the Optimal Level of Intake?” Nutrients, vol. 8, no. 6, June 2016. PubMed Central, doi:10.3390/nu8060359.

5. Protein for Fitness: Age Demands Greater Protein Needs. https://www.todaysdietitian.com/newarchives/040715p16.shtml. Accessed 8 Aug. 2020.

6. Langsetmo, L., Harrison, S., Jonnalagadda, S. et al. Low Protein Intake Irrespective of Source is Associated with Higher Mortality Among Older Community-Dwelling Men. J Nutr Health Aging (2020).

7. Levine, Morgan E., et al. “Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population.” Cell Metabolism, vol. 19, no. 3, Mar. 2014, pp. 407–17. www.cell.com, doi:10.1016/j.cmet.2014.02.006.

8. Wei, Min, et al. “Fasting-Mimicking Diet and Markers/Risk Factors for Aging, Diabetes, Cancer, and Cardiovascular Disease.” Science Translational Medicine, vol. 9, no. 377, Feb. 2017. PubMed Central, doi:10.1126/scitranslmed.aai8700.

9. Whiteside, David. “Looking ‘Beyond Keto’ with Dr. Terry Wahls.” The Paleo Diet®, https://thepaleodiet.com/looking-beyond-keto-dr-terry-wahls.