The four best diets to induce autophagy

Unlocking your cellular superpower with nutrition: learn how autophagy-inducing diets can be used to boost health and longevity.

Empty plate and autophagy
What to know
  • Autophagy involves the breakdown and recycling of old and damaged cells and is important for healthy aging.

  • The ketogenic, Mediterranean, and plant-based diets have been shown to induce autophagy.

  • Fasting and caloric restriction also stimulate autophagy.

  • The key considerations for a diet to induce autophagy are meal timing, energy content, and polyphenol content.

In the quest for longevity and optimal health, the concept of autophagy has garnered significant attention. This natural cellular process plays a crucial role in rejuvenating our cells, clearing out damaged components, and promoting overall well-being.

One powerful way to kickstart autophagy is through dietary choices. As such, several dietary strategies have been highlighted as “autophagy diets.”

From intermittent fasting to ketogenic eating and beyond, this blog will explore the methods that harness the body's innate ability to heal and regenerate through autophagy.

Keto Diet

Ketogenic diet

The ketogenic diet involves severely limiting carbohydrate intake and is modest in protein while allowing a liberal intake of fat. When carbohydrates are restricted, the metabolism is shifted into a state of ketosis, where the body primarily burns fat for fuel. Molecules called ketones are produced, which serve as an alternative energy source to glucose, the type of energy our cells use after we eat carbohydrates.[1]

The keto diet has been studied for its ability to activate autophagic pathways. One such study conducted in rats demonstrated that the keto diet induced autophagy and had a neuroprotective effect. [2]In Another study, also conducted in animals, autophagy was upregulated in the livers of the subjects eating a keto diet.[3]

Fasting

Fasting

Numerous studies have examined the relationship between fasting and autophagy.

Intermittent fasting is a dietary approach that alternates between periods of eating and fasting, focusing not on what you eat but on when you eat.[4]

Several methods of fasting have been explored in relation to autophagy activation. Many studies, but not all, also involve caloric restriction, making it challenging to truly determine if it’s the fasting or the calorie restriction that has the greater impact.

For example, one study focused on mice and fed them two meals per day without restricting calories. Keeping a shortened eating window was sufficient to induce autophagy.[5]

Other research has also found that fasting for various periods of time stimulates autophagy.[6]

Mediterranean Diet

Mediterranean diet

The Mediterranean diet is characterized by a high intake of plants and is rich in dietary fibers, fatty acids, antioxidant and anti-inflammatory substances. Among these substances are polyphenols such as resveratrol, anthocyanins, and ellagic acid, among others. Polyphenols have been shown to stimulate autophagy and potentially have a protective effect when it comes to the development of certain health conditions.[7]

Plant-based

Plant-based diet

A diet that is rich in plants with a modest content of protein may also support autophagy.[8] Vegan diets and low-protein diets are among those that have been studied, and protein restriction has been shown to promote autophagy.[9] Many diets around the world are rich in plants and relatively low in protein, such as the Okinawan diet and the vegetarian approach of the Seventh-day Adventists.

Final words

There is not one single “autophagy diet” or even “longevity diet.” The timing of eating, energy content, and polyphenol content are some key considerations.

Some supplements like Mitopure®, a clinically validated dose of the postbiotic Urolithin A, can induce autophagy. In clinical studies, Mitopure has been shown to improve a specific type of autophagy called mitophagy, resulting in greater cellular energy and better muscle strength and performance.[10] Topical application has been shown to re-energize skin cells to help them better combat intrinsic (biological) and extrinsic (environmental) aging factors.[11]

Promoting autophagy should be a key consideration when it comes to healthy aging, and eating for longevity is just one of the lifestyle factors to consider, among others such as exercise.

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Authors
Jinan Banna, PhD, RD

Jinan Banna, PhD, RD

Professor of Nutrition & Scientific Writer

Jen Scheinman, MS, RDN, CDN

Senior Manager of Nutrition Affairs

References
  1. O'Neill B, Raggi P. The ketogenic diet: Pros and cons. Atherosclerosis. 2020 Jan;292:119-126. doi: 10.1016/j.atherosclerosis.2019.11.021. Epub 2019 Nov 28. PMID: 31805451

  2. Wang BH, Hou Q, Lu YQ, Jia MM, Qiu T, Wang XH, Zhang ZX, Jiang Y. Ketogenic diet attenuates neuronal injury via autophagy and mitochondrial pathways in pentylenetetrazol-kindled seizures. Brain Res. 2018 Jan 1;1678:106-115. doi: 10.1016/j.brainres.2017.10.009. Epub 2017 Oct 19. PMID: 29056525.

  3. Liśkiewicz D, Liśkiewicz A, Grabowski M, Nowacka-Chmielewska MM, Jabłońska K, Wojakowska A, Marczak Ł, Barski JJ, Małecki A. Upregulation of hepatic autophagy under nutritional ketosis. J Nutr Biochem. 2021 Jul;93:108620. doi: 10.1016/j.jnutbio.2021.108620. Epub 2021 Mar 8. PMID: 33705944.

  4. Antunes F, Erustes AG, Costa AJ, Nascimento AC, Bincoletto C, Ureshino RP, Pereira GJS, Smaili SS. Autophagy and intermittent fasting: the connection for cancer therapy? Clinics (Sao Paulo). 2018 Dec 10;73(suppl 1):e814s. doi: 10.6061/clinics/2018/e814s. PMID: 30540126; PMCID: PMC6257056.

  5. Paoli A, Tinsley G, Bianco A, Moro T. The Influence of Meal Frequency and Timing on Health in Humans: The Role of Fasting. Nutrients. 2019 Mar 28;11(4):719. doi: 10.3390/nu11040719. PMID: 30925707; PMCID: PMC6520689.

  6. Dayi T, Oniz A. Effects of the Mediterranean diet polyphenols on cancer development. J Prev Med Hyg. 2022 Oct 17;63(2 Suppl 3):E74-E80. doi: 10.15167/2421-4248/jpmh2022.63.2S3.2749. PMID: 36479482; PMCID: PMC9710397.

  7. Leri M, Scuto M, Ontario ML, Calabrese V, Calabrese EJ, Bucciantini M, Stefani M. Healthy Effects of Plant Polyphenols: Molecular Mechanisms. Int J Mol Sci. 2020 Feb 13;21(4):1250. doi: 10.3390/ijms21041250. PMID: 32070025; PMCID: PMC7072974.

  8. McCarty MF. Nutraceutical and Dietary Strategies for Up-Regulating Macroautophagy. Int J Mol Sci. 2022 Feb 12;23(4):2054. doi: 10.3390/ijms23042054. PMID: 35216170; PMCID: PMC8875972.

  9. Cupisti A, Giannese D, Moriconi D, D'Alessandro C, Torreggiani M, Piccoli GB. Nephroprotection by SGLT2i in CKD Patients: May It Be Modulated by Low-Protein Plant-Based Diets? Front Med (Lausanne). 2020 Dec 3;7:622593. doi: 10.3389/fmed.2020.622593. PMID: 33425967; PMCID: PMC7793896.

    1. Andreux PA, Blanco-Bose W, Ryu D, et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nat Metab. 2019;1(6):595-603. doi:10.1038/s42255-019-0073-4
    2. Singh A, D'Amico D, Andreux PA, et al. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Rep Med. 2022;3(5):100633. doi:10.1016/j.xcrm.2022.100633
    3. Liu S, D’Amico D, Shankland E, et al. Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial. JAMA Netw Open. 2022;5(1):e2144279. doi:10.1001/jamanetworkopen.2021.44279
  10. Topical application of Urolithin A slows intrinsic skin aging and protects from UVB-mediated photodamage: Findings from Randomized Clinical Trials. D D’Amico, AM Fouassier, J Faitg, N Hennighausen, M Brandt, D Konstantopoulos, C Rinsch, A Singh. medRxiv 2023.06.16.23291378; doi: https://doi.org/10.1101/2023.06.16.23291378

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Table of contents
Authors
Jinan Banna, PhD, RD

Professor of Nutrition & Scientific Writer

Jen Scheinman, MS, RDN, CDN

Senior Manager of Nutrition Affairs

Knowledge is power
Sign up to our newsletter

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease. References: *Nutrition studies: 500mg Mitopure® have been shown to (1) induce gene expression related to mitochondria function and metabolism and (2) increase the strength of the hamstring leg muscle in measures of knee extension and flexion in overweight 40-65 year olds. Data from two randomized double-blind placebo-controlled human clinical trials. **Nutrition NOURISH Study: 500mg Mitopure® have been shown to deliver at least 6 times higher Urolithin A plasma levels over 24 hours (area under the curve) than 8 ounces (240ml) of pomegranate juice in a randomized human clinical trial.

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