Exploring Autophagy: Wellness and Beyond

Rebecca Jaspan, MPH, RD, CEDS, CDCES

The cellular process of autophagy is gaining traction in the wellness world and on social media, with video tags on TikTok hitting close to 35 million views.  Some TikTokkers claim that fasting triggers the body to eat itself and jumpstart weight loss while others are linking fasting to healing cancer and diabetes. While autophagy does literally translate to “self-eating”, much of these claims are wildly oversimplified and filled with misinformation. So, what exactly is autophagy and what role could it play in the treatment of disease and slowing of aging?

Understanding Autophagy and Its Importance

Autophagy is your body’s natural process of cleaning out your cells and reusing old and damaged cell parts.  You can think about autophagy as your body’s recycling system. Your cells are complicated little systems that have many parts to keep them functioning.  As with any machine, these parts can be come defective or stop working. Rather than destroying the cell all together, autophagy is the system that allows cells to disassemble and repurpose the usable parts into new cells. Autophagy is also the quality control system for your cells.  When too many defective parts accumulate, this can slow or prevent the cell from functioning properly.  Autophagy helps to optimize cell performance by getting rid of the clutter.

Autophagy occurs when your body’s cells are deprived of nutrients or oxygen or if they are damaged in some way.  When your body is deprived of resources, it has no choice but to ramp up this process to make the most out of its existing resources since your cells aren’t getting fuel or oxygen from an outside source. Essentially, your cell uses its own resources to survive.

How Fasting Influences Autophagy

So what happens in your cells when you deprive them of resources?  The body’s main, preferred source of energy is glycogen, which is a stored form of glucose that comes from the carbohydrates you eat.  When you digest carbohydrates, they break down into sugar, or glucose, that is stored in the muscles and liver as glycogen.  In the couple of hours after eating, insulin levels rise, which causes the glucose that is broken down into your blood to be moved into your cells to be used for energy.  Whatever doesn’t get used is stored in your muscles or liver.  12 hours after fasting, insulin levels drop, and ghrelin, the hormone that signals hunger, will increase.  It takes between 4 and 18 hours of fasting to burn through all of your glycogen stores.  Your body will then begin to break down fat and protein to use for energy.  After 18 hours, your body will transition into a state of ketosis, when it relies primarily on fat as its primary source of energy.  Autophagy begins at the 24-hour mark.  After about 24 hours of fasting, your cells start to get rid of components that are old, damaged, or functioning poorly.  The process of autophagy declines naturally with age and it is thought that fasting-induced autophagy can be a way to reduce the effects of aging and prevent certain diseases.

Autophagy’s Role in Disease Prevention and Aging

There is a growing field of research examining how autophagy may be beneficial in slowing or preventing certain disease processes.  In various studies looking at autophagy and heart disease, it is thought that increased autophagy can exert beneficial effects on the heart and protect it from age-related cardiac deterioration.¹  In one rodent study, fasting lead to decreased cardiac fibrosis, cardiac hypertrophy, and cardiomyopathy with aging.  Additionally, there is evidence that fasting has beneficial effects on the vascular system as an individual ages.²

Research also shows that impairment of the autophagic pathway may play a role in the development of type 2 diabetes.  Pancreatic beta cells are responsible for the synthesis, storage, and release of insulin.  As autophagy increases with age, beta cells become less functional and can result in a reduction of glucose tolerance.  Recent studies show the role of autophagy in maintaining the function of pancreatic beta cells and the release of insulin, but more research needs to be done.³

Navigating the Benefits and Considerations of Enhancing Autophagy

While it is tempting to fast, restrict calories, or try the keto diet in order to enhance autophagy to increase longevity and prevent diseases, this is newer science that should be approached with caution.  There are many factors to consider before trying any of these methods and if you do, it is recommended to do it under the supervision of a doctor and registered dietitian rather than on your own.  It is important to consider what your blood sugar management is like normally.  Are you someone with insulin resistance or do you get shaky and hypoglycemic after going a few hours without food?  For individuals with polycystic ovarian syndrome (PCOS) and insulin resistance, there is research showing that a time-restricted fast of 8 hours, ideally in the hours of 9am-5pm, may be beneficial if they are following a lower glycemic load intake to prevent a spike in insulin when the fast is broken.  This window may not be compatible for many individual’s schedules and difficult to implement in practice.  This reinforces the importance of doing this with the approval and supervision of a doctor and registered dietitian as the execution is much more specific than many people may think.⁵

Further, just as it is more beneficial and sustainable to lose a small amount of weight and keep it off instead of yo-yo dieting or have smaller fluctuations in blood sugar, the same stands true for fasting.  According to the research, a drastic change in eating patterns between weekdays and weekends is thought to contribute to metabolic diseases.  This suggests that if time-restricted fasting is not sustainable and permanent, it may not offer any benefit and could even result in negative health outcomes.⁵

It is also important to consider the psychological effects of fasting or restricting calories.  Not only can going a long time without eating lead to irritability, fatigue, and cognitive impairment, but it could be a risk factor for developing disordered eating or eating disorders.  Additionally, many individuals who restrict calories are more likely to binge after a period of time.  While there is some early promising research on autophagy, many studies have been conducted on animals, not humans.  Additionally, methods to enhance autophagy are not for everyone and pros and cons should be discussed with your medical team.  A lot more research is needed before any clinical recommendations or conclusions can be drawn.

1. Koutouroushis C, Sarkar O. Role of Autophagy in Cardiovascular Disease and Aging. Cureus. 2021;13(11):e20042. Published 2021 Nov 30. doi:10.7759/cureus.20042
2. The relative protective effects of moderate dietary restriction versus dietary modification on spontaneous cardiomyopathy in male Sprague-Dawley rats. Kemi M, Keenan KP, McCoy C, Hoe CM, Soper KA, Ballam GC, van Zwieten MJ. Toxicol Pathol. 2000;28:285–296.
3. Bhattacharya D, Mukhopadhyay M, Bhattacharyya M, Karmakar P. Is autophagy associated with diabetes mellitus and its complications? A review. EXCLI J. 2018;17:709-720. Published 2018 Jul 24. doi:10.17179/excli2018-1353
4. Congdon EE. Sex Differences in Autophagy Contribute to Female Vulnerability in Alzheimer’s Disease. Front Neurosci. 2018;12:372. Published 2018 Jun 22. doi:10.3389/fnins.2018.00372
5. Chaix A, Zarrinpar A, Miu P, Panda S. Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab. 2014;20(6):991-1005. doi:10.1016/j.cmet.2014.11.001