Keto Means
Photo by Pixabay Pexels Logo Photo: Pixabay

Is 16 hours enough for autophagy?

How long do you need to fast for autophagy? The current evidence suggests that anywhere between 18 hours (as evidenced by the eTFR study) to four days will trigger autophagy.

Will Apple cider vinegar break a fast?
Will Apple cider vinegar break a fast?

No, drinking apple cider vinegar will not break a fast. As long as your body sustains a low carb intake, it remains in a state of ketosis. Thereby,...

Read More »
Is eating a whole cucumber too much?
Is eating a whole cucumber too much?

Because cucumber is so low in calories, it's hard to eat too much when it comes to weight management. However, eating too much of anything can...

Read More »

Our cells go through a normal, physiological mechanism in which they quite literally feed on themselves—a process known as autophagy (pronounced aa-TAA-fuh-jee). The word autophagy stems from the Greek prefixes auto- (self) and -phagy (feed on). This form of cellular housekeeping allows our body to remove damaged parts of cells while recycling others. Inducing autophagy, especially through extended fasts, has become a popular habit among the longevity and biohacking crowds as a way to improve healthspan and live longer. But is this safe? How long is too long of an extended fast? Where does the current literature stand in humans? In this article, we dive into the popular (but still relatively uncharted) field of autophagy.

What is autophagy?

Autophagy is a form of cellular housekeeping where misfolded proteins, damaged organelles, and pathogens are degraded and removed from cells. As seen in the diagram below, as the process of autophagy begins, a structure (or autophagosome) starts to form. Once fully enclosed, the autophagosome fuses with a lysosome—an organelle containing enzymes that can degrade and destroy molecules. The fusion of both organelles creates an autolysosome, where the degradation of cellular parts occurs. Other parts are recycled and reused for cellular repair.[1] Autophagy plays a vital role in the homeostasis of cellular health, as the outcome leads to healthier cells and the death and clearance of damaged and dysfunctional ones. Autophagy plays a critical role in many areas of health, including the prevention of numerous diseases like cancer, diabetes, autoimmune disorders, infections, and neurodegenerative and cardiovascular diseases. Like many physiological processes in the body, autophagy declines with age, but various animal and cell studies indicate that increased activation of autophagy may lead to improved longevity and a longer lifespan.[2-3]

Is autophagy good or bad?

The dysregulation of autophagy—too little or too much—can be harmful and lead to abnormal cell growth or cell death. For example, halting autophagy for an extended period can impact cell growth and lead to several disorders, including tumor formation. On the contrary, overstimulation of autophagy in tumor cells allows them to survive under stressful conditions like chemotherapy and hypoxia.[2] Based on the current research, there are safe and practical ways to induce autophagy to a helpful degree and improve the health of our cells and organs.[2-3] But like many topics in the field of longevity—more research in humans is needed to fully understand the outcomes of induced autophagy.

How do you induce autophagy?

What did Jesus say about fruit?
What did Jesus say about fruit?

From Matthew 7:15–20 (KJV): Even so every good tree bringeth forth good fruit; but a corrupt tree bringeth forth evil fruit. A good tree cannot...

Read More »
What meat is lowest in calories?
What meat is lowest in calories?

Meats that are lowest in calories are the ones that are very lean. ... Fat is calorie-dense, so fattier cuts of meat have a higher calorie count....

Read More »

Autophagy can be induced by various stress conditions, including calorie restriction (CR), fasting, and exercise.[2] Certain foods and medications can also stimulate autophagy through different mechanisms.[2-3] Calorie restriction, generally a 10-40% reduction in overall caloric intake, is among the most potent autophagy inducers. Clinical research indicates that long-term calorie restriction (3-15 years) leads to an increased expression of autophagy genes and higher levels of molecules involved in removing dysfunctional proteins and organelles.[4] It’s widely accepted that both CR and fasting may lead to improved health and longevity, and autophagy likely plays a key role in this. Both intermittent fasting and extended fasting also lead to an increase in autophagy activity. In a 2019 crossover study, researchers analyzed numerous markers related to longevity, including the expression of autophagy genes. A group of 11 overweight adults followed an early time-restricted feeding (eTRF) schedule and a normal eating schedule. The eTRF schedule resulted in improved longevity outcomes, including a 22% increase in the production of the autophagy gene LC3A after just four days. A handful of human studies also show extended fasts lead to increased autophagic activity through various mechanisms.[5-7] Exercise also induces autophagy in muscle tissue[8-10]. Autophagy markers immediately increase after short bouts of intense exercise and also over the course of longer moderate-intensity training sessions.[8,10] Some researchers have sought to determine whether exercising after an extended fast may result in greater autophagy activation. However, one study found that exercise intensity was more powerful at inducing autophagy, independent of whether fasting was involved [9].

How long do you need to fast for autophagy?

The current evidence suggests that anywhere between 18 hours (as evidenced by the eTFR study) to four days will trigger autophagy.[5-7] However, only a handful of studies measuring fasting and autophagy exist in humans. As mentioned above, intermittent fasting, calorie restriction, and exercise are all ways to boost autophagy that don’t involve fasting for several days.

What foods inhibit autophagy?

Interestingly, protein-based beverages may decrease autophagy activity. In a randomized control crossover trial, eight males were administered different protein/carb beverages after completing a 36-hour fast. A marker of autophagy activity (LC3II/LC3I ratio) was measured during the fasting vs. the non-fasting periods. A decrease in autophagy occurred when the men sipped on the protein-rich beverages (leucine-rich whey or soy-based protein) but not the carbohydrate-rich ones. The researchers noted that these findings align with rodent studies where branched-chain amino acids tend to suppress autophagy during catabolic conditions (like fasting). Glucose, on the other hand, does not impact autophagy.[7]

Does coffee stop autophagy?

What does being a picky eater say about you?
What does being a picky eater say about you?

Turns out, there's no single explanation for your picky eating habits, but rather, experts suggest a combo of genetics and environment are to...

Read More »
Is toothpaste keto friendly?
Is toothpaste keto friendly?

The diet is also very restrictive that even the sugar in mouthwash and toothpaste can throw your body out of ketosis and affect your results. Jun...

Read More »

Current research suggests that coffee does not stop autophagy. Research done in mice indicates that coffee actually stimulates autophagy in several tissues.[11]

Foods that promote autophagy

Lately, recent studies demonstrate that polyphenols, beneficial compounds found in plants, may play a role in inducing autophagy. Polyphenols stimulate various pathways, which can lead to autophagy and a longer lifespan.[3] For example, resveratrol is a common autophagy inducer found in grape skins and nuts. Other polyphenols include quercetin, green tea catechins, and curcumin. The following foods contain polyphenols that promote autophagy:

Green tea

Grape skin (red wine)

Nuts

Onions

Apples

Berries

Turmeric

Soybeans

Milk thistle

A summary of what we know about autophagy:

Autophagy is a form of cellular housekeeping in which misfolded proteins, damaged organelles, and pathogens are degraded and removed from cells. Autophagy plays a critical role in many areas of health, and like many physiological processes in the body, autophagy declines with age.

Calorie restriction, fasting, and exercise are all potent inducers of autophagy.

Polyphenols, beneficial compounds found in plants, may also play a role in inducing autophagy. Only a handful of studies measuring fasting and autophagy exist in humans. More research is needed to fully understand the benefits and implications of autophagy.

Diana Licalzi, MS, RD

You'll often find Diana whipping up plant-based recipes, sipping on a mocktail, or hiking up a mountain. You can follow her on Instagram at Diana is a Content Strategist and Team Nutritionist at InsideTracker. She is a Registered Dietitian that specializes in plant-based nutrition and type 2 diabetes.hiking up a mountain. You can follow her on Instagram at @dietitian.diana

References:

[1] https://www.nature.com/articles/emm201210

[2] https://pubmed.ncbi.nlm.nih.gov/30172870/

[3] https://www.sciencedirect.com/science/article/pii/S1568163712000529

[4] https://pubmed.ncbi.nlm.nih.gov/26774472/

[5] https://www.tandfonline.com/doi/full/10.1080/15548627.2016.1271513

[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214394/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214394/

[7] https://pubmed.ncbi.nlm.nih.gov/27265181/

[8] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889490/

[9] https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.14-267187

[10] https://journals.physiology.org/doi/full/10.1152/japplphysiol.01116.2014?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org

[11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111762/

How can I lose 20 pounds in a month without exercise?
How can I lose 20 pounds in a month without exercise?

How to Lose 20 Pounds of Fat in 30 Days (Without Doing Any... Rule #1: Avoid “white” carbohydrates. ... Rule #2: Eat the same few meals over and...

Read More »
Is sour cream good for keto?
Is sour cream good for keto?

Regular, full fat sour cream is made from cream and contains far more fat than carbs. Therefore, it's considered keto-friendly. However, low fat or...

Read More »
Is hummus allowed on keto?
Is hummus allowed on keto?

Hummus can definitely be part of your keto diet, but just one or two servings can quickly expend a significant portion of your daily carb...

Read More »
Can you eat unlimited vegetables on keto?
Can you eat unlimited vegetables on keto?

Not Paying Attention to Your Veggie Intake Vegetables have carbohydrates. And that means that you have to watch how much you eat — even lettuce. If...

Read More »