You can't directly "feel" autophagy, but signs it's working include increased energy, better mental clarity, reduced inflammation/pain, improved digestion, and lower appetite, often accompanied by ketone production (fruity breath) during fasting, while lab tests (like Glucose Ketone Index) offer more objective measures, though clinical confirmation requires medical monitoring.
While you can't "feel" autophagy directly, some signs may indicate it's working: Increased energy levels. Better mental clarity. Reduced inflammation.
Depending on the individual's metabolism, significant autophagy may take two to four days of fasting in humans. Autophagy is believed to begin when glucose and insulin levels drop considerably. Animal studies have shown evidence of autophagy after 24 hours of fasting, which starts peaking at around 48 hours of fasting.
Autophagy, the cell's recycling process, generally occurs in five main stages: Initiation (signals trigger), Nucleation/Phagophore Formation (a double membrane starts forming), Elongation & Autophagosome Formation (membrane grows, engulfs cargo into a sphere), Fusion (autophagosome joins a lysosome), and Degradation (lysosomal enzymes break down contents for reuse).
Activation of autophagy helps the host cells to eliminate misfolded, aggregated proteins and injured organelles [1]. Besides its role in cellular homeostasis, autophagy is actively involved in the development, differentiation, and regenerative potential of several embryonic and adult cells [2,3].
Autophagy allows your body to break down and reuse old cell parts so your cells can operate more efficiently. It's a natural cleaning out process that begins when your cells are stressed or deprived of nutrients. Researchers are studying autophagy's role in potentially preventing and fighting disease.
What turns off autophagy? Eating. Glucose, insulin (or decreased glucagon) and proteins all turn off this self-cleaning process. And it doesn't take much.
If Your Fasting Goal Is Autophagy or Gut Rest…
During these fasts, you're pretty much confined to unflavored water (sparkling is OK) and unsweetened herbal tea. That's right: No coffee allowed! And certainly no coffee with butter.
If you're new to fasting, you may experience some bothersome symptoms. Hunger is common because your body may be used to getting fuel at certain times. You may also get headaches, fatigue and mood changes. This is in part because when we don't eat for a period of time, we get low blood sugar (1).
22:2 fasting, also known as the OMAD (One Meal A Day) diet, is a form of intermittent fasting where you fast for 22 hours and eat all your daily calories within a compact 2-hour window, focusing on nutrient-dense foods to support weight loss, improve digestion, and boost mental clarity, though research on its long-term safety and effectiveness is limited. It's an intense, restrictive schedule that helps reduce overall calorie intake and may trigger autophagy (cellular cleanup), but requires careful attention to nutrition during the eating window to avoid deficiencies.
Several studies have shown that induction of autophagy can accomplish rejuvenation of quiescent stem cells that can restore age-related molecular and functional features both in vitro and in vivo (Figures 1D–E; Chen et al., 2009; Zhu et al., 2015; Leeman et al., 2018; Fang et al., 2020; Navarro Negredo et al., 2020; ...
One randomized crossover trial demonstrated that fasting 18 out of 24 hours for less than 1 week with some caloric restriction could increase autophagy markers in the body. Similarly, recent research indicates that one month of fasting 17–19 hours each day increases autophagy signals in humans.
A common question is whether lemon water breaks autophagy. The answer: plain lemon water (without sugar or calories) is unlikely to significantly disrupt autophagy, as the process is mainly sensitive to caloric intake. However, adding sugar or honey would provide energy and could reduce autophagic activity.
During the fasting period, you can consume water, unsweetened black coffee, or tea. 5:2 Diet: This offers more flexibility. You restrict your calorie intake to 500–600 calories on two non-consecutive days of the week and eat normally on the other five days.
People in ketosis may experience a variety of side effects and symptoms, including headaches, stomach upset, and changes to their sleep and energy levels. For a more accurate way of determining ketosis, people can check the levels of ketones in their blood, breath, or urine.
Many medical experts agree that a one-day fast can feel great. But extending beyond three days can begin to cause harm, especially if you have other medical conditions, such as diabetes or heart disease. “A fast longer than a day or two can deplete vitamins, minerals and electrolytes,” Dr. Hopkins says.
Ketosis doesn't change the natural color of urine much, but dehydration (common in ketosis) makes it darker, like amber or dark orange; however, you test for ketones using strips that change from beige to pink, purple, or brown, indicating "negative," "trace," "small," "moderate," or "large" amounts, showing you're producing ketones. The deeper the color on the strip (dark purple/brown), the more ketones are present, though strips measure acetoacetate, not the main ketone, so blood tests are more accurate, especially for high levels.
A 72-hour fast, or fasting for three consecutive days without any food intake, can help your body enter a state of ketosis. Ketosis is a metabolic state in which your body burns stored fat for energy instead of glucose from carbohydrates.
Doctors are cautious about intermittent fasting (IF) due to potential risks like increased cardiovascular death (especially with <8hr windows), hormonal issues for women, muscle/bone loss, side effects (fatigue, headaches), risks for specific groups (diabetics, pregnant/elderly), and the lack of long-term data, with some studies showing similar benefits to general calorie restriction or suggesting risks that outweigh benefits, urging personalized medical advice.
Exercise. Physical activity places controlled stress on cells, which in turn triggers autophagy. Regular exercise, particularly endurance training and high-intensity interval training (HIIT), has been shown to enhance cellular cleanup mechanisms.
Outside of the cells, autophagy improves cognitive function, protects against heart disease, and enhances the immune system. Additionally, the process prevents free radical damage to the tissues and organs. There is also research looking into the role of autophagy in treating and preventing cancer.
Another downside worth considering is the potential for an increased stress response after a fasted workout. Being in a fasted state lowers blood glucose levels, which in turn stimulates cortisol release.