How Does It Work?

Intermittent fasting triggers “evolutionarily conserved, adaptive cellular responses that are integrated between and within organs in a manner that improves glucose regulation, increases stress resistance and suppresses inflammation” (7). Cells activate pathways that help to bolster defenses against stress, both oxidative and metabolic, and “remove impaired or damaged molecules” (7). Intermittent fasting also has extremely powerful effects on the modulation of development and severity of potential disorders, including obesity, cancer, diabetes, neurodegenerative disorders and cardiovascular disease. Biologically, what happens during a fast is the breakdown of triglycerides into fatty acids and glycerol, both of which are used as energy. The liver then converts the fatty acids into ketones, which are also important energy sources, particularly for the brain, in periods of fast.

What Does It Do To Your Body?

While weight loss may be a primary goal for some undertaking intermittent fasting, the list of lifestyle benefits reach far beyond the scope of shedding a few pounds. Almost every organ system in the human body responds to intermittent fasting in ways that not only benefit the humanin question, but also allow their body to adapt to the stresses of a fasting period, making their body more resilient to potential repeated exposure in the future (6). The cells response to fasting periods is to initiate a “coordinated adaptive stress response” that helps trigger DNA repair, autophagy, mitochondrial biogenesis and a reduction in inflammation (10). There is also a huge metabolic effect from the ketones created from fasting. The switch to ketone bodies and fatty acids as a fuel source rather than glucose leads to a “reduced respiratory-exchange ratio” which is an indicator of better “metabolic flexibility and efficiency” (11). Ketones are also very important signaling molecules within the body that have great effects on many cellular and organ functions outside of their role as fuel. These molecules help to regulate many proteins and molecules that influence both overall health and the aging process, including nicotinamide adenine dinucleotide (NAD+) and sirtuins (12),(13).

Does Intermittent Fasting Really Work?

There have been multitudes of studies done that show not only the weight loss benefits, but overall health benefits from intermittent fasting. It makes sense to think about it, we as humans adapted and developed to go through sparse times of food while hunting, and then enjoy our spoils after the “kill”. So the modern 3-meals-a-day goes against our evolutionary design. Additionally, intermittent fasting seems to have more beneficial attributes than just caloric restriction alone. In human models, fasting works to fight against a multitude of mortalities and symptoms associated with them, including obesity, insulin resistance, dyslipidemia, hypertension and inflammation (15).

Autophagy and Fasting

What Causes Autolysis?

 Autolysis, or “self-digestion”, is a process triggered when the lysosome in a cell release digestive fluids to eat away at anything from proteins, fats or even DNA.

How to Induce Autophagy?

 Fasting works to trigger both autophagy and mitophagy while simultaneously inhibiting the mTOR pathway. This allows cells to clear out potentially dying or damaged proteins while also temporarily reducing protein synthesis to conserve resources and energy (6),(10). In fact, fasting and caloric restriction are widely viewed as the best ways to increase autophagy and it’s benefits. Furthermore, fasting lacks the other less desirable side effects that come with other interventions (14).

How Long Do You Need to Fast For Autophagy?

   Autophagy is a process that is constantly occurring in your body. However, in order for your body to begin to respond to the stress of nutrient deprivation, a fast of at least 16 hours is required, with responses increasing the longer one fasts. Autophagic markers vary from tissue to tissue, but saw an upward trend with the initiation of a fast, and correlated positively as time increased, with the peak levels seen at the 24-48 hour mark (14).

Does Autophagy Occur Without Fasting?

Autophagy is a natural process that occurs within our bodies constantly, with or without fasting. However, as we age, the process slows, which leads to many of the symptoms we associate with getting older. Fasting, both at a young age and in our later years, almost acts as a catalyst, speeding up the process of autophagy, giving the naturally-occurring function a boost.

How Long Should You Fast?

There are several different iterations of fasting regiments, and the amount of time you fast is dependent on the program you are following. Time-restricted fasts typically constitute a 16-18 hour fast, and tend to be the most accessible and have the best adherence as far as lifestyle changes are concerned. Alternate-day fasts are exactly what they sound like, with an entire 24 hour period of fasting occurring every other day. For 5:2 fasts, you will fast for 2 days of the week, again avoiding food for the entire 24 hours of the fast day (9).

 How Long Should You Intermittent Fast?

 The main fuel source of the body during fasting times is the ketone, so to understand how long someone needs to fast to have an adequate biological response, we look to that molecule. Ketones within the body remain low during a feeding state, within 8 hours of fasting, levels rise and continue to show an upward trend all the way through 48 hours of fasting (11). It is important to note that before you decide which fasting method to follow, you should consult with a health professional to ensure you are going following the proper steps and to avoid potential “over-fasting” that can turn into starvation.

How Long Is It Safe To Fast?

 Long term, there haven’t been enough studies done to see risks through years of following fasting, however in a 2 year study that had participants on a 12% reduction in daily caloric intake showed an improvement in multiple cardiovascular risk factors in people who are not obese (16).

Benefits Of Fasting


A reduction in food intake conducive to caloric restriction and fasting showed a “robust” increase in life span with both mice and rats showing an increase in lifespan with caloric restriction, up to 27% and 45%, respectively (17). In a study done at the university of Wisconsin, there was a very clear positive link between caloric restriction and both health and life extension. In a different study, done by the National Institute on Aging, they were unable to find a significant increase in lifespan, but found obvious improvements in health over all. (1)


Not only is fasting as effective in weight loss as other diets, but it also improves potential cardiac risk factors in adults (1). Some of these risk factors include blood pressure, resting heart rate, HDL and LDLs, triglycerides, glucose, insulin and insulin resistance. Additionally, a reduction in both the inflammation and oxidative stress seen with atherosclerosis was demonstrated. Interestingly, fasting also improved HRV, or heart rate variability, by improving parasympathetic tone in both humans and rats. HRV is a good indicator of how well someone’s nervous system is functioning. Furthermore, both normal-weight people and obese people showed cardioprotective characteristics and reduced weight after following an alternate-day pattern. When it comes to the question of timing, it takes around 2 to 4 weeks for improvements in cardiovascular health to arise from fasting, and continue throughout the diet, but it can take weeks for all of the effects to dissipate once the patient returns to a normal diet. (3)


For over 100 years, the beneficial effects of fasting on slowing and stopping tumor growth has been documented in animals, with many studies showing that a daily caloric restriction can not only slow the growth of tumors, but help increase the sensitivity to chemotherapy and radiation, thus improving the effectiveness of the treatment as well (4). The suspected mechanism in fasting’s effectiveness at combating cancer cells is the impairment of the metabolism of the cells themselves, which then allows them to be more vulnerable to treatment (5). In a case study done with patients suffering from glioblastoma, fasting was not only able to suppress tumor growth, but also extend patient survival rates (6). While there is promising research about the effects of fasting and cancer in humans, there is not yet much research about its effects on the recurrence of cancer.

Tissue Damage

There is string data that indicates fasting both pre and post-op can have an extremely beneficial effect on tissue damage from either surgery or injury. When performed before surgery, fasting can work to reduce the inflammation triggered by tissue damage, and help heal the area faster than usual. It has also been demonstrated that “2 weeks of preoperative daily energy restriction improves outcomes in patients undergoing gastric bypass surgery” (8). There is also new research coming out on the potential benefits of fasting and reparation of head and neck injuries, with animal models seeing a marked reduction in tissue damage and increased cognitive function after a traumatic brain injury (9).

Is Fasting Good For Diabetics?

Yes, the ability for intermittent fasting to help with specifically obesity and insulin resistance can have great positive effects for diabetics. In one study, healthy participants saw a 2.5% reduction in weight, 4% reduction in fat mass and 57% reduction in insulin levels after 22 days of IM (18). In another study, overweight women were divided into a group who followed the 5:2 method for intermittent fasting and a group that just reduced caloric intake by 25%. While both groups lost a similar amount of weight, the IM group saw a great increase in insulin sensitivity with a bigger drop in wait circumference as well (1). Additionally, animal models have shown that fasting can relieve symptoms often associated with diabetes, like obesity, insulin sensitivity and retinopathy. In human studies, fasting has been so beneficial that it “reversed insulin resistance in patients with prediabetes or type 2 diabetes” (1)

Can Fasting Be Harmful?

When done incorrectly, fasting can turn into starvation, which can become both harmful and dangerous to patients, especially those who are already clinically weakened. However, when done properly, the only real harm fasting causes is an increase in hunger, irritability and a lack of concentration. These side effects are normal and will usually dissipate within the first few weeks of the program (10).

Does Fasting Help Parkinson’s/Alzheimer's?

In animal studies, there is growing evidence that fasting can both slow or even prevent the onset of neurodegenerative diseases like Alzheimer's and Parkinson's (7). The mechanism behind this is that the stimulation of autophagy, increased mitochondrial function and DNA repair that go along with fasting are thought to increase stress resistance in the neurons (7). In short-term studies, older adults saw a marked improvement in their verbal memory retention. As stated above, both caloric restriction and alternate-day fasting work to “reverse the adverse effects of obesity, diabetes and neuroinflammation on spatial learning and memory” (1). In a one year study with adults facing “minor cognitive impairments”, caloric restriction caused a marked improvement in “verbal memory, executive function and global cognition”. Furthermore, in a longer 2-year study, daily caloric restriction aided in improving working memory by a significant margin.

Does Fasting Hurt Muscle Growth?

Autophagy, which is upregulated during fasting periods, is “indispensable” for preventing weakness and loss of muscles. This is because the process by which autophagy works clears out damaged and toxic proteins from within the muscle itself, while also removing dysfunctional organelles, which allows the muscles to operate and grow unhindered (14). A study done on healthy young men in a resistance training program showed that those who fasted daily for at least 16 hours were more adept to lose fat while maintaining muscle over a period of 2 months (19). In both humans and animals, it has been shown that IM can improve physical function. In a study with mice on  an alternate-day intermittent fasting regime, the fasting mice showed better running endurance than their control counterparts. Furthermore, it has been demonstrated that not only does intermittent fasting help with endurance, but it is also proven that it can help improve balance and coordination as well.(1)

Is Intermittent Fasting Bad For Metabolism?

We already touched on intermittent fasting’s effects on metabolism in the section “What does it do to your body?”, but to recap, fasting triggers a change in fuel source within your body from glucose to fatty acids and ketone. This switch reduces the ratio of CO2 produced from oxygen consumed (respiratory-exchange ratio), which shows that fasting and the subsequent energy switch help to streamline energy production, making it more efficient and increasing the flexibility of your metabolism (11).



  1. Effects of Intermittent Fasting on Health, Aging, and Disease
  2. Caloric restriction and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats
  3. When less may be more: calorie restriction and response to cancer therapy
  4. Energy restriction and the prevention of breast cancer
  5. Fasting and cancer: molecular mechanisms and clinical application
  6. Hallmarks of brain aging: adaptive and pathological modification by metabolic states
  7. Preoperative very low-calorie diet and operative outcome after laparoscopic gastric bypass: a randomized multicenter study
  8. Short- term caloric restriction exerts neuroprotective effects following mild traumatic brain injury by promoting autophagy and inhibiting astrocyte activation
  9. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women
  10. Caloric restriction
  11. A time to fast
  12. β-Hydroxy- butyrate: a signaling metabolite
  13. It takes two to tango: NAD+ and sirtuins in aging/longevity control
  14. The effect of fasting or calorie restriction on autophagy induction: a review of the literature
  15. Metabolic slowing and reduced oxidative damage with sustained caloric restriction sup- port the rate of living and oxidative damage theories of aging
  16. Design and conduct of the CALERIE study: comprehensive assessment of the long- term effects of reducing intake of energy
  17. Dietary restriction in rats and mice: a meta-analysis and review of the evidence for genotype-dependent effects on lifespan
  18. Alternate-day fasting in non-obese subjects: effects on body weight, body composition, and energy metabolism
  19. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males

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  • Don Moxley - Director of Applied Science

    Don Moxley is the Director of Applied Science at Longevity Labs. Moxley draws upon his career as an athlete, a sports scientist, and an instructor to lead and educate on the science of autophagy and longevity.