Intermittent Fasting: What is it? How does it work? Is it good for you?

As many of you may already know, recently I took part in a 72 hour fast. You may ask yourself, why would anyone want to deny themselves food for 3 whole days? As it turns out, scientists are discovering a multitude of health benefits of intermittent fasting, from fat loss, increased mental acuity to extending your life span1.

Intermittent fasting has also been shown to be beneficial with diseases like type 2 diabetes, heart disease, age-related neurodegenerative disorders, inflammatory bowel disease, and various forms of cancers.

Rather than go boring you with the physiological detail on how and why fasting improves your health, I have added reference links for anyone who would like to go deeper into the details on the subject. I think the average reader of my blog is more interested in “the what” and does not need to get bogged down in detail, much like the average person wants to know the time but does not care about the mechanics of how a watch works.

heathy people

What can intermittent fasting do for your health?

  1. Improves glucose regulation, increases stress resistance
  2. Enhance intrinsic defenses against oxidative and metabolic stress and those that remove or repair damaged molecules
    >8hrs, the body makes ketones for energy;
  3. They are potent signaling molecules with major effects on cell and organ functions.2
  4. Ketone bodies regulate the expression and activity of many proteins and molecules that are known to influence health and aging. 3,4,5,6
  5. Have profound effects on systemic metabolism
  6. Stimulate expression of the gene for brain-derived neurotrophic factor, with implications for brain health and psychiatric and neurodegenerative disorders.7
  7. Most if not all organ systems respond to intermittent fasting in ways that enable the organism to tolerate or overcome the challenge and then restore homeostasis. 8,9
  8. increased expression of antioxidant defenses
  9. DNA repair, protein quality control, mitochondrial biogenesis and autophagy, and down-regulation of inflammation
  10. improved function and robust resistance to a broad range of potentially damaging insults, including those involving metabolic, oxidative, ionic, traumatic, and proteotoxic stress.9
  11. Autophagy responses enable cells to remove oxidatively damaged proteins and mitochondria and recycle undamaged molecular constituents. These pathways are untapped or suppressed in persons who overeat and are sedentary.9
  12. In humans, intermittent-fasting interventions ameliorate obesity, insulin resistance, dyslipidemia, hypertension, and inflammation.10
  13. increase in insulin sensitivity11,12
  14. Studies in animals show that intermittent fasting enhances cognition in multiple domains, including spatial memory, associative memory, and working memory13;
  15. reversed insulin resistance in patients with prediabetes or type 2 diabetes.14,15
  16. Intermittent fasting improves multiple indicators of cardiovascular health in animals and humans, including blood pressure; resting heart rate; levels of high-density and low-density lipoprotein (HDL and LDL) cholesterol, triglycerides, glucose, and insulin; and insulin resistance.16,17,18,19
  17. reduces markers of systemic inflammation and oxidative stress that are associated with atherosclerosis.20,12,21,22
  18. intermittent fasting increases heart-rate variability by enhancing parasympathetic tone in rats23 and humans.24
  19. preclinical evidence that alternate-day fasting can delay the onset and progression of the disease processes in animal models of Alzheimer’s disease and Parkinson’s disease.7,9 Intermittent
  20. Bolstering mitochondrial function and stimulating autophagy, neurotrophic-factor production, antioxidant defenses, and DNA repair.9,25 
  21. Two recent pilot studies showed that patients with multiple sclerosis who adhere to intermittent-fasting regimens have reduced symptoms in as short a period as 2 months.26,27
  22. Reduces inflammation,20 
  23. There is evidence supporting its use in patients with arthritis.28
  24. Improves the outcomes of surgical procedures.29 
  25. Reduce autoimmune demyelination and improve the functional outcome in a mouse model of multiple sclerosis (experimentally induced autoimmune encephalomyelitis).26,30
  26. Improved insulin sensitivity

So now that you know all the benefits of intermittent fasting, the next question is how to go about it. There are several ways you can get started with intermittent fasting. Here are several of my favorites.

how to do an intermittent fasting

Several ways to do intermittent fasting:

The 12:12 method:

This is a daily fast. Each day commit to only eating between a predetermined 12 hour time frame like 7:00AM-7:00PM. Starting about 8 hours after your last meal, your body has used most of its available stored glucose and starts burning fat for energy by producing ketones. Blood levels of ketones rise within 8 to 12 hours after the onset of fasting, reaching levels of 0.2 to 0.5 mM. So a daily 12 hour fast should be enough to cause ketosis (when the body switches from using stored glucose in the liver to using fat cells for metabolism). These ketone bodies that are produced have far greater benefits to health than mearly burning fat for energy, as listed above. It is the production of these ketones that make intermittent far superior to mear caloric restrictive diets when it comes to improved health benefits.

Some experts prefer a 16:8 method restricts food consumption down to an 8 hour period. Basically, you skip breakfast. Personally, I find this method a bit to restrictive to keep up long term. Plus the fact that the ketone levels don’t start increasing from the 8-12 onset until about 24 hours. 8 to 12 hours after your last meal, you enter the fasted state. At this point your body burns fat much more efficiently because your insulin levels are low.

The 24:24

24:24 involves fasting for 24 hours ever other day. This can be an intense fast with a blistering pace and may not be suitable for beginners.  During the prolonged fasting period, your body begins to detoxify, releasing cholesterol and uric acid into the bloodstream. During this detoxification process, you may experience some side effects such as headaches, dizziness, fatigue, skin rashes, muscle pain, or joint aches. If this happens, it may be beneficial to begin with caloric restriction every other day until you build up to a 24 hour fast.

The 5:2
A 5:2 intermittent fast consists of eating normally for 5 days, Mon-Fri for example, and then fasting for 2 days, like the weekend. While this may seem a bit extreme at first, there is actually good reason to go longer than 24 hours during a fast. At 24 hours, the body begins something called autophagy, and continues to increase by 300% over the next 12-24. Autophagy literally means consuming the body’s own tissue. Autophagy is the body’s way of clearing out old and damaged cells from the system in order to replace them with newer, healthier cells32. This process recycles cellular components like amino acids to make new proteins and mitochondria (the powerhouses of cells) and make new energy for your body cells33. It also breaks down defective proteins in the cell to prevent them from accumulating inside the cell, which may lead to degenerative diseases like cancer and Parkinson’s Disease.

The 72-hour fast
Moving from a 48 hour fast to a 72 hour fast, in addition to the benefits described above, you can also expect your body to start dramatically producing more human growth hormone (HGH) and noradrenaline.  This process can last from 48 to 54 hours after your last meal34.  HGH is an important player in health and vitality. It plays an important role in maintaining, building, and repairing healthy tissue in the brain and other organs, it is responsible for speeding recovery of damaged cells from injury, improving metabolism, and even improving the condition of the skin to help you look younger and healthier.

Additionally, these hormones may play an important role in preventing heart attacks, strokes, and diabetes. Animal and in vitro studies suggest that prolonged fasting may promote stem cell regeneration, shifting from a dormant state to a state of self-renewal.

 Stem cells are like a blank canvas, they can grow into any specialized cell in the body, thereby inducing immune system regeneration. 

If you choose a 72 hour fast, consider not exceeding this practice more than twice a year.  This has shown to be an effective schedule to receive the benefits of rebooting the health of the body.

Conclusion:

The research shows that repeated exposure to intermittent fasting periods results in prolonged adaptive stress response. Your body runs more efficiently. Your digestive system works better. Your immune system functions more effectively, and research has shown that it can prolong the quality and longevity of your lifespan.

While some of the shorter fasts may be easy to incorporate into your routine, with increased time, denying your body food may become more challenging. You may start with a calorie restriction for the days of the prolonged fast in the beginning until your body gets used to it. For example, if you are doing a 5:2, many people will initially experience extreme hunger pains beyond the ability to power through it. Irritability, headaches, lightheadedness, and a reduced ability to concentrate are all common side effects to a body that has not adapted to such an extreme calorie restriction. However, these initial side effects usually disappear within 1 month, as your body adjusts to this new stressor.20,11,12

If you suffer any negative effects of beginning a pattern of intermittent fasting, you can begin by restricting your caloric intake to under 1000 calories on fasting days for the first month and then further reductions to 750 calories followed by 500 calories, etc until you can achieve your goal without symptoms. Remember, this is a marathon, not a sprint. The goal is improved health.

Lastly, A word of caution, intermittent fasting is not for everybody. Before you try intermittent fasting (or any diet), you should check with your primary care physician to be sure it is done in a safe manner. In addition, the following groups should avoid intermittent fasting:

  • Children and teens under age 18.
  • Women who are pregnant or breastfeeding.
  • People with diabetes or blood sugar problems.
  • Those with a history of eating disorders.

References:

  1. Rafael de Cabo, Ph.D., Mark P. Mattson, Ph.D. Effects of Intermittent Fasting on Health, Aging, and Disease. N Engl J Med 2019; 381:2541-2551, December 26, 2019
  2. Newman JC, Verdin E. β-Hydroxybutyrate: a signaling metabolite. Annu Rev Nutr 2017;37:51-76.
  3. Fisher FM, Maratos-Flier E. Understanding the physiology of FGF21. Annu Rev Physiol 2016;78:223-241.
  4. Gälman C, Lundåsen T, Kharitonenkov A, et al. The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARalpha activation in man. Cell Metab 2008;8:169-174.
  5. Imai SI, Guarente L. It takes two to tango: NAD+ and sirtuins in aging/longevity control. NPJ Aging Mech Dis 2016;2:16017-16017.
  6. Lee HC. Physiological functions of cyclic ADP-ribose and NAADP as calcium messengers. Annu Rev Pharmacol Toxicol 2001;41:317-345.
  7. Mattson MP, Moehl K, Ghena N, Schmaedick M, Cheng A. Intermittent metabolic switching, neuroplasticity and brain health. Nat Rev Neurosci 2018;19:63-80.
  8. Anton SD, Moehl K, Donahoo WT, et al. Flipping the metabolic switch: understanding and applying the health benefits of fasting. Obesity (Silver Spring) 2018;26:254-268.
  9. Mattson MP, Arumugam TV. Hallmarks of brain aging: adaptive and pathological modification by metabolic states. Cell Metab 2018;27:1176-1199.
  10. Redman LM, Smith SR, Burton JH, Martin CK, Il’yasova D, Ravussin E. Metabolic slowing and reduced oxidative damage with sustained caloric restriction support the rate of living and oxidative damage theories of aging. Cell Metab 2018;27(4):805.e4-815.e4.
  11. Harvie MN, Pegington M, Mattson MP, et al. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int J Obes (Lond) 2011;35:714-727.
  12. Harvie M, Wright C, Pegington M, et al. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. Br J Nutr 2013;110:1534-1547.
  13. Wahl D, Coogan SC, Solon-Biet SM, et al. Cognitive and behavioral evaluation of nutritional interventions in rodent models of brain aging and dementia. Clin Interv Aging 2017;12:1419-1428.
  14. Furmli S, Elmasry R, Ramos M, Fung J. Therapeutic use of intermittent fasting for people with type 2 diabetes as an alternative to insulin. BMJ Case Rep 2018;2018:bcr-2017-221854.
  15. Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CM. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metab 2018;27(6):1212-1221.e3.
  16. Wan R, Camandola S, Mattson MP. Intermittent food deprivation improves cardiovascular and neuroendocrine responses to stress in rats. J Nutr 2003;133:1921-1929.
  17. Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci U S A 2004;101:6659-6663.
  18. Most J, Gilmore LA, Smith SR, Han H, Ravussin E, Redman LM. Significant improvement in cardiometabolic health in healthy nonobese individuals during caloric restriction-induced weight loss and weight loss maintenance. Am J Physiol Endocrinol Metab 2018;314:E396-E405.
  19. Lefevre M, Redman LM, Heilbronn LK, et al. Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals. Atherosclerosis 2009;203:206-213.
  20. Johnson JB, Summer W, Cutler RG, et al. Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic Biol Med 2007;42:665-674.
  21. Moro T, Tinsley G, Bianco A, et al. 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. J Transl Med 2016;14:290-290.
  22. Kroeger CM, Klempel MC, Bhutani S, Trepanowski JF, Tangney CC, Varady KA. Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: relationship to adipokine modulations. Nutr Metab (Lond) 2012;9:98-98.
  23. Mager DE, Wan R, Brown M, et al. Caloric restriction and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats. FASEB J 2006;20:631-637.
  24. Stein PK, Soare A, Meyer TE, Cangemi R, Holloszy JO, Fontana L. Caloric restriction may reverse age-related autonomic decline in humans. Aging Cell 2012;11:644-650.
  25. Menzies FM, Fleming A, Caricasole A, et al. Autophagy and neurodegeneration: pathogenic mechanisms and therapeutic opportunities. Neuron 2017;93:1015-1034.
  26. Choi IY, Piccio L, Childress P, et al. A diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms. Cell Rep 2016;15:2136-2146.
  27. Fitzgerald KC, Vizthum D, Henry-Barron B, et al. Effect of intermittent vs. daily calorie restriction on changes in weight and patient-reported outcomes in people with multiple sclerosis. Mult Scler Relat Disord 2018;23:33-39.
  28. Müller H, de Toledo FW, Resch KL. Fasting followed by vegetarian diet in patients with rheumatoid arthritis: a systematic review. Scand J Rheumatol 2001;30:1-10.
  29. Mitchell JR, Beckman JA, Nguyen LL, Ozaki CK. Reducing elective vascular surgery perioperative risk with brief preoperative dietary restriction. Surgery 2013;153:594-598.
  30. Cignarella F, Cantoni C, Ghezzi L, et al. Intermittent fasting confers protection in CNS autoimmunity by altering the gut microbiota. Cell Metab 2018;27(6):1222.e6-1235.e6.
  31. M L Hartman,  J D Veldhuis,  et al. Augmented growth hormone (GH) secretory burst frequency and amplitude mediate enhanced GH secretion during a two-day fast in normal men. The Journal of Clinical Endocrinology & Metabolism, Volume 74, Issue 4, 1 April 1992, Pages 757-765
  32. Chia-Wei Cheng, Gregor B. Adams, et al. Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression.
  33. Cell Stem Cell: ARTICLE| VOLUME 14, ISSUE 6, P810-823, JUNE 05, 2014
  34. Danielle Glick, Sandra Barth, and  Kay F. Macleod.Autophagy: cellular and molecular mechanisms. J Pathol. 2010 May; 221(1): 3–12.