Fasting is defined as the abstinence of food for a defined period of time and it has been practised for religious purposes for centuries.
During the last few decades, dietary guidelines have recommended that we avoid going for prolonged periods without food. We have been advised to eat every couple of hours in order to keep blood glucose levels stable, maintain optimal metabolic function and prevent weight gain. However, a growing body of research into fasting is revealing that these recommendations may be flawed.
Fasting and Autophagy
Thanks to the work of Yoshinori Ohsumi, a cell biologist, who won the Nobel Prize in Medicine in 2016 for his research on autophagy, the many benefits of fasting are being revealed and it appears it may even be the key to living healthier for longer.
Autophagy, which is initiated after 12 to 14 hours of fasting, is the process by which cells renew and recycle their components through a number of cellular and enzymatic mechanisms. This can help clear out damaged cells and pathogens, inhibit cancer cells and has even been shown to slow down the ageing process.
Since this discovery there has been a plethora of research into fasting for autophagy and longevity, and this has resulted in the development of a number of fasting plans that have gained popularity in the mainstream.
With many proven benefits and a wealth of information related to fasting, it’s easy to get carried away but fasting isn’t for everyone and it may not necessarily be the solution to your problem. In addition, there are risks and precautions to consider. So, it’s important to understand the facts before deciding whether fasting is an option for you.
What happens during a fast?
After consuming a meal, the body initiates a number of physiological and cellular processes in order to manage and utilise the macronutrients present in the meal.
Carbohydrates are broken down or converted into glucose which is immediately used as energy. Glucose in the blood stream triggers the release of insulin from the pancreas. Insulin then directs excess blood glucose into liver and muscle cells to be stored as glycogen. When these glycogen levels have been replenished, any remaining glucose is transported to the liver where it is converted into lipoproteins. Lipoproteins are then released into the blood stream and taken up by fat cells for storage. Insulin facilitates this uptake, while also inhibiting the release of stored fat.
Amino acids from the breakdown of proteins are either used to rebuild cells, such as muscle cells or for the synthesis of enzymes, hormones, neuropeptides or other cellular products. The remaining amino acids are stored in an amino acid pool for later use.
Fatty acids are converted into triglycerides and cholesterol in the liver. A portion of these are used to build cells, hormones and other cellular products in various tissues. The rest is transported into fat cells for storage.
About four hours after a meal, glucose and insulin levels drop and this activates the release of glucagon from the pancreas. Glucagon acts to break down the glycogen that has been stored in the muscles and liver, therefore releasing glucose into the bloodstream. Glucose once again stimulates the release of insulin, which directs this glucose into storage and prevents the release of stored fat.
Approximately six hours after a meal, ghrelin, the hunger hormone is released from the stomach and sends signal of hunger to the brain. This would normally result in food intake. If abstinence from food continues, studies have shown that ghrelin levels will return to normal within an hour or two and then fluctuate around meal times over the next day.
Cortisol, the stress hormone, also fluctuates over the first 24 hours of fasting. Cortisol attempts to restore glucose levels by converting glycogen to glucose. If cortisol remains elevated for prolonged periods of time, it can activate the conversion of amino acids and muscle protein into glucose through a process called gluconeogenesis.
Approximately 12 to 16 hours after the last meal, glycogen becomes depleted and glucose and insulin levels drop. This is when fat cells begin releasing free fatty acids. Most of the fatty acids are used for energy, some are converted into glucose via gluconeogenesis and some are converted into ketones in the liver. This process is essential for brain function as ketones are one of the very few molecules that are able to cross the blood-brain barrier. In this way, ketones provide energy for neurons when glucose is no longer available.
The presence of ketones in the blood is an indication that the body is using fat stores for energy, this is known as a state of ketos. Ketosis is associated with a number of health benefits including improved mitochondrial function, improved insulin sensitivity, reduced inflammation, increased fat loss, improved brain function and neurogenesis (the development of new neurons). Ketosis is also associated with increased growth hormone which works to preserve muscle mass during fasting.
In addition, autophagy begins after 12 to 16 hours of fasting, therefore setting the stage for regeneration and renewal of various cells throughout the body. A recent study in mice has shown that fasting for 24 hours can activate intestinal stem cells. Another study in mice and humans has revealed that fasting for three days may help regenerate the immune system.
Popular Fasting Plans
There are many popular fasting plans based on intermittent fasting, with flexible fasting periods and little or no restrictions when it comes to food choices.
Intermittent fasting is an eating plan that alternates between periods of fasting lasting 12 to 24 hours (with no food at all) and periods of eating. Some examples of intermittent fasts are:
Time restricted fasting which allows food intake within a certain time-frame only, for example a common time-restricting fasting plan is the 16:8 plan which allows meals within an 8-hour time-frame during the day e.g. between 10am and 6pm, then no food for 16 hours (or until 10am the following day). Water, herbal tea, black tea and coffee are ok during the fast.
24-hour fastor one-meal-a-day fasts allow for one meal a day, followed by 24 hours of fasting.
Modified Fasts is a term for “fasts” that allow some foods during fasting periods. They are easier to follow and have been found to have metabolic benefits. Examples of these include:
The 5:2 Diet, developed by British journalist, Michael Mosley, allows for normal eating 5 days a week, and consuming only 500 calories two days a week.
The Fasting Mimicking Dietdeveloped by cell biologist, Professor Valter Longo, is a five-day plan that allows for 1000 calories on the first day, followed by 800 calories for the next four days. The plan comes with packaged food containing a specific macronutrient ratio.
Prolonged fasts are usually water-only fasts, lasting from 24 hours to several days. Water fasts have become popular due to the work of nephrologist, Dr Jason Fung who uses prolonged fasts to help his diabetic patients. It is important to note that water fasts can have serious consequences such as severe electrolyte disturbances. These types of fasts should only be undertaken with strict medical supervision.
Fasting for weight loss: what the research shows
The overall benefits of a 12 to 14 hour fast include:
Improved mitochondrial function
Reduced insulin resistance
Increased brain-derived neurotrophic factor
Initiating autophagy and cellular repair
Increased resistance to cellular stress
Intermittent fasting has also been shown to improve metabolic markers with reductions in blood pressure, blood glucose and cholesterol levels.
But how does fasting work when it comes to weight loss?
A meta-analysis of 12 clinical trials in 2015 and six studies in 2018 concluded that the effect of intermittent fasting on weight loss and body composition is comparable to continuous calorie restriction after 12 months.
Other studies have shown that participants are less likely to adhere to intermittent fasting when compared to other weight loss plans.
There is also some evidence that the weight loss benefits of intermittent fasting decrease with time. This may be due to poor long-term compliance, poor food choices during eating periods or due to the development of homeostatic responses, where the body adjusts and responds to the new pattern of eating.
There is limited research on how long to continue with a fasting plan or how often to repeat the fast and with very little data on the long-term effects, it’s difficult to make definitive recommendations.
So, while certain forms of fasting are associated with health benefits, the jury is still out on whether it’s a good option for weight loss. More research is needed.
As with any diet, there are always risks. The risks associated with certain forms of fasting include electrolyte disturbances, nutrient deficiencies, dehydration, hypoglycaemia and the development or exacerbation of eating disorders. Some of these can be avoided with proper planning which is why supervision is recommended.
In addition, many of the popular fasting plans have vague guidelines regarding food choices during eating windows, and some encourage unrestricted eating. The premise is that a more flexible diet will lead to better adherence, however, some research has found that participants experienced hunger during fasting periods and therefore tended to over compensate during eating periods. If there is preference towards processed foods during eating windows, this can disrupt the composition of the gut microbiota, leading to immune, metabolic and hormonal abnormalities, therefore counteracting the benefits of the fasting period. It can also set the stage for binge eating and weight fluctuations.
Another concern is the coupling of fasting with a ketogenic diet. While ketosis is associated with many benefits, other factors needs to be considered. Women are more likely to experience hormonal disruption with ketogenic diets, especially those who have adrenal or thyroid issues and this may lead to weight gain, . Also, some ketogenic diets encourage the consumption of highly processed foods and if these are chosen in preference to clean foods, the benefits of fasting may be negated.
It’s important to understand that scientific research and clinical trials are conducted under specific conditions, with participants being regularly monitored and usually given guidelines to follow between reviews. This would influence compliance and therefore results. In real-world scenarios the benefits may not be as definitive or impressive.
Who should avoid fasting?
Fasting is contraindicated in those with diabetes and anyone with a history of eating disorders. In addition, the risks have not been determined for pregnant or breast-feeding women, so these are also contraindications to fasting.
Certain medical conditions, such as thyroid disease, adrenal dysfunction, kidney or heart disease or nutrient deficiencies, can be exacerbated with some forms of fasting, especially if unsupervised.
Anyone with a medical condition or those on medications should always seek medical advice before starting a fasting plan.
What’s the best option?
While research is still in the early stages, it's best to choose the safest option and it appears that a 12-14 hour overnight fast is safe for most people. Recent research has shown that every cell in our body follows a circadian rhythm that can be disrupted by eating at night, therefore having your last meal before 6pm (before the sun goes down) and not eating again until at least 7am or 8am the following day, appears to be how we were designed to eat.
Also, while not technically “fasting”, eating only three healthy meals a day with no snacks in between, will allow your body to efficiently utilise the macro- and micronutrients in the meals, therefore improving your metabolic function and potentiating the benefits of the overnight fast.
Ideally, before attempting any fasting protocol, your body should be in a healthy, balanced state with some degree of metabolic flexibility. The Biome Protocol is able to provide this foundation by helping restore gut function, replenish nutrient stores and enable the body to mobilise fat stores for energy if needed. Therefore, on completion of the 6-week protocol participants are provided with information regarding three safe options for intermittent fasting along with appropriate food choices and supplements that will help maintain the benefits achieved during the protocol, while also enjoying the health benefits of fasting.
1. Alirezaei M, Kemball CC, Flynn CT, Wood MR, Whitton JL, Kiosses WB. Short-term fasting induces profound neuronal autophagy. Autophagy. 2010 Aug;6(6):702-10. doi: 10.4161/auto.6.6.12376. Epub 2010 Aug 14. PMID: 20534972; PMCID: PMC3106288.
2. Arnason, T. G., Bowen, M. W., & Mansell, K. D. (2017). Effects of intermittent fasting on health markers in those with type 2 diabetes: A pilot study. World journal of diabetes, 8(4), 154–164. doi:10.4239/wjd.v8.i4.154
3. Ruth E. Patterson, A Dorothy D. Sears, Metabolic Effects of Intermittent. Journal Article. FastingAnnual Review of Nutrition 2017 37:1, 371-393 https://www.annualreviews.org/doi/abs/10.1146/annurev-nutr-071816-064634
4. Bagherniya, Mohammad & Butler, Alexandra & Barreto, George & Sahebkar, Amirhossein. (2018). The effect of fasting or calorie restriction on autophagy induction: A review of the literature. Ageing Research Reviews. 47. 10.1016/j.arr.2018.08.004.
5. Ohsumi Y. Yoshinori Ohsumi: autophagy from beginning to end. Interview by Caitlin Sedwick. J Cell Biol. 2012 Apr 16;197(2):164-5. doi: 10.1083/jcb.1972pi. PMID: 22508506; PMCID: PMC3328387.
6. Anton SD, Moehl K, Donahoo WT, Marosi K, Lee SA, Mainous AG 3rd, Leeuwenburgh C, Mattson MP. Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity (Silver Spring). 2018 Feb;26(2):254-268. doi: 10.1002/oby.22065. Epub 2017 Oct 31. PMID: 29086496; PMCID: PMC5783752.
7. Min Wei, Sebastian Brandhorst, Mashid Shelehchi, Hamed Mirzaei, Chia Wei Cheng, Julia Budniak, Susan Groshen, Wendy J. Mack, Esra Guen, Stefand Di Biase, Pinchas Cohen, Todd E. Morgan, Tanya Dorff, Kurt Hong, Andreas Michalsen, Alessandro Laviano, Valter D. Longo. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Science Translational Medicine. 15 FEB 2017 Vol. 9, Issue 377, DOI: 10.1126/scitranslmed.aai8700
8. Mihaylova MM, Cheng CW, Cao AQ, Tripathi S, Mana MD, Bauer-Rowe KE, Abu-Remaileh M, Clavain L, Erdemir A, Lewis CA, Freinkman E, Dickey AS, La Spada AR, Huang Y, Bell GW, Deshpande V, Carmeliet P, Katajisto P, Sabatini DM, Yilmaz ÖH. Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging. Cell Stem Cell. 2018 May 3;22(5):769-778.e4. doi: 10.1016/j.stem.2018.04.001. PMID: 29727683; PMCID: PMC5940005.
9. Brandhorst S, Choi IY, Wei M, Cheng CW, Sedrakyan S, Navarrete G, Dubeau L, Yap LP, Park R, Vinciguerra M, Di Biase S, Mirzaei H, Mirisola MG, Childress P, Ji L, Groshen S, Penna F, Odetti P, Perin L, Conti PS, Ikeno Y, Kennedy BK, Cohen P, Morgan TE, Dorff TB, Longo VD. A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metab. 2015 Jul 7;22(1):86-99. doi: 10.1016/j.cmet.2015.05.012. Epub 2015 Jun 18. PMID: 26094889; PMCID: PMC4509734.
10. Cheng CW, Adams GB, Perin L, Wei M, Zhou X, Lam BS, Da Sacco S, Mirisola M, Quinn DI, Dorff TB, Kopchick JJ, Longo VD. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell Stem Cell. 2014 Jun 5;14(6):810-23. doi: 10.1016/j.stem.2014.04.014. Erratum in: Cell Stem Cell. 2016 Feb 4;18(2):291-2. PMID: 24905167; PMCID: PMC4102383.
11. Trepanowski JF, Kroeger CM, Barnosky A, Klempel MC, Bhutani S, Hoddy KK, Gabel K, Freels S, Rigdon J, Rood J, Ravussin E, Varady KA. Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial. JAMA Intern Med. 2017 Jul 1;177(7):930-938. doi: 10.1001/jamainternmed.2017.0936. PMID: 28459931; PMCID: PMC5680777.
12. Leonie K Heilbronn, Steven R Smith, Corby K Martin, Stephen D Anton, Eric Ravussin, Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism, The American Journal of Clinical Nutrition, Volume 81, Issue 1, January 2005, Pages 69–73, https://doi.org/10.1093/ajcn/81.1.69
13. Harris, L., Hamilton, S., Azevedo, L.B., Olajide, J., Brún, C.D., Waller, G., Whittaker, V.J., Sharp, T., Lean, M.E., Hankey, C., & Ells, L.J. (2018). Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis. JBI database of systematic reviews and implementation reports, 16 2, 507-547.
14. 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 Jun 5;27(6):1212-1221.e3. doi: 10.1016/j.cmet.2018.04.010. Epub 2018 May 10. PMID: 29754952; PMCID: PMC5990470.
15. Matt Van Sol. Fasting for 72 hours can reset your entire immune system. The Source. November 21, 2018 thesource.com
16. eimon, Radhika & Roekenes, Jessica & Zibellini, Jessica & Zhu, Benjamin & Gibson, Alice & Hills, Andrew & Wood, Rachel & King, Neil & Byrne, Nuala & Sainsbury, Amanda. (2015). Do intermittent diets provide physiological benefits over continuous diets for weight loss? A systematic review of clinical trials. Molecular and cellular endocrinology. 418. 10.1016/j.mce.2015.09.014.