• Fasting - Part 2. Practical Applications

    How to incorporate the practice of fasting in our everyday life

     

         As we saw in the first part , fasting is the voluntary avoidance of food for health, spiritual, or other reasons. It’s done by someone who is not underweight and has enough stored body fat to live off. When done correctly, fasting should not cause suffering, and certainly never death. Food is easily available, but you choose not to eat it. This can be for any period of time, from a few hours up to a few days or – with medical supervision – even a week or more. You may begin a fast at any time of your choosing, and you may end a fast at will too.


    So, in theory,  anytime we are not eating ,we are intermittently fasting. But let’s dive into the science behind it.


        Intermittent fasting (IF) covers a broad class of dietary interventions that alternate periods of eating and extended fasting on recurring basis. IF interventions can include periodic 24-hour fasts, intermittent energy restriction (e.g., the 5:2 protocol), and time-restricted eating (TRE). Our bodies need a 24 hour continual source of energy just for the basic metabolic housekeeping – keeping the heart pumping blood, liver and kidney functions, the lungs sucking air, brain function etc. Since we do not eat food all the time, we have a system of storing food energy (in the liver and as body fat) for times where we are not eating, like when we are sleeping for example.  At moments like these , our body needs to pull some of the food energy we’ve stored away to keep our vital organs running. This is the reason we do not die in our sleep every single night.
       So, it becomes obvious that IF is not something unusual but a part of everyday, normal life. Yet somehow we have missed its power and overlooked its therapeutic potential. For example, you may be already intermittently fasting every day , between the dinner and the breakfast of the next day, a period that for most people is approximately 10 hours. Although the main benefits of IF start to appear after 12 hours of not ingesting any food, the 10 hours you stayed without feeding your self still count as IF. Just consider the term “breakfast.” It refers to the meal that breaks your fast – which is done daily in the morning. In that sense, even the English language implicitly acknowledges that fasting should be considered a part of everyday life.
        As we saw in the first part of this series,  at its very core, fasting simply allows the body to use its stored sources of energy – blood sugar and body fat. This is an entirely normal process and humans have evolved these storage forms of food energy precisely so that we can fast for hours or days without detrimental health consequences. Blood sugar and body fat is merely stored food energy ready to fuel the body when food is not available. By fasting, we are lowering blood sugar and body fat by using them precisely for the reason we store them. So, if we need to restore balance in our dietary patterns , if we need to achieve metabolic flexibility or if we need to lose weight, we may simply need to increase the amount of time spent burning food energy.

    That’s intermittent fasting.


    Intermittent fasting benefits


    IF’s most obvious benefit is weight loss. However, there are many potential benefits beyond this, some of which have been known since ancient times.  The fasting periods were often called ‘cleanses,’ ‘detoxifications’ or ‘purifications,’ but the idea is similar – to abstain from eating food for a certain period of time. People believed that this period of abstinence from food would clear their systems of toxins and rejuvenate them. Since we talked excessively about the benefits of fasting in general in the first part of this series, in this post i will just mention the most important benefits of IF reported through scientific research :

    • Weight and body fat loss - improved body composition.
    • Lowered blood insulin and sugar levels
    • Lowered blood insulin and glucose levels - Reversal of type 2 diabetes
    • Reduced hemoglobin A1c (A1c) levels
    • Improved mental clarity and concentration
    • Increased energy
    • Increased growth hormone, at least in the short term
    • Improved blood cholesterol profile
    • Increased longevity
    • Activated cellular cleansing by stimulating autophagy
    • Reduction of inflammation

     

    How can we apply in our everyday life the practice of IF?  Here, i am presenting some of the most important protocols.


    Protocols

     

        1.  Time-restricted eating (12:12 fasting, 14:10 - 16:8 fasting, 18:6 fasting, and 20:4 fasting)

        While IF, is a term used to describe a lot of different protocols, it’s most often used to describe something called Time Restricted Eating (TRE)—meaning, restricting the period of time you eat to a set number of hours each day. Time restricted eating, also called time restricted feeding (TRF) in research settings, typically consists of confining all your eating to a 12-hour, 10-hour, 8-hour, 6-hour, or 4-hour window, and fasting the remainder of the day. Lets see them analytically :

    • 12-hour fasting

    Many experts view a 12-hour eating/12-hour fasting window (think: eating breakfast at 8 a.m. and wrapping up dinner by 8 p.m.) as a great, safe place to start for anyone. It shouldn’t be that difficult , since one can fit the 8 hours of sleep in the 12 hour fasting window, therefore the challenge here is to remain without food for 4 more hours.  Piece of cake !

    • 14:10 and 16:8 fasting

    Some of the most popular versions of TRE are the 14:10 or 16:8 fasting plans, which consist of a daily 14-hour and 16-hour fast while confining your eating to an 10-hour and 8-hour window respectively. If you can't live without breakfast, slot your food earlier in the day (8 a.m. to 6 pm or 4 p.m.). If you prefer an early dinner, eat in the middle of the day (11 a.m. to 9 pm or 7 p.m.). If you're someone who regularly goes out with friends for late dinners, schedule your eating hours later in the day (1 pm to 11pm or 9 pm).

    • 18:6 fasting

    Also popular, but a bit more intense, is the 18:6 fasting plan, which is a daily 18-hour fast where you confined your eating to a 6-hour window. If your goal is weight loss and you’ve experienced a plateau on a 16:8 plan, this is the logical next step. While more research is needed, an 18:6 fast likely helps your body burn stored carbohydrates (glycogen) faster so you can start burning fat (in the form of ketones) for fuel, and some believe it may be enough to activate autophagy—a cellular clean-up process that’s associated with longevity.

    • 20:4 fasting

    The most restrictive of the popular TRE regimens is the 20:4 fast (sometimes called the “warrior diet”), which is a daily 20-hour fast where you confined your eating to a 4-hour window. This essentially breaks down to one meal a day and is not for beginners—you need to work your way up. Compared to a 16:8 or 18:6 fast, it’s speculated that you will burn more fat, lose more weight, and experience greater autophagy on a 20:4 diet, since the fasting hours last for almost all day.

     

           2.  Alternate-day fasting (36 hour fast)

          Also under the umbrella of intermittent fasting is alternate-day fasting (ADF). ADF is just how it sounds: You only eat every other day. So, practically,  you fast for 36 hours on a recurring basis. You finish dinner on day 1 at 7 pm for instance, and you would skip all meals on day 2, and not eat again until breakfast at 7 am on day 3. So that is a total of 36 hours of fasting followed by an 12-hour eating window. While some purists only consume water, herbal tea, and moderate amounts of black coffee on fasting days, others employ the 25 percent rule. In this version, you consume 25 percent of your normal caloric intake on fast days. This protocol has shown really good results for weight loss and reducing inflammation and while many clinics often recommend 36-hours fasts 2-3 times per week for reversing type 2 diabetes, alternate-day fasting is a more extreme approach to IF that may be hard to sustain over the long term. For obvious reasons, is not for beginners, and it should be reserved for specific medical cases.

     

        3.   5:2 plan

        A slightly easier variation of ADF, the 5:2 plan allows you to eat normally for five days every week while eating only 500 to 600 calories on the other two days. You can choose whichever two days of the week you prefer, as long as there is at least one non-fasting day in between them. One common way of planning the week on this protocol , is to fast on Mondays and Thursdays, with two or three small meals, then eat normally for the rest of the week. It’s important to emphasize that eating “normally” does not mean you can eat anything. If you binge on junk food, then you probably won’t lose any weight, and you may even gain weight.

     

    Where to place your TRE window?


         The ideal placement of your eating and fasting window will likely depend on a number of factors—work schedule, social obligations, fitness routine, and simply what feels best for your body—but a growing body of research seems to suggest that an earlier eating window may be better. A small but rigorously controlled randomised crossover study from 2019 found that when participants ate between 8 a.m. and 2 p.m., they fared much better than when they ate the same three meals on an 2 p.m. to 8 p.m. schedule.  Moreover , they had lower blood glucose levels during the day and overnight, lower insulin levels, and an ideal cortisol pattern (with levels higher in the morning and lower at night)—all of which suggests an improvement in circadian rhythm. More surprisingly, though, was that after just four days, this earlier eating schedule increased the expression of the SIRT1 gene (associated with longevity and healthy aging) and the LC3A gene (a biomarker of autophagy).

     

     

    How do you manage hunger?


       The million dollar question! “If i am hungry in only 3 hours after eating , how will i be able to fast for many more hours?” … Hunger is not so simple as your stomach being ’empty’. Hunger is, in fact, a highly susceptible state with a complex hormonal regulation at play. In essence, there are two major components to hunger: The unconditioned biological stimuli – that is, the part that will normally stimulate hunger naturally (smells, sights, and tastes of food) and the conditioned stimuli (learned – movie, lecture, morning etc). These conditioned responses can be very powerful and cause great hunger. If for example we consistently eat breakfast every single morning at 7:00am, lunch at 12:00 and dinner at 6:00pm, then the time of the day itself becomes a conditioned stimulus for eating. Even if we ate a huge meal at dinner the night before, and would not otherwise be hungry in the morning, we may become ‘hungry’ because it is 7:00am. The Conditioned Stimulus (time of 7:00) causes the Conditioned Response (hunger). How to combat this? Well, intermittent fasting offers a unique solution. By skipping meals and varying the intervals that we eat, we can break our current habit of feeding 3 times a day. We no longer have a conditioned response of hunger every 3-5 hours.
        And what about the hunger we feel by the unconditioned biological stimuli during our day? The most important thing to realise is, that this type of hunger, usually passes like a wave. It comes and it goes. That is, we may not be hungry one second, but after smelling a steak and hearing the sizzle, we may become quite ravenous. And then, we may engage in an activity and we forget after some minutes completely the steak and our hunger .  Many people worry that hunger during IF will continue to build up until it is intolerable, but this does not normally happen. Approximately 3-6 hours after we eat a meal, we start to feel hunger pangs and may become slightly cranky. But if we simply ignore it and drink a cup of tea or coffee, or we keep ourselves busy with activities , it will often pass.

     

    References


    Heilbronn LK, Smith SR, Martin CK, Anton SD, Ravussin E. Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism. Am J Clin Nutr. 2005 Jan;81(1):69-73. doi: 10.1093/ajcn/81.1.69. PMID: 15640462.


    Tinsley GM, La Bounty PM. Effects of intermittent fasting on body composition and clinical health markers in humans. Nutr Rev. 2015 Oct;73(10):661-74. doi: 10.1093/nutrit/nuv041. Epub 2015 Sep 15. PMID: 26374764.


    Nowosad K, Sujka M. Effect of Various Types of Intermittent Fasting (IF) on Weight Loss and Improvement of Diabetic Parameters in Human. Curr Nutr Rep. 2021 Jun;10(2):146-154. doi: 10.1007/s13668-021-00353-5.


    Halberg N, Henriksen M, Söderhamn N, Stallknecht B, Ploug T, Schjerling P, Dela F. Effect of intermittent fasting and refeeding on insulin action in healthy men. J Appl Physiol (1985). 2005 Dec;99(6):2128-36. doi: 10.1152/japplphysiol.00683.2005. Epub 2005 Jul 28. PMID: 16051710.

     

    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(2):254-268. doi:10.1002/oby.22065

     

    Sydney G O'Connor, Patrick Boyd, Caitlin P Bailey, Marissa M Shams-White, Tanya Agurs-Collins, Kara Hall, Jill Reedy, Edward R Sauter, Susan M Czajkowski, Perspective: Time-Restricted Eating Compared with Caloric Restriction: Potential Facilitators and Barriers of Long-Term Weight Loss Maintenance, Advances in Nutrition, Volume 12, Issue 2, March 2021, Pages 325–333

     

    Bachman JL, Raynor HA. Effects of manipulating eating frequency during a behavioral weight loss intervention: a pilot randomized controlled trial. Obesity (Silver Spring). 2012 May;20(5):985-92. doi: 10.1038/oby.2011.360. Epub 2011 Dec 15. PMID: 22173575.


    Munsters MJ, Saris WH. Effects of meal frequency on metabolic profiles and substrate partitioning in lean healthy males. PLoS One. 2012;7(6):e38632. doi: 10.1371/journal.pone.0038632. Epub 2012 Jun 13. PMID: 22719910; PMCID: PMC3374835.

     

    Sievert K, Hussain S M, Page M J, Wang Y, Hughes H J, Malek M et al. Effect of breakfast on weight and energy intake: systematic review and meta-analysis of randomised controlled trials BMJ 2019; 364 :l42 doi:10.1136/bmj.l42

    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.

     

    Kahleova H, Belinova L, Malinska H, Oliyarnyk O, Trnovska J, Skop V, Kazdova L, Dezortova M, Hajek M, Tura A, Hill M, Pelikanova T. Eating two larger meals a day (breakfast and lunch) is more effective than six smaller meals in a reduced-energy regimen for patients with type 2 diabetes: a randomised crossover study. Diabetologia. 2014 Aug;57(8):1552-60. doi: 10.1007/s00125-014-3253-5. Epub 2014 May 18. Erratum in: Diabetologia. 2015 Jan;58(1):205.

     

    Jamshed, H., Beyl, R. A., Della Manna, D. L., Yang, E. S., Ravussin, E., & Peterson, C. M. (2019). Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans. Nutrients, 11(6), 1234. https://doi.org/10.3390/nu11061234.

     

    Varady, K. A., Bhutani, S., Klempel, M. C., Kroeger, C. M., Trepanowski, J. F., Haus, J. M., Hoddy, K. K., & Calvo, Y. (2013). Alternate day fasting for weight loss in normal weight and overweight subjects: a randomized controlled trial. Nutrition journal, 12(1), 146.


    Johnstone AM, Faber P, Gibney ER, Elia M, Horgan G, Golden BE, Stubbs RJ. Effect of an acute fast on energy compensation and feeding behaviour in lean men and women. Int J Obes Relat Metab Disord. 2002 Dec;26(12):1623-8.


    Johnstone AM, Faber P, Gibney ER, Elia M, Horgan G, Golden BE, Stubbs RJ. Effect of an acute fast on energy compensation and feeding behaviour in lean men and women. Int J Obes Relat Metab Disord. 2002 Dec;26(12):1623-8. doi: 10.1038/sj.ijo.0802151. PMID: 12461679.

     


  • Fasting - Part 1. The science behind it

    "Our food should be our medicine.  Our medicine should be our food.  But to eat when you are sick is to feed your sickness."
                                                   - Hippocrates


        Fasting is one of the most ancient and widespread healing traditions in human history. This solution has been practiced by virtually every culture and religion on earth. Hippocrates of Cos (c460 – c370 BC) is widely considered the father of modern medicine. Among the treatments that he prescribed and championed was the practice of fasting. The ancient Greek writer and historian Plutarch (c46 AD– c120 AD) also echoed these sentiments. He famously wrote, “Instead of using medicine, better fast today”. Ancient Greek thinkers Plato and his student Aristotle were also strong supporters of fasting.
        The ancient Greeks believed that medical treatment could be observed from nature. Humans, like most animals, do not eat when they become sick. For this reason, fasting has been called the ‘physician within’. This fasting ‘instinct’ that makes dogs, cats and humans anorexic when sick. This sensation is certainly familiar to everybody. Consider the last time you were sick with the flu. Probably the last thing you wanted to do was eat. So, fasting seems to be a universal human instinct to multiple forms of illnesses. Thus fasting is ingrained into human heritage, and as old as mankind itself. The ancient Greeks also believed that fasting improves cognitive abilities. Think about the last time you ate a huge meal. Did you feel more energetic and mentally alert afterwards? Or, instead did you feel sleepy and a little dopey? More likely the latter. Blood is shunted to your digestive system to cope with the huge influx of food, leaving less blood going to the brain. Result – food coma.
        Fasting is also widely practiced for spiritual purposes and remains part of virtually every major religion in the world. In spiritual terms, it is often called cleansing or purification, but practically, it amounts to the same thing. The practice of fasting developed independently among different religions and cultures, not as something that was harmful, but something that was deeply, intrinsically beneficial to the human body and spirit.


        So fasting is truly an idea that has withstood the test of time.  But what is exactly fasting and what does science say about it?

    Fasting involves controlled, voluntary abstinence from caloric intake to achieve a physical, mental, or spiritual outcome.

         Our ancestors would regularly go days or even weeks without food. As a result, humans have evolved specific adaptations to survive, and even thrive, during periods of famine. So, in reality, the body  only exists in one of two states – the fed (high insulin) state or the fasted (low insulin) state. Either we are storing food energy (increasing stores) or we are burning stored energy (decreasing stores). It is one or the other, but not both. More analytically :

    Feeding – During meals, insulin levels are raised. This allows uptake of glucose into tissues such as the muscle or brain to be used directly for energy. Excess glucose is stored as glycogen in the liver.
    The post-absorptive phase – 6-24 hours after last meal .   Insulin levels start to fall. Breakdown of glycogen releases glucose for energy. Glycogen stores last for roughly 24 hours.
    Gluconeogenesis – 24 hours to 2 days – The liver manufactures new glucose from lactate and amino acids in a process called “gluconeogenesis”. Literally, this is translated as “making new glucose”. In non-diabetic persons, glucose levels fall but stay within the normal range.
    Ketosis – 2-3 days after beginning fasting – This is when interesting things start to happen for the body. The low levels of insulin reached during fasting, stimulate lipolysis, the breakdown of fat for energy. The storage form of fat, known as triglycerides, is broken into the glycerol backbone and three fatty acid chains. Glycerol is used also for gluconeogenesis. Fatty acids may be used for directly for energy by many tissues in the body, but not the brain. Ketone bodies instead , which are produced from fatty acids during ketosis , are capable of crossing the blood-brain barrier for use by the brain. After four days of fasting, approximately 75% of the energy used by the brain is provided by ketones. The two major types of ketones produced are beta hydroxybutyrate and acetoacetate, which can increase over 70 fold during fasting.
    Protein conservation phase – >5 days – High levels of growth hormone maintain muscle mass and lean tissues. The energy for maintenance of basal metabolism is almost entirely met by the use of free fatty acids and ketones. Increased norepinephrine (adrenalin) levels prevent the decrease in metabolic rate.


       We see that the human body has well developed mechanisms for dealing with periods of low food availability. In essence, what is happening while fasting is a process of switching from burning glucose to burning fat . Fat is simply the body’s stored food energy. In times of low food availability, stored food is naturally released to fill the void. So no, the body does not ‘burn muscle’ in an effort to feed itself, at least until all the fat stores are used.

     

    Lets have a look on the effects of fasting on Hormonal Adaptation

     

    • Insulin

     

        Insulin and insulin resistance are major drivers of obesity. Fasting on the other hand , is the most efficient and consistent strategy to decrease insulin levels. This was first noted decades ago, and widely demonstrated scientifically afterwards. It is quite simple and obvious. All foods raise insulin, so the most effective method of reducing insulin is to avoid all foods. Blood glucose levels remain normal, as the body begins to switch over to burning fat for energy. This effect can be observed in fasting periods as short as 24-36 hours. Longer duration fasts reduce insulin even more dramatically. More recently, alternate daily fasting has been studied as an acceptable technique of reducing insulin.
        Regular fasting, in addition to lowering insulin levels, has also been shown to improve insulin sensitivity significantly. Many argue that this is the missing link in the weight loss puzzle. Most diets reduce highly insulin-secreting foods, but do not address the insulin resistance issue which is crucial in diabetics.  Weight is initially lost, but insulin resistance keeps insulin levels and body weight high. Fasting is an efficient method of reducing insulin resistance.
        Lowering insulin also rids the body of excess salt and water. Insulin causes salt and water retention in the kidney. Very low-carb diets often cause diuresis, the loss of excess water, leading to the contention that much of the initial weight loss is water. While true, diuresis is beneficial in reducing bloating, and feeling ‘lighter’. Some may also note a slightly lower blood pressure. Fasting has also been noted to have an early period of rapid weight loss. For the first five days, weight loss averages 0.9 kg/ day, far exceeding the caloric restriction and likely due to a diuresis of salt and water.

     

    • Growth Hormone

     

       Growth hormone is known to increase the availability and utility of fats for fuel. It also helps to preserve muscle mass and bone density. Secretion is known to be pulsatile, making accurate measurement difficult. Growth hormone secretion decreases steadily with age. One of the most potent stimuli to growth hormone secretion is fasting. Over a five-day fasting period growth hormone secretion is more than doubled. The net physiologic effect is to maintain muscle and bone tissue mass over the fasting period.

     

    • Adrenalin

     

         Adrenalin levels are increased so that we have plenty of energy to go get more food. For example, 48 hours of fasting produces a 3.6% increase in metabolic rate, not the dreaded metabolic ‘shut-down’. In response to a 4 day fast, resting energy expenditure increased up to 14%.   Rather than slowing the metabolism, instead the body revives it up. Additionally, studies show that the adrenalin-induced fat-burning does not depend upon lowering blood sugar. Presumably, this is done so that we have energy to go out and find more food.


    And what about vitamins ,minerals and electrolytes?


        Concerns about malnutrition during fasting are misplaced. Insufficient calories are not a major worry, if the fat stores are quite ample. The main concern is the development of micronutrient deficiency. However, if the fasting regime is accompanied by the use of a multi-vitamin and mineral supplementation that will provide the recommended daily allowance of micronutrients , there should’t be any issue.  It is worth noting, that in 1973 a therapeutic fast of 382 days that resulted in loss of 125 kilos for a patient, was maintained with only a multivitamin potion and had no harmful effect on health . Actually, this man maintained that he had felt terrific during this entire period. The only concern may be a slight elevation in uric acid that has been described in fasting and can be solved by increased water consumption.

    Additionally, evidence suggests four brain health effects linked to fasting:

    • Brain cell re-generation

     

    • Cognitive and psychological benefits

     

    • Resilience to neurological conditions

     

    • Slowing the effects of aging.

     

    This research on brain health is focused on the use of ketones, molecules that as we saw before, are being produced and used by the body as a source of fuel while fasting. Administration of ketones is a well established therapy since decades for intractable epilepsy and seizures. It should be considered early in the treatment of Dravet syndrome and myoclonic-astatic epilepsy (Doose syndrome). A growing body of literature suggests also that the use of ketones may be beneficial in certain neurodegenerative diseases, including Alzheimer disease, Parkinson’s disease, and amyotrophic lateral sclerosis. In these disorders, ketones appears to be neuroprotective, promoting enhanced mitochondrial function and rescuing adenosine triphosphate production. Ultimately , dietary therapy is a promising intervention for cancer, given that it may target the relative inefficiency of tumors in using ketone bodies as an alternative fuel source.


    So, let’s summarise.

        Fasting, but not low calorie diets, results in numerous physiological and hormonal adaptations that all appear to be highly beneficial on many levels. The main benefits of fasting are metabolic flexibility and weight management. In essence, fasting transitions the body from burning sugar to burning fat.  Resting metabolism is NOT decreased but instead increased.  We are, effectively, feeding our bodies through our own fat.  We are ‘eating’ our own fat.  This makes total sense since fat is, in essence, stored food. Fat is food stored away for the long term, like money in the bank.  Short term food is stored as glycogen, like money in the wallet.  The problem we have, is how to access the money in the bank.  As our wallet depletes, we become nervous and go out working to fill it again.  This prevents us from getting access to our stored money in the bank. In the same manner, as our glycogen ‘wallet’ depletes, we get hungry and want to eat.  That makes us look for food, despite the fact that there is more than enough food stored as fat in the body ‘bank’’.  How do we get to that fat to burn it? Fasting provides an easy way in.

     

    References


    Anderson JW, Herman RH, Newcomer KL. Improvement in glucose tolerance of fasting obese patients given oral potassium. Am J Clin Nutr. 1969 Dec;22(12):1589–1596.

    Drenick EJ, Hunt IF, Swendseid ME. Magnesium depletion during prolonged fasting of obese males. J Clin Endocrinol Metab. 1969 Oct;29(10):1341–1348.

    Jackson IM, McKiddie MT, Buchanan KD. The effect of prolonged fasting on carbohydrate metabolism: evidence for heterogeneity in obesity. J Endocrinol. 1968 Feb;40(2):259–260.

    Jackson IM, McKiddie MT, Buchanan KD. Effect of fasting on glucose and insulin metabolism of obese patients. Lancet. 1969 Feb 8;1(7589):285–287.

    Thomson TJ, Runcie J, Miller V. Treatment of obesity by total fasting for up to 249 days. Lancet. 1966 Nov 5;2(7471):992–996.

    Stewart, W. K., & Fleming, L. W. (1973). Features of a successful therapeutic fast of 382 days' duration. Postgraduate medical journal, 49(569), 203–209. https://doi.org/10.1136/pgmj.49.569.203

    de Groot, S., Pijl, H., van der Hoeven, J., & Kroep, J. R. (2019). Effects of short-term fasting on cancer treatment. Journal of experimental & clinical cancer research : CR, 38(1), 209. https://doi.org/10.1186/s13046-019-1189-9

    Grajower, M. M., & Horne, B. D. (2019). Clinical Management of Intermittent Fasting in Patients with Diabetes Mellitus. Nutrients, 11(4), 873. https://doi.org/10.3390/nu11040873

    Furmli, S., Elmasry, R., Ramos, M., & Fung, J. (2018). Therapeutic use of intermittent fasting for people with type 2 diabetes as an alternative to insulin. BMJ case reports, 2018, bcr2017221854. https://doi.org/10.1136/bcr-2017-221854

    Wilhelmi de Toledo F, Grundler F, Bergouignan A, Drinda S, Michalsen A (2019) Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects. PLoS ONE 14(1): e0209353. https://doi.org/10.1371/journal.pone.0209353

    Klein S, Holland OB, Wolfe RR. Importance of blood glucose concentration in regulating lipolysis during fasting in humans. Am J Physiol. 1990 Jan;258(1 Pt 1):E32-9. doi: 10.1152/ajpendo.1990.258.1.E32. PMID: 2405701.
    Ho KY, Veldhuis JD, Johnson ML, et al. Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man. J Clin Invest. 1988 Apr;81(4):968-75.

    Zauner C, Schneeweiss B, Kranz A, et al. Resting energy expenditure in short-term starvation is increased as a result of an increase in serum norepinephrine. Am J Clin Nutr. 2000 Jun;71(6):1511-5.

    Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011 Oct 27;365(17):1597-604. doi: 10.1056/NEJMoa1105816.
    Bailey EE, Pfeifer HH, Thiele EA. The use of diet in the treatment of epilepsy. Epilepsy Behav. 2005;6:4–8.

    Huttenlocher PR. Ketonemia and seizures: metabolic and anticonvulsant effects of two ketogenic diets in childhood epilepsy. Pediatr Res. 1976;10:536–540.

    Otto C, Kaemmerer U, Illert B, et al. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides. BMC Cancer. 2008;8:122.
    Nebeling LC, Miraldi F, Shurin SB, Lerner E. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr. 1995;14:202–208.

    Maswood N, Young J, Tilmont E, et al. Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson’s disease. Proc Natl Acad Sci U S A. 2004;101:18171–18176.

    Kim DY, Davis LM, Sullivan PG, et al. Ketone bodies are protective against oxidative stress in neocortical neurons. J Neurochem. 2007;101:1316–1326.

    Bough KJ, Wetherington J, Hassel B, et al. Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neurol. 2006;60:223–235. An elegant study correlating seizure protection with changes in gene expression, biochemistry, and electrophysiology.

    Murphy P, Likhodii S, Nylen K, Burnham WM. The anti-depressant properties of the ketogenic diet. Biol Psychiatry. 2004;56:981–983.



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