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Our modern lifestyles are slowly killing us: by overeating and being excessively sedentary, we might have brought upon ourselves an epidemic in metabolic diseases.

Our body is has not had time to adapt and so is not optimised for our modern way of life. We can’t change that overnight, nor even in the course of a few generations. Evolution is slow.

Throughout evolution, food deprivation was most likely one of the biggest energetic and evolutionary challenges our species faced - it is likely that many of our ancestors could only acquire food during daytime, having to fast for long hours, perhaps days, in between. It is also likely that long periods of seasonal food scarcity was common. So, those who were able to endure in these conditions ended up being favoured by evolution.

The fact that our bodies store fat as a backup long-term, high-energy source, and that we can survive relying solely on it for a fair amount of time, is an indication of how human evolution prepared us (and maybe even optimised us) to go through periods of fasting.

Liver carbohydrate stocks in the form of glycogen are our main and most immediate source of energy. On average, it takes around 12 to 16 hours for our body to exhaust its carbohydrate stocks, after which it switches to burning fat. However, if you increase your energy expenditure by exercising, this time can be substantially shortened. When these glycogen stores are depleted, fatty acids are mobilised from adipose cells and metabolised in the liver to produce ketone bodies, which are then released into the bloodstream and used as fuel. If you keep restocking your glycogen levels by ingesting carbohydrates, it’s more unlikely that you’ll need to use fat as fuel.

Let me clarify that fasting is not the same as starving. Starvation is an extreme form of fasting that leads to chronic nutritional insufficiency, which can result in degeneration and death. Nevertheless, and depending on body weight and composition, our fat reserves and switching to a fat-fuelled metabolism through ketone bodies, free fatty acids, and gluconeogenesis (the production of glucose from proteins) can allow the majority of humans to survive 30 or more days in the absence of food.

Intermittent and periodic fasting diets 

Fasting is distinct from continuous caloric restriction, in which the total daily caloric intake is systematically reduced, but meal frequency is maintained. In fasting diets, periods of non-fasting, with regular caloric intake, are intercalated with periods of fasting. 

There are many different approaches to these diets, varying mainly on the length and pattern of the fasting periods. Intermittent fasting diets can be on alternate days, or on two non-consecutive days per week (Michael Mosley's 5:2 diet), for example, whereas periodic fasting can last three or more days every two or more weeks. 

Any pattern of fasting to non-fasting is possible, as long as it is not counterproductive by either leading to severe nutritional deficiencies or to binge eating in the non-fasting period. 

Calling it fasting doesn’t necessarily mean that you have to endure 24 hours without any food intake. A common approach is limiting your feeding time on your fasting day to a window of 8 hours or less, followed by a period of 16 hours or more without any significant food intake. A simple way to do this is to just skip breakfast and lunch several days each week. In fact, although breakfast is commonly regarded as being fundamental for weight control, recent scientific evidence has somewhat discredited this concept by showing that eating breakfast may not have any discernible effects on weight loss. It is possible that the classic habit of having three meals a day plus snacks in between may need an update. 

Typically, the main goal for most people who engage in a fasting diet is to lose weight. And it works well for that effect, mainly because most people find continuous caloric restriction diets difficult to maintain. The advantage of intermittent or periodic caloric restriction is that the struggle to resist food is intercalated with normal feeding – you have something to look forward to. 

Research comparing the efficacy of intermittent and continuous energy restriction plans has shown that intermittent fasting can be as effective as continuous dieting for weight loss. A study even showed that intermittent fasting was superior to daily food restriction in decreasing body fat. 

Similarly to ketogenic diets, during fasting your body starts obtaining energy from stored fat - fasting allows the depletion of carbohydrate stocks and boosts the body's capacity to use fats as fuel. The result is that you end up losing fat (as long as you don’t binge eat in your food intake periods).  


Although glucose is the primary source of energy in our body, ketones may actually be a more efficient fuel. The switch to a ketone-fuelled metabolism induces changes in cellular processes that lead to an increase in energy production. This is particularly relevant in the brain - given its higher energy demand when compared to other tissues, a ketone-based metabolism can enhance the brain’s efficacy in generating energy, and consequently induce functional improvements.  

But besides weight loss, and all the health benefits derived from losing weight, intermittent fasting can have other positive outcomes. 

Intermittent fasting and chronic low-grade inflammation

All major diseases, including cardiovascular and metabolic diseases, cancer, and neurodegenerative disorders, are associated with inflammation, either restricted to the affected tissues, or systemic, i.e., in the whole body. In fact, chronic low-grade inflammation is increasingly recognized as a contributing or even determinant factor in a number of pathologies. In intermittent fasting diets, the decreased energy intake can help decrease the levels of systemic inflammation, leading to numerous health benefits. 

In cardiovascular health, for example, intermittent fasting can decrease the incidence of cardiovascular diseases by reducing blood pressure and heart rate, as well as by protecting the heart against ischemic damage due to myocardial infarction. 

Inflammation is also associated with the development of tumours. By decreasing inflammatory responses, intermittent fasting may decrease the likelihood of tumour development. In fact, research has even indicated that fasting can help reverse disease processes in different types of cancer. 

Animal studies on the effects of intermittent or periodic fasting have even shown that it can increase lifespan. Inflammation is one of the main driving forces in aging and, in fact, an increased longevity due to fasting has been observed in many different animal models. 

Bulletproof Intermittent Fasting: Mental Performance Protocol

Step 1: Finish dinner by 8 pm. No snacking after dinner.
Step 2: Drink Bulletproof Coffee in the morning. No coffee after 2:00 PM or you won’t sleep.
Step 2.5 (optional) – Work out
This is not necessary to gain muscle and lose fat, but it helps. I’d suggest high intensity weight training.
Step 3: Do not eat until 2pm. This means you’ve not had anything to eat except Bulletproof Coffee for 18 hours.
Step 4: Eat as much Bulletproof food as you like for 6 hours (until 8 pm)
The number of meals you eat during this time is irrelevant, as is the amount of calories.

Here is a sample day of Bulletproof Intermittent Fasting:
7:00 AM: Drink Bulletproof Coffee.
2:00 PM: Break fast with foods from the Bulletproof Diet.
7:00 PM: Eat your last meal before beginning the fast.

Other health benefits of intermittent fasting

Many of the health benefits of intermittent fasting are the result of switching to a ketone-fuelled metabolism. Research on subjects undergoing intermittent fasting diets has shown that it induces marked changes in energy metabolism, including a more efficient fatty acid mobilization and the consequent elevation of ketone levels. Ketones are known to have beneficial health effects, particularly on the brain, improving cognitive function in patients with Type 1 diabetes, mild cognitive impairment, and early Alzheimer’s disease. 

The benefits of intermittent fasting may also arise from an antioxidant effect: studies have also provided evidence of an increase in the levels of antioxidant enzymes and a prevention of age-related decreases in antioxidant enzymes as a result of alternate day fasting. Furthermore, fasting can also potentiate the elimination of cellular waste and increase the resistance to neurotoxins. This is important, for example, for a number of neurodegenerative disorders that include abnormal accumulation of protein aggregates, such as Parkinson’s and Alzheimer’s disease, which can be counterbalanced by the increased removal of damaged molecules. 

In fact, the neurological effects of intermittent fasting can be substantial. Alternate-day fasting has been shown to potentiate the production of several molecules that promote the survival and genesis of neurons, as well as the strengthening of the connections between neurons, having therefore a high impact on cognitive performance. 

Most of the scientific evidence on the effects of intermittent fasting comes from animal studies. However, since all mammals have organs that use glucose as a fast energy source, and long-lasting fat storages in adipose tissue, it is likely that fasting has similar effects in different mammals. And research has indeed supported this view, since studies in humans have been consistently matching these findings. 

Who should not fast?

Fasting is not recommended to everyone. Pregnant and nursing women should not fast since the effects of fasting on foetuses or newborn children are unknown; children should also not fast, as well as people with certain medical conditions, namely those with eating disorders, liver or kidney diseases, anaemia, or those who have a major illness or underwent surgery. Obviously, if you have a weakened immune system, or chronic conditions such as high blood pressure or diabetes, for example, it may be possible to fast, but you should get medical advice before engaging in a fasting diet.  

There have also been indications of a possible sex-specific effect of intermittent fasting - in a study on humans where glucose tolerance and insulin sensitivity were assessed after 22 days of alternate day fasting, glucose tolerance was found to be impaired in women and unchanged in men, whereas insulin sensitivity was unchanged in women and improved in men. Although the number of studied subjects was quite low, these results are still worth mentioning - keep them in mind just in case. 


Cahill GF Jr (2006). Fuel metabolism in starvation. Annu Rev Nutr, 26:1-22. doi: 10.1146/annurev.nutr.26.061505.111258

Casazza K, et al (2013). Myths, presumptions, and facts about obesity. New Eng J Med, 368 (5), 446-54. doi: 10.1056/NEJMsa1208051

Dhurandhar EJ, et al (2014). The effectiveness of breakfast recommendations on weight loss: a randomized controlled trial. Am J Clin Nutr, 100(2):507-13. doi: 10.3945/ajcn.114.089573

Fontana L (2009). The scientific basis of caloric restriction leading to longer life. Curr Opin Gastroenterol, 25(2):144-50. doi: 10.1097/MOG.0b013e32831ef1ba

Fontana L and Klein S (2007). Aging, adiposity, and calorie restriction. JAMA, 297(9):986-94. doi: 10.1001/jama.297.9.986

Hall KD (2012). Quantitative Physiology of Human Starvation: Adaptations of Energy Expenditure, Macronutrient Metabolism and Body Composition. In: Comparative Physiology of Fasting, Starvation, and Food Limitation. Berlin, Heidelberg: Springer Berlin Heidelberg, pp. 379–393. doi: 10.1007/978-3-642-29056-5_22

Harvie M, et al (2013). 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, 110 (8), 1534-47. doi: 10.1017/S0007114513000792

Heilbronn LK, et al (2005). Glucose tolerance and skeletal muscle gene expression in response to alternate day fasting. Obes Res, 13(3):574-81. doi: 10.1038/oby.2005.61

Longo VD & Mattson MP (2014). Fasting: molecular mechanisms and clinical applications. Cell Metab, 19 (2), 181-92. doi: 10.1016/j.cmet.2013.12.008

Mattson MP (2012). Energy intake and exercise as determinants of brain health and vulnerability to injury and disease. Cell Metab, 16 (6), 706-22. doi: 10.1016/j.cmet.2012.08.012

Mattson MP, et al (2014). Meal frequency and timing in health and disease. Proc Natl Acad Sci U S A, 111 (47), 16647-53. doi: 10.1073/pnas.1413965111

van Praag H, et al (2014). Exercise, energy intake, glucose homeostasis, and the brain. J Neurosci, 34 (46), 15139-49. doi: 10.1523/JNEUROSCI.2814-14.2014

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Guest Author

This article was contributed by a guest author with expert knowledge in their field.

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