Live, Fast, Die Old – Intermittent Energy Restriction Diets




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Intermittent energy restriction (IER), or intermittent fasting, is a form of calorie restriction diet. The principle is simple: periods of non-fasting are intercalated with periods of fasting.

IER is not about starvation followed by binge eating: non-fasting periods have regular caloric intake, while during fasting periods, little or no food is consumed. Fasting periods can vary: they can be on alternate days, two non-consecutive days per week (the 5:2 diet), or any other ratio of fasting to non-fasting periods – there are many different variations. Also, you don’t necessarily go 24 hours without eating; on your fasting day you can limit your feeding time to a window of 8 hours or less, followed by a fasting period of 16 hours or more – you can simply skip breakfast and lunch several days each week.

The rationale is that it takes about 12 to 16 hours for your body to consume its liver glycogen stock (the main source of energy, derived mostly from carbohydrate storage), after which it switches to burning fat. But if you restock your glycogen levels by eating sooner, you make it harder for your body to burn fat as fuel. When these glycogen stores are exhausted, fatty acids are mobilized from adipose cells and metabolized in the liver cells to produce ketone bodies, which are then released into the bloodstream and used as fuel throughout the body and brain.

Besides the aimed weight loss, there are claims that intermittent fasting can have general beneficial health effects and, specifically, positive effects on brain function. Indeed, ketones have recently been shown to have neuroprotective functions.

Is IER effective? Most importantly, is it safe and beneficial?

There are many myths and misinformation surrounding diets, especially those designed for weight loss. For example, breakfast is often advertized as being fundamental for weight control, but scientific evidence has mostly been contradictory and recent findings even suggest the opposite. The daily three-meals-plus-snacks pattern has become the standard during the last decades, but a shift in eating patterns may be needed.

IER may be one alternative pattern. Many people find continuous calorie restriction diets difficult to maintain, but IER allows the sacrifice of dietary restriction to be intercalated with normal feeding habits. A study comparing the efficacy of intermittent and continuous energy restriction over 8 weeks found that intermittent dieting was as effective as continuous dieting for both weight loss and weight maintenance at 12 months. Another study actually showed that IER was superior to a daily energy restriction program in reducing body fat and in improving insulin sensitivity.

Although animal studies have demonstrated numerous beneficial effects of IER on brain function and resistance to injury and disease, evidence that similar effects occur in humans is still scarce. However, metabolic changes that occur during fasting that warrant a steady supply of energy to cells are highly conserved among mammals.

We all have organs that uptake and store glucose such that it is rapidly mobilized when needed, on one hand, and longer-lasting energy storages, such as fatty acids in adipose tissue, on the other hand. Therefore, it is likely that fasting has similar effects in different mammals.

Evidence from animal studies

Animal studies have provided significant evidence showing that IER increases lifespan and improves overall health. IER in rodents decreases accumulation of abdominal fat, increases insulin sensitivity, and decreases cardiovascular diseases by reducing blood pressure and heart rate; IER can also protect the heart against ischemic damage in an animal model of myocardial infarction.

Fasting can also lower the incidence of tumors or even reverse disease processes in animal models of various cancers. Inflammation is increasingly recognized as a contributing factor for cancer cell growth and, because excessive energy intake promotes inflammation, it is likely that suppression of inflammation plays a role in the inhibition of tumor growth by IER.

Experimental data suggest that the beneficial effects of IER may involve an adaptive cellular stress responses that protect against more severe stress. IER may also act by having antioxidant effects: alternate day fasting has been shown to increase levels of antioxidant enzymes and prevent age-related decrements in antioxidant enzymes. Fasting also seems to stimulate mechanisms for the removal of damaged molecules and cellular structures.

All these processes are highly relevant for preventing or even reversing the pathological processes of numerous neurological diseases: IER can protect neurons against oxidative stress in animal models of neurodegenerative disorders; also, diseases that include abnormal accumulation of protein aggregates, such as Parkinson’s and Alzheimer’s disease, can be counteracted by the increased removal of damaged molecules.

Research shows that most brain regions are affected by dietary energy restriction. IER can protect both the central and the peripheral nervous system against dysfunction and degeneration in a myriad of animal models. IER increases the resistance to neurotoxins and has neuroprotective effects in animal models of Parkinson’s, Alzheimer’s, Huntington’s, and Charcot-Marie-Tooth diseases, and protects the brain and spinal cord against acute traumatic and ischemic injury, improving functional outcome after stroke.

In mouse models of demyelinating diseases, such as multiple sclerosis, IER improves motor performance by reducing demyelination. Alternate-day fasting stimulates the production of several different proteins and trophic factors that promote neuronal survival, neurogenesis, and the formation and strengthening of synapses in the brain. Long-term IER also results in improved performance of mice on a range of cognitive tasks.

Evidence from studies in humans

Data collected from subjects under severe dietary restriction indicate that humans undergo many of the same adaptations of energy restricted animals. When humans switch from eating three full meals each day to an IER diet, they show marked changes in energy metabolism that include reduced levels of insulin and increased insulin sensitivity, fatty acid mobilization, and elevation of ketone levels. Ketones are known to have beneficial effects on cells with a high energy demand, such as neurons in the brain. Indeed, compared with glucose, ketones produced during fasting provide a more robust and steady energy substrate for neurons.

Increased ketone levels have been shown to improve cognitive function in patients with Type 1 diabetes, mild cognitive impairment, and early Alzheimer’s disease. IER also improved verbal memory in normal elderly human subjects.

Obesity is known to promote inflammation, and IER has been shown to also decrease inflammation in human subjects. In fact, all major diseases, including cardiovascular diseases, diabetes, neurodegenerative disorders, arthritis, and cancers involve chronic inflammation in the affected tissues and, in many cases, in the whole body. By decreasing inflammation, IER may hamper the development of many of these pathologies.

Evolution favors fasting

There is an interesting anthropologic argument in favor of IER: the survival and propagation of our species has relied heavily on the need to acquire food, which was probably scarce for many of our ancestors and primarily consumed during daytime, leaving long hours of overnight fasting. Evolution might therefore have favored those with the ability to perform at a high level, both physically and mentally, under limited food availability. Food deprivation (and intermittent running) was probably the most common energetic challenge to our brains and bodies and might have induced crucial adaptive responses.

By suppressing these responses, through overeating and having a sedentary lifestyle, we might have brought upon ourselves an increased risk of numerous diseases. The fact that wild animals and hunter-gatherer humans rarely suffer from obesity, diabetes, and cardiovascular disease is highly representative.

No harm in giving it a try.

References

Casazza K, Fontaine KR, Astrup A, Birch LL, Brown AW, Bohan Brown MM, Durant N, Dutton G, Foster EM, Heymsfield SB, McIver K, Mehta T, Menachemi N, Newby PK, Pate R, Rolls BJ, Sen B, Smith DL Jr, Thomas DM, & Allison DB (2013). Myths, presumptions, and facts about obesity. The New England journal of medicine, 368 (5), 446-54 PMID: 23363498

Harvie M, Wright C, Pegington M, McMullan D, Mitchell E, Martin B, Cutler RG, Evans G, Whiteside S, Maudsley S, Camandola S, Wang R, Carlson OD, Egan JM, Mattson MP, & Howell A (2013). The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. The British journal of nutrition, 110 (8), 1534-47 PMID: 23591120

Longo VD, & Mattson MP (2014). Fasting: molecular mechanisms and clinical applications. Cell metabolism, 19 (2), 181-92 PMID: 24440038

Mattson MP (2012). Energy intake and exercise as determinants of brain health and vulnerability to injury and disease. Cell metabolism, 16 (6), 706-22 PMID: 23168220

Mattson MP, Allison DB, Fontana L, Harvie M, Longo VD, Malaisse WJ, Mosley M, Notterpek L, Ravussin E, Scheer FA, Seyfried TN, Varady KA, & Panda S (2014). Meal frequency and timing in health and disease. Proceedings of the National Academy of Sciences of the United States of America, 111 (47), 16647-53 PMID: 25404320

van Praag H, Fleshner M, Schwartz MW, & Mattson MP (2014). Exercise, energy intake, glucose homeostasis, and the brain. The Journal of neuroscience : the official journal of the Society for Neuroscience, 34 (46), 15139-49 PMID: 25392482

Image via Pressmaster / Shutterstock.

Sara Adaes, PhD

Sara Adaes, PhD, has been a researcher in neuroscience for over a decade. She studied biochemistry and did her first research studies in neuropharmacology. She has since been investigating the neurobiological mechanisms of pain at the Faculty of Medicine of the University of Porto, in Portugal. Follow her on Twitter @saradaes
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