Intermittent Fasting and Health

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By Mark P. Mattson, Ph.D.Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD.

Text of Intermittent Fasting and Health

  • HEALTH Naturally MAGAZINE

    Intermittent Fasting and HealthIntermittent Fasting and Health By Mark P. Mattson, Ph.D.By Mark P. Mattson, Ph.D.

    The results of recent research refute the notion that eating many small meals throughout the day is healthier than skipping meals.

    Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD.

    Animal studies suggest that intermittent fasting (IF or periodic short fasts of 16-36 hours) can promote optimal health and protect against a broad range of chronic maladies including diabetes, cancers, cardiovascular disease and neurodegenerative brain disorders. Moreover, IF can reduce cellular damage and improve functional outcome in animal models of stroke, epilepsy and trauma. Studies of overweight human subjects show that IF diets promote loss of abdominal fat with retention of lean mass, and can be effective in preventing and treating diabetes, cardiovascular disease, cancers and inflammatory disorders such as asthma.

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    Intermittent Fasting and Health | Mark P. Mattson, Ph.D.

    Our research suggests that IF promotes health by imposing a mild transient challenge to the brain and body, which stimulates cells in ways that improve their function and protects them against injury and disease. From an evolutionary perspective, eating three meals plus snacks is not normal. Humans are designed for IF diets and, based on evidence described and referenced below, a return to such eating patterns may go a long way towards squelching the current epidemics of obesity, diabetes and the many diseases associated with these conditions.

    Intermittent fasting (IF) can be defined as going 16-36 hours with little or no food periodically, typically 1-3 times each week. The three IF diets that are currently the most popular are:

    Variations of Intermittent FastingVariations of Intermittent Fasting

    the 5:2 diet in which one eats normally 5 days each week, and eats no more than 600 calories 2 days each week1, 2;

    alternate day fasting in which the person alternates between normal eating and 600 calorie days3 and

    time-restricted eating in which food is consumed only during a 4-8 hour time period every day4.

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  • A valuable feature of studies of laboratory animals such as rats and mice is that experiments can be performed under tightly controlled conditions. In contrast to human studies, in animal studies there are no problems with compliance with an IF diet (the animals have no choice), and there is little or no variability among individuals in their genetics or lifestyle. Research on animal models of human diseases has been critical for the development of effective treatments for patients. This is true for cancers, cardiovascular disease, diabetes, many different infectious agents, and some neurological disorders including depression and multiple sclerosis. However, the most common treatments for these diseases can have prominent side effects, and may themselves pose a considerable risk of death. In contrast, IF poses little or no risk as an intervention for the primary prevention and/or treatment of many diseases.

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    Intermittent Fasting and Health | Mark P. Mattson, Ph.D.

    Studies of laboratory animals and humans have shown clear improvements of a wide range of health indicators including:

    Studies of laboratory animals and humans have shown clear improvements of a wide range of health indicators including:

    1) reduced blood pressure and resting heart rate, and increased heart rate variability (changes similar to those of endurance exercise training)5

    2) reduced blood glucose and insulin levels, and an associated increase in insulin sensitivity (changes that protect against diabetes)6-8

    3) reduced abdominal fat with maintenance of muscle mass7, 9

    4) reduced levels of inflammation and oxidative stress (which may protect against conditions such as asthma and autoimmune disorders)10, 11

    5) improved mood and cognitive function12

    Animal Studies Show that IF is a Powerful Protector Against DiseasesAnimal Studies Show that IF is a Powerful Protector Against Diseases

    Intermittent Fasting Improves Many Aspects of HealthIntermittent Fasting Improves Many Aspects of Health

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  • IF can protect neurons against dysfunction and degeneration in animal models of several different neurological disorders. In a transgenic mouse model of Alzheimers disease, IF ameliorates learning and memory deficits21. In a model of Parkinsons disease in which mice are exposed to a neurotoxin, IF reduced degeneration of dopaminergic neurons and lessened motor impairment22. In a mouse model of an inherited form of Parkinsons disease, IF reversed neurological symptoms23. Huntingtons disease is a fatal inherited disorder that involves the degeneration of neurons in a region of the brain called the striatum that controls body movements. In mice engineered with the defective human gene that causes Huntingtons disease, IF reduces brain damage and associated symptoms24. While remarkably beneficial in animal models of Alzheimers, Parkinsons and Huntingtons diseases, IF may not be a panacea for all neurodegenerative disorders. IF did not delay the onset of symptoms, and hastened the progression of the disease in a mouse model of amyotrophic lateral sclerosis (ALS)25. The reason for the failure of IF to benefit ALS mice may be the result of an impaired ability of the spinal cord motor neurons affected in ALS to respond to IF.

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    Intermittent Fasting and Health | Mark P. Mattson, Ph.D.

    The most commonly used IF diet for animal studies is alternate day fasting where the animals go 24 hours with no food (and free access to water) every other day6. This IF diet inhibits the formation and growth of tumors and reduces IGF-1 levels in rodents, indicating a potential for IF in cancer risk reduction and cancer treatment13, 14. IF counteracts diabetes and obesity by reducing overall energy intake, by increasing insulin sensitivity, and by promoting fat oxidation8, 15. Rats maintained on an IF diet exhibit improvements in multiple risk factors for cardiovascular disease, including reductions in levels of circulating triglycerides and cholesterol and a reduction in both diastolic and systolic blood pressure5, 8. Moreover, IF protects the heart against ischemic damage in a rat model of myocardial infarction16.

    The first two neurological disorders that IF was found to counteract in animal models were epileptic seizures and ischemic stroke. In a rat model, severe epileptic seizures cause damage to neurons in the hippocampus, a brain region critical for learning and memory. However, many hippocampalneurons in rats maintained on an IF diet were not damaged by the seizures, and learning and memory ability was preserved17. Stroke is a major cause of death and disability worldwide. In both rat18 and mouse11 stroke models, IF protected neurons from dying and also improved functional outcome. IF can also improve recovery from spinal cord injury and traumatic brain injury in animal models19, 20.

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    Intermittent Fasting and Health | Mark P. Mattson, Ph.D.

    The liver is the major source of energy for the body when regular meals are consumed. Glucose in foods and drinks is transferred from the intestines into the blood, and is then taken up by liver cells which retain glucose in a storage form called glycogen. Between meals glucose is released from glycogen stores and enters the blood, where it is distributed to cells throughout the body and brain to provide the energy required to sustain their function. However, the liver stores only enough glucose to last for 10-12 hours after a meal. Therefore, fasting for more than 12 hours results in a shift in energy metabolism such that fats become the major source of fuel. Studies in human subjects have shown that IF is more effective than low calorie diets (eating regular meals, but reducing the size of each meal) in reducing abdominal fat and retaining muscle mass7. Moreover, a recent study showed that when mice are fed high fat food that normally makes them obese, when they are allowed to eat the food only during an 8 hour time period each day, they do not become obese26. Because Americans usually spread out their consumption of food and caloric beverages throughout most of their waking hours, they might improve their health by simply restricting the time period during which they eat to 8 hours or less each day.

    IF Promotes Fat Burning and the Production of Beneficial KetonesIF Promotes Fat Burning and the Production of Beneficial Ketones

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    Intermittent Fasting and Health | Mark P. Mattson, Ph.D.

    During IF, fats are broken down (lipolysis), and fatty acids are released into the blood and transported into liver cells, where they are converted to ketone bodies in a process involving beta-oxidation to produce acetyl CoA. This is then used in the synthesis of the ketones beta-hydroxbutyrateand acetoacetate. The ketonesare then released into the blood and distributed throughout the body and brain where they are used as energy source by cells. Upon entering cells, ketonebodies can be metabolized to acetyl CoA which then enters the citric acid cycle resulting in the generation of ATP. Ketonesprovide a critical source of energy for heart and muscle cells and neurons during fasting. For example, in the fed state glucose provides nearly 100% of the energy for neurons, whereas during prolonged fasting ketonescan