Emerging findings from studies of animal models and human subjects suggest that intermittent energy restriction periods of as little as 16 hours can improve health indicators and counteract disease processes. The mechanisms involve a metabolic shift to fat metabolism and ketone production, and stimulation of adaptive cellular stress responses that prevent and repair molecular damage (Mattson et al., 2014).
Unlike modern humans and domesticated animals, the eating patterns of many mammals are characterized by intermittent energy intake. Animals in the wild don’t consume 3 meals everyday, they most likely feed irregularly, when there is food available, and sometimes according to specific circa rhythm (daily cycle tidal cycle and / or annual cycle). The implications of these cycles go beyond feeding patterns and encompass processes like breeding, hibernation, migration, hormonal regulation, sleeping patterns and others.
Hominid species have been around for a couple of millions of years, eating three meals and a few snacks – like we do today – is not normal from an evolutionary perspective. For human ancestors food was probably scarce and it was consumed during daylight hours, leaving long hours of overnight fasting. In hunter-gathered societies, conditions like diabetes, cardiovascular disease and obesity were fairly rare.
Agricultural societies 10,000 years ago allowed for eating everyday at least once or twice, maybe only the lucky ones. But even then, people did not suffer from modern diseases until concentrating in big cities in the late 19th century. Today, obesity and associated diseases of our modern societies (diabetes, cardiovascular/cerebrovascular disease, cancers, and Alzheimer’s disease) are overwhelming health care systems.
Although many aspects of diet and lifestyle influence metabolic status and disease trajectory during the life course, emerging findings suggest that the influences of the frequency and timing of meals on health may be large.
CELLULAR AND MOLECULAR MECHANISMS.
Studies of intermittent energy restriction on animal models have shown to forestall or even reverse diseases like cardiovascular disease, various forms of cancers, neurodegenerative diseases, as well as diabetes. These diseases haven been studied with a high interest mostly because of their prevalence in the population. However, fasting strategies may prove helpful for many other poor conditions of health, mostly because of their integrative effect on the whole body.
Adaptative stress response
Animals maintained on intermittent energy restrictions (IER) exhibit numerous changes, suggesting heightened adaptive stress responses at the molecular, cellular, and organ system levels. IER increases levels of the antioxidant enzymes in muscle cells of mice, and these effects are accentuated by exercise.
Numerous studies have shown that IER can protect neurons against oxidative, metabolic, and proteotoxic stress in animal models of neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. IER can also protect the heart against ischemic damage in an animal model. Alternate-day fasting stimulates the production of several different neuroprotective proteins. Moreover, IER can boost brain health by increasing the production of trophic factors that promote neuronal survival, neurogenesis, and the formation and strengthening of synapses in the brain.
When humans change their eating patterns, from eating three full meals per day to an IER diet, they exhibit robust changes in energy metabolism characterized by increased insulin sensitivity, reduced levels of insulin and leptin, mobilization of fatty acids, and elevation of ketone levels.
Animal models have consistently shown that IER inhibits and even reverses the growth of a range of tumors, including neuroblastoma, breast, and ovarian cancers. Ketogenic diets may potentiate the antitumor effects of IER. Recent case studies in human patients suggest potential applications of IER in the treatment of a range of cancers, including breast, ovarian, prostate, and glioblastoma.
All major diseases, including cardiovascular disease, diabetes, neurodegenerative disorders, arthritis, and cancers involve chronic inflammation in the affected tissues and, in many cases, systemically. Overweight and obesity promote inflammation, and IER suppresses inflammation in human subjects and animal models of diseases.
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.
Autophagy: Improved Repair and Removal of Damaged Molecules and Organelles
Studies suggest that consuming two meals a day with complete food restriction in between the meals is sufficient to lower blood glucose and lipid levels. This simple dietary approach activates a cell ‘‘cleansing system’’ called autophagy in liver, fat, brain, and muscle that helps prevent obesity and diabetes. Cells possess dedicated mechanisms for the removal of damaged molecules and organelles.
The process of autophagy breaks down parts of your cells in order to recycle them in the creation of new cells. Cytoplasm consists of fluid inside of a cell (excluding the nucleus). During autophagy, cytoplasm and organelles (small structures with specific functions) are removed and recycled. This process keeps your body in balance by self-removing cells that are no longer functioning optimally or appropriately.
The purpose of autophagy is not the simple elimination of materials, but instead, autophagy serves as a dynamic recycling system that produces new building blocks and energy for cellular renovation and homeostasis (proper balance). Moreover, the impairment or activation of autophagy contributes to pathogenesis of diverse diseases, from neurodegenerative diseases such as Parkinson disease to inflammatory disorders such as Crohn disease (Mizushima et al. 2011).
Autophagy is typically triggered by a cell’s starvation of nutrients. It is believed that insulin suppresses autophagy while glucagon can activate the process. After eating, your body releases insulin, while fasting causes a release of glucagon as your body’s blood sugar starts to decrease. Glucagon signals your body to use glycogen in your liver to increase your blood sugar.
There is a lot of research dedicated to methods to activate autophagy due to the many health benefits including cancer prevention and homeostatic properties in the nervous system. However, it also appeals to many people due to the anti-ageing properties and increased metabolic effects. As autophagy has many effects on cellular renovation, it would be reasonable to assume that autophagy can contribute to whole-body rejuvenation.
DIET CHANGES TO BOOST AUTOPHAGY
Interestingly, many regimes that promote longevity include calorie restriction. Fasting is, in fact, the most effective way to trigger autophagy, together with Ketogenic diets.
Ketosis, a diet high in fat and low in carbs brings the same beneficial metabolic changes. By not overwhelming the body with an external load, it gives the body a break to focus on its own health and repair. In the keto diet, you get about 75 percent of your daily calories from fat, and 5 to 10 percent of your calories from carbs. This shift in calorie sources causes your body to shift its metabolic pathways. It will begin to use fat for fuel instead of the glucose that’s derived from carbohydrates.
Low glucose levels occur in both diets and are linked to low insulin and high glucagon levels, and glucagon level is the one that initiates autophagy. When the body is low on sugar through fasting or ketosis, it brings the positive stress that wakes up the survival repairing mode.
A calorie-restricted diet has been demonstrated to exert several beneficial effects, such as increasing lifespan, counteracting ageing, modulating immune cell profile activity and reducing insulin resistance as well as preventing some stages of the carcinogenesis process. Caloric restricted diets can also result in increasing the number of stem cells, which is a factor that plays a major role in tissue homeostasis and growth (Bragazzi et al. 2019). If you’re interested in trying to stimulate autophagy in your body, nutritional and health experts recommend starting by adding fasting and regular exercise into your routine.
However, you need to consult your doctor if you’re taking any medications, are pregnant, breastfeeding, or wish to become pregnant, or have a chronic condition, such as heart disease or diabetes.
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