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Dr Aidin Rawshani

Effects of intermittent fasting on health, ageing and disease

What is intermittent fasting?

Intermittent fasting (IF) is one of the world’s most popular health trends. The first studies that studied the effectiveness of intermittent fasting, also called periodic fasting, were published by Dr. Weindruch and Dr. Sohali in 1997. Their report was published in the world’s leading medical journal, The New England Journal of Medicine. The study showed that reduced food intake (calorie restriction, i.e. eating fewer calories) has remarkable effects on biological aging and life expectancy of animals.

Intermittent fastin concept – empty plate on blue background, copy space

As early as 1997, researchers suggested that the benefits of caloric restriction were explained by reduced production of harmful substances known as reactive oxygen species (ROS). These substances are produced in all cells throughout the body in connection with the cell manufacturing fuel.

All cells of the body have small “nuclear works” (so-called mitochondria) that produce energy for the body. A residual product in the production of fuel is precisely free oxygen radicals (ROS) that leaks out of mitochondria and damages the cells other structures.

Intermittent fasting reduces the presence of harmful substances in the body

Since 1997, hundreds of further studies have been carried out and the effect of intermittent fasting has been studied, which means fasting for short periods. Intermittent fasting is a kind of calorie restriction, since one is not allowed to eat any calories during much of the day. Today, it is considered that calorie restriction reduces the release of harmful oxygen radicals.

Intermittent fasting causes the body to shift from sugar to fat as fuel

Several research groups have suggested, based on their research, that intermittent fasting leads to a shift in how the body produces energy. Intermittent fasting causes the liver to gradually slide over from burning sugar (glucose) to releasing ketones that can be used by the body’s cells as fuel. The ketones themselves make the liver using fatty acids released from the adipose tissue during fasting. In English, this transition from burning glucose (sugar) to fat is called metabolic switching.

Dictionary FastePeriod: The period of fasting.Food Window: The period when it is allowed to eat food.

How to eat at intermittent fasting?

There are different methods of intermittent fasting. The most popular methods are as follows.

The 16:8 method

With the 16:8 method, skips breakfast and limit the dining window to 8 hours. The fasting period therefore lasts 16 hours. This is the most common method among those that apply intermittently fasting.

Eat-Stop Eat

This method involves fasting for 24 hours, once or twice a week, for example, by not eating from dinner one day until dinner the next day.

The 5:2 method

With this method, you consume only 500-600 calories two days a week, but normally eat the other 5 days of the week. You do not get fasting two consecutive days.

Calorie restriction is the safest way to lose weight

We at diabeteson.com believe that one can lose weight with the help of most diets. In fact, research shows this. You can lose weight by eating low-carbohydrate diet, low-fat diet, protein-rich diet, Atkins diet, etc. Currently, there is no convincing evidence that a particular diet would have benefits for metabolism, but weight loss is always due to consuming more calories than eating. This means that the weight loss seen in low-carbohydrate diets is likely to be explained by eating less food (fewer calories). However, it is different difficult to maintain different diets. Eating a very low-calorie diet leads to very rapid weight loss and often an equally rapid weight gain after a few weeks or months, as one fails to maintain the diet.

Intermittent fasting also provides a calorie restriction. The peculiarity of intermittent fasting is the long fasting, during which the body gets a chance to rest, and the production of harmful oxygen radicals becomes less. Many people consider the 16:8 method to be the easiest to hold. Whatever type of intermittent fasting you choose, it is important not to eat too much during the dining window.

Intermittent fasting provides clear weight loss

Weight loss is the most common reason for starting with intermittent fasting. By eating fewer meals, intermittent fasting can lead to an automatic calorie restriction. In addition, intermittently fasting changes some hormone levels, which can facilitate weight loss. In addition to lowering insulin levels and increasing growth hormones, the release of the hormone norepinephrine (norepinephrine), which helps burn fat.

Metabolism increases during fasting

Due to these changes in hormone levels, short-term fasting can increase your metabolism by 3 -14%. By eating less and burning more calories, so intermittent fasting leads to weight loss. A study from 2014 showed that intermittent fasting can cause 3 -8% weight loss for 3-24 weeks, which is very much. Another study showed that intermittent fasting causes less muscle loss than other methods of prolonged calorie restriction. The main reason that intermittent fasting is successful is that it helps you eat fewer calories in total.

Health benefits in intermittent fasting

Research has shown that many of the benefits of intermittent fasting can be evolutionary mechanisms. Our cells have an ability, come by millions of years of evolution, that optimizes how cells use and store energy. During fasting, several functions are activated in cells that lead to optimization of how energy is consumed and reduced production of harmful substances.

Animal experiments clearly show that intermittent fasting has beneficial effects on several diseases, such as obesity, type 2 diabetes and type 1 diabetes, cardiovascular disease, cancer and neurodegenerative brain diseases (Alzheimer’s, vascular dementia). It would seem that it is favorable to switch from the burning of sugar to the burning of ketondes. There are also studies that suggest that this improves mental and physical performance, in addition to improved resistance to several diseases.

How does intermittent fasting affect various diseases?

Cognitive Functions

Studies in animals show that intermittent fasting improves several cognitive factors such as memory and executive ability. In a clinical study, older adults who applied a short-term calorie restriction experienced an improved verbal memory. There is a need to conduct additional studies of intermittent fasting and cognition in elderly people, especially considering that there are no treatments that improve brain aging and reduce the progression of dementia.

Obesity and Diabetes

In animal models, intermittent fasting improves insulin sensitivity and prevents the development of obesity. On the island of Okinawa, the traditional population usually maintains a regime of intermittent fasting and they have a low incidence of obesity and diabetes, as well as very long life expectancy. The population of Okinawan usually consumes a low-calorie diet, but nutritious foods. People who use a caloric diet but who still receive sufficient nutrients were shown to have low levels of the hormone IGF-1, the growth hormone GH, as well as minor inflammation and stress in the body (oxidative stress).

A comprehensive study showed that daily calorie restriction improves many risk factors for cardiovascular diseases in normal-weight people. Several minor studies including overweight adults showed that intermittent fasting is as effective for weight loss as standard diets. Studies investigating the effect of daily calorie restriction compared to intermittent fasting have not noted a significant difference between factors such as weight loss, insulin sensitivity, blood pressure or blood lipids.

Cardiovascular Diseases

Intermittent fasting improves blood pressure, heart rate at rest, blood lipids (HDL and LDL), triglycerides, glucose, insulin sensitivity and fasting insulin levels. Intermittent fasting additionally reduces inflammation and stress in the body. These risk factors improve already within 2 – 4 weeks. If you stop fasting, the risk factors return to their original value after a couple of weeks.

Cancer

More than a century ago, scientists described the positive effect of fasting and calorie restriction on tumors in animals. Since then, numerous studies in animals have shown that daily calorie restriction or intermittent fasting reduces the incidence of tumors and slows the growth of many types of tumors, while increasing their sensitivity to chemotherapy (chemotherapy) and radiation. Similarly, intermittent fasting is believed to impair energy consumption in cancer cells, inhibit their growth and make them more susceptible to various treatments.

Clinical trials have investigated the effect of daily calorie restriction in men with prostate cancer and individuals with brain tumour (glioblastoma), the results suggest that intermittent fasting can slow tumor growth and prolong survival. However, more studies are required for this to be applied in cancer care. No studies have yet established whether intermittent fasting affects relapses of cancer in humans.

As regards intermittent fasting and cancer, there are currently no safe studies, so we cannot recommend intermittent fasting for any type of cancer treatment. All cancer treatment should be handled in full by specialist doctors.

Dementia

Population studies suggest that excessive energy intake, especially in adult years, increases the risk of stroke, Alzheimer’s disease and Parkinson’s disease. There is strong evidence that intermittent fasting can delay the onset and development of disease processes in animal models, such as Alzheimer’s disease and Parkinson’s disease. Intermittent fasting increases the stress resistance of nerve cells by several mechanisms, such as strengthening the function of cell nuclear power plants (mitochondria) and stimulating the recovery of harmful substances (autophagy), protecting against antioxidants and DNA repair.

Read more: Diabetes and dementia

Asthma and inflammation of joints

Weight loss reduces the symptoms of asthma in obese patients. In one study, patients who tested intermittent fasting had minor asthma symptoms and airway resistance improved. Intermittent fasting is also expected to be beneficial in joint inflammation (rheumatoid arthritis), and there is actually evidence supporting its use in patients with arthritis.

The rest of this article is for particularly interested and for health professionals.

Intermittent fasting and metabolic switching

Glucose and fatty acids are the main sources of energy for the cells of the body. After meals, glucose is used as energy, and fat is stored in adipose tissue as triglycerides. During periods of fasting, triglycerides break down to fatty acids and glycerol, which are used to extract energy. The liver converts fatty acids into ketone bodies, which are an important source of energy for many tissues, especially the brain. In non-phased conditions, the ketone bodies in the blood are low and in humans ketones rise within 8 to 12 hours after you start fasting and reach levels. The time interval of the “metabolic switch” differs between different organisms and animals.

Ketone bodies (ketones)

Ketone bodies are not just molecules used for fuel during periods of solid; they are potent signal molecules with large effects on cell and organ functions. Ketone bodies regulate the expression and activity of many proteins and molecules known to affect health and aging. These molecules include peroxisomproliferator receptor γ coactivator 1α (PGC-1α), fibroblast growth factor, nicotinamide adenine dinu-kleotide (NAD+), sirtuins 24 polypolymerase 1 (PARP1) and ADP-ribosyl cyclase (CD38).

The liver is the organ responsible for extracting energy from either sugar or fat (triglycerides) which in turn turns into ketones

What happens in your body’s cells when you fasten is quite complicated and requires deep understanding in biology to understand. To summarize these processes, one can describe the effect of intermittent fasting as cells slow down all anabolic processes (synthesis, growth and reproduction), promote maintenance and repair systems, improve stress resistance, recover damaged molecules, stimulate mitochondrial biogenesis and promotes cell survival. All these effects support improvements in health and disease resistance.

Metabolic adaptations in intermittent fasting

When you fasten for 10 hours or more, sugar stores are emptied into the liver and the body turns to burn triglycerides (TG) to free fatty acids (FFA) in the fat cells. FFA released into the circulation is transported to the liver, where they produce the ketone bodies acetoacetate and β-hydroxybutyrate (β-Hb). FFA also activates factors inside the nucleus of cells (peroxisomproliferator-activated receptorα (PPAR-α) and activating transcription factor 4), resulting in the production and release of a protein called fibroblast growth factor 21 (FGF21), this protein has a widespread effect on the cells β-Hb and acetoacetate are actively transported to cells where they can be metabolized to acetyl CoA, which in turn generates an energy molecule called ATP.

A central component in energy recovery in the cell

A central component for energy recovery and regulation in all our cells is called mTOR (mammalian target of rapamycin). Metabolism is an extremely complex subject but at the same time energy recovery and conversion of bioenergy is central to several age-related diseases such as diabetes, cancer, cardiovascular diseases, natural biological aging and many other factors. Many people do not know that the machinery that regulates energy and metabolism in the body is called mTOR. When fasting, sugar levels (glucose) and amino acids in the body decrease, which reduces the activity of mTOR. A reduced activity of mTOR leads to the upregulation of autophagy, a physiological process whereby the cell “eats up” waste products and damaged molecules inside the cell. Autophagy exists within most organisms and is considered to be the “recovery system” of cells.

Intermittent fasting and cellular stress

An illustration showing how harmful particles accumulate in all cells of the body. These harmful particles must be disposed of by various systems of the cell in order not to harm the body.

Several studies have shown that many of the benefits of intermittent fasting are not due solely to weight loss. The health benefits in addition to weight loss include improvements in sugar regulation, blood pressure and heart rate. Repeated exposure to fasting results in lasting adaptive reactions that improve your ability to withstand future challenges and illnesses. Cells react to intermittent fasting by engaging in a coordinated adaptive stress response that leads to increased expression of antioxidant defense, DNA repair, protein quality control, mitochondrial biogenesis and autophagia, in addition, reduces inflammation in the body.

Intermittent fasta protects against the following

Oxidative stress — Biochemical process in which either reactive oxygen compounds produced by the organism damage cells and organs.Metabolic stress — Metabolic stress metabolism in the cells is strained. It is caused mainly by a lack of oxygen. Proteotoxic stress — Physiological process that leads to damaged proteins that in turn damage to the cell.Stimulates autophagia and mitophagia — Autophagia is a physiological process whereby the cell “recycles” damaged substances and mitophagia involves degradation and reuse of mitochondria ( cell nuclear power plants) Inhibits mTOR — Brakes the central energy regulatory system of the cell and slows the production of proteins

What hormones affect during intermittent fasting?

When you apply intermittent fasting, several things happen in your body. For example, your body adjusts hormone levels to make stored body fat more available for the burning and extraction of energy. Your cells also initiate important repair processes and change the expression of important genes.

Here are some changes that occur in your body

Human Growth Hormone (HGH): The levels of growth hormone rise as much as 5-fold. This has benefits for fat burning and muscle mass.Insulin: Insulin sensitivity improves and insulin levels drop dramatically. Lower insulin levels make stored body fat more accessible.Cell repair: When fasting, your cells initiate cellular repair processes. This includes autophagy, in which cells break down and remove old and dysfunctional proteins that build up inside cells.Gene expression: There are changes in the expression of genes that are related to longevity and protect against various diseases.

Key health benefits of intermittent fasting

Weight Loss: As mentioned above, intermittent fasting can help you lose weight and stomach fat, without deliberately limiting calories. Insulin resistance: Intermittent fasting can reduce insulin resistance, lower blood sugar by 3 -6% and the fasting insulin levels by 20 -31%, which should protect against type 2 diabetes.Inflammation: Some studies show reductions in markers of inflammation, an important impetus for many chronic diseases.Heart: Intermittent fasting can reduce “bad” LDL cholesterol, blood triglycerides, inflammatory markers, blood sugar and insulin resistance, all of them are risk factors for heart disease.

Cancer: Animal studies suggest that intermittent fasting can prevent cancer.

Anti-aging: Research shows that intermittent fasting prolongs the life expectancy of different animals and possibly even humans. Keep in mind that the research is still at an early stage. Many of the studies were small, short-term or performed on animals. Many questions have not yet been answered in studies on humans.

Intermittent fasting, health and natural ageing

To date, no studies have shown that intermittent fasting prolongs life in humans, but studies show that the diet improves several factors and reduces the risk of suffering severe illnesses that contribute to a shortening of life expectancy. However, several studies have investigated the efficacy of intermittent fasting among different animals and primates. Goodrick and colleagues reported that the average life expectancy of rats increased by up to 80%. The effect of calorie restriction on health and longevity varies and can be influenced by factors such as gender, diet, age and genetic factors. A meta-analysis showed that the calorie restriction increases median life expectancy by 14 to 45% in rats. In humans, it has been noted that intermittent fasting leads to weight loss, reduces the level of insulin resistance, improves blood lipids, lowers blood pressure and reduces inflammation.

References

Rafael de Cabo, Mark P. Mattson. Effects of Intermittent Fasting on Health, Aging, and Disease. N Engl J With 2019; 381:2541 -2551

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