Dr. Guofang Chen, a German doctor at our hospital, was invited by Diabetes International to write a review article on the concept, history and value of food restriction therapy, which is worth reading. Food restriction therapy has a long history in Europe and the United States, but is still in its infancy in China. The beneficial effects of food restriction therapy on multiple systems and aspects of the body have been demonstrated in animal experiments and some clinical studies. This article outlines the concept of food restriction therapy, dietary strategies, effects on the body, and clinical applications. The concept of dietary restriction is the reduction of daily energy intake through calorie restriction (CR) or dietary restriction (DR) for the purpose of preventing or treating certain diseases and benefiting health. Generally, calorie intake is reduced to 60-85% of the daily energy requirement, while ensuring the body’s basic needs for nutrients. The history of food restriction therapy in the West can be traced back to more than 500 years ago. According to records, Luigi Cornaro (1464-1566), an Italian nobleman, followed his doctor’s advice to control his diet and live frugally since he was 35 years old, and eventually lived to the age of 102, while the average life expectancy in Europe was less than 30 years at the same time. The annual Islamic festival of Ramadan and the ancient Chinese Taoist practice of Pian Gu are intended to cultivate the body and nourish the mind, but can be considered essentially different expressions of caloric restriction. Food restriction was first used clinically to treat obese patients and severely obese type 2 diabetics, but its widespread use was limited by the state of medical care and the side effects of food restriction at the time. Since the beginning of this century, with the improvement of medical treatment and awareness, research on food restriction therapy has gradually increased, and food restriction therapy is becoming a hot spot for clinical and basic research. In the process of development and refinement of fasting therapy, researchers agree that total fasting is not recommended due to many adverse effects and serious complications, while supplemented fasting with low-calorie supplementation has similar health benefits as total fasting with significantly fewer adverse effects and better compliance and safety. It has the advantages of better compliance and higher safety, and is therefore commonly used in clinical and basic research. Dietary strategies in food restriction therapy The specific forms of food restriction therapy are not uniform in foreign studies. According to the degree of calorie restriction, it can be divided into low calorie restriction (reducing daily calorie requirement by 15%-40%), very low calorie restriction (400kcal/d or even lower); according to the length of restriction, it can be divided into short duration (generally ≤7-9 days), long duration (>9 days); according to the frequency of restriction, it can be divided into intermittent restriction (2 days of restriction per week, rest of normal diet), alternate day restriction, continuous The frequency of restriction can be divided into intermittent restriction (2 days per week, rest of normal diet), alternate day restriction, continuous restriction, etc. Italian scholar Fontana and his research group followed up more than 20 cases of 30% calorie restriction and more than 20 cases of typical Western diet for 3-15 years, with an average of 6.5 years, to investigate the relationship between food restriction and cardiovascular disease risk, which is the longest study reported so far on the duration of food restriction intervention. In all types of studies, patients were given a certain amount of low-calorie diet during the period of food restriction to meet the basic metabolic needs and nutritional balance of the body, and the diet maintained the appropriate ratio of protein, carbohydrate, and fat, while ensuring the supply of electrolytes such as sodium, potassium, and chloride. The food restriction program introduced by Professor Qin Jian of the First Hospital of Sun Yat-sen University in China, which was first introduced from abroad, using a gradient food restriction and gradient recovery strategy of buffer period – fasting period – recovery period, has been preliminarily proven to be effective in the domestic population with metabolic syndrome-related diseases, some Gastrointestinal disorders and autoimmune diseases in domestic population have better efficacy. The effects of dietary restriction on the body 1. The effects of dietary restriction on overall health Dietary restriction can extend the survival time of many organisms (including unicellular organisms, invertebrates, and vertebrates) and extend their average and maximum life span. Studies in mammals have shown that diet restriction can delay aging, reduce morbidity and mortality from aging-related diseases, reduce the risk of cardiovascular disease, improve insulin resistance and metabolic syndrome, reduce the risk of tumor development, and modulate the immune system. Most of the current research results originate from animal experiments, and there are relatively few clinical data on human studies. Large samples of controlled clinical trials are needed to further verify the effects of food restriction in the population and related mechanisms. 2. The effect of food restriction on physical and mental behavior Animal studies showed that the activity of mice increased in the early stage of food restriction, mainly due to the increase of foraging activity in expectation of food, and this activity gradually decreased as the time of food restriction increased, so the overall activity after food restriction tended to decrease. In humans, however, there is no transient increase in activity after food restriction, and this is replaced by a more gradual and sustained decrease in activity. The explanation for this phenomenon is that animals are involuntarily restricted, so there is an early increase in foraging activity, whereas in human-initiated restriction, there is no subjective willingness to forage. The levels of neuropeptides associated with feeding in the hypothalamus, such as neuropeptide Y (NPY) and Agouti-regulated peptide (AgRP), increase after restriction, causing hunger. Whether this hunger disappears or gradually decreases after a long period of fasting is a major concern for researchers. In vivo studies in mice showed that hunger was not significantly reduced after a long period of fasting (100 d). However, studies in obese type 2 diabetic patients have found a significant reduction in hunger after very low calorie restriction. In terms of cognitive function, the risk of developing neurodegenerative diseases such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease increases each year with age. In contrast, food restriction can act on signaling pathways such as insulin, FoxO transcription factors, and sirtuins to promote the production of neurotrophic factors and antioxidants, protect nerve cells, and prevent the development of neurodegenerative pathologies. Several studies have reported that food restriction can prevent aging-related memory loss. In terms of reproductive capacity, the maternal energy supply is not sufficient to support pregnancy during fasting restriction, when maternal reproductive capacity decreases to protect it from conception during this phase. In contrast, when the restriction stops, her reproductive capacity is quickly restored and enhanced. In addition to the effects on physical activity, hunger, cognitive function, and reproductive capacity, fasting can also have a positive impact on psychological behavior. Clinical studies have shown that restriction does not cause eating disorders, decreased quality of life, depressed mood, or cognitive impairment. On the contrary, restriction can improve most of the above mentioned psychological or behavioral events. 3. The effect of food restriction on the organism’s organ level Food restriction has a significant effect on several organs in the body. The proportion of body fat loss was greater than the proportion of body weight loss, and it is presumed that body composition was reconstructed with less fat tissue and more muscle tissue after restriction. In the brain, food restriction slows down the renewal rate of membrane phospholipids and accelerates the renewal of synaptic vesicle proteins, thus removing damaged membrane proteins in time and slowing down the cellular aging process. The beneficial effects of food restriction on the heart have been fully recognized. Total cholesterol, LDL cholesterol, triglycerides, fasting glucose insulin, systolic blood pressure and diastolic blood pressure were significantly reduced after food restriction, and the risk of atherosclerosis was reduced; meanwhile, left ventricular diastolic function and heart rate variability index, which are indicators of cardiac aging, were maintained at relatively young levels, suggesting that cardiac function aging was delayed after food restriction. In rats with drug-induced liver injury, food restriction enhanced the ability of compensatory liver repair and protected liver tissues; prolonged fasting was also able to regulate cytochrome P450 activity in hepatocytes, maintaining it at a level similar to that of young rats. With increasing age, the body undergoes atrophic muscle loss, and studies in rodents and primates have confirmed that food restriction can prevent aging-related muscle loss. In addition, food restriction has positive beneficial effects on bones, skin, lungs, kidneys and digestive tract, and these effects are mostly related to its anti-oxidative stress effect mechanism. 4, the clinical application of food restriction therapy Clinically, food restriction therapy can be used for the prevention and treatment of endocrine metabolic diseases such as obesity, type 2 diabetes, fatty liver, polycystic ovary syndrome, intractable autoimmune diseases such as rheumatoid arthritis, neurodermatitis, chronic eczema, psoriasis, and some digestive system diseases such as constipation, chronic enteritis, irritable bowel syndrome, Crohn’s disease, etc.. During the process of food restriction, people experience varying degrees of hunger, fatigue, dizziness, bad breath, depression, poor concentration, decreased libido, anovulation, hyperuricemia, and transient transaminase elevation, which mostly resolve on their own in the later stages of food restriction or after the end of food restriction. Food restriction therapy is contraindicated when patients present with or have acute or severe chronic diabetic complications, hyperuricemia, liver disease (except fatty liver), renal failure, chronic infections (e.g., tuberculosis), extensive tumors, metastatic cancer, or psychiatric system disorders. In conclusion, food restriction therapy is a safe, effective, and relatively inexpensive strategy to prevent and treat disease and delay aging. With the standardized guidance of physicians and active cooperation of patients, food restriction can be safely implemented and provide significant benefits to patients.