Calorie restriction

Caloric intake control, and reduction for overweight individuals, is recommended by US dietary guidelines and science-based societies.[1][2][3][4][5][6] Calorie restriction is recommended for people with diabetes[7][8] and prediabetes,[8] in combination with physical exercise and a weight loss goal of 5-15% for diabetes and 7-10% for prediabetes to prevent progression to diabetes.[8] and mild calorie restriction may be beneficial for pregnant women to reduce weight gain (without weight loss) and reduce perinatal risks for both the mother and child.[9][10] For overweight or obese individuals, calorie restriction may improve health through weight loss, although a gradual weight regain of 1–2 kg (2.2–4.4 lb) per year may occur.[2][4]

The term "calorie restriction" as used in the study of aging refers to dietary regimens that reduce calorie intake without incurring malnutrition.[11] If a restricted diet is not designed to include essential nutrients, malnutrition may result in serious deleterious effects, as shown in the Minnesota Starvation Experiment.[12] This study was conducted during World War II on a group of lean men, who restricted their calorie intake by 45%[13] for six months and composed roughly 77% of their diet with carbohydrates.[12] As expected, this malnutrition resulted in metabolic adaptations, such as decreased body fat, improved lipid profile, and decreased resting heart rate. The experiment also caused negative effects, such as anemia, edema, muscle wasting, weakness, dizziness, irritability, lethargy, and depression.[12]

Typical low-calorie diets may not supply sufficient nutrient intake that is typically included in a calorie restriction diet.[14][15][16]

People losing weight during calorie restriction risk developing side effects, such as cold sensitivity, menstrual irregularities, infertility, or hormonal changes.[17]

Decreasing caloric intake by 20-30%, while fulfilling nutrient requirements, has been found to remedy diseases of aging, including cancer, cardiovascular disease, dementia, and diabetes in humans, and result in an average loss of 7.9 kilograms (17 lb) in body weight, but because of the long lifespan of humans, evidence that caloric restriction could prevent age-related disease in humans is still emerging.[18][19]

A calorie restriction study started in 1987 by the National Institute on Aging showed that calorie restriction did not extend years of life or reduce age-related deaths in non-obese rhesus macaques.[20] It did improve certain measures of health, however.[21] These results were publicized as being different from the Wisconsin rhesus macaque calorie restriction study, which also started in 1987 and showed an increase in the lifespan of rhesus macaques following calorie restriction.[20]

In a 2017 report on rhesus monkeys, caloric restriction in the presence of adequate nutrition was effective in delaying the effects of aging.[22][23] Older age of onset, female sex, lower body weight and fat mass, reduced food intake, diet quality, and lower fasting blood glucose levels were factors associated with fewer disorders of aging and with improved survival rates.[22] Specifically, reduced food intake was beneficial in adult and older primates, but not in younger monkeys.[22] The study indicated that caloric restriction provided health benefits with fewer age-related disorders in elderly monkeys and, because rhesus monkeys are genetically similar to humans, the benefits and mechanisms of caloric restriction may apply to human health during aging.[24][25]

According to scientific reviews, accumulating data suggests dietary restriction (DR) – mainly intermittent fasting and caloric restriction – results in many of the same beneficial changes in adult humans as in studied organisms, potentially increasing health- and lifespan beyond[26] the benefits of healthy body weight.[26][27] Which protocols of and combinations (e.g. see caloric restriction mimetic and AMPK) with DR are effective or most effective in humans is largely unknown and is being actively researched. A geroscience field of "precision nutrigeroscience" is proposed that also considers the potential need for adjustments of nutritional interventions per individual (e.g. due to differences in genetics and age).[27] The mechanisms of these effects include autophagy and a decline in inflammaging.[26] Intermittent fasting refers to periods with intervals during which no food but only e.g. water and tea/coffee are ingested – such as a period of daily time-restricted eating with a window of 8 to 12 hours for any caloric intake – and could be combined with overall caloric restriction and variants of the Mediterranean diet which usually has benefits of long-term cardiovascular health and longevity.[28]

Calorie restriction preserves muscle tissue in nonhuman primates[29][30] and rodents.[31][32] Mechanisms include reduced muscle cell apoptosis and inflammation;[31] protection against[32] or adaptation to[29] age-related mitochondrial abnormalities; and preserved muscle stem cell function.[33] Muscle tissue grows when stimulated, so it has been suggested that the calorie-restricted test animals exercised more than their companions on higher calories, perhaps because animals enter a foraging state during calorie restriction. However, studies show that overall activity levels are no higher in calorie restriction than ad libitum animals in youth.[34] Laboratory rodents placed on a calorie restriction diet tend to exhibit increased activity levels (particularly when provided with exercise equipment) at feeding time. Monkeys undergoing calorie restriction also appear more restless immediately before and after meals.[35]

Preliminary research indicates that sirtuins are activated by fasting and serve as "energy sensors" during metabolism.[36] Sirtuins, specifically Sir2 (found in yeast) have been implicated in the aging of yeast,[37] and are a class of highly conserved, NAD⁺-dependent histone deacetylase enzymes.[38] Sir2 homologs have been identified in a wide range of organisms from bacteria to humans.[37][39]

Some research has pointed toward hormesis as an explanation for the benefits of caloric restriction, representing beneficial actions linked to a low-intensity biological stressor such as reduced calorie intake.[40] As a potential role for caloric restriction, the diet imposes a low-intensity biological stress on the organism, eliciting a defensive response that may help protect it against the disorders of aging.[41] In other words, caloric restriction places the organism in a defensive state so that it can survive adversity.[40]

As of 2019, current clinical guidelines recommend that hospitals ensure that the patients get fed with 80–100% of energy expenditure, the normocaloric feeding. A systematic review investigated whether people in hospitals' intensive care units have different outcomes with normocaloric feeding or hypocaloric feeding, and found no difference.[42] However, a comment criticized the inadequate control of protein intake, and raised concerns that hypocaloric feeding safety should be further assessed with underweight critically ill people.[43]