Caloric restriction (CR), or calorie restriction, is a dietary regimen that restricts calorie intake, where the baseline for the restriction varies, usually being the previous, unrestricted, intake of the subjects. Calorie restriction without malnutrition has been shown to improve age-related health and to slow the aging process in a wide range of animals and some fungi.
CR is one of the few dietary interventions shown to increase both median and maximum lifespan in a variety of species, among them yeast, fish, rodents and dogs. There are ongoing studies on whether CR works in nonhuman primates, on its effects on human health, and on the metabolic parameters associated with CR in other species. The results so far are positive, but the studies are not yet complete, due to the long lifespan of the species. Among the current studies, one at UCSF, with Nobel laureate Elizabeth Blackburn as part of the investigation team, is looking at long-term CR practitioners, including the psychological factors that keep them motivated to stay on a CR diet.
Calorie restriction is a feature of several dietary regimens, including the Okinawa diet  and the CRON-diet.
In 1934, Mary Crowell and Clive McCay of Cornell University observed that laboratory rats fed a severely reduced calorie diet while maintaining micronutrient levels resulted in life spans of up to twice as long as otherwise expected. These findings were explored in detail by a series of experiments with mice conducted by Roy Walford and his student Richard Weindruch. In 1986, Weindruch reported that restricting the calorie intake of laboratory mice proportionally increased their life span compared to a group of mice with a normal diet. The calorie-restricted mice also maintained youthful appearances and activity levels longer and showed delays in age-related diseases. The results of the many experiments by Walford and Weindruch were summarized in their book The Retardation of Aging and Disease by Dietary Restriction (1988) (ISBN 0-398-05496-7).
The findings have since been accepted and generalized to a range of other animals. Researchers are investigating the possibility of parallel physiological links in humans. In the meantime, many people have independently adopted the practice of calorie restriction in some form.
 Effects on humans
 Positive effects
 Cardiovascular risks reduced
Some research has shown CR to reduce atherosclerosis risk factors.
A small study of long-term CR practitioners studied the effects of a diet with 10-25% less calorie intake than the average "Western" diet. Mean Body mass index (BMI) was 19.6 in the CR group; the matched group BMI was 25.9, comparable to the BMI for middle-aged people in the US.
The mean BMI in the CR group dropped from 24 (range of 19.4 to 29.6) to 19.5 (range of 16.5 to 22.8) over periods of 3–15 years. Nearly all the decrease in both BMI and cardiovascular risk factors occurred in the first year. Adjusting for age, the average total cholesterol and LDL (bad) cholesterol levels in the CR group were below those seen in all but the lowest 10% of the population. The average HDL (good) cholesterol levels were in the 85th to 90th percentile range for normal middle-aged US men.
The calorie-restricted group also fared much better than the control group in terms of average blood pressure (100/60 vs. 130/80 mm Hg), fasting glucose, fasting insulin (65% reduction), body mass index (19.6 ± 1.9 vs. 25.9 ± 3.2 kg/m2), body fat percentage (8.7% ± 7% vs. 24% ± 8%), C-reactive protein, carotid IMT (40% reduction), and platelet-derived growth factor AB.
The CR group had triglyceride levels as low as the lowest 5% of Americans in their 20s. (The CR group age-range was 35-82.) Systolic and diastolic blood pressure levels in the CR group were about 100/60, a level more typical of 10-year-olds. Fasting plasma insulin concentration was 65% lower. Fasting plasma glucose concentration was also lower.
The principal investigator in this study noted an apparent lower rate of cardiovascular aging, with arteriosclerosis progress indicators particularly slowed.
The comparison group's statistics aligned approximately with the US national average on the dimensions considered. Fasting plasma insulin levels and fasting plasma glucose levels are used as tests to predict diabetes.
The American CALERIE study began in 2007 and investigates the effects of a 25% reduction in calorie intake on healthy adults over a period of two years. The effect of CR on IGF-1 serum levels seen in rodents appears to only manifest in humans when protein intake is not much higher than the Recommended Dietary Allowance
 Improved memory
A 2009 research paper showed that a calorie restricted diet can improve memory in normal to overweight elderly. The diet also resulted in decreased insulin levels and reduced signs of inflammation. Scientists believe that memory improvement in this experiment was caused by the lower insulin levels, because high insulin levels are usually associated with lower memory and cognitive function. However, that relation seems to be age-specific since another study, when analyzing people older than 65, those who were underweight had a higher dementia risk than normal or overweight people.
 Health concerns
Although studies show that calorie restriction can improve longevity and health in model organisms, and studies in humans demonstrate reduced risk factors for major diseases, the long-term effects on humans are still unknown.
 Musculoskeletal losses
In addition to the benefits, short-term studies in humans report loss of muscle mass and muscle strength, and reduced bone mineral density.
Several studies revealed that dieters who restricted calories for 12 months had lower muscle mass and a reduced capacity to perform exercise compared with those who lost similar amounts of weight from exercise alone. Another study concluded that those who lost weight with the help of the CR diets are more prone to develop a loss of bone at the level of hip and spine, the area most at risk for bone fractures. Some specialists say that minor mineral losses can be prevented with supplements of vitamin D and calcium.
 Low BMI, high mortality: a non-issue?
CR diets typically lead to reduced body weight, and in some studies, low body weight has been associated with increased mortality, particularly in late middle-aged or elderly subjects. One of the more famous of such studies linked a BMI lower than 18, for women, with increased mortality from noncancer, non?cardiovascular disease causes. The authors attempted to adjust for confounding factors (cigarette smoking, failure to exclude pre-existing disease); others argued that the adjustments were inadequate.
"... epidemiologists from the ACS (American Cancer Society), American Heart Association, Harvard School of Public Health, and other organizations raised specific methodologic questions about the recent Centers for Disease Control and Prevention (CDC) study and presented analyses of other data sets. The main concern ... is that it did not adequately account for weight loss from serious illnesses such as cancer and heart disease ... [and] failed to account adequately for the effect of smoking on weight ... As a result, the Flegal study underestimated the risks from obesity and overestimated the risks of leanness."
While low body weight in the elderly can be caused by conditions associated with aging (such as cancer, chronic obstructive pulmonary disorder, or depression) or of the cachexia (wasting syndrome) and sarcopenia (loss of muscle mass, structure, and function),  the results of a large epidemiological study published in the fall of 2011 show that the association between BMI<21 (under 140lbs for a 5'9" tall individual) and increased mortality persists even when confounders like age, smoking, and disease are carefully controlled for.  To date, there are no human studies that have demonstrated a positive or even neutral association between low body weight and longevity.
In any case, epidemiological studies of body weight are not about CR as used in anti-aging studies; they are not about calorie intake to begin with, as body weight is influenced by many factors other than energy intake. Moreover, "the quality of the diets consumed by the low-BMI individuals are difficult to assess, and may lack nutrients important to longevity." Typical low-calorie diets rarely provide the high nutrient intakes that are a necessary feature of an anti-aging calorie restriction diet. As well, "The lower-weight individuals in the studies are not CR because their caloric intake reflects their individual ad libitum set-points, and not a reduction from that set-point."
 Triggering eating disorders
Concerns are sometimes raised that CR can make people feel hungry all the time and may lead to obsessing about food, causing eating disorders. However, a controlled study of human CR found no increase in eating disorder symptoms or other harmful psychological effects, in line with extensive earlier research. In those who already suffer from a binge-eating disorder, calorie restriction can precipitate an episode of binge eating, but it does not seem to pose any such risk otherwise.
 Not for the young, or those with low body fat
The effect of these diets on people who want to lose weight is controversial. Although calorie restriction may provide quick weight loss, several studies have shown that the body adjusts to the new diet in about six months. Researchers argue that people who have little body fat should not use this method of losing weight but rather should exercise more because calorie restriction in this case can be harmful. The reason for this is that after the body's fat reserves have been burned for energy, the proteins within muscle tissue will be consumed. In severe cases where individuals do not acknowledge the dangers they are exposing themselves to, they may suffer serious loss of the muscle mass.
Especially in children, adolescents and young adults (under approximately 21), calorie restriction is not advised because this type of diet may interfere with the natural physical growth, as it has been observed in laboratory animals. In addition, mental development and physical changes to the brain take place in late adolescence and early adulthood that could be negatively affected by calorie restriction. Pregnant women are recommended not to try losing weight with this method. It has been shown that a low BMI is a risk factor in pregnancy as it may result in ovulatory dysfunction (infertility), and mothers who are underweight are more prone to preterm delivery.
Individuals trying lose weight on a CR diet of less than 1,500 calories a day need to be monitored by a specialist in order to prevent potential side effects.
 Miscellaneous concerns
It has also been noted that people losing weight on such diets risk developing cold sensitivity, menstrual irregularities and even infertility and hormonal changes.
Moreover, calorie restriction has been reported in mice to hinder their ability to fight infection, and some evidence suggests that in patients with amyotrophic lateral sclerosis calorie restriction accelerates the onset of the disease.
Excessive calorie restriction may result in starvation, unless metabolism is also slowed by some means. CR should not be confused with anorexia nervosa or other eating disorders. If such a pattern is repeated for prolonged periods, the body may burn lean tissue (including but not limited to muscle and collagen) along with its remaining fat reserves. The combination of starvation and the associated lethargy and decreased physical activity can result in muscular atrophy, reducing quality of life.
Beyond using lean tissue as energy source, the presence of catabolic hormones, such as cortisol, and lack of anabolic ones, such as insulin, disrupts protein synthesis, amino acid uptake and weakens the immune system. Commenting on a study where CR showed generally positive effects, one researcher warned that "[i]t is possible that even moderate calorie restriction may be harmful in specific patient populations, such as lean persons who have minimal amounts of body fat."
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