Decades ago, in the
1930s, researchers working with lab rats made an interesting discovery. Animals
that had been deprived of food seemed to live longer than rodents that were fed
to satisfaction, raising the intriguing idea that maybe near-starvation was a
good, rather than bad thing, for health.
Follow up studies,
particularly in yeast, confirmed the trend and some forward-thinking scientists
even began restricting their caloric intake in the hopes of seeing some extra
years.
Research
Calorie restriction (CR), or caloric restriction, is a
dietary regimen that is based on low calorie intake. "Low" can be
defined relative to the subject's previous intake before intentionally
restricting calories, or relative to an average person of similar body type. Based
on the multiple studies, calorie restriction without malnutrition has been
shown to work in a variety of species, among them yeast, fish, rodents and dogs
to decelerate the biological aging process, resulting in longer maintenance of
youthful health and an increase in both median and maximum lifespan. However,
it was found that the life-extending effect of calorie restriction could not be
considered universal. Wild mice, for instance, do not live longer when on a
calorie restricted diet.
In spite of the numerous media releases on CR being the
promising approach to the life extension, in humans, the long-term health
effects of moderate CR with sufficient nutrient are still unknown.
Two main lifespan studies have been performed, involving
nonhuman primates (rhesus monkeys). One, which begun in 1987 by the National
Institute on Aging, published interim results in August 2012, indicating that
CR confers health benefits in these animals, but did not demonstrate increased
median lifespan; maximum lifespan data are not yet available, as the study is
still ongoing. A second study by the University of Wisconsin, beginning in 1989,
issued preliminary lifespan results in 2009, and final results in 2014.
The results did not bring the vindication calorie
restriction enthusiasts had anticipated. It turns out the skinny monkeys did
not live any longer than those kept at more normal weights. Some lab test
results improved, but only in monkeys put on the diet when they were old. The
causes of death — cancer, heart disease — were the same in both the underfed
and the normally fed monkeys.
Lab test results showed lower levels of cholesterol and
blood sugar in the male monkeys that started eating 30 percent fewer calories
in old age, but not in the females. Males and females that were put on the diet
when they were old had lower levels of triglycerides, which are linked to heart
disease risk. Monkeys put on the diet when they were young or middle-aged did
not get the same benefits, though they had less cancer. But the bottom line was
that the monkeys that ate less did not live any longer than those that ate
normally.
Rafael de Cabo, lead author of the diet study, published
online on Wednesday in the journal Nature, said he was surprised and
disappointed that the underfed monkeys did not live longer. Like many other
researchers on aging, he had expected an outcome similar to that of a 2009
study from the University of Wisconsin that concluded that caloric restriction
did extend monkeys’ life spans.
Now, with the new study, researchers are asking why the
University of Wisconsin study found an effect on life span and the National
Institute on Aging study did not.
There were several differences between the studies that
some have pointed to as possible explanations.
The composition of the food given to the monkeys in the
Wisconsin study was different from that in the aging institute’s study.
The University of Wisconsin’s control monkeys were
allowed to eat as much as they wanted and were fatter than those in the aging
institute’s study, which were fed in amounts that were considered enough to
maintain a healthy weight but were not unlimited.
The animals in the Wisconsin study were from India. Those
in the aging institute’s study were from India and China, and so were more
genetically diverse.
“These results suggest the complexity of how calorie restriction
may work in the body," says NIA Director Dr. Richard J. Hodes. “Calorie
restriction's effects likely depend on a variety of factors, including
environment, nutritional components and genetics.”
Mechanisms of CR
Although the supposed positive effect of CR for human
health was discovered in the first half of last century, its mechanisms are
largely unknown. Many hypotheses have been proposed, but none are conclusive.
Briefly, some argue that the diminished energy intake forces an optimization of
the metabolism. Since CR also delays development in mice, others say it slows
down the entire genetic program, indirectly affecting aging. CR's effects on
several forms of cellular damage have been reported but the results are
inconclusive as far as the underlying mechanism is concerned. Interestingly,
there have been experiments in mice that seem to mimic CR by disrupting certain
hormonal levels. Basically, by diminishing certain hormones or their receptors
scientists observed changes in animals similar to those observed under CR, as
described elsewhere in more detail. Therefore, hormonal changes may play a role
in CR. At present, it is safe to say that we do not know the mechanisms by
which CR may (or may not) extend lifespan.
Evolutionary Roots
Caloric restriction may have its evolutionary roots as a
survival mechanism, allowing species to survive on scraps when food is scarce
in order to continue to reproduce. However, that restriction only has lasting
positive effects if the overall diet is a balanced one, which may not always be
the case in conditions of famine. (That also explains why anorexia is so
unhealthy: people who starve themselves
become malnourished). It is possible the strategy developed as a way to protect
species from consuming toxic plants or foods, when it was not always obvious
which sources were verboten.
Negative Effects
of CR
Overeating is not healthy, that is clear, but calorie
restriction might not be healthy as well. Medical professionals warn that malnutrition
may result in serious deleterious effects, as it has been shown in the Minnesota
Starvation Experiment. This study was conducted during World War II on a group
of lean men, who restricted their calorie intake by 45% for 6 months, and
composed roughly 90% of their diet with carbohydrates. As expected, this
malnutrition resulted in many positive metabolic adaptations (e.g. decreased
body fat, blood pressure, improved lipid profile, low serum T3 concentration,
and decreased resting heart rate and whole-body resting energy expenditure),
but also caused a wide range of negative effects, such as anemia, lower
extremity edema, muscle wasting, weakness, neurological deficits, dizziness,
irritability, lethargy, and depression.
Musculoskeletal
losses
Short-term studies in humans report loss of muscle mass
and strength and reduced bone mineral density. The authors of a 2007 review of
the CR literature 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."
Low BMI, high
mortality
CR diets typically lead to reduced body weight, yet
reduced weight can come from other causes and is not in itself necessarily
healthy. In some studies, low body weight has been associated with increased
mortality, particularly in late middle-aged or elderly subjects. Low body
weight in the elderly can be caused by pathological conditions, associated with
aging and predisposing to higher mortality (such as cancer, chronic obstructive
pulmonary disorder, or depression) or of the cachexia (wasting syndrome) and
sarcopenia (loss of muscle mass, structure, and function). One of the more
famous of such studies linked a body mass index (BMI) lower than 18 in 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.
Triggering eating
disorders
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.
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