Calorie Restriction: Good for Humans

Results from the most recent two year CALERIE trial of human calorie restriction were published earlier this year, but the associated publicity materials have only just now made it to the presses.

Calorie restriction, or to be more precise calorie restriction with hopefully optimal but at least adequate nutrition, is the practice of reducing calorie intake while maintaining a suitable level of micronutrients in the diet. Reducing recommended dietary intake by about 25% is a common target, as was the case in this study. That would mean somewhere around 1500 calories per day for the mythical completely average individual. It is just about impossible to achieve this goal without structuring a very healthy diet that is comparatively low in processed sugars and the like, which is an added bonus. When you are settled into a healthy calorie restricted diet, hunger is nowhere near the bugbear that people like to make it out to be, while the short term benefits are fairly obvious and arrive quickly, including lowered chronic inflammation, reduced visceral fat tissue, lower blood pressure, less sleep needed, and so forth.

The short term benefits of a calorie restricted metabolism to health have been established and measured extensively over the past few decades. The evidence shows they are altered in much the same way in people as in mice. Unlike mice, however, people do not live 40% longer when calorie restricted - we would have noticed by now. There have been religious orders across the course of history where this would have been the case, and in our time many members of the Calorie Restriction Society have been practicing calorie restriction with optimal nutrition for somewhat longer than the CALERIE program has existed. There is a good evolutionary explanation for the difference in the calorie restriction response when comparing short-lived and long-lived species: famines are seasonal, and a season is a large fraction of a mouse lifespan but a small fraction of a human life span. Thus only the mouse evolves a relatively large plasticity of life span in response to food scarcity.

But from a mechanistic point of view - how exactly does this all work under the hood, what are cells and tissues actually doing to extend life - there is still a long way to go if you are looking for the complete explanation. The challenge here is that near every measure and aspect of cellular biochemistry changes in response to nutrient availability. Aging is slowed, but why, exactly? Which of the scores of likely candidates are contributing, and to what degree? Picking apart cause and effect has been the subject of decades of ever-expanding research so far, and looks set to take decades more yet. It is a fair wager to suggest that we will likely see the first crude rejuvenation therapies based on repair of cellular damage before the emergence of a comprehensive accounting of the calorie restriction response and its effects on aging.

Don't let that stop you from giving it a try, however. Like exercise, calorie restriction is backed by the gold standard of scientific evidence when it comes to things you can do today that are expected to have a noticeable positive effect on your present and future health. The interesting take in the commentary here, from a perspective of having read the paper a few months back, is that researchers expected to see more in the way of benefits than they did. That might be explained by the lesser degree of calorie restriction obtained versus that aimed for, which itself was smaller than that of some animal studies:

NIH study finds calorie restriction lowers some risk factors for age-related diseases

Results from a two-year clinical trial show calorie restriction in normal-weight and moderately overweight people failed to have some metabolic effects found in laboratory animal studies. However, researchers found calorie restriction modified risk factors for age-related diseases and influenced indicators associated with longer life span, such as blood pressure, cholesterol, and insulin resistance. "The study found that this calorie restriction intervention did not produce significant effects on the pre-specified primary metabolic endpoints, but it did modify several risk factors for age-related diseases. It is encouraging to find positive effects when we test interventions that might affect diseases and declines associated with advancing age. However, we need to learn much more about the health consequences of this type of intervention in healthy people before considering dietary recommendations. In the meantime, we do know that exercise and maintaining a healthy weight and diet can contribute to healthy aging."

CALERIE was a two-year randomized controlled trial in 218 young and middle-aged healthy normal-weight and moderately overweight men and women to measure these outcomes in a CR group, compared with a control group who maintained their regular diets. The calorie restriction participants were given weight targets of 15.5 percent weight loss in the first year, followed by weight stability over the second year. This target was the weight loss expected to be achieved by reducing calorie intake by 25 percent below one's regular intake at the start of the study. The calorie restriction group lost an average of 10 percent of their body weight in the first year, and maintained this weight over the second year. Though weight loss fell short of the target, it is the largest sustained weight loss reported in any dietary trial in non-obese people. The participants achieved substantially less calorie restriction (12 percent) than the trial's 25-percent goal, but maintained calorie restriction over the entire two-year period. The control group's weight and calorie intake were stable over the period.

The study was designed to test the effects of calorie restriction on resting metabolic rate (after adjusting for weight loss) and body temperature, which are diminished in many laboratory animal studies and have been proposed to contribute to its effects on longevity. The study found a temporary effect on resting metabolic rate, which was not significant at the end of the study, and no effect on body temperature. Although the expected metabolic effects were not found, calorie restriction significantly lowered several predictors of cardiovascular disease compared to the control group, decreasing average blood pressure by 4 percent and total cholesterol by 6 percent. Levels of HDL ("good") cholesterol were increased. Calorie restriction caused a 47-percent reduction in levels of C-reactive protein, an inflammatory factor linked to cardiovascular disease. It also markedly decreased insulin resistance, which is an indicator of diabetes risk. T3, a marker of thyroid hormone activity, decreased in the calorie restriction group by more than 20 percent, while remaining within the normal range. This is of interest since some studies suggest that lower thyroid activity may be associated with longer life span.

A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity

To determine CR's feasibility, safety, and effects on predictors of longevity, disease risk factors, and quality of life in nonobese humans aged 21-51 years, 218 persons were randomized to a 2-year intervention designed to achieve 25% CR or to AL diet. We conclude that sustained CR is feasible in nonobese humans. The effects of the achieved CR on correlates of human survival and disease risk factors suggest potential benefits for aging-related outcomes that could be elucidated by further human studies.
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