Does Calorie Restriction Extend Human Life?

Calorie restriction (CR), a technique that entails significantly reducing the number of calories
consumed while simultaneously ensuring the intake of an optimal amount of nutrients, has been demonstrated to extend the life span of almost every species of animal in which it has been tested. But will it extend human life?

Historical Case Study

The earliest record of successful human calorie restriction was that documented by Luigi Cornaro, a Venetian nobleman born in 1467. After finding himself in ill health after the age of 35 because of his excessive eating and drinking, he took the advice of his physicians and began restricting his diet to the equivalent of 12 ounces of food and 14 ounces of wine per day. His writings on the subject, which have been translated and published under several titles including Discourses on the Temperate Life, described his successful regimen at four successive ages.

“Being arrived at my ninety-fifth year, God be praised, and still finding myself sound and hearty, content and cheerful, I never cease to thank the Divine Majesty for so great a blessing, considering the usual condition of old men,” Cornaro wrote in his fourth and final discourse. “These scarcely ever attain the age of seventy, without losing health and spirits, and growing melancholy and peevish. Moreover, when I remember how weak and sickly I was between the ages of thirty and forty, and how from the first, I never had what is called a strong constitution; I say, when I remember these things, I have surely abundant cause for gratitude, and though I know I cannot live many years longer, the thought of death gives me no uneasiness; I, moreover, firmly believe that I shall attain to the age of one hundred years.”1

CR Research in the 1990’s

Fast forward to 1991. A closed, self-supporting ecological system in the Arizona desert known as Biosphere 2 was the site of a study (supported in part by the National Institutes of Health and the Life Extension Foundation) involving four men and four women whose challenges in food cultivation necessitated a calorie restricted diet.2 One of those men was the famed calorie restriction researcher and advocate, gerontologist Roy L. Walford, MD.

Calorie intake averaged 1,784 for the first six months and increased to just 2,000 calories for the remainder of the two-year experiment. This resulted in a decline in body mass index of 19% among the male participants and 13% among the women.

During the course of the study, blood and urine were collected and analyzed every eight weeks. In comparison with values measured before entry into the Biosphere, some remarkable changes were observed. For example, blood glucose levels decreased by an average of 21%, insulin by 42%, and cholesterol by 30%. In addition, systolic blood pressure decreased by 25% and diastolic blood pressure by 22%. “We conclude that healthy nonobese humans on a low-calorie, nutrient-dense diet show physiologic, hematologic, hormonal, and biochemical changes resembling those of rodents and monkeys on such diets,” reported Dr. Walford and colleagues in their summary of the findings. “With regard to the health of humans on such a diet, we observed that despite the selective restriction in calories and marked weight loss, all crew members remained in excellent health and sustained a high level of physical and mental activity throughout the entire 2 years.”

While the findings of the Biosphere 2 study indicated beneficial effects for calorie restriction in humans, the two-year investigation was far from the type of decades-long longitudinal study needed to confirm the regimen’s effects on life span. Here we have a conundrum since, to accomplish this, one would need to design a study that would ideally involve life-long calorie restriction. The challenges of this type of study would be significant. Researchers conducting the investigation would need to be replaced as they retired or died. And how likely would it be that one could find human subjects willing to undergo a lifetime of restricted calories?

Larger and Long-Term Clinical Trials

Turns out, such a group already exists. CR Society International, founded by Roy Walford, Lisa Walford, and Brian Delaney in 1994, consists of several thousand men and women who practice calorie restriction in hope of retarding aging. As of this writing (2018), the group is still going strong. Research reported in the Proceedings of the National Academy of Sciences in 2004, conducted by gerontologist Luigi Fontana and colleagues, documented findings from 18 CR Society members who had practiced calorie restriction for six years.3 In addition to a leaner body mass and less body fat, the group had lower blood pressure, total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, fasting glucose, fasting insulin, C-reactive protein (CRP, a marker of inflammation) and other factors than a comparison group. Carotid artery intima media thickness, a measure of atherosclerosis, was approximately 40% less among those who practiced calorie restriction.

In the Comprehensive Assessment of Long term Effects of Reducing Intake of Energy (CALERIE) two-year clinical trial, the effects of a 25% reduction in calorie intake undertaken by 143 volunteers was compared to those experienced by 75 control subjects who were allowed to consume as much food as they wanted. In several analyses of the data, researchers (including Dr. Fontana) uncovered a number of benefits in association with calorie restriction, including a reduction in whole-body oxidative stress,4 and less whole-body and regional adiposity.5

“Accumulating data from observational and randomized clinical trials indicate that CR in humans results in some of the same metabolic and molecular adaptations that have been shown to improve health and retard the accumulation of molecular damage in animal models of longevity,” write Dr. Fontana and colleagues in a 2017 article titled “Calorie restriction in humans: An update.”6 “In particular, moderate CR in humans ameliorates multiple metabolic and hormonal factors that are implicated in the pathogenesis of type 2 diabetes, cardiovascular diseases, and cancer, the leading causes of morbidity, disability and mortality.”

Calorie Restriction Mimetics

For those who lack the willpower to restrict the amount of food consumed on a daily basis, calorie restriction mimetics—dietary compounds whose effects on gene expression mimic those of calorie restriction—may be a viable alternative. Compounds identified so far include resveratrol, pterostilbene, fisetin and grape seed extract.

The Bottom Line

Despite the challenges involved in assessing the benefits of calorie restriction in humans, researchers have persisted in their attempts to evaluate the regimen’s effects during the past couple of decades. Future research may find that CR practitioners are indeed biologically, if not chronologically, far younger than than those who consume much more food and calories and can look forward to many more years of good health and happiness.

References

  1. Cornaro L. Discourses on the Temperate Life. Benjamin White, London: 1779.
  2. Walford RL et al. J Gerontol Series A. 2002 June 1;57(6):B211-B224.
  3. Fontana L et al. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6659-63.
  4. Il'yasova D et al. Aging Cell. 2018 Apr;17(2).
  5. Das SK et al. Am J Clin Nutr. 2017 Apr;105(4):913-927.
  6. Most J et al. Ageing Res Rev. 2017 Oct;39:36-45.

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