CALERIE Study

But what happened after the study? In both the Minnesota Starvation Experiment and trials with US Army Rangers, subjects tended to regain their old weight quickly once they were freed from calorie restriction—and sometimes even more. The leaner they started, the more strongly their body seemed to drive them to overeat in order to put body fat back on. After the CALERIE study, by contrast, even though their metabolism was reduced by about 100 calories per day, two years after the end of the study the subjects maintained about 50 percent of the weight loss. They must have developed new eating habits and behaviors that allowed them to maintain their weight without signs of increased vulnerability to eating disorders. In fact, after prolonged calorie restriction, cravings for sweets and fatty foods can decrease.

A slowed metabolism, a “slowing of the pace of life,” is expected to contribute to longevity, and it could explain the reduction in oxidative stress throughout the body during the first year of calorie restriction. Even when you culture blood cells from people who practice calorie restriction, they become significantly more resistant to damage from free radicals, perhaps because the antioxidant activity of cellular enzymes doubles when bathed in calorie-restricted blood. In addition, two different biomarker algorithms for calculating “biological age” found that calorie restriction slows the rate of aging, apparently independently of the extent of weight loss. According to one estimate, the ad libitum control group aged at an average rate of 0.7 “years” per year and the calorie-restriction group by only 0.1 on average. By this algorithm (the Klemera-Doubal method), the calorie-restriction group seemed to hardly age at all.

The many facets of the physiological, psychological, and aging-related benefit attributed to this sustained, moderate (11.9-percent) calorie restriction must be interpreted with the caveat that the composition of the food changed along with the amount. A large part of the calorie restriction was achieved through reduced fat intake. The type of fat was not specified, but given the fact that the main sources of fat in the American diet are typically meat and dairy products, followed by desserts such as donuts, cookies, and cake, the reduction in fat could have brought an overall improvement in diet quality that would at least partly explain the measured effects. Aside from this caveat, the CALERIE study suggests that even “normal-weight” people should eat less if they want to improve their health and live longer.

Thinking Better with Fewer Calories

Studies observing more than five million men and women found that abdominal obesity in men and women over 65 is associated with an increased likelihood of developing cognitive impairment and dementia. In rodents, restricting calorie intake is considered one of the most effective dietary interventions for improving cognitive performance. But in humans? There appear to be no studies on calorie restriction in dementia, but there are about a dozen randomized controlled trials on the cognitive effects in those who are cognitively healthy or only mildly impaired.

While hardly any of the individual studies were able to demonstrate significant improvements, when all the studies were pooled together, reducing calorie intake did appear to confer a cognitive benefit. But most of the roughly 1000 subjects were obese, so this benefit is likely attributable more to the weight loss than to the calorie restriction itself. And it was relatively easy to achieve. When overweight, nearly obese older men and women (with a BMI of 29.9) were advised to reduce their calorie intake by 30 percent for three months, they achieved only a reduction of about 12 percent and lost about 2.5 kilograms, yet their verbal memory improved significantly.

Participants in the CALERIE intervention group achieved an average reduction of 12 percent. At the end of the two years, they had better working memory (short-term memory) than the randomized members of the control group. Interestingly, the cognitive improvement was linked primarily to the lower protein intake. This was examined directly in a study titled “Effect of diet on cognition and flight performance of pilots.” Pilots at a commercial airline were randomized, in sequence, to eat a high-carbohydrate, high-protein, high-fat, or normal diet for four days, and then their flight performance was assessed in a full-motion flight simulator. Compared with the other three diet types, the pilots’ flight performance suffered when they ate a lot of protein.

More stringent fasting seems to have rather mixed effects on cognition in the short term. Randomized subjects who had eaten nothing for a day felt more “mentally fatigued” than others who ate about 500 calories spread over the day, but on objective tests of cognitive performance they did equally well. Given the potential to be psychologically influenced, there was a randomized controlled double-blind study with 48-hour calorie deprivation. How do you conceal from someone whether they are eating or not? Subjects were given indistinguishable pastes that either contained virtually no calories or provided several thousand calories per day. Surprisingly, two days of near-zero calories had no effect on cognitive performance, activity, sleep, or mood in healthy young adults. From an evolutionary perspective, that makes sense. It is presumably a survival advantage to remain cognitively fit during times of food scarcity.

Possible Disadvantages of Calorie Restriction

Calorie restriction has been touted as a fountain of youth. The nearly universal benefit observed in the CALERIE study supports the potential advantages of moderate calorie restriction for health and longevity, but without the disadvantages seen with extreme restrictions: loss of libido, declines in physical strength and bone mass, menstrual disturbances, infertility, sensitivity to cold, slower wound healing, blood pressure that is too low, and psychological problems such as depression, emotional blunting, and irritability (not to mention walking around constantly hungry).

Two of the most dangerous problems—impaired wound healing and slower recovery from infections—may potentially be remedied by temporarily returning to unrestricted eating in the event of injury or illness. In dieting rats and mice, full wound-healing capacity was restored days or weeks after resuming full feeding, which, however, occurred before the animals were wounded. That may be useful for planned surgeries, but is probably largely irrelevant for unexpected injuries.