The longevity diet's premise is seductively simple: cutting your calorie intake well below your usual diet will add years to your life.
New research published on Wednesday, however, shows the extreme, emaciating diet doesn't increase lifespan in rhesus monkeys, the closest human relatives to try it in a rigorous, long-running study. While caveats remain, outside experts regarded the findings as definitive, particularly when combined with those from a similar study.
"If there's a way to manipulate the human diet to let us live longer, we haven't figured it out yet and it may not exist," said biologist Steven Austad of the University of Texas Health Science Center's Barshop Institute for Longevity and Aging Studies, who wrote an analysis of the study in Nature.
Since 1934, research has shown that lab rats, mice, yeast, fruit flies and round worms fed 10 percent to 40 percent fewer calories than their free-eating peers lived some 30 percent longer. In some studies, they lived twice as long.
Such findings have spawned a growing community of believers who seek better health and longer life in calorie-restricted (CR)diets, as promised in the 2005 book "The Longevity Diet," including 5,000 members of the CR Society International. The research has also prompted companies like Procter & Gamble and Nu Skin Enterprises to develop drugs to mimic the effects of calorie restriction.
The new study, from the National Institute on Aging, part of the U.S. National Institutes of Health, suggests a surprising disconnect between health and lifespan. It found that most of the 57 calorie-restricted monkeys had healthier hearts and immune systems and lower rates of diabetes, cancer or other ills than the 64 control monkeys. But there was no longevity pay-off.
"You can argue that the calorie-restricted animals are healthier," said Austad. "They have better cholesterol profiles, less muscle loss, less disease. But it didn't translate into greater longevity. What we learn from this is you can un-link health and longevity."
Younger immune systems, less heart disease
The NIA study, launched in 1987, is one of two investigating whether eating just 70 percent of the calories in a standard lab diet extends life in a long-lived primate. The Wisconsin National Primate Research Center's study, begun in 1989, also uses rhesus monkeys, whose physiology, genetics and median lifespan (27 years) are closer to humans than are the rodents in earlier calorie-restriction research.
Initial results were promising. In 2006 the NIA group reported that calorie-restricted monkeys had younger-seeming immune systems. Wisconsin reported that after 20 years of eating like birds, the monkeys were less likely to get heart disease, diabetes, cancer and other diseases of aging.
They also lived longer: By 2009, 80 percent of the free-eating Wisconsin monkeys had died of age-related illness, but only 50 percent of calorie-restricted monkeys had. Those findings, the scientists reported at the time, showed "that CR slows aging in a primate species."
Experts on aging have since waited for the NIA to weigh in, and the verdict was a shock: "The calorie-restricted monkeys lived no longer than the other monkeys," NIA's Julie Mattison, who helped lead the study, told Reuters.
The oldest animals in each group had the same incidence of tumors, heart disease and general deterioration. While the abstemious monkeys had some improved health markers such as cholesterol and triglyceride levels, Mattison said, "that didn't translate into better survival."
The NIA study showed that even monkeys starting calorie restriction early in life, from 1 to 14 years of age, had no lifespan edge over their gourmand peers. With 19 of the 40 monkeys whose eating was restricted starting in youth still alive, the NIA scientists calculated, the chance that they will outlive free-eating monkeys is less than one-tenth of 1 percent.
Perhaps more surprising, health markers were often worse in monkeys that began calorie restriction as young adults than older ones, the opposite of what scientists expected. And more of the animals that started calorie restriction when young died of causes unrelated to aging than did their free-eating peers. "There may be something about calorie restriction that makes animals more susceptible to death from other causes," said Austad.
A killer control group
Scientists offered several explanations for why the NIA's findings differ from more encouraging results in the Wisconsin study.
The Wisconsin monkeys' diet had seven times the table sugar (28 percent of calories, like Americans' diets) as the NIA's (4 percent). The Wisconsin control monkeys also ate however much they wished; the NIA control monkeys ate a fixed amount and, as a result, weighed less.
That suggests the longevity diet didn't really extend lifespan in the Wisconsin monkeys: It only seemed to because the control monkeys ate themselves into an early grave.
"Comparing calorie restriction to what you think is a normal diet but is in fact an unhealthy diet with too much food and too much sucrose can trip you up," said Austad. "If you keep your control animals to a healthy weight, as the NIA did, a diet that produces extreme emaciation has no further effect on longevity."
Most problematic, many of the Wisconsin study's calorie-restricted monkeys died of causes unrelated to aging, such as anesthesia used in some experiments and gastrointestinal bloat.
Only by not counting those deaths did the Wisconsin scientists find a statistically significant longevity effect, said Wisconsin's Ricki Colman, a leader of that study.
It is too soon to know how the NIA study will affect the development of drugs aimed at replicating calorie restriction's benefits without the hunger pangs. They include mannoheptulose, a compound derived from unripe avocados that "tricks cells into thinking they ate less," said George Roth, CEO of privately held GeroScience.
Roth helped launch the NIA study and is a co-author of the new paper. He believes there is still good evidence in favor of calorie restriction, including the Wisconsin study's findings. GeroScience is working with Procter & Gamble to use mannoheptulose as a lifespan-increasing supplement for dogs and hopes to raise money for a clinical trial in people.
LifeGen Technologies, co-founded by a leader of the Wisconsin study, is testing a nutraceutical that mimicked some genetic changes seen with calorie restriction in rodents. The company was bought by Nu Skin Enterprises in 2011.
The NIA and Wisconsin teams are continuing to collect data to see if calorie restriction suddenly proves more beneficial. "But what I take away from these studies is that extreme emaciation may not be the correct paradigm," said University of Texas biologist Austad. "If I were them (companies or scientists banking on this), I'd be worried."