Eating less as a strategy to live longer only works for animals… and in the laboratory

Eating less makes you live longer, but only if you’re a laboratory animal. A review of scientific advances in caloric restriction showed its positive impact on metabolism. However, the vast majority of studies were done with rats, flies, worms and yeast. For ethical reasons and for duration, there are hardly any experiences with humans. There are, however, a number of natural experiments whose results are contradictory. Specialists warn of the risks of low-calorie diets and bet on a controlled, varied and balanced diet.

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In 1917, a group of American researchers discovered that starving rats lived for nearly three years, while the rest of the well-fed colony died before 24 months. More recent work has shown that, without going through malnutrition, mice and laboratory rats live between 20% and 50% longer than those who eat what they want. In other organisms, such as fruit flies, nematodes and yeasts, all invertebrates, the energy reduction extended their life two to three times. But human beings are not made of yeast.

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The review published in the journal Science highlights how, despite the amount of animal studies, “it is currently not possible to know whether calorie-restricted diets affect the biological aging of people. Unlike mice, it would be necessary to carry out controlled studies over many years to assess the long-term benefits for the longevity and health of humans.” Some experiments have been carried out with non-human primates that point to a delay in aging and, in particular, to a healthier old age.

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This research reviews three major groups of ketogenic diets, which seek to force fat burning, different forms of intermittent fasting or variations in restriction, for example, of proteins or of some amino acids. Although each type of diet works differently, they share an impact on the process and speed of cellular metabolism.

Nutritionist Julio Basulto recalls that “it is not easy to transfer the possible benefits to a mouse to humans.” A first hurdle is that caloric restriction leads to weight loss, with all the good it can bring. But that makes it difficult to separate the impact on longevity itself. The paper’s authors list other problems in transferring what was seen in the laboratory to people. For example, the rodents used by scientists have been selected for decades for accelerated development (shortened testing) or early reproduction. This distorts any intervention in their longevity.

Okinawa lessons

The potential negative impacts of calorie restriction on humans are also poorly understood. These effects can include a weakened immune system, decreased heat tolerance, or decreased libido. Basulto adds:

– The people who benefit most from these diets are those who are overweight, but did not enter the studies. However, in the real world, adding calorie restriction to someone who has an eating disorder can make things worse.

One of the largest natural experiments with humans was taking place on Okinawa, an island in southern Japan. There they have the longest life expectancy in the developed world, and 50 people in 100,000 live 100 years or more, five times the proportion observed in other parts of the planet. Furthermore, the number of causes of death among the elderly is 50% lower than among the rest of Japanese. From a nutritional point of view, the big difference is that their calorie intake was 17% lower than that of their countrymen or 40% lower than that of Americans. The military occupation of the latter country after World War II, however, introduced the Western diet to the island, and today those born in this century already have the same life expectancy as the rest of Japan.

Luigi Fontana, director of the Health and Longevity Research Program at the University of Sydney, Australia, acknowledges that “it is impossible to obtain longevity data in humans… However, many biological longevity markers are emerging and we see that they have improved remarkably ”. Fontana is an outspoken advocate of calorie restriction:

— The secret of healthy longevity can be found in a combination of actions I highlighted in my book — referring to a work I published last year, “The path to longevity: The secrets to living a long, happy, healthy life ” (in Portuguese, “The way to longevity: The secrets to living a lasting, happy and healthy life”).

Osteoporosis and fractures

In the 1990s and the first decade of this century, there was an experiment that happened to study the impact of lack of food on metabolism.

The Biosphere 2 project aimed to create a complete artificial ecosystem to test life on other planets. A supply problem forced all eight participants into a 29% calorie reduction for 18 months. Although restricted, it was a plant-based diet, with fiber and protein in satisfactory amounts. They observed improvement in several markers already seen in mice, such as decreased levels of insulin, cholesterol and triglycerides, increased cortisol and decreased blood pressure and glucose concentration.

But they did not alter indices in key elements of metabolism, such as the developmentally relevant protein IGF-1, testosterone or DHEA sulfate, a hormone related to the passage of time. They also lost bone mass, especially in areas prone to osteoporosis and fractures, such as the hip or femur. Furthermore, years later, a review of the experiment found that Biosphere 2 volunteers suffered from chronic hypoxia, and this lack of oxygen could have corrupted the results.

One of the members of the experiment was Roy Walford, a professor of pathology who became very popular in the 1980s with the book “The 120-year diet: how to double your vital years” (in Portuguese, “The 120-year diet: how to double your vital years”). One of the founders of the Calorie Restriction Society, Walford died aged 79.

No science behind fasting

The only scientific study that analyzes the markers cited by Luigi Fontana is CALERIE-2. Developed by the US National Institute on Aging (NIA), its acronym refers to an assessment of the long-term effects of reducing calorie intake.

It was developed at several American universities with 220 healthy and non-obese people. After two years of sustained caloric reduction of 25% (in another group it was 12.5%, and in a third, this amount of calories was burned through physical exercise), a decrease in oxidative stress markers and a slowdown was observed. of metabolism.

However, the low adherence to the program casts doubt on the results. The NIA itself warns today that “there is not enough evidence to recommend any type of fasting diet or calorie restriction.”

Professor of nutrition at the University of Navarra J. Alfredo Martínez does not agree with the use of metabolic markers as indicators of future longevity. Like others before, he highlights the difficulty of applying these diets to humans.

— The life cycle of a mouse is very short. We cannot leave a person eating little and wait 80 years – argues Martínez.

In addition, he adds, “development theories link underage eating in early life to various illnesses in adulthood.”

Extreme cases were the impact of famine on thousands of Dutch children during World War II or those held in the orphanages of Romanian dictator Ceaucescu. For adults, “that diets prolong life has not been proven nor will it be easy to prove,” adds Martínez, who is also director of the Precision Nutrition and Cardiometabolic Health Program at the IMDEA Food Institute.

The questions don’t stop there. The researcher at the CSIC Ascensión Marcos Institute of Science and Technology for Food and Nutrition recalls that “the microbiota is involved and suffers from this type of diet”.

Science is increasingly convinced that intestinal flora not only affects the digestive system, the entire body depends on these commensal microbes. Marcos believes that good nutrition education is needed more than any of these diets.

— We eat very poorly and the food industry gets in the way. In some of these diets, such as fasting, there is no science behind it – concludes.

In fact, researchers from the Department of Health Studies at the UOC and the University of Leicester (UK) are recruiting a group of women who have just entered menopause to investigate intermittent fasting. The person responsible for the study, Salvador Macip, recalls that at this stage of a woman’s life, “aging accelerates” and hence the interest in caloric restriction to delay it.

“Like the authors of Science magazine, I’m very skeptical today, but not about the future,” he says.

The big problem Macip highlights is that “true aging markers” have not been identified. In rats, they have already detected some, “we open them up and see how their tissues age.” In humans, they will look for them in the blood.

In the study that is about to begin, half the women will follow an intermittent fasting diet, but both groups will eat the same number of calories. They therefore seek to separate the effect on weight from the impact on longevity.

“We hope to find these markers,” he finishes.