Cracking the Isoleucine Paradox: Boost Weight Loss and Longevity with Increased Consumption

Recent studies have contested the assumption that all calories yield the same effects. The study implies that a cutback in isoleucine, a type of amino acid, in a diet can greatly impact health. Findings through observing mice showed extended lifespans, lower risk of cancer and reduced frailty despite a significant increase in calorie intake. These outcomes underscore the significance of the composition of diet over calories and introduce potential dietary interventions for better health.

Many believe that "a calorie is a calorie," but recent scientific findings suggest otherwise. It is possible to increase the consumption of certain types of calories while simultaneously improving health.

"We like to say a calorie is not simply a calorie," says Dudley Lamming, a metabolism researcher and professor at the University of Wisconsin School of Medicine and Public Health. "Each component of your diet impacts your health beyond serving as a calorie, and we have been focusing on one such component that is widely consumed."

Lamming is the lead author of a new study targeting mice. The study, published in 'Cell Metabolism', showed that trimming down the intake of the amino acid isoleucine resulted in longer lifespan, lower rates of cancer and obesity, and less frailty while the mice consumed more calories.

Amino acids are the primary structural units of proteins, which hold a significant link to healthy aging, an area of interest for Lamming and his colleagues.

Previous research, obtained from UW-Madison's Survey of the Health of Wisconsin, demonstrated that people with higher body mass index (BMI) measurements consume more isoleucine. Foods such as eggs, dairy, soy protein, and a variety of meats are rich in isoleucine.

To delve deeper into its effects on health, Lamming and his peers fed genetically mixed mice either a balanced diet, a diet low in about 20 types of amino acids or a diet with two-thirds less isoleucine. The mice were allowed to consume as much as they desired.

"The mice on the lowered isoleucine diet experienced fat loss and became leaner very quickly," Lamming noted. Mice on the low-isoleucine plan lived longer, up to 33% longer for males and 7% for females. These mice displayed better health based on 26 health metrics, including muscle strength, endurance, tail usage and even hair loss.

Prior studies have linked increased lifespan with diets low in protein, amino acids, or calories in young mice. "Starting such a dietary change in older mice and observing substantial improvements in lifespan and healthspan is encouraging," commented Lamming.

The mice fed with lower isoleucine consumed significantly more calories than the other mice in the study. They burned more calories, resulting in loss and maintenance of lean body weight due to metabolic adjustments, rather than increased physical activity.

In addition, the mice maintained stable blood sugar levels and the male mice had less age-related prostate enlargement. Cancer, which is the leading cause of death in diverse mice strains, was less prevalent among the low-isoleucine males.

Dietary amino acids have been linked with a gene called mTOR, known to influence aging in mice and other animals, and a hormone that regulates response to cold and is considered a potential diabetes drug for humans. However, the mechanism linking reduced isoleucine intake and these significant health benefits is not completely understood. Lamming believes that the results may contribute to future cause-effect studies.

“The lesser benefits we observed in female mice compared to male mice may help us understand this mechanism,” he adds.

Although the findings are promising, isoleucine is essential for human survival. Reducing a significant percentage of isoleucine from a daily nutrition plan without assistance from preformulated diets can be challenging.

“We can’t just switch everyone to a low-isoleucine diet,” Lamming says. “But narrowing these benefits down to a single amino acid gets us closer to understanding the biological processes and maybe potential interventions for humans, like an isoleucine-blocking drug.”

The Survey of the Health of Wisconsin showed that people vary in isoleucine intake, with leaner participants tending to eat a diet lower in isoleucine. Other data from Lamming’s lab suggest that overweight and obese Americans may be eating significantly more isoleucine than they need.

“It could be that by choosing healthier foods and healthier eating in general, we might be able to lower isoleucine enough to make a difference,” Lamming says.