Can reducing isoleucine help you eat more, weigh less, and increase longevity?

You may have heard that a calorie is a calorie, but new research by the University of Wisconsin School of Medicine and Public Health study suggests not all calories are the same.

The study in mice suggests that reducing a certain amino acid (isoleucine) may improve your health. It found increased lifespans, less frailty, and reduced cancer rates despite higher calorie intake. This data suggests the significance of diet composition versus calorie counting and possibly ways to advance human health.

Dudley Lamming, a professor and metabolism researcher at the University of Wisconsin School of Medicine and Public Health states, “We like to say a calorie is not just a calorie. Different components of your diet have value and impact beyond their function as a calorie, and we’ve been digging in on one component that many people may be eating too much of.”

The Role of Amino Acids in Healthy Aging

Lead author Lamming published his study in the journal Cell Metabolism, which found that reducing intake of isoleucine (an amino acid) can increase lifespan, improve body composition, and reduce frailty as they age in addition to reducing cancer and prostate issues while the mice ate more calories.

Protein is made up of a variety of amino acids. Lamming and his team want to evaluate how they’re connected to healthy aging.

Results from previous research from UW–Madison’s Survey of the Health of Wisconsin found that Wisconsinites with higher body mass index measurements (more overweight or obese) appear to eat more isoleucine, an essential amino acid that your body can’t make. Sources of isoleucine include eggs, dairy, soy protein, and several kinds of meat.

Dietary Studies with Interesting Results

To understand the health effects of isoleucine, Laming and his colleagues from various disciplines at UW-Madison fed a group of genetically diverse mice one of three diets: a balanced control diet, a diet low in 20 amino acids, or a diet developed to reduce two-thirds of the diet’s isoleucine. The study started when the mice were 6 months old (equal to a 30-year-old human). The mice were allowed to eat as much as they desired.

“Very quickly, we saw the mice on the reduced isoleucine diet lose adiposity — their bodies got leaner, they lost fat,” says Lamming, while the bodies of the mice on the low-amino-acid diet also got leaner to start, but eventually regained weight and fat.

How Diet, Aging, and Disease Prevention Relate

On average, mice on the low-isoleucine diet lived 35% longer for males and 7% longer for females. In addition, the low-isoleucine mice were in better shape based on over 25 health measures such as muscle strength, tail use, endurance, and hair loss.

“Previous research has shown lifespan increase with low-calorie and low-protein or low-amino-acid diets starting in very young mice,” says Lamming, whose work is supported by the National Institutes of Health. “We started with mice that were already getting older. It’s interesting and encouraging to think a dietary change could still make such a big difference in lifespan and what we call ‘healthspan,’ even when it started closer to mid-life.”

Mice on the low-isoleucine diet ate significantly more calories than the other study mice, which could have been to compensate for receiving less isoleucine, according to Lamming. However, they burned more calories and kept leaner body weights from adjustments in metabolism, not increased exercise.

They maintained more stable blood sugar levels and male mice had less age-related prostate enlargement. The low-isoleucine male mice were also less likely to develop a tumor, despite cancer being the leading cause of mortality in the diverse strain of mice in the study.

Amino acids are associated with a gene known as mTOR which appears to be a trigger for the aging process in mice and other animals in addition to a hormone that regulates the body’s response to cold. It’s been considered as a possible diabetes drug in humans.

The rationale and mechanism of how low-isoleucine intake is beneficial is not quite understood. Lamming believes the results of this study may fuel future research to discover causes.

“That we see less benefit for female mice than male mice is something we may be able to use to get to that mechanism,” he says.

The Human Diet and Future Research

As isoleucine is an essential amino acid, we need it to survive. “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.”

People’s intake of isoleucine varies, according to the Survey of the Health of Wisconsin with leaner participants usually consuming a diet lower in isoleucine. Other data from Lamming’s lab indicate that overweight and obese Americans may be eating much 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.

What can you do now to live longer and leaner?

1.      Reduce intake of excess dietary sugars from sweetened drinks and high-calorie desserts.

2.      Cut back on processed and fast food, which is high in calories, fat, sugar, and sodium.

3.      Drink more water and less regular and diet soft drinks.

4.      Limit or avoid alcohol given the link between alcohol and cancer risk.

5.      Get enough sleep to maintain healthy blood pressure, sugar, and lipids.

6.      Eat plenty of vegetables and fruit, as well as whole grains, beans, lentils, nuts, and seeds.

7.      Reduce intake of red meat and processed meat. Include more plant-based sources of protein which are lower in isoleucine.

8.      Do regular exercise-including cardio and strength training.

9.      Keep your mind active through social and intellectual activities.

10. See your doctor regularly for checkups.

Lisa Andrews, MEd, RD, LD

Reference:

“Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice” by Cara L. Green, Michaela E. Trautman, Krittisak Chaiyakul, Raghav Jain, Yasmine H. Alam, Reji Babygirija, Heidi H. Pak, Michelle M. Sonsalla, Mariah F. Calubag, Chung-Yang Yeh, Anneliese Bleicher, Grace Novak, Teresa T. Liu, Sarah Newman, Will A. Ricke, Kristina A. Matkowskyj, Irene M. Ong, Cholsoon Jang, Judith Simcox and Dudley W. Lamming, 7 November 2023, Cell Metabolism.
DOI: 10.1016/j.cmet.2023.10.005