UW-Madison lab researching effects of low-protein diets

Researchers at UW-Madison are exploring the potential positive effects that low-protein diets may have on human health and longevity. 

Dudley Lamming, a metabolism researcher at the university’s School of Medicine and Public Health, began this journey after seeing a peculiar trend in a study from 2014 on how mice reacted to various controlled diets. He noticed the mice who had the least amount of protein in their diets were healthier than the others. 

“There’s a growing realization that a calorie is not just a calorie, that a calorie has implications beyond just its caloric content,” Lamming said in a release. “What our research is showing is that protein calories are not the same as other calories.”

Since that realization, Lamming and student researchers in his lab have been honing in on specific proteins that may hold the key to improving human diets. In both animal models and human studies, they’ve found that diets containing large amounts of three branched-chain amino acids — known as BCAAs — are linked with conditions like obesity and diabetes. 

At the same time, diets with low levels of these BCAAs have been found to improve these conditions and enable mice to live longer. According to a release from UW-Madison, scientists aren’t yet sure exactly how BCAAs affect metabolism, though evidence suggests that lowering intake of these proteins “seems to encourage faster metabolisms and healthier blood sugar control.” 

The findings of Lamming’s laboratory may seem surprising, given that many modern dieting programs suggest adding more proteins due to the feeling of fullness they provide and other factors. Plus, the release notes, high-protein diets are crucial for athletes and others working to gain muscle. 

But at the same time, obesity is recognized as a significant public health crisis, with the national adult obesity rate reaching over 40 percent in recent years. Lamming sees his team’s findings as evidence that approaches to dieting and nutrition could be improved. 

Earlier this year, Lamming and graduate students Nicole Richardson and Deyang Yu published two studies aimed at better understanding BCAA restriction. These proteins make up three of the nine essential amino acids needed by humans to survive. 

In a study published in January, laboratory mice were given a diet containing one-third the typical amount of BCAAs. The male mice who ate this diet for their full lifespans lived about 30 percent longer on average. But female mice in the study saw no benefit. The researchers aren’t sure why this difference was seen, but Lamming says it points to a need for more studies that include mice of both sexes, as most previous studies used only males. 

A second scientific study from May of this year examined the differences between the three BCAAs, which include valine, leucine and isoleucine. They found that restricting isoleucine in particular has “by far the most potent effect.” 

Meanwhile, diets low in valine had similar but less pronounced effects. And reducing leucine in diets appears to have no benefit, and could actually produce a negative effect, the release shows.

Lamming and his colleagues began by feeding mice a typical “Western” diet with high levels of fat and sugar. Unsurprisingly, the mice became obese after a few months. But when they began feeding the same mice the same diet with lower levels of isoleucine, the mice ate more food but actually lost weight. This was due to a higher metabolic rate leading to more calories being burned. 

Studies on humans have reinforced Lamming’s findings. Using information from a statewide public health study called the Survey of Health in Wisconsin, his team found that increased levels of isoleucine in human diets were linked to a higher body mass index.

Conducting comprehensive long-term controlled diet studies in humans is “nearly impossible,” the release shows. But Lamming’s research group are testing low-BCAA diets in smaller-scale human studies, in hopes of gleaning more insight into the relationship between these proteins and human health. 

“I think we’re on track to find a diet that people could adhere to without restricting calories, that would still enable them to live a long and healthy life,” Lamming said.