A diet that improves the biomarkers of metabolic health, and that could potentially slow the aging process, has moved a step closer to reality.

"We've known for years that restricting the amino acid methionine in the diet produces immediate and lasting improvements in nearly every biomarker of metabolic health," said the senior author. "The problem is that methionine-restricted diets have been difficult to implement because they taste so bad."

Until now. Restricting methionine normally involves diets formulated with elemental (e.g., individual) amino acids. Individual amino acids are the building blocks of proteins. But diets made from elemental amino acids taste bad, and few are willing to tolerate the regimen.

The authors developed the methods to selectively delete methionine from casein, the main protein in milk and cheese. The lab then conducted the proof-of-concept testing to establish that oxidized casein could be used to implement methionine restriction without the objectionable taste of the standard elemental diet.

More than two-thirds of Americans are overweight or have obesity. More than 40 percent of adults have prediabetes or type 2 diabetes.

"A diet that offsets all the major components of metabolic disease would have an enormous impact on the nation's health, and the world's," said the lead author of the study.

A palatable, methionine-restricted diet could also ease a major frustration for those struggling to manage their weight. Each year, millions of people improve their metabolism and lose weight by reducing how much they eat. But eventually, most people gain back those pounds.

"Calorie restriction is an effective weight-management tool. But for most people it is also very, very difficult to follow long-term," said the author. "This struggle is one of the major reasons our scientists explore every avenue to find solutions to the obesity epidemic."

Although the oxidized casein diet represents a major advance, the team say more research is needed. Their study, published in the journal iScience, involved mice. Translating the results to produce a methionine-restricted human diet, which is far more complex and involves multiple sources of protein, will be challenging.

In the short term, a practical solution may be to develop a palatable group of modified proteins to serve as the basis of a therapeutic diet. People would follow the diet for a limited period while under medical supervision.

https://www.cell.com/iscience/fulltext/S2589-0042(21)00438-7

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