Chinese scientists have raised concerns that lab mice may have been “fed wrong,” as the purified diets commonly used in lab mice fail to reflect the complexity of real-world food intake, potentially skewing current understanding of human disease and life sciences.

The opinion piece, led by Professor Wen Lixin from Hunan Agricultural University in central China, was published on Feb. 27 in Cell Metabolism, a subsidiary of the science journal Cell.

Scientists have questioned the use of purified diets in the past, but Wen’s piece is among the strongest in framing the issue as a broader methodological concern.

Designing diets for lab animals is a key experimental variable in biomedicinal research, affecting everything from metabolic reactions to chemical responses. 

To ensure study reproducibility, labs typically use a purified diet standard, the most widely used of which was introduced by the American Institute of Nutrition in 1993 and typically constitutes 14% to 20% casein — a type of protein found in milk — starch, sucrose, and soybean oil, along with added vitamins and minerals.

Such purified diets can be used to isolate variables, allowing researchers to alter a single dietary component while keeping others constant. For example, increasing fat and sugar is commonly used to model “high-fat, high-sugar” diets.

However, in 2016, Wen’s team found that whole-food diets — also known as “chow” and including minimally processed ingredients such as grains, soybeans, and wheat bran — may produce results more reflective of actual human diets. These additional components interact with gut microbiota, influencing immune and metabolic processes.

In studies using purified diets, lard appeared harmful to metabolic health; yet research based on whole-food diets suggested that moderate lard intake could help maintain metabolic balance.“We began to wonder whether some discrepancies between successful animal experiments and failed clinical outcomes might originate at the experimental stage,” Wen told domestic media.

Subsequent experiments by the team showed that diet type could also alter the effects of astaxanthin — a marine-derived antioxidant investigated for its potential to improve cognitive function — possibly explaining why the compound shows strong results in animal studies for Alzheimer’s disease, but limited benefits in clinical settings.

“More concerning is that diet choice may be systematically shaping research conclusions,” said Guo Fangrui, the piece’s first author and a Ph.D. student at the Hunan Agricultural University. “For example, the anti-cancer drug tamoxifen was significantly less effective in mice fed natural diets, but this interference was absent in purified diets.”

The researchers called for more careful selection of diets for animals used in experiments, noting that purified diets suit tightly controlled, mechanism-focused studies, whereas whole-food diets are suited to long-term and real-world nutrition research.

“Methodological simplicity and reproducibility should not be (researchers’) only priorities,” the authors wrote. “Purified diets should be used as context-dependent tools, rather than universal standards in animal research.”

A related opinion piece by U.S. researchers published alongside the article in Cell Metabolism expressed similar concerns and recommended a more nuanced selection of laboratory animal diets. They added that research using purified diets should be cross-validated with research based on whole-food diets in certain contexts.

Editor: Marianne Gunnarsson.

(Header image: VCG)