Low cysteine diet found to trigger rapid fatloss in one week

A new study has discovered that an amino acid cysteine-free diet leads to a one-week weight loss of 30% of body mass in mice.

The paper, published in Nature, explains that cysteine depletion disrupts the metabolic pathways in mammalian cells that convert food into energy, forcing the rapid burning of fat stores to meet energy demands.

“While driving weight loss in the clinic remains a key future mission, we are most excited for the moment about the profound, fundamental aspects of metabolism revealed in this study,” says co-senior study author professor Evgeny Nudler, Ph.D., at New York University (NYU) Grossman School of Medicine, US.

The researchers add that the study does not directly suggest a new weight-loss method since cysteine is found in nearly all foods. They employed gene editing to make the mice unable to make the amino acid.

Plants over red meat

According to the researchers, a cysteine-free diet requires patients to consume a specially formulated solution, which many would find challenging. 

Cysteine had the most excellent weight loss effect compared to removing other essential amino acids.Also, since the amino acid is involved in various cellular pathways, inhibiting it via a drug risks making organs vulnerable to everyday toxins, including medications, warn the researchers.

However, they suggest considering diet changes, as fruits, vegetables, and legumes contain much lower levels of cysteine and its precursor, the sulfur-containing amino acid methionine, than red meat.

Previous literature has linked taking low-sulfur amino acids to health benefits, while the new study reveals the benefits are caused by cysteine depletion, not methionine restriction.

“Given that achieving maximum cysteine deprivation weight loss in the mice was dependent on both diet and deletion of the gene, moving forward we can now restore cysteine production genetically in specific cells or tissues and determine the role of each in the dramatic weight loss we observed,” says co-senior author professor Dan Littman, from the Department of Pathology and Department of Cell Biology, at NYU Grossman School of Medicine.

“We hope in the future to hijack parts of this process to induce a similar weight loss in humans but without completely removing cysteine,” he adds.

Dual stress responses further bring weight loss

The study claims to be the first to examine the effects of removing cysteine, or any of the nine essential amino acids, from diets. These amino acids are needed to build proteins and make up most of the body’s enzymes, tissues, and signaling molecules.

Cysteine had the most substantial weight loss effect compared to removing other essential amino acids.

At the cellular level, the absence of cysteine disrupted oxidative phosphorylation, which is the primary process for producing the energy provider adenosine triphosphate (ATP). Thus, carbon skeletons could not be used as they were excreted through the urine. This led the body to opt for stored fats to make energy instead.

Cysteine restriction also activated two responses: one that helps cells recover from stress and another that responds against too many harmful molecules (reactive oxygen species) that can damage DNA.

The researchers were surprised to see the responses in normal cells, which had previously been seen in cancer cells. The simultaneous responses strengthened each other.

Cellular stress responses caused GDF15 to increase, making mice averse to food while breaking down the fat-making enzyme.Ultimately, the responses caused the hormone GDF15 to increase, making mice averse to food while breaking down the fat-making enzyme.

Weight management and amino acids in research

In other research, a study suggested that reducing the intake of the amino acid isoleucine extends the lifespan of mice, making them leaner and less frail as they age and reducing cancer and prostate problems.

Switching out animal products with plant-based foods — even those defined as “unhealthy” by the plant-based diet index — was deemed effective for weight loss in adults diagnosed with type 1 diabetes by a new study.

Researchers also discovered the ancient origins of bombesin, a neurohormone crucial in regulating appetite. They suggest their finding paves the way for potential applications in nutrition such as developing treatments for obesity.