Lose 30% Of Your Weight In Days: The Scientific Discovery That Challenges Everything We Know

Scientists have discovered that removing an amino acid called cysteine ​​from the diet of mice caused rapid and significant weight loss, up to 30% in one week. This happened because the body went into a state of stress, burning more fat and using energy less efficiently. The effect was reversible; when the mice returned to their normal diet, they regained their weight. The discovery could help in the development of new strategies to treat obesity.

Obesity is a growing problem worldwide, affecting about 40% of the population of the United States and one in six people on the planet. To try to combat this situation, scientists have been studying different diets, such as reducing carbohydrates, fats and, more recently, amino acids, which are the building blocks of proteins.

In this study, researchers from NYU Grossman School of Medicine, USA, investigated what happens when certain amino acids are removed from the diet of mice.

They found that removing a specific amino acid, called cysteine, led to surprising weight loss: the mice lost up to 30 percent of their body weight in just one week, and this loss was quickly reversed when they returned to their normal diet.

Cysteine ​​is important because it plays a role in several essential functions in the body. It helps produce glutathione (a powerful antioxidant that protects cells) and is also involved in the production of Coenzyme A (CoA), a key substance for generating energy in cells.

When mice were deprived of cysteine, their bodies went into a state of “alert,” activating cellular stress responses and leading to a change in the functioning of their metabolism.

This resulted in a less efficient energy generation process, which ended up forcing the body to burn more fat, but in an accelerated and unsustainable way. Interestingly, the mice that lost weight due to the lack of cysteine ​​did not become sick, nor did they become more active or lethargic.

The weight loss was not caused by extra movement, but by internal changes in the body. They also began to eat less, demonstrating a kind of rejection of food.

But even when scientists restricted the food of other mice without removing cysteine ​​from their diet, the weight loss was not as great. In other words, the absence of this amino acid had a direct and unique effect.

The researchers also checked to see whether the weight loss was caused by problems with nutrient absorption or by changes in intestinal bacteria, but found nothing to explain the difference.

Cysteine ​​deprivation was the main factor. And most surprisingly, when the mice returned to eating normal food, they regained the weight within a few days, and when they returned to the cysteine-free diet, they lost weight again. This shows that the process is completely reversible.

Another important point of the study was that weight loss occurred mainly through the burning of fat and not muscle. The researchers also noted that the mice’s fat tissue underwent changes, becoming more “active,” similar to the type of fat that burns calories instead of storing them.

This study opens the door to future research on how to manipulate metabolism through diet, especially to treat obesity and other metabolic-related diseases.

Cysteine, although little studied so far, has shown itself to be a key piece in this puzzle, and its controlled withdrawal can have important and useful effects, as long as it is done very carefully and under scientific guidance.

This figure shows how removing an amino acid called cysteine ​​from the diet can cause rapid loss of body fat in mice. The experiments compare two types of mice: a group with normal function (called Het, or heterozygous) and a group with a genetic defect that prevents internal production of cysteine ​​(called KO, or knockout). Both groups were fed controlled amounts of food for a few days, but then given a diet without cysteine ​​to observe the effects. Panel (a) shows the timeline of the experiment: the mice were put on a diet with and then without cysteine, in a controlled amount. In graphs (b), (c) and (d), we see that the KO mice stopped eating when cysteine ​​was removed (b), did not change their physical activity level much (c), but started burning more fat (d). Graph (e) shows that the KO mice lost significantly more fat than the normal (Het) mice, even though they ate the same amount. The images (f) show fat under the microscope: the knockout mice on the cysteine-free diet have almost no more adipose tissue. The images (g) indicate that this fat loss was not caused by cell death. The images (h) show an increase in a protein (UCP1) linked to fat burning, suggesting that fat has been "activated" to produce energy.

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Unravelling cysteine-deficiency-associated rapid weight loss

Alan Varghese, Ivan Gusarov, Begoña Gamallo-Lana, Daria Dolgonos, Yatin Mankan, Ilya Shamovsky, Mydia Phan, Rebecca Jones, Maria Gomez-Jenkins, Eileen White, Rui Wang, Drew R. Jones, Thales Papagiannakopoulos, Michael E. Pacold, Adam C. Mar, Dan R. Littman, and Evgeny Nudler

Nature. 21 May 2025. 

DOI: 10.1038/s41586-025-08996-y

Abstract:

Around 40% of the US population and 1 in 6 individuals worldwide have obesity, with the incidence surging globally1,2. Various dietary interventions, including carbohydrate, fat and, more recently, amino acid restriction, have been explored to combat this epidemic3,4,5,6. Here we investigated the impact of removing individual amino acids on the weight profiles of mice. We show that conditional cysteine restriction resulted in the most substantial weight loss when compared to essential amino acid restriction, amounting to 30% within 1 week, which was readily reversed. We found that cysteine deficiency activated the integrated stress response and oxidative stress response, which amplify each other, leading to the induction of GDF15 and FGF21, partly explaining the phenotype7,8,9. Notably, we observed lower levels of tissue coenzyme A (CoA), which has been considered to be extremely stable10, resulting in reduced mitochondrial functionality and metabolic rewiring. This results in energetically inefficient anaerobic glycolysis and defective tricarboxylic acid cycle, with sustained urinary excretion of pyruvate, orotate, citrate, α-ketoglutarate, nitrogen-rich compounds and amino acids. In summary, our investigation reveals that cysteine restriction, by depleting GSH and CoA, exerts a maximal impact on weight loss, metabolism and stress signalling compared with other amino acid restrictions. These findings suggest strategies for addressing a range of metabolic diseases and the growing obesity crisis.