This Drug Mimics a Diet and Blocks Weight Gain—Without Cutting Calories

Researchers have found that a drug called buthionine sulfoximine (BSO) can mimic the powerful anti-obesity effects of a specialized diet, offering a promising new approach for weight management that doesn’t require dietary restriction.

The study, published April 7 in the journal Aging, demonstrates that BSO prevents fat accumulation while allowing normal eating habits – an advantage over many current weight loss approaches that rely on appetite suppression or strict dietary changes.

How a Drug Could Replace a Challenging Diet

The research, led by scientists at the Orentreich Foundation for the Advancement of Science, builds on previous findings about sulfur amino acid restriction (SAAR) – a specialized diet that drastically reduces methionine and cysteine intake. While SAAR has shown remarkable health benefits in laboratory animals, including a 50% weight reduction in obese mice within just three weeks, implementing this diet in humans has proven challenging.

“Data demonstrate that BSO recapitulates the SAAR-induced anti-obesity effects and that GSH plays a mechanistic role,” the researchers noted in their paper, referring to glutathione (GSH), a compound that appears central to how both the diet and the drug work.

The investigation focused on whether pharmacologically lowering GSH levels in the body – which naturally happens during the SAAR diet – could produce similar benefits without requiring dietary changes. This approach could potentially provide an easier path to the same health improvements.

Impressive Results in Preventing Fat Accumulation

The research team conducted a 13-week study with obese mice on high-fat diets. They divided the mice into four groups: one receiving a control diet (CD), another receiving the SAAR diet, a third receiving the SAAR diet plus N-acetylcysteine (NAC) which increases GSH, and a fourth receiving the control diet plus BSO.

Compared to mice on the standard high-fat diet, those receiving BSO showed significantly less weight gain. While not quite as dramatic as the effects of the SAAR diet itself, the BSO-treated mice maintained stable weight throughout the study despite consuming a high-fat diet.

Key Findings from the BSO Treatment

• Prevention of further weight gain despite high-fat diet consumption
• Reduction in liver fat droplet frequency (31% of control group levels)
• Decreased epididymal fat depot weight (75% of control group levels)
• Reduced total body fat mass (72% of control group)
• Preservation of lean muscle mass (unlike the SAAR diet, which reduced it)
• No reduction in food intake (unlike many traditional weight loss treatments)

Particularly notable was that BSO selectively targeted fat accumulation without affecting lean mass, a significant advantage over many current weight management approaches that often result in muscle loss along with fat reduction.

“BSO mice exhibited all SAAR-induced changes, with two notable differences, i.e., a smaller effect size than that of the SAAR diet and a higher predilection for molecular changes in kidneys than in the liver,” the researchers reported.

Understanding the Underlying Mechanism

The study delved into the molecular mechanisms behind BSO’s effects. Both the SAAR diet and BSO decrease glutathione (GSH) levels in the body, which appears to trigger a cascade of beneficial metabolic changes.

At the molecular level, BSO decreased the expression of genes involved in fat production and storage, including Scd1, Gpam, Mogat1, and Mogat2. This mirrors some of the effects seen with the SAAR diet, though the diet had additional impacts on genes involved in fat breakdown that weren’t observed with BSO.

Interestingly, while the SAAR diet exerted its strongest effects in the liver, BSO showed more pronounced activity in the kidneys. Despite these differences in where they primarily acted, both approaches resulted in increased serine levels in the liver – a change linked to reduced fat production.

Safe Alternative to Dietary Restriction

With obesity affecting millions worldwide and contributing to numerous chronic diseases, finding effective and practical interventions is crucial. Traditional weight management often requires strict dietary adherence or medications that reduce appetite, approaches many find difficult to maintain long-term.

The researchers monitored several health markers throughout the study to assess BSO’s safety. Plasma indicators of liver and kidney function remained normal, suggesting that continuous BSO administration at the tested dose didn’t cause toxicity to these organs over the 13-week period.

What makes this discovery particularly promising is that BSO has already been used in human clinical trials for other conditions, potentially streamlining its approval process for treating metabolic disorders.

Future Directions and Promise

Could this compound represent a new approach to treating obesity and metabolic disorders without the need for strict dietary changes? The research team believes the findings warrant further investigation.

They concluded that “BSO dose-response studies in animals and pilot studies in humans to combat obesity are highly warranted,” noting that the compound’s ability to prevent fat gain without reducing food intake or lean mass makes it particularly promising.

As research continues, this pharmacological approach could potentially offer a practical alternative for those struggling with weight management, addressing a critical healthcare challenge through a novel mechanism that targets the fundamental processes of fat accumulation rather than simply reducing caloric intake.