New Compound Mimics Anti-Obesity Benefits of Restricted Diet Without Bone Loss

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A new study published in the journal Aging-US has found that the compound D, L-buthionine-(S, R)-sulfoximine (BSO) can mimic the anti-obesity benefits of a sulfur amino acid restricted (SAAR) diet in mice without causing the bone loss typically seen with SAAR diets. The researchers compared the effects of a SAAR diet, SAAR plus a glutathione precursor, and a normal diet plus BSO, and found that while the SAAR diet reduced body fat it also lowered bone mineral density, increased marrow fat, and weakened bone strength. Crucially, BSO was able to reproduce the anti-obesity effects without the detrimental bone impacts.

Why it matters

Obesity is a major public health concern, but current anti-obesity strategies that restrict sulfur amino acids can have unintended negative effects on bone health. The finding that BSO can provide the anti-obesity benefits without the bone loss suggests it could be a promising compound to further investigate as a potential therapy that avoids the skeletal harm associated with sulfur amino acid restriction.

The details

The study, led by researchers from the Orentreich Foundation for the Advancement of Science, used diet-induced obese male mice fed high-fat diets and compared several dietary interventions: a control methionine-replete diet, a SAAR diet (low methionine, no cysteine), SAAR plus the glutathione precursor N-acetylcysteine (NAC), and a control diet plus BSO in drinking water. The team found that while the SAAR diet reduced body fat, it also lowered trabecular and cortical bone mineral density, increased marrow adiposity, reduced osteoblast numbers, and weakened bone biomechanical strength. Supplementing the SAAR diet with NAC reversed the bone defects, implicating cysteine/glutathione restriction in the bone loss. Crucially, BSO was able to reproduce the anti-obesity effects of SAAR without causing the same detrimental bone impacts.

• The study was published on March 2, 2026 in the journal Aging-US.

What’s next

The authors call for further mechanistic studies to define how glutathione lowering drives fat loss yet spares bone under BSO treatment, investigations of age-at-onset, tissue-specific, and sex-specific effects, and long-term safety studies to assess off-target or delayed adverse effects of BSO before any clinical development.