Abstract

S-Methyl cysteine sulfoxide (SMCSO) is an organosulfur compound with demonstrated hypocholesterolemic, anti-diabetic, and antioxidant benefits in rodents. However, the doses used have limited translatability for humans. We explored whether SMCSO could blunt development of diet-induced metabolic syndrome features in mice using doses that are potentially more translatable and achievable in humans. Male mice (C57BL/6; n = 54) were randomly assigned into one of five groups: [1] normal-diet; [2] high-fat-diet; or high-fat-diet with [3] 60 mg kg−1, [4] 170 mg kg−1, or [5] 350 mg per kg per body weight (BW) of SMCSO, respectively. Doses were administered five days per week for 12 weeks via gavage. Repeated measure analysis of variance (ANOVA) was used to determine changes over time. One-way ANOVA with Dunnett's post hoc analysis determined differences between groups for all parametric data, with Kruskal–Wallis with Dunn's test used for non-parametric data. The high-fat fed group (group 2) was the comparator for all analyses with statistical significance set at p < 0.05. High-fat fed mice experienced weight gain, impaired glucose tolerance, elevated total cholesterol, high-density lipoprotein-cholesterol (HDL-C), and measured low-density lipoprotein-cholesterol (mLDL-C), compared to normal-diet fed mice (all p < 0.05). Adding 170 mg kg−1 and 350 mg per kg BW per day of SMCSO reduced diet-induced elevations in HDL-C (−11 to −12%), whilst 350 mg per kg per BW day lowered triglycerides (−16%), compared to high-fat fed mice (all p ≤ 0.05). Other cardiometabolic parameters were not significantly altered. SMCSO did not improve glucose tolerance, mLDL-C, or blunt weight gain in high-fat fed mice. The higher SMCSO doses (170 and 350 mg per kg BW per day) lowered diet-induced elevations in HDL-C, although the mechanism is unclear. Whether this finding has relevance to human health remains unknown.

Keywords

Diet-induced metabolic syndrome, s-methyl cysteine sulfoxide, high-fat diet, cholesterol metabolism, mouse model, cardiometabolic health

Document Type

Journal Article

Date of Publication

1-1-2026

Publication Title

Food & Function

Publisher

Royal Society of Chemistry

School

Nutrition and Health Innovation Research Institute / School of Medical and Health Sciences / Centre for Precision Health / Centre for Integrative Metabolomics and Computational Biology / School of Science

Funders

This work was supported by an Edith Cowan University Early-Mid Career Researcher Grant (number G1006477) awarded to AS, enabling us to complete this project; a National Heart Foundation Future Leadership Fellowship (ID: 102817) awarded to JRL; a National Health and Medical Research Council of Australia Emerging Leadership Investigator Grant (ID: 1172987) awarded to LCB, and a National Heart Foundation of Australia Post-Doctoral Research Fellowship (ID: 102498) awarded to LCB.

Grant Number

NHMRC Number : 1172987

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Comments

Hill, C. R., Balmer, L., Abbiss, H., Hodgson, J. M., Lewis, J. R., Shafaei, A., & Blekkenhorst, L. C. (2026). S-Methyl cysteine sulfoxide: Its effects on cardiometabolic outcomes in high-fat fed C57BL/6 mice and relevance to human health. Food & Function, 17, 4375–4388. https://doi.org/10.1039/d5fo04816h

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Link to publisher version (DOI)

10.1039/d5fo04816h