Methylsulfonylmethane as a Bioactive Nutraceutical: Molecular Mechanisms, Clinical Evidence, Combination Therapy, Dosing, and Safety
9 affiliations
- 1Department of Orthopaedic Surgery, Hallym University Kangnam Sacred Heart Hospital, 1 Singil-ro, Yeongdeungpo-gu, Seoul 07441, Republic of Korea
- 2Incheon Terminal Orthopedic Surgery Clinic, Inha-ro 489beon-gil, Namdong-gu, Incheon 21574, Republic of Korea
- 3International Academy of Regenerative Medicine, Inha-ro 489beon-gil, Namdong-gu, Incheon 21574, Republic of Korea
- 4Bareun Neurosurgery Clinic, 39 Daenong-ro, Heungdeok-gu, Cheongju-si 28402, Republic of Korea
- 5Miso Pain Clinic, 1569 Bongyeong-ro, Yeongtong-gu, Suwon-si 16703, Republic of Korea
- 6Hongje Oneul Teun Teun Clinic, 442 Tongil-ro, Seodaemun-gu, Seoul 03629, Republic of Korea
- 7The Board of Clinical Research, International Academy of Musculoskeletal Medicine, Kowloon, Hong Kong SAR, China
- 8Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- 9Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, China
Abstract
Methylsulfonylmethane (MSM; dimethyl sulfone) is an organosulfur nutraceutical used primarily for joint symptoms, although its molecular actions and clinical applicability beyond osteoarthritis remain uncertain. This narrative review integrates pharmacological, preclinical, and human evidence on MSM, with emphasis on musculoskeletal disorders, multi-ingredient formulations, dosing, safety, toxicology, and clinical monitoring. Experimental studies implicate NF-κB and NLRP3 signaling, redox regulation, sulfur metabolism, and AMPK/mTOR/ULK1-related autophagy; however, most pathway-level evidence remains preclinical. Human clinical evidence is comparatively most developed for knee osteoarthritis, although it remains limited to small, short-term randomized trials reporting modest symptomatic improvement rather than established structural or disease-modifying benefit. Recent evidence syntheses also identify signals for glucosamine–MSM and glucosamine–chondroitin–MSM combinations, although certainty is limited and the independent contribution of MSM cannot be determined. Tendon studies largely evaluate multi-ingredient products, preventing attribution of benefit to MSM alone. Evidence in cardiometabolic disease, gastrointestinal health, exercise recovery, and toxicant exposure is preliminary. MSM is not a direct metal chelator and should not replace established chelation therapy. Short-term studies have used approximately 1–6 g/day with generally mild gastrointestinal adverse effects, whereas long-term safety, formal drug-interaction data, and clinically validated biomarker-guided dosing remain undefined. MSM should therefore be considered an adjunct with indication-dependent evidence rather than a broadly applicable anti-inflammatory or detoxification supplement.
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BibTeX
@article{yoon2026methylsulfonylmethane,
title = {{Methylsulfonylmethane as a Bioactive Nutraceutical: Molecular Mechanisms, Clinical Evidence, Combination Therapy, Dosing, and Safety}},
author = {Yonghyun Yoon and Jihyo Hwang and Jungyoun Kim and Jonghyeok Lee and Seungbeom Kim and Youngmo Kim and King Hei Stanley Lam},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27208967},
url = {https://www.mdpi.com/1422-0067/27/20/8967},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Methylsulfonylmethane as a Bioactive Nutraceutical: Molecular Mechanisms, Clinical Evidence, Combination Therapy, Dosing, and Safety
AU - Yonghyun Yoon
AU - Jihyo Hwang
AU - Jungyoun Kim
AU - Jonghyeok Lee
AU - Seungbeom Kim
AU - Youngmo Kim
AU - King Hei Stanley Lam
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27208967
UR - https://www.mdpi.com/1422-0067/27/20/8967
AB - Methylsulfonylmethane (MSM; dimethyl sulfone) is an organosulfur nutraceutical used primarily for joint symptoms, although its molecular actions and clinical applicability beyond osteoarthritis remain uncertain. This narrative review integrates pharmacological, preclinical, and human evidence on MSM, with emphasis on musculoskeletal disorders, multi-ingredient formulations, dosing, safety, toxicology, and clinical monitoring. Experimental studies implicate NF-κB and NLRP3 signaling, redox regulation, sulfur metabolism, and AMPK/mTOR/ULK1-related autophagy; however, most pathway-level evidence remains preclinical. Human clinical evidence is comparatively most developed for knee osteoarthritis, although it remains limited to small, short-term randomized trials reporting modest symptomatic improvement rather than established structural or disease-modifying benefit. Recent evidence syntheses also identify signals for glucosamine–MSM and glucosamine–chondroitin–MSM combinations, although certainty is limited and the independent contribution of MSM cannot be determined. Tendon studies largely evaluate multi-ingredient products, preventing attribution of benefit to MSM alone. Evidence in cardiometabolic disease, gastrointestinal health, exercise recovery, and toxicant exposure is preliminary. MSM is not a direct metal chelator and should not replace established chelation therapy. Short-term studies have used approximately 1–6 g/day with generally mild gastrointestinal adverse effects, whereas long-term safety, formal drug-interaction data, and clinically validated biomarker-guided dosing remain undefined. MSM should therefore be considered an adjunct with indication-dependent evidence rather than a broadly applicable anti-inflammatory or detoxification supplement.
SN - 1422-0067
ER -