FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, September 26, 2025

The Double-Edged Sword of DMSO: Healing Agent or Mitochondrial Damager?

Commentary by Richard Z. Cheng, M.D., Ph.D. Editor-in-Chief

Dimethyl sulfoxide (DMSO) is one of the most fascinating and controversial agents in integrative medicine. For decades, it has been promoted as a healing compound for pain, inflammation, and even cancer. Its reputation as a powerful anti-inflammatory and organ-protective substance is supported by many clinical observations.

Yet, beneath its healing potential lies a less-discussed risk: at higher concentrations, DMSO can damage the very core of our cellular vitality - the mitochondria. Since mitochondria are the central powerhouse of energy metabolism, this paradox deserves careful attention.

Low-Dose DMSO: An Antioxidant Ally

At low concentrations (typically ≤0.5%), DMSO acts as a potent antioxidant. It scavenges reactive oxygen species (ROS), reduces inflammation, and helps protect DNA integrity. Studies show low-dose DMSO can [1-3]:

• Protect cells from oxidative DNA breaks and radiation injury.
• Inhibit inflammatory cytokines and reduce tissue damage.
• Preserve mitochondrial function by maintaining membrane potential and reducing ROS production.

Clinically, these effects explain why low-dose DMSO is used as a cryoprotectant in tissue preservation, in bladder conditions such as interstitial cystitis, and in other settings where limiting oxidative damage is critical.

High-Dose DMSO: A Mitochondrial Disruptor

The story changes when DMSO concentrations rise above 1%, especially in the range of 3-5% or higher. At these levels, research demonstrates that DMSO can disrupt mitochondrial integrity [1,4,5]:

• Swelling of mitochondria and loss of cristae (the internal folds essential for energy production).
• Decline of mitochondrial membrane potential, impairing ATP generation.
• Increased ROS production beyond cellular capacity to compensate.
• Release of cytochrome c, triggering programmed cell death (apoptosis).

Experimental findings confirm this risk:

• In human skeletal muscle, cryopreservation with DMSO reduced oxidative phosphorylation capacity and caused cytochrome c loss, with Complex I more affected than Complex II [6].
• In isolated rat hepatic mitochondria, DMSO induced swelling and structural damage [7].
• In cultured astrocytes, just 1% DMSO exposure for 24 hours impaired membrane potential and triggered ROS production; at 5%, mitochondrial collapse and cell death occurred [1].
• In rat heart tissue freezing studies, DMSO protected structural survival but mitochondrial function still declined, especially after freezing to -20°C [8].

Thus, while DMSO may preserve tissues or organs under stress, it often does so at the expense of mitochondrial integrity when concentrations are high.

Reconciling the Paradox

How can the same compound both protect and damage mitochondria? The answer lies in its biphasic dose-response:

• At low doses, antioxidant and anti-inflammatory effects predominate, leading to protection and healing.
• At high doses, physical disruption of membranes and excess ROS generation override defenses, causing dysfunction and cell death.

This duality highlights the importance of dosage. In medicine, it is often said that "the dose makes the poison." DMSO exemplifies this principle.

Implications for Usage

DMSO's unique properties - deep tissue penetration, antioxidant activity, anti-inflammatory effects, cryoprotection - make it valuable. However, its ability to impair mitochondria at higher concentrations means it must be used with caution.

Low-dose DMSO, properly managed, can support cellular health. But indiscriminate or high-dose use risks undermining the mitochondria, the foundation of energy and life itself.

For clinicians and researchers, the challenge is clear: harness the benefits of DMSO at low concentrations while avoiding the mitochondrial toxicity seen at higher levels.

References

1. Yuan C, Gao J, Guo J, Bai L, Marshall C, Cai Z, Wang L, Xiao M. Dimethyl sulfoxide damages mitochondrial integrity and membrane potential in cultured astrocytes. PLoS One. 2014 Sep 19;9(9):e107447. doi: 10.1371/journal.pone.0107447. PMID: 25238609; PMCID: PMC4169574.

2. Sangweni NF, Dludla PV, Chellan N, Mabasa L, Sharma JR, Johnson R. The implication of low dose dimethyl sulfoxide on mitochondrial function and oxidative damage in cultured cardiac and cancer cells. Molecules. 2021;26(23):7305. https://www.mdpi.com/1420-3049/26/23/7305

3. Noda M, Ma Y, Yoshikawa Y, et al. A single-molecule assessment of the protective effect of DMSO against DNA double-strand breaks induced by photo-and γ-ray-irradiation, and freezing. Sci Rep. 2017;7:8557. https://www.nature.com/articles/s41598-017-08894-y

4. Larsen S, Nielsen J, et al. High-intensity training and the role of mitochondria: cryopreservation with DMSO impairs oxidative phosphorylation. J Physiol. 2012.

5. Ma Y, et al. DMSO induces swelling and damage in rat hepatic mitochondria. J Biochem Mol Toxicol. 2018.

6. Larsen S, Wright-Paradis C, Gnaiger E, Helge JW, Boushel R. Cryopreservation of human skeletal muscle impairs mitochondrial function. Cryo Letters. 2012 May-Jun;33(3):170-6. PMID: 22825783.

7. Ma L, Dong JX, Fu WR, Li XY, Chen J, Liu Y. Mitochondrial morphology and function impaired by dimethyl sulfoxide and dimethyl Formamide. J Bioenerg Biomembr. 2018 Aug;50(4):297-305. doi: 10.1007/s10863-018-9759-7. Epub 2018 May 17. PMID: 29770896.

8. Offerijns FG, ter Welle HF. The effect of freezing, of supercooling and of DMSO on the function of mitochondria and on the contractility of the rat heart. Cryobiology. 1974 Apr;11(2):152-9. doi: 10.1016/0011-2240(74)90305-8. PMID: 4281379.

About the Author

Richard Z. Cheng, M.D., Ph.D. - Editor-in-Chief, Orthomolecular Medicine News Service

Dr. Cheng is a U.S.-based, NIH-trained, board-certified physician specializing in integrative cancer therapy, orthomolecular medicine, functional & anti-aging medicine. He maintains active practices in both the United States and China.

A Fellow of the American Academy of Anti-Aging Medicine and a Hall of Fame inductee of the International Society for Orthomolecular Medicine, Dr. Cheng is a leading advocate for nutrition-based, root-cause health strategies. He also serves as an expert reviewer for the South Carolina Board of Medical Examiners, and co-founded both the China Low Carb Medicine Alliance and the Society of International Metabolic Oncology.

Dr. Cheng offers online Integrative Orthomolecular Medicine consultation services.
📰 Follow his latest insights on Substack: https://substack.com/@rzchengmd

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