Non-Hodgkin’s Lymphoma Reversal with Dichloroacetate
Journal of Oncology
Volume 2010 (2010), Article ID 414726, 4 pages
Non-Hodgkin’s Lymphoma Reversal with Dichloroacetate
Germany’s 1Klinik im Alpenpark is located in Defreggerweg 2-6, Ringsee, 83707 Tegernsee.
2Foundation for Collaborative Medicine and Research 24 Midwood Drive Greenwich, Connecticut 06830, United States
Received on June 4, 2010, and accepted on July 23, 2010.
Michael A. Carducci is the academic editor.
Copyright © 2010 Dana F. Flavin. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Stage 4 Non-Follicular Hodgkin’s Lymphoma (NHL), discovered in June 2007, was completely remitted after a 3-month course of standard chemotherapy in a 48-year-old male patient. Nasopharynx and neck lymph gland tumors reappeared almost a year later. The patient started self-administering dichloroacetate (DCA) 900 mg daily after rejecting all proposed chemotherapies, and four months later, a PET scan revealed total remission. He hasn’t developed a tumor since his last PET scan in May 2009 while taking DCA continuously.
With 66,000 new cases in 2009, Non-Hodgkin’s lymphoma (NHL), a cancer of the lymphatic system that can begin anywhere in the body, affected 400,000+ people in the United States. . Low-grade fever, sweating, swollen lymph nodes, general malaise, and exhaustion are common NHL symptoms. Despite the fact that it responds well to conventional treatments like chemotherapy and radiation , More aggressive newer therapies, such as chemotherapy and whole-body radiation therapy followed by stem cell transplants, are being developed. . While some patients have experienced a full remission as a result of these treatments , The quality of life compromises sustained by aggressive therapies are known to other patients., seek out alternative treatment options, many of which are unconventional or still in the experimental stage, either with medical professionals or on their own. Dichloroacetate is one such treatment..
A byproduct of water chlorination is DCA. [6, 7] in which aerobic glycolysis is blocked. It has been applied to treatment for more than 30 years.  as a potential medication for the treatment of severe metabolic diseases like diabetes and hypercholesterolemia [5, 9] Also, in North America, the treatment of congenital lactic acidosis in children. . The bioavailability  and pharmacokinetics  of DCA have been well researched over several decades in adults , children [13, 14], and animals . DCA is generally well tolerated as a medication at concentrations between 10 mg and 50 mg per kilogram, while extended exposure is linked to peripheral neuropathy. . Its activation of the pyruvate dehydrogenase enzyme (PDH) of the mitochondria decreases glycolysis and reactivates glucose oxidation, a favorable approach to ameliorate lactic acidosis .
Instead of using the glucose oxidation system that healthy cells do for energy, cancer cells primarily use a system of glycolysis. Cancer seems to be a type of intracellular lactic acidosis brought on by a PDH-level block in the oxidation of glucose. Lactic acid levels in cancer cells rise as a result of the glycolysis metabolism of glucose, which also lowers intracellular pH.  significant changes in the intracellular biochemistry that follow. Aerobic glycolysis, also referred to as the “Warburg Effect,”, inhibits mitochondrial respiration, which promotes the growth of cancer cells . DCA reverses this glycolysis causing several major detrimental changes in the cancer tumor cells.
DCA primarily blocks pyruvate dehydrogenase kinase (PDK). The phosphorylation activity of PDK prevents pyruvate dehydrogenase (PDH) from functioning. When this kinase is inhibited by DCA, the PDH is reactivated, causing the mitochondria to stop being hyperpolarized and instead become depolarized. This depolarization activates the mitochondrial K+ channels, which then cause the cytosolic K+ to fall. Caspases 3 and 9, which are vital components of apoptosis, are inactivated when PDH is blocked by PDK in cancer cells. In combination with a rise in intracellular H2O2, DCA reactivates these caspases, triggering the release of cytochrome c from the mitochondria. As it initiates the caspase cascade, cytochrome c release is a crucial activation step for cell death. . DCA has an impact on cancers both in vitro and in vivo. Normal cells do not experience these effects.
The release of mitochondrial calcium (Ca++) is dichloroacetate’s other significant impact on cancer cells. The growth and proliferation of transcription factors are linked to the rise in Ca++ in cancer cells. The rate-limiting enzyme in DNA synthesis, ornithine decarboxylase, is also activated by calcium. , and the inhibitor of apoptosis NFAT . When calcium levels drop as a result of the addition of DCA, the cell is further propelled toward apoptosis and cell replication is reduced. In addition to altering the cellular membrane, cytoplasm, and mitochondria in a significant way, DCA , A cell cycle arrest in the Gap 1 phase (G1), which also increases apoptosis, is the final result of DCA. .
In 2007, a positron emission tomography (PET) scan revealed that the NHL had completely resolved after being successfully treated with six sessions of Rituxan plus CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone) over the course of three months. By August 2008, he had not had any additional treatments, and the PET scan revealed that his tumors had returned in his neck lymph glands and nasopharynx. He had been experiencing a low-grade temperature of 99.8, sweating, and exhaustion.
In August 2008, the Non-Hodgkin’s Lymphoma patient started self-administering 900 mg of dichloroacetate (DCA) daily at a dose of 10 mg/kg after rejecting conventional therapy. He also added 750 mg of thiamine daily to protect his nerves from toxicity. [15, 23]. A PET scan performed four months later revealed total remission. Since his last PET in May 2009, he has continued to receive DCA and thiamine and has remained tumor-free. His blood tests every month reveal that every parameter is within normal limits.
An NHL patient who had received chemotherapy and had been in remission for about a year complained in August 2008 of pain and tenderness in his neck region, where protrusions were evident upon inspection. To determine the nature of the issue and the degree of lymphatic involvement, a PET was performed.
Figure 1 depicts several new hypermetabolic foci in the head and neck that are consistent with recurrent lymphoma. These include a new hypermetabolism in the right postlateral aspect of the nasopharynx, measuring 3.2 2.2 cm; a new hypermetabolic adenopathy in the right neck involving the right jugulodigastric region, right jugular chain, and right posterior triangle extending to the base of the neck; the largest node
Figure 1: August 2008 PET scan.
Figure 2: December 2008 PET scan.
A PET scan performed four months after the patient started taking 750 mg of DCA daily for self-medication revealed no evidence of malignancy. After a few weeks, symptoms vanished, and 4 months later, the PET scan results shown in Figure 2 show that the previously identified foci of abnormal activity in the nasopharynx and neck had disappeared. No abnormal foci of metabolic activity were seen, and there was no sign of the disease returning.
A growing number of patients are pursuing therapies on their own, with various results; some are harmful and dangerous, while others may extend their lives but should still be carried out under medical care. Understandably, doctors frequently find themselves unable to administer or counsel patients on how to utilize their preferences morally, leaving the patient to fend for themselves. The use of dichloroacetate in cancer patients is still being researched, despite the fact that this case and others anecdotally have had beneficial outcomes that may be explained by the current considerable research on the pharmacology and toxicology of the treatment the patient chose. To test DCA sensitivity, we are currently looking at in vitro tumor samples. As some patients’ tumors respond favorably or clear up, we are also examining laboratory parameters for a potential laboratory association in responders to particular enzyme levels. DCA does not seem to be tumor type specific.
Even in the presence of oxygen, tumor cells preferentially use glycolysis to produce adenosine triphosphate (ATP), a phenomenon known as aerobic glycolysis or the “Warburg Effect.”. Pyruvate dehydrogenase (PDH), a gate-keeping enzyme for the entry of pyruvate into the mitochondrial tricarboxylic acid (TCA) cycle , is phosphorylated by the enzyme pyruvate dehydrogenase kinase, which inhibits it in cancer cells. . Because to PDK’s suppression of PDH, glucose oxidation is switched to glycolysis, which promotes the growth of tumors. . It has been demonstrated that DCA inhibits this phosphorylation by PDK at the level of the mitochondrial membrane, reducing glycolysis in favor of glucose oxidation. Major alterations are made possible by this return to a healthy metabolism of glucose, such as a reduction in intracellular Ca++ and stabilization of the mitochondria, which enable the reactivation of caspases in cancer cells and cause apoptosis. .
Although the consequences of DCA, which are brought on by the reactivation of mitochondrial respiration, are not without complications, it is puzzling why it seems to primarily affect cancer cells while the majority of normal cells are unaffected. . A daily thiamine intake for humans of several hundred milligrams can significantly reduce reversible, minimal nerve damage.  and animals . The dosage of thiamine varies depending on whether it is taken orally or intramuscularly, from 50 mg to 100 mg daily. .
As many diseases’ mitochondrial dysfunction appears to be a common pathological denominator, correcting mitochondrial dysfunction may be one of the major future pharmacological targets for treating many diseases. Additionally, lactic acidosis is recognized as a malarial consequence.  mitochondrial involvement, and most recently, Chronic Fatigue Syndrome . DCA has also been shown to help considerably in diabetes  and familial hypercholesterolemia .
A Non-Hodgkin’s lymphoma patient who took 10 mg/kg [750 mg] of dichloroacetate daily on his own initiative experienced a complete remission of his Non-Hodgkin’s lymphoma cancer after four months. He has maintained this remission to this day by continuing to take his DCA dosage in addition to taking 750 mg of thiamine to prevent the slight tingling and numbness in the nerves of the fingers and toes He has continued his DCA/thiamine regimen despite medical recommendations to not self-medicate, citing his anxiety that stopping DCA would cause the condition to resurface.
For the use of DCA in cancer treatment, there is not enough information to make firm judgments. To validate and confirm DCA’s efficacy and maintenance levels throughout the gamut of cancer therapy, controlled research must be done.
Conflict of Interests
No conflicts of interest have been reported by the author. The paper’s writing and content are the sole responsibility of the author.
We applaud Jimmy Xu from Carnegie Mellon University for his assistance. The Valerie Beth Schwartz Foundation funded this project.
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