Gout Study has exceeded 50,000 ‘likes’ on Facebook, making it the largest worldwide online gout community. Through this Facebook community, people from around the world are coming together to converse with others about living with this painful condition. Established in March 2011, Gout Study provides news, health, and wellness information, as well as information about clinical research opportunities. Gout Study statistics show how well-received and helpful the various tips and resources are to the community but it is the direct feedback from the community that drives the cause. To learn more about the Gout Study community, “like” the page at www.Facebook.com/GoutStudy.
Low rates of Influenza immunization in Ontario
A recent study revealed that Influenza vaccine coverage among children aged 6 to 23 months in Ontario is low, despite a universal vaccination program and high primary care visit rates. By using hospital records, all infants born alive in Ontario hospitals from April 2002 through March 2008 were identified. Immunization status was ascertained by linkage to physician billing data and children were categorized as fully, partially, or not immunized depending on the number and timing of vaccines administered. Influenza immunization was low for the first influenza season of the study period (1% fully immunized during the 2002-2003 season), increased for the following three seasons (7% to 9%), but then declined (4% to 6% fully immunized during the 2006-2007 to 2008-2009 seasons). Maternal influenza immunization, having a pediatrician as the primary care practitioner, high visit rates, and better continuity of care were all significantly associated with full immunization. The authors concluded that interventions to improve coverage should target both physicians and families. Pediatrics. 2012 Jun;129(6):e1421-30. PMID: 22585770
Naturopathic profession recognized under Health Professions Act in Alberta
A new regulation under the Health Professions Act establishes the College of Naturopathic Doctors of Alberta (CNDA) and gives that body the authority to establish requirements for entry into the profession and ongoing professional development. The CNDA serves to define the entry level and continued competence qualifications for Naturopathic Doctors in Alberta; administer standards of practice and professional conduct, and; investigate naturopathic-related complaints on behalf of the public. “Today, Albertans can have confidence when they reach out to a member of the College of Naturopathic Doctors of Alberta, that they have a naturopathic doctor who meets stringent competency and practice requirements,” said Dr. Allissa Gaul, founding president of the CNDA. “We offer Albertans a distinct system of primary health care that is an art, a science, a philosophy and a practice of diagnosis and assessment, treatment and prevention of illness, and we applaud this government for making health and wellness a priority to benefit Albertans.”
Integrated Health Clinic Cancer Care Centre
Integrated Health Clinic Cancer Care Centre
We showcased the Integrated Health Clinic in the September 2009 issue of IHP. Dr’s Karen and Gurdev Parmar have been busy for the past three years.
Karen and Gurdev founded the clinic in 2000, with the mission statement of the facility serving as a guiding force governing all patient interactions; “at Integrated Health Clinic, we strive to treat all of our patients with compassion and respect, providing treatment options that are individualized for healing and quality of life”. The facilities golden rule is to ensure “every patient receives five- star service”.
Word has spread across the country and the continent as to the cutting- edge treatments offered at the facility. Patients come to Fort Langley from near and far seeking the exceptional standard of care, reputation, and commitment to the best available medicine the facility has been delivering for over a decade. Not a week ago while meeting with a highly reputable naturopathic oncologist in the Toronto area was I informed of several patients the ND had personally referred to visit the Fort Langley facility for treatments not available anywhere else in Canada.
Dr. Gurdev Parmar has entrenched himself in the Canadian and North American landscape as an elite level practitioner of integrative oncology. Something the Parmar’s had been planning for several years has recently come to fruition; the establishment of the Cancer Care Centre adjacent to the Integrated Health Clinic. The Cancer Care Centre is an 1800 sqft facility dedicated to the ever- growing patient base seeking the oncology expertise of Gurdev, his associate Dr. Johan Ghazali, and the other essential team members. Of similar timing was a major clinical advance for the team; offering of localized hyperthermia treatments for cancer. The continued pursuit of cutting- edge technologies and treatments necessitated the creation of the Cancer Care Centre to accommodate the growing patient base seeking such services. The establishment of both local and whole body hyperthermia treatments are the newest gems in the team’s pursuit of offering the very best in available cancer treatment options.
Gurdev highlights Locoregional Hyperthermia (LRHT) as an incredibly effective and truly integrative treatment. He describes it as truly integrative because “it is not a stand alone therapy. It works best in conjunction with chemotherapy and radiation. We have clearly seen patients having highlyimproved responses to conventional treatment when we apply LRHT”. “The key is coordinating the hyperthermia treatments with the patients chemotherapy/ radiation schedule”. Gurdev also describes the therapy as an important tool for palliative care, and as having a role as a monotherapy. “We have seen LRHT alone, in advanced and refractory patients, achieve reduction in tumour burden, improve QOL, and improve survival”. Gurdev highlights that the greatest success with LRHT is anticipated in the management of solid tumours. “For leukemias, lymphomas, testicular cancer, conventional treatments are the key. Integrative Oncology has less to offer in the primary treatment of these patients”.
After two years of experience with LRHT in which over 3,000 treatments were applied, Gurdev is thrilled that IHC is now offering fever range whole body hyperthermia (WBHT). WBHT applied in the fever range involves heating the core body temperature to 40 degrees celsius for five to six hours. This is used to augment chemotherapy in metastatic disease, as well as in leukemias and lymphomas.
The team has done an incredible job of creating positive working relationships with surrounding conventional and integrative oncologists. Referrals from other ND’s and local oncologists are a frequent occurrence. Gurdev continues to have a special working relationship with the team at the Lions Gate Hospital chemotherapy clinic, further ensuring integrative oncology reaches as many patients as possible. Gurdev maintains the ambition of serving as a residency site for the FABNO program, although progress in this area has met with some obstacles. A Canadian site is yet to serve as a residency facility for the FABNO designation, and many of the obstacles centre upon this. Likewise, the process of the naturopathic education research counsel (NERC) securing funding for the residents is another obstacle. Although having taken several years of diligence to deliver, the centre is 99%+ poised to meet this milestone, with the residency program linked to, or “offered through”, Bastyr University. Residents from Canada and the USA will be accepted.
The offering of LRHT at the facility has resulted in the arrival of patients from across Canada, the USA, and even as far away as New Zealand and South Africa. The Integrated Health Clinic and the newly created Cancer Care Centre have been offering leading- edge cancer treatments for many years prior to the arrival of LRHT, and several strategies remain mainstays in addition to the welcomed arrival of LRHT.
Such strategies include IV vitamin C, dichloroacetate (DCA), working with patients to improve diet and implement exercise, as well as nutritional/ nutraceutical/ functional food/ botanical supplementation Gurdev involves himself with many projects outside of practice, including roles on the Board of OncANP, the Editorial Board of the International Journal on Oncothermia, and the Board of Governors of CCNM. Gurdev highlights a very critical aspect of cancer care across Canada and most industrialized nations; far too much attention is centred on cancer treatment.
The best way to combat cancer is through prevention, and also through better screening. Early detection for most cancers is a major determinant of survival and QOL. Gurdev is a powerful advocate for improvements in screening technologies, as well as improvement in access to screening services. This important message is disseminated through the many avenues Gurdev gives back to the profession in an educational role.
Dr. Karen Parmar, Cofounder of the Integrated Health Clinic, has temporarily taken a step back from the practice. The arrival of her forth son, two horses, and a hobby farm have become her priorities in the immediate future, as has home-schooling of their eldest two sons for the past two years. She has plans of rejoining the team in the future, continuing her work in the areas of women’s health, pediatrics, and fertility. Karen maintains her role as the President of the College of Naturopathic Physicians of BC.
We at IHP feel the immense contributions of the Parmar’s to the profession is often over shadowed by their tremendous advances in clinical therapeutics their patients have come to be so grateful for. The Integrated Health Clinic and the Cancer Care Centre have established themselves as a centre of excellence for integrative medicine in Canada and beyond. The hundreds of ND’s who will have their careers molded by the efforts of Karen and Gurdev is among their greatest professional achievements.
Holly Fennell, ND
Holly Fennell, ND
InsideOut Health Solutions
IHP is excited to profile a highly successful and motivational Naturopathic Doctor, Holly Fennell. Holly founded InsideOut Health Solutions in 2005; the clinic is centrally located at Yonge and Summerhill in Toronto. Starting in a 500 square foot clinic, her practice quickly outgrew the space. The clinic now occupies the fourth floor of her building and is 1600 square feet.
InsideOut is comprised of Holly, Erin Truscott, ND, three registered massage therapists (Douglas Aboud, Heather Atkinson, Andrea Purdy), a psychotherapist (Lori Dennis), a social worker (Nelson Parker), and an office manager (Jaene Castrillon). Holly sees an average of 10-15 patients each day. Erin Truscott, ND, assists by running IV shifts that can accommodate up to seven patients at a time.
Holly graduated from CCNM with the recognition that she needed a better understanding of how the healthcare system operated in Ontario. She had a mandate to understand the benefits of the system and to determine what was lacking. She realized that a truly collaborative approach among healthcare practitioners was rare but absolutely necessary for the success of an integrated clinic.
Her motivation in opening InsideOut was to create an integrative health care centre that fostered confidence and acceptance of naturopathic medicine and naturopathic doctors as primary health care providers. She believes that naturopathic medicine serves the community best through a collaborative approach.
Many patients consider Holly as their case manager; she involves their entire healthcare team, including family doctors, oncologists, physiotherapists, and chiropractors, among others. To provide exemplary care, Holly believes that she must understand and appreciate the contribution of every practitioner on the team, striving to add value by filling in the gaps in treatment management and by incorporating naturopathic modalities into patient care. She notes that although it is important to remain humble, it is essential to assert confidence when inserting herself into the healthcare team.
Holly has found that sharing individually tailored, concrete treatment plans of action with both patients and their healthcare teams has proven highly beneficial. She feels that this practice effectively pulls everyone together and fosters a team approach. In Holly’s experience, medical doctors appreciate this communication. In addition, she finds that this direct communication can unburden patients who may be anxious about discussing naturopathic treatment options with their physicians and medical team. Holly re-iterated throughout the interview that it is not the patient’s responsibility to convince medical doctors that naturopathic doctors are highly skilled practitioners providing evidence-based recommendations; instead, this is the naturopathic doctor’s responsibility.
Referrals from medical doctors have contributed to the tremendous success that InsideOut has achieved. Holly has a close professional relationship with world-renowned sports physician, Dr. Anthony Galea, whom she has known since 2005 when the Toronto Argonauts hired her to be part of their medical team; Holly was the first naturopathic doctor ever hired by the Canadian Football League. She toured with the Argonauts for four seasons and was on the front lines as she huddled with the team doctors on the field at every game. This professionally life-changing experience drove her to formulate and develop an electrolyte product that would serve as a superior alternative to the commercially available products that Holly considered inadequate. This product was quickly adapted by many players and continues to be used by several professional athletes and doctors. Holly considers Dr. Galea a powerful mentor and says that his compassion as a physician drives her to excel in patient care.
Holly also works closely with highly sought after plastic surgeon, Dr. Trevor Born whose clinics are state-of-the-art surgical facilities, devoted to providing the latest surgical and non-surgical breakthroughs in cosmetic and reconstructive plastic surgery. Dr Born has remarkably influenced Holly’s career and he refers patients to her for pre- and post-operative care. He has even taken her into his post-operative suite to treat patients that can benefit from IV therapy immediately following surgery. In fact, after several years of working together, Dr. Born and Holly identified the key nutrients required for healing and health maintenance and created a line of pre- and post-operative supplements. The line has been a huge success and has bridged the naturopathic and medical communities in a very positive way (to learn more, visit http://tmbcosmeticsurgery.com/medical-spa/nutritionalsupplements. html).
Finally, Dr.Vineet Nikore, an emergency room doctor, sports medicine doctor, and pain specialist, is another source of referrals for InsideOut. Holly considers him to be a wealth of knowledge and is proud that he respects her skills and training as a naturopathic doctor. She believes that he exemplifies the most important quality in a doctor: openness. Dr.Nikore has a keen interest in how naturopathic medicine can aid his patients’ care.
It is evident that Holly works hard to develop relationships with medical experts in multiple fields. She believes that this has been a major contributing factor to her success and growth as a clinician. It even guides the choices of nutraceutical companies and laboratories that InsideOut associates with. She does not support one brand but the best products from many different companies. Holly is grateful for the support from companies such as Douglas Labs, Pascoe, and Biotics Research. She stocks her dispensary with companies that stand behind their products both scientifically and ethically. The clinic also offers many integrated laboratory tests by such companies as Metametrix, Doctor’s Data, and Gamma Dynacare. Holly has developed relationships with the group of experts employed by these companies and maintains regular contact with them for current research in the field and on products.
Holly is passionate about excellence in patient care and management and IHP is grateful that she allowed us a glimpse into her practice. The success that InsideOut Health Solutions has cultivated should be motivational for healthcare providers to collaborate and create stronger bridges amongst various professions.
Dichloroacetate (DCA)
Dichloroacetate (DCA)
Application in cancer management
Abstract Most cancer cells use anaerobic glycolysis for energy production, despite the fact that oxygen is present. This is termed the Warburg effect and results from mitochondrial dysfunction, which prevents mitochondria-based glucose oxidation. As a result, cancer cells upregulate glucose receptors and significantly increase glucose uptake, creating a large difference between malignant cells and normal cells. Glycolysis results in lactic acidosis and this can facilitate tumour growth by breaking down the extra-cellular matrix allowing for expansion, increasing cell mobility and metastatic potential, and by activating angiogenesis. Dichloroacetate (DCA) is known to environmental scientists as a by-product of water chlorination and is a metabolite of industrial solvents. In this regard, it has been implicated in a variety of life-threatening toxicities and considered a human health hazard. However, DCA has been known for years to physicians and researchers as an investigational drug for certain metabolic diseases such as inborn errors of mitochondrial function in children, as well as a potentially promising therapy for cancer. DCA works by stimulating mitochondrial function and by inhibiting the family of regulatory pyruvate dehydrogenase kinases (PDK). This activates pyruvate dehydrogenase (PDH) and at the expense of glycolysis, reverses the Warburg effect, diminishing the growth advantage of highly glycolytic tumours. DCA has been studied in multiple different formats: in vitro, in vivo, as monotherapy, and in conjunction with other drugs. It has shown signs of benefit in multiple cancers, including glioblastoma, ovarian cancer, endometrial cancer, breast cancer, lung cancer, colorectal cancer, and in metastatic carcinomas. The evidence available for DCA in the treatment of various cancers is reviewed. Clinical pearls from the practice of Gurdev Parmar, coauthor if this article and a Fellow of the American Board of Naturopathic Oncology are provided.
Introduction
Most cancer cells use anaerobic glycolysis for energy production, despite the fact that oxygen is present. This is termed the Warburg effect and results from mitochondrial dysfunction, which prevents mitochondria-based glucose oxidation (Bayley 2012). Since glucose oxidation is far more efficient at generating ATP compared with glycolysis, cancer cells upregulate glucose receptors and significantly increase glucose uptake. This creates a large difference between malignant cells and normal cells and offers the potential for a very selective therapeutic target, since glycolysis is not seen in normal tissue apart from skeletal muscle during strenuous exercise (Michelakis 2008). Glycolysis results in lactic acidosis, which has the ability to cause toxicity to surrounding tissues and to the cancer cells themselves. However, lactic acidosis can facilitate tumour growth by breaking down the extra-cellular matrix allowing for expansion, increasing cell mobility and metastatic potential, and by activating angiogenesis (Gatenby 2004). Thus, the metabolic remodeling in cancer cells that primarily utilize glycolysis may provide a survival advantage.
Dichloroacetate (DCA) is known to environmental scientists as a by-product of water chlorination and is a metabolite of industrial solvents (Stacpoole 2011). In this regard, it has been implicated in a variety of life-threatening toxicities and considered a human health hazard (IRAC 2004).
However, DCA has been known for years to physicians and researchers as an investigational drug for certain metabolic diseases such as inborn errors of mitochondrial function in children, as well as a potentially promising therapy for cancer. DCA works by stimulating mitochondrial function and by inhibiting the family of regulatory pyruvate dehydrogenase kinases (PDK) (Papandreou 2011). This activates pyruvate dehydrogenase (PDH) and at the expense of glycolysis, reverses the Warburg effect, diminishing the growth advantage of highly glycolytic tumours. DCA has been studied in multiple different formats: in vitro, in vivo, as monotherapy, and in conjunction with other drugs. It has shown signs of benefit in multiple cancers, including glioblastoma, ovarian, endometrial, breast, lung, colorectal, and in metastatic carcinomas (Michelakis 2008). This article will review the evidence available for DCA in the treatment of various cancers. Clinical pearls from the practice of Gurdev Parmar, coauthor of this article and a Fellow of the American Board of Naturopathic Oncology are also provided.
Mechanism of Action
A metabolic modulator, DCA is a small molecule and when taken orally can achieve 100% bioavailability (Bonnet 2007). Due to its limited size, DCA can penetrate into the traditional chemotherapy sanctuary sites, including the brain (Michelakis 2008). In vitro, DCA activates PDH by inhibiting PDK and acts in a dose-dependent fashion. This results in a decrease of lactate levels in both the blood and the cerebrospinal fluid by more than 60% (Stacpoole 1989). The metabolic fate of glucose; either entry into glycolysis within the cell cytoplasm or oxidation within the mitochondria via the Kreb’s cycle; is controlled by the gate-keeping mitochondrial enzyme, PDH. Thus, the activation of PDH shifts cell metabolism away from anaerobic glycolysis and towards glucose oxidation. The activation of PDH also causes numerous other anti-cancer effects within the cell.
DCA has an effect on the polarization of the mitochondrial membrane, due to the enhanced activity of PDH. Several human cancer cells have high mitochondrial membrane potential, including non-small cell lung cancer, breast cancer, and glioblastoma cell lines, when compared with non-cancer cell lines (Bonnet 2007). By decreasing the polarization potential, DCA causes an opening of mitochondrial transition pores. This allows the movement of reactive oxygen species, such as hydrogen peroxide, and cytochrome c from the mitochondria to the cytoplasm of the cell, inducing apoptosis through the activation of caspases (Seth 2011). Neoplastic cell lines also express a lower level of potassium channels, which contributes to apoptosis resistance. The mitochondrial remodeling that occurs due to DCA has another downstream effect, since mitochondria also control calcium concentrations and calcium and potassium concentrations are related. DCA upregulates and actives potassium channels in cancer cells, but not in normal cells. This inhibits tumour growth without causing toxicity (Bonnet 2007).
The initial half-life with the first dose of DCA is less than an hour, but this half-life increases to several hours with subsequent doses. With chronic use, serum levels plateau (Mori 2004). In clinical trials for lactic acidosis, sepsis, burns, and cirrhosis, doses have ranged from 25 to 100mg/kg per day orally or intravenously (Stacpoole 2003).
Evidence
DCA has been studied for the treatment of glioblastomas (GBM). In GBM cell lines from 49 patients, DCA reversed mitochondrial hyperpolarization and did not affect the polarization of normal brain tissue (Michelakis 2010). Five consecutive patients with primary GBM were also treated with DCA. Three of these patients had recurrent GBM with disease progression after several chemotherapies and standard treatment, and thus were considered appropriate for palliative therapy. The remaining two patients were newly diagnosed after debulking surgery and DCA was administered in addition to standard treatment. Patients were treated with a starting dose of 12.5mg/kg orally twice a day for 1 month, at which point the dose was increased to 25mg/kg orally twice a day. Following this, a dose de-escalation protocol was initiated, whereby the dose was decreased by 50% when dose-limiting toxicity occurred. The patients were followed for 15 months. None had hematologic, hepatic, renal, or cardiac toxicity. Peripheral neuropathy was the only apparent toxicity and it resolved when the dose was decreased to 6.25mg/kg orally twice a day. Three of the patients showed evidence of radiologic regression on MRI. Four of the patients were clinically stable at month 15 of DCA therapy and alive at month 18 (Michelakis 2010).
In one study examining the use of DCA on ovarian cancer cell lines, the researchers utilized mitaplatin, a compound with two DCA units appended to a platinum center that when reduced also releases cisplatin, a common chemotherapy drug (Dhar 2009). Platinum compounds are used in half of all cancer therapies (Galanski 2005). However, the use of cisplatin to treat malignancies has been limited because of side effects and acquired resistance, which is a failure to execute apoptosis despite initiation of the apoptotic cascade (Siddik 2003). The combination of cisplatin and DCA provides a dual killing mechanism. Through this unique mechanism, mitaplatin attacks both nuclear DNA with cisplatin and mitochondria with DCA selectively in cancer cells. A separate study examined the use of DCA alone on epithelial ovarian cancer cells. These cancer cells are under intrinsic oxidative stress that alters metabolic activity and reduces apoptosis. DCA was able to reverse the increased oxidative stress and induce apoptosis (Saed 2011).
A study of DCA on endometrial cell lines showed that DCA treatment initiated apoptosis in five low to moderately invasive cancer cell lines and had no effect on a non-cancerous cell line (Wong 2008). Two highly invasive endometrial adenocarcinoma cell lines were found to be resistant to DCA-induced apoptosis. Thus, DCA does not have evidence of efficacy in some cancer types. Tumour acidity is a driving force in invasion and metastases and the buffering of extracellular acidity can inhibit the spread of metastases. This was shown in a mouse model for metastatic breast cancer (Robey 2011). In this study, DCA alone or in combination with bicarbonate did not increase systemic alkalosis. DCA monotherapy was not effective in reducing tumour size or metastases or improving survival time. This outcome may be a function of hypoxia in the tumour microenvironment (Robey 2011). However, in another study of breast cancer cells, DCA was studied in combination with arsenic trioxide, a drug that is typically used in promyeloid leukemia (Sun 2011). The combination of the drugs was more effective at inhibiting cell proliferation and inducing cell death than either drug alone.
A recent study examining lung carcinoid cell lines utilized DCA in combination with other platinum-based chemotherapeutic drugs, including satraplatin and picoplatin (Fiebiger 2011). The carcinoid cell lines were sensitive to the majority of chemotherapeutics in vitro. Even in highly chemoresistant cell lines, DCA was able to inhibit their growth by 22% and sensitized the cells to some of the platinum-based drugs (Fiebiger 2011). In a study of colorectal cancer cells, DCA was tested alone and in combination with 5-Fluorouracil (5-FU), the classical chemotherapy agent that has been the first line regimen for treating colorectal cancer (Meyerhardt 2005). Four human cell lines were treated in total. Cell cycle and apoptosis were measured by flow cytometry and the expression of apoptosisrelated molecules was assessed by western blot. The results showed that DCA inhibited the viability of colorectal cancer cells and had a synergistic anti-proliferation effect in combination with 5-FU (Tong 2011). Therefore, DCA appears to be helpful when used in combination with other chemotherapy drugs.
Finally, a recent case report has investigated the use of DCA for cancer treatment in a palliative setting (Khan 2011). A 71-year-old male with poorly differentiated carcinoma of unknown primary metastatic origin to the right leg and liver achieved excellent palliation of leg pain by using oral DCA after failing conventional therapy (Khan 2011). This patient was treated with 500mg three times a day (the equivalent of 21mg/kg) on a 2 week on and 1 week off cycle. After 8 months, the patient was able to eliminate the use of opiates, including morphine, and did not experience any side effects from DCA treatment. To help prevent peripheral neuropathy, the patient was simultaneously treated with R+ alpha lipoic acid (ALA), acetyl L-carnitine, and benfotiamine (Khan 2011). These additional therapies may be useful for patients undergoing DCA therapy.
Clinical Pearls
Dr. Gurdev Parmar, ND, FABNO is the founder and medical director of the Integrated Health Clinic in Fort Langley, British Columbia. Dr. Parmar has been supervising patient’s using oral DCA for several years, and has now used it in well over a hundred patients. Patients are typically started at 15mg/kg/day in divided doses, either 2 weeks on and 1 week off, or 5 days on and 2 days off. In Dr. Parmar’s opinion, the break is critical for limiting the only known significant side effect of reversible peripheral neuropathy. The dose is then titrated up to 40-50mg/kg/day, by increments of 7.5mg/kg/day every 1-3 months, depending on the patient’s Karnofsky score and co-morbidities. Dr. Parmar rarely exceeds an oral dose of 45 to 50 mg/kg/day.
Dr. Parmar has also used IV DCA for the past year, and has treated approximately 30 patients with the IV form of DCA. The starting dose used was 20mg/kg per IV, once to twice weekly. Many patients were escalated up to 50mg/kg per IV once to twice weekly. In conjunction with this treatment, IV ALA and Intravenous Vitamin C are administered. In addition, an oral supplement regime of ALA, acetyl-L-carnitine, and vitamin B1 are recommended to help limit neuropathy, and doubled to treat it if it does occur. When patients develop neuropathy, they are asked to stop DCA treatment altogether until symptoms start to improve. At that point, they are started at 7.5mg/kd/day and slowly titrated to the highest tolerated dose, not to exceed the dose that previously caused the neuropathy.
In terms of side effects that have been noted, Dr. Parmar has had one patient develop motor and sensory, seemingly central nervous system related symptoms. This patient developed symptoms including confusion, twitching, fatigue and muscle weakness. (coloredmanga.com) This occurred in the absence of any peripheral neuropathy in the hands and feet, and at a dose of 47 mg/kg/day. This patient was however also receiving several adjunctive therapies concurrently to the DCA, which included herbs that could have induced the drug, or down-regulated its metabolism and excretion. In fact, he was taking over 30 different herbal preparations previously prescribed by a herbalist, including very high doses of artemisinin, a known neurotoxic agent (Schmuck 2002).
Dr. Parmar has had several patients that have had a significant response to DCA, with partial to complete responses on imaging, due to DCA monotherapy. One patient with stage IV colorectal cancer who was no longer receiving conventional therapy due to lack of benefit, had no evidence of disease after almost a year of DCA therapy. Another colorectal cancer patient was rapidly metastasizing prior to DCA therapy. For two years since she initiated DCA therapy, her disease has been stable. Finally, several patients with GBM have received DCA alongside local-regional hyperthermia, which has led to significant improvements on repeated MRI and contrast CT. Dr. Parmar’s Integrated Health Clinic is currently working to collate this information on a database, with plans for publication thereafter. He is particularly interested in the tumour microenvironment, and the positive metabolic and immunogenic effects of hyperthermia alongside novel treatments such as DCA.
Conclusion
After many years of use, the only documented side effect of DCA is dose-dependent reversible peripheral neuropathy (Michelakis 2008). DCA activates PDH and shifts the metabolism of cancer cells towards glucose oxidation. In addition, DCA decreases the polarization potential of the mitochondria, causing an opening of mitochondrial transition pores and leading to apoptosis. There is direct preclinical evidence of anticancer effects of DCA with glioblastoma, ovarian, endometrial, breast, lung, and colorectal cancer. Though DCA appears more effective in combination with other chemotherapy drugs, it is not effective in all cell lines. The lack of mitochondrial hyperpolarization in certain types of cancer including lymphomas, neuroblastomas, and sarcomas indicates that DCA may not be effective in these cases (Chen 1988). There is limited evidence for the direct use of DCA in human patients, but funding for trials is a challenge since DCA is a generic drug and industry support may be limited. DCA treatment is still considered experimental is not endorsed by the authors. DCA therapy should only be used as an adjunct to current best practices and does not replace standard of care. Clinical experiences from the practice of a Fellow of the American Board of Naturopathic Oncology support the general safety and efficacy of the supervision of patients wanting to receive the experimental treatment of DCA, both orally and intravenously.
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Wong JY, Huggins GS, Debidda M, Munshi NC, De Vivo I. Dichloroacetate induces apoptosis in endometrial cancer cells. Gynecol Oncol. 2008;109(3):394-402.
Amoxicillin for the treatment of acute rhinosinusitis
Although evidence to support antibiotic treatment for acute rhinosinusitis is limited, antibiotics are commonly used. This randomized, placebo-controlled study was conducted to determine the incremental effect of amoxicillin treatment over symptomatic treatments for 166 adults with uncomplicated, clinically diagnosed acute rhinosinusitis. A ten-day course of either amoxicillin (1,500 mg/d) or placebo was administered in three doses per day. All patients received a 5- to 7-day supply of symptomatic treatments for pain, fever, cough, and nasal congestion to use as needed. The mean change in Sinonasal Outcome Test-16 scores was not significantly different between groups on days three or ten but differed at day seven favoring amoxicillin (mean difference between groups of 0.19; 95% CI, 0.024 to 0.35). There was no statistically significant difference in reported symptom improvement at days three or ten, whereas at day seven more participants treated with amoxicillin reported symptom improvement (P = 0.02). No between-group differences were found for any other secondary outcomes and no serious adverse events occurred. The authors concluded that among patients with acute rhinosinusitis, a ten-day course of amoxicillin compared with placebo did not reduce symptoms at day three of treatment. JAMA. 2012 Feb 15;307(7):685-92. PMID: 22337680
Use of antidiabetic agents increase the risk of pancreatic cancer
This case-control study was conducted to explore the association between the use of antidiabetic drugs, diabetes, and the risk of pancreatic cancer. Using the UK-based General Practice Research Database (GPRD), cases included patients with a first-time diagnosis of pancreatic cancer (N = 2,763, mean age 69.5±11.0 years). Six controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the GPRD before the index date. Long-term use (≥30 prescriptions) of metformin was not associated with an altered risk of pancreatic cancer (OR 0.87; 95% CI 0.59-1.29), but there was a suggestion of effect modification by gender, as long-term use of metformin was linked to a decreased risk in women (OR 0.43; 95% CI 0.23-0.80). Long-term use of sulfonylureas (≥30 prescriptions; OR: 1.90; 95% CI 1.32-2.74) and insulin (≥40 prescriptions; OR 2.29; 95% CI 1.34-3.92) were both associated with an increased risk of pancreatic cancer. The authors concluded that use of sulfonylureas and insulin was associated with an increased risk of pancreatic cancer and use of metformin was associated with a decreased risk of pancreatic cancer in women only. Am J Gastroenterol. 2012 Apr;107(4):620-6. PMID: 22290402
Beetroot juice and novel beetrootenriched bread products have blood pressure-lowering effects
Two separate randomly controlled, single-blind, cross-over, postprandial studies were performed in normotensive volunteers to investigate ambulatory blood pressure (BP) following consumption of either four doses of beetroot juice (BJ) (N = 18; 0, 100, 250, and 500 g), or three bread products (control bread, red beetroot- and white beetroot-enriched breads (N = 14; 0, 100, and 100 g beetroot, respectively). Total urinary nitrate/nitrite (NOx) was measured at baseline, and at two, four, and 24 h post-ingestion. Over a 24 h period, BJ consumption significantly, and in a near dose-dependent manner, lowered systolic BP (SBP; P < 0.01) and diastolic BP (DBP; P < 0.001) compared to control and the beetroot-enriched bread products lowered SBP and DBP (red beetroot-enriched bread, P < 0.05), with no statistical differences between the varieties. Total urinary NOx significantly increased following the consumption of 100 g (P < 0.01), 250 g (P < 0.001) and 500 g BJ (P < 0.001) and after red beetroot-enriched bread ingestion (P < 0.05). These data demonstrated the BP-lowering cardioprotective effects of a low dose of beetroot, which seem to be unaffected by processing. Br J Nutr. 2012 Mar 14:1-9. PMID: 22414688
N-acetylcysteine supplementation for the prevention of atrial fibrillation after cardiac surgery: meta-analysis
Oxidative stress may play a pivotal role in the pathophysiology of atrial fibrillation, the most common type of arrhythmia after cardiac surgery. Since N-acetylcysteine (NAC) is a free radical scavenger, it may attenuate this pathophysiologic response and reduce the incidence of postoperative atrial fibrillation (POAF). This meta-analysis was conducted to assess the efficacy of NAC supplementation on the prevention of POAF. Medline and Embase were systematically reviewed for studies published up to November 2011, in which NAC was compared with controls for adult patients undergoing cardiac surgery. Eight randomized trials (n = 578) were included and outcome measures included the incidence of POAF and hospital length of stay (LOS). NAC supplementation was found to significantly reduce the incidence of POAF (OR 0.62; 95% CI 0.41-0.93; P = 0.021) compared with controls, but had no effect on LOS (weighted mean difference 0.07; 95% CI 0.42-0.28; P = 0.703). The authors concluded that prophylactic NAC supplementation might effectively reduce the incidence of POAF but note that the overall quality of current studies is poor. Adequately powered randomized controlled trials with POAF incidence as a primary outcome measure are necessary before concrete conclusions can be made. BMC Cardiovasc Disord. 2012 Feb 24;12(1):10. PMID: 22364379
