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The Integrative Medicine Center at the University of Kansas is an outpatient clinic located in the heart of a large university medical center. The primary focus of our work is care for patients with chronic health conditions. What we learn from our patients informs our research in both basic science and clinical trials. Understandings we gain from the research improve our treatment protocols, so the process comes full circle. This is definitely translational medicine at work, translating research findings into new therapies and treatment guidelines. One of our goals is to expedite the transmission of biomedical research outcomes into clinical practice.
Our services range from wellness check-ups to cancer treatment, and we see every age group from pediatric to adult and geriatric. Our staff includes medical doctors, naturopathic doctors, advanced practice nurses, nutritionists, and neurofeedback practitioners, and the center provides more than 4,000 patient visits a year. We have a fellowship program for primary care physicians in integrative medicine and a master's degree and certificate program for nutritionists.
In our clinic, we may have an infinite number of diagnoses walk through the door, but everything comes down to the biochemistry of the individual patient. We look at diet, nutrients, and metabolism, at genetics, detox, and heavy metals. We have found that if we do not first understand the dynamics of the patient's biochemistry, we can try treatment after treatment, but we are not going to be able to make them better.
I [Jeanne Drisko] initially trained with Dr. Hugh Riordan two decades ago, when he was director of the Biocenter in Wichita, Kansas (now the Riordan Center). When I completed my training, I was asked by the Dean of the School of Medicine, Dr. Deborah Powell, to come to Kansas City and establish an integrative medicine program at KU Medical Center. That was in 1997, but at the time, no one in the institution wanted to have the program in their department. In 1998, Dr. Sterling Williams came to the university from Columbia Presbyterian in New York, where Dr. Mehmet Oz also practiced, so Dr. Williams was well versed in integrative medicine. When he assumed leadership of Obstetrics and Gynecology, he knew that he wanted integrative medicine services to be available to his patients, so he invited me to develop this program in 1998.
I had a little closet that had been a storage room. It was really gross, but I outfitted it quite well and started working out of this little closet without even a budget. (They did pay a modest salary.) I developed an education program, teaching medical students and started writing research grants. The grants began coming through, one after another, so that built the program. Then the clinical practice was added, and we moved to this wonderful space. (integrativemed.kumc.edu)
At the time we moved to the new clinic space, I had grateful patients who were very interested in seeing this work established at the University of Kansas and continue beyond me. They raised the money to create an endowed chair, the Riordan Endowed Chair of Orthomolecular Medicine, and I was appointed the first recipient. After I retire, the role will be passed on to someone else, so this work will continue, hopefully, into perpetuity.
Intravenous Ascorbate and Cancer
We are especially pleased to have had the opportunity to perform in-depth research on intravenous vitamin C (ascorbate). We had a paper published recently in Science in Translational Medicine that has been very well received by our conventional colleagues.
Translational research. The study included cell tissue, animal studies, and human clinical trials, all linked. The basic science research for these studies was performed primarily by Mark Levine, MD, at the NIH and by Qi Chen, PhD, here at the University of Kansas. These studies have been subsequently replicated and validated all around the world. In this research, we exposed cancer cell lines in vitro to concentrations of ascorbate and to various types of chemotherapy. We screened 48 different cancer cell lines and found that more than 75% were reduced by ascorbate exposure
Animal models. Our research showed that intravenous ascorbate provided therapeutic benefit in animal models of cancer and that there is promise of benefit in humans. The research found that high concentrations of ascorbate, at concentrations easily achievable in humans, can kill cancer cells without the addition of chemotherapeutic agents, through physiological processes that include autophagy, apoptosis, and necrosis. Normal cells remain unharmed.
We also investigated four cell lines in various animal models using ovarian, pancreatic, and prostate cancers and glioblastoma, injecting these cell lines into mice and then treated them with high-dose ascorbate alone. The ascorbate injections inhibited cancer growth in all four types of cancer. In the pancreatic cancer model, which is exceptionally resistant to gemcitabine treatment, ascorbate alone reduced the cancer growth by 30% to 40%, before we combined it with chemotherapy. (All this work has been published and these citations appear at the end of the article.) The ascorbate leaves the bloodstream, penetrates the interstitial space, and is converted into hydrogen peroxide, which functions as chemotherapy. The beauty of it is that normal cells have the mechanism to eliminate hydrogen peroxide, but cancer cells do not. They have lost certain normal protective mechanisms, so when a huge oxidative burst occurs, the cancer cells go into cell death.
Clinical trial. In the human component of the study, our first priority was to show that the treatment was safe. In the foundational research, there have been decades of use showing that no harm is incurred with therapeutic doses of IV vitamin C. This was the first time a study had been performed in which human subjects received intravenous infusions at 75 or 100 grams twice a week for a year. No one knew with absolute certainty whether the intravenous vitamin C was going to be safe. No significant adverse events occurred.
This was also the first time we were able to show that giving intravenous ascorbate in conjunction with chemotherapy was safe in advanced ovarian cancer patients. The study consisted of two arms, one receiving chemotherapy alone, and the other receiving chemotherapy (paclitaxel and carboplatin) with intravenous ascorbate. One unexpected finding was that the ascorbate seemed to reduce some of the side effects of chemotherapy. The women who received IV C seemed to tolerate the chemotherapy better, with fewer side effects. This was an unanticipated, but significant finding that we could really celebrate.
Although we cannot make definitive statements regarding efficacy, because the study was not powered for effects, there was a trend. The women who received the IV C seemed to do better than those who did not. This was a small clinical trial, and you never know for certain what you will find when you do a large human study.
Contraindications. When using intravenous ascorbate, we screen patients for two specific health issues. One is a low G6PD blood test which correlates with the potential for hemolysis of red blood cells when the ascorbate is administered. The second finding is oxalate kidney stones, because IV C does have the potential to worsen or precipitate oxalate kidney stones. We do not infuse these two groups of patients in our clinic with vitamin C.
Oral versus intravenous ascorbate. Authors such as Tom Levy have suggested that the effects of oral ascorbic acid are the same as those of intravenous ascorbate. Qi Chen's work, when she was at the NIH, showed clearly that ascorbate must be administered intravenously (or in the case of animals, in the peritoneal cavity), or it cannot reach the correct levels in the bloodstream. This was also the finding of Mark Levine at the NIH, prior to the work of Qi Chen. The initial studies were performed in healthy people, and later in conjunction with cancer patients, confirming that intravenous administration of vitamin C is necessary to reach concentrations high enough to be effective.
Future directions. The ground work has been laid for the use of IV ascorbate in clinical practice, and also in research. At this point, we would like to have the support of the National Cancer Institute to provide federal funding for this research to go forward.
More conventional oncologists are becoming interested in providing intravenous ascorbate with chemotherapy. Typically the oncologist administers the chemotherapy and enlists an integrative physician in the community to perform the IV C infusions. This appears to be the beginning of a synergism between the two types of providers, which I find very exciting. I receive more requests now from conventional oncologists asking for the names of people in their community or their region who might be able to provide IV vitamin C.
In terms of the research, one of our priorities is to clearly establish the details of the mechanisms by which vitamin C kills cancer cells, but conserves normal cells. We believe that is a major question to answer, one that will help us establish biomarkers to identify which patients are most likely to respond well to treatment, and those least likely to benefit.
We also need clinical trials to test the efficacy of IV C. Our research and that of many other phase 1 trials have shown that intravenous ascorbate is non-toxic and that it reduces the toxicity of chemotherapy. Although we just published a trial on specific effects on tumor tissue, there have been no formal trials to track tumor response and clinical outcomes, which are true measures of efficacy. We need a larger trial to establish those clinical benchmarks. I also want to look at pharmacokinetic evaluation of ascorbate in children. Although IV vitamin C has been given to children, no one has done a formal study with children to date.
We're planning a trip to China in June to expand this work in populations there. There is definitely interest. For our next research project we want to explore the possibility, the feasibility, of a clinical population-based study in China. Given the environmental effects of pollution, this is of major concern to the Chinese government. There is also interest in Japan, Canada, and in European countries. This is a topic of universal interest that has generated research all over the world.
The TACT Study
The KU Integrative Medicine Center was an active participant in the Trial to Assess Chelation Therapy. This study, funded by the NIH, involved more than 1700 adults with a history of cardiovascular disease and myocardial infarction. The research was performed by conventional cardiologists with the participation of integrative medicine physicians.
Patients were randomized to receive either EDTA chelation or a placebo. The formula consisted of EDTA as the chelator, as well as vitamins, minerals, and other nutrients. Since chelation can remove not only harmful heavy metals, but also beneficial minerals, it was important to follow patient blood levels, to assure that the excretion of heavy metals was not damaging the kidneys.
The chelation formula. The IV infusion included 7 grams of vitamin C. We believe that IV C is an important component of the formula due to its beneficial effects on the vasculature. It is of concern that some physicians now see chelation strictly as an antioxidative therapy and believe they should be taking the pro-oxidative IV C out of the chelation formula. Two important findings indicate otherwise. First, the pro-oxidative burst of IV C can be a highly effective tool in supporting mitochondrial health. Secondly, the study clearly defined improvements in the vasculature. (I cannot describe those benefits in detail here because we have not yet published our findings, but I can tell you that they are clinically important.)
Patient subsets within the study. We do know that diabetic patients in the study experienced a significant reduction in the incidence of recurrent heart attacks, angina, and stent placement. These patients were largely on maximal therapy and yet of all the study participants, diabetic patients benefitted most. There was another sub-group of participants who could not tolerate statin medication or did not take statins and they also benefited significantly from IV vitamin C use.
One of our upcoming research projects is to develop animal models using ketogenic diet, intravenous ascorbate, and hyperbaric oxygen to establish baselines on each of those therapies individually, and then combine the therapies to determine if there is synergistic benefit. These are areas in which we developed interest as a result of what we have been seeing in the clinic.
Epilepsy. Traditionally, the ketogenic diet is a high-fat, moderate-protein diet with either no carbohydrate or minimal carbohydrate. The most extreme ketogenic diet is used for people with epilepsy, and it is currently provided in pediatric hospitals around the country.
Alzheimer's disease. We are also finding benefit in use of the ketogenic diet for Alzheimer's disease patients to support brain health.
Cancer care. In our clinic we have observed that cancer patients on the ketogenic diet do better; and we are also finding that intravenous ascorbate augments that process. The concept is to use ketosis to change the metabolism of cancer patients, based on the work of Dr. Thomas Seyfried and his colleague Dr. Dominic d'Agostino at the University of South Florida, as reported in his book, Cancer as a Metabolic Disease.
This form of EEG therapy uses diagnostic brain mapping to establish a baseline of the patient's brainwave patterns. Neurofeedback training is subsequently used to help the patient shift those patterns. A colleague in California, Jay Gunkelman, is beginning a study under a Defense Department grant with Gulf War veterans. We are interested in duplicating some of that research here at KU Integrative Medicine Center.
Traumatic brain injury. Using neurofeedback, patients who have suffered significant traumatic brain injury with bleeds or stroke have achieved tangible gains in their functioning.
Autistic spectrum disorder. Children on the autism spectrum have a certain characteristic pattern evident in the mapping. The neurofeedback enables us focus our training in a way that helps them reengage. Like all therapies, it does not work for everyone: it is not a panacea. However, for the people we help, it can be life-changing.
Substance abuse. Some of this work came out of the Menninger Clinic in Topeka with Elmer Green, Patricia Norris, Keith Farian, and Jim Peniston, in a vast body of work on altered states. When Jim was at the Menninger Foundation with the Greens, he had a flash of insight during one of these deep state trainings that led to the development of a therapy called alpha-theta crossover, which he then used successfully with a group of Vietnam vets for substance abuse. In that initial study, at the two year follow-up, only three of the twenty participants had relapsed.
Post-traumatic stress disorder. Jim Peniston subsequently observed that this type of neurofeedback also seemed to help people with PTSD. Another psychologist/researcher, Eugenia Bodenhamer-Davis at the University of North Texas does primary research and offers neurofeedback in her clinic. She and her husband, Richard Davis, a therapist in private practice, have documented exceptional benefits using this therapy.
Essentially the process involves reducing alpha waves and elevating theta waves while maintaining beta waves. During the state that results, individuals may experience a release of stored memories throughout the body. This is not like reliving trauma – rather it is the experience of an adult in a safe place looking at that experience and being able to work through it. The benefits can be remarkable.
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