Last week I discussed the dismal results of the “Gonzalez Trial” for cancer of the pancreas,* as reported in an article recently posted on the website of the Journal of Clinical Oncology. I promised that this week I’d discuss “troubling information, both stated and unstated [in the report],” and also some ethical issues. More has come to light in the past few days, including Nicholas Gonzalez’s own voluminous, angry response to the JCO article. I’ll comment upon that below, but first a brief review.
The trial was begun in 1999 under the auspices of Columbia University, after Rep. Dan Burton had pressured NCI Director Richard Klausner to fund it. It was originally conceived as a randomized, controlled trial comparing the “Gonzalez Regimen” to standard chemotherapy for cancer of the pancreas. In the first year, however, only 2 subjects had been accrued, purportedly because those seeking Gonzalez’s treatment were not willing to risk random assignment to the chemotherapy arm. In 2000, the protocol was changed to a “prospective, cohort study” to allow potential subjects to choose which treatment they would follow. Gonzalez himself was to provide the ‘enzyme’ treatments.
After that there was little public information about the trial for several years, other than a few determination letters from the Office of Human Research Protections and a frightening account of the experience of one subject treated by Gonzalez. By 2006 or so, those of us who pay attention to creeping pseudomedicine in the academy were wondering what had become of it. About a year ago we found out: the trial had been quietly “terminated” in 2005 after it met “pre-determined stopping criteria.” As explained here, that meant that the Gonzalez group had not fared well.
Four years after the trial’s ‘termination,’ the report was finally published: The Gonzalez cohort had not only fared much worse than the cohort that received chemotherapy, but it had fared worse than a comparable group of historical controls. Here, again, is the survival graph from the JCO paper:
The Gonzalez group had also fared much worse in ‘quality of life’ scores, which included a measure of pain.
Now let’s read between the lines. Forgive me for taking shortcuts; I’m a little pressed for time. (more…)
Althought I and other SBM bloggers have criticized state medical boards for not doing enough to protect patients from physicians who practice pseudoscientific medicine and quackery, they do nonetheless serve a purpose. Moreover, critical to medical boards doing even the limited amount of enforcement that they do is the ability of health care providers or other citizens to submit anonymous complaints against physicians who are not practicing up to the standard of care or who may be in other ways taking advantage of patients. Unfortunately, the other day I found out via one of the that I frequent of a very disturbing case in Kermit, Texas. Two nurses who were dismayed and disturbed by a physician peddling all manner of herbal supplements reported him to the authorities. Now, they are facing jail:
In a stunning display of good ol’ boy idiocy and abuse of prosecutorial discretion, two West Texas nurses have been fired from their jobs and indicted with a third-degree felony carrying potential penalties of two-to-ten years’ imprisonment and a maximum fine of $10,000. Why? Because they exercised a basic tenet of the nurse’s Code of Ethics — the duty to advocate for the health and safety of their patients.
The nurses, in their 50s and both members of the American Nurses Association/Texas Nurses Association, reported concerns about a doctor practicing at Winkler County Memorial Hospital in Kermit. They were unamused by his improperly encouraging patients in the hospital emergency department and in the rural health clinic to buy his own herbal “medicines,” and they thought it improper for him to take hospital supplies to perform a procedure at a patient’s home rather than in the hospital. (The doctor did not succeed, as reportedly he was stopped by the hospital chief of staff.)
How can this be? This is how:
One of the more bizarre and unpleasant “CAM” claims, but one taken very seriously at the NIH, at Columbia University, and on Capitol Hill, is the cancer “detoxification” regimen advocated by Dr. Nicholas Gonzalez:
Patients receive pancreatic enzymes orally every 4 hours and at meals daily on days 1-16, followed by 5 days of rest. Patients receive magnesium citrate and Papaya Plus with the pancreatic enzymes. Additionally, patients receive nutritional supplementation with vitamins, minerals, trace elements, and animal glandular products 4 times per day on days 1-16, followed by 5 days of rest. Courses repeat every 21 days until death despite relapse. Patients consume a moderate vegetarian metabolizer diet during the course of therapy, which excludes red meat, poultry, and white sugar. Coffee enemas are performed twice a day, along with skin brushing daily, skin cleansing once a week with castor oil during the first 6 months of therapy, and a salt and soda bath each week. Patients also undergo a complete liver flush and a clean sweep and purge on a rotating basis each month during the 5 days of rest.
Veteran SBM readers will recall that in the spring of 2008 I posted a series of essays* about this regimen and about the trial that compared it to standard treatment for subjects with cancer of the pancreas. The NIH had funded the trial, to be conducted under the auspices of Columbia, after arm-twisting by Rep. Dan Burton [R-IN], a powerful champion of quackery, and much to the delight of the “Harkinites.”
In the fall of 2008 I posted an addendum based on a little-known determination letter that the Office for Human Research Protections (OHRP) had sent to Columbia during the previous June. The letter revealed that the trial had been terminated in October, 2005, due to “pre-determined stopping criteria.” This demonstrated that Gonzalez’s regimen must have been found to be substantially worse than the current standard of care for cancer of the pancreas, as ineffective as that standard may be. I urge readers who require a review or an introduction to the topic to read that posting, which also considered why no formal report of the trial had yet been made available.
Now, finally, the formal report has been published online by the Journal of Clinical Oncology (JCO):
Four years ago I received an e-mail inquiry about Protandim. I had never heard of it; but I looked it up and wrote a quick, informal, somewhat snarky answer that got posted on the Internet. It got a lot of attention. Googling for Protandim now brings up my critique right after the Protandim website itself: that can’t be good for sales. Over the years, several e-mails and blog comments have informed me that I was wrong (usually offering testimonials or calling me closed-minded), and recently I’ve been getting inquiries asking if I’ve changed my mind now that a clinical study has been published. I haven’t.
Instead of providing antioxidants directly, Protandim is supposed to stimulate the body to produce its own antioxidants. The website tells us it is “the only supplement clinically proven to reduce oxidative stress by 40%, slowing down the rate of cell aging to the level of a 20 year old.” It provides “thousands of times more antioxidant power than any food or conventional antioxidant supplement.” It signals the body’s genes to produce the enzymes SOD (superoxide dismutase) and CAT (catalase) that act as catalysts to neutralize free radicals and are not “used up” like ingested antioxidants are. It “creates a cascade of your body’s natural catalytic antioxidants that are able to destroy millions of free radicals per second.” It raises the level of glutathione by 300%. Glutathione is good, apparently.
What is Protandim? It’s a combination of Milk thistle, Bacopa extract, Ashwagandha, Green tea extract, and Turmeric extract. I looked these up in the Natural Medicines Comprehensive Database. None of them is known to have any significant clinical benefit from antioxidant effects. Some of them are listed as “not enough information” to know if they are safe. One has estrogenic properties and more than one has known side effects and potential interactions with other drugs. The only one that even sounds remotely like it might have some pertinent data behind it is green tea. Green tea contains antioxidant catechins that are “thought to possibly have a protective effect against atherosclerosis and heart disease” and contains flavonoids that “might reduce lipoprotein oxidation; however benefits have not yet been described in humans.”
A Pubmed search for “Protandim” yielded only 3 studies: One in mice, one in cell cultures and one in humans. (more…)
When I started this series on Functional Medicine, David Gorski suggested looking at Mark Hyman’s web page, which I had seen months before, but thought did not reveal much. That was a wrong. It shows a lot, and I suggest bloggers et al review it.
So I decided on a fourth “functional medicine” (FM) installment, in search of what it FM really is. On the Mark Hyman web page and in his Public TV monolog fund-raiser, Hyman follows a seven point outline of what he believes Fuctional Medicine (“FM”) is. If one follows the 7 “keys” as he writes, optimum health, “ultra-wellness” happens. Here are the points:
- Environmental inputs
- Gut & digestive health
- Energy/Mitochondria/Oxidative Stress
- Mind body
In searching for just what FM is, one has to in a way read between lines. Claiming to treat the “underlying cause” of a condition raises the usual straw man argument that modern medicine does not, which of course is untrue. It also implies that there are underlying causes known to them and not to straights. FM claims to treat chronic disease which FM claims is inadequately treated by medicine. FM claims to be a more advanced approach both in conceptual thinking and in practical management. Such claims are on the face doubtful, but hard to disprove. The way to find out would be to analyze cases they manage and critique them.
I tried to see specific examples of treatments but the web page text book links were not working at the time. I understand others have seen the contents and perhaps can add some information. I sense a difference between “CAM” and FM – at least among the MDs and DOs – is that FMers tend to use methods and substances with some degree of scientific or biochemical rationale, even if not proved, moreso than many of the CAMers. Many seem to practice both systems or do not distinguish between the two systems. In order to get a sense of the degree to which FM is known, I requested from the web page the names of practitioners in a 50 mile radius of my home (near Palo Alto, Calif.). The names ranged from Santa Cruz (40 miles) to Berkeley (50) and San Francosco (40) and Marin County (Sausalito – 50 miles) The population of that area is about 5 million. They sent 46 names: MD/DO 31 – (including a nephrologist formerly on the staff of my teaching hospital) PhD 1 DC 8 Lac 3 ND 2 RN 1 Because I had become aware of FM only 1-2 years ago, I thought 46 was a relatively large number. The Web page lists four text books published in the past few years. A manuscript of the first one is available on line for downloading (not functioning when I tried.) . 21st Century Medicine: A New Model for Medical Education and PracticeMonograph Set – Functional Medicine Clinical Monograph Set – CME Available Textbook of Functional Medicine Clinical Nutrition: A Functional ApproachAs mentioned, I could not activate the links to those books, and did not have time to get to them individually. No authors were listed.
In 1994, Congress enacted the Dietary Supplement Health and Education Act (DSHEA). This act allows for the marketing and sales of “dietary supplements” with little or no regulation. This act is the work of folks like Tom Harkin (who took large contributions from Herbalife) and Orrin Hatch, whose state of Utah is home to many supplement companies.
DSHEA has a couple of very important consequences (aside from filling the pockets of supplement makers). (more…)
Revised 7/23/9 to correct an error.
While there are many taxonomies of alternative medicines, one thing almost all alternative therapies have in common is they are originally the de novo discovery of one lone individual. Working outside of the mainstream, they are the gadflies who see farther because those around them are midgets.
- Hanneman conceives of homeopathy, the treatment of all disease.
- Palmer conceives the cause of all disease and its treatment in chiropractic
- Mikao Usui, while having a mid-life crisis, conceives Reiki.
Virgin births all. These pioneers boldly go where no man has gone before.
Others have been less acclaimed after seeking out new life. An example is Virginia Livingston, MD, the discoverer of the cause of all cancer (1). She discovered a bacterium, the cause of cancer, she called Progenitor cryptocides, which, unfortunately only she could grow. Her therapies include an autogenous ‘vaccine” made from your own urine, which will probably preclude widespread use even in alternative therapies circles. I wonder if Jenny would object to vaccines if there were naturally derived from the patients urine?
Discovering a new form of pathogenic microbiology that no one else can see or grow is not uncommon, since people seem to be unable to recognise artifact on slides, be it Oscillococcinum being seen by Joseph Roy 200 years ago or Virginia Livingston in the 1960s. Sometimes I regret the discovery of H. pylori as a cause of gastritis as it gives the alternative microbiologists a medical Galileo to point at. H. pylori is used as an example, erroneously, of a bacteria causing disease that was laughed at by the medical establishment (Parenthetically, as my flawed memory has it, while I was an Infectious Disease Fellow the data for H. pylori came trickling in. I remember discussing the papers with one of my attendings who was an expert in GI infections. We all thought it was an interesting hypothesis and waited further data with interest. I cannot remember anyone dismissing the idea out of hand with derisive laughter. But then, I remain convinced that infections are the cause of all disease, at least the diseases that matter).
First, Mitchell and Webb took on homeopathy. This week, it’s bogus (word choice intentional) “nutritionists“:
Functional Medicine – What is it?
After extensive searching and examination, my answer is still – only the originators of “FM” know. Or, at least one must assume they know, because so far as I can see, I certainly see nothing that distinguishes “FM” from other descriptions of sectarian and “Complementary/Alternative Medicine” practices. A difference may lie in the advocates’ assumptions to have found some “imbalance” of body chemistry or physiology before applying one or more unproved methods or substances. From what I could determine, the “imbalance” or dysfunction is usually either imaginary or at least presumptive. And the general principles are so poorly defined as to allow practioners vast leeway to apply a host of unproven methods.
I figured there would be several ways to find out. One would be to read FM’s material – mainly what “they” placed on the Internet. Another would be to enter the system and find out as a patient or as a prospective practitioner what it is that “FM” claims to be. The third would be to listen to a practitioner or advocate on tape, disk, radio, etc.