The fish oil (FO) story began when a young Danish doctor noticed that there were no heart attacks in Greenland. Large epidemiological studies were initiated, mechanistic investigations followed, and a huge amount of fascinating data emerged. Today, we know more about FO than most other dietary supplements.
Fish oil contains large amounts of omega-3 fatty acids which are thought to be beneficial in treating hypertriglyceridemia, preventing heart disease. In addition, FO is often recommended for a wide variety of other conditions, such as cancer, depression, and macular degeneration. Perhaps the most compelling evidence exists in the realm of inflammatory diseases; the mechanism of action of FO is well-studied and includes powerful anti-inflammatory properties.
Australian rheumatologists just published a study of FO supplements for patients suffering from rheumatoid arthritis (RA). Specifically, they examined the effects of high versus low dose FO in early RA employing a ‘treat-to-target’ protocol of combination disease-modifying anti-rheumatic drugs (DMARDs).
Patients with chronic RA <12 months’ who were DMARD-naïve were enrolled and randomised 2:1 to FO at a high dose or plaacebo (low dose FO for masking). These groups were given 5.5 or 0.4 g/day, respectively, of eicosapentaenoic acid + docosahexaenoic acid. All patients received methotrexate (MTX), sulphasalazine and hydroxychloroquine, and DMARD doses were adjusted according to an algorithm taking disease activity and toxicity into account. DAS28-erythrocyte sedimentation rate, modified Health Assessment Questionnaire (mHAQ) and remission were assessed three monthly. The primary outcome measure was failure of triple DMARD therapy.
The results indicate that, the FO group, failure of triple DMARD therapy was lower (HR=0.28 (95% CI 0.12 to 0.63; p=0.002) unadjusted and 0.24 (95% CI 0.10 to 0.54; p=0.0006) following adjustment for smoking history, shared epitope and baseline anti–cyclic citrullinated peptide. The rate of first American College of Rheumatology (ACR) remission was significantly greater in the FO compared with the control group (HRs=2.17 (95% CI 1.07 to 4.42; p=0.03) unadjusted and 2.09 (95% CI 1.02 to 4.30; p=0.04) adjusted). There were no differences between groups in MTX dose, DAS28 or mHAQ scores, or adverse events.
The authors conclude that FO was associated with benefits additional to those achieved by combination ‘treat-to-target’ DMARDs with similar MTX use. These included reduced triple DMARD failure and a higher rate of ACR remission.
These findings are most encouraging, particularly as they collaborate those of systematic reviews which concluded that evidence is seen for a fairly consistent, but modest, benefit of marine n-3 PUFAs on joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity, and use of non-steroidal anti-inflammatory drugs and …there is evidence from 6 of 14 randomized controlled trials supporting a favourable effect of n-3 LCP supplementation in decreasing joint inflammation in RA. And you don’t need to buy the supplements either; regularly eating lots of fatty fish like mackerel, sardine or salmon has the same effects.
So, here we have an alternative, ‘natural’, dietary supplement or diet that is supported by reasonably sound evidence for efficacy, that has very few adverse effects (the main one being contamination of the supplement with toxins), that generates a host of potentially useful effects on other organ systems, that is affordable, that has a plausible mechanism of action…. Hold on, I hear some people interrupting me, FO is not an alternative medicine, it is mainstream! Exactly, an alternative medicine that works is called….MEDICINE.
Guest post by Louise Lubetkin
Those who recognize and appreciate a fine example of pseudoscientific baloney when they see one know that there is no richer seam, no more inexhaustible source, than the bustling, huckster-infested street carnival that is alternative medicine. There one can find intellectual swindlers in abundance, all offering outrageously implausible claims with the utmost earnestness and sincerity. But the supreme prize, the Fabergé egg found buried among the bric-a-brac, surely belongs to that most convincing of illusionists, the physician reborn as an ardent advocate of alternative medicine.
Why would any physician, exhaustively trained in the basic sciences that underpin every aspect of medical practice, decide to toss aside the entire canon in favor of a return to blatant mumbo jumbo?
There can be only two possible explanations, and they’re mutually exclusive.
First is the unsavory possibility that the physician who embraces alternative medicine is a cynical charlatan who knows full well that what is being offered is worthless, but sees it as a path to a more lucrative form of practice that is largely paid for out of pocket, in cash, requiring no tedious insurance company paperwork and avoiding the unpleasant possibility of Medicare audits.
And then there is the opposite explanation: the physician has actually become a true believer, in which case the wholesale rejection of his or her scientific training is essential in order to resolve the uneasy tension between what the physician knows to be fundamentally true and what he or she ardently believes and wishes were true. The two are diametrically opposed: one is a system of thinking in which each component has been painstakingly validated, assessed and reassessed over time, and revised where necessary with the emergence of new knowledge. The other is a simply a belief system founded on faith and wishful thinking.
Alternative medicine, particularly in the realm of cancer, has a long history of attracting people who are seduced by simplistic explanations of this dauntingly implacable and hugely complex constellation of diseases and become gripped by a messianic conviction that this is the true path to a cure. Never mind that such explanations have usually been around for a very long time and have been repeatedly debunked in carefully conducted studies. There is usually an element of paranoia involved: they see themselves as martyrs and explain the medical profession’s indifference to this revolutionary truth as a conspiracy designed to maintain a profitable status quo by silencing dissidents, especially when they arise from within the medical profession itself.
Which of these explanations is the correct one in any particular situation is not always easy to discern. Take the case of Nicholas James Gonzalez, M.D., a New York physician turned alternative practitioner whose practice focuses largely on the treatment of advanced cancer by nutritional means.
THE ORIGINS OF GONZALEZ’S TREATMENT
Gonzalez presents himself as a true believer who became a convert to alternative medicine after coming across the work of William Donald Kelley, D.D.S., a Texas orthodontist who had his own Damascene conversion when his doctors told him that he was dying of pancreatic cancer and that there was nothing more that they could do for him. Undeterred, Kelley claimed that he had cured himself by means of a rigorous diet combined with frequent self-administered coffee enemas. After thus miraculously dragging himself (and his enema bucket) back from the banks of the River Styx, Kelley decided to abandon straightening children’s teeth in favor of treating people with advanced cancer – perhaps not the most logical career move, to be sure, but Texas is Texas.
Probably the most famous of Kelley’s patients was the actor Steve McQueen, who, in the advanced stages of mesothelioma, turned to the erstwhile orthodontist in search of a cure. Not surprisingly, McQueen died despite Kelley’s ministrations, an unfortunate turn of events which Kelley rationalized away by claiming that he had in fact successfully cured McQueen, but that the medical establishment had subsequently had McQueen murdered in order to prevent him “blowing the lid off the cancer racket.”
But back to Gonzalez.
Like Kelley before him, Gonzalez bases his treatment on the work of James Beard, a long-dead Scottish embryologist who, more than 100 years ago, put forward the notion that all cancer was caused by wayward cells called trophoblasts. Trophoblasts are the cells which organize around the developing embryo very early in pregnancy, and which ultimately give rise to the placenta. Beard, of course, lived and died long before the advent of electron microscopy, the unraveling of the structure of DNA and a myriad other crucial discoveries that have helped to elucidate the hugely complex phenomenon that is collectively referred to as cancer. While his observations concerning the similarities between the invasiveness of cancer and the ability of the primitive placenta to tunnel its way into the uterine wall were undoubtedly astute, they are inadequate to explain what is now known about the etiology and progression of cancer.
Having observed that the placenta’s invasion of the uterine wall ceased at the very moment that the fetal pancreas became active, he took a leap of faith and postulated that it was the fetal pancreatic enzymes that were responsible for arresting the growth and invasion of the trophoblast layer. Beard went further, suggesting that quite apart from their role in digestion, pancreatic enzymes actually represent the body’s main defense against cancer, and therefore it should be possible to control cancer by administering large quantities of pancreatic enzymes.
This hundred-year-old hypothesis forms the cornerstone of the cancer treatment program devised by Gonzalez. (It should also be mentioned that Gonzalez doesn’t limit himself to the treatment of cancer, but uses the same methodology for treating a range of chronic degenerative diseases, including multiple sclerosis, presumably on the assumption that wayward trophoblasts are responsible for these, also, although it is difficult to imagine exactly how.)
Beard rightly surmised that pancreatic enzymes could not be successfully administered by mouth because the acid environment of the stomach would inactivate them immediately. Furthermore, being proteins themselves, any orally administered pancreatic enzymes would be quickly broken down by the gastric enzyme pepsin. Beard therefore advocated administering the enzymes by hypodermic injection.
In this, and in other ways, Beard seems to have been considerably more circumspect about his theory and its therapeutic implications than his modern day acolytes. It is interesting to note that he conspicuously refrained from making any claim that his method was a cure for cancer. A contemporary account of the public debate over Beard’s theory of cancer origins and treatment, which appeared in 1907 in the New York Times, is available here.
Much has happened since Beard’s day, it’s true, but gastric physiology and the essentials of protein digestion have not changed an iota. Pepsin is still pepsin, and the stomach is still awash in acid. Nevertheless, Gonzalez insists that the oral route is perfectly adequate. This odd departure from otherwise strict historical orthodoxy may have more to do with regulatory issues than pharmacokinetics: the type of enzymes he uses are viewed as dietary supplements by the Food and Drug Administration (FDA) rather than as prescription drugs, and are therefore unregulated.
In addition to pancreatic enzymes taken by mouth, Gonzalez prescribes a restrictive diet (which, even for those whom be pronounces to be obligate vegetarians, includes raw liver), and a staggering number of nutritional supplements which patients must take at regular intervals throughout the day and night.
The dietary guidelines he issues to his patients contain an amazing array of obviously unsound statements which bespeak not only a total abandonment of logical thinking on the part of their author, but also a casual disregard for objective fact, as though the solid benchmarks of physiology and biochemistry, such as pH, were just another narrative.
And then of course there’s the obligatory detoxification, without which no alternative treatment regimen could possibly be considered complete. But beyond its role as a doctrinal tenet, the notion that the body is inadequate to the task of handling its own waste holds a special utility for the practitioner of alternative cancer treatment. By insisting on regular and vigorous detoxification, the practitioner can reinforce the idea that the treatment regime – in this case, the pancreatic enzyme barrage – is working so well that the patient’s liver and bloodstream are in danger of being overrun by waste products from tumor breakdown. This must be a great boost to a patient in the advanced stages of cancer who is grimly contemplating his umpteenth coffee enema of the week and struggling to swallow another round of 30 supplement pills. However, most self-respecting physicians and patients would surely like to have that comforting assertion about massive tumor destruction confirmed with some kind of objective test such as imaging. And if the liver is really so hobbled by its task that it has to be supported by regular retrograde sluicing with tepid coffee, perhaps a few blood tests of liver function might be in order? It appears that such considerations are purely for pedants and infidels: real believers have no need for such niceties.
And then there are the supplements, in staggering quantities and bewildering combinations:
Five times during your waking hours take:
- 16 pancreas glandular tissue
- 1 magnesium citrate 60mg
With two doses of pancreas glandular take
- 2 chicken collagen type II
During breakfast and dinner (twice daily) take:
- 1 amino acids
- 1 Calsym (vitamin D3 and calcium carbonate)
- 1 thyroid (sic)
- 1 vitamin E 100 IU
During each meal (3 times daily) take:
- 1 adrenal glandular
- 2 vitamin C
- 1 Atlantic kelp
- 2 Formula #1 (sic)
- 1 liver
- 1 lung
- 2 magnesium citrate 60mg
- 1 digest aid
- 1 multivitamin
- 1 multimineral
- 3 pancreas glandular tissue
- 3 thymus glandular tissue
- 1 vitamin 400 IU
During lunch only take:
- 1 beta carotene 25,000
- 1 copper gluconate
- 1 potassium citrate
- 1 vitamin A 10,000 (which incidentally is twice the recommended daily allowance)
At bedtime take:
- 2 iron
- 2 magnesium citrate 60mg
- 4 RNA/DNA (sic)
At 3:30am take:
- 16 pancreas glandular tissue
The patient following such a program would take 187 supplement pills daily. Regardless of the dosage of active ingredients involved, the sheer volume and weight of excipients that are ingested during any one 24 hour period is surely something to take into account, especially in a patient debilitated by the ravages of advanced cancer. In a regimen that puts such emphasis on detoxification this is a curious departure indeed.
In 1999, Gonzalez published a paper in the journal Nutrition and Cancer (abstract here) claiming that he had achieved significantly increased survival in 11 patients with inoperable pancreatic cancer by treating them with what he described as “an aggressive nutritional therapy with large doses of pancreatic enzymes.”
Now bear in mind that pancreatic cancer is one of the most aggressive and deadly of all malignancies. The majority of people with pancreatic adenocarcinoma, which is by far the commonest form of pancreatic cancer, die within a few months of their diagnosis; only one in five patients survive the first year, and just four percent of patients live five years beyond diagnosis.
So when Gonzalez published his paper asserting that 9 of the 11 patients (81%) whom he had treated with this regimen survived one year, while 5 (45%) survived two years, and the remaining 4 patients were still alive and holding their own at the 3 year mark, people sat up and took notice.
Despite the fact that this was a very small study, and rife with biases (not least, an obvious selection bias: a further 12 patients who were unable to comply fully with the treatment were excluded from the analysis), it was sufficiently positive a report in an otherwise unrelievedly gloomy prognostic landscape that it prompted further investigation. Ultimately a full-fledged phase III clinical trial comparing Gonzalez’ nutritional protocol to the standard chemotherapy regimen in pancreatic cancer patients was sponsored by the National Institutes of Health and was carried out at Columbia University.
Perhaps not surprisingly, the trial turned out to be hugely contentious and very unorthodox. As a means of eliminating experimental bias, clinical trials are typically “blinded” and randomized – i.e., they are carefully designed so that patients are randomly assigned to one group or the other, and neither the patients nor the physicians know which treatment they are receiving. But in this case there was no way that the trial could be randomized or blinded. Patients could choose whether to undergo chemotherapy or to be assigned to the Gonzalez protocol group, so both they and the investigating physicians knew what treatment they were getting from the beginning.
When it became apparent, as it quickly did, that the results were not going to reflect well on his treatment protocol. Gonzalez began clamoring loudly for an investigation, claiming that the clinical trial had been deliberately rigged to discredit him. (Those interested in the background to the clinical trial, including a very thorough discussion of its ethical and scientific implications, can read about it in several installments, titled “The Ethics of CAM Trials” (parts I-V), here.)
The results of the clinical trial were reported in a paper published in October, 2009, in the Journal of Clinical Oncology (article here). To summarize the results, the 32 patients who underwent traditional chemotherapy lived more than three times as long (14 months vs 4.3 months), and had a measurably better quality of life, including less pain than those treated by the Gonzalez protocol – and since pancreatic cancer is notoriously painful, this is a hugely important consideration in any treatment, regardless of whether or not it extends survival.
But perhaps the most extraordinary and disturbing aspect of the paper was this paragraph, in the Methods section, describing the Gonzalez protocol:
“The enzyme treatment included orally ingested proteolytic enzymes, nutritional supplements, detoxification, and an organic diet (unaltered from the pilot study). Patients received three pancreatic enzyme and two magnesium citrate capsules with each meal. The patients also took specified numbers of capsules with magnesium citrate and Papaya Plus every 4 hours on an empty stomach. The dose for patients with stage II disease was 69 enzyme capsules, and the dose for patients with stages III or IV was 81 capsules per day. After day 16, patients had a 5-day rest period and then resumed treatment on day 22. Treatment could be adjusted by the physician and could be increased for cancer progression. A diet that required at least 70% of the food to be raw or minimally cooked was required. All food was organic. Prescribed detoxification procedures included coffee enemas twice each day; skin brushing and cleansing; salt and soda baths; and a liver flush, clean sweep, and purging.”
Excuse me? A liver flush? What is that, exactly? And could someone please explain what is meant by “a clean sweep”? And purging? If it’s not an indelicate question, might we be told exactly what that consists of?
How this extraordinary paragraph found its way into print, unchallenged, in the venerable Journal of Clinical Oncology is unfathomable. Why didn’t the editors, or the authors, for that matter, feel that it might be useful – in fact, essential – to (a) append an explanation of exactly what was meant by these terms, and (b) to include some kind of rationale for their use?
And then, of course, there’s the larger question of how the institutional review board at Columbia managed to sidestep the ethical issues inherent in approving a trial that was set up to compare the apples of standard treatment with the oranges of liver flushes and clean sweeps. If there was genuine clinical equipoise here we’re in deep, deep trouble.
You might think that this study, with its damning result, would be the end of it. But you’d be wrong. Gonzalez has written a book, a paranoid, self-exculpatory monologue, a martyr’s manifesto detailing what he perceives as his deliberate persecution at vast public expense by a pernicious cancer industry mafia whose goal is to silence him forever. (Presumably the hit man who got Steve McQueen was no longer available?)
So what are we to make of Gonzalez? Is he a cynical fraud or does he genuinely believe that coffee enemas, skin brushing and massive doses of supplements are capable of holding back the tsunami of cancer?
At the end of the day it hardly matters: either way, he’s a dangerous man.