On SBM we have documented the many and various ways that science is abused in the pursuit of health (or making money from those who are pursuing health). One such method is to take a new, but reasonable, scientific hypothesis and run with it, long past the current state of the evidence. We see this with the many bogus stem cell therapy clinics that are popping up in parts of the world with lax regulation.
This type of medical pseudoscience is particularly challenging to deal with, because there is a scientific paper trail that seems to support many of the claims of proponents. The claims themselves may have significant plausibility, and parts of the claims may in fact be true. Efforts to educate the public about such treatments are frustrated by the mainstream media’s lazy tendency to discuss every study as if it were the definitive last word on a topic, and to site individual experts as if they represent the consensus of scientific opinion.
Recent claims made for low dose naltrexone (LDN) fit nicely into this model – a medical intervention with interesting research, but in a preliminary phase that does not justify clinical use. And yet proponents talk about it as if it is a medical revolution.
Background on Naltrexone
Naltrexone is an FDA approved drug that binds to and inhibits opiate receptors – whose primary known function is to bind endogenous opiates (endorphins and enkephalins) and reduce pain. These are the same receptors that morphine, heroine, and other opiate drugs bind to. The primary use of naltrexone is to rapidly reverse opiate toxicity, or in the chronic treatment of opiate addiction.
But biology is always more complex than our initial understanding of any system. Evolution has a tendency to use what is at hand, and so receptors and hormones have been frequently co-opted for other uses over evolutionary history. This is partly why medications often have side effects – the target of the drug is used for more than just the desired effect.
There is also evidence that opiate receptors exist on other cell types, including cells involved in immune function, and activating or inhibiting these receptors may therefore modulate immune function or other biological functions. So far so good – all interesting and fairly standard basic science.
Translational Research
In the case of LDN the major problem comes at the level of translational research – taking what we are learning from basic science and applying it to specific clinical applications. It should be noted that this type of research is very unpredictable. Most of the promising leads provided by basic science do not lead to effective treatments. There are many possible reasons for such failure to translate to clinical outcomes. It is possible that the basic science picture is still significantly incomplete, and the piece or pieces that are missing alter the ultimate clinical effect of the intervention. It is also possible that the basic science is simply wrong in one or more of its conclusions. Further, the basic science may be correct, and the predicted outcome legitimate, but the size of the effect clinically insignificant, and therefore not seen in clinical trials.
Or, the basic science may be looking at markers that are associated with the biological or disease process they are interested in, but are not causally related (just downstream effects), and therefore manipulating the markers has no effect. Or the markers may be very nonspecific and completely incidental. For example, many things will activate the immune system incidentally, resulting in elevated markers for immune activity. But modifying these markers, or even immune activity may do nothing for the underlying disease or process you want to treat.
There are therefore many blind alleys. The basic science should therefore be used cautiously, to point in the direction of potential translational research – but not to justify clinical treatments.
Translational and other clinical research then proceeds to preliminary pilot studies. These types of studies are generally small and either open (not blinded) or with some blinding. They are not large, rigorous, and reliable clinical trials. The purpose of pilot studies is to see if a new treatment or approach is basically safe, and if it has any potential. You want to make sure that patients do not do clearly worse on the treatment. The point of preliminary research is to justify larger clinical trials – not to support clinical claims.
I have discussed previously the work of John Ioannidis that indicates that most published research is wrong. Don’t take this the wrong way – on scientific questions the research eventually works itself out. But when you take any question that has been fairly definitively answers, and then look back through the literature, many if not most of the preliminary studies published on the question turn out to have been wrong in retrospect. The take home lesson for this is that, when you are at the pilot study stage most positive studies will not pan out when more rigorous studies are done.
This should not be surprising. There are multiple factors that are known to bias small or poorly controlled studies toward the positive – placebo effects, experimenter bias, and publication bias just being the most obvious.
If you read the conclusions to even very positive pilot studies you will find, “This study indicates that treatment X is well-tolerated by patients with disease Y,” or “This study indicates that larger clinical studies are warranted.” When researchers have to couch their conclusions in terms that will get past peer-review, that is all they can say. Problems arise, however, when proponents (whether or not they are the researchers) begin to make clinical claims that go beyond such caution.
Low-Dose Naltrexone
So what is the current state of the science of LDN? At this point the basic science shows that opiate receptors, as I indicated, do more than modulate pain. This means they are a potential target for the development of new drugs, or new applications of existing drugs. While naltrexone is an antagonist – it inhibits opiate receptors – LDN causes a compensatory upregulation of native endorphins and enkephalins, which last beyond the effects of the naltrexone itself. This means, paradoxically, that a daily dose of LDN can be used to chronically increase endorphin and enkephalin levels.
This is all perfectly reasonable, but still a bit preliminary, basic science. It indicates the potential for translational research – nothing more.
What about the clinical evidence? A search of PubMed for “low-dose naltrexone” reveals only pilot and preliminary studies. The quick bottom line is that there does not appear to be a single medical application of LDN (outside of addiction) that is supported by a class I clinical trial, let alone a consensus of rigorous studies. What we do see is a smattering of pilot studies for a few diseases.
One study on fibromyaligia found symptomatic relief and reduced pain and tenderness. Beyond being preliminary, such effects could simply be due to increased endorphins (natural pain reducers), without having to invoke any other mechanism.There are also a few studies looking at Crohn’s disease and experimental allergic encephalitis (EAE – a rat model of multiple sclerosis) with some positive effects. The EAE study adds the further element of extrapolating from an animal model to a human disease.
There is also a pilot study of LDN in autism. While one outcome measure was positive, the rest were negative – which to me is a negative study. At the very least, LDN looks less promising for autism than for either painful or autoimmune diseases, which does make sense given that autism is a very different and complex disorder.
So far this would all be just an obscure corner of medical research, hardly worth the public’s attention and of use only to medical researchers looking for promising leads to follow up. But here is where the pseudoscience comes in – some advocates are promoting LDN as a breakthrough medical treatment for a long list of diseases and disorder, going well beyond the research.
The website, lowdosenaltrexone.org, embellishes the preliminary research and presents LDN as an effective treatment. They list that it is effective for:
Cancers:
* Bladder Cancer
* Breast Cancer
* Carcinoid
* Colon & Rectal Cancer
* Glioblastoma
* Liver Cancer
* Lung Cancer (Non-Small Cell)
* Lymphocytic Leukemia (chronic)
* Lymphoma (Hodgkin’s and Non-Hodgkin’s)
* Malignant Melanoma
* Multiple Myeloma
* Neuroblastoma
* Ovarian Cancer
* Pancreatic Cancer
* Prostate Cancer (untreated)
* Renal Cell Carcinoma
* Throat Cancer
* Uterine Cancer
Other Diseases:
* ALS (Lou Gehrig’s Disease)
* Alzheimer’s Disease
* Ankylosing Spondylitis
* Autism Spectrum Disorders
* Behcet’s Disease
* Celiac Disease
* Chronic Fatigue Syndrome
* CREST syndrome
* Crohn’s Disease
* Emphysema (COPD)
* Endometriosis
* Fibromyalgia
* HIV/AIDS
* Irritable Bowel Syndrome (IBS)
* Multiple Sclerosis (MS)
* Parkinson’s Disease
* Pemphigoid
* Primary Lateral Sclerosis (PLS)
* Psoriasis
* Rheumatoid Arthritis
* Sarcoidosis
* Scleroderma
* Stiff Person Syndrome (SPS)
* Systemic Lupus (SLE)
* Transverse Myelitis
* Ulcerative Colitis
* Wegener’s Granulomatosis
Right there we have a huge red flag – a treatment that works for a long list of diseases with different etiologies. Many of the diseases on the list are auto-immune, and therefore an immunosuppresant could theoretically be applied to many auto-immune diseases. But many of the diseases on the list are not auto-immune.
Treating a long list of cancers is another red flag, as well as HIV/AIDS. The justification for this is that LDS “boosts the immune system,” this phrase alone also being another indication of a dubious treatment. Scientists do not talk of “boosting” the immune system because this concept is too vague to be of any use. The immune system in healthy individuals is probably already operating within optimal parameters, especially since immune activity is a trade off between fighting off invaders while not causing too much damage to the host. Increasing immune activity, therefore, does not always equal improving immune function. In individuals who have a weakened immune system because of chronic disease, poor nutrition, or toxicity their immune systems can be restored to more normal function with treatment – but these are often specific treatments that address an underlying cause.
Further, there is an inherent contradiction in simultaneously treating diseases that are auto-immune (the immune system attacking the host), and immunodeficiency diseases (like AIDS) and claiming to treat cancer by “boosting” immune activity. Increasing immune activity actually worsens auto-immune diseases, and suppressing the immune system would worsen AIDS. This is a difficult contradiction to resolve.
The end result is just another bogus treatment with claims that are literally too good to be true, based upon pre-clinical or preliminary evidence only. Proponents have turned into proselytizers – saying on their website:”
If you or someone you know has connections in the media, the medical community, or to those in developing countries involved in AIDS policy or treatment, please let them know about LDN.
Truly promising and science-based treatments do not need an organization to promote them. The science will speak for itself.
Conclusion
The opiate system and drugs to manipulate it are standard biomedicine, and we may see an expansion of the indications for naltrexone as the clinical research progresses. I would also not be surprised at all if this line of research does not pan out – we simply cannot tell at this stage.
Meanwhile, the LDN community are turning a promising if preliminary treatment into essentially what is snake oil by promoting it for an implausibly long and contradictory list of indications. They are making the classic mistake of extrapolating prematurely from preliminary evidence, and relying heavily on anecdotes. Anecdotes are just another form of preliminary evidence (a particularly weak form at that) that should only be used to indicate promising new research, but not as a basis for clinical claims.
Ironically, LDN promoters may in fact harm research into LDN by giving it a bad name. Researchers may be reluctant to hitch their careers, or funding agencies commit resources, to a treatment that has a dubious reputation. If the research is promising it will still get done, but if anything it is likely to be slowed by the efforts of the LDN promoters.
This is just one of the many ways in which pseudoscience poisons the system.
- Yes, But. The Annotated Atlantic. [Last Updated On: November 7th, 2009] [Originally Added On: November 7th, 2009]
- Health Insurance Benefit Costs by Region [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- For an Operator, Please Press... [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Pollyanna With a Pen: Maine Governor Signs 18 New Health Care Bills into Law [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- AMA Sounds the Alarm, Medicare Making Yet Another Attempt to Cut Reimbursement [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Mass Governor Asks Blue Cross to Keep Higher Employer Contribution [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Lifespan and Care New England Plan Monopoly (Again) [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Dirigo Health: Con Artists, Liars, and Thieves? [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- New Orleans: Health Challenges [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- August a Flurry of Activity [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Maine's Dirigo Health Savings One-Third of Original Estimate [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- “Methodolatry”: My new favorite term for one of the shortcomings of evidence-based medicine [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Suzanne Somers’ Knockout: Dangerous misinformation about cancer (part 1) [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- A science-based blog about GMO [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- A Not-So-Split Decision [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Military Medicine in Iraq [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- The effective wordsmithing of Amy Wallace [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- A Science Lesson from a Homeopath and Behavioral Optometrist [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Join CFI in opposing funding mandates for quackery in health care reform [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Mainstreaming Science-Based Medicine: A Novel Approach [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Those who live in glass houses… [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- J.B. Handley of the anti-vaccine group Generation Rescue: Misogynistic attacks on journalists who champion science [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- When homeopaths attack medicine and physics [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- The cancer screening kerfuffle erupts again: “Rethinking” screening for breast and prostate cancer [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- All Medicines Are Poison! [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- When Loud Wins: Will Your Tax Dollars Pay For Prayer? [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- It’s All in Your Head [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- The Skeptical O.B. joins the Science-Based Medicine crew [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- The Tragic Death Toll of Homebirth [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- What’s the right C-section rate? Higher than you think. [Last Updated On: November 8th, 2009] [Originally Added On: November 8th, 2009]
- Recombinant Human Antithrombin – Milking Nanny Goats for Big Bucks [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- Does C-section increase the rate of neonatal death? [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- Man in Coma 23 Years – Is He Really Conscious? [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- Why Universal Hepatitis B Vaccination Isn’t Quite Universal [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- Ontario naturopathic prescribing proposal is bad medicine [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- Naturopaths and the anti-vaccine movement: Hijacking the law in service of pseudoscience [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- The Institute for Science in Medicine enters the health care reform fray [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- Neti pots – Ancient Ayurvedic Treatment Validated by Scientific Evidence [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- Early Intervention for Autism [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- A temporary reprieve from legislative madness [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- A critique of the leading study of American homebirth [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- Lose those holiday pounds [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- Endocrine disruptors—the one true cause? [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- Evidence in Medicine: Experimental Studies [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- Midwives and the assault on scientific evidence [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- The Mammogram Post-Mortem [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- An Influenza Recap: The End of the Second Wave [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- The End of Chiropractic [Last Updated On: December 13th, 2009] [Originally Added On: December 13th, 2009]
- Cell phones and cancer again, or: Oh, no! My cell phone’s going to give me cancer! (revisited) [Last Updated On: December 20th, 2009] [Originally Added On: December 20th, 2009]
- Another wrinkle to the USPSTF mammogram guidelines kerfuffle: What about African-American women? [Last Updated On: December 20th, 2009] [Originally Added On: December 20th, 2009]
- Acupuncture, the P-Value Fallacy, and Honesty [Last Updated On: December 20th, 2009] [Originally Added On: December 20th, 2009]
- The One True Cause of All Disease [Last Updated On: December 20th, 2009] [Originally Added On: December 20th, 2009]
- Communicating with the Locked-In [Last Updated On: December 20th, 2009] [Originally Added On: December 20th, 2009]
- Are the benefits of breastfeeding oversold? [Last Updated On: December 20th, 2009] [Originally Added On: December 20th, 2009]
- Measles [Last Updated On: December 20th, 2009] [Originally Added On: December 20th, 2009]
- Radiation from medical imaging and cancer risk [Last Updated On: December 21st, 2009] [Originally Added On: December 21st, 2009]
- Multiple Sclerosis and Irrational Exuberance [Last Updated On: December 21st, 2009] [Originally Added On: December 21st, 2009]
- Medical Fun with Christmas Carols [Last Updated On: December 22nd, 2009] [Originally Added On: December 22nd, 2009]
- Lithium for ALS – Angioplasty for MS [Last Updated On: December 23rd, 2009] [Originally Added On: December 23rd, 2009]
- “Toxins”: the new evil humours [Last Updated On: December 24th, 2009] [Originally Added On: December 24th, 2009]
- 2009’s Top 5 Threats To Science In Medicine [Last Updated On: December 24th, 2009] [Originally Added On: December 24th, 2009]
- Buteyko Breathing Technique – Nothing to Hyperventilate About [Last Updated On: December 26th, 2009] [Originally Added On: December 26th, 2009]
- The Graston Technique – Inducing Microtrauma with Instruments [Last Updated On: December 29th, 2009] [Originally Added On: December 29th, 2009]
- The “pharma shill” gambit [Last Updated On: December 29th, 2009] [Originally Added On: December 29th, 2009]
- Ginkgo biloba – No Effect [Last Updated On: December 30th, 2009] [Originally Added On: December 30th, 2009]
- Oppose “Big Floss”; practice alternative dentistry [Last Updated On: January 1st, 2010] [Originally Added On: January 1st, 2010]
- Causation and Hill’s Criteria [Last Updated On: January 3rd, 2010] [Originally Added On: January 3rd, 2010]
- The life cycle of translational research [Last Updated On: January 10th, 2010] [Originally Added On: January 10th, 2010]
- The anti-vaccine movement strikes back against Dr. Paul Offit [Last Updated On: January 10th, 2010] [Originally Added On: January 10th, 2010]
- Osteoporosis Drugs: Good Medicine or Big Pharma Scam? [Last Updated On: January 10th, 2010] [Originally Added On: January 10th, 2010]
- Acupuncture for Hot Flashes [Last Updated On: January 10th, 2010] [Originally Added On: January 10th, 2010]
- The case for neonatal circumcision [Last Updated On: January 10th, 2010] [Originally Added On: January 10th, 2010]
- A victory for science-based medicine [Last Updated On: January 10th, 2010] [Originally Added On: January 10th, 2010]
- James Ray and testosterone replacement therapy (TRT) [Last Updated On: January 10th, 2010] [Originally Added On: January 10th, 2010]
- The Water Cure: Another Example of Self Deception and the “Lone Genius” [Last Updated On: January 12th, 2010] [Originally Added On: January 12th, 2010]
- Be careful what you wish for, Dr. Dossey, you just might get it [Last Updated On: January 13th, 2010] [Originally Added On: January 13th, 2010]
- You. You. Who are you calling a You You? [Last Updated On: January 15th, 2010] [Originally Added On: January 15th, 2010]
- The War on Salt [Last Updated On: January 16th, 2010] [Originally Added On: January 16th, 2010]
- Is breech vaginal delivery safe? [Last Updated On: January 16th, 2010] [Originally Added On: January 16th, 2010]