[HD: This is a shorter-than-usual post – a bite-sized morsel intended to address a recent comment on one of my blog posts about the utility of low-dose naltrexone (LDN) for the treatment of hypothyroidism due to Hashimoto’s thyroiditis.]
One of the commenters on my blog recently left the following comment about her experience with hypothyroidism:
…Coming from a research background I decided to look into things. And there IS a treatment! Low Dose Naltrexone. There is research and evidence that it can lower the immune attack, prevent, and occasionally reverse hypothyoidism. Why didn’t my Endo know about this? Is it because Naltrexone is not sold in the 4.5mg amounts needed, and so not promoted to doctors by pharmaceutical companies?
I am now on it (thanks to a functional Dr) and my chronic fatigue has lifted! I also sleep better at night and have lost weight…
Holy crap, is this true?! There’s a way to cure Hashimoto’s thyroiditis? This is amazing! Unbelievable! I’m so stoked! Where can I get this stuff?! Wait…why have I never heard of this treatment?
Most of you who see “lame”-stream doctors like me have never been offered low-dose naltrexone for your Hashimoto’s thyroiditis because there is no clinical data to support its use in hypothyroidism. Not limited clinical data. Not preliminary clinical data. NO clinical data. There is not a single study in a peer-reviewed journal demonstrating the clinical efficacy of low-dose naltrexone for the treatment of hypothyroidism due to an autoimmune attack on the thyroid. If you can prove me wrong, I will print the study and eat the paper.
I realize this is going to come off as me picking on the commenter, which is not my intention. However, when someone says that she has a background in research and then proceeds to claim that there is evidence to support her assertion that LDN has evidence behind it, I have to challenge her when the evidence is absent.
Let’s do a little experiment. Go ahead and open up a new tab in your browser. Go on, now. I’ll wait. Got it? Good. Search “naltrexone hashimoto’s.” Scroll down the page. What do you notice about the composition of the results? Go 7-10 pages deep into the results. Notice anything different? No, you don’t. It’s all anecdotal “evidence,” mostly from fringe blogs, all citing the same few, historical, miraculous “cures” of other conditions (not thyroid!) that led to the promulgation of LDN as a legitimate therapy for…almost everything.
There is one shining light on page 2 of the results, a well-researched piece by Steven Novella, MD (not ND or PharmD), Low Dose Naltrexone – Bogus or Cutting Edge Science? Although this post on Science-Based Medicine is from 2010, the concepts hold up well. And, at least with respect to research on LDN for thyroid dysfunction, not much has changed since then.
Continuing with our experiment, let’s go to one of the most commonly used and respected medical search engines, PubMed. C’mon, humor me. Open up the tab. Good. Now search “naltrexone and hashimoto’s.” What do you see?
Zero results? That can’t be right! There’s tons of stuff on the Google results! This must be a conspiracy. The pharmaceutical companies just don’t want doctors to know about this treatment because then they’d lose money on millions of Synthroid prescriptions!
Right, of course. The U.S. government (PubMed.gov, people) is in bed with the pharmaceutical companies, conspiring to keep doctors in the dark about this miraculous cure-all.
Moving on, perhaps the original search terms were too restrictive. Maybe I created a “false positive” just to illustrate a point. Maybe I’m no more honest than any of the folks out there pushing this treatment. Well, let’s try a broader search on PubMed, “naltrexone and thyroid.” That should be a fairer assessment of what kind of data is out there, yes?
Sixteen results. That’s what you get. Spoiler alert: none of these papers offers any clinical evidence that LDN can be used to treat, reverse, or otherwise cure hypothyroidism due to Hashimoto’s thyroiditis.
But Google shows 67,300 results for “naltrexone hashimoto’s!” You can’t tell me there’s nothing to it! I won’t believe you! I won’t, I won’t, I won’t, I won’t!
To paraphrase William Shakespeare, “Methinks thou doth protest too much.” I don’t care how much you want to believe that there is good data supporting a course of action on which you’ve already embarked. Wanting to believe it’s true does not make it true.
I’m really glad that this issue was raised on my blog, as it is illustrative of a critical concept: Google searches ≠ research, for the most part (Google Scholar notwithstanding). A web site with “naltrexone” in the title should be viewed with a healthy dose of skepticism, as the bias should be obvious based on the title. Blog posts written by people detailing their personal experience with LDN do not constitute evidence of its efficacy. For that matter, blog posts written by clinicians, detailing their “amazing results” using LDN, also do not constitute evidence.
At this point, I’d like to make it clear that I’m not saying LDN can’t possibly have a beneficial effect in people with hypothyroidism due to Hashimoto’s thyroiditis. What I’m saying is, we don’t know. To suggest otherwise, no matter how much anecdotal evidence there is on the web, is irresponsible.
But how can you say that all these testimonials don’t constitute evidence?
Easily. Just as you can offer up blog after blog claiming success with using LDN for hypothyroidism, I can proffer hypotheses as to why it appears to work:
- There is a powerful placebo effect with any drug that has the type of hype surrounding LDN. The small community of fringe practitioners promulgating this therapy tends to attract followers who have similar missionary-like zeal. With all these people extolling the virtues of LDN, do you think you will be more or less likely to believe it’s working?
- LDN has actually been studied for use in other conditions, where it has shown potential promise. As it may be useful for fibromyalgia, and the symptoms of fibromyalgia and hypothyroidism overlap significantly, perhaps LDN is treating something other than the hypothyroidism. In other words, maybe the patient with “uncontrolled hypothyroidism” actually has fibromyalgia (or something else) that responds to LDN.
- The mechanism of action of LDN is thought to involve chronically increasing endorphin levels through partial blockade of opiate receptors. Perhaps any positive effects from the drug are due simply to increased endorphin levels, which naturally reduce pain (and possibly improve other symptoms).
- With respect to weight loss, we already have access to an FDA-approved medication called Contrave, which is a combination of naltrexone and bupropion. Obviously, there is some utility of naltrexone for weight loss, so we don’t need to invoke a beneficial effect on thyroid function to explain some weight loss (though I should make it clear that naltrexone alone has not been shown to be a powerful weight loss drug).
So what if LDN isn’t making the thyroid any better? If I feel better on it, isn’t that all that matters?
While I agree that the ultimate goal is to make you feel better, I would simply urge you to consider this: when you use an unstudied thyroid therapy like LDN – despite claims that side effects are minimal to non-existent – you have little idea if there will be any serious short or long-term adverse effects. In addition, this therapy is said to “boost immune function,” which is a nonscientific, throwaway phrase. But it does create a contradiction with respect to the myriad conditions LDN is said to improve. I think Dr. Novella says it best:
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.
All I am asking here is for precision when discussing untested and unproven therapies. If you come to me and say, “I have hypothyroidism, I didn’t feel well, my TSH was normal, and then I started LDN and now I feel better,” I can’t argue with that statement. I’m glad you feel better. But let’s not extrapolate your situation to mean that LDN is an appropriate treatment for hypothyroidism or that it can cure Hashimoto’s.
Low-dose naltrexone needs to be studied in the context of a randomized, double-blind, placebo-controlled trial. I’d be interested in seeing pre-intervention thyroperoxidase antibody levels and post-intervention levels, in addition to the usual thyroid function tests we use to guide thyroid hormone dosing in clinical practice. Study participants should have low-normal TSH levels at baseline but have reduced quality-of-life (QOL) scores on a standardized questionnaire. They should have no history of opiate or alcohol-dependence, and they should not be taking any drugs with a central nervous system effect (antidepressants, stimulants, etc.). They should also be free of other diseases thought to respond to LDN. If a trial like this shows both benefit and safety of LDN, then consider me intrigued.
One more cautionary tale before I wrap this up. Selenium, a mineral necessary for proper thyroid hormone metabolism, has been studied in people with Hashimoto’s thyroiditis. Many in the medical community got very excited when selenium supplementation was shown to lower thyroperoxidase antibody levels – the antibodies that cause thyroid destruction. We thought that this might be a disease-modifying drug – the holy grail for treating autoimmune hypothyroidism. Unfortunately, despite lowering antibody levels, selenium was not shown to actually reduce the need for thyroid hormone. In other words, these patients continued to require the same dose of thyroid hormone as before they started taking selenium. On top of that, when you look at the trials that have shown decreased antibody levels with selenium use, these trials have been conducted in parts of the world where selenium deficiency is more common (than in the U.S., where it is not common at all).
My point is, there are all kinds of interesting theories out there when it comes to medicine, and many of them sound quite plausible. Spoiler alert #2: most of these theories will never pan out in real life. So, be open to new ideas, but be skeptical. And do not claim that there is research to support an unstudied treatment that you just really, really, really want to believe in.
Have you used LDN? What’s been your experience? Why do you think it worked/didn’t work? Are you a physician or other clinician who prescribes LDN? What kind of results have you seen? Are you a researcher currently studying LDN? Comment below!
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