Read the covers of tabloids while standing in line to check out at the grocery store, and you will likely see an alt-med headline about the secret “thyroid cure” (or similar nonsense) that your doctor doesn’t want you to know. Setting aside how ludicrous it is to get your health advice from such a rag, I’m putting the shoe on the other foot today.
I want to talk about what the medical community actually knows about the hot topic of selenium and the thyroid, versus what your naturopath doesn’t know. Now that I think about it, perhaps a better title for this post would have been “Selenium and the Thyroid – Secrets Your Naturopath Doesn’t Know and Doesn’t Want You to Know She Doesn’t Know.”
Sure, there have been some interesting medical journal articles on the subject of whether selenium supplementation can treat thyroid disorders. But, like many things in medicine, this is not a binary issue of selenium: good or bad? It’s way more nuanced than that, and I’m afraid you won’t get that level of evidential dissection from your naturopath or your “chiropractic physician.” I’m throwing quotes around that last one – the chiropractor who won this season of The Bachelorette described himself in this fashion. I wonder how long it will take Rachel, an apparently intelligent attorney, to realize she’s engaged to a tool. Yes, I watch the Bachelor franchise; don’t judge me. But do keep it in mind when you judge the validity of my scientific conclusions – I’m probably not as smart as I sound if I enjoy watching that rubbish.
First, a quick primer on selenium (Se). Remember, this is not a medical-o-pedia site; other sources can take you as far into the weeds as you wish to go for the basics. After you’re satisfied, come back here for the clinically relevant part of the discussion.
What is Se and how do we get it in our diets?
Se is a trace mineral that, in the United States, mainly comes from plant foods (remember this includes bread and cereals, made from grains). It also comes from meat and seafood. The amount of Se in the food we eat mainly depends on the concentration of Se in the soil where that food was grown. In the U.S., the Se content of soil is mostly robust, so Se deficiency is extremely rare. Let me underscore that point: unless you have active Crohn’s disease or terrible malabsorption problems from a surgery like gastric bypass, you are probably Se sufficient. Now, if you live in many European countries (low Se content of soil), among other places, you have a much better chance of being Se deficient. More about why this is so important later.
Why is Se important for the thyroid?
Several enzymes in the thyroid gland are selenoproteins, meaning that Se is incorporated into their molecular structure. One of the most important of these enzymes is glutathione peroxidase, which protects the gland against oxidative damage. Eyes glazing over yet? Hold on, I’m almost done with the most boring parts. Se is also incorporated into iodothyronine deiodinases, meaning it plays an essential role in the metabolism of thyroid hormones – like the conversion of T4 to T3, the active form of thyroid hormone.
To summarize, Se is necessary for making thyroid hormone, and it is also important for protecting the thyroid against damage by removing oxygen free radicals generated during the production of thyroid hormone.
Selenium and Hashimoto’s Thyroiditis
There have been a couple of handfuls of studies looking at using Se supplements in the treatment of Hashimoto’s Thyroiditis (HT). As you know, HT is responsible for most cases of hypothyroidism. The standard of care for the treatment of hypothyroidism due to HT (or any other cause) is thyroid hormone replacement therapy, because we haven’t discovered a good treatment to prevent, reverse, or stop the autoimmune attack on the thyroid seen in HT. Obviously, if we could find a safe, easy, effective treatment for the autoimmune attack, that would be the holy grail of thyroidology.
Enter Se. The first blinded, placebo-controlled Se supplementation trial in 2002 (Gärtner et al, JCEM) showed improvements in thyroperoxidase antibody (TPO Ab) levels and well-being. In the few subjects whose TPO Abs normalized completely, the ultrasound echotexture of their thyroids also greatly improved, suggesting a reversal of the inflammatory process. HT cured! Swallow some Se and roll the credits! Not so fast. The patients in this trial were all on thyroid hormone replacement therapy with levothyroxine to maintain TSH in the normal range. There was no change in TSH, FT4, or FT3 levels in the treatment or placebo groups. Although it was not specifically studied, one could hypothesize that the levothyroxine requirement would have stayed exactly the same, despite seeing a decrease in TPO Abs in the Se-treated subjects.
But people felt better in the Se-treated group. That must mean something!
Yes, I agree that finding is interesting. The numbers were fairly small (25 patients in the treatment group reported improved well-being, compared to 6 patients in the placebo group) but statistically significant. Why the benefit? Well, there are studies suggesting that low selenium intake (like in Germany, where this study was conducted) is associated with a greater incidence of mood disorders and depression. The turnover rate of some neurotransmitters is altered in Se deficiency, so there may be some kind of direct, beneficial effect of Se supplementation on the brain. At this point, we just don’t know enough to say why it may work.
I say “may work,” because there have since been similar studies that clearly show a reduction in TPO Ab titers at 3, 6, and 12 months; however, none of the trials involving levothyroxine-treated HT patients has investigated clinically meaningful outcomes, such as levothyroxine dose reduction or disease remission. In all but one study of levothyroxine-untreated HT patients, there has been no change in TSH, quality of life, or ultrasound echotexture between Se and placebo. The one positive study (Pirola et al, Endokrynol Pol, 2016) showed a statistically significant restoration of euthyroidism in Se-treated subjects with subclinical hypothyroidism, compared to placebo. A similar study (Esposito et al, J Endocrinol Invest, 2017), also conducted in Italy, showed no effect of Se on thyroid function or ultrasound echotexture.
What is extremely important to note is that all of the Se supplementation trials were conducted in European countries or other countries in which Se deficiency actually exists. In the trials that measured Se levels, the participants were mildly deficient at entry. At the end of each study, Se levels were typically higher, but in only one trial did Se levels exceed the upper end of normal. This speaks to the question of whether Se has an effect by correcting a marginal deficiency versus by reaching a supraphysiologic concentration.
In my opinion, Se works to lower TPO Abs by correcting a marginal deficiency. One of the reasons why I believe this is because the clinical trial evidence has shown that thyroid hormone levels remain unchanged with Se supplementation. This makes sense in light of other studies showing that deiodinase (the enzyme involved in making thyroid hormone) activity only decreases in the setting of severe Se deficiency. So, correcting a mild deficiency is not going to improve thyroid hormone levels at all. Contrast this to studies showing that glutathione peroxidase (the enzyme that protects the thyroid against oxidative damage) activity decreases even in cases of mild Se deficiency. It then makes sense that correcting this deficiency would improve glutathione peroxidase activity, thereby lowering TPO Abs.
But the million dollar question for those of us in the U.S. – who take in 93 mcg (women) and 134mcg (men) of Se per day, compared to 40 mcg/day in Europeans – is will Se supplementation prove to do anything that is clinically meaningful? If Se lowers TPO Abs to the same degree in Se-sufficient Americans as it does in Se-deficient Europeans, will that have any impact on thyroid hormone levels? If not, then it’s not likely to change the patient’s need for thyroid hormone, so what’s the point of taking it?
All of this hype around Se is a classic example of how one small, interesting, positive study (the German 2002 Se supplementation trial) was able to generate enough buzz that recommending Se made its way into clinical practice. Taking all of the Se trial data into account is also a great example of the pitfalls of generalizing study results to populations very different from the study population.
What we need is a large Se supplementation trial performed in the U.S. Unfortunately, there does not seem to be one in the pipeline. However, the ongoing CATALYST trial (Chronic Autoimmune Thyroiditis quALitY of life Selenium Trial) is being performed in Europe and is scheduled to finish in 2018. I expect this to provide the most solid evidence to date of whether there is benefit to taking Se, at least in a population that will likely prove to be marginally Se-deficient at baseline. This trial has enrolled 472 levothyroxine-treated patients with HT; they have been randomized to receive 200 mcg/day selenium-enriched yeast or placebo for 12 months. The primary outcome will be quality of life measures, so we should learn whether Se actually increases well-being.
Se + [fill in the blank] Trials
I found a couple of recent trials looking at the combination of Se and myo-inositol (MI) for the treatment of Hashimoto’s Thyroiditis. What the heck is myo-inositol, you ask? Inositol is a sugar alcohol, and myo-inositol is one of its most prominent forms, serving as the structural basis of many secondary messengers. It plays a role in TSH signaling, regulation of iodination, and the sensitivity of thyroid hormone-making cells to TSH.
Of the two studies I found, the more robust is an Italian trial (Nordio et al, Eur Rev Med Pharmacol Sci, 2017) that enrolled patients with subclinical hypothyroidism due to HT who were not taking levothyroxine. It found that subjects given Se (83 mcg) + MI (600 mg) showed a statistically significant reduction in TSH and an increase in FT4, while subjects given Se alone did not. As expected, both groups showed decreases in TPO Ab levels. Interestingly, both groups showed improvement in well-being scores. Again, this could be due to the possibility that Se has a direct effect on the brain with respect to mood. In addition, MI has previously been shown to have some benefit in depression, panic, and OCD.
So, should everyone with newly discovered HT run out and buy Se and MI? Or maybe just MI if you’re an American, since we are generally a Se-sufficient population? If you said yes, then clearly you haven’t read enough of my stuff yet.
The role of selenium +/- other supplements in treating Hashimoto’s Thyroiditis in the U.S.
First, while I could be wrong, I don’t believe that Se is going to prove to be of much help in Se-sufficient populations, unless it is ultimately shown to act more like a drug than a mineral-replacement, when administered in supraphysiologic doses. Second, despite the common perception that vitamin and mineral supplements are harmless, they aren’t. It is quite possible to overdose on supplements, and Se is no exception. In a Se-sufficient population like the U.S., liberal use of it is more likely to result in Se toxicity. Symptoms include: nausea, vomiting, abdominal pain, diarrhea, hair loss, brittle nails, peripheral neuropathy, and the characteristic smell of garlic in sweat and breath. Also, one study has shown an increased risk of developing type 2 diabetes in men who took Se.
As far as the combination of Se and MI, I doubt it will prove to be a long-term solution to the thyroid destruction seen in HT. It’s also just way too early to get excited about it; we see positive, early results all the time that fail to replicate in later studies. In my opinion, it is unlikely that Se will have enough of an impact on the autoimmune attack to allow MI’s effect on thyroid hormone synthesis to outpace the ongoing destruction of the thyroid. As far as MI without Se, that has not been studied as a treatment for HT. But I seriously doubt that taking just MI would alter the typical clinical course of HT, which is the development of progressive, overt hypothyroidism.
What’s the harm in just trying selenium and seeing if it does anything good?
This would be a good time to explain why medical doctors practice evidence-based medicine, as opposed to the fly-by-the-seat-of-their-pants witchcraft practiced by naturopaths. We have a treatment for hypothyroidism due to HT that is safe, easy, and effective for the vast majority of people – levothyroxine. I understand that all the doomsday thyroid blogs out there would have you believe that HT will deal a death blow to your good health, but it simply isn’t true. If you don’t feel better with levothyroxine, it may be time to consider that it’s not your thyroid. If you and your endocrinologist are pretty sure it is your thyroid, then you might consider a trial of T3 therapy, as long as you are willing to keep your expectations low.
If, after all that, you feel poorly and have no answers, well…I’m still pretty sure that messing around with Se + the add-on supplement-du-jour is not going to durably improve your sense of well-being. But, as long as you have been adequately educated about the pros and cons, you don’t get your hopes up, and you have an end-point for the self-experimentation, it’s probably not going to hurt.
What does have the potential to hurt is the way treatments like Se are implemented by fringe practitioners, without adequate knowledge on the practitioner’s part and, therefore, without adequate counseling of the patient. I take issue with naturopaths who hand over bottles of supplements and tell someone, “this will make you feel better.” The placebo effect is strong, but it also tends to wane over time. So if Se isn’t the answer for someone, she may very well feel better for a few weeks or even a few months, but then she will revert back to baseline and wind up in my office, even more frustrated than when she started. So, when you ask “what’s the harm?,” I would answer that spinning your wheels using therapies that have marginal evidence may waylay you on your journey to better health. And, mind you, it’s not just one detour. Practitioners who utilize non-evidence-based treatments often have an unlimited number of rabbit holes they can send you down, which could stall any forward progress for months to years.
Just because modern medicine does not yet have a cure for Hashimoto’s Thyroiditis (unless you believe that low-dose naltrexone fits the bill), it doesn’t mean it’s a good idea to load patients up with the latest supplements, all in the name of treating the underlying cause of autoimmune hypothyroidism. I often see this desire to “go to the root of the problem” used as justification to send patients on fruitless, expensive quests to feel better. What’s amazing to me is, despite the fact that people who see me don’t feel better after months or years of working with their naturopath, they still complain that I’m just treating the symptoms, while their naturopath was actually treating the root cause. Forget about pointing out that the “treatment” wasn’t working. They have become invested in the idea of treating the disease, not the symptoms, and reeducation is often impossible, While I understand the intuitive appeal of treating the root cause, sometimes that isn’t the most effective way to help someone feel better.
Come back soon for Part 2 of Selenium and the Thyroid, where we will explore the evidence for selenium in preventing postpartum thyroiditis, treating Graves’ disease (autoimmune hyperthyroidism), and treating thyroid eye disease.
What do you think about selenium and hypothyroidism? Comment below!
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