This is Part 2 of Selenium and the Thyroid. The first post delved into the role (or lack thereof) for selenium (Se) in hypothyroidism due to Hashimoto’s thyroiditis. If you haven’t yet read the first one, I recommend doing that now, as it contains background information you won’t want to miss. Seriously, y’all, this is edge-of-your-seat type stuff. Go read it. For those who have already, you may be interested to know that Rachel (from The Bachelorette) reached out to me via email after publication of that post and had this to say: “Bryan is a wonderful, intelligent, sincere man who came on the show for the right reason – to find love. I’ve never felt this strongly about anyone else, so I decided to follow my heart and let this amazing journey take us where it will. I know that I want to spend the rest of my life with this incredible person, and I’m willing to overlook the fact that he tries to inflate his credentials by referring to himself as a ‘chiropractic physician.'”
Ahhhhh…c’mon, admit it…I totally had you going with all those Bachelorisms, right up until the end, no? OK, fine, whatever. You got me; Rachel did not send me an email. But when she comes to her senses, dumps Bryan, and chases down that hunky runner-up (Peter), I’ll be here if she wants to admit I was right.
Anyway…Part 2 will cover the role for Se in: hyperthyroidism due to Graves’ disease, treating thyroid eye disease, and preventing postpartum thyroiditis. On with the show:
Selenium for Graves’ disease
Much like the data for Se in Hashimoto’s Thyroiditis, the data for Se in Graves’ disease comes from regions where Se deficiency actually exists. Therefore, the applicability of this data to the United States is likely limited. Unlike the Hashimoto’s data, however, the Graves’ data is more compelling. Though not all trials have shown a positive impact, there are several trials that show Se supplementation speeds the restoration of biochemical euthyroidism (normal thyroid hormone levels) when used in conjunction with antithyroid drug therapy (methimazole). Some of these trials also demonstrate higher rates of remission (normal thyroid function after stopping antithyroid drug therapy) with Se supplementation.
It is important to note that the first few studies looking into this used a cocktail of Se + antioxidants, so the positive effect could not be attributed solely to Se. However, subsequent trials have looked at adding just Se to methimazole, so the positive results are more impressive.
The most robust trial investigating the question of whether Se should be a standard add-on to antithyroid drug therapy is expected to finish in 2018. Unfortunately for us Americans, this is a European trial, so we can assume the participants will have at least marginal Se deficiency. The GRASS (GRAves’ Disease Selenium Supplementation) trial has enrolled nearly 500 people with Graves’ on antithyroid drug therapy and randomized them to Se-enriched yeast 200 mcg daily vs placebo for 24-30 months. The investigators will determine whether Se speeds remission, decreases antithyroid drug failures, and leads to better quality of life.
Selenium for thyroid eye disease
This subject is quite interesting, in that the EUropean Group On Graves’ Orbitopathy (EUGOGO) has recommended the use of Se in mild Graves-related eye disease, based on the results of a single trial. Actually, the most interesting aspect of this is that they refer to themselves as “you-go-go,” which conjures up many images, none of which are remotely scientific in nature. In any case, there was a randomized, double-blind, placebo-controlled trial (Marcocci et al, New Engl J Med, 2011) to determine the effect of Se or pentoxifylline in 152 patients with mild Graves’ orbitopathy (GO). Subjects were given sodium selenite 100 mcg twice daily, pentoxifylline 600 mg twice daily, or placebo for 6 months. The patients were followed for 6 more months after withdrawal of treatment. They found that Se, but not pentoxifylline, was associated with improved quality of life, less eye involvement, and delayed progression of GO at 6 months. At 12 months (after 6 months of no medication or placebo), the results were confirmed.
The above study did not determine the Se status of its patients; but, we can again assume the patients were marginally deficient based on the location of the trial. There are data from other studies showing an association between low Se levels and the presence of GO, so there may very well be an increased risk of this problem in Se-deficient populations.
Given that I occasionally recommend Se to my patients with mild to moderate GO – but have no idea whether it really works in my Se-sufficient population – I’d love a trial performed in North America. Finally, we’re getting one. The investigators plan to enroll 151 patients with GO and give them Se for 6 months; the primary outcome will be health-related quality of life, using a standardized score to grade the GO.
Selenium for prevention of postpartum thyroiditis
Like the data for Graves’ orbitopathy, the data for prevention of postpartum thyroiditis comes mainly from just one paper out of Italy (Negro et al, JCEM, 2007). The paucity of data surprised me, as I’ve heard Se recommended – not infrequently – for women in the U.S. In the Italian study, about 150 pregnant, TPO Ab+ subjects were studied, with roughly half given selenium 200 mcg daily and half given placebo during and after pregnancy. In the Se group, TPO Abs decreased, thyroid echogenicity improved, and fewer patients developed postpartum thyroid dysfunction or permanent hypothyroidism. These are impressive results but, again, I’m not sure we can extrapolate these results to imply benefit in the American, Se-sufficient population.
Extra food for thought
Though parts 1 and 2 of this post have focused on the utility of Se supplementation in functional thyroid disorders, I would like to conclude by looking at two issues that tend to scare people – cancer and death. There are data to suggest that lower selenium levels may correlate with a higher risk of developing thyroid cancer, and that thyroid cancer may be at a higher stage. The mechanism is not clear, but it has been hypothesized that the antioxidant properties of selenoenzymes are relevant in carcinogenesis and tumor progression.
So, clearly we should all take Se, right? It is better to be safe than sorry, so shouldn’t we make sure our levels are “topped off?” Well, first, it’s not at all clear that giving Se to deficient people decreases the risk of thyroid cancer. Second, there are trials showing a U-shaped relationship between Se levels and the risk of disease, including death from cancer and all-cause mortality. So it’s bad to be Se-deficient, and it’s bad to have it coming out of your ears.
The conclusion to draw from all this is simple, obvious, and so not sexy: all things in moderation. It’s a lesson I’d love to see embraced by the alternative medicine community, but I won’t hold my breath. I regularly see their patients coming in with vitamin D levels twice the upper limit of what we now consider to be safe (50-60 ng/mL), completely suppressed TSHs with high T3 levels (more pig thyroid is better!), and enough B12 supplements to supply every vegan in the U.S. for a year.
My final word for my fellow Americans: regarding selenium use in Se-sufficient populations, I would say the jury is still out.
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