Tuesday, June 30, 2015

Too Much of a Good Thing - Selenium: Little More Than in Many 'Multis' Can Trigger Subclinical Hypothyroidism, Less Selenium (25% of the RDA) Cuts 13% Body Fat in 10 Weeks

Three things make this study special #1 it's human study, #2 it was conducted in a metabolic ward and #3 it didn't use potentially toxic Se supplements
If you ask around about how you can accelerate your metabolism, selenium and iodine, which are both important players in the concert of thyroid hormones, are usually among the first supplements to be mentioned. The bad news is: If you are not deficient in one of them, taking copious amounts of either of them may well slow down your metabolism significantly.

In view of the fact that the mechanism that triggers this side effect for selenium is a bit more straight forward than it is for iodine, I would like to start this new series with the initially mentioned essential trace element.
Learn more about your thyroid, T3, and T4 at the SuppVersity

Green tea messes w/ your thyroid hormones

TSH alone is not a good measure of thyroid health

Fructose prevents decline of T3 while dieting

T2 has thyroid-suppressing ef-fects as T3 & T4

Dieting makes you "hypothyroid" - temporarily

Levothyroxine may not be enough →T4+T3?
Now, from previous SuppVersity posts on things like zinc or chromium (both may worsen your insulin sensitivity in high doses), you will be well aware that despite being "essential", i.e. it being absolutely necessary to have them in your diet, consuming too much of these "essentials" can and usually will backfire.

In the case of selenium the consequences became most obvious in a 2003 study from the U.S. Department of Agriculture (USDA). In said study (Hawkes. 2003b), which was conducted by researchers from the Western Human Nutrition Research Center and Department of Nutrition in Davis, CA, the scientists didn't even have to use copious amounts of supplemental selenium to slow down their subjects' thyroid and have them gain weight.
Table 1: Sample meal plan for one week. I've taken this from a previous paper by the same researchers (Hawkes. 2003), in which they used the protocol for the first time - albeit for a different purpose..
Rather than that, Wayne Chris Hawkes and Nancy L. Keim fed healthy men foods which were either naturally high or low in selenium for 120 days. What's so great about this study is that it was conducted in a well-controlled manner with all subjects being confined to a metabolic research unit for the whole study period.Thus, the scientists were able to ensure that the selenium intake for all subjects was 47 μg/d (595 nmol/d | almost the RDA) for the first 21 d, before they were randomly assigned to consume diets containing either 14 µg/day (n = 6 | 25% of the RDA) or 297 (n = 5) μg/day (177 nmol/d or 3.8 μmol/d | 5.4x the RDA) for the remaining 99 days, which was long enough to cause significant changes in blood selenium and glutathione peroxidase and more.
Brazil nuts & selenium: "How much is too much?" A weighty question answered solely based on toxicity, not thyroid hormone metabolism, here.
This is one of the few cases, where rodent studies are in fact totally misleading: The fact that this study leaves no doubt that higher selenium intakes produce lower thyroid hormone level is particularly interesting, because that's the exact opposite of what happens in rodent studies. In said studies, selenium depleted rats had increased T4 and rT3 (slows down metabolism), and decreased T3 levels (Berry. 1992; ,Köhrle. 1993). In the human study at hand, however, only T3 responded to selenium and in the opposite direction, increasing when selenium was restricted and decreasing when selenium was increased.

As Hawkes and Keim point out, "[t]his difference may be due to the fact that serum T 3 in humans comes mainly by deiodination of T 4 in liver, whereas serum T3 in rats is released mainly preformed from the thyroid" - that's a significant difference, because it implies that the selenium containing deiodinase enzymes that convert T4 to T3 and deactivate T3 are far more critical in man vs. mice / rats. In addition, it may be relevant that most rat studies induced a state of profound selenium deficiency, with glutathione peroxidase activities suppressed by as much as 90%, whereas the mild selenium deficiency in the study aat hand lead to a decrease in plasma glutathione peroxidase activity of only 12% in the low selenium group.
In contrast to what you may have expected based on "broscience" the levels of the active thyroid hormone 3,3′,5-triiodothyronine (T3) in the subjects blood decreased in the high selenium group, increased in the low selenium group, and was significantly different between groups from day 45 onward.
Figure 1: Changes in relevant markers of thyroid and lipid metabolism (left | p < 0.05 for inter-group differences), as well as changes in lean and fat mass (right | only the reduction in body fat in the low selenium group was statistically sign.)
In spite of a compensatory increase of thyrotropin (TSH) in the high selenium group, the T3 levels of the subjects in the high selenium group kept declining, while those of the subjects on the low selenium diets kept increasing (the T4 levels didn't change significantly in either group).

Against that background, it's not really surprising that the high selenium group began to gain while the low selenium group began to lose weight by day 64 (the weight gain is not reflected in in the data in Figure 1, because taken on it's own, the 700g the subjects gained were not significantly; that's in contrast to the inter-group difference with p = 0,001). It did thus take no more than 6 weeks on the high vs. low selenium diet to trigger measurable effects not just on the subjects' metabolism, but also on their body weight; and by day 92, the weight gain / loss in the high vs. low selenium groups was pronounced and uniform enough to be statistically significant.
Table 2: Composition of the low selenium and high selenium diets fed to men - I would like to point out that there was more than enough iodine in the diets, so this was not the reason the thyroid levels plummeted and the fat began to creep up in the high selenium group.
Bottom line: The RDA for selenium is 55 mcg in both men and women (60 mcg for pregnant and lactating women). That "only" 279 mcg/day which is still 30% less than the upper intake level of 400 mcg/day and far away from the toxic range, but only slightly more than what you'll find in many "high potency multi-vitamins" (they often contain 150-200 mcg per serving), are enough to trigger significant changes in thryoid hormone metabolism is surprising. But the evidence is compelling: Decreases of serum T3 and compensatory increases in thyrotropin suggest nothing else but a subclinical hypothyroid response that was triggered by the high(er) selenium intake from day 22-99.

In that, it's questionable whether excluding high selenium foods from your diet altogether is much better. After all, the significant decrease in body fat was paid for not just by fat loss, but also a 12% reduction in glutathion peroxidase which could mean that your cellular defense system will be impaired, if you follow a low selenium diet for more than just a few weeks (75% lower than the RDA) | Comment on Facebook!

Addendum: What about supplements? In a follow up study, the researchers tested whether the same effects would be seen if they used 300mcg of selenium yeast (Hawkes. 2008). That's much different from the organic selenium in the foods from the study at hand and it did - still surprisingly - not results in a similar reduction in thyroid function (I would like to highlight that there were none of the purported benefits, either). The question whether that's coincidence or has something to do with the different forms of selenium and/or the particular foods used in the study at hand has unfortunately not been answered, yet. It does yet remind you not to freak out over selenium in your diet - even though, I still wouldn't generally recommend supplementation with higher doses of selenium; also because selenium supplementationof 140 or more μg/day to prostate cancer patients may increase risk of prostate cancer mortality (Kenfield. 2015) and previous studies that showed a reduced risk of developing PCA couldn't be replicated (Algotar. 2013).
References:
  • Berry, Marla J., and P. Reed Larsen. "The Role of Selenium in Thyroid Hormone Action*." Endocrine reviews 13.2 (1992): 207-219.
  • Hawkes, Wayne Chris, Fulya Zeynep Alkan, and Lynn Oehler. "Absorption, distribution and excretion of selenium from beef and rice in healthy North American men." The Journal of nutrition 133.11 (2003a): 3434-3442.
  • Hawkes, Wayne Chris, and Nancy L. Keim. "Dietary selenium intake modulates thyroid hormone and energy metabolism in men." The Journal of nutrition 133.11 (2003b): 3443-3448.
  • Hawkes, Wayne Chris, et al. "High-selenium yeast supplementation in free-living North American men: no effect on thyroid hormone metabolism or body composition." Journal of trace elements in medicine and biology 22.2 (2008): 131-142.
  • Kenfield, Stacey A., et al. "Selenium Supplementation and Prostate Cancer Mortality." Journal of the National Cancer Institute 107.1 (2015): dju360.
  • Köhrle, J. "Thyroid hormone deiodination in target tissues--a regulatory role for the trace element selenium?." Experimental and clinical endocrinology 102.2 (1993): 63-89.