Thyrotoxins: Soy, Hormonal Contraceptives, Gut Bacteria or Simply Inflammation - Ladies (and Gents), You've Got the Choice, Hypothyroidism Lies Just Beyond the Corner.

Image 1: Thyroid for energy para-
thyroid for bone metabolism.

I don't know about you, but sometimes I get the feeling I am not doing enough for the female readers of this blog. And, while even this blogpost is not exclusively addressed to the ladies, the majority of hypothyroid patients are women. Part of the explanation for this phenomenon can be found in the title of this blogpost, already. Both, soy, as well as hormonal contraceptives are "ladylike", these days. Accordingly, overcolonization of Bifidobacterium and Lactobacillus, or inflammation is all that remains for "real men" (who obviously do not take synthetic gestagens and probably refrain from consuming soy products) to catch up on their female fellow sufferers. But before I totally confuse you, let's take a look at the most recent scientific results.

Still ahead of print is a paper by Claudia Lorenz and colleagues (Lorenz. 2011) in which the scientists report on the effects the synthetic gestagen levonorgestrel (LNG), which is "a widely used component of several hormonal contraceptives, such as the birth control pill, progestogen only pill or the emergency contraceptive pill" has on thyroid function of tadpoles (X. laevis). While this obviously is no adequate model for the human endocrine system, their finding that despite lack of histopathological changes in the thyroid glands, the aquatic organisms developed full blown hypothyroidism, which was presumably mediated via a large increases in prolactin and consequent interference with the thyroid system, would warrant further investigations in mammals and humans to exclude the possibly hitherto overlooked, histopathologically nondescript side effects of widely prescribed hormonal contraceptives, which is something the scientists from the German Institute of Freshwater Ecology and Inland Fisheries were obviously less interested in.

Figure 1: Isoflavone content in mg per 100g of various commercially available soy foods
(data calculated on the basis of soyfoods.com)

Much sturdier are the results a research group from India present in a paper published in the June issue of the Indian Journal of Medical Research (Mittal. 2011). The scientists  conducted a  randomized, double blind, placebo-controlled trial on 43 oophorectomised women [women who had their ovaries removed] to evaluate the effect of soy isoflavones (75 mg/day for 12 wk) on serum thyroid profile (free T3, free T4, TSH, TBG and anti–TPO antibody titres) at baseline, 6 and 12 wk after randomization.

Notice: You get the same overall amount of isoflavones that was administered to the women in this study from roughly 40g of mature soybeans, uncooked roasted soybeans or soy flour. Alternatively you can also drink 850ml soy "milk" or have a protein shake with 40g soy isolate (cf. figure 1).

The desired decrease in menopausal symptoms aside [induced by the estrogenic activity of the isoflavones], Mittal et al. found a 7% decrease in serum free T3 levels from 4.0 to 3.76pmol/l after 12 weeks and a 75% increase in TSH [thyroid stimulating hormone] the scientists obviously preferred to VERSCHWEIGEN in their abstract, in order to draw the ridiculously skewed conclusion that the

modest reduction in serum free T3 levels in the isoflavone group in the absence of any effect on other thyroid parameters might be considered clinically unimportant

If the data in table III of the studies (cf. figure 2) is not simply false, the above statement is at least premature. What's more is that the huge standard deviations (+/-3.01uIU/ml) of the TSH values after 12 weeks of treatment suggest that thyroid function may actually have compromised in some subjects, but in these cases even more severely. Allegedly, the "normal range of TSH is 0.5-5.5 micro IU/ml" and TSH increased in control, as well (cf. figure 2), but both the onset of the effect and the small dosage of isoflavones that has been used in this study would warrant further investigations into the effects of longer duration and/or higher dosages of isoflavone supplementation.

Figure 2: Serum value of Free T4, free T3 and TSH in control and soy treated women after 12 weeks.
(data adapted from Mittal. 2011)

In view of the positive reputation of soy products as being "cholesterol free", "low in fat" and "especially healthy for women", it cannot be excluded that a group of presumable female customers eats several of the products from figure 1 everyday and would thus potentially be exposed more than twice the amount of isoflavones used in the study for years. A continuous decline in the responsiveness of the thyroid to thyroid stimulating hormone (TSH), of which the decline in T3 despite rising TSH values is indicative, could easily make thyroid patients out of health-conscious costumers.

Contraceptives and soy, are yet by far not the most reliable tools to mess up your thyroid. Data from a  recent paper by Kiseleva et al. (Kiseleva. 2011)

are arguments in favour of the assumption of the possible role of PM [probiotic microorganisms] of the genera Bifidobacterium and Lactobacillus in triggering ATD [autoimmune thyroid disease] by the mechanism of molecular mimicry.

Or in other words, because the anti-bodies that attach to those two microorganisms are structurally almost identical to thyroid anti-bodies, it is possible, if not likely, that what was meant by our body as a means to ward off intestinal bacteria ends up attacking our thyroid, because the anti-bodies cannot distinguish one from another. The scientists do yet emphasize that

The data obtained in silico and in vitro should be proven by use of animal models and clinical studies for extrapolations to the whole body. Possible antigenic properties of components/proteins of bifidobacteria and lactobacilli, selectively binding anti-TPO and anti-Tg should be taken into consideration.

They also point out that current diagnostics using ELISA may even mistake "normal" bacterial antibodies for thyroid antibodies due to cross reactions which "can lead to unspecific false positive results and, hence, to an incorrect diagnosis."

Figure 1:  Drugs influencing thyroid economy
towards hyper (left) and hypothyroidism (right)
(adapted from Economidou. 2011)

The last thyroid related paper (Economidou. 2011) for today comes from Foteini Economidou, MD, PhD at the Department of Intensive Care Medicine of the University of Athens and his colleagues, whose review on Thyroid Function During Critical Illness may be of greater importance to many "hypothyroid" patients out there, than you would think. Reduced thyroid function is a protective mechanism the human body employs, when it is severely energy restricted or inflamed. Reduced TSH levels despite normal to low T4 and often low levels of T3, which are accompanied by increases in the purportedly unactive thyroid metabolite rT3, are clear signs of what is also called the euthyroid sick syndrome [euthyroid = healthy thyroid], where decreases in thyroid functions are only secondary to other health conditions (i.e. hypothyrodism is a symptom not a cause of your ailments) including constant dieting and (hidden) inflammation. You should keep that in mind, when even high doses of levothyroxin (T4) tablets won't solve your "pseudo-hypothyrodism". Chances are, the whole package would not produce any noticeable effects, because your body regulated the deiodinase enzymes, so that the inactive T4 will never be broken down to T3 or - if it is - the latter will immediately be "deactivated" into rT3. As Economidou et al. point out:

Only a few studies have examined the use of supplemental thyroid hormone therapy in critically ill [if you are chronically starved or inflamed you may consider yourself critically ill] general medical patients. Brent and Hershman examined the effect of thyroid hormone therapy in medical intensive care unit patients. The patients included in the study had serum T4 levels <5 µg/122 with no evidence of intrinsic thyroid dysfunction and were given either T4 or placebo intravenously [notice due to the low absorption of oral T3, the doses were obviously much lower than those you or your hypothyroid friend are taking] on a daily basis. There was no significant difference in mortality [take that as "no difference in how you will feel" in case of the euthyroid sick syndrome] between the two groups and the T4 replacement was detrimental to the restoration of normal pituitary-thyroid regulation.

This leads the scientists to conclude that ...

"levothyroxine therapy applied for the management of the euthyroid sick syndrome is not expected to have any effect because of the pronounced inhibition of conversion of T4 to T3 in these patients" (Economidou. 2011)

Bottom line, don't fix the symptoms (low thyroid) by popping T4 like candy (you know it doesn't help you), but try to find the original cause of disease, which -contraceptives, soy, gut bacteria and inflammation and overdieting aside (by the way, is it just me or do you also feel like you knew a young lady where all these come together) - could also be one of the drugs I listed in figure 3.