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Seafood is an excellent source of iodine, but many people get most of their iodine from iodized table salt.

I assume you would have expected me to forget that I promised to do my very best to turn the "too much of a good thing" article on selenium I wrote a week ago into a series, right? Well, you obviously don't know me well enough, then, because here's installment #2 of this new series. One that is closely related to #1, but was significantly more difficult to write.

Why's that? Well, if you took a look at the literature discussing the effects of iodine supplementation on thyroid function, you'd know why it was ... well, "complicated" and not exactly unambigous to say the least.
In view of the fact that it would go beyond the scope of any single article to discuss the detailed effects of iodine and iodine supplements in the various thyroid disease states, I will focus solely on the beneficial and detrimental effects of iodine in more or less healthy individuals. Furthermore, I will not go into details as far as...

• Table 1: The spectrum of iodine deficiency disorders - click to see all (Delange. 1994)

  the important role of iodine in brain and general physical development and the ~30% increase in iodine requirements in pregnant women (Delange. 2000; Zimmermann. 2004 & 2011),
• the role of iodine in psychiatric disease (Hetzel. 2000), and
• the influence of (inorganic) iodine in the environment on human / general mammalian health (Fuge. 1987)

are concerned. What I would like to mention, at least, is the often-cited role of iodine in breast cancer, because the purported protective effect of iodine from supplements or food (Cann. 2000; Funahashi. 2001) is one of the reasons many women consume iodine supplements in dosages that could be more of a threat than a blessing for their health. That's bad news in view of the fact that the "evidence" of breast cancer protective effects is still in the hypothetical state and "rigorous retrospective and prospective studies are needed to confirm this hypothesis" (Cann. 2000).
Things we can say about iodine that are above all relevant for both, men and women, is that it is essential for normal thyroid function. Just as it is the case for selenium (discussed in the last installment of this series), though, the effects of supplemental iodine on thyroid function are far from being conclusive. While a lack of iodine will force the thyroid to increase it's efficacy by - eventually - developing goiterous growth, the dietary and even more so the supplemental ingestion of copious amounts of iodine (>1mg) do something most people won't expect: They reduce the function of the thyroid glands.

Figure 1: On a population-based study, high(er) iodine intakes are associated with higher TSH levels and thus reduced thyroid function, while high intakes are associated with increased TSH and reduced thyroid fct. (Laurberg. 1998).

It is thus not surprising that populations with low and high iodine intake tend to develop opposite thyroid disorders with

• goiter and thyroid hyperfunction being more prevalent among populations with low(er) iodine intakes, and 
• impaired thyroid function (=subclinical and clinical hypothyroidism) being more prevalent among populations with relatively high iodine intakes (Lauerberg. 1998). 

This does not mean, that "half-deficient" intakes were best, even though there's evidence that a mild = non-goitrogenic iodine deficiency partly protects against autoimmune thyroid disease (Laurberg. 1998). In that US scientists warn that it is not sure, in how many cases the iodine induced reduction in thyroid function "may result from the adverse effect of excess iodine on thyroid function in persons with underlying thyroid disease such as Hashimoto’s thyroiditis, history of subacute thyroiditis, or silent postpartum lymphocytic thyroiditis" (Hollowell. 2002).
It is thus all the more important to take the little experimental evidence there is into consideration. In that, the often-seen drops in thyroid function in response to the ingestion of large quantities of iodine are often ascribed to the so-called Wolff-Chaikoff which is supposed to reduce the thyroid function for no longer than a few a days and then, through the so-called "escape" phenomenon, the organification of intrathyroidal iodide resumes and the normal synthesis of thyroxine (T4) and triiodothyronine (T3) returns (Markou. 2001). Now, the problem is: The phenomenon is not always as short-lived as it is supposed to be

Table 2: Taking high amounts of iodine can significantly reduce thyroid function or induce goiter. Specifically in the subgroups of the population mentioed above (Roti. 2000)

"in a few apparently normal individuals, in newborns and fetuses, in some patients with chronic systemic diseases, euthyroid patients with autoimmune thyroiditis, and Graves' disease patients previously treated with radioimmunoassay (RAI), surgery or antithyroid drugs, the escape from the inhibitory effect of large doses of iodides is not achieved and clinical or subclinical hypothyroidism ensues [and may require temporary or permanent treatment with thyroid medications]" (Markou. 2001). 

Even if you believe you know you don't suffer from any of the aforementioned thyroid problems taking 10mg or more of iodine may be likened to Russian Thyroid Roulette, because it always entails the risk of iodide-induced hypothyroidism. Usually the hypothyroidism is transient and regresses within 2-3 weeks after iodide withdrawal, but as Markou et al. highlight there's a small subgroup of patients who develop transient iodine-induced hypothyroidism that must be followed long term thereafter because many will develop permanent primary hypothyroidism.

Figure 2: People with a previous history of painful subacute thyroiditis (SAT) are highly susceptible to the hypothyroid effects of 300mg/day iodine compared to people who had surgery for benign thyroid nodules (Roti. 1990).

Overall, it should be noted, though that the human body is pretty good at managing high intakes of iodine. While iodine-induced hypothyroidism was also reported in patients with no apparent thyroid disease the number of scientifically verified reports like the mild reversible hypothyroidism that was observed in elderly patients consuming iodinated glycerol by Drinka et al. (1998) or the two Japanese patients with anorexia nervosa developed iodine-induced hypothyroidism after they had consumped of large quantities of OshaberiKombu, a Japanese food that is extensively consumed on lowe energy diets and contains approximately 13.4 mg of iodine per 100g (Matsubayashi. 1998).

All in all the aforementioned examples are yet the exception to the rule. A rule which is evidenced in studies like Markou et al. (2000), in which the authors administered 80 mg potassium iodide (which is also the form of "iodine" in Lugol's solution) to 30 normal children 8 to 14 years old for 3 months and found that none developed overt or subclinical hypothyroidism. That does not mean that the iodine was without effect, but what the scientists observed was the expected transient elevation in serum TSH values (5–8 mU/L) as a result of the Wolff-Chaikoff effect. An effect that abated without further medical intervention on part of the researchers after 3-4 weeks when the TSH returned to normal levels despite the continuation of iodide treatment (Markou. 2000).
References:

• Cann, Stephen A., Johannes P. van Netten, and Christiaan van Netten. "Hypothesis: iodine, selenium and the development of breast cancer." Cancer Causes & Control 11.2 (2000): 121-127.
• Caldwell, Kathleen L., et al. "Iodine status of the US population, National Health and Nutrition Examination Survey, 2005–2006 and 2007–2008." Thyroid 21.4 (2011): 419-427.
• Delange, François. "The disorders induced by iodine deficiency." Thyroid 4.1 (1994): 107-128.
• Delange, Francois. "The role of iodine in brain development." Proceedings of the nutrition society 59.01 (2000): 75-79.
• Denef, Jean-François, Marie-Christine Many, and M. F. van Den Hove. "Iodine-induced thyroid inhibition and cell necrosis: two consequences of the same free-radical mediated mechanism?." Molecular and cellular endocrinology 121.1 (1996): 101-103.
• Drinka, Paul J., and Wolfram E. Nolten. "Effects of iodinated glycerol on thyroid function studies in elderly nursing home residents." Journal of the American Geriatrics Society 36.10 (1988): 911-913.
• Fuge, R. "Iodine in the environment: its distribution and relationship to human health." Trace substances in environmental health-XXI. 1987.
• Funahashi, Hiroomi, et al. "Seaweed prevents breast cancer?." Cancer Science 92.5 (2001): 483-487.
• Hetzel, Basil S. "Iodine and neuropsychological development." The Journal of nutrition 130.2 (2000): 493S-495S.
• Hollowell, Joseph G., et al. "Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III)." The Journal of Clinical Endocrinology & Metabolism 87.2 (2002): 489-499.
• Laurberg, Peter, et al. "Iodine intake and the pattern of thyroid disorders: a comparative epidemiological study of thyroid abnormalities in the elderly in Iceland and in Jutland, Denmark." The Journal of Clinical Endocrinology & Metabolism 83.3 (1998): 765-769.
• Many, Marie-Christine, et al. "In vitro study of acute toxic effects of high iodide doses in human thyroid follicles." Endocrinology 131.2 (1992): 621-630.
• Matsubayashi, Sunao, et al. "Iodine-induced hypothyroidism as a result of excessive intake of confectionery made with tangle weed, Kombu, used as a low calorie food during a bulimic period in a patient with anorexia nervosa." Eating and Weight Disorders-Studies on Anorexia, Bulimia and Obesity 3.1 (1998): 50-52.
• Markou, K., et al. "Effects of chronic iodide administration in thyroid function in children and adolescents with a history of transient congenital hypothyroidism." 27th Annual Meeting, Greek Endocrine Association, Nicosia Cyprus. Vol. 82. 2000.
• Roti, Elio, et al. "Iodine-Induced Hypothyroidism in Euthyroid Subjects with a Previous Episode of Subacute Thyroiditis*." The Journal of Clinical Endocrinology & Metabolism 70.6 (1990): 1581-1585.
• Roti, E., and A. G. Vagenakis. "Effect of excess iodide: clinical aspects." Werner and Ingbar’s The Thyroid–Braverman LE and Utiger RD. Ed, Lippincott (2000): 316-329.
• Sang, Zhongna, et al. "Exploration of the safe upper level of iodine intake in euthyroid Chinese adults: a randomized double-blind trial." The American journal of clinical nutrition 95.2 (2012): 367-373.
• Zanzonico, Pat B., and David V. Becker. "Effects of time of administration and dietary iodine levels on potassium iodide (KI) blockade of thyroid irradiation by 131I from radioactive fallout." Health Physics 78.6 (2000): 660-667.
• Zimmermann, M., and F. Delange. "Iodine supplementation of pregnant women in Europe: a review and recommendations." European Journal of Clinical Nutrition 58.7 (2004): 979-984.
• Zimmermann, Michael B. "The role of iodine in human growth and development." Seminars in cell & developmental biology. Vol. 22. No. 6. Academic Press, 2011.

Poultry is high in tryptophan and so is spirulina, cod, soy beans, parmesan and pork. They all have higher tryptophan contents than turkey. So, it doesn't always have to be poultry ;-)

As a waredownloadsoft reader you know that "[n]utrition plays a key role in the maintenance of muscle and bone mass, and dietary protein deficiency has in particular been associated with catabolism of both muscle and bone tissue" (Dukes. 2015). You will also be aware that leucine and some other amino acids play a particularly important role in the accrual and maintenance of muscle mass.

Until today, l-tryptophan, the amino acid the "happy neurotransmitter" serotonin is not among the usual suspects when it comes to building muscle. If the results of a recent study from the Georgia Regents Univ. translate into practic-ally relevant research, this may change soon (Dukes. 2015).
The aim of said study was to test the hypothesis that the essential amino acid tryptophan, and its metabolite kynurenine, might directly affect muscle metabolism in the setting of protein deficiency. To this ends, adult mice (12 mo) were fed a normal diet (18% protein), as well as diets with low protein (8%) supplemented with increasing concentrations (50, 100, and 200 uM) of kynurenine (Kyn) or tryptophan (Trp; 1.5 mM) for 8 weeks.

Table 1: Dietary formulations for the different groups in the study | Kyn, kynurenine; Trp, tryptophan (Dukes. 2015).

To be able to elucidate the exact mechanisms that made the mice that received Trp supplementation on top of the low protein diet leaner and more muscular than any other group, the scientists conducted an additional study on myoprogenitor cells which were also treated with Trp and Kyn in to determine their effects on cell proliferation and expression of myogenic differentiation markers.

Figure 1: Body composition (% body fat and % lean mass) of the rodents on the different diets (Dukes. 2015).

Ok, I have to admit the differences of the body composition of the rodents is not extremely impressive, but if you take into account that the changes were driven by significant differences in some of the most important drivers of skeletal muscle hypertrophy, you will probably understand why they still made the waredownloadsoft news.

Figure 2: An anlysis of muscle samples revealed significant increases in the myostatin suppressing protein follistatin, IGF-1 and leptin, as well as slight decreases in myostatin (Dukes. 2015).

The enzyme-linked immunosorbent assays the scientists conducted show significant increases in skeletal muscle insulin-like growth factor-1, leptin, and the myostatin antagonist follistatin with Trp supplementation. The corresponding mRNA microarray and gene pathway analysis that were performed on muscle samples of the rodents demonstrate that the pro-anabolic mTor/eif4/p70s6k pathway molecules were significantly upregulated in muscles from mice on Kyn and Trp supplementation. Increases in myoprogenitor cell activity, were yet only seen with tryptophan (not shown in Figure 2). Its metabolite kynurenine, however, didn't have any effect on MyoD, myogenin & myosin heavy chain.
References:

• Dukes, Amy, et al. "The aromatic amino acid tryptophan stimulates skeletal muscle IGF1/p70s6k/mTor signaling in vivo and the expression of myogenic genes in vitro." Nutrition (2015).
• Lin, Frank D., Trevor K. Smith, and Henry S. Bayley. "A role for tryptophan in regulation of protein synthesis in porcine muscle." The Journal of nutrition 118.4 (1988): 445-449.
• Musumeci, Giuseppe, et al. "Importance of serotonin (5-HT) and its precursor l-tryptophan for homeostasis and function of skeletal muscle in rats. A morphological and endocrinological study." Acta histochemica 117.3 (2015): 267-274.
• Sanfilippo, S., R. M. Imbesi, and S. Sanfilippo Jr. "Effects of a tryptophan deficient diet on the morphology of skeletal muscle fibers of the rat. Preliminary observations at neuroendocrinological and submicroscopical levels." Italian journal of anatomy and embryology= Archivio italiano di anatomia ed embriologia 100 (1994): 131-141.

Symptoms of hypo- and hypothyroidism (figure from youngstershub.com)

In previous articles about overtraining I've already touched on the possibility that training too much and eating to little can put you into a state where your TSH levels are low, even if the same goes for your free T3 and free T4 values.

Normally, your hypothalamus should correct low levels of the two active thyroid hormone T3 and T4 by increasing TSH. This physiological up-and-down is what doctors use to diagnose hypo- and hyperthyroidism by measuring TSH and in many cases only TSH - text-book practice, but still questionable against the background of the latest science.
Yes, even though everybody knows that you cannot judge the speed of a car by measuring how far its driver pushed the gas pedal into the floor, TSH remains the most commonly used endocrine test in clinical practice, when it comes to testing thyroid function; and this is despite the fact that more and more scientists are questioning the use of TSH, in general, and the reference ranges in particular.

Figure 1: Prevalence of thyroid antibodies across TSH intervals in women (top) and men (Spencer. 2007).

Speaking of reference ranger, if your TSH level is within the 1-1.5 mU/L range, you're considered "normal" (Biondi. 2013; Fontes. 2014; Vadiveloo. 2013). If your TSH is above 4.2-4.5 mU/L doctors believe this would indicate that your free T3 and free T4 levels were low, i.e. that your thyroid is not producing enough thyroid hormones and you're diagnosed hypothyroid - and this is where the problems begin.

After all, there is also an argument that a highly significant number of patients (up to 30%) with TSH above 3.0 mU/L have an occult autoimmune thyroid disease that may remain undiagnosed (Spencer. 2007 | see Figure 1). The same goes for people with subclinical hypothyrodism, simply because textbooks still say that TSH was all you need to test the health of your patients' thyroid.

Figure 2: High(er) rates of thyroid antibodies in non-frail vs. frail elderly women are suggestive of a protective effect of thyroid antibodies (Wang. 2010).

In contrast to young people, in whom thyroid diseases (esp. hypothyroidism and autoimmune diseases) will often remain undiagosed if doctors rely on TSH, only.

Elderly patients (i.e. 70 plus years), on the other hand, may be falsely diagnosed with hypothyroidism due to age-related increase in TSH ranging to up to 6.0 mU/L - and that despite the fact that that there are no or irrelevantly small changes in free T3 and free T4. This is particularly important, because ill health effects as they are seen in young individuals are rare or non-existent in elderly patients with autoimmune thyroid diseases nor hypothyroidism.

Rather than being detrimental, a 2010 study by Wang et al., which found that elderly subjects with raised titres of thyroid autoantibodies are less frail than age-matched peers (see Figure 2), suggests that having anti-thyroid antibodies in the blood can actually protect older women from the age-induced loss of muscle mass and function - surprising, isn't it? In view of the fact that the TSH levels of elderly patients usually have to rise above 6-7 mU/L before there is an actual decline in T4 below the normal range, the upper limit for TSH in the elderly should be increased (Hadlow. 2013).
References:

• Biondi, Bernadette. "The normal TSH reference range: what has changed in the last decade?." The Journal of clinical endocrinology and metabolism 98.9 (2013): 3584.
• Fontes, Rosita, et al. "Reference interval of thyroid stimulating hormone and free thyroxine in a reference population over 60 years old and in very old subjects (over 80 years): comparison to young subjects." Thyroid research 6.1 (2013): 1-8.
• Hadlow, Narelle C., et al. "The relationship between TSH and free T4 in a large population is complex and nonlinear and differs by age and sex." The Journal of Clinical Endocrinology & Metabolism 98.7 (2013): 2936-2943.
• Lewandowski, Krzysztof. "Reference ranges for TSH and thyroid hormones." Thyroid Research 8.Suppl 1 (2015): A17.
• Rodondi, Nicolas, et al. "Subclinical hypothyroidism and the risk of coronary heart disease: a meta-analysis." The American journal of medicine 119.7 (2006): 541-551.
• Spencer, C. A., et al. "National Health and Nutrition Examination Survey III thyroid-stimulating hormone (TSH)-thyroperoxidase antibody relationships demonstrate that TSH upper reference limits may be skewed by occult thyroid dysfunction." The Journal of Clinical Endocrinology & Metabolism 92.11 (2007): 4236-4240.
• Vadiveloo, Thenmalar, et al. "Age-and gender-specific TSH reference intervals in people with no obvious thyroid disease in Tayside, Scotland: the Thyroid Epidemiology, Audit, and Research Study (TEARS)." The Journal of Clinical Endocrinology & Metabolism 98.3 (2013): 1147-1153.
• Wang, George C., et al. "Thyroid autoantibodies are associated with a reduced prevalence of frailty in community-dwelling older women." The Journal of Clinical Endocrinology & Metabolism 95.3 (2010): 1161-1168.

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.
Now, from previous waredownloadsoft 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.
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.
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.