The thyroid gland is in charge of a number of bodily functions. One of its important functions is to control our metabolism. What affects peripheral thyroid receptor function that may interfere with our metabolic rate? It is clear that low thyroid function is associated with obesity, with depression and many other conditions. It is a broad field of inquiry. Here I would like to narrow that inquiry down to two areas. What do we know about thyroid receptor malfunction? And how does energy intake impact the thyroid?
Interference with the Thyroid
Thyroid hormone (T3), to be effective, must pass from the serum into the cell, and it uses transmembrane transporters to do so. T3 must then find its receptors, located intracellularly, at the nuclear membrane. Currently, four different thyroid hormone receptors are recognized: alpha-1, alpha-2, beta-1 and beta-2. T3 must then plug into its receptors. Activated thyroid receptors become transcription factors that modulate gene expression. Activating nuclear thyroid receptors leads to the multiple functions given to the thyroid gland to perform, including boosting our metabolic rate.
Particular medications have been shown to disrupt thyroid function at this level. For example, the benzodiazepine class of anxiolytics is known to interfere with T3 transport into cells.[1]
Endocrine-disrupting chemicals in our environment can negatively impact our nuclear thyroid receptors as well. Polybrominated diphenylethers (PDEs) and polychlorinated biphenyls (PCBs) have been shown to disrupt thyroid receptor function.[2] PDEs are common flame retardants, used in foam, plastics (even computer cases), furniture, etc. PCBs, though banned in the US in 1979, may still be found in hydraulic fluids and lubricants, and manufacturing of plasticizers, fluorescent lights, capacitors, etc. They are toxic and extremely stable, continuing to pollute our soil and waterways—and our thyroid receptors.[3]
Certain genetic mutations can also interfere. A mutation of the alpha-1 receptor, for example, has been studied in rodents, demonstrating reduced thyroid function in this genetic strain due to an inability of T3 to bind to its receptor.[4]
Energy Intake & Thyroid
Energy intake is another factor that can affect thyroid function. Both calorie and carbohydrate restriction can negatively impact thyroid hormone metabolism. A hypocaloric, low carbohydrate diet consisting of 800 kcal daily for four days resulted in a striking decrease in both T3 and fT3 and an increase in rT3.[5] Raising the carbohydrate content to greater than 200 kcal from carbohydrates, however, sustained higher T3 levels. Low calories alone can also compromise thyroid function. Irrespective of carbohydrate content of the diet, when caloric content of the diet dropped to 600 kcal/day, T3 levels were compromised.[6] This is also true of the fasted state. Whether fasting for only 30 hours (healthy subjects) or for 10 days, a decrease in T3 and an increase in rT3 was observed.[7]
It is clear that to keep thyroid receptor function optimal, we need to clean up our environment, paying attention to avoidance of flame retardants and other chemicals that interfere with receptor function. We also would do well to avoid the use of benzodiazepines at much as possible. Keeping our calorie intake above about 800 per day and keeping our dietary carbohydrate content at least at 200 daily calories will help maintain healthy thyroid function.
References
[1] Kragie L, Forrester ML, Cody V, et al. (1994). Computer-assisted molecular modeling of benzodiazepine and thyromimetic inhibitors of the HepG2 iodothyronine membrane transporter. Mol Endocrinol. Mar;8(3):382-91.
[2] Lu M, Du J, Zhou P, et al. (2015). Endocrine disrupting potential of fipronil and its metabolite in reporter gene assays. Chemosphere. Feb;120:246-51.
[3] http://www.deq.state.or.us/lq/cu/nwr/PortlandHarbor/docs/SourcePCBs.pdf
[4] Baumgartner, A. (2000). Thyroxine and the treatment of affective disorders: an overview of the results of basic and clinical research. Int J Neuropsychopharmacol. 3:149-165.
[5] Reinhardt W, Holtermann D, Benker G, et al. (1993). Effect of small doses of iodine on thyroid function during caloric restriction in normal subjects. Horm Res. 39(3-4):132-7.
[6] Kelly, Greg. (2000). Peripheral Metabolism of Thyroid Hormones: A Review. Altern Med Rev 5(4):306-333.
[7] Palmblad J, Levi L, Burger A, et al. (1977). Effects of total energy withdrawal (fasting) on the levels of growth hormone, thyrotropin, cortisol, adrenaline,noradrenaline, T4, T3, and rT3 in healthy males. Acta Med Scand. Jan;201(1-2):15-22.
