Last week I discussed the secondary effects of low carb/ketogenic diets and the role that insulin plays in maintaining a well stimulated thyroid. This week I wanted to discuss the impact of hypothyroidism (under-active thyroid) on lipid metabolism and atherosclerosis.
What is your thyroid?
Thyroid hormones act on almost every kind of cell in your body to increase cellular activity or metabolism. If there is too much or too little thyroid hormone, the metabolism of your entire body is impacted. Your thyroid produces the following three hormones: Thyroxine (T4), Triiodothyronine (T3) and Calcitonin. We will focus on T3 and T4 because of their crucial role in metabolic function and the regulation of energy in the body. Essentially your thyroid creates T3 and T4 hormones from iodine and Tyrosine; it then releases them into circulation by a signal from your brain via the pituitary. The release of these hormones is vital to adult metabolic function and are integral in the uptake of carbohydrates in to skeletal muscle and adipose tissue via the positive transcriptional regulation of the muscle/fat- specifically GLUT4. The link between your thyroid and insulin lies in GLUT4.
Both insulin and thyroid hormones act on GLUT4 transporters. In the case of GLUT4, thyroid hormones play a role in the number of GLUT4 receptors expressed in cells. If you have a high level of insulin in your system your cells express more GLUT4 which allow for greater uptake and regulation of glucose. However, if you have too much insulin and body fat, your cells down regulate GLUT4 expression. It is believed that thyroid hormone receptors and myoD form a complex with MEF2 to regulate GLUT4 expression.
Most studies on insulin resistance and thyroid function have been produced on diabetics and obese people; and it is has been clearly determined that when blood glucose levels rise, so does insulin release. But in a constantly elevated state of blood glucose, more and more insulin is released until insulin sensitivity is reduced. As a results of insulin insensitivity a hyper-glycemic state is created and diabetes occurs. The medical and nutritional industry have resorted to low carb diets as a tactic to increase insulin sensitivity and reduce body fat by way of a caloric deficit; and these tactics work! However, at the complete opposite end of the spectrum lives a whole host of problems due to a lack of insulin and thyroid hormone which directly impact lipid metabolism.
According to a review of ‘Thyroid and lipid metabolism’ by Pucci E, “Thyroid hormones affect the synthesis, mobilization and degradation of lipids in the body. More specifically, thyroid hormones best-known effects on lipid metabolism include: (a) enhanced utilization of lipid substrates; (b) increase in the synthesis and mobilization of triglycerides stored in adipose tissue; (c) increase in the concentration of non-esterified fatty acids (NEFA); and (d) increase of lipoprotein-lipase activity. While severe hypothyroidism is usually associated with an increased serum concentration of total cholesterol and atherogenic lipoproteins, the occurrence of acute myocardial infarction (AMI) in hypothyroid patients is not frequent. However, hypothyroid patients appear to have an increased incidence of residual myocardial ischemia following AMI. Even in subclinical hypothyroidism, which is characterized by raised serum TSH levels with normal serum thyroid hormone concentrations, mild hyperlipidemia is present and may contribute to an increased risk of atherogenesis.”
Müller MJ, et al.in review of Klin Wochenschr work states that, “Thyroid hormones per se have only a minor influence on plasma triglyceride (TG) levels, but they induce an acceleration of TG turnover and chylomicron clearance rate. In addition, the hepatic lipogenic capacity is increased in hyperthyroidism and reduced in hypothyroidism. However, hepatic total and very low-density lipoprotein (VLDL) triglyceride output is decreased by thyroid hormones due to a reduced re-esterification and a simultaneously increased oxidation of newly synthesized fatty acids. Hypothyroid livers, by contrast, reveal an increased VLDL secretion. Despite their reduced lipogenesis, obese hypothyroidism is often accompanied by a hypertriglyceridaemia type III. The simultaneous stimulation of the synthesis of fatty acids, which are still in part converted to TG, and the degradation of TG contributes to the enhanced thermogenesis in hyperthyroid patients.”
In conclusion it appears that a lack of thyroid hormone disrupts your body’s ability to manage cholesterol, particularly VLDL and other atherogenic properties, leading to elevate blood lipid levels similar to that of a diabetic. In diabetic patients the cause of hypothyroidsim is a down regulation of thyroid hormones due to a lack of insulin sensitivity causing what appears to be a down regulation in GLUT4 transporters or requirement of thyroid hormone. This same cause and effect can occur in seemingly healthy individuals who eat a diet absent of carbohydrates. In turn, low carb ketogenic dieters run the risk hypothyroidism just like their obese, monosaccharide eating diabetic counterparts; which directly impacts fat metabolism in the body. The most interesting component of hyporthyroidism is that years may pass before it is detected. None obese, low carb dieters can go years with out knowing they have a problem. It would seem that a balanced diet low in high glycemic carbs would be the best middle ground.
- Pucci E, et al. Int J Obes Relat Metab Disord. (2000). Thyroid and lipid metabolism Retrieved from https://www.ncbi.nlm.nih.gov/m/pubmed/10997623/
- Müller MJ, et al. Klin Wochenschr (1984). Thyroid hormone action on intermediary metabolism. Part II: Lipid metabolism in hypo- and hyperthyroidism.
- Retrieved from https://www.ncbi.nlm.nih.gov/m/pubmed/6708390/?i=2&from=/10997623/related
- Kunal B. Kapadia et al Pharmacol Pharmacother (2012) Association between altered thyroid state and insulin resistance Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356957/
- Shaohui Huang et al (2007) The GLUT4 Glucose Transporter Retrieved. Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA Retrieved from: http://www.cell.com/cell-metabolism/fulltext/S1550-4131(07)00067-8