The Influence of Energy Depletion by Metformin or Hypocaloric Diet on Thyroid Iodine Uptake in Healthy Volunteers: a Randomized Trial

Sci Rep. 2019 Apr 1;9(1):5396. doi: 10.1038/s41598-019-41997-2.


Sufficient thyroid iodine uptake is needed to ensure effective radioactive iodine (RAI) treatment, which is mediated by the sodium-iodide symporter (NIS). Activation of AMP-activated-protein-kinase (AMPK), leads to decreased NIS expression and thyroid iodine uptake in in vitro and animal models. Clinically relevant conditions that lead to AMPK activation include metformin use and hypocaloric conditions. Here, we aim to assess the effects of metformin and hypocaloric diet on thyroid iodine uptake in healthy volunteers. Healthy male volunteers were included and randomized. Group 1 (n = 8) received metformin, group 2 (n = 7) followed a hypocaloric diet (1500 kcal/day), superposed on a moderate iodine restriction diet; Baseline measurements included thyroid iodine-123 (I-123) uptake and TSH, fT4, T3 and rT3 levels. After two weeks, thyroid function and I-123 uptake measurements were repeated. Baseline characteristics were similar between groups. Levels of TSH and fT4 were similar after each intervention. T3 decreased after hypocaloric diet and metformin (-0.2 ± 0.19 nmol/L, p = 0.0327; respectively -0.13 ± 0.13 nmol/L, p = 0.0282), resulting in decreased T3/rT3 ratios. There was no significant difference in thyroid I-123 uptake after each intervention. In conclusion, metformin treatment and hypocaloric diet resulted in a significant decrease in T3 levels and T3/rT3 ratios in healthy volunteers, without significant effects on thyroid iodine uptake. We found no indications that metformin or hypocaloric diet will have clinically relevant effects on RAI uptake.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Biological Transport / drug effects
  • Diet, Reducing / methods*
  • Energy Metabolism / drug effects*
  • Healthy Volunteers / statistics & numerical data*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Iodine Radioisotopes / pharmacokinetics
  • Iodine Radioisotopes / urine
  • Male
  • Metformin / pharmacology*
  • Thyroid Gland / drug effects*
  • Thyroid Gland / metabolism*
  • Thyrotropin / blood
  • Thyroxine / blood
  • Triiodothyronine / blood
  • Young Adult


  • Hypoglycemic Agents
  • Iodine Radioisotopes
  • Triiodothyronine
  • Iodine-123
  • Thyrotropin
  • Metformin
  • Thyroxine