Low-dose oral tri-iodothyronine does not directly increase food intake in man N. M. Martin, 1 C. J. Small, 1 J. L. Lee, 2 S. Ellis, 2 W. S. Dhillo, 1 K. L. Smith, 1 W. M. Kong, 1 G. S. Frost 2 and S. R. Bloom 1 1 Department of Metabolic Medicine, Hammersmith Hospital, Imperial College London, London, UK 2 Nutrition and Dietetic Research Group, Hammersmith Hospital, Imperial College London, London, UK Previously, we have shown that low-dose tri-iodothyronine (T3) increases food intake in rodents. This randomised, double-blind, placebo-controlled study aimed to investigate the effects of low-dose T3 on food intake in normal body weight individuals. However, despite an elevation in fT3 comparable to our earlier studies, administration of low- dose T3 in the fasted state did not stimulate food intake in man. Keywords: appetite, energy expenditure, food intake, thyroxine, tri-iodothyronine Received 13 December 2005; returned for revision 9 March 2006; revised version accepted 19 March 2006 Introduction It is difficult to establish whether increased appetite in hyperthyroidism results directly from increased circu- lating thyroid hormones or indirectly from associated weight loss and/or increased energy expenditure (EE). Recently, we have reported that low-dose oral tri- iodothyronine (T3) directly stimulated food intake in rodents of normal body weight [1]. This study was designed to investigate the effects of low-dose T3 on food intake in man. We present data from a randomized double-blind, placebo-controlled, crossover study designed to establish whether low-dose T3 directly stimulates food intake in man. Methods Subjects The study was approved by the local Research Ethics Committee (2002/6379). Eleven males aged 21–30 years (24.3  1.0), body mass index (BMI) 20–26 kg/m 2 , were recruited and screened, as previously described [2]. Subjects gave informed written consent. Blood tests con- firmed normal biochemistry including thyroid function. For 24 h before and after each study day, subjects com- pleted a food diary [2] and fasted from 21:00 before both study days. Subjects attended on two separate occa- sions, at least 5 days apart. Preparation of T3 or placebo Each 5 mg of T3 tablet (Schering, Quebec, Canada) was encapsulated in a gelatin capsule (Pharmacy Department, Hammersmith Hospital, London, UK). Placebo treatment consisted of gelatin capsules identical in appearance. Study design During a run-in period, a venous cannula was inserted, and a baseline blood sample was taken [plasma free T3 (fT3), free thyroxine (fT4) and thyroid-stimulating doi: 10.1111/j.1463-1326.2006.00613.x Correspondence: Prof. S. R. Bloom, Department of Metabolic Medicine, Hammersmith Hospital, Imperial College London, 6th Floor Commonwealth Building, London W12 0NN, UK. E-mail: s.bloom@imperial.ac.uk RESEARCH LETTER # 2006 The Authors Journal Compilation # 2006 Blackwell Publishing Ltd Diabetes, Obesity and Metabolism, 9, 2007, 435–437 j 435