Context. Calorie restriction (CR) retards aging in mammals. It has been hypothesized that a reduction in triiodothyronine (T3) hormone may increase lifespan by conserving energy and reducing free-radical production.

Objective. To assess the relationship between long-term CR with adequate protein and micronutrient intake on thyroid function in healthy lean weight-stable adult men and women.

Design, Setting, Participants. In this study, serum thyroid hormones were evaluated in 28 men and women (mean age 52 ± 12 yr) consuming a CR diet for 3-15 yr (6 ± 3 yr), 28 age- and sex-matched sedentary (WD) and 28 body fat-matched exercising (EX) subjects, who were eating Western diets.

Main Outcome Measures. Serum total and free thyroxin (T4), total and free T3, reverse T3, TSH (TSH) concentrations.

Results. Energy intake was lower in the CR group (1779 ± 355 kcal/d) than in the WD (2433 ± 502 kcal/d) and EX (2811 ± 711 kcal/d) groups (P < 0.001). Serum T3 concentration was lower in the CR group than in the WD and EX groups (73.6 ± 22 vs. 91.0 ± 13 vs. 94.3 ± 17 ng/dl, respectively) (P 0.001), while serum total and free T4, reverse T3 and TSH concentrations were similar among groups.

Conclusions. Long-term CR with adequate protein and micronutrient intake in lean and weight-stable healthy humans is associated with a sustained reduction in serum T3 concentration, similar to that found in CR rodents and monkeys. This effect is likely due to CR itself, rather than to a decrease in body fat mass, and could be involved in slowing the rate of aging.