The aim of this study was to determine whether definite diet changes affect adrenocortical activity and/or adrenal androgen metabolism. A controlled experimental diet study with four consecutive diet periods (repeated measure design) was carried out in six healthy adult volunteers. Four nearly isoenergetic diets, two normal (N) moderately protein-rich, one protein-rich (P), and one low protein lactovegetarian (L), were fed. At the end of each 5-day diet period a blood sample and two 24-h urine specimens were obtained from each subject. Plasma levels of dehydroepiandrosterone sulfate (DHEAS) were elevated with diet L (6.5 Ϯ 1.4 vs. 5.3 Ϯ 1.1 mol/L; P Ͻ 0.05) compared to diet N, whereas other plasma hormones, including cortisol and insulin-like growth factor I did not vary markedly. A marked increase of 60% was seen in the urinary 24-h output of 3␣-androstanediol glucuronide with diet P. Urinary 24-h excretion rates for C peptide, free cortisol, DHEAS, and total 17-ketosteroid sulfates were clearly reduced with diet L compared to those with diet N or P. Our results show that a lactovegetarian diet can reduce adrenocortical activity (at least after a short term diet change). In addition, this vegetarian nutrition leads to a particular metabolic situation (elevated plasma DHEAS and reduced urinary DHEAS output) that usually is characteristic of fasting. Peripheral androgen metabolism as reflected by urinary 3␣-androstanediol glucuronide appears to be influenced only by high protein intake (diet P). Further research (controlled dietary long term investigation) is required 1) to validate whether the effects of diet on adrenocortical activity represent sustained endocrine changes and 2) to elucidate the underlying mechanism. (J Clin Endocrinol Metab 83: 2132-2137, 1998 N UTRITIONAL factors such as fasting (1-3), low calorie diets (4), or acute oral glucose load (5) are known to influence the serum levels and metabolism of adrenal androgens (AA). Differences in circulating levels of dehydroepiandrosterone (DHEA) (6) and certain androgen metabolites (7) have been reported for subjects consuming either vegetarian or omnivorous diets. Urinary 24-h excretion rates of adrenal and gonadal androgen metabolites decreased in middle-aged North American blacks when switching from a customary meat-containing Western diet to a vegetarian diet (8). Even when only certain dietary components (e.g. carbohydrates, fat, or dietary fiber) are changed, plasma levels of DHEA sulfate (DHEAS) and/or cortisol can be affected (9 -11). However, more detailed information on the effects of definite diet changes on AA metabolism and the related adrenocortical activity is lacking. In particular, controlled feeding studies checking the responses of both circulating and urinary hormones (including androgen metabolites and cortisol) have not been conducted to date.To address this issue, the hormonal responses to different, nearly isoenergetic diets [normal (N), protein rich (P), and lactovegetarian (L)] were investigated in a controlled diet stu...