Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients

Abstract

OBJECTIVE: In obese patients, brain serotonergic stimulation via orally administered 5-hydroxy-tryptophan (5-HTP), the precursor of serotonin, causes decreased carbohydrate intake and weight loss. Since diabetes mellitus is associated with depressed brain serotonin, hyperphagia and carbohydrate craving, we hypothesized that in diabetic patients, orally administered 5-HTP stimulates brain serotonergic activity and thus normalizes eating behaviour. To test this hypothesis, we investigated whether in diabetic patients: 1) predicted brain serotonin concentrations are depressed as a result of decreased availability of the precursor, tryptophan; and 2) oral 5-HTP is effective in reducing energy and carbohydrate intake. SUBJECTS AND METHODS: 25 overweight non-insulin dependent diabetic outpatients were enrolled in a doubleblind, placebo-controlled study, and randomized to receive either 5-HTP (750 mgad) or placebo for two consecutive weeks, during which no dietary restriction was prescribed. Energy intake and eating behaviour, as expressed by macronutrient selection, were evaluated using a daily diet diary. Plasma amino acid concentrations and body weight, as well as serum glucose, insulin and glycosylated haemoglobin were assessed. RESULTS: 20 patients (nine from the 5-HTP group and 11 from the Placebo group) completed the study. Brain tryptophan availability in diabetic patients was signi®cantly reduced when compared to a group of healthy controls. Patients receiving 5-HTP signi®cantly decreased their daily energy intake, by reducing carbohydrate and fat intake, and reduced their body weight. CONCLUSIONS: These data con®rm the role of the serotonergic system in reducing energy intake, by predominantly inhibiting carbohydrate intake, and suggest that 5-HTP may be safely utilized to improve the compliance to dietary prescriptions in non-insulin dependent diabetes mellitus.

Preliminary fMRI findings concerning the influence of 5‐HTP on food selection

“…The cerebral influence of 5‐HTP intake to food stimuli seems to share similarities with studies that examined brain activity in altered states of hunger (Santel et al., 2006; Small et al., 2001) and in individuals with a clinical weight profile (Cangiano et al., 1992, 1998; Ceci et al., 1989; Cornier et al., 2009; Davids et al., 2009; Santel et al., 2006). The results obtained in the 5‐HTP group are consistent with observations made by Davids et al.…”

“…In light of the results presented here as well as the findings of previous studies (Cornier et al., 2009; Davids et al., 2009), it seems that 5‐HTP aids the activation of regions that relate to the evaluation of reward, macronutrient selection, and enteroceptive awareness of internal physiological needs. This is probably one of the primary reasons that studies which prescribe 5‐HTP to obese individuals show significant weight decrease as it aids the activation of structures responsible for external caloric evaluation and internal physiological demands (Cangiano et al., 1992, 1998; Ceci et al., 1989). Moreover Tataranni et al.…”

“…A vitamin C capsule (125 mg) was used for the control condition. Vitamin C was thought to be a reasonable placebo particularly for this study due to the fact that it has not been suggested to mediate food selection (Cangiano et al., 1992, 1998; Morris et al., 1987). Conventional placebo pills that have been used in other pharmacological research were sugar pills (dextrose), over the counter analgesics as well as vitamins (Tilburt, Emanuel, Kaptchuk, Curlin, & Miller, 2008).…”

“…The day before the study, participants were asked to fast overnight (excluding dietary supplements/medication) and abstain from alcohol for at least 24 hr. The supplements were taken on an empty stomach 30–45 min prior to scanning in order to ensure digestion (Cangiano et al., 1992, 1998). Prior to scanning, participants were asked to imagine their favorite food for 2 min and focus on texture, smell, and taste (Pelchat et al., 2004).…”

“…They observed that obese females, when administered with 5‐HTP (8 mg kg −1  day −1 ) for a period of 35 days, not only lose weight and decrease their food intake but they also show anorexia‐related symptoms (e.g., early satiety). Furthermore, normalizing depressed brain TRP levels with additional supplementation can lead to weight loss in obese patients (Cangiano et al., 1992, 1998). …”