PAPER Sensory and gastrointestinal satiety effects of capsaicin on food intake MS Westerterp-Plantenga1*, A Smeets1 and MPG Lejeune1 1Department of Human Biology, Maastricht University, Maastricht, The Netherlands BACKGROUND: Decreased appetite and increased energy expenditure after oral consumption of red pepper has been shown. OBJECTIVE: The aim of the present study was to assess the relative oral and gastrointestinal contribution to capsaicin-induced satiety and its effects on food intake or macronutrient selection. METHODS: For 24 subjects (12 men and 12 women age: 35710 y BMI: 25.072.4 kg/m2 range 20���30), 16 h food intake was assessed four times during 2 consecutive days by offering macronutrient-specific buffets and boxes with snacks, in our laboratory restaurant. At 30 min before each meal, 0.9 g red pepper (0.25% capsaicin 80 000 Scoville Thermal Units) or a placebo was offered in either tomato juice or in two capsules that were swallowed with tomato juice. Hunger and satiety were recorded using Visual Analogue Scales. RESULTS: Average daily energy intake in the placebo condition was 11.571.0 MJ/d for the men and 9.470.8 MJ/d for the women. After capsaicin capsules, energy intake was 10.470.6 and 8.370.5 MJ/d (Po0.01) after capsaicin in tomato juice, it was 9.970.7 and 7.970.5 MJ/d, respectively (compared to placebo: Po0.001 compared to capsaicin in capsules: Po0.05). En % from carbohydrate/protein/fat (C/P/F): changed from 4673/1571/3972 to 5274/1571/3372 en% (Po0.01) in the men, and from 4874/1472/3873 to 4274/1472/3273 en% (Po0.01) in the women, in both capsaicin conditions. Satiety (area under the curve) increased from 689 to 757 mmh in the men and from 712 to 806 mmh in the women, both (Po0.01). Only in the oral exposure condition was the reduction in energy intake and the increase in satiety related to perceived spiciness. CONCLUSIONS: In the short term, both oral and gastrointestinal exposure to capsaicin increased satiety and reduced energy and fat intake the stronger reduction with oral exposure suggests a sensory effect of capsaicin. International Journal of Obesity (2005) 29, 682���688. doi:10.1038/sj.ijo.0802862 Published online 21 December 2004 Keywords: energy intake sensory satiety postingestive satiety macronutrients composition cephalic phase response Introduction The increasing incidence of obesity is a recognized medical problem in developed countries.1 Obesity is a major factor for a number of comorbidities such as coronary heart diseases, hypertension, noninsulin-dependent diabetes mel- litus, pulmonary dysfunction, osteoarthritis and certain types of cancer.2���4 The main factor causing the development of obesity is a positive energy balance through a decreased physical activity and increased energy intake, especially fat intake. Weight loss and loss of body fat can thus be achieved by reducing energy intake and/or increasing energy expenditure. Treatment of obesity is beneficial in that even modest weight loss reduces the risk for mortality and morbidity in obese subjects and leads to beneficial health effects.5���7 Modest weight loss is a realistic goal for most subjects5,7 and can be achieved by reducing energy intake. However, weight-maintenance after weight loss has rarely been shown, and weight regain usually occurs,8���12 indicating that subjects are not able to change their eating and activity behavior adequately.13 Interventions aimed to improve weight loss and weight maintenance and to prevent the development of obesity in already overweight subjects are therefore neces- sary. A rapidly growing therapeutic area, largely embraced by the general public, is the use of natural herbal supplements. One of these agents is capsaicin, the pungent principle of hot red pepper. Capsaicin has been reported to reduce adiposity in rats, which can be partly explained by the enhancing effects on energy and lipid metabolism via catecholamine secretion from the adrenal medulla through sympathetic activation of the central nervous system.14,15 In a series of Received 3 August 2004 revised 29 September 2004 accepted 30 September 2004 published online 21 December 2004 *Correspondence: Dr MS Westerterp-Plantenga, Department of Human Biology, Maastricht University, PO Box 616, Maastricht 6200 MD, The Netherlands. E-mail: m.westerterp@hb.unimaas.nl International Journal of Obesity (2005) 29, 682���688 & 2005 Nature Publishing Group All rights reserved 0307-0565/05 $30.00 www.nature.com/ijo

human studies, Yoshioka et al16���19 showed an increase in diet-induced thermogenesis and a decrease in respiratory quotient immediately after a meal to which red pepper (capsaicin) was added. This finding implies a shift in substrate oxidation from carbohydrate to fat oxidation. This increase in the facultative phase of diet-induced thermogenesis was probably due to beta-adrenergic stimulation.16 They also showed a decreased appetite, decreased cumulative food intake18 and increased energy expenditure17,19 after con- sumption of red pepper. In those studies by Yoshioka, capsaicin was given orally as red pepper. Therefore, the reducing effect on energy intake could be due to the sensory effect of capsaicin or the postingestive, gastrointestinal effect. We assessed the sensory and gastrointestinal contributions to the possible satiety effect of capsaicin by offering the same dosage of capsaicin in tomato juice (sensory and gastrointest- inal exposure) or in capsules (gastrointestinal exposure) that were swallowed with tomato juice. Subjects and method Subjects In all, 30 male and female Caucasian subjects, aged 20 to 50 y, were recruited for this study. They underwent a medical screening. Body weight was measured on a digital balance (Seca, model 707, Hamburg Germany weighing accuracy of 0.1 kg) with subjects in underwear, in a fasted state and after voiding their bladder. Height was measured using a wall- mounted stadiometer (Seca, model 220, Hamburg, Ger- many). Attitude towards food intake was determined using a Dutch translation of the Three Factor Eating Questionnaire (TFEQ).20,21 The first factor of the TFEQ (F1) measures cognitive restrained eating: control of food intake by thought and will power. The second factor (F2) represents disinhibition: an incidental inability to resist eating cues, or inhibition of dietary restraint, and emotional eating.20,21 The third factor (F3) examines the subjective feeling of general hunger.20,21 Selection resulted in 24 eligible subjects who were in good health, nonsmokers, not using medication, not under diet- ary restraint and at most moderate alcohol users. Moreover, they were used to eating spicy foods at least once a week. The subjects comprising 12 men and 12 women were normal weight to moderately overweight and were of age: 35710 y BMI: 25.072.4 kg/m2 range 20���30. Scores on the TFEQ factors: F1, 572 F2, 672 F3, 472 indicated that the subjects were not dietary restraint (cutoff point in our population: F1 �� 9), did not show a tendency to disinhibi- tion and did not show a very high general feeling of hunger as indicated by F3.13,21 All subjects gave their written informed consent. The Medical Ethics Committee of the Academic Hospital in Maastricht approved of the study. Procedure Subjects came to the laboratory on 2 consecutive days, four times, during 4 consecutive weeks. Every time they received macronutrient-specific buffet-style meals, and after every meal a fresh box of snacks for in between meals. Before each meal, the previous box of snacks with leftovers had to be delivered. The snacks were labeled ���not for children��� to prevent the subjects from sharing them with others. Subjects were instructed not to eat or drink other items than those being offered during the experimental days, except plain water, black coffee or tea. Breakfast and lunch consisted of a buffet with high- and low-fat food items, that is, high-fat: croissants with butter and cheese, croissants with butter and sausages, croissants with butter and ���light��� jam, sausage rolls, chocolate rolls, full- fat milk, full-fat yoghurt, cream to be added to coffee low- fat: rolls with low-fat margarine and low-fat cheese, low-fat margarine and smoked meat, low-fat margarine and jam, currant buns, sticky sugar buns, skimmed milk, low-fat yoghurt, sugar to be added to coffee, and coffee and water. Dinner consisted of a buffet with high- and low-fat food items, that is, high-fat salads, soups, mashed potatoes, baked potatoes, vegetables with high-fat sauces, high-fat meat, high-fat cream desserts low-fat salads, soups, cooked potatoes, vegetables with low-fat sauces, low-fat meat and low-fat ���cream��� desserts. The boxes of snacks consisted of high-fat, and low-fat, sweet and savory biscuits, in the four possible combinations. All these are normal food items in the Netherlands, and all food items were liked by the subjects (hedonic scores: 7877 mm on a 100 mm Visual Analogue Scale). Each time the subject received one of the four following treatments during 2 days, in random order, 30 min before each meal: 0.9 g red pepper (0.25% capsaicin 80 000 Scoville Thermal Units, commercially available highest suggested dosage) either in 200 ml of tomato juice or in two capsules, or placebo (200 ml plain tomato juice or plain capsules). When capsules were offered, these were swallowed with 200 ml tomato juice. Spiciness and hedonics of the juice was recorded every time it was offered. Before the dosage was confirmed, the spiciness of the red pepper in tomato juice was assessed. Subjects got offered two series of concentrations of 0.00, 0.05, 0.1, 1, 2, 4, 5, 6, 8, 10 and 12 g/l red pepper in tomato juice in random order: the first series contained the concentrations from 0.00 to 8 g/l the second series contained the concentrations from 6 to 12 g/l. It was given in two separate series on separate days in order not to disturb the scores by offering a juice that was too spicy. In between two drinks, subjects had a piece of white bread and a sip of carbonated mineral water. Subjects scored the spiciness and hedonics of each drink. Spiciness was increased significantly compared to plain juice at a concen- tration of 0.1 g/l (1773 mm VAS vs 472 mm VAS Po0.05) they found it very spicy at 6.0 g/l (6477 mm VAS), and they found it too spicy at 12.0 g/l (9278 mm VAS). Subjects indicated that scores of 15���50 mm VAS represented a clear detection of spiciness from 50 to 80 mm VAS, scores represented a very spicy solution and scores of 80���100 mm VAS represented that the solution was too spicy. The Capsaicin: sensory and gastrointestinal satiety MS Westerterp-Plantenga et al 683 International Journal of Obesity