Original Article

International Journal of Obesity (2007) 31, 121–130. doi:10.1038/sj.ijo.0803351; published online 25 April 2006

Body fat loss achieved by stimulation of thermogenesis by a combination of bioactive food ingredients: a placebo-controlled, double-blind 8-week intervention in obese subjects

A Belza1, E Frandsen2 and J Kondrup1

  1. 1Department of Human Nutrition, Centre for Advanced Food Studies, The Royal Veterinary and Agricultural University, Frederiksberg C, Denmark
  2. 2Department of Clinical Physiology and Nuclear Medicine, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark

Correspondence: A Belza, Department of Human Nutrition, The Centre for Advanced Food Studies, The Royal Veterinary and Agricultural University, Rolighedsvej 30, DK-1958 Frederiksberg C, Denmark. E-mail: anbe@kvl.dk

Received 30 December 2005; Revised 14 March 2006; Accepted 16 March 2006; Published online 25 April 2006.





A combination of tyrosine, capsaicin, catechines and caffeine may stimulate the sympathetic nervous system and promote satiety, lipolysis and thermogenesis. In addition, dietary calcium may increase fecal fat excretion.



To investigate the acute and subchronic effect of a supplement containing the above mentioned agents or placebo taken t.i.d on thermogenesis, body fat loss and fecal fat excretion.



In total, 80 overweight–obese subjects ((body mass index) 31.2plusminus2.5 kg/m2, meanplusminuss.d.) underwent an initial 4-week hypocaloric diet (3.4 MJ/day). Those who lost>4% body weight were instructed to consume a hypocaloric diet (-1.3 MJ/day) and were randomized to receive either placebo (n=23) or bioactive supplement (n=57) in a double-blind, 8-week intervention. The thermogenic effect of the compound was tested at the first and last day of intervention, and blood pressure, heart rate, body weight and composition were assessed.



Weight loss during the induction phase was 6.8plusminus1.9 kg. At the first exposure the thermogenic effect of the bioactive supplement exceeded that of placebo by 87.3 kJ/4 h (95%CI: 50.9;123.7, P=0.005) and after 8 weeks this effect was sustained (85.5 kJ/4 h (47.6;123.4), P=0.03). Body fat mass decreased more in the supplement group by 0.9 kg (0.5; 1.3) compared with placebo (P<0.05). The bioactive supplement had no effect on fecal fat excretion, blood pressure or heart rate.



The bioactive supplement increased 4-h thermogenesis by 90 kJ more than placebo, and the effect was maintained after 8 weeks and accompanied by a slight reduction in fat mass. These bioactive components may support weight maintenance after a hypocaloric diet.


body fat loss, energy expenditure, capsaicin, caffeine, green tea



Some food ingredients may possess a stimulatory effect on human energy expenditure (EE), and enhance satiety. Such compounds, given alone or in combination, may be of value in the prevention of weight gain and regain. Currently, the literature has focused on compounds such as tyrosine, catechins, capsaicin (CAP), caffeine and calcium. Catechins from green tea, especially polyphenol catechin epigallocatechin gallate (EGCG), have been shown (although not consistently1), to increase sympathetic nervous system (SNS) activity, thermogenesis and fat oxidation, and to decrease fat accumulation in humans2, 3 and rodents.4, 5, 6, 7

Capsaicin is the pungent principle in hot pepper. It has been shown that CAP added to meals increases EE and fat oxidation8, 9 and decreases appetite9, 10 in humans, probably by stimulating sensory pathways in the mouth and in the gastrointestinal regions, leading to activation of SNS in a dose-dependent manner.11, 12

The effect of caffeine on appetite and thermogenesis is rather weak, and a supplement with caffeine 200 mg t.i.d. did not produce weight loss in obese subjects.13 However, caffeine is a potent amplifier of thermogenesis when given in conjunction with other SNS agonists such as ephedrine, CAP or catechins.14, 15, 16, 17

Supplementation with tyrosine may enhance the noradrenaline synthesis. It has been shown that tyrosine supplementation together with other sympathomimetics decreased food intake in rats in a synergistic fashion.18, 19, 20

Despite some inconsistencies21 there is evidence to suggest that high-calcium intake given as a supplement, or in high-calcium diets, can produce weight loss.22, 23, 24, 25, 26

The effects of these ingredients may be potentiated in a synergistic fashion when given in combination. The mode of action may be an enhancement of SNS activity through increasing the noradrenaline (NA) level, which causes suppression of hunger, enhanced satiety and increased EE, covered in part by increased fat oxidation. Noradrenaline synthesis in SNS may be enhanced by increasing the substrate supply of the NA precursor tyrosine (Figure 1). Tyrosine may potentiate the effect of CAP, as CAP may activate the sympathetic nerves by stimulating NA release into the synaptic cleft.27, 28 However, the adrenergic receptor stimulation of NA is short-lived because NA is rapidly removed by catechol O-methyltransferase.29 Catechins inhibit the enzyme4, 30, 31 and may prolong the effect of CAP. Sympathetic nervous system activity is dependent on the production of cyclic adenosine-mono-phosphate (cAMP). The cAMP response is short-lived, but can be prolonged by an intake of methylxanthines such as caffeine.

Figure 1.
Figure 1 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

Possible mode of action of stimulating the noradrenergic neuron by the bioactive compound. Step 1: Enhanced synthesis of noradrenalin (NA) by increasing the substrate supply of the NA precursor tyrosine (TH). Step 2: Capsaicin (CAP) activate the sympathetic nerves via specific receptors by stimulating the release of NA into the synaptic cleft, where NA interacts with the adrenergic receptors. Step 3: NA is rapidly inactivated in the synaptic cleft by catechol O-methyltransferase (COMT) by methylation of the 3-hydroxyl group in the catechol ring. Catechins inhibit COMT and may prolong the effect of CAP. Step 4: SNS activity is dependent on cyclic adenosine-mono-phosphate (cAMP) for activating protein kinase (PK). cAMP is hydrolyzed by phosphodiesterase to AMP. Caffeine inhibits phosphodiesterase and may prolong noradrenergic activity. Other steps: NAT: noradrenalin reuptake transporter on the postsynaptic axon, alpha1-AR: alpha1-adrenergic receptor, alpha2-AR: alpha2-adrenergic receptor, MAO: monoamine oxidase which inactivate NA by oxidative removal of the amino group.

Full figure and legend (88K)

Calcium supplementation may decrease intracellular Ca2+ in adipocytes, followed by a decrease in lipogenic gene expression, thereby promoting lipolysis.22, 23, 24 Other studies suggest that dietary calcium can bind fatty acids in the gut and decrease fat absorption.26, 32

We have previously tested the combination of CAP, green tea extract, tyrosine, caffeine and calcium and found that a 7-day supplementation could significantly decrease 24-h energy balance by 200 kJ/day.33 The aim of the present study was therefore to examine whether the effect of the compound was maintained after 8-week supplementation and could prevent a weight regain after initial 4-week weight loss.


Subjects and methods


Ninety-three healthy Danish overweight to obese adults (mean body mass index (BMI): 31.3plusminus2.6 kg/m2, age: 46.2plusminus11.8 years, 23 males) were recruited. All subjects were weight stable (withinplusminus3 kg) 2 months before study inclusion, and were nonsmoking, nonathletic and had no daily use of medication except for anticonception and antihypertensive compounds. The subjects followed a normal Danish habitual diet with rare use of hot spices and no extreme intake of dairy products or coffee/tea. The subjects were recruited by advertisement in newspapers. All subjects gave their written consent after having received verbal and written information about the study. The Municipal Ethical Committee of Copenhagen and Frederiksberg approved the study as being in accordance with the Helsinki II Declaration.

Experimental protocol

The study period was 12 weeks in total. The intervention design was an 8-week, randomized, 2-arm, parallel, placebo-controlled, and double-blind intervention. Before the randomized intervention a weight loss was initiated by 4 weeks treatment by a 3.4 MJ/day low calorie diet (LCD) (Speasy®, Dansk Droge, Ishøj, Denmark), consisting of six meals of 37 g formula suspended in 250 ml water. The diet provided 75 g protein (7 g caseinat, 68 g soy protein), 96 g carbohydrate (16 g maltodextrin, 80 g fructose), 15 g oat fibres, and 12 g unsaturated fat per day. Of the 93 subjects enrolled in the LCD phase, 80 subjects lost more than 4% (>3 kg) of their initial body weight after the 4-week LCD treatment, which was the predefined requirement for inclusion in the weight maintenance phase of the study. Of the 13 subjects who did not continue in the maintenance phase of the study one subject did not meet the above criteria and was excluded. The other 12 subjects had dropped out of the LCD phase due either to lack of ability to follow the study protocol (12, whereof four were men) or illness (one female subject).

The 80 subjects (BMI: 31.2plusminus2.5 kg/m2, age: 47.6plusminus11.0 years, 18 males) were randomized into three groups: placebo (n=23, four men), simple release bioactive group (n=29, eight men) and enterocoated release bioactive group (n=28, six men). The simple and enterocoated release bioactive supplements were identical apart from the release form. The bioactive supplements were administrated as nine tablets in total per day, containing green tea extract (1500 mg – whereof 375 mg catechins and 150 mg caffeine), tyrosine (1200 mg), anhydrous caffeine (150 mg), calcium carbonate (3890 mg, whereof 2000 mg elementary calcium) simple or controlled (enterocoated) release form of CAP (1.2 mg approx 240.000 heat units) (Table 1). The CAP containing tablets were of similar dosage, but differed in release form. The CAP compound in the simple release formulation was released in the stomach, whereas in the controlled release formulation the CAP component was enterocoated in order to delay uptake until the small intestine. The placebo tablets contained 50/50 microcrystalline cellulose and maltodextrin and could not be distinguished from the bioactive supplements with respect to quantity, colour, taste, smell or appearance. Active or placebo supplements were taken as three tablets 60 min before breakfast, lunch and dinner. The study compounds were distributed to the subjects in tablet bottles. As a compliance indicator the subjects returned the tablet bottle every fortnight and the remaining tablets were counted.

During the weight maintenance phase all subjects received instruction in following a slightly hypocaloric diet. The diet was estimated to yield an energy deficit of 1250 kJ/day compared to individual daily energy requirements calculated from an isoenergetic educational system.34 The dietary advice was reinforced by dietetic consultations every fortnight. However, the compliance to the dietary advice was not assessed apart from estimation of whether the prescribed energy deficit was consistent with the body fat loss produced.

The subjects were not allowed to change their dietary and beverage habits (including intake of coffee and tea), use of spices, level of physical activity, nonsmoking status, and use of medication, throughout the study period.

Furthermore, the subjects were supplied with a booklet containing identical questions for each day to be completed daily throughout the weight maintenance phase. The questionnaires included questions about compliance to treatment (accurate time for intake and number of tablets taken), side effects and general well-being.

Assessment of anthropometric measures

Body weight, waist/hip circumference, and blood pressure were assessed before and after the LCD phase (week 4), at 4 weeks into the weight maintenance phase (week 8), and at completion (week 12, i.e. last day of the study). Body weight was measured to the nearest 0.05 kg on a decimal scale (Lindeltronic 8000, Copenhagen, Denmark), height to the nearest 0.5 cm, and waist/hip circumference to the nearest 0.5 cm. Heart rate and blood pressure were measured using an automatically inflating cuff (digital blood pressure meter model UA-743, A&D Company Ltd, Tokyo, Japan). The subjects were instructed to fast 10 h before each assessment except for &frac12; l of water, and to refrain from energetic physical activity for 24 h.

Body composition, fat-free mass (FFM), and fat mass (FM) were estimated by bioelectrical impedance analysis using an Animeter (HTS-Engineering Inc., Odense, Denmark)35 before and after the LCD phase (week 0 and 4) and at completion (week 12, last day of the weight maintenance phase). The measurement was made under the same standardized conditions as described above. Body composition was also assessed by Dual Energy X-ray Absorptiometry (DEXA)-scanning (Lunar DPX-IQ, Lunar Radiation Corp., GE, Madison, Wisconsin, USA)36 before and at completion of the weight maintenance phase. The DEXA-scans were performed as whole body scans in the slow mode (45 min). For quality assurance and equilibration a calibration block was scanned each morning and a spine phantom was scanned on a weekly basis. However, the scanner broke down twice (total duration of 2 weeks), midway in the study, and it was necessary to replace the X-ray bulb. Owing to the delays in assessment of body composition by DEXA-scans the standardization of subjects was poor. Furthermore, when comparing data before and after the break downs it was found that these were noncomparative. It was therefore decided to omit the DEXA scan results.

Respiratory measurements

All participants underwent assessments of resting metabolic rate (RMR) and respiratory quotient (RQ) by indirect calorimetry using a ventilated hood system (described in detail elsewhere37). Resting metabolic rate was calculated using a formula assuming a fixed protein catabolism,38 as the error of calculating RMR by omitting the exact correction from urinary nitrogen is negligible and too weak to estimate for a short period. The precision of the ventilated hood system was validated by an alcohol burning test on a weekly basis; CV% was 1.5.

The respiratory measurements were of 5-h duration, from 0800 to 1300 hours, and were conducted at initiation and completion of the weight maintenance phase (first and the last day of supplementation). Before each 5-h respiratory measurement the participants rested in a supine position for 30 min. Between 0800 and 0900 hours two baseline measurements (2 times 25 min) were assessed. Participants then ingested 1/3 of the daily dose of medication and 25-min respiratory measurements were repeated eight times during the next 4 h. The participants were instructed to fast except for &frac12; l of water from 2200 hours on the evening before the measurement. However, the subjects refrained from water drinking in the last hour before the respiratory measurement and cannot therefore have introduced any confounding by raising SNS activity, sympathetic vasoconstrictor activity, or cardiac vagal tone.39, 40 The subjects refrained from other than habitual medication and alcohol and energetic physical activity for 24-h before the two respiratory measurements. To limit diurnal variation and inter- and intrasubject variations, all measurements were carried out according to an identical time schedule.

Urine and fecal samples

The subjects collected all feces throughout three consecutive days in 1 week before each respiratory measurement. All feces were collected in preweighed containers. The fecal samples were weighed and frozen at -20°C. The samples were freeze-dried and homogenized before analysis, and samples from the same collection period were pooled. Fecal energy was obtained using a bomb calorimeter (Ika-calorimeter system C4000 Heitersheim, Germany). CVintra and CVinter were 0.1 and 0.2%, respectively. The samples were acid hydrolyzed with 3 N HCl before fat content was measured. Total fat content was measured by a method modified after Bligh and Dyer (1959).41

In addition, all subjects collected 24-h urine during each feces collection period. Three tablets with a total of 240 mg 4-aminobenzoic acid (PABA) were taken at meal times as a biomarker of complete urine samples.42 The volume and density of each 24-h urine collection were determined, and four samples were frozen at -20°C until further analysis. Urine samples were analyzed for aromatic amines (PABA) by colorimetric method using a spectrophotometer (Stasar; Gilford Instruments Laboratories Inc., Oberlin, OH, USA) with CVintra and CVinter 2.3% and 2.1%, respectively. Urine samples with a PABA recovery of < 85% were considered incomplete urine collections and excluded from the results. Nitrogen content in both collections was measured using the Dumas method with a nitrogen analyzer (NA1500, Carlo Erba Strumentazione, Milan, Italy). CVintra and CVinter were 1.1% and 1.6%, respectively. Urinary calcium concentration was measured using atomic absorption on a Spectra AA-200 (Varian, Victoria, Australia). CVintra was 2.1% and CVinter was 2.9%. Urinary content of catecholamines was determined using a commercial radioimmunoassay kit from Labor Diagnostika Nord, Nordhorn, Germany. CVintra and CVinter were 4 and 6%, respectively, for both NA and adrenaline.

Statistical analysis

The effect of the bioactive compound was first assessed by analyzing the two groups together as one group vs placebo. Subsequently, the two bioactive groups were compared. No significant difference was found between the two bioactive groups regarding fat loss, and the thermogenic effect of the supplement at first and last exposure of treatment. There was thus no indication of any effect of the release form on thermogenesis and fat loss.

All results are given in mean and standard deviation (s.d.). The level of significance was set at <0.05. Statistical analyses were performed with SAS 8.2 (SAS Institute, Cary, NC, USA). All data were analyzed based on intention-to-treat. Before the statistical analysis all data were tested for normality by Shapiro-Wilk W-test and variance homogeneity and data transformed if necessary. Differences between supplements were tested by analysis of variance (general linear models (GLM)), with or without adjusting for various confounders (Table 2). Post hoc comparisons were made, with Turkey–Kramer adjustment of significance levels for the pairwise comparison, using unpaired t-test when the analysis indicated significant treatment effect.

Respiratory measurements (4-h RMR and RQ) were tested by mixed linear models procedure as repeated measurement adjusted for baseline level. Furthermore, after subtraction of the baseline level ratings, RMR and RQ were calculated as an area under the curve (AUC). Difference between initiation and completion of the weight maintenance phase was tested by ANCOVA adjusted for baseline both within and between supplements.

The relationship between changes in 4-h RMR (AUC) and anthropometric and hemodynamic measures during the intervention was tested in a Pearson correlation test.

Relationship between 4-h RMR and change in FM during the weight maintenance phase was tested by linear regression.

Owing to lack of compliance to collect feces correctly only samples which were within two standard deviations of the mean fecal fat and energy content were included in the statistical analysis. Urine samples with a PABA recovery 85–115% were considered complete urine collections and were included in the statistical analysis.

Difference between treatments in the prevalence of self-reported adverse events (AE) was tested by homogeneity test.



Drop outs

Five participants (whereof four men) dropped out of the weight maintenance phase owing to lack of ability to follow the study protocol (n=2 bioactive compound), illness (n=1 placebo) and chronic nausea/vertigo (n=1 placebo, female subject, n=1 bioactive compound).

Body weight and composition

There was no difference at LCD baseline between the groups that were later randomized into the three weight maintenance groups. No significant difference was found between groups with respect to BMI, waist circumference, body weight and composition. In both groups (pooled active group and placebo group) BMI, waist circumference, body weight and composition were reduced significantly at completion of the LCD phase compared to baseline levels. However, the changes were not significantly different between the groups (Table 2).

At initiation of the randomized weight maintenance phase baseline BMI, waist circumference, body weight and composition were not significantly different between groups (Table 3). Between initiation and completion of the supplementation period body weight, BMI and waist circumference were reduced significantly in both groups. In the placebo group body weight decreased by 1.1plusminus2.4 kg (n=23, P=0.04) and in the active group by 1.3plusminus2.2 kg (n=57, P<0.0001). This difference was not statistically significant (Table 2).

Fat mass was reduced by 1.8plusminus2.1 kg in the active group (P<0.01), vs 0.8plusminus2.4 kg in the placebo group (P=NS) (active vs placebo P<0.08). As the size of the weight loss in the LCD phase and fat mass size are known determinants of the weight loss during the randomized part of the trial, we analyzed the changes in fat mass in the randomized phase with initial body fat mass (P<0.04) and weight changes in the LCD phase (P<0.001) as covariates. In this analysis the fat loss of 1.8plusminus2.1 kg in the active group was significantly greater than that of 0.8plusminus2.4 kg in the placebo group, the difference being 1.0 (95% CI 0.3: 1.7) kg fat (P<0.05). The reduction of percentage of total body fat supported these findings. The percentage of body fat mass was significantly reduced, by 1.6plusminus2.0% (P<0.0001), between initiation and completion of the weight maintenance phase in the active group. Percentage of body fat mass was insignificantly reduced in the placebo group by 0.7plusminus2.4%. The group difference tended a significance, 0.9% (95% CI 0.2:1.6, P=0.075). When adjusted for the percentage body fat mass (P<0.04) at initiation of the supplementation period and weight changes in the LCD phase (P<0.001) the change of percentage of total body fat was significantly different between groups, active group: -1.7plusminus2.1% vs placebo: -0.6plusminus2.4% (P=0.03).


Compliance to treatment (intake of tablets) in the placebo and active group was 95plusminus7 and 95plusminus8%, respectively. No significant difference was found between groups.

Resting metabolic rate and respiratory quotient

Acute exposure to the bioactive compound caused a significant increase in 4-h repeated measurement of RMR (adjustment for baseline RMR and gender) on the first day of the supplementation period (Figure 2a) compared to placebo (P=0.04). This effect was maintained after 8-week subchronic supplementation (Figure 2b) (P=0.02). Calculated as AUC RMR (Figure 2a) the bioactive supplement caused a significant acute increase of 87.3 (81.8: 92.9) kJ/4 h, (P=0.005) as compared to placebo. After 8-week supplementation the significant increase was 85.5 (79.3:91.7) kJ/4 h, (P=0.03), (Figure 2b) compared to placebo. Furthermore, there was no significant change in 4-h measurements of RMR between the first and last exposure to treatment in any of the groups, which suggests that the thermogenic effect was not attenuated during chronic treatment. The bioactive supplement caused a 2.4% increase in 4-h RMR (99.7plusminus19.2 kJ/4 h, P<0.001) when adjusted for the interaction between time and treatment (P=0.9).

Figure 2.
Figure 2 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

(a and b) Baseline subtracted change in resting metabolic rate (RMR) (meanplusminuss.e.) during 4-h measurement in the two subgroups. (a) Acute effect at first exposure of supplement: placebo group (age: 51.0plusminus10.5 years, n=23, four male subjects) and bioactive group (age: 46.6plusminus11.0 years, n=52, 14 male subjects). (b) Effect of last exposure after 8-week supplementation: placebo group (age: 51.7plusminus10.9 years, n=21, 3 male subjects) and bioactive group (age: 47.2plusminus10.8 years, n=52, 11 male subjects).

Full figure and legend (45K)

There was no significant linear relationship between the increase in RMR and the change in FM between initiation and completion of the weight maintenance phase when tested as thermogenic effect of acute, subchronic exposure or mean value of the two exposures vs body fat loss.

Baseline values and 4-h repeated measurements of RQ were unchanged in both treatments at initiation and completion of the supplementation period. Furthermore, the changes in 4-h RQ and baseline values between start and completion of the weight maintenance phase showed no significant difference between supplements.

Hemodynamic measures

In both groups heart rate, systolic and diastolic blood pressures were reduced significantly at completion of the LCD phase compared to baseline levels (Table 2). Between initiation and completion of the weight maintenance phase heart rate, systolic and diastolic blood pressures were not significantly different from the changes in the placebo group. However, heart rate was increased significantly by 5.6% (3.2plusminus7.6 bpm, P=0.003) in the active group, but this change was not different from the increase in the placebo group of 2.5plusminus6.6 bpm (P=0.8). No relationship was found between changes in hemodynamic measures and RMR.

Fecal excretion of energy and fat

Although insignificant, the active group excreted 13% more fecal fat between the LCD and weight maintenance phase compared to placebo, 0.4 g/day (95% CI: -0.8; 1.6, P=0.7). No significant difference in fecal fat excretion was found between groups in the LCD phase (Table 3). Change in excretion of fecal energy between the LCD phase and the weight maintenance phase was not significantly different between groups.

Urinary excretion of nitrogen, calcium and catecholamines

Nitrogen excretion was not significantly different between groups between the LCD and weight maintenance phase. Change in calcium excretion tended to be significantly higher level in the bioactive compound group compared to placebo, 44.2 mg/day (95% CI: 39.1; 49.4), P=0.07. No significant difference between groups was found in the changes in NA and adrenaline between the LCD and weight maintenance phase.

Self-reported adverse events

The two groups were homogeneous with respect to the frequency of specific types of self-reported AE and total sum of self-reported AEs during the 8-week supplementation (P=NS) (Table 4). However, the placebo supplement gave rise to a higher frequency of headaches than bioactive supplement (Table 4). No difference was found between groups in regard to gastro-intestinal problems (P=NS).



The results of the present study are consistent with the previously reported thermogenic properties of this particular bioactive compound.33 It is encouraging in this context that the thermogenic effect seems to be maintained after an 8-week supplementation. We observed no tendency to an adaptation in the thermogenic response after 8 weeks of treatment. Although we find it likely, we have no evidence that the effect is maintained beyond the 8 weeks. However, we would like to draw attention to the fact that the sustained effect over 8 weeks is in contrast to the tachyfylaxia that develops for caffeine alone, and also for some tested selective beta3 agonists in humans. In the present study the highly selective beta3 agonist L-796568 was highly thermogenic at first exposure in humans,43 but lost all thermogenic potency after 4 weeks.44

In previous human studies CAP has been given as red pepper in single meals. However, the content of CAP and pungency differs in the species of Capsicum Annuum L.45 It is therefore difficult to compare studies unless the pungency is reported in Scoville heat units. Previous studies have shown that addition of approximately 30 mg CAP to meals could increase SNS activity10, 46 and diet induced thermogenesis,9, 47 which is in agreement with the present findings of 2.4% increased RMR with a lower dosage of CAP (1.2 mg). The increased thermogenesis at a lower dosage of CAP may be explained by a synergy between the bioactive agents in the compound. A synergy between CAP and caffeine has been found of Yoshioka et al.14 in a study where acute administration of a combination of red pepper (Saemaul Kongjang) and caffeine in combination increased 24-h EE by 3% compared to red pepper administrated alone.

Long-term weight maintenance after a body weight loss is often unsuccessful. Weight regain is observed in most studies, indicating that most subjects are not able to change their eating habits or level of physical activity. Lejeune et al.8 investigated whether a 3-month supplementation of CAP (135 mg/day) could prevent a weight regain after a 6.6% weight loss. Weight maintenance was not improved by CAP supplementation and no effect was found on EE, but fat oxidation was higher after the weight maintenance period.

We have previously suggested that a local action of CAP in the gastric mucosa may be required to provide the essential stimulation of SNS. Two studies have shown that the stimulating effect of CAP may occur both in the mouth and in the gastrointestinal regions by stimulating sensory pathways activating SNS in a dose-dependent manner.11, 12 However, in the present study we found no differences between the simple and controlled release versions of the compound on stimulation of thermogenesis, which contradicts our previous findings about the lack of thermogenic effect of the enterocoated version.33

Even though there was a significant and maintained thermogenic effect of the compound after 8 weeks of supplementation, we failed to find a significant association between body fat loss and change in RMR. This suggests that a suppression of food intake produced by the bioactive supplements may be at least as important. However, a simple calculation suggests that the thermogenic effect could account for most of the fat loss. It has been observed in both human and animal studies that CAP and catechins can increase fat oxidation and inhibit fat accumulation. We found no change in RQ when supplementing with the bioactive compound. However, there are inconsistencies in the evidence of changes in fat utilization with CAP supplementation.8, 9, 46, 47 Other compounds, such as caffeine and green tea extract (catechins and caffeine), have also been shown to increase lipid oxidation by enhancing SNS activity.2 A recent study has shown that catechins and caffeine interact synergistically in suppression of fat accumulation in mice.17 It is thought that the adrenergic receptor stimulation of NA can decrease fat accumulation or promote body fat loss by increasing thermogenesis and the release of fatty acids for combustion, and in the case of a central action, mimic the natural effect of satiety on appetite control. Furthermore, a green tea extract rich in EGCG has been shown to increase SNS activity acutely, and to increase 24-h EE and fat oxidation in humans.2 However, in the present study the relative contribution of the specific catechins isomers is not known. Interestingly, Kao et al.48 found that only EGCG, but not related catechins, could significantly reduce blood concentrations of leptin, insulin, glucose, cholesterol and triglycerides in rats. This could indicate that the effect of green tea is dependent of the specific catechins content. However, this theory has to be conformed by future studies.

Kovacs et al.1 investigated whether a 13-week supplementation of green tea extract (573 mg catechins/day) could prevent a weight regain after a 7.5% weight loss. Weight maintenance was not affected by green tea supplementation and no significant effect on EE and subjective sensation of hunger or satiety was found. However, Kovacs et al.1 found that high caffeine consumption (>300 mg/day), without regard to green tea supplementation, had a significant effect on sensation of satiety and decreasing levels of leptin, but that weight regain was significantly higher in the high caffeine group. Despite a lower intake of catechins and caffeine in the present study compared to Kovacs et al.1 (573 mg catechins/day and 369 mg habitual caffeine/day) we found a significant effect of 8-week supplementation on EE (increased) and body FM (decreased). However, the effects of the present food ingredients could be synergistically potentiated when given in combination and thus have a measurable effect. Otherwise CAP would seem to be the main contributor to the maintained increased thermogenic effect of the compound.

Klaus et al.7 have recently shown that EGCG could decrease the bioavailability of dietary fat in a dose-dependent manner. They showed an increased content of fecal fat after 4 weeks of supplementation. We observed also an increased level of fecal fat, but this was not significant.

The lack of showing an enhanced fecal fat loss does not support previous findings that high-calcium intake could increase fecal fat excretion. In a human study by Jacobsen et al.26 it was found that a calcium-rich diet could significantly increase fecal fat loss 2.5-fold or 350 kJ/day and this finding is confirmed in other human studies.25, 32, 49, 50 An explanation for the apparent discrepancy to our results could be that we instructed the subjects to take the supplement one hour before the main meals. The effect of calcium may be dependent on calcium being ingested as a supplement together with a meal or as part of a calcium-rich meal in order for calcium to bind to fatty acids in the gut.

The present study confirms our previous findings of a good safety profile of the compound.33 The frequency of self-reported AE was similar to that in the placebo group (Table 4) and no difference between treatments was found in the hemodynamic factors.

The present study confirms the previously reported thermogenic properties of the compound. The supplementation increased 4-h RMR by 90 kJ more than placebo, and the study extends previous findings by showing that the effect was maintained after 8 weeks, and was accompanied by a slight reduction in fat mass. However, further investigations are needed to evaluate the long-term use of the compound. The thermogenic effect is likely to exceed 300–400 kJ/day when the supplement is taken 3 times/day, without any detectable hemodynamic adverse effects. In conclusion, the combination of these bioactive food ingredients may be of value in supporting weight maintenance after a weight reduction.



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We thank John Lind and Inge Timmermann for their expert technical assistance, and Arne Astrup and Søren Toubro for critical reading of the manuscript. The study was supported by a grant from Metabolife Inc, San Diego, CA, USA. The dietary supplements containing the ingredients examined in the present paper were manufactured by Alpine Health Products, Salt Lake City, Utah, and are not commercially available.



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