Resting energy expenditure (REE) decreases in response to caloric restriction [1–4]. In the obese, this decline in REE results in a decreasing rate of weight loss during periods of low calorie dieting. There have been attempts to inhibit the adaptive decrease in energy expenditure that occurs through aerobic exercise [5–7], but a previous study from our group [8] demonstrated that the institution of aerobic exercise did not affect the adaptive decrease in thermogenesis which is believed to be mediated by a change in sympathetic nervous system (SNS) activity.

Capsaicin from chili pepper is known to stimulate thermogenesis through a central nervous mechanism, but at doses required to observe this metabolic effect intolerable gastrointestinal side effects occur. Studies suggest that capsinoids such as dihydrocapsiate (DCT) found in the non-pungent CH-19 sweet pepper share the positive metabolic characteristics of capsaicin without inducing gastrointestinal side effects [9–13]. DCT has a hot taste threshold estimated at approximately 1,000 times that of capsaicin, but both capsaicin and DCT stimulate TRPV1 receptors in the gut which bring about activation of the SNS, which can increase lipogenesis and thermogenesis [10]. Extracts of CH-19 sweet have been shown to increase body temperature, oxygen consumption, sympathetic nervous system activation, and to lead to weight loss in two studies [11, 14].

The present study was designed to examine the effects of DCT on both adaptive thermogenesis as the result of caloric restriction with a high protein very low calorie diet (VLCD) and to determine whether DCT would increase post-prandial energy expenditure (PPEE) in response to a 400 kcal/60 g protein liquid test meal.

The capsinoids are found in all tested cultivars of the Capsicum genus of plants which includes chili peppers [15, 16]. The capsinoids include capsiate, dihydrocapsiate, and nordihydrocapsiate which are structural analogs of the capsaicin, dihydrocapsaicin, and nordihydrocapsaicin found in hot chili peppers. Capsaicin results in a hot sensation in the oral cavity, but the capsinoids are not perceived as hot because they are hydrolyzed as they cross the oral mucosa. Capsinoids including dihydrocapsiate stimulate thermogenesis in animals, and activate the neuronal TRPV1 receptors on vagal afferent nerves in the intestine leading to increased sympathetic nervous system activity with uncoupling of oxidative phosphorylation leading to heat production [10, 17].

In this small double-blinded, randomized, placebo controlled trial, we found that the consumption of a nonpungent capsiate supplement by overweight and obese subjects significantly increased post-prandial energy expenditure when combined with a high protein, very low calorie diet on an outpatient basis. The increase is estimated to be equivalent to an increase in daily energy expendtiture of approximately 100 kcal for a 100 kg individual. Hill et al using data from national surveys have estimated that changing energy balance favorably by 100 kilocalories per day could prevent the secular trends in weight gain observed in the U.S. population [18].

Total daily energy expenditure is composed of basal metabolic rate, postprandial thermogenesis, and physical activity thermogenesis. An adaptive reduction in EE in response to energy restriction can be observed in any component of total EE, traditionally divided into resting and non-resting EEs (including physical activity and non-exercise activity EEs), and thermic effect of food [19]. However, these changes are usually observed in resting EE in individuals undergoing dietary restriction for longer periods of time. In this study there was individual variation on the adaptive thermogensis in our study subjects at 4 weeks. There were no significant changes observed at the group level in any of our study groups after 4 weeks of VLCD and DCT supplementation. Inoue et al. previously reported that a significant increase of oxygen consumption was detected in the subjects with BMI over 25 in resting status when they ingested capsinoids for 4 weeks [12]. In this context, a marked reduction of body weight by VLCD in this study may have more impact on resting energy expenditure than that of capsinoids.

Subjects in all three groups lost significant amounts of body weight and fat mass but there were no significant differences observed in weight or fat loss among the groups. The severe restriction of calorie intake in the VLCD may have overshadowed any potential effects of capsinoids. While there were prior investigations establishing the effects of capsaicin and capsiates on satiety, the VLCD did not allow assessment of food intake as a practical measure of effects on satiety [20, 21].

In this clinical trial, the impact of capsiate supplementation was tested on an outpatient basis where compliance with diet is always problematic and undoubtedly influenced the observations made here. This small metabolic study was not designed to assess long-term effects on weight and body composition.

It has been reported in several small clinical trials that capsinoids suppress body fat accumulation [11, 13, 22]. Josse et al has recently reported that 10 mg of capsinoids resulted in a shift on substrate utilization toward lipid [23]. Using indirect calorimetry, we observed that DCT supplementation blunted the increase in post-prandial respiratory quotient at day 28 seen in the placebo group suggesting that DCT increased fat oxidation. Further studies are needed to assess the impact of the predicted differences in energy expenditure related to DCT supplementation on weight loss and weight maintenance in free-living populations.