The main findings of this investigation were that, versus a placebo, 10 mg of capsinoids induced a rise in resting oxygen consumption, a decline in RER, an increase in plasma norepinephrine, and a decline in serum FFAs at rest. We also observed that 10 mg of capsinoids blunted the small but significant rise in blood lactate observed at the onset of exercise seen in the placebo group (0 mg).
Our original hypothesis was that we would see the aforementioned changes in VO2, RER and catecholamines at rest, in line with previous studies [2–4], and that these differences would carry over and be maintained or even augmented during exercise. This type of response has been observed with another adrenergic agonist, caffeine . We did not observe this response and, in fact, aside from the slightly lower blood lactate seen with capsinoid ingestion there was no effect at rest that carried over into exercise. Thus, we propose that the usual adrenergic response associated with exercise may have been greater than that which was induced by capsinoids at rest thereby overriding any significant differences seen during the exercise phase. Hence, there was no synergistic or additive effect at this intensity of exercise. Figure5 shows that the increases seen in plasma epinephrine and norepinephrine during exercise far exceed the magnitude of increase seen at rest with 10 mg of capsinoids. Therefore, it is not surprising that these subtle differences between treatments disappeared with exercise. Our findings do, however, further support claims that capsinoids have their greatest thermogenic effect at rest.
The consumption of 10 mg of capsinoids resulted in a rise in plasma norepinephrine and a decline in RER. Both of these findings suggest that capsinoids increased whole-body lipid oxidation at rest. Furthermore, both plasma glycerol and serum FFA concentration decreased concomitantly possibly indicating the body's increased reliance on circulating lipids as fuel at that time; without tracer-based estimates of appearance and disappearance we are unable to confirm our thesis. Similar findings with respect to lipid metabolism were reported in a longer term study by Kawabata et al . Researchers fed human subjects CH-19 sweet peppers (0.13 g/kg before each meal [0.4 g/kg total]) for 2 weeks and controlled their diet. Those who consumed capsinoids showed a decrease in visceral fat (assessed by CT scan), a decrease in resting RER, and a significantly greater weight loss compared to the control group. Moreover, there was a significant correlation between weight lost and SNS activity (R2 = 0.66; P < 0.05) . In a more recent study, 80 overweight men and women were fed 6 mg/d of capsinoids or placebo for 12 weeks. While total body weight and % body fat did not differ between groups, the capsinoid group showed reductions in visceral fat assessed by DXA and increases in fat oxidation assessed by indirect calorimetry . While these studies certainly show evidence for capsinoids being adrenergic system stimulants and activating lipid oxidation, they do little to shed light on a potential mechanism. As previously mentioned, tracer-based measures are required to assess the mechanistic underpinnings responsible for the decline in RER and increased lipid oxidation and visceral fat loss with capsinoids. With respect to capsinoids' positive effect on the sympathetic nervous system (SNS), this phenomenon has been demonstrated consistently in other human studies [2–4].
We also observed an increase in metabolic rate as indicated by the increase in resting VO2 with the consumption of capsinoids. Our findings are similar to most [2, 4] but not all  of those reported previously in humans showing increased oxygen consumption and heat production indicative of SNS activation. Moreover, as also reported previously , we demonstrated that capsinoids did not affect resting heart rate measures despite the observed changes in plasma norepinephrine and energy expenditure. In a study by Ohnuki et al. , increases in resting oxygen consumption were reported to be in the range of ~5% with consumption of 0.1 g/kg of CH-19 sweet peppers (i.e. for a 70 kg male, this corresponds to 7 g of CH-19 sweet peppers and ~5 mg purified capsinoids [0.3-1.0 mg capsinoids/g pepper ]). We report here that 10 mg of purified capsinoids extracted from CH-19 sweet peppers, a much larger dose, induced a significant rise in resting oxygen consumption of a little more than 20% or 70 ± 13 ml/min. Therefore, the increase in resting VO2 observed in our study, although greater in magnitude possibly due to the larger dose, seems to be in line with other published research [2, 4]. Although we did not measure core body temperature in the current study, with a dose of 0.1 g/kg of CH-19 sweet peppers, researchers observed a significant increase in core body temperature 10-60 min post ingestion further supporting an increase in thermogenesis with capsinoids .
This study was the first to assess the effect of capsinoids and aerobic exercise together in humans on measures of substrate oxidation and energy expenditure. None of the observed resting differences between groups were maintained with exercise. However, at the onset of exercise, the ingestion of 10 mg of capsinoids blunted the rise in blood lactate observed in the placebo group, although significant, this effect was quite subtle. A number of mechanisms are thought to affect lactate production and clearance during exercise, especially at the onset. These include oxygen availability, pyruvate dehydrogenase activation, lactate dehydrogenase isozymes, as well as lactate transporter content . While we cannot be entirely sure as to why lactate did not increase to the same extent in both groups at the start of exercise, we speculate that it may be due to an increased reliance by the 10 mg capsinoids group on available FFAs as fuel early in exercise as opposed to glycogen. Although quite plausible, further studies would need to confirm this hypothesis.
The results of the current study lead us to believe that capsinoids' effects on resting metabolism do not carry over into exercise. It is entirely possible, however, that our exercise regimen may have been too intense and that a lower intensity exercise such as a fast-paced walk would have allowed us to see maintenance of some of the resting metabolic and thermogenic effects. Further studies are needed to assess this, possibly implementing an exercise regimen that more closely mimics daily routines of the general North American population, i.e. activity that is less strenuous and shorter. It would also be interesting to test the effect of capsinoids with a 45-60 minute brisk walk and to monitor for 1 hour post-exercise to allow for a more complete metabolic recovery. Moreover, a test of the effect of capsinoids under these conditions in overweight and obese, sedentary persons may reveal effects during exercise not seen in fit, normal weight individuals.
In conclusion, 10 mg of purified capsinoids resulted in increased thermogenesis following ingestion in young, healthy, physically active males. In this crossover, double-blind, acute trial, compared to a placebo, capsinoids increased resting energy expenditure by ~20%, and based on several observations relating to lipid metabolism (decreased RER, decreased levels of FFAs and glycerol in blood, increased SNS activity), capsinoid ingestion induced greater lipid oxidation at rest. Although none of these effects carried over into exercise, the blunted lactate response with capsinoids 30 min into the exercise bout suggests an altered substrate use, namely a greater reliance on fat as fuel, at the start of exercise. This study, in conjunction with the current literature, further proves that the subtle metabolic effects of capsinoids are most pronounced at rest and as demonstrated in this trial, they seem to be superseded by a moderate exercise regimen.