Effects of phenylcapsaicin supplementation on physical performance and mechanical, metabolic, biochemical, perceptual and electrophysiological fatigue

Resumen

Dietary supplements are nutritional complements which ingested in conjunction with a healthy diet may improve health and/or sports performance. By their own definition, these substances are legal and not banned by international agents such as the World Antidoping Agency. Accordingly, these products are free-sale, which makes them highly popular between different athletic populations. As it is presented in chapter 1 capsaicinoids are a group of compounds naturally found in spicy fruits like chili peppers. Due to their clinical and ergogenic potential applications, new scientific research has been conducted around these compounds in the last two decades. Over the last decade, another group of capsaicinoids analogues called capsinoids has also been studied to reduce the discomfort generated when capsaicin is orally ingested. Capsinoids are mainly found in CH-19 Sweet peppers, a type of non-pungent peppers which have been genetically modified to eliminate the natural spiciness of capsaicinoids. Both substances, capsaicinoids and capsinoids, interact with the transient receptor potential vanilloid 1 (TRPV1), which exerts the most important physiological functions of these substances. However, capsinoids are well-documented as a poor bioavailable group of compounds. Moreover, after their ingestion, capsinoids are rapidly metabolized and conjugated, resulting in non-detectable circulating levels in the bloodstream. By contrast, after their ingestion, different capsaicin formulations have a fast effect on different tissues, such as the small intestine, liver, and stomach, which may be extrapolated to peripheral tissues such as the skeletal muscle. On the other hand, the use of oral capsaicin has been reported to be conflictive due to its pungent characteristics that can increase the risk of discomfort during exercise. Therefore, the formulation of new capsaicin analogues that can reduce the optimal physiological dose seems to be a priority approach on this field. For this reason, during the last years a new group of synthetic analogues of traditional capsaicin known as “capsaicyns” has been developed. Among these substances it is found one of special interest called phenylcapsaicin (PC), which has emerged as an alternative to traditional oral purified capsaicin supplementation. PC is a microencapsulation of 98% of PC and 1-1.5% lipidic excipients and cellulose as primary metabolic vehicles. In addition, as it was aforementioned, TRPV1 agonist drugs have exhibited improvements on several pathophysiological conditions, such as chronic musculoskeletal and neuropathic pain, gastrointestinal disruptions (e.g., gastroduodenal mucosal injury) and metabolic disorders (e.g., overweight). On the other hand, sport performance seems to be enhanced through lower ratings of perceived exertion, reductions on discomfort and an increase on mechanical performance (e.g., total volume load). In this regard, the physiological effects of capsaicin are mediated by reductions in inflammatory hyperalgesia, downregulating voltage-activated calcium channels, and influencing thermoception, being all of them common links between healthcare and performance fields. TRPV1 are presented in small diameter nerve fibers which are involved in the processing of nervous signals. Accordingly, in the peripheral nervous system TRPV1 are mainly found in III and IV afferent nerve fibers, a type of peripheral afferent fibers linked to the development of central fatigue by affecting both supraspinal and spinal levels of the nervous system during different tasks, as well as to the detection of a large variety of nociceptive stimuli. Although the mechanisms presented in this section may be relevant to the sports performance field, current direct research on humans’ performance is scarce. In this regard, Before the research intervention of this doctoral thesis was conducted, only 5 studies had evaluated the impact of capsaicinoids or capsinoids supplementation on resistance training outcomes in humans. Overall, the findings of these studies suggest a positive impact of capsaicinoids and capsinoids on strength endurance until exhaustion and the perceptual responses to resistance training. In this sense, these substances provide a “counter-fatigue” effect driven by their analgesic improvement in pain and discomfort through their TRPV1 interaction and the enhancement of muscle contraction due to the increase of calcium release from the sarcoplasmic reticulum. For instance, in a previous study, the group that ingested purified capsaicin (12 mg) performed more repetitions in all the sets of a 4x70% of one repetition maximum (1RM) back squats (SQ) protocol until muscle concentric failure. This effect elicited a significantly increase in the total volume performed in the supplementation condition (measured as total weight lifted). The literature addressing the effects of capsaicinoids or capsinoids on high-intensity interval training is negligible. To date, only two experiments have evaluated this type of exercise under these substances’ supplementation. The first study showed a lack of an ergogenic effect on a repeated sprints protocol, which contrasts with the findings of the second study. In this second study, it was reported an enhancement in the number of efforts performed and the time to reach 90% of oxygen uptake consumption peak (VO2 peak) without changes in VO2 values after 12 mg of purified capsaicin supplementation in a high-intensity interval exercise. The neuromuscular improvements of capsaicin increase in 13 extra efforts and 188 s extra time the task in the supplementation condition compared to placebo. Furthermore, overall-body ratings of perceived exertion (RPE-OB) was maximum in both groups, which suggests that capsaicin improves the total number of efforts until exhaustion or reduces the neuromuscular effort when volume is matched. However, in spite of the positive effect of capsaicin in peripheral neuromuscular performance, how it impacts on sport bioenergetics and central adaptations to exercise remains unclear. Finally, the metabolic and bioenergetic impact of capsacicin and its analogues is poorly studied in the current literature. In this regard, only two studies have reported the metabolic effects of a capsaicinoids or capsinoids on substrate oxidation in healthy individuals. In the first study, participants exhibited equal respiratory exchange ratios (RER) after ingesting 12 mg of capsiate supplementation during cycling exercise performed at 70% of the maximal aerobic speed. In the second study, a meal with 10 g of hot peppers (i.e., without standardizing the active agent) 2.5 hours prior to 1 hour of aerobic exercise at 60% VO2peak showed an increase in RER compared to placebo. In addition, only one study has addressed substrate oxidation standardizing maximal fat oxidation (MFO), which is critical for a real objective evaluation of these variables. However, this study was conducted in overweight participants, which may not be extrapolated to other populations due to the reduced metabolic flexibility of this population.