Nutrition Performance - Capsiate: The Latest Thermogenic

The poor regulation of supplements and sports foods allows athletes and coaches to be the target of marketing campaigns based on exaggerated claims and hype rather than documented benefits. However, some sports supplements and sports foods offer real advantages to the athlete or bodybuilder. Some products work by producing a direct ergogenic (performance-enhancing) effect (e.g., creatine, caffeine). Other products can be used by athletes to meet their nutritional goals and, as an indirect outcome, allow them to achieve optimal performance (e.g., protein-carbohydrate drinks).

Further, several herbal medicines may have therapeutic medicinal (although not ergogenic) value applicable to athletes (e.g., St. John´s wort). Finally, some products may help optimize body composition (e.g., thermogenic supplements). The latest thermogenic candidate appears to be capsiate, a non-pungent capsaicin analog.

Thermogenesis: Dissipation of Energy Derived from Food as Heat

Not all the energy in foods is transferred to adenosine triphosphate (ATP; the universal energy carrier in cells). Instead, a portion of this energy becomes heat. On average, 35 percent of the energy in foods becomes heat during ATP formation. However, in certain types of fat tissue, called brown fat, sympathetic nervous stimulation (“fight-or-flight” response) causes liberation of large amounts of heat.

Brown fat tissue is the major site of thermogenesis in the newborn and is especially prominent in the mammalian fetus. The largest accumulation of brown fat tissue envelops the kidneys and adrenal glands, and smaller amounts surround the blood vessels of the mediastinum (the broad, median partition between the pleurae of the lungs) and neck. The mass of brown fat tissue peaks at the time of birth and gradually decreases during the early weeks of life.

This type of fat contains a large number of mitochondria (powerhouses of cells) and many small globules of fat instead of large fat globules. In these cells, the process of oxidative phosphorylation (the formation of ATP by using energy derived from electron transport to oxygen) in the mitochondria is mainly “uncoupled.” That is, when the cells are stimulated by the sympathetic nerves, the mitochondria produce a large amount of heat, but almost no ATP, so almost all the released oxidative energy immediately becomes heat. Radiating energy away as heat enables the body to spend, rather than store, energy.

As ATP production diminishes, the dynamics of the catabolic breakdown and biosynthesis of stored nutrients shifts to catabolism to replenish the ATP. Theoretically, therefore, weight reduction should accompany a higher activity of brown fat. Indeed, a possible link between obesity and deficient brown fat function has been researched. For example, evidence indicates that thermogenesis is defective in instances of obesity. However, direct evidence that the defects reside in brown fat tissue is tenuous.

Two types of external stimuli trigger thermogenesis: 1) the ingestion of food and 2) prolonged exposure to cold temperature, both of which stimulate the tissue via sympathetic innervation via the hormone norepinephrine

(noradrenaline). The sympathetic signal has a stimulatory and hypertrophic effect on brown fat tissue. This results in enhanced expression of the uncoupling protein (UCP) in the inner membrane of the mitochondrion.

UCPs are thought to play important roles in energy expenditure, maintenance of body weight and thermoregulation.

Uncoupling protein 1 (UCP1) is expressed exclusively in brown fat tissue⁴ and is a key molecule of thermogenesis in brown fat tissue. UCP2 ubiquitously expresses it and genetic studies have linked it to energy dissipation in humans.⁵ UCP3 is an identified protein in skeletal muscle and is also expressed in brown fat tissue in rodents.⁶ UCP3 in skeletal muscle is up-regulated by fasting.⁷ It’s currently thought to act as a transporter protein of fatty acids, rather than to thermogenesis or energy balance.⁸

Clearly, ephedra is the most popular thermogenic supplement known to mankind. Ephedra enhances release of norepinephrine from sympathetic neurons. Thus, it increases thermogenesis and hence, resting energy expenditure. Ephedra also functions as an anorectic (appetite suppressor).

Capsiate Gets Into the Act

The capsicum species, native to tropical America, incorporates such peppers as the cayenne, red and chili. Chili is the Aztec name for the cayenne pepper, and it has been used by Native Americans as food and medicine for over 9,000 years.² The medicinal properties of capsicum are attributable to a compound know as capsaicin, although other capsaicinoids are also available.² Capsaicin is regarded as a pain reliever, possibly blocking pain fiber by depleting substance P, the neurotransmitter mediating pain signals to the brain.³

Further, capsaicin as been reported to 1) elevate body temperature;¹² 2) stimulate the secretion of catecholamines (norepinephrine, epinephrine),¹³ 3) promote energy expenditure;¹⁴ and 4) suppress body fat accumulation in experimental animals.¹⁵ However, capsaicin is strongly pungent and neurotoxic, which largely prohibits its administration to humans.

Dr. S. Yazawa and co-workers reported that CH-19 Sweet, a non-pungent cultivar of Capsicum annuum L, rarely contains pungent capsaicinoids, but contains a large amount of two capsaicinoid-like substances.¹⁶ The chemical structures of these two substances have been identified and named capsiate and dihydrocapsiate by Dr. K. Kobata and colleagues.¹⁷

Recently, Dr. Yoriko Masuda and co-workers from Japan examined whether continuous administration of capsiate promotes energy expenditure in mice.⁹ They measured respiratory gas by indirect calorimetry. Indirect calorimetry measures the consumption of oxygen. In other words, it measures the heat produced by oxidative processes. Furthermore, they examined whether capsiate affects the uncoupling proteins (UCPs) in brown fat tissue, white fat tissue (“lard”), and skeletal muscle.

Results indicated that oxygen consumption (i.e., energy expenditure) was significantly higher in the capsiate group than in the control group. Also, carbohydrate and fat oxidation (“biologic burning”) was significantly higher in the capsiate group than in the control group. Consequently, the mean body weight of mice in the capsiate group was significantly lower than that of mice in the control group. The relative weights of epididymal and perirenal fat in the

capsiate group were significantly lower than those in the control group, and continuous administration of capsiate suppressed abdominal fat accumulation.

Further, UCP1 content in the brown fat tissue mitochondrial fraction was significantly higher than that in the control group. In brown fat tissue, UCP1 messenger RNA (mRNA; the class of RNA molecules that specifies the amino acid sequence of a protein and carries this message from DNA to the site of protein synthesis in cytoplasm) levels were significantly higher in the capsiate group than in the control group, but UCP2 and UCP3 mRNA levels did not differ between the groups. In epididymal fat, UCP2 levels were significantly higher in the capsiate group than in the control group, and UCP1 mRNA levels were higher than in the control group. However, UCP3 mRNA levels in epididymal fat did not differ between groups.

The increase in brown fat tissue UCP1 may contribute to the promotion of energy metabolism and the suppression of body fat accumulation induced by capsiate. In a previous study by Dr. K. Ohnuki and co-workers, capsiate was shown to promote the secretion of epinephrine (adrenaline) in mice,¹⁰ suggesting capsiate activates the sympathetic nervous system. Further, the same research group examined whether capsiate activates the sympathetic nervous system in rats.¹¹ A single dose of capsiate increased the SNS index (an index of sympathetic nervous activity) in rats at 30 minutes after the administration, compared to the control group.

Bottom Line

Continuous administration of capsiate raises oxygen consumption, an index of energy expenditure, suggesting that capsiate-treated mice burned more calories. According to Dr. Masuda and co-workers, “This study suggests that capsiate, a non-pungent capsaicin analog, may be an alternative to capsaicin for the therapeutic treatment of obesity in humans.” It should be noted, however, that in adult humans, brown fat tissue plays little part in thermogenesis. Nevertheless, there are several reports linking UCP2 to energy expenditure in humans. UCP2 may be involved in the regulation of the resting metabolic rate and the prevention of obesity in humans. Clearly, well-controlled human studies are needed before any conclusions can be drawn.

Scientific Truths are Subject to Change!

Certainly, some sports supplements and sports foods offer real advantages to the athlete and bodybuilder (see, for example, references 18-32). However, it’s my experience that most exercise physiologists, sports medicine specialists and nutritionists are not familiar with the latest scientific findings on sports nutrition and ergogenic aids. (There are a huge number of sports nutrition papers in scientific journals such as International Journal of Sports Nutrition and Exercise Metabolism, Journal of Applied Physiology and Medicine & Science in Sports & Exercise).

When I began my sports medicine/exercise physiology training some years ago, I was informed by one of my teachers that creatine supplementation does not improve exercise performance. However, I was already familiar with numerous scientific papers demonstrating ergogenic effects of creatine supplementation. Thus, I concluded that all teachers could not be trusted.

Further, I was informed by a nutrition teacher that protein and amino acid supplements are nothing but a waste of money. Although the value of very high