Background
Capsiate and other capsinoids are substances naturally present in chili peppers. Although structurally related to capsaicin, the substance that causes pungency in hot peppers, capsinoids have almost no pungency. Attracting less attention to themselves than the pungent capsaicin, capsinoids were not reported until 1998, when biologists first isolated them in a unique variety of chili peppers, CH-19 Sweet, that is devoid of capsaicin.

Mechanisms of Action
Capsaicin feels hot in the mouth because it activates sensory receptors on the tongue otherwise used to detect thermal heat. This receptor type is called Transient Receptor Potential Vanilloid 1, or TRPV1. TRPV1 receptors are also located in the gut and in other organs. It is commonly said that hot peppers help people in the tropics “cool off.” This theory is consistent with the peripheral vasodilatory effect of capsaicin that has been shown to lower skin temperature in humans exposed to a hot environment [Nelson AG, 2000]. In a temperate environment, to compensate for heat loss and because of intrinsic effects of capsaicin mediated by increments in sympathetic nervous system activity [Kawada et al. 1986], ingestion of hot peppers causes an increase in energy expenditure, or thermogenesis [Yoshioka, 1998].

 

Like capsaicin, capsinoids activate TRPV1 receptors [Iida et al. 2003, Nagy et al. 2004]. TRPV1 receptors in the mouth, however, do not react to capsinoids because they are located slightly below the surface in the oral cavity where capsinoids cannot reach it due to their structural differences from capsaicin. (If pure capsaicin and capsiate are diluted in water, it takes 1000 times as much capsiate before a person can taste it.) On the other hand, both capsaicin and capsinoids activate TRPV1 receptors in the gut to approximately the same extent. Research has indicated that receptors in the gut may be as important as those on tongue for the metabolic effects of capsaicin and capsinoids. It is notable that when capsinoids are administered to humans by mouth, they cannot be demonstrated in the circulation [Ajinomoto Co., data on file]. This fact lessens concerns about untoward activation of TRPV1 receptors in other parts of the body.

Potential Role in Weight Management

 

Stimulation of TRPV1 receptors in the gut is known to bring about activation of the sympathetic nervous system, which has effects on multiple organs, including fat and muscle to increase thermogenesis and affect substrate selection and tissue accretion. While the exact mechanisms, and the relative importance of each mechanism are still under investigation, as are the effects of capsinoids on appetite and satiation, both oxygen consumption and body temperature increase are observed in humans following capsinoid administration [Ohnuki et al., 2001a]. Animal studies also demonstrate these increases, as well as suppressed in body fat accumulation [Ohnuki et al., 2001b; Ohnuki et al., 2001c].

Combined with the effects on energy metabolism and lack of pungency, their favorable safety profile makes capsinoids a promising weight management agent in humans. Capsaicin, on the other hand, has been considered not useful for weight management in humans due to its unpleasant sensory qualities [Diepvens, 2007].

Safety Studies
Purified extracts of the sweet chili pepper which contains capsinoids have been extensively studied through a wide range of laboratory, animal and human testing.

A partial listing of the safety studies conducted includes:

  • Single dose toxicity study (rats)
  • 26-week oral toxicity study (rats)
  • Teratology studies (rats and rabbits)
  • Two generation reproduction study (rats)
  • Genotoxicity studies (mice)
  • Pharmacokinetics (rats)
  • Single dose oral administration study (humans)
    • Blood pressure and heart rate
    • Blood chemistry, hematology and urinalysis
    • Pharmacokinetics

Capsinoids have a very favorable safety profile, and pharmacokinetics studies conducted to date indicate that they are not absorbed into the circulation.

 

The capsinoid 26-week oral load test estimated a no observed adverse effect level (NOAEL) of 178 mg/kg/day for male and 356 mg/kg/day for female rats. Capsinoids had no effect on reproductive performance and on the next generation at the levels tested in the teratology studies (rats and rabbits) and the two generation reproduction study (rats), nor were they found to be mutagenic in the genotoxicity studies.

Capsinoids are hydrolyzed before absorption and breakdown to fatty acids and to vanillyl alcohol. According to human studies conducted to date, capsinoids are not present in the bloodstream following oral administration. Single dose oral administration of up to 30 mg capsinoids in healthy volunteers did not raise blood pressure or heart rate.

Characteristics of Capsinoids: Summary

  • Capsinoids are well-studied potential candidates for dietary supplements and food ingredients that elicit some of the favorable effects experienced as a result of eating hot chili peppers.
  • The “hot taste threshold” of capsinoids is very low, estimated at approximately 1000 times that of capsaicin. Capsinoids are regarded as virtually non-pungent and are well tolerated orally by many people who tried them. In contrast, capsaicin is extremely pungent and usually tolerated only at very low levels orally.
  • Both capsaicin and capsinoids stimulate TRPV1 receptors in the gut. Stimulation of TRPV1 receptors in the gut is known to bring about activation of the sympathetic nervous system, which has effects on multiple organs, including fat and muscle to increase thermogenesis and affect substrate selection, and tissue accretion.
  • Capsinoids are hydrolyzed and break down to fatty acids and to vanillyl alcohol. According to available studies conducted, capsinoids are not absorbed into the bloodstream. Meanwhile, animal study showed that capsaicin (in the form of dihydrocapsaicin) was absorbed into the bloodstream.
  • Capsinoids have a very favorable safety profile, as demonstrated in rigorous laboratory, animal and human studies.

Sources
Diepvens K. et al., Amer J of Physiology-Regulatory Integrative and Comparative Physiology 292:R77-R85, 2007.

Iida T. et al., Neuropharmacol 44:958-967, 2003.

Inoue N. et al., Biosci Biotechnol Biochem 71:380-389, 2007.

Kawabata F. et al., Biosci Biotechnol Biochem 70:2824-2835, 2006.

Kawada T. et al., J Nutr 116:1272-1278, 1986.

Masuda Y. et al., J Appl Physiol 95:2408-2415, 2003.

Nagy I. et al., Eur J Pharmacol 500:351-369, 2004.

Nelson A.G. et al., Wilderness Environ Med 11:152-6, Fall 2000.

Ohnuki K. et al., Biosci Biotechnol Biochem 65:2033-2036, 2001(a).

Ohnuki K. et al., Biosci Biotechnol Biochem 65:2735-2740, 2001(b).

Ohnuki K. et al., J Nutr Sci Vitaminol 47:295-298, 2001(c).

Yoshioka M. et al., British Journal of Nutrition 80:503-10, 1998.