Active Component:

• WS-3, WS-5, WS-12 or WS-23

• Iodine

 

Form:
Frostamide-3, Frostamide-5, Frostamide-12 and Frostamide-23 come as white powders to be added at 20mg to 50mg per serve of finished product. These performance ingredients are certified and guaranteed in purity using Fourier Transform (Infra-Red) Raman Spectroscopy. They impart a cooling taste profile.

 

Recommended Application:

• 20mg - 50mg per serve of finished product (do not exceed recommendations)

  • Endurance training 

  • Thermogenic

  • Energy enhancement

  • Weightloss

 

Research Highlights:

• Potent thermogenic activity in fat

• Encourages conversion of white fat to brown thermogenic fat in adipose tissue

• Increased glucose metabolism and reduction of obesity

• Reduces pain sensitivity

• Stimulating

 

Permissible Label and Advertising Claims Under FSANZ:

• Necessary for the normal production of thyroid hormones

• Necessary for normal energy metabolism

 

Research Details:

The WS family of compounds were developed as more potent and selective ‘cooling sensation’ agents derived from menthol with less of its distinct flavour for use in foods. Their potency makes them well-suited for use as agonists of the cold-sensing receptor TRPM8, where they have been demonstrated to be selective and have high activity (Leffingwell, 2007).

 

WS-12 has been studied in particular for its potential application as a treatment for neuropathic pain, selectively activating TRPM8 channels which ease pain by inhibiting nociceptive neuronal currents via the same mechanisms as an ice-pack without activating the noxious-cold perception experienced by ice that is too cold against the skin (Sherkheli, Gisselmann, Vogt-Eisele, Doerner, & Hatt, 2008).

 

However, one of the most noteworthy effects of these compounds is their capability to increase the activity of brown fat, induce a browning of white fat and encourage a thermogenic phenotype as a result of the body’s attempts to counteract the perceived cold by warming up. This results in reversal of high-fat diet induced obesity and increased glucose metabolism (Jiang, Zhai, Yan, Li, Li, Zhang, & Sun, 2017). Further, it has been demonstrated that chronic activation of TRPM8 protects against obesity and diabetes by upregulating the thermogenic protein Uncoupling Protein 1 in brown fat, which also increases locomotor activity thus providing an ‘energy boost’ due to the increased glucose utilisation (Ma, Yu, Zhao, Luo, Chen, Ni, & Li, 2012; Kozyreva, Kozaruk, Tkachenko, & Khramova, 2010). Insufficient activity of TRPM8 has been linked to obesity and reduced body temperature highlighting its importance in maintaining a lean phenotype (Reimúndez, Fernández-Peña, García, Fernández, Ordás, Gallego, & Señarís, 2018; Almeida, Hew-Butler, Soriano, Rao, Wang, Wang, & Garami, 2012).

TRPM8 activation in skeletal muscle has been linked to increased glucose utilisation and upregulation of PGC-1a, resulting in enhanced endurance (Li, Li, Xiong, Liu, Lv, Qin, & Xu, 2018). In fact, the TRPM8 channel has been described as a testosterone receptor, mediating some of the effects of androgens (Asuthkar, Elustondo, Demirkhanyan, Sun, Baskaran, Velpula, & Zakharian, 2015). There is some evidence to suggest that many of the rapid, acute effects of testosterone are mediated by the TRPM8 receptor, including sex drive and aggression (Asuthkar, Demirkhanyan, Sun, Elustondo, Krishnan, Baskaran, & Zakharian, 2015; Mohandass, Krishnan, Gribkova, Asuthkar, Baskaran, Nersesyan, & Alexander, 2020). Further, it has been demonstrated that the TRPM8 channel colocalizes with the androgen receptor, and they may regulate one-another’s activity, making TRPM8 receptor agonists true androgenic agents in their ability to modulate the androgen receptor (Gkika, Lolignier, Grolez, Bavencoffe, Shapovalov, Gordienko, & Etienne, 2020).

 

References:

Almeida, M. C., Hew-Butler, T., Soriano, R. N., Rao, S., Wang, W., Wang, J., & Garami, A. (2012). Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature. Journal of Neuroscience, 32(6), 2086-2099.

 

Asuthkar, S., Demirkhanyan, L., Sun, X., Elustondo, P. A., Krishnan, V., Baskaran, P., & Zakharian, E. (2015). The TRPM8 protein is a testosterone receptor II. Functional evidence for an ionotropic effect of testosterone on TRPM8. Journal of Biological Chemistry, 290(5), 2670-2688.

 

Asuthkar, S., Elustondo, P. A., Demirkhanyan, L., Sun, X., Baskaran, P., Velpula, K. K., & Zakharian, E. (2015). The TRPM8 protein is a testosterone receptor I. Biochemical evidence for direct TRPM8-testosterone interactions. Journal of Biological Chemistry, 290(5), 2659-2669.

 

Gkika, D., Lolignier, S., Grolez, G. P., Bavencoffe, A., Shapovalov, G., Gordienko, D., & Etienne, M. (2020). Testosterone‐androgen receptor: The steroid link inhibiting TRPM8‐mediated cold sensitivity. The FASEB Journal.

 

Jiang, C., Zhai, M., Yan, D., Li, D., Li, C., Zhang, Y., & Sun, W. (2017). Dietary menthol-induced TRPM8 activation enhances WAT “browning” and ameliorates diet-induced obesity. Oncotarget, 8(43), 75114.

 

Kozyreva, T. V., Kozaruk, V. P., Tkachenko, E. Y., & Khramova, G. M. (2010). Agonist of TRPM8 channel, menthol, facilitates the initiation of thermoregulatory responses to external cooling. Journal of Thermal Biology, 35(8), 428-434.

 

Leffingwell, J. C. (2007). Cool without Menthol & Cooler than menthol and Cooling compounds as Insect Repellents. From the Internet: URL: http://www. leffingwell. com/cooler—than—menthol. htm [updated Apr. 5, 2006].

Ma, S., Yu, H., Zhao, Z., Luo, Z., Chen, J., Ni, Y., .& Li, L. (2012). Activation of the cold-sensing TRPM8 channel triggers UCP1-dependent thermogenesis and prevents obesity. Journal of molecular cell biology, 4(2), 88-96.

 

Li, C., Li, J., Xiong, X., Liu, Y., Lv, Y., Qin, S., & Xu, L. (2018). TRPM8 activation improves energy expenditure in skeletal muscle and exercise endurance in mice. Gene, 641, 111-116.

 

Mohandass, A., Krishnan, V., Gribkova, E. D., Asuthkar, S., Baskaran, P., Nersesyan, Y., & Alexander, B. M. (2020). TRPM8 as the rapid testosterone signaling receptor: Implications in the regulation of dimorphic sexual and social behaviors. The FASEB Journal, 34(8), 10887-10906.

 

Reimúndez, A., Fernández-Peña, C., García, G., Fernández, R., Ordás, P., Gallego, R., & Señarís, R. (2018). Deletion of the cold thermoreceptor TRPM8 increases heat loss and food intake leading to reduced body temperature and obesity in mice. Journal of Neuroscience, 38(15), 3643-3656.

 

Sherkheli, M. A., Gisselmann, G., Vogt-Eisele, A. K., Doerner, J. F., & Hatt, H. (2008). Menthol derivative WS-12 selectively activates transient receptor potential melastatin-8 (TRPM8) ion channels. Pakistan journal of pharmaceutical sciences, 21(4).