Description: 1,4-Dioxacycloheptadecane-5,17-dione is an macrocyclic hydrocarbon which modulates the ergogenic system including PGC1α and PPARα. Liquid flavour based PPARα ligand. , (1R*,2S*)-N-(4-Methoxyphenyl)-5-methyl-2-(1-methylethyl) cyclohexane carboxamide 25 mg, 1,4-Dioxacycloheptadecane-5,17-dione is a TRPM8 agonist.
Concentration: 50 mg per ml
Substantively: 24 hours
Organoleptic: Warm vanilla and musk flavour.
Use: PPARα ligand and weight loss/anabolic.
Active Ingredients: (1R*,2S*)-N-(4-Methoxyphenyl)-5-methyl-2-(1-methylethyl) cyclohexane carboxamide 25 mg, 1,4-Dioxacycloheptadecane-5,17-dione 25mg.
Application: 1ml in beverage daily in the morning. I.e.: smoothie or juice.
Ingredients: Vegetable glycerine, (1R*,2S*)-N-(4-Methoxyphenyl)-5-methyl-2-(1-methylethyl) cyclohexane carboxamide 25 mg, 1,4-Dioxacycloheptadecane-5,17-dione 25mg, flavour.
Elimination: Metabolised in liver.
Legal Status: Legal in Australia, food additive FEMA.
Unique Sales Points:
- Food Approved
- Promotes leanness and hardness
- Clinical evidence of activity
- Long acting
The primary macrocyclic structure is a PPARα ligand.1,2 Peroxisomes are small intracellular organelles found in animal cells that perform metabolic functions including respiration, oxidation of fatty acids, and cholesterol metabolism. Peroxisome proliferator-activated receptors (PPARS) are nuclear hormone factors. 3 PPARs were first identified in rodents in 1990. Structurally PPARs are similar to steroid or thyroid hormone receptor and are stimulated in response to small lipophilic ligands. 4 PPARα is expressed predominately in the liver, and to a lesser extent, in muscle, in the heart, and in bone. In the liver, PPARα plays a crucial role in fatty acid oxidation, which provides energy for peripheral tissues. It also elevates mitochondrial and peroxisomal fatty acid β oxidation rates, such as liver, heart muscle, kidney, skeletal muscle, retina, and brown adipose tissues, and have a potential role in oxidant/antioxidant pathways. 5,6
The Transient Receptor Potential Cation Channel Member 8 (TRPM8) is an androgen receptor involved in the detection and measurement of cold temperatures 7,8,9 It is related to cell proliferation, cell growth and anabolic activity. 10,11,12 TRPM8 also regulates energy metabolism and controls the clock gene and clock-controlled genes in brown adipose tissue. This is achieved through upregulation of REV-ERBα/β genes.13
(1R*,2S*)-N-(4-Methoxyphenyl)-5-methyl-2-(1-methylethyl) cyclohexane carboxamide is a potent TRPM8 agonist, four times more potent than the ligand menthol.14 Modulation of REV-ERB, CLOCK and CLOCK -like gene expression is further evidenced by menthol’s modulation of the sleep/waking cycles of various species with genes conserved in humans. 15,16 It is reasonable to assume that the higher affinity to for the TRPM8 and longer half-life regarding metabolism, confers greater activity and comparable efficacy with SR9009.
Research Evidence and Efficacy.
1Pereira-Fernandes, A., Vanparys, C., Vergauwen, L., Knapen, D., Jorens, P.G., & Blurst, R. (2014). Toxicogenomics in the 3T3-L1 cell line, a new approach for screening of obesogenic compounds. Toxicological Sciences, 140(2), 352-363.
2Kim, S.H., Nam, G.W., Lee, H.K., Moon, S.J., & Chang, I.S. (2006). The effects of Musk T. on peroxisome proliferator-activated receptor [PPAR]-α activation, epidermal skin homeostasis and dermal hyaluronic acid synthesis. Archives of dermatological research, 298(6), 273-282.
3Michalik, L., & Wahli, W. (2006) Involvement of PPAR nuclear receptors in tissue injury and wound repair. The journal of clinical investigation, 116(3), 598-606.
4Tyagi, S., Gupta, P., Saini, A.S., Kaushal, C., & Sharma, S. (2011) The peroxisome proliferator-activated receptor: a family of nuclear receptors roles in various diseases. Journal of advanced pharmaceutical technology & research, 2(4), 236.
5Rigamonti, E., Chinetti-Gbaguidi, G., & Staels, B. (2008). Regulation of macrophage functions by PPAR-α, PPAR-ỿ, AND LXRs in mice and men. Arteriosclerosis, thrombosis, and vascular biology, 28(6), 1050-1059.
6Lefebvre, P., Chinetti, G., Fruchart, J.C., & Staels, B. (2006). Sorting out the roles of PPARα in energy metabolism and vascular homeostasis. The Journal of Clinical Investigation, 116(3), 571-580.
7Asuthkar, 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.
8Bidaux, G., Roudbaraki, M., Merle, C., Crepin, A., Delcourt, P., Slomianny, C., … & Mauroy, B. (2005). Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement. Endocrine-related cancer, 12(2), 367-382
9 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.
10Zhang, L., & Barritt, G.J. (2006). TRPM8 in prostate cancer cells: a potential diagnostic and prognostic marker with a secretory function? Endocrine-Related Cancer, 13(1), 27-38.
Research Evidence and Efficacy.
11Yee, N.S., Zhou, W., & Lee, M. (2010). Transient receptor potential channel TRPM8 is over expressed and required for cellular proliferation in pancreatic adenocarcinoma. Cancer letters, 297(1), 49-55.
12Bai, V.U., Murthy, S., Chinnakannu, K., Muhletaler, F., Tejwani, S., Barrack, E.R., … & Reddy, G. (2010). Androgen regulated TRPM8 expression: a potential m RNA marker for metastatic prostate cancer detection in body fluids. International Journal of oncology, 36(2), 443-450.
13Moraes, M.N., de Assis, L.V.M., dos Santos Henriques, F., Batista Jr, M.L., Guler, A.D., & de Lauro Castrucci, A.M. (2017). Cold sensing TRPM8 channel participates in circadian control of the brown adipose tissue. Biochimica et Biophysica Acta (BBA) -Molecular cell research, 1864(12), 2415-2427.
14Leffingwell, 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]
15Chen, S., (2016). Light Dependant regulation of Sleep/Wake states by Prokineticin 2 in Larval Zebrafish (Doctoral dissertation, California Institute of Technology).
16Buhr, E.D., (2008). Differential effects of physiological temperature changes on central versus peripheral circadian clocks in mice (Doctoral dissertation, Northwestern University).