IrithinTM, Powerful Fat burner with all-natural-source complex via fermentation

Published: admin | Format: 2017-02-27

What is IrithinTM?

IrithinTM is one all-natural-source thermogenesis activation complex via fermentation and extraction from GENABOLIX.

It’s the blend of beta-Hydroxybutyrate (3-hydroxybutyric acid, BHB), beta-amino-isobutyric acid (BAIBA), extract of grains of paradise (GOP) and gamma-butyrobetaine salt(GBB).

It has synergistic effect on fat loss by multiple pathways.

It can trigger thermogenesis and decrease body fat.

It induces the transformation of white adipose tissue into brown adipose.

 

Source

BHB: Beta-Hydroxybutyrate (BHB, 3-hydroxybutyric acid) is a “ketone body” which is produced in the liver, mainly from the oxidation of fatty acids, and is exported to peripheral tissues for use as an energy source. D-BHB is a metabolic intermediate that constitutes 70% of ketone bodies produced during ketosis. D-BHB is produced via two-step process in recombinant Escherichia coli.

 

BAIBA: Beta-aminoisobutyric acid (BAIBA) is an amino acid that your body produces in response to exercise. BAIBA originates both as a catabolite of the amino acid valine, and of the nucleobase thymine. Thymine degradation gives rise to the R-enantiomer[1], and the S-enantiomer is a degradation product of valine[2]. BAIBA is produced via two steps fermentation, and the substrate thymine is produced from hydrolyzed yeast.

 

GOP: Aframomum melegueta (of the family Zingiberaceae) is a spice in the Ginger family with the common name of 'Grains of Paradise'(GOP). The spice is used in West Africa for the purposes of alleviating stomachache and diarrhea as well as hypertension with some limited reports on it being used for Tuberculosis and a remedy for snakebites and scorpion stings. Our GOP ingredient is supercritical CO2 extracted from GOP, containing at least 12.5% of 6-Paradol.

 

GBB: GBB is a highly water-soluble derivative of gamma-amino butyric acid and a biological precursor of L-carnitine. GBB is extracted from Ganoderma lucidum spore powder.

 

Functions

The blend of ingredients in IrithinTM will synergistic ignite your body’s fat burning up and help optimize energy expenditure. IrithinTM switches on the metabolically inactive white adipose tissue (WAT) so that it acts more similar to the most proficient thermogenic tissue in the body--brown adipose tissue (BAT) or brown fat. IrithinTM also contains thermogenic activators that further enhance fat burning and thermogenesis.

There are two types of fat, WAT and BAT, exist in mammals including adult humans. While WAT stores excess calories and an excessive accumulation of fat causes obesity, BAT is responsible for cold- and diet-induced thermogenesis, and thereby contributes to the control of whole-body energy expenditure (EE) and body fat content.

 

BHB

The ketone body BHB is a convenient carrier of energy from adipocytes to peripheral tissues during fasting or exercise. Ketone body contribution to the overall energy metabolism in the heart and other extrahepatic tissues increases significantly after prolonged exercise, during fasting, adherence to low carbohydrate ketogenic diet (LCKD) and in the neonatal period[1]. Microinjections of BHB in the paraventricular or ventromedial nucleus of the rat hypothalamus demonstrated that BHBA increases the firing rate of the sympathetic nerves to brown adipose tissues (BAT) within minutes following injection[2]. Intracerebroventricular BHB infused rats could decreased body weight[3]. Infusions of BHB into the 3rd brain ventricle initiated higher binding of GDP to BAT mitochondria compared with the saline-infused control rats[4].

 1.png

Fig 1.Cellular signaling functions of the ketone body BHB.

Other functions[5]:

Ø  Increase resistance to obesity

Ø  Increase oxidative stress resistance

Ø  Decrease glycogenesis

Ø  Improve Mitochondrial function

Ø  neuroprotective effects

 

BAIBA

BAIBA is produced naturally by the human body – it’s formed from the catabolism of thymine[6]. During exercise, the increase of PGC-1α protein triggers the secretion of BAIBA from exercising muscles to blood (concentration 2 to 3 µM in human serum). BAIBA plasma concentrations were inversely correlated with cardiometabolic risk factors in a large human cohort study (Community-based Framingham Heart Study) in 20 weeks and were increased by 17% during exercise training in subjects of the HERITAGE Family Study[7].

When mouse or human white fat cells are exposed to BAIBA, some of them become fat-burning "beige" fat cells. Beige (or BRITE) fat cells contain the protein UCP-1 - also known as "thermogenin" because it burns triglycerides to produce heat. After BAIBA reaches the white fat tissue, it activates the expression of thermogenic genes via PPARα receptors, is regulated by PGC-1α and increases expression of brown adipocyte-specific genes. After being released into the blood stream, BAIBA starts a thermogenic program in fat tissue, raising energy expenditure and reducing weight gain when tested in mice. Analysis of body composition using MRI demonstrated BAIBA treatment significantly decreased body fat in the mice (body fat, control = 13.1% ± 1.25%; BAIBA = 9% ±0.92%, p = 0.02) [8]. Another study showed that BAIBA was able to curb adiposity by 27% and reduce fat mass by 40%[9].

2.png

 

Other functions:

Ø  Increase lipolysis and the beta-oxidation of fatty acids (“fat burning”) [8]

Ø  Increase body temperature and energy expenditure

Ø  Increase ketogenesis (increasing BHB concentration in the liver)[10]

Ø  Reduce food intake (suppress hunger)

Ø  Recreased cardiometabolic risk

 

GOP:

GOP could increase energy expenditure and improve fat Loss by activating BAT and reducing adipogenesis via PPARδ pathway. A single-blind, placebo-controlled clinical trial on 19 healthy men showed that after 4 weeks the group consuming GOP extract(40mg/day) had a significantly greater increase in energy expenditure, due to increasd BAT activity, than the group not receiving the GOP extract [11]. Daily oral ingestion of GOP extract (30 mg/d) for 4 wk in 19 non-obese female volunteers aged 20-22 y increased whole-body EE (p<0.05), suggestting that GP extract may be an effective and safe tool for reducing body fat, mainly by preventing visceral fat accumulation[12].

GOP extracts and 6-paradol activate thermogenesis in brown adipose tissue, and may open up new avenues for the regulation of weight loss and weight maintenance in rats[13].

6-Shogaol and 6-gingero, the constituents of GOP extract (also found in ginger) acted as specific PPARδ ligands and stimulated PPARδ-dependent gene expression in cultured human skeletal muscle myotubes, reduced adipogenesis in the same cell line [14].

Other functions:

Ø  Anti-inflammatory activity[15]

Ø  Improve lipid profile[16]

Ø  Lowered blood pressure

Ø  Attenuate hepatotoxicity (chemical-driven liver damage)

 

GBB:

GBB could dramatically increase endogenous L-carnitine production, which means that GBB can give you better anabolic effect than the majority of products featuring L-Carnitine.

Ø  Increasing L-carnitine level and metabolizing fat:

One study conducted on infants showed plasma carnitine concentrations increased 3 fold when fed GBB[17]. Another mice trial showed administration of GBB increased the concentration of L-carnitine in the plasma, brain, liver and kidney significantly, and decreased in long-chain fatty acids, palmitic acid and stearic acid levels in liver significantly. Administration of GBB may be more useful than that of L-carnitine itself for treatment of primary deficiency of carnitine due to a functional defect of the carnitine transporter [18]. GBB could be used with or in place of L-carnitine to increase free carnitine concentrations in muscle[19].

L-Carnitine is responsible for metabolizing fat. After breaking down the stored fat, it mobilizes the fatty acids into the bloodstream. L-carnitine is an essential element in the β-oxidation of long-chain fatty acids, because it helps to carry the fatty acids as acylcarnitine esters across the mitochondrial inner membrane for energy production.

Ø  Radical scavenger properties:

High concentration of GBB (1 mM) attenuated significantly the H2O2-induced decrease in LVDP. The results suggest that GBB in isolated rat heart decreased the development of mechanical dysfunction induced by infusion of hydrogen peroxide [20].

Ø  Cardioprotective activity:

The vasoprotective effect of GBB could be due to the reduction of oxidative stress in vascular wall. GBB attenuated the development of endothelial dysfunction in an experimental model of hypertension[21]. Increasing GBB levels while preserving the L-carnitine content in vascular tissues attenuated the development of endothelial dysfunction induced by a high glucose concentration[22].Gamma-butyrobetaine to rats showed elevated vasodilating activities[23].

Ø  Increasing NO levels:

These vasodilating activities were attributed to increases in nitric oxide concentrations in blood. GBB induced transient increases in nitric oxide (NO) concentrations in rat blood and myocardium.

Since nitric oxide has been shown to increase energy metabolism, it is herein understood by the inventors that increases in NO levels will lead to increased catabolism of fatty acids, which will increase the utilization of adipocytes leading to reduced fat content in the body[24].

 

Safety and Dosage

BHB: highest estimated intake of BHBr would be 50 g/day, and the lowest estimated intake would be from 22 g/day.

BAIBA: The data surrounding the optimal oral dosage of BAIBA in humans is seriously lacking. From mice studies, 500mg daily for the average male is a recommendation dosage.

GOP: Subjects in the human study reported no side effects associated with supplementation of 30mg/day and 40mg/day. recommended dosage to try between 30mg/day and 80mg/day total grains of paradise extract. Advanced users may use 120mg/day

GBB: toxicity of GBB is extremely low (LD50 = 7000 mg/kg subc.)[25] Health people: 50-100mg/day to give you equal effect of L-carnitine 3g/day. Athletes or obese people: 150mg/day


 

 

References:

1. Veech, R. L., Chance, B., Kashiwaya, Y., Lardy, H. A., and Cahill, G. F. Jr. Ketone bodies, potential therapeutic uses. IUBMB Life 2001,51, 241–247.

2. Sakaguchi, T., Arase, K., & Bray, G. A. Effect of intrahypothalamic hydroxybutyrate on sympathetic firing rate. Metabolism – Clinical and Experimental, 1988, 37, 732-735.

3. Sun, M., Martin, R. J., & Edwards, G. L. ICV beta-hydroxybutyrate: Effects on food intake, body composition, and body weight in rats. Physiology & Behavior, 1997, 61, 433-436.

4. Arase, K., York, D. A., Shargill, N. S., & Bray, G. A. (1987). Effect of cerebroventricular infusions of insulin and beta-hydroxybutyrate on food-intake and thermogenesis in the rat. Clinical Research, 35, A767.

5. John C. Newmana,b, Eric Verdin, Beta-hydroxybutyrate: Much more than a metabolite, Diabetes Research and Clinical Practice, 2014, 106(2):173-81

6. Solem, E. The absolute configuration of β-aminoisobutyric acid formed by degradation of thymine in man. Clinica Chimica Acta. 1974,53, 183–190.

7. Bouchard C, Leon AS, Rao DC, Skinner JS, Wilmore JH, Gagnon J. The HERITAGE family study. Aims, design, and measurement protocol. Med Sci Sports Exerc. 1995;27:721–729

8. Roberts LD et al,β-Aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors, Cell Metab. 2014,19(1):96-108

9. Begriche, K., Massart, J., Abbey-Toby, A., Igoudjil, A., Letteron, P., & Fromenty, B. (2008). β-Aminoisobutyric Acid Prevents Diet-induced Obesity in Mice With Partial Leptin Deficiency; Journal of Obesity, 16, 2053-2067

10. Caroline Maisonneuve et al, Effects of zidovudine, stavudine and β-aminoisobutyric acid on lipid homeostasis in mice: possible role in human fat wasting, Antiviral Therapy, 2004, 9:801–810

11. J Sugita et al, Grains of paradise (Aframomum melegueta) extract activates brown adipose tissue and increases whole-body energy expenditure in men, British Journal of Nutrition, 2013, 110(4):1-6

12. Sugita J, Yoneshiro T, et al; “Daily ingestion of grains of paradise (Aframomum melegueta) extract increases whole-body energy expenditure and decreases visceral fat in humans”; Journal of Nutritional Science and Vitaminology; 2014, 60(1): 22-27.

13. M Iwami, Extract of grains of paradise and its active principle 6-paradol trigger thermogenesis of brown adipose tissue in rats, Autonomic Neuroscience Basic & Clinical, 2010, 161(1-2):63-7

14. Misawa K  et al. Ginger extract prevents high-fat diet-induced obesity in mice via activation of the peroxisome proliferator-activated receptor δ pathway. J Nutr Biochem. 2015, 26(10):1058-67

15. Ilic NM et al. Anti-inflammatory activity of grains of paradise (Aframomum melegueta Schum) extract. J Agric Food Chem. 2014 Oct 29;62(43):10452-7.

16. Adefegha, Stephen A. et al; “Alligator pepper/Grain of Paradise (Aframomum melegueta) modulates Angiotensin-I converting enzyme activity, lipid profile and oxidative imbalances in a rat model of hypercholesterolemia”; Pathophysiology; 23(3), 191 – 202;

17.Olson AL et al, gamma-Butyrobetaine hydroxylase activity is not rate limiting for carnitine biosynthesis in the human infant, J Nutr. 1987, 117(6):1024-31.

18. Higashi Y et al, Effect of gamma-butyrobetaine on fatty liver in juvenile visceral steatosis mice, J Pharm Pharmacol.,2001, 53(4):527-33.

19.J. M. Benz, er al. Effects Of γ-Butyrobetaine and L-carnitine on carnitine concentrations in various muscle tissues of finishing pigs, Swine Day 2007, 187-189

20.Akahira M, Hara A, Abiko Y. Effect of MET-88, a gamma-butyrobetaine hydroxylase inhibitor, on myocardial derangements induced by hydrogen peroxide in the isolated perfused rat heart. Fundam Clin Pharmacol. 1997,11(4):356

21. Kalvins I, Veveris M. Latvian patent Nr. 11727

22. Vilskersts R et al. Elevated vascular gamma-butyrobetaine levels attenuate the development of high glucose-induced endothelial dysfunction, Clin Exp Pharmacol Physiol. 2013,  40(8):518-24

23. Sjakste N, Kleschyov J L, Baumane L, Dzintare M, Meirena D, Sjakste J, Sydow K, Munzel T, Kalvinsh I. Endothelium- and nitric oxide-dependent vasorelaxing activities of gamma-butyrobetaine esters: possible link to the antiischemic acitivites of mildronate. Eur J Pharmacol. Jul. 8, 2004; 495(1):67-73

24. US2008279967A1

25. Rotzsch W, Lorenz I, Strack E. On the toxicity of carnitine and some related substances. Biologica et Medica Germanica. 1959;3:28-36



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