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Gencor Nutrients, Inc.: 2014 HCS

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New Way to Activate the Master Metabolic Switch: ActivAMP

By Dr. Paul Clayton, Chief Scientific Advisor, Gencor

The enzyme 5′ adenosine monophosphate-activated protein kinase, or AMP-K, can be regarded as a metabolic master switch that determines inter alia whether available calories are stored for future use, or utilized to meet immediate requirements, i.e. during exercise. Aerobic exercise, for example, generates hypoxia and increasing levels of cAMP in skeletal muscle. This activates AMP-K in muscle and liver. Broadly, activated AMP-K instructs the body to stop storing energy and start burning it.

Endurance (aerobic) exercise favors improved capillary networks and more efficient contractile mechanisms, while resistance (anaerobic) exercise favors increased muscle mass.1 Both types of exercise activate AMP-K, which triggers mitochondrial neogenesis and GLUT4 expression, making the muscles fitter.2 Related benefits include improved insulin sensitivity and plasma lipid profiles. Activated AMP-K also increases fat burning via beta oxidation, inhibits cholesterol synthesis by down-regulating HMG CoA reductase3 and inhibits fat formation by down-regulating acetyl CoA carboxylase.

The net effects of this AMP-K induced cascade are improved muscular performance, visceral and other fat loss, and the reversal of metabolic senescence.4,5 

New Ways to Activate AMP-K 

Recent research has demonstrated that the activation of AMP-K by resistance (anaerobic) exercise is mediated by the up-regulation of genes that code for a family of at least three proteins called sestrins.6,7 The sestrins appear to be induced by physical stresses detected by transponder systems in muscle and bone.

Several traditional xeno-hormetic herbs have been screened for sestrin/AMP-K activity, and South Korean experts identified the herb Gynostemma pentaphyllum as a candidate for research. Traditionally made into a tonic for the frail and elderly, its documented benefits reproduce the effects of exercise or AMP-K activation. The scientists established that this herb did indeed activate AMP-K, presumably via sestrin up-regulation, and an extract of Gynostemma pentaphyllum standardized to its active constituents, the two saponins Damulin A and B, is now available as ActivAMP.

Proof of Concept: Pre-clinical 

Pre-clinical work found that ActivAMP exerted the same metabolic effects in ob/ob mice as the herb did in humans, and prevented weight gain.8 

Proof of Concept: Clinical 

Earlier this year, an ActivAMP study was published in the prestigious journal Obesity.5 In a double-blind trial, 80 subjects with BMI (body mass index) between 25 and 30 were randomized to active or placebo groups and treated for 12 weeks. The active group received capsules containing 450 mg ActivAMP per day. No recommendations were made regarding diet or exercise. At trial end, total abdominal fat area, body weight, body fat mass, percent body fat, and BMI were significantly decreased (p=0.044, p<0.05, p<0.0001, p<0.0001, and p< 0.05, respectively) in the active group compared to the placebo group. The reductions in visceral adiposity were particularly marked, as they are following exercise. No significant changes in any safety parameter were observed.


1 Baar K (2006). Training for endurance and strength: lessons from cell signaling. Med Sci Sports Exerc. 38(11):1939–1944.

2 Burcelin R, Crivelli V, Perrin C et al (2003) GLUT4, AMP kinase, but not the insulin receptor are required for hepatoportal glucose sensor-stimulated muscle glucose utilization. J Clin Invest 111:1555–1562.

3 Davies SP, Carling D, Munday MR, Hardie DG (1992) Diurnal rhythm of phosphorylation of rat liver acetyl-CoA carboxylase by the AMP-activated protein kinase, demonstrated using freeze clamping. Effects of high fat diets. Eur J Biochem 203:615–623.

4 Calabrese V, Cornelius C, Cuzzocrea S et al (2011.) Hormesis, cellular stress response and vitagenes as critical determinants in aging and longevity. Mol Aspects Med. 32:279–304.

5 Park SH, Huh TL, Kim SY, Oh MR et al (2014). Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): A randomized, double blind, placebo-controlled trial. Obesity (Silver Spring). (1):63-71.

6 Lee JH, Budanov AV, Karin M (2013). Sestrins orchestrate cellular metabolism to attenuate aging. Cell Metab. 18(6):792-801.

7 Lee JH, Budanov AV, Talukdar S et al. Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3. Cell Metab. 2012 Sep 5;16(3):311-21.

8 Gauhar R, Hwang SL, Jeong SS et al (2012). Heatprocessed Gynostemma pentaphyllum extract improves obesity in ob/ob mice by activating AMP-activated protein kinase. Biotechnol Lett. 34(9):1607-16.

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