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From: Treating C-IBS low motility with a Nutritional Supplement (Garcinia Cambogia)

Posted by screeb , 28 May 2013 · 2,163 views

I have been on G. Cambogia for 6 weeks and have started to lose weight, (to answer Rose's first question). There are good effects and bad effects.
A good effect is that the adipose tissue inhibitor causes one's belly to get smaller and one's muscle to get more fat. This is good for workouts such that one can work out longer.
I belive G. Cambogia is helping Gastroparesis by reducing Hypoxia Factor Inducible 1 (HIF-1) genes. The mucosa in the GI tract is subject to large variations in blood perfusion, and therefore PO2. During fasting, (Gastroparesis or delayed gastric emptying), the blood flow is low (5% of cardiac output) which then rises significantly to 30% after a meal. In addition, the mucosa has a steep oxygen gradient from the epithelial cells adjacent to the nearly anoxic lumen to the cells near the highly perfused sub-mucosa. Hypoxia-inducible factor-1 alpha (HIF-1alpha) functions as a master regulator of cellular and systemic homeostatic response to hypoxia by activating transcription of many genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. EC cells (enterochromaffin cells) are hypoxia responsive and the production of the HIF-1 alpha-related mechanisms accompanies the pathway activation. Normal EC cells express HIF-1 alpha, a hypoxia mediated pathway in these cells, caused activation of HIF-1 alpha protein levels. Increasing O2 to 100% inhibited signaling, transcription and significantly lowered HIF-1 alpha levels (ca. 75% of control).[i]
The carotid body, a peripheral chemosensor no bigger than a grain of rice, is the most perfused organ per gram weight in the body and receives blood via an arterial branch arising from internal or external carotid artery. A proposed underlying mechanism for hyperactivity of the chemoreceptors is the relative activity of HIF-1 alpha.[i] Increased HIF-1 alpha-dependent NOX2 mRNA (which encodes NADPH oxidase, a pro-oxidant enzyme that generates superoxide--producing reactive oxygen species [ROS]) expression, triggers glomus cell depolarization (type of cell in Carotid Body), leading to sympathetic activation.[ii]
Garcinia Cambogia causes decreased activation of HIF-1 causing decreased sympathetic activation such that less pain projects from gut pathway causing decreased Locus coeruleus firing causing decreased perception of visceral pain. The less intense the pain pathway "whispers down the lane",
the less the level of norepinephrine in the brain and therefore G. Cambogia which produces decreased HIF-1 is decreasing norepinephrine where the major effect of decreased locus coeruleus firing is a decrease in perception of visceral pain that causes increased locus coeruleus firing via alpha-2 norepinephrine receptors in the locus coeruleus. Combining these two sub-programs into a super program , the G. Cambogia decreases HIF-1, causing increased sugar causing decreased LHA/OX-A. Remember, we are dealing in long term overactivity of the proximal colon, so reducing peristalsis (proximal colon activity) is a good thing. It makes the stools less compressed and dryed out.
Tryptophan hydoxylase (TPH) transcription is positively regulated by HIF-1, therefore decreased TPH is caused by decreasd HIF-1. Tryptophan is a precursor for serotonin (5-HT), and TPH is the equivalent of phenyl analine hydroxylase. BH4 (Tetra hydrobioperin) is used in the phenyl analine hydroxylase reaction. BH4 is an essential co-factor for NOS (nitric oxide synthase) that is intracellularly produced from GTP via GTP cyclohydrolase I and acts as a redox switch in the oxygen domain of NOS. Reduced levels of BH4 impair production of NOS and lead to increased superoxide radical production.  However, G. Cambogia is Decreasing HIF-1 levels and then TPH.  This decreases the BH4 deficiency, that has been associated with diabetic complications including gastroparesis. The above condition is a double negative; therefore, increased availability of BH4 and nNOS (neuronal) causes uncoupling which results in unimpaired nitrergic relaxation and thus reduced gastroparesis.
A  bad effect of G Cambogia is mental spaceyness which may be caused by reduced insulin increasing blood sugar going to the brain. At the brain, this decreases norepinephrine output causing increased blood flow, associated with globalization of the brain, ( a negative side effect that doesn't allow concentration on a particular subject, ex. a verbal task in the Broca's area).

Source: Treating C-IBS low motility with a Nutritional Supplement (Garcinia Cambogia)


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