Resveratrol - Scientific Review on Usage, Dosage, Side Effects. Sources and Structure. Sources. Resveratrol is a polyphenolic compound present in grapes, and is most well known for its presence in red wine. Interestingly, the popularity of resveratrol is due to its discovery in red wine and subsequent hypothesizing that it may be able to explain the 'French paradox' of Heart Disease. Resveratrol Weight Loss 2011 ChevyNorth Americans tend to have minute levels in the diet. Interestingly, it is classified as a phytoalexin (plant toxin). Its reason for existence is to protect grapes from infection, as it is synthesized in response to Bothrytis cinerea infection. Stilbenes tend to be most well known for occurring in the Vitis family (Grape family) although they extend to many plants. Food products or other common consumables that have a resveratrol content include: Note: 1umol of Resveratrol is equal to approximately 0. The Vitis family of plants. Structure. Resveratrol can exist in one of two isomers: trans- resveratrol and cis- resveratrol. The configuration greatly changes the structure: Trans- resveratrol is commonly seen as the active form of resveratrol. As the simple change results in a largely different molecule, many actions seen from trans- resveratrol are not seen with cis- resveratrol. These actions include modulation of the inflammation response. Cis- resveratrol is still an anti- oxidant. Chemical Stability. When implemented into a gel base, trans- resveratrol stored at 4. C does not convert into its cis isomer over a period of 3. Sirtuin System. Sirtuins are a class of 7 protein messengers in mammalian cells with a myriad of effects. Mitochondrial Biogenesis. Resveratrol has been noted to exert many actions in a manner that is dependent on SIRT1. It seems unlikely that resveratrol directly activates SIRT1, although an activation of SIRT1 does appear to exist with resveratrol and it is currently thought to be downstream of directly influencing other molecular targets. Resveratrol may act on SIRT1 secondary to acting on AMPK in various tissues. Bioavailability and Absorption. Resveratrol has a good absorption but low bioavailability when orally administered to man, as evidence by one study noting an oral dose of 2. L in the serum while 0. L. At an oral dose of 2. It appears the concentration of resveratrol in the blood is more dose- efficient (more bioavailable) in the morning relative to the PM. However, the time until peak levels in the blood (Tmax) and the peak levels (Cmax) are delayed and reduced, respectively. Overall exposure (AUC) does not change with the balanced meal. Bioavailability is another issue though, as conjugation begins at this stage. Kinetics (Supplementation)When ingested orally, resveratrol is taken up from the intestines to the liver (like any xenobiotic). It can be sulphated at either location.
Coingestion with bioflavonoids causing competitive inhibition that may free up Resveratrol by having the other bioflavonoids act in a sacrificial manner. Kinetics (Food products)Resveratrol's absorption is relatively the same in ethanol as it is in water. Three studies looked at 2. Resveratrol information from Drugs.com. Animal studies in mice suggest there might be benefits of weight loss. Cell Metabolism 2011;14: 612-622. The Guardian - Back to home. Resveratrol pills may mimic effects of exercise and low. Resveratrol also reduced both sleeping and resting. However, resveratrol has low bioavailability anyways at around 1. Food can have an advantage due to ingestion of compounds that increase bioavailability (like Quercetin) but capsules can be micronized to increased bioavailability 3. Additionally, it would be hard to get very large dosages through wine without saying farewell to your liver (in regards to Alcohol)3. Cytology (Cellular Kinetics)Resveratrol appears to be readily taken up into cells, as evidenced by rapid serum depletion of resveratrol when injected into human subjects. It has also been found in colon, lung, and heart tissue after oral administration. Metabolism. After ingestion of resveratrol, it can be conjugated by liver P4. The results are resveratrol sulphate (via sulphation) and two glucuronides, resveratrol- O- glucuronide and resveratrol- C- glucuronide. Excretion. Resveratrol is excreted in both the urine and the feces. Half- life of the resveratrol molecule appears to be in the range of 1- 3 hours, and can be extended slightly (2- 5 hours) with multiple doses. It is mostly excreted within a day, and has a half- life of a few (1- 3) hours. Blood levels are relatively dose- dependent, and the 'peak' level of blood concentration is slowly pushed backwards (up to 9. It can get into cells as well, when should preclude its metabolic actions. Its only real downfall is that it is heavily conjugated by the liver (P4. Longevity. 4. 1. Hypothesized Mechanisms. In Drosophilia and C. Elegans (two research creatures), the mechanism of longevity appears to be activation of Sirt. NAD+ dependent histone deacetylase protein. These genes include takeout (expression related to food intake), which is related to Juvenile Hormone (insect- exclusive) and life- extension. Studies in Drosophilia and C. Elegans. It appears that resveratrol reliably increases lifespan in these two non- mammalian models. Studies in Mammals. In mammalian models of premature aging, resveratrol does not seem to be indicative of enhanced lifespan per se. At this moment in time, it appears that resveratrol 'adds life to years' rather than 'adds years to life'. It may protect against common causes of death (covered in heart health and cancer metabolism) as well as metabolic syndrome, which could then push the median lifespan higher and exert a 'pseudo- life extension' appearance; however, a novel life extension mechanism independent of lifestyle that can be attributed to resveratrol appears to be lacking. Neurology. 5. 1. Neurokinetics. Resveratrol is able to cross the mammalian blood brain barrier, and incorporate itself into brain tissue. Cerebral Blood Flow. Resveratrol, at doses between 2. Glutaminergic Neurotransmission. Resveratrol may suppress glutamate release from neurons. There are unclear effects of resveratrol on the glutaminergic receptors. While in general it appears to suppress overactivation of glutaminergic signalling (all three major receptor subsets), some neuroprotective effects appear to be prevented by blocking the receptor. It is possible that resveratrol is a weak agonist of sorts while outcompeting stronger agonists. In regards to seizures induced by kainic acid (acting via kainate receptors, one of the glutamate receptor isoforms), resveratrol appears to be able to reduce seizures and hippocampal neurotoxicity. This appears to be well replicated in rat models, although it failed in the one more sensitive to kainic acid. In morphine tolerant mice (experiencing upregulations in NR1 and NR2. B subunits of NMDA receptors which contributes to morphine tolerance. Although the mechanism is not known, it appears to be through preventing a scaffolding protein from supporting NMDA receptors in the membrane. Glial Interactions. Glial cells are cells used to support neurons, and are highly involved in neurological systems being associated with their own form of plasticity and metabolic coupling. Glial cells, particularly the astrocytes, are intimately involved in neurotransmission between neurons and are further implicated in glutaminergic neurotransmission. It is hypothesized. It seems that under periods of ammonia toxicity that this enzyme is downregulated due to increased oxidative stress. This mechanisms can be used to explain neuroprotection from ammonia, and it may also contribute to the observed anti- glutaminergic effects of resveratrol. Neuroprotection. Resveratrol has also been shown in some studies to be synergistic with Melatonin supplementation in preventing beta- amyloid induced neurotoxicity. Alzheimer's. In age- accelerated mice (SAMP8), it appears that lifelong supplementation of resveratrol may increase lifespan and delay biomarkers of Alzheimer's (beta- amyloid and tau protein aggregation). Atherosclerosis. When investigating SIRT1 levels of the endothelium of persons with coronary artery bypass, they were found to be expressed at lower levels in artherosclerotic arteries relative to normal vessels (about 6. Blood Flow and Vasorelaxation. When looking at the endothelial nitric oxide synthase enzyme (e. NOS), resveratrol can upregulate e. NOS m. RNA in isolated endothelial cells (HUVEC and EA. Resveratrol possesses both of these properties, being able to reduce the expression of the NOX4 subunit of NADPH oxidase. There is also a recoupling effect on e. NOS (by mitigating some of the pathological changes seen in unhealthy states)Resveratrol is being investigated for its benefits to the endothelium as it is a direct free radical scavenger (specifically ROS) at 1. Relaxation of the vessel wall by these agents tends to be impaired in chronic disease, and resveratrol may reverse or attenuate this impairment. L (the lower dose to mimic moderate wine consumption; 0. KCl or phenylephrine induced contraction nor the EC5. Blood Pressure. Several rat studies using resveratrol that note benefits to the endothelium and vasorelaxation have noted that reductions in resting blood pressure may not occur. Cardiac Tissue. Mechanistically, the protein quinone reductase NQO2 appears to have remarkably high affinity for resveratrol with a KM of less than 5. M. Interventions and Survey Research. Resveratrol has been investigated for its contribution to heart health after a meta- analysis first found a significant risk reduction associated with 1- 2 glasses (1. L) of wine daily. Insulin sensitivity and Diabetes. Resveratrol, per se, has been shown to increase insulin sensitivity when supplemented obese persons at 1. HOMA index and measured at 1. Interactions with Cell Cycles. Fat cells are borne from mesenchymal cells, which are pluripotent stem cells that can turn into muscle cells (myocytes), fat cells (adipocytes), bone cells (osteoblasts) or cartilage (chondroblasts). A general overview of how resveratrol affects fat metabolism is that it hinders mesenchymal cells from turning into adipocytes and thus indirectly favors the other pathways.
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