Resveratrol – The Full Spectrum Health Molecule
In 1997 Jang et al. published a short paper in the scientific journal Science. Its title was "Cancer chemopreventive activity of resveratrol, a natural product derived from grapes". On less than four pages, the researchers from the University of Illinois at Chicago described a discovery that came as a "scientific bombshell". After all, the paper suggested that resveratrol, a previously largely ignored phytoalexin found in grapes and other food products, could be the most potent natural anti-cancer agent known to man.
Figure 1: Effect of resveratrol on tumorigenesis in the two-stage mouse skin model. Six groups of 20 female CD-1 mice
(4 to 5 weeks old) were treated with high doses of a potent carcinogen alone, or in conjunction with different doses of resveratrol
for 18 weeks (Jang. 19947). The reduction in tumor incidence and the number of tumors speaks for itself.
In high enough dosages, resveratrol did not just ameliorate, but even prevented the otherwise inevitable growth of skin cancer in a rodent model of the carcinogenesis – an outstanding result that sparked the interest of hundreds of researchers world-wide.
Figure 2: Number of peer-reviewed studies on resveratrol that were published
between January 1997 and July 2015 (Pubmed)
Until today, more than 7600 peer-reviewed scientific studies have investigated the myriad of beneficial health effects of the resveratrol molecule of which scientists once thought that it was 'just another anti-oxidant'. In that, the anti-carcinogenic effects of resveratrol are only one out of many literally 'vital' health benefits that have been observed in response and associated with the use of resveratrol in countless cell and animal studies, as well as an ever-increasing number of clinical human trials:
As a potent inhibitor of oxidative stress and inflammation, resveratrol has been shown to prevent, treat, or cure atherosclerosis, diabetes mellitus, chronic obstructive pulmonary disease, cancer, Alzheimer's and even cancer – all diseases that are associated with radical oxygen specimen (ROS)-induced chronic inflammation, mitochondrial decay and/or DNA damage (Lagouge. 2006; Bisht. 2010; Shukla. 2011; Smoliga. 2011).
Figure 3: Resveratrol can be used to cure diseases, but its true strength is in prevention.
By reducing or extinguishing chronic inflammation, resveratrol reduces the risk of a whole host
of potentially fatal inflammatory diseases.
While long-term human studies are still on their way, studies such by Ghanim et al. (2010 & 2011) prove that the underlying beneficial effects on chronic inflammation, which promote the development of the previously listed inflammatory diseases, occur in humans, as well.
In rodent models of diet-induced obesity, resveratrol was found to improve insulin sensitivity and lipid management, as well as to lower body weight, consistently (Lagouge. 2006). In that, it is particularly noteworthy that the metabolic improvements and the changes in body weight can occur independently. Studies such as Baur et al (2006), for example, confirm that potent improvements in glucose tolerance occur even if the amount of resveratrol that's used is way too low to trigger meaningful weight loss (Baur. 2006).
Figure 4: Recent human studies have confirmed Resveratrol's potent effect on blood glucose
general an post-prandial glucose levels (left), as well as overall insulin sensitivity (right), impressively (Brasnyó. 2011)).
It is thus no wonder that similar beneficial effects on glucose management have been observed in humans, even though the low oral bioavailability of resveratrol is a major obstacle to its successful use in clinical trials (see discussion towards the end of this article). Nevertheless, Studies like Brasnyó et al. (2011), for example, report highly health relevant improvements in postprandial glucose levels and reductions in HOMA-IR, the classic marker of pathological insulin resistance.
Next to its anti-diabetic effects, resveratrol has also been found to Prevent and partly reverse the progression of non-alcoholic fatty liver disease (NAFLD; Shang. 2008; Bujanda. 2008; Faghihzadeh. 2015).
Figure 5: In their 2014 clinical human trial, Faghihzadeh et al. observed a significant reduction in the severity
of steatosis (0 = none, 4 = really severe) compared to placebo (p = 0.02) in 50 NAFLD patients who were supplemented
with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks (Faghihzadeh. 2014).
Even though, the evidence is still scarce, resveratrol is thus one of the most promising natural treatment options for people who are either suffering, or at the risk of developing NAFLD.
Only partly related to its beneficial effects on body weight, glucose and lipid metabolism are Resveratrol's beneficial effects on cardiovascular and endothelial health. These effects, which have recently been confirmed in clinical human trials (e.g. increases in cerebral blood flow and flow-mediated dilation; Kennedy. 2010; Wong. 2011), are most likely being mediated by resveratrol's ability to significantly increase the production of nitric oxide (Wallerath. 2002, 2005; Leikert. 2002). An effect for which resveratrol has also become also commonly used ingredient in premium quality pre-workout products and supplements that are designed to improve male and female sexual desire and performance.
A recently published study by Timmers et al., which proves that resveratrol exerts almost same beneficial effects on critical parameters of cellular aging as caloric restriction in human beings, provides initial evidence of the existence of similar anti-aging effects in man, as they have been observed in various animal models (Pearson. 2008; Barger. 2008).
Figure 6: Lifespan extension by resveratrol in various species. The ability of resveratrol to
extend organismal lifespan is conserved from yeast to mammals. HFD: high-fat diet,
SD: standard diet, N.O.: not observed. a Resveratrol supplementation reduced the
risk of death from a high-calorie diet by 31% (Bhullar. 2015)
Many scientists are yet still skeptical, and expect significant increases in life-expectancy to occur in man, just like in mice, only on high calorie diets. In view of the fact that that's exactly the way many inhabitants of the industrialized world eat, the impact of chronic resveratrol supplementation could still be huge, though. Since long-term studies to prove and quantify these effects are on their way, we may soon be able to say for sure how significant the anti-aging effects in human beings are.
Just like its anti-aging effects, resveratrol's potent anti-cancer effects have been fully established only in animal studies, yet. The fact that there's "still a large void in human research" (Smoliga. 2011), is yet soon going to change as pertinent clinical human trials are already on their way (Singh. 2015). In spite of the paucity of evidence, practitioners all around the world exploit the resveratrol's ability to sensitize various forms of cancer to the toxic effects of the chemotherapy (Gupta. 2011; Kim. 2014; Huang. 2014), even today.
If you take another look at this long list of benefits, you may ask yourself why nobody has yet suggested to put resveratrol into the drinking water for everyone to benefit. A good idea, but a problematic one.
The problem is: More than 99% of Orally Ingested Resveratrol Won't Make it into the Bloodstream
With a bioavailability scientist quantify as "considerably less than 1%" (Walle. 2011), more than 99% of the precious antioxidant in the average oral resveratrol supplement won't even make it into your bloodstream. The molecules are broken down or metabolized by the bacteria in your gut, the cells in your intestinal walls, or the liver, which acts as a gatekeeper between the intestines and the general blood circulation, way before they can exert any of the previously listed health benefits.
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