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Wednesday, September 15, 2010

Resveratrol vs. Steroids in smokers and COPD patients

A new German study published online ahead of print in the Journal of Pharmacology and Experimental Therapeutics showed that Resveratrol may be more effective in depressing inflammation in smokers and COPD patients than corticosteroids.

Resveratrol, a polyphenol compound produced in a range of plants, is a protective chemical secreted by plants to ward off infection from attacks of bacteria or fungi. Resveratrol has been studied for a wide range of health applications in humans and first garnered significant attention as the main factor behind the “French Paradox”.

The French Paradox refers to the puzzling circumstance of low heart disease prevalence in the French population despite a diet which includes significant amounts of calories from fats and oils. Given that red wine is a staple of many French diets, and Resveratrol is found in red grapes in relatively high concentration, some scientists have associated the Resveratrol with protective heart health benefits. What makes this a head scratcher is that the average glass of red wine contains only 1-2mg of Resveratrol – a dosage level which is way below dosage levels deemed effective in Resveratrol research studies. But the fact still remains that French citizens who consume red wine on a regular basis seem to have less incidence of heart disease.

Resveratrol has shown promising results in smokers and people with COPD as we described in a previous article (click here to read more). The new German study further explored Resveratrol as an antioxidant and anti-inflammatory agent for smokers and COPD specifically to understand whether it might be more effective than steroids in reducing inflammation.

It has been previously established in past research studies that corticosteroids, a common treatment option for airway inflammation in smokers and COPD patients, are not particularly effective over the long-term in relieving symptoms associated with inflammation. As the German research team noted, “The use of corticosteroids in COPD is disputed, since their anti-inflammatory properties are impaired in smoking-related COPD compared to other chronic inflammatory lung diseases such as asthma.” (Knobloch J, et al. Resveratrol impairs the release of steroid-resistant inflammatory cytokines from human airway smooth muscle cells in COPD. JPET. Epub ahead of print, DOI:10.1124/jpet.110.166843)

To understand why, it is important to understand what causes inflammation in the first place. The cycle operates like this – cigarette smoke damages the cells of the lungs lining and airway muscle cells. Over time, the volume of damage inflicted by cigarette smoke causes the affected cells to malfunction. The most notable way they malfunction is an inappropriately overwhelming response to the presence of bacteria or fungi in the lungs.

Normally, when the cells detect bacteria or fungi, they send out signals (in the form of proteins known as cytokines). These signals are intended to boost production of white blood cells (macrophages as an example) to attack and kill the invading bacteria or fungi.

In smokers and COPD patients, however, the cell response to the presence of bacteria or fungi is dramatically more intense. Huge amounts of cytokines are produced and an overwhelming number of white blood cells respond. The lung tissues fill up with both the proteins and white blood cells and swell. The combination of swelled tissue and extra fluid in the lungs is described as inflammation. This inflammation in turn makes it harder to breathe because the airways are narrowed and not as much oxygen can be inhaled.

Corticosteroids are widely prescribed for reducing inflammation as anyone who has bad knees, hips, or back can attest. They are effective in reducing the body’s response to a perceived threat or injury. However, in smokers and COPD patients, some of the proteins that signal production of white blood cells have shown to be resistant to steroid’s effects, thereby diluting their anti-inflammatory properties.

Antioxidants have been receiving greater focus as an alternative because a number of them have been shown to be effective in reducing the production of cytokines and in moderating the free radical damage inflicted by inhaling cigarette smoke.

In this study, the German research team sought to test Resveratrol versus Dexamethasone (corticosteroid) in reducing the presence of cytokines in human lung tissue samples (specifically, human airway smooth muscle cells or HASMC). They recruited 3 sets of 10 patients – 10 non-smokers, 10 smokers who were considered healthy and free of lung disease, and 10 smokers diagnosed with COPD.

The study subjects agreed to a biopsy of their lung tissue into which the research team introduced a cytokine known as TNF-alpha (tumor necrosis factor alpha). The presence of TNF-alpha in lung tissue in turn signals the cells to produce other cytokines (Interleukin-8, for example) and chemicals (GM-CSF, granulocyte macrophage-colony stimulating factor, for example) to pass the “alert…infection detected” signal on to produce white blood cells in response.

Then the researchers introduced Dexamethasone into one set of the lung tissue samples from each group (non-smokers, smokers, COPD), Resveratrol into another set of the samples, and maintained a control/baseline set of tissue samples that received no injections.

The results showed that Dexamethasone was effective in reducing the number of inflammation-related proteins and chemicals in non-smokers, and that its effectiveness by comparison in smokers and COPD patients was notably reduced. This was determined by counting the number of cytokines and other signaling chemicals in the cell samples before and after treatment with Dexamethasone.

By contrast, the smoker and COPD cells treated with Resveratrol showed significantly lower counts of cytokines and other white blood cell signaling chemicals. As the study team noted, “In contrast to dexamethasone, resveratrol reduced IL-8 release from TNFalpha-stimulated HASMCs down to baseline level in all three cohorts.” (researcher-speak meaning that Resveratrol eliminated nearly all the inflammation related protein IL-8, by the way, the same was true of the signaling chemical GM-CSF).

Further, the researchers’ results showed that repeated administration of Resveratrol at lower dosage levels provided similar benefits to a single, large dose. The reason this is interesting is related to the point discussed above related to the “French Paradox”. Red wine contains a low dosage of Resveratrol (1-2mg per glass) and so one wouldn’t think that such a low dose would provide health benefits given that past Resveratrol research studies typically have had to administer large dosage levels in order to generate statistically significant responses.

Scientists have theorized that repeated low to moderate dosage of Resveratrol over time may, in effect, improve the body’s response to the antioxidant in such a way as to provide similar benefits to single, large doses. This study seems to provide support for this point of view. That said there is no current guideline for appropriate dosage level of Resveratrol in humans for any health condition. What seems more important than the specific dosage is continually replenishing the body’s supply of it.

Resveratrol is widely available in dietary supplement form in daily dosages ranging from 20mg up to 1000mg – it is sometimes sold as Grape Seed Extract. If you decide to purchase and try Resveratrol, make sure though that you check the supplement facts box of the product you are interested in prior to purchasing. While a label might indicate that there is 200mg of Grape Seed Extract in the product, Resveratrol is typically found in concentrations of 8% to 20%. So if you bought a 200mg Grape Seed Extract thinking you were getting 200mg of Resveratrol, you might really be getting 16mg-40mg of Resveratrol. Reputable supplement marketers will clearly identify the concentration level of Resveratrol in their product – steer clear of those who don’t.

As always, please check with your doctor before consuming Resveratrol to ensure there are no counter-indications with your individual health status. If you don’t want to try a Resveratrol supplement, consider adding red grapes, peanuts and/or red wine to your diet. All three of these sources provide 1-2mg Resveratrol per serving.

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