Nutritional Medicine , Separating Fact from Fiction
Resveratrol: Supplement facts/anti-aging, obesity, cardiac, chronic diseases, cancer, all being researched
Resveratrol Supplement Facts
Food supplements can come in all forms: pills, intravenous, food, additives, topical, granules, paste, gel, beverages and/or as a functional food. Resveratrol supplements are currently a hot sales market item and are already being used by consumers to extend life and to prevent/treat conditions such as obesity, diabetes, CHD, Alzheimer’s, menopause, cancer, autoimmune disorders, viral diseases and even wrinkles.
Most of the current supplements on the market get their resveratrol from Japanese knotweed, a cheaper form of resveratrol than red grapes. Patented formulas are also on the market that claim to contain superior quality extractions from red grape skins of a certain variety, and/ or altered bioavailability where both water and fat soluble absorptions of resveratrol along with Sirt 1 activities are chemically increased.
The bioavailability and dosages for resveratrol are largely unknown due to a lack of human clinical trials in general and well-designed studies specifically. The human studies that are available have not controlled for known variables thus there are no guidelines or standardization of realistic dosage parameters. Dosages of 150 mg per day have been used in clinical trials with no adverse effect (Timmers, 2011; Yoshino, 2012). Others claim that up to 500 mg per day of resveratrol have been used in clinical trials with no recorded side-effects. Differences will be seen when implemented in a personalized medicine platform because humans are different with varying genotypes, lifestyles, needs, health/lifestyles and medications. Health professionals need to know how resveratrol will affect their patients when a comprehensive treatment plan is designed which means the clinical trials need to be designed to provide some answers.
. Human clinical trials revealed that obese subjects lost weight and many metabolic parameters normalized while insignificant changes were noted in the normal weight subjects with normal metabolic parameters (Timmers, 2011 Yoshino, 2012). This is a clear indication that body weight is at least one variable affecting resveratrol's mechanism(s) of action and expected results.
An important fact to keep in mind is that the FDA doesn’t regulate resveratrol supplements so there’s no guarantee that the dosage listed on the label is the actual amount present in the capsule. Often supplements will vary in content and purity of the intended compound. Consumer Labs, an independent testing and quality control organization, analyzed nine different resveratrol supplements and reported that two had far less resveratrol than what the label stated. One supplement claimed to contain 400 mg of a “red wine grape complex” but contained only 2.2 mg of resveratrol per caplet. The recommended dosages varied from 50 mg to 1,020 mg per day. Furthermore, the cost of supplements varies widely, and each manufacturer arbitrarily sets the suggested dosage, rarely basing it on human clinical trial evidence (Smoglia 2011).
A reliable set of recommendations for the use of resveratrol in humans was just released from the first International Conference on Resveratrol held in Denmark. The consensus was "there was just not enough evidence to justify the use of resveratrol beyond the dosage that can be obtained from human consumption" (Vang 2013; Somalia, 2011). Very little resveratrol will be obtained from the human diet.
Studies continue to find ways to increase the bioavailability of resveratrol supplements and/or possible analogues (Walle, 2011; Linus Pauling 2008). The overall bioavailability of resveratrol supplements and foods vary and are generally considered to be low. Bioavailability can be increased through chemical manipulation. Structure modifications can and are being made that will slow down resveratrol’s metabolism. Resveratrol is being combined with other nutraceuticals that act in a similar fashion via activation of one or more of the theorized anti-aging mechanisms. A carrier molecule for more complete absorption could be designed. Many exciting opportunities exist for resveratrol’s career as the “fountain of youth”.
Food and Supplement Sources
Resveratrol is produced in grape skins to protect the grapes from pathogenic bacteria, fungal infections, and environmental stresses (Lippi J, 2010). Resveratrol is found in the highest dietary concentrations in skin of the Muscadine red grape. Resveratrol concentrations vary by the type of grape and where it is primarily grown such as follows: in France (Beaujolais, Midi, Rhone, Bordeaux, Burgundy; concentrations may average 3.7-7.1 g/L), Spain (Pinot Noir, Merlot, Grenache; from 2.5 to 14 mg/L, and the U.S. (Muscadine up to 32g/L). (Lippi, 2010) Japanese knotweed is also high in resveratrol and is a frequent source for the manufacture of supplements.
Other abundant natural sources of resveratrol are the grape varieties, muscadine berries, and Catawba juice or jam. Raspberries, mulberries, blueberries, bilberries, cranberries, and peanuts contain the compound as do some inedible plants such as eucalyptus, spruce, lily, Scots pine, eastern white pine, and Japanese knotweed. Interestingly, Japanese knotweed is on the noxious weed list and is prohibited to grow, sell or distribute (Michigan Dept. of Natural Resources, 2012).
Environmental factors influence the amount of resveratrol in grapes. Resveratrol is synthesized in response to invading bacteria, disease and/or fungi. Since fungal infections are more common in cooler climates, grapes grown in these regions have higher concentrations of the phytochemical. Grapes grown in cold, mold-friendly climates (e.g. France’s Bordeaux region and the Willamette Valley of Oregon) produce grapes with higher resveratrol content than those grown in dry, temperate climates. Unhealthy or stressed grapes have the highest concentration of resveratrol.
Resveratrol concentrations likewise are related to the length of time grapes remain in their skins during the fermentation process. Red wine is fermented with the skins, allowing the liquid to absorb the resveratrol; the skins are removed during white wine production, reducing the amount of resveratrol that’s extracted.
Information about the resveratrol content of food is scarce and must be viewed in the context that it may vary within the same food group. Oregon State University’s Linus Pauling Institute provides tables listing the resveratrol content of certain foods (see table 1 on the dietary content of resveratrol in foods and table 2 for information on the resveratrol content in wines).
The fruits mentioned in the table are available, but they aren’t as easily stored as red wine. Still, obtaining the same doses from foodstuffs as those used in clinical trials through dietary manipulation is impractical, thus creating a massive market for resveratrol supplements.
As discussed, only small amounts of resveratrol are found in a normal diet. In the animal and human studies conducted thus far the dose of resveratrol used has been much larger than any amount someone can obtain through diet alone. Resveratrol supplements may contain a dosage equivalent to hundreds of bottles of wine, but typically they contain a much smaller dose than those used in research. Most supplements contain 20 to 500 mg of resveratrol. To get a dose equivalent to that used in some animal studies, a person would have to consume 2,000 mg or more of resveratrol per day. This amount, of course, would be less if one were using a product with a higher bioavailability than the resveratrol extracted from foodstuffs.
Few human studies evaluating the potential benefits or long-term risks of resveratrol supplements have been reported (Smoglia, 2011). Until research utilizing improved study designs are available, health professionals should refrain from recommending resveratrol supplements for anti-aging or disease prevention. Education should be promoted, encouraged and positive when client queries regarding supplementation with resveratrol are brought up.
One day we may be able to offer conclusive, evidence-based dietary recommendations. Until then, we should continue to recommend clients eat a plant-based diet that’s abundant in antioxidant-rich foods such as red grapes, berries, and peanuts to help prevent chronic disease. Moderate red wine intake may be beneficial to long-term health. Blueberries, in particular, have been reported to be high in resveratrol, but a study source was not found.
POTENTIAL DRUG/HERB INTERACTION
A review expressing concern over the possible interaction between drugs utilizing the cytochrome P-450 isoenzymes pathway(a metabolic pathway involved in drug metabolism) along with resveratrol and/or its analogues (Detample, 2012) was published. Adverse side-effects may be possible with these interactions, especially at 'high' doses of a chemically altered form of resveratrol that has increased bioavailability. Most humans can tolerate up to 1 gram/day of resveratrol if they are not taking medications, yet this too needs clinical validation as 5 g has also been mentioned.
One excellent example of an interaction was pointed out in a study done on a well-known immunosuppressant, Cyclosporine or CyA. Cya has a narrow therapeutic window; bioavailability of CyA is higher when resveratrol is taken. This would be considered a critical interaction because of the small range this medication needs to stay in to avoid complications (Colombo, 2014).
Resveratrol may have additive effects when used with anti-platelet drugs such as Plavix, Persantine, and Coumadin. It may increase or decrease antivirals. Since we know it may affect blood sugar, there may be interactions between insulin and other medications for diabetes control.
A perfect example of a potential herb-herb interaction was demonstrated when curcumin was combined with resveratrol in the presence of tumor bearing mice. A chemopreventive effect was amplified utilizing the herbs together as opposed to separately. Again, being careful not to jump conclusions from animals to humans, a synergistic action between the two herbs was noted (Malhotra, 2014).
RDN’s and DTRs could clearly benefit from the inclusion of evidence-based information on such interactions or even potential interactions in Herb-Herb and Food-Drug Interaction pocket books or personal digital assistant (PDA).
Clearly we need more study and guidance in this area before supplement education can be considered in medical nutrition therapy or incorporated into public health recommendations.
Current Trends and Future Possibilities
The current trend in the use of resveratrol supplements seems to be to promote longevity and to slow down the aging process. Despite overriding evidence of increased life span in subjects ranging from yeast to small animals, it is premature to extrapolate these results to humans, although tempting to do so. While human clinical trials are emerging, the number of subjects has generally tended to be low, study designs poor, variables overlooked, standardized endpoints missing, follow-up too short showing that much work needs to be done on overhauling our research designs in clinical trials.
To date, resveratrol has been noted to have numerous actions related to health benefits including the following:
· estrogenic activity (Linus Pauling, 2008;Castillo 2013)
· anti-inflammatory abilities (Smoglia, 2011)
· cardioprotection (Tome- Carneiro, 2013)
o decrease in apolipoprotein B; decrease in oxidized LDL;increase in adiponectin; increased anti-platelet function; decrease in cholesterol
· anti-aging (Pyo 2013, Smoglia 2011)
· improves oxidation and mitochondrial function (Boutant,2013; Park S J 2012)
· improved insulin sensitivity (Kitada 2013)
o may lower glucose levels in diabetes
· anti-viral properties (Clouser 2012)
· antioxidant (Farghali 2013)
These health benefits could assist in treating diseases given the right "formulation" or to prevent various age-related diseases given the evidence-based guidelines needed to make not only population-based recommendations, but disease prevention recommendations based on a genetic profile and used in a patient-centered model.
Pharmaceutical companies jumped on the opportunity to develop new drugs based on the positive results of earlier resveratrol research such as listed above. Resveratrol, or its analogues, are the topic of a plethora of multi-faceted studies by drug companies. The primary diseases being researched include the following:
· Cancer (Castillo-Picardo 2013; Hseih W 2013)
· Neuromuscular Disease (Langley 2013; Poulsen 2013; Fuller H 2013;Sato 2013)
· Diabetes (Kitada 2013; Renaud 2013)
· Multiple Sclerosis (Shindler 2010)
· Obesity (Yoshino 2012; Timmers 2011; Poulsen 2013)
· CHD (Tome-Carneiro 2013; Khurana 2013)
o Prevention of the progression of heart failure (Gu,2014)
· Alzheimers (Mecocci 2012)
Despite the conflicting findings in many of these studies, there are some diseases that deserve discussing in the interest of safety. Cancer has shown encouraging results when resveratrol is added to the treatment regimen for some cancers, but only in specific types of cancer. Patients that have cancers estrogenic in nature (i.e. breast, ovaries, etc.) should never be exposed to resveratrol as it may stimulate abnormal cellular growth.
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Go to the Store and Order Pure Encapsulations Unique Resveratrol Formulation under Specialty Care Supplements
Remember, as with all supplements, this information is not intended to diagnose or treat any illness.
Suggested Use: 1 capsule per day, with a meal Resveratrol - Resveratrol is a compound often associated with the health benefits of red wine, because of its powerful antioxidant and cardioprotectant properties. It promotes cardiovascular health through its antioxidant action and its ability to promote healthy platelet function and maintain healthy arachidonic acid metabolism. Pure Encapsulations Resveratrol is derived from one of the richest known sources, Polygonum cuspidatum, an herb utilized for centuries.
Antioxidant and cardiovascular support-Resveratrol is a compound often associated with the health benefits of red wine, because of its powerful antioxidant and cardioprotectant properties. It promotes cardiovascular health through its antioxidant action and its ability to promote healthy platelet function and maintain healthy arachidonic acid metabolism. Pure Encapsulations Resveratrol is derived from one of the richest known sources, Polygonum cuspidatum, an herb utilized for centuries.
Resveratrol is standardized to contain 20% trans resveratrol and 10% emodin, providing enhanced cardiovascular and antioxidant support.
REFERENCE: Zhuang H, Kim YS, Koehler RC, Dore S. Potential mechanism by which resveratrol, a red wine constituent, protects neurons. Ann N Y Acad Sci 2003 May;993:276-86.