Introduction
As resveratrol gains popularity in the media and throughout the medical community it is important to keep up-to-date on any positive or negative news that is confirmed on resveratrol. This essay is a starting point for information sharing with regards to resveratrol and the science surrounding it. I approached this essay hoping to explain resveratrol and its related components in an easy-to-understand way.
Please feel free to "suggest, correct, or add" what you feel could be useful in keeping this page accurate and current. Your input into this Knol is encouraged and appreciated!
Keep in mind I am not a doctor nor do I have any formal training in supplement or drug research. I am just sharing what I have learned on my own and am looking forward to learning more.
What is Resveratrol?
Resveratrol (3,4’,5-trihydroxystilbene) is a phytoalexin produced naturally by several plants as an antibiotic substance to fight fungi, bacteria, ultra violet rays, and various other attacks on its health. As a nutritional supplement, resveratrol is most commonly produced from the root of the Japanese Knotweed (polygonum cuspidatum) of which large quantities are grown in China. Knotweed isn't the only source of Resveratrol, it can also be found in the skin of grapes, cranberries, peanuts, and various other naturally grown plants.
Resveratrol was originally found in the roots of the White Hellebore in 1940. More recently resveratrol has become popular among scientist when it was shown that trans-resveratrol activated the SiRT1 enzyme. Resveratrol is fat soluable and can be found in the cis- and trans- form. The most commonly used form in studies and supplementation is trans-resveratrol.
Resveratrol gained it's popularity in the media when researchers derived a thesis that the "French Paradox" (the ability for those living in France to consume a high caloric and high fat laden diet and in turn live longer then the average human) could be explained by the high consumption of red wine in the typical French diet. To this date there isn't any hard proof showing this to be the case. There also isn't any evidence to support that it is not. The reason for skepticism is because the amount of resveratrol in a bottle of wine is so little you would have to drink upwards of 500-1000 bottles a day to receive the positive affects researchers believe is obtainable through appropriate human dosages.
It is important to note that many companies market resveratrol supplements as "Red Wine" pills and the media also uses this terminology as well. However, those supplements do not necessarily contain "trans-resveratrol" or may have very little of its content in their product. Make sure when looking to buy resveratrol it clearly states on the bottle how much (preferrably in milligrams, mg's) of trans-resveratrol is in their product. Other wise you may end up with a product not comparable to those used in professional studies.
There has been some preliminary research that suggests resveratrol could have many positive effects on the human body. The following is a list of those possibilities: treatment or cure of Type II – Diabetes, the ability to lower LDL (bad cholesterol) levels, use as a powerful antioxidant, increase exercise tolerance and stamina, fight heart disease, slow or reverse memory loss, life extension effects, anti-cancer, anti-viral, and anti-inflammatory effects. As you can see these are some serious potentially life changing effects.
Resveratrol and Bioavailability
Bioavailability is part of the science known as “pharmacokinetics.” Ok, so what is pharma-co-ka whatics? Pharmacokinetics is the study of what your body does to a drug from entry into your body, its movement within the body, and then how it moves out of the body. So to take it one step further many pharmacology and supplement studies focus on how a drug affects your body, this is opposite, how does your body affect the drug.
As a part of pharmacokinetics bioavailability is used to describe the measurement of how much of an active drug/supplement reaches the systemic circulation and is available at the site of action. Now that’s a bit confusing for some, including myself, until I decoded what is being said there. Think of it like this; when you ingest a drug it travels through your body and passes through the digestive system, through the intestinal wall and then on to the liver (This process is also what is known as something being "metabolized".) By going through this the drug can be broken down and lose some of its potency. When this occurs it can cause less of a drug to actually make it to where it needs to go.
The importance of this is that when a drug, metabolite, or supplements are taken orally, bioavailability becomes a big concern. If your body breaks down the entire drug prior to making it to the final destination it is basically useless. Oral medications that are not very water-soluble are often known for their poor bioavailability due to their inability to pass through the metabolizing process unscathed.
Why is bioavailability so important when it comes to trans-resveratrol? For starters if the "good parts" of a drug or supplement don't make it to the intended destination then there is no chance it is going to work. We as humans metabolize ingested supplements at different rates. It is necessary to make sure you are taking the proper dose and this can be different based on your own metabolism. The faster your body metabolizes a supplement the less likely it is for the effective amount of that supplement to reach its intended destination at lower doses compared to a human with a lower metabolism.
Keep in mind that many non-human resveratrol studies, especially those done with rats, are given at much higher doses of resveratrol or approximately 50mg/KG of body weight. Since rats have different metabolisms then humans it is recommended humans take a lower dose to get a comparable effect.
Resveratrol and Stomach Sensitivity
As you research resveratrol you will come across other people's experiences which tend to vary drastically. However, a common statement is that by taking resveratrol people complain about diarrhea and stomach cramping. It has been said this can last for a few days until you get used to it or it can never go away. It is important to know the reason behind the "stomach sensitivity." The answer is most likely "Emodin!"
So what is emodin? It is a natural crystalline substance that belongs to the family of compounds called "anthraquinones." It is an inhibitor of protein tyrosine kinase, possesses antiviral, immunosuppressive, anti-inflammatory and anticancer effects. A common effect of consuming emodin is it's laxative effect which is typically noticed at doses as low as 10mg per day. This can cause diarrhea and cramping for some people who consume large amounts.
Emodin is often mixed with resveratrol by manufacturers and the amounts are not always disclosed. This is why it is important to know the source of your resveratrol and have its contents verified by reputable independent testing laboratories. Reputable companies will disclose the amounts of emodin in their products.
SIRT1 and Resveratrol
SIRT1, a sirtuin, can be explained as our bodies "judge and jury" as to whether or not a cell should live or die. When our body ages or is under attack our cells have to make a decision. The decision is to either give up and die or to fight and try to repair itself from the damage that’s being done to it. SIRT1 is an enzyme that can help tell the cell what it should do. So if there is more SIRT1 available, or activated, there is a better chance for that cell to try and repair itself and live on.
Resveratrol has been shown in studies to activate the SIRT1 enzyme which in turn helps tell a cell it should try to survive and repair itself. The resveratrol also helps to increase mitochondrial function within the cell. This can help a cell, and in turn our bodies, to burn more fat, recover faster, increase endurance, mimic the effects of calorie restriction diets, and improve insulin sensitivity, among many other things.
Resveratrol’s ability to activate SIRT1 has become so important in research that it is said to have the potential to cure or treat numerous diseases such as prostate cancer, diabetes, MELAS syndrome, anti-aging, and numerous other possibilities. Only time, research, and perhaps a little luck will tell.
Micronized Resveratrol
Earlier in this essay I spoke about the importance of bioavailability and resveratrol. We know that when a drug or supplement is taken orally it must pass through our digestive system and is metabolized. Many substances that are not very water soluble have a hard time making it through this process without first being eliminated or structurally broken down. This means it never makes it to its desired destination in our bodies. To make these types of substances more bioavailable, a method called "micronization" is implemented.
"Micronization is the process of reducing the average diameter of a solid material's particles. Usually, the term micronization is used when the particles that are produced are only a few micrometres in diameter. However, modern applications (usually in the pharmaceutical's industry) require average particle diameters of the nanometer scale."
For example: Talcum powder is approximately 10 microns (1 micron, or um, is a millionth of a meter). Human hair is approximately 70 um in diameter. Micronized supplements are known to be under 10um and sometimes smaller then 1um making it onto the nanometer scale.
So, if trans-resveratrol is micronized does it become more bioavailable?
I have not been able to find any published human studies showing the answer to this is a 100% yes. That said, my research into micronized resveratrol leads me to believe that in fact it is. It is believed Sirtis Pharmaceuticals (recently acquired by Glaxo Smithkline) experimental drug SRT501 is a micronized version of resveratrol that the company claims is up to 1000 times more potent then standard resveratrol. The company states SRT501 is a, "formulation of resveratrol with improved bioavailability" and it also states that the company is, "focused on discovering and developing proprietary, orally available, small molecule drugs..." Ok, so what are the other components and how small is "small molecule" drugs? I don't like to assume but I am fairly certain GlaxoSmithKline wouldn't pay $720 million for a company if it weren't producing something much better then the readily available supplement grade resveratrol. I guess only time will tell.
Resveratrol Dosages
Most of the "trustworthy" resveratrol companies out there claim that 500mg per 50 pounds of body weight is a proper dosage for a human to take. I happen to agree with this but want to add a bit more to it. If you're a 200lb person looking to start taking trans-resveratrol then I would suggest a slow ramp-up period to maximum dosage.
Take it slow by beginning with a very small dose to make sure you don't have any severe reactions. The EPA has listed resveratrol as a non-toxic and numerous human trials have been completed safely, so there "should not" be any major problems. However, just in case, take it slow for the first week. After your body becomes familiar with resveratrol you can increase your dosage.
I would suggest following a trans-resveratrol dosage plan similar to the one I've outlined below:
200lb person:
• Week 1 = 100mg trans-resveratrol daily.
• Week 2 & 3 = 500mg trans-resveratrol daily.
• Week 4, 5, & 6 = 1000mg trans-resveratrol daily.
• Week 7, 8, & 9 = 1500mg trans resveratrol daily.
• Week 10 and beyond = 2000mg trans-resveratrol daily.
After your first week "trial" I think it is safe to increase your dosage to 25% of the maximum recommended dose of 500mg per 50 pounds of body weight. There after increase your dose by an additional 25% until you reach the maximum recommendation. This is not to say that 500mg per 50lbs is the right dose for you. You may find that a smaller dose is better for you or vice versa. Research studies have been safely completed using substantially higher doses then the standard recommended dose.
*Please not if you are using micronized resveratrol that your dosage should not exceed 500mg per 100 pounds of body weight.
News Articles
"Hoping Two Drugs Carry a Side Effect: Longer Life"
http://www.nytimes.com/2008/07/22/health/research/22long.html
By Nicholas Wade, July 22nd, 2008, The New York Times
http://www.nytimes.com/2008/07/22/health/research/22long.html
By Nicholas Wade, July 22nd, 2008, The New York Times
"Resveratrol Found to Improve Health, But Not Longevity in Aging Mice on Standard Diet"
http://www.nia.nih.gov/NewsAndEvents/PressReleases/pr20080703resveratrol.htm
July 3rd, 2008, National Institute on Aging
http://www.nia.nih.gov/NewsAndEvents/PressReleases/pr20080703resveratrol.htm
July 3rd, 2008, National Institute on Aging
"A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice"
http://www.plosone.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.pone.0002264
June 5th, 2008, PloS One
http://www.plosone.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.pone.0002264
June 5th, 2008, PloS One
"Resveratrol May Prevent Breast Cancer"
In Test Tube, Red Wine Supplement Blocks Estrogen Toxicity
http://www.webmd.com/breast-cancer/news/20080707/resveratrol-may-prevent-breast-cancer
By Daniel J. DeNoon, July 7th, 2008, WebMD Health news
In Test Tube, Red Wine Supplement Blocks Estrogen Toxicity
http://www.webmd.com/breast-cancer/news/20080707/resveratrol-may-prevent-breast-cancer
By Daniel J. DeNoon, July 7th, 2008, WebMD Health news
RPT-Glaxo customised "red wine" drug potent in mice
Nov 4th, 2008 Reuters
Ben
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Quite an interesting post -- you seem to have found quite an audience. I have a bit of background in sir2 biology and might be able to help you get through some of the scientific literature if you are interested. Please let me know if I can be of assistance.
I appreciate the offer and will certainly contact you with questions in the future. Also, please feel free to contribute to this Knol if you find information that you feel is related and helpful to others.
Mark
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Anonymous
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Awesome start...