Q: How is resveratrol different from other active ingredients more commonly found in animal products?
Dr. Patrick Lawless: I think one of the most interesting things about Resveratrol is its capability to affect inflammation in a wide array of tissues in many different species of organisms, including humans, horses and dogs. Resveratrol was the focus of an overwhelming amount of inflammation research over the past 15 years or so.
The most interesting thing about Resveratrol to me as a scientist is that it approaches inflammation in a completely different way than most of the anti-inflammatories that are being used in animal health. Most of your NSAIDs act on the cyclooxygenase enzyme, which is basically a downstream mediator of inflammation. In other words, once you have cyclooxygenase in the system, it is already eliciting an inflammatory response in the body. Therefore, cyclooxygenase inhibition is a very reactive means of inhibiting or dampening inflammation in the body’s tissues.
One of the unique things about Resveratrol is that it actually controls inflammation at the gene expression level, more upstream in the inflammatory process. Therefore, Resveratrol administration is a more proactive means of dampening the body’s inflammatory response in comparison with the cyclooxygenase inhibition characteristic of traditional NSAIDs. Basically Resveratrol binds to a nuclear cofactor called NF-kappaB that is responsible for production of many different mediators that are involved in the inflammatory process, including cyclooxygenases, interleukins, lipoxygenases and peroxidases.
The analogy I like to use is: if we think of inflammation being water flowing from a faucet, cyclooxygenase or COX2 inhibitors essentially are similar to building a poorly constructed dam that slows down the flow of water or inflammation but does not reduce the flow of water or inflammation from the faucet. COX2 inhibitors bind to inflammatory mediators once they are in the system and are already causing inflammation to occur.
In contrast, Resveratrol is more analogous to turning down the tap to reduce the amount of inflammatory mediators that enter the system in the first place. Therefore, Resveratrol, due to its mode of action, is a more proactive approach to inflammation than traditional NSAIDs, which in general are COX2 inhibitors.
In some instances, such as after injury or after surgery, there is substantial inflammation occurring as the body uses inflammation to heal damaged tissue and to fight off potential infections. In these situations, there is a sound scientific basis for using a combined approach to control inflammation. Use of Resveratrol in conjunction with NSAIDs may reduce the total amount of inflammatory mediators being produced through gene expression and bind many of the inflammatory mediators that are already present in the body’s tissues. While there have not been formal safety trials conducted in animals with the combined administration of Resveratrol and COX2 inhibitors, veterinarians have routinely used Resveratrol along with COX2 inhibitors such as firocoxib in certain situations and have reported much more success than they would have just using a COX2 inhibitor or an NSAID alone.
Q: What about sirtuins? Resveratrol has been demonstrated to increase sirtuin activity. Most people focus on sirtuin activation increasing longevity or lifespan in some research trials. Could you speak about Resveratrol’s effects on metabolic function through its sirtuin activation?
Dr. Pat: Sirtuins have been identified relatively recently, in the early 2000s. Sirtuins were the first set of genes that were identified to exert anti-aging effects or to increase longevity in animals. Resveratrol was the first compound shown to activate sirtuins, and thus Resveratrol has drawn considerable attention from scientists studying sirtuins, aging and longevity. Exercise and calorie restriction, or fasting, have also been shown to activate sirtuins.
The positive effects of Resveratrol on aging individuals appears to be through its capability to reduce chronic inflammation and to improve metabolism. We now understand that sirtuin activation causes an increase in gene expression of an enzyme (PGC1-alpha) that has a profound effect on metabolism. Specifically, sirtuin activation and PGC1-alpha upregulation result in a phenomenon known as mitochondrial biogenesis. This term refers to an increase in the density and size of mitochondria within cells. For those of you who may not remember the function of mitochondria from your high school biology classes, these are the structures within cells where metabolic reactions occur at the cellular level to convert organic substances we consume as food into cellular energy that drives our entire existence. In short, Resveratrol administration has been demonstrated to promote healthy aging in part by its capability to improve metabolic efficiency in animals through mitochondrial biogenesis.
A lot of people tend to think of metabolism as a relatively perfect process where food is flawlessly converted into energy. Metabolism is actually a very imperfect process, and its imperfections have negative effects on the body and its tissues. Metabolism generates free radicals such as ozone and peroxides that are very reactive. These free radicals cause damage to cell membranes in particular and can result in premature cell dealth. Muscle and nervous system tissue (brain and nerves) are some of the most metabolically active tissues in the body and are therefore most susceptible to damage from free radicals generated during metabolism. Resveratrol is a potent antioxidant that can neutralize excess free radicals in the body, in addition to improving metabolic efficiency.
With sport horses, it's all about inflammation and controlling it. Can you talk about the oxidative stress that a sport horse produces and how to combat that?
Dr. Pat: As I mentioned earlier, free radical generation and oxidative stress occurs naturally with metabolism. So obviously when you are exercising vigorously, as is the case with sport horses, the body is having to metabolize food into energy at a rapid pace to supply the energy necessary to engage in these vigorous physical activities. With increasing metabolic rates there is a corresponding increase in the rate of free radical generation.
Oxidative stress refers to conditions where there is an abundance of oxygenated free radicals present in the body. This is detrimental to health and performance because these free radicals actually cause damage, or death to cells, in metabolically active tissues, particularly muscle tissue. Resveratrol is a potent antioxidant that neutralizes free radicals and therefore protects muscle tissue from the damaging effects of oxidative stress. By protecting muscle tissue from free radicals and oxidative stress, Resveratrol administration may improve performance and reduce recovery time.
Dr. Patrick Lawless, PhD, is the president and founder of Thrive Animal Health.
All content is for informational purposes only. Consult with a veterinarian or equine practitioner regarding the health and wellness of your animals.