By Rob Clarke Driven Sports
Resveratrol has been a focal point of discussion for health and body composition for many years now. While this naturally-occurring phenol has failed to live up to expectations, scientists believe they have an answer.
That answer is a synthetic drug that mimics the proposed actions of resveratrol. But why not resveratrol itself?
This is an interesting question as there has been – and still is – a lot of hype surrounding this compound. It was originally discovered over seventy years ago in the skins of grapes and to some degree in red wine (which is made from black grapes if you didn’t already know), but it wasn’t until the past couple of decades that it was pinned as the wondrous chemical behind the French Paradox. This paradox states that the French have low incidence of heart disease despite their typical diets being somewhat rich in saturated fats. It was believed that the resveratrol content of the red wine they often drank opposed the effects of the saturated fat.
It has since been found that the resveratrol content of red wine is far too low to be the source of the French paradox. In actual fact, it is a prime example of scientists and health enthusiasts aiming to pin the effects of a multitude of factors on a single chemical or cause. But the first suggestion did not stop a whirlwind of studies being conducted and published showing any number of positive effects for mind, body and health. These include cardio protection via cholesterol-control, anti-diabetic effects, neuro-protection, anti-inflammatory effects, cancer-prevention, and even anti-viral effects. Another effect noted in the research is that resveratrol acts as a calorie restriction mimetic. This is what gets obesity researchers excited - as do the life extension crew as calorie restriction is believed to extend life expectancy (although there may be a little more to it).
But here is the caveat you’ve been expecting since the opening paragraph: all these great effects are shown in rodents and never quite seem to be reproducible in humans. It seems that the body has no trouble absorbing resveratrol through the intestinal wall, but apparently of the 70% or so that gets through the liver takes offence to and rapidly changes the structure. Officially, it is "conjugated" into glucuronate and sulfonate forms. Very, very little of the resveratrol can escape this fate. Even if you take a massive dose with the aim of overwhelming the enzymes that conjugate the resveratrol, you still fail to reach an adequate level in circulation – at least to the standards expected for the chemopreventive effects (plasma concentrations reach just less than half the absolute minimum required).
Incidentally, some supplements now include sulfonate and glucuronate inhibitors along with resveratrol as a means to increase the concentration of unadulterated resveratrol in the system. This is definitely a great idea on the surface. I am still unsure of how effective it actually is though. But big pharma have other ideas, and this includes the SRT series, including the central topic of this article, SRT1720.
The key concept of SRT1720 is that it targets a specific protein from the sirtuin family – specifically SIRT1. If you recognize that name, it’s because I’ve referenced it a couple of times on the blog already. It is one of the chief nutrient sensors of the cell. It is usually when there is a sudden energy deficit that it kicks into gear along with AMPk. It works in concert with other proteins to switch the body over from a storage state to a stored-energy-burning state (a good phrase to describe this escapes me right now). I discussed this in part two of the recent cardio series and also in part two of the transdermal CO2 series. As you may have guessed from these previous articles, a sudden energy deficit usually occurs during activity (and can also occur during fasting). In other words, activating SIRT1 chemically could be the “exercise pill” that resveratrol was touted as being five years ago. And that is what researchers believe. The whole incentive behind this research is basically so people can continue unhealthy lifestyles but be able to take a pill to avoid the unhealthy side effects. Basically.
The proof of SRT1720 so far is in rodents – a requisite prior to human trials based on stringent drug trial laws. In the study mice were fattened up and split into two groups – one given the drug and one not. Those treated had reductions in liver triglycerides and an improvement in insulin sensitivity. The drug group lived longer than the non-drug group, which is clearly a positive sign. However they did not live as long as mice do when they aren’t abnormally fattened up.
The real question on the lips of many of you, of course, is where’s the relevance for bodybuilders? If scientists ever work it out, it could signal a drug that can convince your body it has done exercise (like cardio) without the actual activity involved. Bodybuilders at their core are not a lazy bunch by any stretch. In fact, we pride ourselves on our drive and willingness to do the sort of thing that Joe Normal simply does not. That’s why, in the words of Dave Ramsey, "normal is fat, broke, and stupid.” The benefit of something like SRT1720 is not to make up for laziness, it is to convince the body to send the same signals it would following cardio, only without the additional stress and damage to the muscle. I don’t personally condone cardio, but that won’t stop bodybuilders from doing it. Something like SRT1720 just might.
Interestingly, research into SRT1720 is going to essentially cease. This is because they believe they have a better candidate in the pipeline. That would be SRT1720’s sibling SRT2104. The trials with SRT2104 will ultimately determine the success of sirtuin activators for the future. In the mean while, keep exercising and eating healthily.
Source: Rafael de Cabo, et al. SRT1720 improves survival and healthspan of obese mice. Aug 2011. Scientific Reports vol 1 (70). doi:10.1038/srep00070.