Thursday, April 4, 2013

Resveratrol Dying The Death It Deserves

Red herring is an English-language idiom that commonly refers to a logical fallacy that misleads or detracts from the actual issue.[1] It is also a literary device employed by writers that leads readers or characters towards a false conclusion, often used in mystery or detective fiction.”

I posted the following over a year ago, after a resveratrol researcher was discovered to have committed a massive fraud:

“The French Paradox arose from the fact that the French eat lots of saturated fat (especially dairy fat) yet have low rates of heart disease. Since we knew that eating saturated fat caused heart disease, clearly something had to protect them from heart disease.

“Resveratrol [a compound found in small amounts in red wine] was the candidate, since we all know those Frenchies drink red wine all day. (Don't you love how this science was justified by a crude stereotype?)

“Of course now we know that saturated animal fat not only doesn't cause heart disease, but that eating lots of dairy fat is protective from heart disease. The French Paradox disappears. Resveratrol is no longer needed [to explain it], nor is red wine.

So why the heck are they still studying resveratrol?

I got a good bit of push-back on that position.  Taylor, in the comments, said:

“The problem with this post is that it implies that the positive view of resveratrol was largely driven by this guy's research when in fact his research is only a very small fraction of the positive research on resveratrol.”

Which is a fair point, given that from the press on resveratrol you would think it’s on the verge of giving us longer, healthier lives.  Taylor wasn’t alone, Mark Sisson had a similar view:

“What I’m saying is that one guy fabricating his research doesn’t invalidate all the other research others have conducted on resveratrol.”

The problem is that if resveratrol was so effective, you wouldn’t need to fabricate research demonstrating its effectiveness.

And it turns out that the data from resveratrol isn’t so clear as we’ve been led to believe.  In the Pipeline is one of the blogs I’ve been following for a while. The author, Derek Lowe, is an organic chemist, and has “worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases.”  His take on resveratrol is: Would I Take Resveratrol? Would You?:

“The bottom line? Resveratrol is a very interesting compound, and potentially useful. But the details of its actions aren't clear, and neither, honestly, are the actions themselves. Given the importance of the processes we're talking about - cellular metabolism, which is intimately involved with aging and lifespan, which is intimately involved with defenses against cancer - I don't feel that the situation is clear enough yet to make an intelligent decision. So no, I don't take resveratrol. But I'd be willing to if the fog ever clears.”

Right.  I agree 100% with that position, I just don’t think that resveratrol will ever prove to be any more than a red herring.

Well, the fog is starting to clear. “Dude, Where's My Red Wine Pill? The strange saga of resveratrol, the wonder drug that never was.”:

“If ever there was a drug tailor-made for overweight Americans, this seemed to be it. Six months later, Sirtris—the company Sinclair cofounded to develop resveratrol-based drugs—had its IPO. Eleven months after that, in April 2008, GSK bought Sirtris outright for $720 million, or nearly double its stock-market valuation. Five years later, contra the headlines, there are still no red-wine longevity pills on the horizon. What happened?…”

“…The company launched several clinical trials of possible sirtuin-activating drugs. But then, one by one, those trials were halted, at least two of them due to unexpected side effects. That leaves only one Sirtris compound, SRT2104, still under active study, for psoriasis and ulcerative colitis.

“In the labs, as well, the sirtuin theory of aging was taking heavy fire. In 2011, another group published a paper in Nature that challenged Sinclair’s research directly: His results, it was claimed, were an artifact of the way he did his experiments. The Science paper, published earlier this month, was Sinclair’s triumphant rebuttal, outlining in precise detail how resveratrol and friends actually work on the sirtuin pathway. Just four days later, GSK pulled the plug….”

“…Says Sinclair, who is still a scientific adviser to GSK: “We know the science is real; the problem now is to push it over the goal line. If they don’t end up as drugs in our lifetime, it's not the fault of scientists, and more of a business decision.”

Read the whole thing, but big corporations don’t toss $720 million investments just… because.  Somebody at GSK disagrees with Dr. Sinclair.  So do I.

Which leaves me pretty comfortable with the summary of the post script to my original post:

“I'll pass. Call me in 50 years when you finish the long-term studies.”

Now I don’t know if other folks are still studying resveratrol. I imagine they are, and will continue to do so so long as someone is willing to pay for it. Hey, a job’s a job, even if you’re a PhD.

And if you’ve got psoriasis or ulcerative colitis?  Try the Paleo diet.  You won’t have to wait for resveratrol.

(Here’s lots more on resveratrol at In the Pipeline.)