On December 2, pharmaceutical giant GlaxoSmithKline quietly halted a clinical trial of SRT501, a concentrated form of resveratrol, which is the much-hyped substance found in red wine grapes.
The reason this matters is that SRT501 had been one of the most closely watched molecules in the Big Pharma pipeline ever since 2008, when GlaxoSmithKline snapped it up in a $720 million acquisition of Sirtris Pharmaceuticals -- the company that first suggested resveratrol might be useful for treating age-related diseases.
SRT501 was being tested in a rare form of cancer called multiple myeloma, but Glaxo had grander plans for it and similar molecules. As Sirtris discovered, resveratrol modulates a gene called sir2, which produces the enzyme sirtuin. In mice, turning this gene on extends life by as much as 30 percent. Glaxo has been studying sirtuin-modulating drugs in a range of diseases common in aging people, including diabetes, psoriasis and colon cancer.
Resveratrol will no longer be part of that research, Glaxo says. Signs of trouble first emerged back in the spring, when the company halted the multiple myeloma trial because several patients developed kidney failure. Glaxo investigated, and concluded that the kidney complications may have stemmed from the underlying cancer, but that the SRT501 clearly didn't help matters. The resveratrol formulation "was not well tolerated, and side effects of nausea/vomiting/diarrhea may have indirectly led to dehydration, which exacerbated the development of the acute renal failure," said GSK spokeswoman Melinda Stubbee in an e-mail.
What scares me most about this news is that resveratrol is an incredibly popular over-the-counter supplement among healthy people who think it will help them live longer. Sales hit $30 million in 2008 and were forecast to double this year, according to Nutrition Business Journal. Resveratrol is widely available in mega-doses online and from health food stores.
And a lot of that excitement has been generated by Sirtris. The company's co-founder, Harvard scientist David Sinclair, became something of a media darling after he discovered resveratrol's effect on sir2 in the early 2000s. Sinclair was featured on "60 Minutes" and on an ABC News television special called "Live to Be 150 ... Can You Do It?" On the ABC program, which aired in 2008, Sinclair and Barbara Walters toasted each other with red wine, and Walters asked how many glasses she would have to drink to get the anti-aging benefits. "A thousand bottles a day," Sinclair answered.
Despite Sinclair's insistence that resveratrol's utility in humans had yet to be proven, media attention spawned an entrepreneurial free-for-all. Dozens of companies popped up offering free trials of resveratrol on the Internet. Some of them featured clips of Sinclair, as if to imply he had endorsed specific resveratrol supplements. (He had not.) Thousands of consumers were scammed into signing up for monthly shipments of resveratrol for $90 or more a month.
Many people believe the natural form of the red-wine supplement is perfectly safe and maybe even a lifesaver. Some blame Glaxo for somehow adulterating resveratrol when they turned it into a drug. A patient commenting last week on a Website for multiple myeloma patients called SRT501 "a corruption of the natural resveratrol molecule created by Glaxo to allow them to patent it and control the distribution through pharmaceutical channels."
But the fact is, "SRT501 is resveratrol," Stubbee says. It's purified and concentrated, but other than that, it's no different from the molecule found in your typical vineyard. Resveratrol seems to activate the longevity gene to some extent, but it's "not selective, meaning that it does many other things," she says. In the multiple myeloma trial, those things were not so pleasant.
Glaxo is now focusing on developing far more selective compounds, Stubbee says. They have no chemical relationship to resveratrol. "There are no further plans to develop SRT501."
To me, the moral of this story is clear: Just because something is natural doesn't mean it's safe. Sure, you can go to your local health food store and self-medicate with huge doses of resveratrol if you're so inclined. But if your goal is to live longer, I'd think twice.
Follow Arlene Weintraub on Twitter: www.twitter.com/awjourn
(Little know fact: most recalls are done voluntarily before the FDA actually steps in and are not for FDA approved drugs. They're usually for contaminated foods [often with labels like "natural" or "whole"], OTC remedies, and supplements. It's pretty rare for drugs that had to get FDA approval to be pulled. http://www.fda.gov/Safety/Recalls/default.htm)
And many of the companies that produce dietary supplements are owned by pharmaceutical companies. They recognize a free lunch when they see it.
in botanicals the socalled active " pharmacologically " active substance exists in a matrix. if it is isolated than it isnt in a natural buffer and causes an imbalance etc
the precedures for properly harvesting the right variety of herb sorting it for quality then turning it step by step many steps into a tablet or sort of like thick apple butter or liquid is detailed in 5000 year old texts [ samhitas of Ayur Veda , mainly Charaka and Sushruti ]
maharishi ayur Veda herbal medicines are natural and safe
incorporating master herbalism into MD practice requires the same process of understanding and learning another " language ' as does interfaith understanding
e.g.doctors who are athiest or agnostic or indifferent to beleif in God, might not understand [ or have considered ] that herbs and spices are god -given medicine and the knowledge of proper use and not use is also god-given [ in this sense natural pharmacologically active organic phyto"chemicals " are intelligent design ]
eventually some seperate subject matters in Living section health sections and religion section will integrate into one wholistic understanding of what Health is
ideally in synergistic herbal formulas as in Maharishi Ayur Veda rasayanas
fund more studies on the known naturally-occurring medicinal properties of herbs and spices.
anti-aging is most effectively done in conjunction with meditation: people who learned transcendental meditation (TM) after 5 years had biological age 12 years younger than chronological age
Alexander C.N., Transcendental Meditation and longevity. Journal of Personality and Social Psychology 57: 950-964, 1989.
Alexander C. N.The effects of Transcendental Meditation compared to other methods of relaxation in reducing risk factors, morbidity, and mortality. Homeostasis 35, 243-264, 1994.
Schneider R.H. Long-term effects of stress reduction on mortality in persons > 55 years of age with systemic hypertension. American Journal of Cardiology 95: 1060-1064, 2005.
Wallace R.K. The effects of the Transcendental Meditation and TM-Sidhi program on the aging process. International Journal of Neuroscience 16: 53-58, 1982.
Transcendental Meditation reduces hypertension, obesity, and diabetes in patients with coronary heart disease
This study of 103 people with coronary heart disease found that individuals practicing Transcendental Meditation for four months had significantly lower blood pressure; improved blood glucose and insulin levels (which signify reduced insulin resistance); and more stable functioning of the autonomic nervous system compared to controls.
C. Noel Bairey Merz, M.D Preventive and Rehabilitative Cardiac Center at Cedars-Sinai,
Archives of Internal Medicine,2006
Given that Glaxo's SRT 501 was not simply a purified form of natural resveratrol, it was a synthetic form complexed with a solubility agent, if there are any lessons here at all to be learned regarding resveratrol they are to:
1. Avoid synthetic resveratrol, or any supplement with cyclodextrin or Tween 80 ( solubility agents).
2. Stay away from micronized resveratrol. There is no evidence that it is any more effective, and in bio availability studies, the AUC values are actually lower with micronized resveratrol, whereas the peak blood plasma levels spike initially and then quickly subside. This may be an undesirable property of micronized resveratrol vs non-micronized powder, which has a more even concentration in plasma over time. Avoid micronized resveratrol. There is no evidence that it is effective.
Besides emphasizing the danger of the appeal to nature (http://en.wikipedia.org/wiki/Appeal_to_nature), Weintraub also sets up the fact that true scientific research should be the determinant for what drugs (and supplements are drugs) can be sold. Despite Glaxo gambling almost a billion dollars, they backed out because the science indicated one very important thing: resveratrol is a bad product.
Unfortunately for Glaxo, the laws state that you can't make specific claims without providing exhaustive research that is clinically reproducible (although Big Sup is working hard to further erode those laws). Fortunately for the supplement industry, the current laws also say that as long as they don't make any specific claims, they can beat around the bush all they want about what they want us to think their product does and can put in on the shelves without even demonstrating that it's safe. Shameful.
During the past year there have been several human clinical trials done by the most reputable and distinguished traditional medical institutions in the world, such as Albert Einstein Med College, Northumbria University, Harvard, Stanford and others which have concluded that resveratrol does in deed possess extraordinary medical applications in cancer, diabetes, vasodilation, auto immune conditions and cardiovascular disease. In two human trials at AE Medical College resveratrol demonstrated better glucose tolerance and mitochondrial function improvement that the default drug, Metformin, used by diabetics. Before you throw the baby out with the bath water you might bother to send an hour informing yourself.