An Important Point About Supplements

I have noted an important point about supplements in at least one previous post:

In any case, most of these near future products would have to be injected to have the desired effect. The human digestive system is very good at breaking down complex compounds - especially those relating to human biochemistry - before they get anywhere near the bloodstream.

This was posted as part of a commentary on resveratrol, a calorie restriction mimetic compound that has been generating some excitement in the old school portions of the healthy life extension community. I talked a little about resveratrol in a recent Longevity Meme Newsletter:

Resveratrol has been in the news recently. It is a supplement found in red wine that triggers some of the same beneficial effects on health and longevity as calorie restriction in animal studies:


Does this mean that you should run out and start ordering resveratrol? No, not unless you can afford to throw away that money. Taking resveratrol supplements now is a bet - you are betting that this substance, quick to decay and difficult to keep potent even in laboratories, will still be useful and viable in pill form. The history of the supplement industry shows this to be a bad bet; you are almost certainly going to lose. Many substances backed by wonderful scientific studies have turned out to have little or no effect - for one reason or another - when taken as supplements.

I agree that resveratrol is a step forward for the world of supplements - the discovery certainly demonstrates the power and utility of modern bioinformatics. I plan to take it myself, but only after a vendor steps forward to demonstrate that their resveratrol pills are as effective in studies as laboratory preparations.

Here is a comment from an Immortality Institute thread on resveratrol:

Sinclair and his team at Harvard tested the biological activity of many conventional resveratrol supplements available on the market before the thought of "Longevinex" was ever conceived of. It was in response to Sinclair's findings that existing resveratrol supplements showed no biological activity due to oxidation that health journalist Bill Sardi contacted chemists in the industry to develop a resveratrol supplement which is protected from oxidation. Sinclair has claimed that he has received no compensation from the Longevinex company, and announced on a mailing list that he planned to pursue legal action against Longevinex for using his name to promote their product without his consent. Other than perhaps initially testing(?) the compound for Sardi, Sinclair made it sound as if he had no financial connection with them.

Sinclair found that only research-grade resveratrol produced under hypoxic conditions and sealed under nitrogen during storage were found to have significant biological activity. The compound simply oxidizes rapidly... think of a sliced apple which turns brown after a short time. Longevinex is the first supplement to be produced under a nitrogen environment, and sealed in an air-tight capsule with a nitrogen bubble inside to protect from oxidation. For the same reason, the resveratrol in red wine is quickly oxidized in less than a day after the bottle is opened. Since wine can be purchased in the plastic collapsable bags, some have chosen to supplement with resveratrol in this fashion. However, one would have to drink over 10 glasses of typical red wine per day to get the same amount of resveratrol, if my memory serves; although some red wines contain more resveratrol than others.

Another problem with resveratrol is that it rapidly forms conjugates both in the digestive tract and during the initial pass through the liver. Quercetin can saturate and bind to the same compounds which conjugate with resveratrol, so Longevinex also includes quercetin in the pill. However, it is a small amount, and my guess is that all of the quercetin, plus all of the resveratrol in the pill will become conjugated. A possible solution to this is to take extra quercetin (say 500mg) shortly before taking Longevinex. Two published studies now have found that resveratrol rapidly forms conjugates and is likely not bioavailable. Quercetin is believed to inhibit this conjugation, and quercetin also helps to activate the same gene that resveratrol does, albeit less potently.

Some things to ask yourself about any new supplement backed up by good laboratory work:

  • Do the pills deliver the same potency and compound used in the laboratory?
  • Will your body break it down before it does anything?
  • Has the pill form been demonstrated to have the same (or any) beneficial effects in scientific studies?
  • Is spending time, effort and money on this as effective for your future healthy and longevity as putting the same resources towards serious anti-aging research?

In all fairness, that last question is a tough one - but it is something you should think about. I think that we would all benefit from less time spent on pills and more time spent on advanced medicine: telomeres, stem cells, cancer therapies, mitochondria and real anti-aging medicine.

UPDATE 11/25/2006: For more thoughts in the same vein, in the wake of more recent resveratrol science and publicity, you should read one of the more recent posts on the subject.


You quote sinclair as saying:

"only research-grade resveratrol produced under hypoxic conditions and sealed under nitrogen during storage were found to have significant biological activity. The compound simply oxidizes rapidly..."

And there is mentioned additional degradation in digestion. So I ask:

1. Are there any research-grade commercial pills
available on the market? If so, would you be willing to indicate a trade name to me?

2. If such are available, will the digestion problem make it an exercise in fultility or might there be some benefit all the same?

Thank you,
David S. Devor

Posted by: David S. Devor at June 14th, 2006 2:04 AM

Not a question I can answer well; you should head over to the nootropics community portion of the Immortality Institute forums and ask there:

They're pretty knowledgeably on the finer details of who sells which supplements at what quality.

Posted by: Reason at June 14th, 2006 7:29 AM

Several studies on the PubMed archives of medical studies indicate that resveratrol is stable at room temperature, unsealed. The study indicates that the substance is stable under these conditions.

While I am not an expert, it may be wise to investigate these claims that only the most expensive reveratrol supplements will work to fight aging.

Posted by: William at November 2nd, 2006 1:09 AM

I would like additional information regarding the lack of stability of the resveratrol compound attributed to D. Sinclair. Antetodal evidence, i.e. the French population's attributed benefit from taking red wine throught the digestive system, suggests there could be beneficial effects from this compound at less than lab conditions.

Posted by: Hal at November 3rd, 2006 10:59 AM

According to Der Spiegel #50/2006, page 155, the mice ate 22 mg per kg body weight DAILY! Longevinex publicity material shrewdly confuses monthly with daily dose by offering 30 x 15 mg polyphenols = 450 mg/month as equivalent to what the mice ate. And they don't say what percentage of the polyphenols are resveratrol.Furthermore they claim the figures they produce are from a study by an independent lab, but they don't say the name of the lab or what the lab is independent of. It may be independent of Outer Mongolia for all we know.

Posted by: Gropius Plundermutt at December 15th, 2006 4:05 AM

What about the red wine studies - do we know if red wine actually helps prevent heart attacks? If so do we know if revestrol is the reason ? If so why does this revestrol not get oxidized.. or maybe it does and it is still effective.

Posted by: Steve at December 20th, 2006 4:45 PM

please keep me posted on the best source of this material. I am 69 and as old as I want to be. My son gave me a month's worth of this stuff for Christmas and I need to find out how to replenish my cupboard right away.

Posted by: Joanna Cowell at January 5th, 2007 4:48 AM

My husband thinks the only way he can get any bebefits from resveratrol is by buying the $200.00 a month kind. Can he get just as much "benefit" (I'm still skeptical) from the 15.00 bottle?

Posted by: Wendy at February 18th, 2007 11:18 AM

So now I'm totally confused! So can someone please tell me if this $15 a bottle of resveratrol works or am I wasting my money?

Posted by: kathy lasota at June 7th, 2007 7:02 AM

I can attest that I have been taking 1 Longevinex capsule daily for over 1 year. I am 63, very active, play tennis at least 1x/week level 3.5. I have increase endurance, strength, and need less less sleep. Before starting Longevinex, I needed to take Naproxin before and the next day after playing. No longer needed, and I do not get sore from strenous activities.
I do not know if I will live longer, but I am sure feeling much younger!!

Posted by: Larry at July 24th, 2008 8:05 AM

I also would like to know if I can get the same benefits from a $15 bottle as I would get from buying the expensive kind?

Posted by: Linda Hensinger at December 28th, 2008 11:43 AM

You people should do your biochemistry homework first! Resveratrol undergoes extensive metabolism when taken orally. We do not even know what the effects are of the metabolite of resveratrol The majority of studies on resveratrol have been cell culture studies, including normal human cells and bacteria. Remember,....lengthening the telomeres of one's chromosomes...may may you more susceptible to mutational changes! The evidence is not there be taking this stuff in large quantities. This is what I teach my medical students.
Douglas S. Shearer, Ph.D., M.D.

Posted by: Dr. Douglas Shearer at February 10th, 2009 9:01 PM

My father has been diagonised with pancreatic cancer,along with Siddha Ayurvedha he is supplemented him with reseveratrol and found to have wonderful changes in him,There is no pain,his appetite has improved,he can sleep well.So far,So good,So What

Posted by: Abraham Clancy Ross at February 11th, 2009 10:09 AM

With all due respect to Dr. Shearer, there are many studies regarding the value of resveratrol. While we are unsure of the mechanism by which resveratrol acts, we are sure of its benefits.

Posted by: Gerardo at March 22nd, 2010 10:41 AM

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