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:

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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.