....
The part about cleaning the facility might be a joke, but I wonder about the strong laxative side effects, since
mine have only gotten worse.
Mine have gotten better. I hired a cleaning lady.
Seriously: I take two grams morning and again at night. Sometimes with lecithin, sometimes in milk (or a chocolate egg cream -- milk, seltzer, resveratrol and Fox's U-Bet chocolate syrup). Usually little or no laxative effect, but sometimes it builds up. It may be influenced by other things in the diet. Skipping one or two doses gets things back to normal. The various things I've tried to mitigate the effect are only partly effective. (These were HMB for the butyrate, Inawe did not report good effects with another butyrate compound- Calcium butyrate - so I've not pursued that, a Chinese Herb, Bai Zhi, and Kaopectate, i.e. bismuth subsalicylate).
If I take more than two grams at a time twice a day, or three grams once a day, I will have the problem. This amount seems to be specific to individuals. For my wife, more than 250 mg once a day seems to be the tipping point. Missminni, your tipping point seems to be somewhat under 1 gram twice a day. Another person found it to be 500 mg. Some people take 5 or more grams regularly, no problem. I can't. Is a longer life worth it, if it has to be spent on the toilet? Once a day dosing, at night, with an individually determine maximum tolerated dose may be the best course.
It is possible to use other sirtuin activators. The more potent that I know are silymarin (best bound with phosphatidyl choline (lecithin) as in the product Siliphos ®,) and diadzein, which is not readily available without other soy isoflavones. Unfortunately, silymarin is known to be a laxative for some people. Diadzein was available a dozen years ago, for weightlifters and body builders, but they decided with little direct evidence that it was estrogenic. Yet some people did claim a muscle-building effect.
The people who market Siliphos Silymarin claim a 10 fold increase in serum levels over powder-in-a-capsule. If this delivery system works for resveratrol, one won't need such large doses. Since Silymarin is readily available as a supplement, it may be worth trying to see if it is tolerable. Beyond-a-century sells an 80% extract as powder, and 80% capsules are available from a number of sources. My estimates are that one needs twice the dose of 80% Silymarin to achieve the same sirtuin-activating effect as with resveratrol. The blood levels of resveratrol bound to lecithin, should be something Hedgehog could measure, or perhaps Anthony could have done.
The laxative effect is known to be due to the Caco cells in the small intestine secreting too much chlorate, and is known to be mitigated by butyrate, which is available as a prescription medication for a genetic disorder affecting the intestines (inawe posted a link to the abstract. in pubmed.) If one could obtain a prescription, or perhabs a pharmacy abroad, that might be what's needed. The Caco cells are also those that passively pass resveratrol into the blood, or conjugate it with a sugar or a sulfur-containing molecule. (Anyone with more specific knowledge please add to this.) People differ genetically in their enzyme levels for these processes. Perhaps the diarrhea indicates one is absorbing an effective dose, or perhaps it indicates the opposite, that one can't absorb enough to be effective. I don't know.
I plan to continue resveratrol for my own use, and I think most people would benefit if they could. Over the past year I've had remarkably positive effects for my osteoarthritis, my average fasting glucose levels seem to have declined by about 20 mg/dl. If the Cardiotrack were more accurate for measuring lipids I could report that too, but it will have to wait for my physical in the next few months. The first two parameters are consistent with a CR mimetic effect. Even if they weren't, the pain relief and increased mobility are worth it for me.