Again, I personally will not have our company make anything under 250mg. In my opinion I simply do not think it's very useful. However, if you corner me in an elevator telling me you only want 100mg, and ask me where to get a 100mg capsule if I can't produce it myself... even after I explained that I don't believe such small dose is worth while, it's not a hard thing for me to point to a competitor's product if I am asked to recommend a strictly 100mg capsule.
Who else in the industry would do this? Certainly not my competitors. While they are trying to produce a one capsule fits all, I am making different products and dosages for different people.
A
Anthony,
I am having a very difficult time trying to understand your reasoning here regarding dosage. Now granted, a set dosage has not been determined in Humans yet. However, you seem to feel that a dosage under 250mg is "not very useful in your opinion". Everyone is entitled to their opinion Anthony. However, do you expect other people as well as myself to trust an "opinion"? An Opinion based on what? We need to ask: 1). Does Anthony have any "proof" or "theory based on some type of experiment where he tested 250mg of Resveratrol against than 100mg of Resveratrol? 2). Was Anthony an assistant on the original Resveratrol mice experiment team or was he connected with any of the Resveratrol experiments? If the answer is "no" to both questions, then Anthony, why should anyone believe that 100mg of Resveratrol is not enough for daily use?
Please help us understand.
And I wrote this with out mentioning any brands! (lol)
Just fixed the quotation markers -- Max
Forgive me if I butt in, but determining optimum dosage level is complicated. 100 mg may well be good dose for some people. Resveratrol is glucuronidated and sulfonated by CYP, UGT and SULT enzymes, and we know that different people have different genetically determined phenotypes of these enzymes. Some groups, particularly East Asians, tend to have a variant version of several of these enzymes that is much less efficient than is typical of most Caucasians. The result is that they can require much less of certain drugs to obtain the same effect. See citations below for some studies.
One of the PhDs who contribute to this forum performed an independent dose-versus-blood-serum-level study of resveratrol with several subjects; the single Asian subject obtained a serum level roughly twice that seen with a given dose than seen for the other subjects. If you search for hedgehog's posts you can find this, as well as references to Boocock's study on human pharmokinetics of resveratrol (more on that later.)
My point is basically "different strokes for different folks." This applies also to combining with other phytochemicals to block the actions of these enzymes in order to obtain higher serum levels of resveratrol. For some it is not necessary, and may have unwanted side effects in others. 100 mg could be a helpful dose for many, but is quite probably inadequate for others.
Boocock's
paper (abstract below) indicated a non-linearly increasing dose-response curve showing, as one would expect, greater serum levels for a greater dose. The serum levels they obtained even with a 5 gram dose were inadequate to obtain the cancer preventative effects noted
in vitro. Sinclair's studies have found a roughly linear dose-effect response in rodents, and in the human subjects in Phase II studies measuring blood sugar. Toxicity studies have found resveratrol to be well-tolerated with few side effects. None of the many subjects in Sirtris' study showed tendon or joint pain, the main complaint in these forums with high-dose and even low doses of resveratrol. Sirtris was testing with 2.5 and 5 grams. It seems possible that other supplements such as are more likely to be taken by contributors to this forum may have caused an interaction leading to these effects.
In view of the above, it's not unreasonable to conclude that the higher the resveratrol dose, the better the effects will be. Attempts to extrapolate Sinclair's and Auwerx's rodent studies to humans led to an estimate of 250 to 400 mg as the minimal dose to achieve the beneficial effects seen. This was a consensus opinion reached by contributors to these forums in 2007 and early 2008. (The quality of posts to this forum have declined considerably since then, BTW. There was a collaborative atmosphere as opposed to the oppositional attitude that has arisen.) Certainly many contributors to this forum find benefits and no problems with 250 or 400 mg, and even with much higher doses.
Should Anthony market a 100 mg pill? I'll let him explain that. Again. I haven't seen a 100 mg capsule of 99% resveratrol without additives like IP6 or quercetin, but then I haven't looked.
FAROOQ, S. (1998) Ethnicity and clozapine metabolism (letter). British Journal of Psychiatry, 173, 87.
JANN, M.W., CHANG, W. H., LAM, Y., et al(1993) Comparison of haloperidol and reduced haloperidol plasma levels in four different ethnic populations. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 16, 193 -202.[CrossRef]
LIN, K.-M. & FINDER, E. (1983) Neuroleptic dosage for Asians. American Journal of Psychiatry, 140, 490 -491.[Free Full Text]
LIN, K.-M., POLAND, R.E., NUCCIO, I., et al (1989) A longitudinal assessment of haloperidol doses and serum concentrations in Asian and Caucasian schizophrenia patients. American Journal of Psychiatry, 146, 1307 -1311.[Abstract/Free Full Text]
MASELLIS, M., BASILE, V. S., ÖZDEMIR, V., et al (2000) Pharmacogenetics of antipsychotic treatment: lessons learned from clozapine. Biological Psychiatry, 47, 252 -266.[CrossRef][Medline]
Cancer Epidemiology Biomarkers & Prevention 16, 1246, June 1, 2007. doi: 10.1158/1055-9965.EPI-07-0022
Phase I Dose Escalation Pharmacokinetic Study in Healthy Volunteers of Resveratrol, a Potential Cancer Chemopreventive AgentDavid J. Boocock1, Guy E.S. Faust1, Ketan R. Patel1, Anna M. Schinas2, Victoria A. Brown1, Murray P. Ducharme2, Tristan D. Booth3, James A. Crowell4, Marjorie Perloff4, Andreas J. Gescher1, William P. Steward1 and Dean E. Brenner5
1 Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine, Leicester University, Leicester, United Kingdom; 2 MDS Pharma Services; 3 Royalmount Pharma, Montreal, Canada; 4 Chemopreventive Agent Development Research Group, National Cancer Institute, Bethesda, Maryland; and 5 Departments of Internal Medicine and Pharmacology, University of Michigan Medical School and VA Medical Center, Ann Arbor, Michigan
Requests for reprints: Andreas J. Gescher, Department of Cancer Studies and Molecular Medicine, Leicester Royal Infirmary, Robert Kilpatrick Clinical Sciences Building, Leicester University, Leicester LE2 7LX, United Kingdom; Phone: 44-116-223-1856; Fax: 44-116-223-1855. E-mail: ag15@le.ac.uk
The red grape constituent resveratrol possesses cancer chemopreventive properties in rodents. The hypothesis was tested that, in healthy humans, p.o. administration of resveratrol is safe and results in measurable plasma levels of resveratrol. A phase I study of oral resveratrol (single doses of 0.5, 1, 2.5, or 5 g) was conducted in 10 healthy volunteers per dose level. Resveratrol and its metabolites were identified in plasma and urine by high-performance liquid chromatography-tandem mass spectrometry and quantitated by high-performance liquid chromatography-UV. Consumption of resveratrol did not cause serious adverse events. Resveratrol and six metabolites were recovered from plasma and urine. Peak plasma levels of resveratrol at the highest dose were 539 ± 384 ng/mL (2.4 µmol/L, mean ± SD; n = 10), which occurred 1.5 h post-dose. Peak levels of two monoglucuronides and resveratrol-3-sulfate were 3- to 8-fold higher. The area under the plasma concentration curve (AUC) values for resveratrol-3-sulfate and resveratrol monoglucuronides were up to 23 times greater than those of resveratrol. Urinary excretion of resveratrol and its metabolites was rapid, with 77% of all urinary agent-derived species excreted within 4 h after the lowest dose. Cancer chemopreventive effects of resveratrol in cells in vitro require levels of at least 5 µmol/L. The results presented here intimate that consumption of high-dose resveratrol might be insufficient to elicit systemic levels commensurate with cancer chemopreventive efficacy. However, the high systemic levels of resveratrol conjugate metabolites suggest that their cancer chemopreventive properties warrant investigation. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1246–52)
Edited by maxwatt, 23 February 2009 - 01:58 PM.