Robert Rolen wrote:

>I also thought you might be interested in something I ran across that
>might allow you to lower your aspirin dose.
>
>[I and Kitty take aspirin for many more reasons than its ability to inhibit
>inflammatory and coagulative eicosanoid production. One of those major
>reasons is the antiglycative properties of aspirin, with respect to which
>more is better. we only keep our dose as low as it is, distributed and with
>food, in order to minimize the possibility of negative intestinal effects
>and too much anticoagulation. --Paul]

I wasn't quite aware of the extent of the research on aspirin's
antiglycative properties. These caught my eye if anyone else is interested.
http://groups.google.com/group/sci.life-extension/browse_thread/thread/3eb4532f9\
b7a8607/776a00fa519ceee9?q=aspirin+glycation&rnum=1#776a00fa519ceee9
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra\
ct&list_uids=8150030
Increased susceptibility to metal catalysed oxidation of diabetic lens beta
L crystallin: possible protection by dietary supplementation with
acetylsalicylic acid.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra\
ct&list_uids=8557952
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra\
ct&list_uids=8611656
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra\
ct&list_uids=9135951
Effects of aspirin or basic amino acids on collagen cross-links and
complications in NIDDM.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra\
ct&list_uids=10766412
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra\
ct&list_uids=10821123
Influence of acetylsalicylic acid on oxidation of native and glycated
low-density lipoprotein.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra\
ct&list_uids=11006510
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra\
ct&list_uids=11423486
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra\
ct&list_uids=12049635
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8\
309673&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra\
ct&list_uids=1623937
Prevention of cataract in diabetic rats by aspirin, paracetamol
(acetaminophen) and ibuprofen.

[big snip of unresponded items by --Paul]

>http://www.bioperine.com/BioWithCur.htm looks like 2g of curcumin
>with 20mg bioperine can get you up into the 0.2microg/ml range
>
>[This is not a peer reviewed source of information and therefore cannot be
>considered as any kind of evidence. The abstract which the site is
>referring to is below. It does not state the concentration of curcumin
>reached after supplementation and since the full text article is not freely
>available the numbers given on this site cannot be verified. However the
>abstract does state that the increase in bioavailability was 2000% when
>20mg of piperine was administered along with 2g of curcumin in humans.
>
>Planta Med. 1998 May;64(4):353-6.
>Influence of piperine on the pharmacokinetics of curcumin in animals
>and human volunteers.
>Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS.
>Department of Pharmacology, St. John's Medical College, Bangalore, India.
>
>The medicinal properties of curcumin obtained from Curcuma longa L. cannot
>be utilised because of poor bioavailability due to its rapid metabolism in the
>liver and intestinal wall. In this study, the effect of combining piperine, a
>known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the
>bioavailability of curcumin in rats and healthy human volunteers. When curcumin
>was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were
>achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg
>increased the serum concentration of curcumin for a short period of 1-2 h post
>drug. Time to maximum was significantly increased (P < 0.02) while elimination
>half life and clearance significantly decreased (P < 0.02), and the
>bioavailability was increased by 154%. On the other hand in humans after a dose
>of 2 g curcumin alone, serum levels were either undetectable or very low.
>Concomitant administration of piperine 20 mg produced much higher
concentrations
>from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the
>increase in bioavailability was 2000%. The study shows that in the dosages
used,
>piperine enhances the serum concentration, extent of absorption and
>bioavailability of curcumin in both rats and humans with no adverse effects.
>
>Publication Types: Clinical Trial
>PMID: 9619120
>
>-°Olafur]
>
>
>which is about equal to http://en.wikipedia.org/wiki/Curcumin Molar mass
>368.38 g/mol >>>> 0.2mg/L == 0.54microM, so maybe you're not getting
>high enough to get to the 70microM IC50.
>
>[Again this is not a peer reviewed source of information. Since anyone can
>write whatever he wants on Wikipedia.org there is no way to make sure the
>information contained there is correct. However the molar mass you gave
>for curcumin is correct and so are your computations; the only problem is
>that the 0,2mg/L figure cannot be verified. -°Olafur]
>
>[A major reason why the information at the bioperine.com site is useless
>without access to the full paper text, is that the dosage of 2g/kg for rats
>is not identified with respect to whether it was by weight of rat or by
>weight of food. Clearly, the information at the site is meant for the
>promotion of the value of bioperine rather than for any value toward
>scientific dosage computation. Thus, although Robert's calculations are
>correct, the end effect is another example of the old adage "garbage in,
>garbage out". --Paul]

Actually, I was refering to the limited (n=8) non-peer reviewed
bioavailability plot that you'll see if you scroll down a little farther
below the rat plot http://www.bioperine.com/BioWithCur.htm

[Thanks for pointing that out. I had missed it entirely. --Paul]

[That plot is where I thought he got the 0,2mg/L figure from. -°Olafur]


The strange thing is, if you compare my 0.54microM estimate with the
0.51microM estimate for the 4g dose in the study below, it would seem as if
the 20mg of piperine is only doubling bioavailability (granted it is only a
peak plasma concentration comparison rather than AUC).

[I suspect that the bioavailabity varies greatly with the source of curcumin and
the state of the humans taking it. The data at piperine.com, if valid at all,
may have been taken under conditions generated to show the best possible effect
from the use of piperine. OTOH, it may be that piperine will multiply the
bioavailability by 20 times under all conditions of taking curcumin. Without
fully controlled tests on sufficient numbers of people under different
conditions and with different sources of curcumin there is no way to be sure.
--Paul]


Perhaps the piperine people are preferentially publishing a partial picture
of the P450 impeding piperine pill popping plasma plots.

I'm sorry. That was just wrong.

[I am not sure what you think was "wrong", but I thought your long alliteration
was genius level and got a big chuckle out of it :-) --Paul]


>http://www.findarticles.com/p/articles/mi_m0FDN/is_1_7/ai_83582834
>Phase I clinical trial of curcumin, a chemopreventive agent, in
>patients with high-risk or pre-malignant lesions - Abstracts
>Alternative Medicine Review, Feb, 2002
>Curcumin (diferuloylmethane), a yellow substance from the root of the
>plant Curcuma longa Linn., has been demonstrated to inhibit
>carcinogenesis of murine skin, stomach, intestine and liver. However,
>the toxicology, pharmacokinetics and biologically effective dose of
>curcumin in humans have not been reported. This prospective phase-I
>study evaluated these issues of curcumin in patients with one of the
>following five high-risk conditions: 1) recently resected urinary
>bladder cancer; 2) arsenic Bowen's disease of the skin; 3) uterine
>cervical intraepithelial neoplasm (CIN); 4) oral leucoplakia; and 5)
>intestinal metaplasia of the stomach. Curcumin was taken orally for 3
>months. Biopsy of the lesion sites was done immediately before and 3
>months after starting curcumin treament. The starting dose was 500 mg/
>day. If no toxicity > or == grade II was noted in at least 3 successive
>patients, the dose was then escalated to another level in the order of
>1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. The concentration of
>curcumin in serum and urine was determined by high pressure liquid
>chromatography (HPLC). A total of 25 patients were enrolled in this
>study. There was no treatment-related toxicity up to 8,000 mg/day.
>Beyond 8,000 mg/day, the bulky volume of the drug was unacceptable to
>the patients. The serum concentration of curcumin usually peaked at 1
>to 2 hours after oral intake of crucumin and gradually declined within
>12 hours. The average peak serum concentrations after taking 4,000 mg,
>6,000 mg and 8,000 mg of curcumin were 0.51 +/- 0.11 microM, 0.63 +/-
>0.06 microM and 1.77 +/- 1.87 microM, respectively. Urinary excretion
>of curcumin was undetectable. One of 4 patients with CIN and 1 of 7
>patients with oral leucoplakia proceeded to develop frank malignancies
>in spite of curcumin treatment. In contrast, histologic improvement of
>precancerous lesions was seen in 1 out of 2 patients with recently
>resected bladder cancer, 2 out of 7 patients of oral leucoplakia, 1
>out of 6 patients of intestinal metaplasia of the stomach, 1 out of 4
>patients with CIN and 2 out of 6 patients with Bowen's disease. In
>conclusion, this study demonstrated that curcumin is not toxic to
>humans up to 8,000 mg/day when taken by mouth for 3 months. Our
>results also suggest a biologic effect of curcumin in the
>chemoprevention of cancer.
>
>Maybe bioperine would have significantly increased these levels.
>
>[It probably would have. The above study is PMID: 11712783 and the
>concentrations reached for the 4000 mg, 6000 mg and 8000 mg doses were 0,51
>microM, 0,63 microM and 1,77 microM. What is strange about this is that
>these numbers are similar to the 0,54microM you calculated above using the
>0,2mg/L figure which apparently was reached when taking piperine along with
>curcumin. Since in that study curcumin was taken along with piperine, one
>would expect the concentration reached to be much higher than in the study
>above since pirerine increases the bioavailability of curcumin by about
>2000%. This tells me that either the 0,2mg/L figure is incorrect or that
>these studies are for some reason not comparable. It is clear though that
>without piperine you will not reach anywhere close to the 70microM IC50
>value for inhibition of TXA2 by curcumin. Whether taking piperine along
>with curcumin will get you close to the 70microM concentration cannot be
>determined by these abstracts. Obviously more research is needed in this
>area.
>
>[Actually, I think Robert got the 0.54 microM from simply using my personal
>dosage of curcumin with bioperine and the rat data at the bioperine.com
>website. However, since the real meaning of rat data is unknown without the
>full text of the paper, if I use the data from the paper above, assume a
>linear increase of serum concentration with dosage and that the amount of
>bioperine I take (11 mg each meal) is sufficient to increse the
>biolavailability by 2000%, then my 3250 mg daily dosage should give me a
>serum amount of (very roughly) 3250 x 2000% x 1.77 / 8000 == 14 microM. I
>would not want to increase it any more since my polyphenol load is already
>quite high (polyphenols raise homocysteine levels) and any prothrombotic
>potential because of blood clotting is already taken care of by multiple
>other of my supplement, dietary and lifestyle factors. --Paul]
>
>BTW curcumin is derived from the spice turmeric and I decided to check how
>much curcumin is contained in turmeric. When searching pubmed I didn't
>find any abstract which stated the percentage of curcumin in turmeric.
>However the full text article of PMID: 16081279 states the following:
>"Curcumin (diferuloylmethane) is a low molecular weight polyphenol, first
>chemically characterised in 1910, that is generally regarded as the most
>active constituent of and comprises 2–8% of most turmeric preparations 3
>and 4." According to this quote turmeric contains about 2-8% curcumin.
>-°Olafur]
>

I don't know how credible this is, but it looks like you can get a
comparatively high 4.0% to 6.5% total curcumin content out of the Alleppey
tumeric http://www.foodproductdesign.com/archive/2001/0301sr.html

[BTW, part of the reason why Olafur and I could not understand where you were
getting your starting number before was because you used "you" and "you're" in
place of "one" and "one is" (as you just did again in the sentence above). Since
you had just been using "you" to refer to me and my dosage of aspirin, I thought
that the "you" and "you're" still referred to me. In future, please be more
careful to distinguish between the specific "you" directed at a particular
individual (ie. the seond person "you"), and the incorrect use of "you" in place
of "one" (ie. a third person usage). In fact, best of all, do not ever use "you"
in place of "one"! If you don't like "one" then use "a person" or "someone". So
for example, your sentence above would read in part: "but it looks like a person
can get" or "it looks like someone can get". --Paul]

[Different varieties of turmeric may vary in respect to their curcumin content
but a good rule of thumb is to search for one with a strong yellow color.
Curcumin is a yellow compound and is responsible for the yellow color of
turmeric so a strong yellow color would be an indicator that it contains high
amounts of curcumin (PMID: 12409634). -°Olafur]

Thanks for the informative reply and I look forward to seeing the new NSC,
Rob Rolen