12 replies to this topic

[opales]

Ok, I have seen all these great reports about curcumin here, it seems especially promising in AD. However, I know MR has been suspicious about curcumin but have not been sure why. Today someone posted this at the CR society list, I can't remember has this ever been discussed here?

Megadosing of curcumin would not seem advisable:

"Studies with curcumin, given to rats and mice and to humans in phase
I trials, have shown an increased risk of developing hyperplasia in
the colon in rats, thyroid hyperplasia and liver adenoma in mice, and
progression of premalignant disease in some patients...Our finding
that curcumin induces degradation of the tumor suppressor WT p53 also
indicates that curcumin treatment in healthy people might lead to
accumulation of DNA-damaged cells by inhibiting their p53-induced
apoptosis."

Source: Proc Natl Acad Sci U S A. 2005 April 12; 102(15): 55355540.
Published online 2005 April 4. doi: 10.1073/pnas.0501828102.
Copyright © 2005, The National Academy of Sciences.

The full text is available online, free of charge, at:

http://www.pubmedcen...bmedid=15809436

or http://tinyurl.com/s4829

I bet the above mentioned properties of curcumin are not mentioned in LEF's curcumin review...

[FunkOdyssey]

Confusing, especially in light of these human results:

Wednesday, August 2, 2006

NEW YORK (Reuters Health) - Compounds found in curry and onions may help prevent colon cancer in those at risk, according to findings from a small study released this week.

In the study, patients with pre-cancerous polyps in the colon who took a pill containing a combination of curcumin, which is found in the curry spice turmeric, and quercetin, an antioxidant found in onions, experienced a marked reduction in both the size and number of polyps.

"We believe this is the first proof of principle that these substances have significant effects in patients with FAP (familial adenomatous polyposis)," Dr. Francis M. Giardiello of The Johns Hopkins School of Medicine in Baltimore said in a statement.

FAP is an inherited disorder characterized by the development of colorectal polyps and eventually colon cancer.

The potential of curcumin to prevent and/or treat cancer in the lower intestines surfaced in studies in lab rats fed curry, as well as in observational studies of Asian populations that consume a lot of curry. Quercetin has also been shown to have anti-cancer potential.

In their study, Giardiello and colleagues gave five FAP patients who had five or more polyps in their lower intestinal tract with 480 milligrams of curcumin and 20 milligrams of quercetin three times daily.

"All five patients had a decreased polyp number and size from baseline after a mean of 6 months," the team reports in the medical journal Clinical Gastroenterology and Hepatology.

The average number of polyps dropped by 60 percent, and the average size dropped by 51 percent.

Side effects were minimal. One patient experienced nausea and sour taste within a couple of hours of taking the pill, which subsided after three days and did not recur, and another patient reported mild diarrhea.

Of the two compounds, the researchers believe curcumin is the key cancer-fighting agent. "The amount of quercetin we administered was similar to what many people consume daily; however, the amount of curcumin is many times what a person might ingest in a typical diet," Giardiello explained.

The team says larger trials, comparing curcumin-quercetin capsules with dummy "placebo" pills, are needed to confirm these findings.

SOURCE: Clinical Gastroenterology and Hepatology, August 2006.

[neogenic]

Funk, this was with people with polyps. I am not sure this refutes the thought process above.

[FunkOdyssey]

Polyps in the colon are either a result of hyperplasia or they are premalignant adenomas.

Studies with curcumin, given to rats and mice and to humans in phase
I trials, have shown an increased risk of developing hyperplasia in
the colon in rats, thyroid hyperplasia and liver adenoma in mice, and
progression of premalignant disease in some patients

If curcumin causes hyperplasia, adenomas, and progression of premalignant disease, why is it eliminating / reducing colon polyps uniformly in these patients?

[opales]

There was an interesting and amusing response on the list, not hard on the science but rather good pointers nevertheless.

Thank you for this very important caveat, and for the full text link.

Curcumin has been on my phytochemical "back burner" for almost two years
after a strange experience with a myeloid dysplasia patient, who took it as
a supplement (containing 190 mg curcumins) on the advise of his ND - with
the result that his hemoglobin dropped within days to below 8 g/dL.
Fortunately, I did not take anymore curcumin supplements myself except as an
occasional spice. Then I read two months ago again so much good news about
curcumin, in PubMed and from other sources that I started adding
turmeric/curcumin in high doses to my rather extensive phytochemical regimen
- only to kick it out the minute after I read your post and the paper.

There are other examples of phytochemicals that have a dark side by acting
bi-phasic (inhibitory at low doses and up-regulating/promoting at high doses
or vice versa) or agonistic in one environment/context and antagonistic in a
different context.
Quercetin is one of them (inhibiting eNOS!), genistein (bi-phasic), curcumin
and green tea antagonistic on keratinocytes, indoles inhibiting SIRT1,
resveratrol (topical!) stimulating DNA damage under UVA irradiation, EGCG
promoting matrix metalloproteinase ....... etc. These are recent examples
from my growing list of caveats slowly filling a new "dark" folder.

All of which does not mean that we should not use these wonderful gifts of
nature to our best advantage, but we need to be very cautious, keep our eyes
open all the time for new research results, and find ways to roughly
determine appropriate doses. With herbs and phytochemicals in general,
low doses may not do much or nothing at all, so high doses may be required
for any kind of therapeutic effect, but - how high is enough or too high ?

I hope my WT p53s did not take too much beating from high-dose curcumin
and will recover within days being bathed in resveratrol, green and black
tea, pomegranate, ginger, acai, olive leaf, rosemary, blueberry and all the
other extracts plus pounds of fruits and vegetables and sunshine.

I think the above examples kind of reveal some of the uncertainties pertaining to many substances out there, and these things almost NEVER get mentioned in the biased reports of supplement industry or the optimistic hypings of on-line health forums (with an added touch of implanted viral marketers). This has been one of the reasons for my skeptical attitude regarding many substances, expecially as there seems to wide range of seemingly mundane (exercising, keeping calories under control) but extremely robustly supported interventions that people cannot even here always comply with yet are quick to make the desperate dive to more simplistic solutions in their surge of positive outcome bias.

BTW, again, I recommend ANYONE INTRESTED IN HEALTH ASPECT OF LIFE EXTENSION, whether CRing or not, to follow the CR society mailing list, it has very high quality discussions and even more impressive archives. This place would have helluva higher quality discussions if more people did that. Remember though, that because of (often) high level of discussion I think many newbie questions are frowned upon, which is good because it keeps the quality high and quantity manageable. So don't start dashing posts just for your own convinience there, do your reserch beforehand and if you still can't find an answer, then it may be appropriate to fire away. We certainly don't want to ruin or degrade their extremely useful list by adding irrelevant noice there, I think that becomes the eventual faith of many once-extremly-valuable on-line medias.

Join the CR society mailing list
http://lists.calorie...restriction.org

More lists and more info:
http://lists.calorie...restriction.org

The archive search function
http://cr.timtyler.org/search/

Edited by opales, 24 August 2006 - 02:55 PM.

[biknut]

I think the key word here is "Megadosing".

A lot of people seem to think if a little is good, then more must be better.

[scottl]

ALL colon cancer starts out as polyps.


The answer to these confusing results almost certainly lies in the fact that curcumin messes with one of the P450 class of enzymes (as does bioperine). This is probably why MR does not like it, as he does not like bioperine.

Firstly I need to state that I do not understand P450 in all its complexity. There was an article about it in mind and muscle mag a few months back.

The larger view of P450 when I learned about it was in terms of phase I and Phase II detoxification i .e. substances are first processed by phase I and then phase II enzymes. Sometimes the intermediate produced by phase I is a.....harmful substance and e.g. if one induced phase I detoxification enzymes, and phase II is not working well this is a problem as these harmful intermediates accumulate. Thus the effects of things which mess with the P450 system (there are many specific enzymes with their own names) are complex and depends on tbe state of the person's P450 system to begin with.

Edited by scottl, 24 August 2006 - 05:35 PM.

[xanadu]

I agree with biknut, it's likely the megadosing that has something to do with it. Curcumin in the form of tumeric has been used for thousands of years with great results. It just goes to show that if a little is good, a whole lot isn't always better.

[doug123]

Opales (Olli): don't you think the CR group members could fall victim to positive outcome bias as well? I'm not questioning their group or the integrity of the info there. I think the positive outcome bias would apply equally to everyone.

[opales]

Opales (Olli): don't you think the CR group members could fall victim to positive outcome bias as well?  I'm not questioning their group or the integrity of the info there.  I think the positive outcome bias would apply equally to everyone.

Yes of course, everyone is affected to a degree but some people more readily recognize it, I am not sure what you are after here. I do think many there have rather optimistic expectations about CR (not everyone), which quite possibly delievers only modest gains in life expectancy. But the fact they are practising CR in the first place, which can be difficult yet has MUCH more robust scientific support that any other (non mundane) intervention in terms of health, so that almost by default implies to me that people there are more realistic about the situation.

Anyway, there are quite prominent reseachers participating in discussions and many other active ones hold a Ph.D., plus a culture of rigorous scientific argumentation and debate leads to superiority of their list to that of any other on line forum in terms of health in my humble opinion.

[doug123]

I would trust that your evaluation of the information available at the CR group (which I have not visited yet) is accurate.

All of us are somewhat affected by biases of our own; and I think you would agree. It's always the best idea to begin by cross checking data for oneself, no matter who posts it. There are always going to be individuals who try to fool us into believing total nonsense and I've seen you destroy arguments based on ignorance and false authority with such style I'm still in awe.

An example is your posting in:

Most bang for buck for achieving immortality, MPrize vs. supps
http://www.imminst.o...T&f=6&t=8392&s=

In fact, it was your postings that FIRST informed me of the significance of the Mprize and the importance of supporting REAL life extension science rather than pills that have such exceptionally weak evidence to support their purported effects it's not even funny.

[opales]

I would trust that your evaluation of the information available at the CR group (which I have not visited yet) is accurate. 

All of us are somewhat affected by biases of our own; and I think you would agree.  It's always the best idea to begin by cross checking data for oneself, no matter who posts it.  There are always going to be individuals who try to fool us into believing total nonsense and I've seen you destroy arguments based on ignorance and false authority with such style I'm still in awe. 

Note that I especially recommend using the CR archives, they are AMAZING from health practitioners point of view. Most if not not all purportedly life extending supplements or health interventions have usually been discussed in detail there. My strategy on any given issue has been searching posts by individuals whom I consider reliable source of analysis (such as MR but also others), rather than read what your average "Joe the CR guy" has to say about it. I would read the whole discussions if I had more time, but restricting oneself to just few posters is a good way to reduce the noise without too much loss of valuable information.

Yes everyone is more or less utilizing some sort of heuristics; otherwise this place (universe) would just be too complex to handle. However, obviously some heuristics are better than others and it is especially useful to recognize the common-to-most-humans biases in one's own thinking. IMO, in addition to learning about the form of logical argument and logical fallacies, I think recognizing cognitive biases is one of the most efficient ways of improving one's thinking, it should be taught in the first grade!!!

Few useful links
http://en.wikipedia..../Cognitive_bias
http://en.wikipedia....ognitive_biases
http://en.wikipedia....wiki/Heuristics

Interestingly, Nick Bostrom stated in his closing presentation at Transvision 2006 that recognizing biases does not often lead to actually not complying with them, I guess they are just so deeply rooted in the hardwiring of human brains.
Here is Nick's (apparently incomplete) closing presentation webcast.

http://www.cs.helsin...incomplete).mov

Slides do not seem to be available but following paper covers the same information in form of a publication, it is about a method of eliminating the status quo bias in public policy discussions, and the method is applied to cgnitive enhancement especially.
http://www.nickbostr...s/statusquo.pdf

Ok, we are little off topic here [lol], this is actually MUCH more important than curcumin though.

[doug123]

To go off topic a bit more too. The reason I trust Michael is because I've checked his references and they check out. He knows where to extrapolate and where he can't. However, I'd like to see what he would say about the study I quoted below...

Michael said:

No supplement has ever shown a demonstrable increase in maximum LS in normal, healthy, well-cared-for organisms -- ie, relative to a control group with mean & max LS of >900 & 1200 days, respectively, in mice. By contrast, this is routinely achieved in modern CR studies.

Well -- it seems, by my cursory evaluation, there might be evidence to suggest otherwise

Life Sci. 1997;61(11):1037-44.

Treatment with L-deprenyl prolongs life in elderly dogs.Ruehl WW, Entriken TL, Muggenburg BA, Bruyette DS, Griffith WC, Hahn FF.

Deprenyl Animal Health, Overland Park, KS 66210, USA.

Eighty two beagle dogs ranging in age from 2.8 to 16.4 years and in weight from 6.3 to 15.8 kg were allotted to 41 pairs and administered placebo or 1 mg/kg L-deprenyl orally once daily for 2 years and 10 weeks. When survivorship for all dogs in the study was analyzed there was no significant difference between the L-deprenyl and placebo treated groups, most likely due to the (expected) survival of virtually all young dogs in both groups for the duration of the study. To assess whether L-deprenyl treatment begun in later life might enhance canine longevity in a fashion similar to that documented in rodents we also examined survival in a subset of elderly dogs who were between the ages of 10 and 15 yrs at the start of tablet administration and who received tablets for at least 6 months. In this subset, dogs in the L-deprenyl group survived longer (p < 0.05) than dogs in the placebo group. Twelve of 15 (80%) dogs in the L-deprenyl group survived to the conclusion of the study, in contrast to only 7 of 18 (39%) of the dogs who received placebo (P=0.017). Furthermore, by the time the first L-deprenyl treated dog died on day 427, 5 placebo treated dogs had already succumbed, the first on day 295. Specifically with respect to dogs, the findings reported herein suggest daily oral administration of 1 mg/kg L-deprenyl prolongs life when begun in relatively healthy dogs 10-15 years of age and maintained for the duration of the individual's life, but in any event for no less than six months.

PMID: 9307048 [PubMed - indexed for MEDLINE]

This study is a JOKE if you ask me. Deprenyl Animal Health -- THAT's a biased group if you asked me. It's like if I started the "supplment x acid Animal Health" group and published data to say the dogs lived an extra SIX months longer w/R-lipoc acid...I'd check how much extra cash the supplement x lobby stuck in my pocket if I were you...

Here's where I think that study went wrong (ALL kinds of bias -- in selection and otherwise -- to support their conclusion):

http://bmj.bmjjourna...ull/323/7303/42

Education and debate
Systematic reviews in health care
Assessing the quality of controlled clinical trials
This is the first in a series of four articles

Peter Jüni, research fellow a, Douglas G Altman, professor of statistics in medicine b, Matthias Egger, senior lecturer in epidemiology and public health medicine c.

a Department of Social and Preventive Medicine, University of Bern, Bern, 3012 Switzerland, b Imperial Cancer Research Fund Medical Statistics Group, Centre for Statistics in Medicine, Institute of Health Sciences, Oxford OX3 7LF, c Medical Research Council Health Services Research Collaboration, Department of Social Medicine, University of Bristol, Bristol BS8 2PR

Correspondence to: M Egger m.egger@bristol.ac.uk

The quality of controlled trials is of obvious relevance to systematic reviews. If the "raw material" is flawed then the conclusions of systematic reviews cannot be trusted. Many reviewers formally assess the quality of primary trials by following the recommendations of the Cochrane Collaboration and other experts. 1 2 However, the methodology for both the assessment of quality and its incorporation into systematic reviews and meta-analysis are a matter of ongoing debate.3-5 In this article we discuss the concept of study quality and the methods used to assess quality.

Components of internal and external validity of controlled clinical trials

Internal validity---extent to which systematic error (bias) is minimised in clinical trials

  * Selection bias: biased allocation to comparison groups

    * Performance bias: unequal provision of care apart from treatment under evaluation

    * Detection bias: biased assessment of outcome

    * Attrition bias: biased occurrence and handling of deviations from protocol and loss to follow up
    * External validity---extent to which results of trials provide a correct basis for generalisation to other circumstances

    * Patients: age, sex, severity of disease and risk factors, comorbidity
    * Treatment regimens: dosage, timing and route of administration, type of treatment within a class of treatments, concomitant treatments
    * Settings: level of care (primary to tertiary) and experience and specialisation of care provider
    * Modalities of outcomes: type or definition of outcomes and duration of follow up

Summary points

    Empirical studies show that inadequate quality of trials may distort the results from systematic reviews and meta-analyses
    The influence of the quality of included studies should routinely be examined in systematic reviews and meta-analyses
    The use of summary scores from quality scales is problematic---it is preferable to examine the influence of key components of methodological quality individually
    Based on empirical evidence and theoretical considerations, the generation and concealment of the allocation sequence, blinding, and handling of patient attrition in the analysis should always be assessed

Edited by nootropikamil, 25 August 2006 - 09:54 AM.