I provided the link to the abstract in this thread, right below the quote. I had to pay to get the full text. I'm not sure it completely proves curcumin causes cancer or has the other dangers, but humans have never been exposed to it in vivo due to it's lack of bio-availability. So effectively delivering it in a lipo form deserves caution, including knowledge of the published dangers. We have evolved to cope with compounds that can be made from low temp, low pressure, DNA-based "cells" and curcumin is an example of this class. But we have not specifically been exposed to it internally in the past, so it's not completely clear it should be treated as something safer than pharmaceuticals. If smaller mammals do not have the bio-availability problem, then maybe we still have some of the general genetic design that confers some protection to being exposed to it directly in the blood stream. This is the case with resveratrol, which does not have the dangers reported above for curcumin, and resveratrol is still not being delivered as effectively as the new curcumin forms are attempting. So that's two "orders of magnitude" that pure curcumin in the blood could be more dangerous than glucuronated and sulfonated forms of resveratrol in the blood.I haven't been provided a link, or study so I am continuing with this product.
Even large doses of resveratrol have to be considered carefully because they are way outside the range of evolutionary adaptation. Comparable examples are high dose selenium and I.V. vit C. The second most reliable result of taking resveratrol (as reported and tabulated in the resv forum) is fairly serious tendon and/or ligament injuries in those taking more than 1 g/day. No one knows the dangers of doing it long term. Again, just a brief look indicates that if someone takes a "deliverable" form of high-dose curcumin, they should expect much worse until research says otherwise. My comments do not apply if someone has a life-threatening disease that has a trial going on, like colon cancer, prancreatic cancer, or Alzheimer's. Then by all means, take resv and curcumin to the max.
Here is more from the 2005 "anti-curcumin" work:
Here, we report that
curcumin induces p53 degradation and, thus, inhibits p53-
induced apoptosis. Curcumin induced degradation of p53 under
conditions of defective ubiquitination, like several NQO1 inhibitors
including dicoumarol (14, 15, 20, 21, 23). Curcumin was also
shown to induce degradation of different proteins, including
cyclin D1 (39), p185ErbB2 (40, 41), c-Jun (42), CEBP, and
CEBP (43). It will be interesting to determine whether these
proteins are degraded by curcumin also by an ubiquitin independent
mechanism.
NQO1 is a flavoenzyme that catalyzes two electron reduction
of quinones and some other electrophiles by using NAD(P)H as
an electron donor. We found that curcumin inhibits NQO1
activity. Like dicoumarol that competes with NAD(P)H for
binding to NQO1, curcumin also disrupted WT p53-NQO1
complexes and induced p53 degradation. Curcumin inhibits the
activity of thioredoxin reductase (29), another flavoprotein that
uses NADPH as an electron donor (44). These findings suggest
that curcumin may displace NAD(P)H from NQO1 and possibly
also from other NAD(P)H using enzymes and, thus, inhibit their
activity.
Our studies have shown that curcumin and dicoumarol destabilize
WT p53 by inhibiting NQO1 activity and promoting the
dissociation of p53–NQO1 complexes. Curcumin and dicoumarol
might also affect p53–NQO1 interaction by causing
changes in the p53 molecule itself. Many of the cellular functions
of p53 are regulated by various redox regulating p53-interacting
proteins including thioredoxin (reviewed in ref. 15). Curcumin
inhibits the activity of thioredoxin reductase, resulting in reduced
binding of p53 to DNA, possibly due to changes in p53
folding (29). In addition to inhibiting NQO1 activity, curcumin
might, therefore, also change the folding of p53 in a manner that
disrupts NQO1–p53 complex formation. It was recently reported
that NAD and NADH bind to p53 tetramers and change their
conformation (45). NADH also induces a conformational
change in NQO1 (46) and increases p53–NQO1 interaction (22).
Thus, NAD(P)H could affect both p53 and NQO1 to promote
their interaction and p53 stabilization. We have shown that
NQO1 is physically associated with the 20S proteasomes and this
association prevents the degradation of p53 that is bound to
NQO1 (22). Thus, by displacing NAD(P)H and dissociating NQO1–p53 complexes, curcumin and dicoumarol promote the
ubiquitin-independent 20S proteasome-mediated degradation of
p53. We have previously shown that binding of NQO1 to the
human cancer hot-spot p53 R273H mutant was 3-fold higher
compared to its binding to WT p53 (23). The failure of dicoumarol
and curcumin to effectively dissociate NQO1–p53 R273H
complexes can explain the resistance of the p53 R273H mutant
to degradation by both of these compounds. However, R273H
can still be degraded by the ubiquitin-dependent pathway by
overexpression of Mdm2 (23) or by the ubiquitin-independent
pathway by knocking down NQO1 by siRNA.
22. Asher, G., Tsvetkov, P., Kahana, C. & Shaul, Y. (2005) Genes Dev. 19, 316–
321.
23. Asher, G., Lotem, J., Tsvetkov, P., Reiss, V., Sachs, L. & Shaul, Y. (2003) Proc.
Natl. Acad. Sci. USA 100, 15065–15070.
29. Moos, P. J., Edes, K., Mullally, J. E. & Fitzpatrick, F. A. (2004) Carcinogenesis
25, 1611–1617.
39. Mukhopadhyay, A., Banerjee, S., Stafford, L. J., Xia, C., Liu, M. & Aggarwal,
B. B. (2002) Oncogene 21, 8852–8861.
40. Hong, R. L., Spohn, W. H. & Hung, M. C. (1999) Clin. Cancer Res. 5, 1884–1891.
41. Tikhomirov, O. & Carpenter, G. (2003) Cancer Res. 63, 39–43.
42. Uhle, S., Medalia, O., Waldron, R., Dumdey, R., Henklein, P., Bech-Otschir,
D., Huang, X., Berse, M., Sperling, J., Schade, R. & Dubiel, W. (2003) EMBO
J. 22, 1302–1312.
43. Balasubramanian, S. & Eckert, R. L. (2004) J. Biol. Chem. 279, 24007–24014.
44. Mustacich, D. & Powis, G. (2000) Biochem. J. 346, 1–8.
45. McLure, K. G., Takagi, M. & Kastan, M. B. (2004) Mol. Cell. Biol. 24, 9958–9967.
Edited by zawy, 18 September 2009 - 01:48 PM.