5 replies to this topic

[Kalliste]

We've had endless discussions on how to increase the bioavailability of curcumin, so this is kind of interesting.

 

How does curcumin work with poor bioavailability? Clues from experimental and theoretical studies

Discussion

Despite a wide range of pharmacological activities of curcumin reported in the past decades, a paradox remains regarding the pharmacology of curcumin owing to its physicochemical properties leading to the poor systemic bioavailability. Moreover, although nature endows curcumin ideal molecular functionalities as enzymes inhibitors, which include two hydrophobic phenyl domains connected by a flexible α, β-unsaturated β-diketo linker, and the phenolic and carbonyl functional groups located on the ends and at the center of the molecule to potentially participate in hydrogen bonding with target biomolecules (Fig. 1), numerous in vitro experiments indicated the low potency in enzyme inhibition². The experimentally reported inhibitory activities of curcumin are much lower than those predicted based on its chemical structure^41,42.

Low stability has been considered to be a hurdle for the clinical application of curcumin. Based on our experimental comparison of the O₂^.–-scavenging activities and fAβ(1–42) formation inhibiting activities of curcumin and its degradation products mixture and theoretical docking studies of the molecular mechanisms of enzyme inhibition of curcumin, we proposed that the degradation products curcumin are actually the main bioactive molecules in executing the biological activities of curcumin.

Our conclusion is consistent with previous observations. First, curcumin and its metabolites always have poor bioavailability in vivo, even with high doses⁶, however, its pharmacological activities have been widely recognized. Our finding provides a plausible explanation to the apparently contradictory observations. Second, it has been found that curcumin and its degradation products also possess similar pharmacological profiles in anti-cancer, anti-inflammation and antimicrobial activities, which is consistent with our conclusion that the bioactive degradation products of curcumin are important contributors to its pharmacological activities^2,43,44. Third, a recent in vivo study showed that the degradation products aforementioned are the major human metabolites after curcumin consumption and their levels are much higher than those of curcuminoids¹⁶. Forth, when curcumin was added to inhibit lipoxygenase, the binding of selected degradation products rather than parent curcumin was proven by X-ray diffraction and mass spectrometry⁴⁵, providing direct evidence supporting our theory.

Conclusion

In summary, our novel experimental and theoretical findings suggested that the degradation products should play important roles in executing the biological and pharmacological activities of curcumin. Our finding not only provides a plausible explanation for the seemingly contradictory observations regarding biological activities of curcumin, it is also highly significant for the therapeutic application of this natural product against various human diseases.

http://www.nature.co...icles/srep20872

[joelcairo]

Not to comment on the merit or significance of this study, but it's consistent with what I have come to believe. There's a web blogger named Margaret who suffers from smoldering myeloma and who is a well-known proponent of curcumin. She has a slow-progressing disease and is in the interesting position of being able to monitor the objective and subjective effects of taking different forms of curcumin. She has experimented with "high-bioavailability" ones, but they don't work as advertised and she keeps going back to plain old hard-to-absorb, sweat-yellow-out-of-your-pores curcumin.

 

[Kalliste]

Also read her blog, it's very good. She and board local Timar motivates me to buy the fresh Turmeric roots.

[aribadabar]

going back to plain old hard-to-absorb, sweat-yellow-out-of-your-pores curcumin.

Curcumin or turmeric?

Edited by aribadabar, 01 March 2016 - 03:46 AM.

[joelcairo]

AFAIK she takes curcumin, although I was describing my own experience where you have yellow-tinged sweat when taking say 2-3+ grams a day. I wondered if I was crazy, but I looked it up online and found other people reporting the same thing.

 

Margaret's site is easy to find in Google. I forget if she takes the kind if curcumin that has piperine or not. It's a chronological blog, so you have to dig around a bit to find the most recent entry where she mentions what specifically she takes.

[niner]

One thing though-- Before you ever get metabolites, the curcumin has to get into the system.  That's what most of the formulation work in the fancy products is aimed at.  The question of whether metabolites and breakdown products are biologically active is legitimate and interesting.  It's important to have experimental endpoints that you can look at, whether that's plasma concentrations of the various curcuminoids, breakdown products, and metabolites, or (preferably) a biological response.  This paper is mostly theoretical, so it could use some experimental backup.   I think one of the notable accomplishments of this paper is shining a light on the breakdown products.  I don't recall seeing that in any of the papers looking at the PK of formulated curcumin.  Curcumin is complicated...