Study The Essential Medicinal Chemistry of Curcumin

[Genetic Freak]

Considering I generally include turmeric in most food preparations, the following paper makes for depressing reading:

The Essential Medicinal Chemistry of Curcumin

Kathryn M. Nelson, Jayme L. Dahlin, Jonathan Bisson, James Graham, Guido F. Pauli,
and Michael A. Walters

ABSTRACT:
Curcumin is a constituent (up to ?5% ) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (panassay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases.
No doubleblinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.

CONCLUSIONS: FUTURE CURCUMIN RESEARCH:
At first, curcumin appeared to offer great potential for the development of a therapeutic from a Natural product (turmeric) that is classified as a “generally recognized as safe” material. Unfortunately, no form of curcumin, or its closely related analogues, appears to possess the properties required for a good drug candidate (chemical stability, high water solubility, potent and selective target activity, high bioavailability, broad tissue distribution, stable metabolism, and low toxicity). The in vitro interference properties of curcumin do, however, offer many traps that can trick unprepared researchers into misinterpreting the results of their investigations.
With respect to curcumin/curcuminoids and in vivo studies and clinical trials, we believe there is rather “much ado about nothing”. Certainly, the low systemic exposure levels reported in clinical trials do not support its further investigation as a therapeutic..

http://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.6b00975

 

[CFC]

Thanks for posting mate. I'll be interested to read this more fully when I get a chance. The bioavailability issue is very well known which is why various delivery methods have been tried commercially.

 

[Swim15]

Interesting...gonna read more when I get a minute. Haven't looked in depth yet but would this apply to injectible curcumin?

 

[RedXIII]

curc is metabolized in the liver, almost killed off entirely. This can be circumvented by a prep dose of piperine, the active stimulant in black and white peppercorn and also the chem that gives the spice... its spice. A cup of (freshly ground) peppercorn tea roughly 15-20 min before dosing on curc will turn the almost useless stomach irritant into a wonder drug. The combination of pip and curc has effects that can be considered on par with other "smart drugs". This combination has to be taken with a decent meal to prevent stomach issues and even so there is the risk of experiencing "burning ring syndrome", which is just a fancy way of saying sometimes your asshole will burn for a min or so durring/after taking a shit. This is really the only negative side effect i have noticed (its nothing extreme, pretty much the sensation you get when using cheap toilet paper or irritating your bung-hole from excessive wiping).

This combination i take almost daily with my breakfast and include a vitamin B-complex pill, chewy multivitamin (Mmm) and a side of grapefruit juice (quinine). The effects i can compare to a mild dose of amphetamine without any of the horrendous side effects. Fantastic focus, energy and even a mood-lift (probably from the brain-fog being lifted). The days that i do not take this combination i find myself noticeably slower thinking, much less focused and just generally lethargic. It also works great as a hangover treatment, although it doesn't take care of the headache.

Curc is known for its anti-inflammatory properties along with being a good facilitator of digestion (along with piperine). Since starting this regiment i have also noticed a MASSIVE decrease in joint pain along with the dissipation of my 'ADHD' symptoms. In my past, opiate/oids were always my go to and pharmacutical amphetamines where always being pushed on me to 'fix' the attention and focus issues. The opiates almost killed me and the amphetamine made me want to kill myself, this combination is a god-send for me and i sware by it, even asking several friends to try the pepper/turmeric combo to see if it was more then a placebo and warm body rush from the black pepper tea. 3:3 agree that there is something going on, although not all that noticeable at first.

In conclusion, this cant be judged by the "effect" as if you are looking for a strong punch (or high rather) you wont get it from this. Imagine the focus and drive from amphetamine without any of the (forced) euphoria, high and negative side effects normally experienced with pharma-stims. The euphoria comes naturally when you notice that reading a book is quite enjoying now, playing chess is something you can now not only sit through but also enjoy. Focus that keeps you from losing your place in a paragraph and helps you to absorb the information and not just "read".

READ::: I CANNOT STRESS ENOUGH TO DO YOUR OWN RESEARCH!
This combination works great for me and a few of my friends but, can cause health issues and modify drug effects for certain people with certain drugs/supplements (especially the high levels of quinine in grapefruit). You are responsible for your own shit, dont blame me if you screw yourself up because you solely took the word of a forum phreak. Most, if not every (required by law?) vitamin and OTC supplement has "Do not take without consulting your doctor" scribbled on the side. It would be wise to at least invest some time researching these chemicals on your own and how they can interact with any substances you take (regularly and recreationally, even caffeine*) along with any medical conditions you may have that can be adversely effected.
(*piperine will make one cup of coffee have the effect of drinking a whole pot for me)


All that being said, I swear by it and practically live off this mix. Figured i would share something that has made, for me personally, a profound difference on mind and body.
Hope this helps.

Ps. anyone with more info on this combination they may have came across surfing around, please post. Im always looking for more on this as it doesn't seem too well studied.

 

[Swim15]

I've always used bioperine with curcumin/turmeric and never noticed anything like that but damn would I like to.

Do you guys have opinions on what would be more effective? A large dose of turmeric with bioperine or a small(er) dose of curcumin with bioperine?

 

[RedXIII]

I've always used bioperine with curcumin/turmeric and never noticed anything like that but damn would I like to.

Do you guys have opinions on what would be more effective? A large dose of turmeric with bioperine or a small(er) dose of curcumin with bioperine?

I have tried piperine/curcumin extract capsules in the past but, found myself also dosing on extra turmeric powder capsules and a side of pepper tea anyway. When the bottle ran dry, my daily dose turned to just the tea (albeit strong) and two (400mg i think) caps of turmeric powder. I didnt notice a difference. Unsure but, i think piperine and or curcumin break down rather quick and pre-packaged extracts dont seem worth the money when a coffee grinder and big tub of whole black peppercorn can be cheaply purchased anywhere. I know that piperine is pretty volatile and i notice a huge difference between pre-ground pepper and freshly ground so it wouldn't not surprise me if the extracts are hit or miss. I like to load up my coffee maker with half to a full cup of black pepper i just ran through the electric coffee grinder and use about 6 cups of water to get most of the goodies out. Turmeric seems to be fine in capsule form (still haven't worked out how to cook with it -.-) but the pepper is really what does the trick for me and I have had success for quite some time with just making tea. Ive grown to love the spicy taste and the warm body rush that spices generally give in high doses.

There is a pretty simple extract technique involving ethanol/water that can be done at home for a relatively pure piperine extract and they even went so far as to say it can be crystallized in its purest form, i dont think its worth the effort or the waste of booze

 

[Genetic Freak]

Curcumin is metabolized in the liver, almost killed off entirely. This can be circumvented by a prep dose of piperine, the active stimulant in black and white peppercorn and also the chem that gives the spice... its spice. A cup of (freshly ground) peppercorn tea roughly 15-20 min before dosing on curc will turn the almost useless stomach irritant into a wonder drug. The combination of pip and curc has effects that can be considered on par with other "smart drugs". This combination has to be taken with a decent meal to prevent stomach issues and even so there is the risk of experiencing "burning ring syndrome"...

From the limited research available addition of piperine shows slight increase in serum concentration:

There was an increase in the AUC though not significant and an increase in bioavailability of curcumin by about one and a half times as compared to curcumin given alone in both rats and humans.

Pl( parameters (Mean SEM) of curcumin when given alone and with piperine:
Cm, (observed values) when curcumin was given alone was only 0.006 +/- 0.005 ug/mL at 1 h..
Whereas when piperine was added the Cmax (observed value) was increased to 0.18 +/- 0.16 ug/mL and was attained earlier, i.e. at 0.75 h.

There is evidence that piperine is a potent inhibitor of drug metabolism, and glucuronidation altering the disposition and bioavailability of a large number of drugs. Further piperine at 20mg in humans has also been shown to produce earlier T-max, higher C-max and AUC of drugs like propranolol and theophylline. This property of piperine suggests that it may be involved in inhibiting the metabolism of curcumin and enhancing its bioavailability.

In conclusion, the study shows that piperine enhances the serum concentration and bioavailability of curcumin in rats and man probably due to increased absorption and reduced metabolism.

Atal, C. K., Dubey, R. K., Singh, J. J. (1985) Pharmacol. Exp. Ther. 232, 258—262.

Bano, G., Raina, R. K., Zutshi, U., Bedi, K. L, John, R. K., Sharma, S. C. (1991) Eur.J. Clin. Pharrnacol. 14,615—617.

http://sci-hub.bz/10.1055/s-2006-957450

 

[Genetic Freak]

Considering I generally include turmeric in most food preparations, the following paper makes for depressing reading:

The Essential Medicinal Chemistry of Curcumin

Kathryn M. Nelson, Jayme L. Dahlin, Jonathan Bisson, James Graham, Guido F. Pauli,
and Michael A. Walters

ABSTRACT:
Curcumin is a constituent (up to ?5% ) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (panassay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases.
No doubleblinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.

CONCLUSIONS: FUTURE CURCUMIN RESEARCH:
At first, curcumin appeared to offer great potential for the development of a therapeutic from a Natural product (turmeric) that is classified as a “generally recognized as safe” material. Unfortunately, no form of curcumin, or its closely related analogues, appears to possess the properties required for a good drug candidate (chemical stability, high water solubility, potent and selective target activity, high bioavailability, broad tissue distribution, stable metabolism, and low toxicity). The in vitro interference properties of curcumin do, however, offer many traps that can trick unprepared researchers into misinterpreting the results of their investigations.
With respect to curcumin/curcuminoids and in vivo studies and clinical trials, we believe there is rather “much ado about nothing”. Certainly, the low systemic exposure levels reported in clinical trials do not support its further investigation as a therapeutic..

http://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.6b00975

Bump..

 

[Lachdanan]

If you want piperine, White pepper is better than black, IIRC.