50 replies to this topic

[zoolander]

Bring it on.

Curcumin steps up to the plate................the pitch...........BOOM!

recent studies released this week

Immune system

Inhibition of homodimerization of Toll-like receptor 4 by curcumin.

Youn HS, Saitoh SI, Miyake K, Hwang DH.

USDA, ARS, Western Human Nutrition Research Center, and Department of Nutrition, University of California, Davis, Meyer Hall, One Shields Ave., CA 95616, USA.

Toll-like receptors play a key role in sensing microbial components and inducing innate immune responses. Ligand-induced dimerization of TLR4 is required for the activation of downstream signaling pathways. Thus, the receptor dimerization may be one of the first lines of regulation in activating TLR-mediated signaling pathways and induction of subsequent immune responses. LPS induces the activation of NF-kappaB and IRF3 through MyD88- or TRIF-dependent pathways. Curcumin, a polyphenol found in the plant Curcuma longa, has been shown to suppress the activation of NF-kappaB induced by various pro-inflammatory stimuli by inhibiting IKKbeta kinase activity in MyD88-dependent pathway. Curcumin also inhibited LPS-induced IRF3 activation. These results imply that curcumin inhibits both MyD88- and TRIF-dependent pathways in LPS-induced TLR4 signaling. However, in TRIF-dependent pathway, curcumin did not inhibit IRF3 activation induced by overexpression of TRIF in 293T cells. These results suggest that TLR4 receptor complex is the molecular target of curcumin in addition to IKKbeta. Here, we report biochemical evidence that phytochemicals (curcumin and sesquiterpene lactone) inhibit both ligand-induced and ligand-independent dimerization of TLR4. Furthermore, these results demonstrate that small molecules with non-microbial origin can directly inhibit TLRs-mediated signaling pathways at the receptor level. These results imply that the activation of TLRs and subsequent immune/inflammatory responses induced by endogenous molecules or chronic infection can be modulated by certain dietary phytochemicals we consume daily.

Cytotoxic effect of curcumin on Giardia lamblia trophozoites.

Perez-Arriaga L, Mendoza-Magana ML, Cortes-Zarate R, Corona-Rivera A, Bobadilla-Morales L, Troyo-Sanroman R, Ramirez-Herrera MA.

Departamento de Fisiologia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Guadalajara, Jalisco, CP 44340, Mexico.

Giardia lamblia is one of the most important worldwide causes of intestinal infections produced by protozoa. Thus, the search for new alternative therapeutic approaches for this parasitic disease is very important. Common drugs used to control and eradicate this infection, frequently exhibit side effects that force patients to abandon treatment. The present work evaluates the anti-protozoan activity of curcumin, the main constituent of turmeric. Axenic G. lamblia (Portland 1 strain) cultures were exposed to different concentrations of curcumin. Its effects were evaluated on parasite growth, adhesion capacity and parasite morphology. We also evaluated the capacity of curcumin to induce an apoptosis-like effect. All curcumin concentrations inhibited trophozoite growth and adhesion in more than 50% in dose and time dependent manner. Morphological changes were described as protrusions formed under the cytoplasmic membrane, deformation due to swelling and cell agglutination. Curcumin induced apoptosis-like nuclear staining in dose and time dependent manner. In conclusion, curcumin exhibited a cytotoxic effect in G. lamblia inhibiting the parasite growth and adherent capacity, induced morphological alterations, provoked apoptosis-like changes. Future in vitro and in vivo experiments are endowed to elucidate the effect of curcumin in an experimental model of G. lamblia infection, analyze the involvement of ion channels in the swelling effect of curcumin during an apparent osmotic deregulation in G. lamblia trophozoites. This will lead to the proposal of the action mechanism of curcumin as well as the description of mechanism involved during the activation process for the apoptotic-like effect.

Antio-oxidant

Curcumin activates defensive genes and protects neurons against oxidative stress.

Scapagnini G, Colombrita C, Amadio M, D'Agata V, Arcelli E, Sapienza M, Quattrone A, Calabrese V.

Institute of Neurological Sciences, National Research Council (CNR), Catania, Italy., Blanchette Rockefeller Neurosciences Institute, West Virginia University, Rockville, Maryland.

Spices and herbs often contain active phenolic substances endowed with potent antioxidative properties. We had previously shown that curcumin, the yellow pigment in curry, strongly induced HO-1 expression and activity in rat astrocytes. In the CNS, HO-1 has been reported to operate as a fundamental defensive mechanism for neurons exposed to an oxidant challenge. Treatment of astrocytes with curcumin upregulated expression of HO-1 protein at both cytoplasmic and nuclear levels, as shown by immunofluorescence analysis under laser-scanning confocal microscopy. A significant expression of quinone reductase and glutathione Stransferase, two members of phase II detoxification enzymes, was found in astrocytes exposed to 5-15 microM curcumin. Moreover, the effects of curcumin on HO-1 activity were explored in cultured hippocampal neurons. Elevated expression of HO-1 mRNA and protein were detected after 6 h incubation with 5-25 microM curcumin. Higher concentrations of curcumin (50-100 microM) caused a substantial cytotoxic effect with no change in HO-1 protein expression. Interestingly, pre-incubation (18 h) with curcumin resulted in an enhanced cellular resistance to glucose oxidase-mediated oxidative damage; this cytoprotective effect was considerably attenuated by zinc protoporphyrin IX, an inhibitor of heme oxygenase activity. This study gives additional support to the possible use of curcumin as a dietary preventive agent against oxidative stress-related diseases.

PMID: 16677086 [PubMed - in process]

Anti-arthritic

Turmeric extracts containing curcuminoids prevent experimental rheumatoid arthritis.

Funk JL, Oyarzo JN, Frye JB, Chen G, Lantz RC, Jolad SD, Solyom AM, Timmermann BN.

Arizona Center for Phytomedicine Research, Department of Medicine, Department of Cell Biology and Anatomy, University of Arizona, Tucson, 85724, USA. jfunk@u.arizona.edu

Turmeric has been used for centuries in Ayurvedic medicine as a treatment for inflammatory disorders including arthritis. On the basis of this traditional usage, dietary supplements containing turmeric rhizome and turmeric extracts are also being used in the western world for arthritis treatment and prevention. However, to our knowledge, no data are available regarding antiarthritic efficacy of complex turmeric extracts similar in composition to those available for use as dietary supplements. Therefore, the studies described here were undertaken to determine the in vivo efficacy of well-characterized curcuminoid-containing turmeric extracts in the prevention or treatment of arthritis using streptococcal cell wall (SCW)-induced arthritis, a well-described animal model of rheumatoid arthritis (RA). Arthritic index, a clinical measure of joint swelling, was used as the primary endpoint for assessing the effect of extracts on joint inflammation. An essential oil-depleted turmeric fraction containing 41% of the three major curcuminoids was efficacious in preventing joint inflammation when treatment was started before, but not after, the onset of joint inflammation. A commercial sample containing 94% of the three major curcuminoids was more potent in preventing arthritis than the essential oil-depleted turmeric fraction when compared by total curcuminoid dose per body weight. In conclusion, these data (1) document the in vivo antiarthritic efficacy of an essential oil-depleted turmeric fraction and (2) suggest that the three major curcuminoids are responsible for this antiarthritic effect, while the remaining compounds in the crude turmeric extract may inhibit this protective effect.

PMID: 16562833 [PubMed - indexed for MEDLINE]

More info about curcumin (in the form of a PDF monograph) can be found here

[FunkOdyssey]

What are your thoughts on the addition of bioperine to curcumin formulations in an effort to increase absorption by inhibiting cytochrome p450? Seems to be a very controversial topic.

[FunkOdyssey]

The best value I can find for curcumin w/o bioperine is Now Foods Curcumin, which sells for $7.50 for 60 caps of 655mg 95% curcuminoid extract at papanature.com. They use a high quality branded raw material, Sabinsa Curcumin C3 Complex:

http://www.curcuminoids.com/home.htm

If anyone finds anything better/cheaper, let me know.

[scottl]

What are your thoughts on the addition of bioperine to curcumin formulations in an effort to increase absorption by inhibiting cytochrome p450?  Seems to be a very controversial topic.

I believe AORsupport brought this to our attention and you can search his posts, though Zoolander and I have discussed this several times as well. I'm still in the avoid the stuff camp.

[FunkOdyssey]

Ah yes... I'll save everyone some time here:

When we saw the enhanced bioavailability conferred on curcumin by piperine, AOR was initially excited, as bioavailability of curcumin in humans is very low (and proportionately much lower than in rodents, in whom very promising research has been performed). Once we began digging into the research on this substance, however, we concluded that it would be irresponsible to systematically increase exposure to this phytochemical.

It's worth gaining some understanding of exactly why piperine enhances the bioavailability of some substances (and only some: there seems to be a widespread belief in the industry that piperine enhances absorption of all nutrients, such that you see piperine mixed in with almost any supplement you care to mention -- even basic multivitamins). While there are several mechanisms at work, the primary one is the inhibition of detoxification enzymes, including a highly nospecific effect on the Phase I (cytochrome P450) enzymes, and an impairment of glucuronidation (a Phase II conjugation process). Piperine is "a potent inhibitor of UDP-GDH [UDP-glucose dehydrogenase (UDP-GDH)]” and of "glucuronidation potentials of rat and guinea pig liver and intestine" [1]. It is "a nonspecific inhibitor of drug metabolism which shows little discrimination between different cytochrome P-450 forms. Oral administration of piperine in rats strongly inhibited the hepatic AHH [arylhydrocarbon hydroxylase] and UDP-glucuronyltransferase activities." [2] "Piperine caused a concentration-related decrease in UDP-glucuronic acid content and the rate of glucuronidation in the [intestinal] cells. ... Rate of glucuronidation ... was dependent on the endogeneous level of UDP-glucuronic acid. At 50 microM piperine, the rate of glucuronidation was reduced to about 50% of the basal rate. Piperine caused noncompetitive inhibition of hepatic microsomal UDP-glucuronyltransferase with Ki of 70 microM." [3]

Substances whose bioavailability is inhibited by being biotransformed by these enzymes will therefore have their bioavailability enhanced by piperine. This is the basis, in particular, for its enhancement of curcumin bioavailability. The problem with this is that these enzymes also protect us from a variety of toxic substances -- which is, after all, why we have them in the first place.

Thus, "piperine was found to promote DNA damage and cytotoxicity induced by benzo[a]pyrene (B[a]P [a carcinogenic compound formed as a result of incomplete combustion of organic materials, found in engine exhaust, coal-, oil-, and wood-burning stove emissions, poorly-tuned furnaces, cigarette smoke, industrial soot, charred foods, incinerators, coke ovens, and asphalt processing, and secondarily in contaminated drinking water] in cultured V-79 lung fibroblast cells ... due to mechanisms that decrease the activities of [the detoxification enzymes] GST [glutathione S-transferase] and UDP-GTase [uridine diphosphate glucuronyl transferase] and increase the formation of a B[a]P-DNA adduct.” [4] Likewise [3] finds that piperine inhibits the "Rate of glucuronidation of 3-hydroxybenzo (a) pyrene ... dependent on the endogeneous level of UDP-glucuronic acid. "

It also "enhances the bioavailability of aflatoxin B1 in rat tissues," although the net effect of this is unclear [5]; aflatoxin is a mycotoxin that often contaminates corn and peanuts that are not kept dry and refrigerated, and is still a major cause of hepatocelluar carcinoma in China and much of the developing world. While under control in OECD countries, it is certainly not absent from the food supply, and enhancing its bioavialability is prima facie a bad idea.

Independently of impaired detoxification, "Piperine ... also reacted with nitrite and produced compounds showing mutagenicity in bacteria without metabolic activation." [6]

It should be noted that in other models, piperine appears to be protective against aspects of the cancer process, but the state of research is not clear enough to allow anyone to perform a reliable risk-to-benefit analysis of piperine. Healthy life extensionists, in our judgement, should avoid it.

To your health!

AOR

1. Reen RK, Jamwal DS, Taneja SC, Koul JL, Dubey RK, Wiebel FJ, Singh J. Impairment of UDP-glucose dehydrogenase and glucuronidation activities in liver and small intestine of rat and guinea pig in vitro by piperine. Biochem Pharmacol. 1993 Jul 20;46(2):229-38.

2. Atal CK, Dubey RK, Singh J. Biochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism. J Pharmacol Exp Ther. 1985 Jan;232(1):258-62.


3. Singh J, Dubey RK, Atal CK. Piperine-mediated inhibition of glucuronidation activity in isolated epithelial cells of the guinea-pig small intestine: evidence that piperine lowers the endogeneous UDP-glucuronic acid content. J Pharmacol Exp Ther. 1986 Feb;236(2):488-93.

4. Chu CY, Chang JP, Wang CJ. Modulatory effect of piperine on benzo[a]pyrene cytotoxicity and DNA adduct formation in V-79 lung fibroblast cells. Food Chem Toxicol. 1994 Apr;32(4):373-7.

5. Allameh A, Saxena M, Biswas G, Raj HG, Singh J, Srivastava N. Piperine, a plant alkaloid of the piper species, enhances the bioavailability of aflatoxin B1 in rat tissues. Cancer Lett. 1992 Jan 31;61(3):195-9.

6. Wakabayashi K, Nagao M, Sugimura T. Mutagens and carcinogens produced by the reaction of environmental aromatic compounds with nitrite. Cancer Surv. 1989;8(2):385-99.

That it enhances bioavailability of some (again, not all) substances is not disputed. The point, again, is that glucuronidation is a central detoxification process. Unless you have a totally toxin-free diet -- no overcooked foods, no pesticide residues in your meats and vegetables, no trace quantities of mycotoxins in your bread, etc -- and unless you have no sex steroids in your system, you rely on these processes to protect you against cancer on a continuous basis. Inhibiting them for a few hours every day to get better bioavailability out of your supplements is rather to mix up one's priorities.

To your health!

AOR

[scottl]

Thanks for digging them out.

[doug123]

The best value I can find for curcumin w/o bioperine is Now Foods Curcumin, which sells for $7.50 for 60 caps of 655mg 95% curcuminoid extract at papanature.com.  They use a high quality branded raw material, Sabinsa Curcumin C3 Complex:

http://www.curcuminoids.com/home.htm

If anyone finds anything better/cheaper, let me know.

I would hate to jump in with a dose of VIRAL MARKETING...but in this case I can say you asked for it. Sabinsa is a great company -- they have WHO (World Health Organization) and OU (Orthodox Union) Kosher certification on their entire operation. I do not mess with Bioperine -- it seems it allows too much in...



I just ordered 1 kilo of Sabinsa's Curcumin C3 extract. Here is the COA from the last batch -- a limited edition "embargoed" batch that has already sold out -- I had for sale previously:

http://nootropics.ip...-1117559847.jpg

The bottler split the kg into 10 100 gram containers; we are selling each 100g for $15 each. It's much more affordable in raw material form. If you don't know how to encapsulate your own powders; all you need is a scale and follow this guide I made. http://nootropics.ip...p?showtopic=602 or you can use cap em quick.

We also give away 1,000 free Torpac Capsules with every order over $100 -- when I get un lazy enough, I'll have to make a page to sell the capsules. I thought it would be better to just give them away.

Here is the COA for the capsules; which I paid Torpac $0.50 to place into bags of 1,000 when I ordered 75,000.

http://nootropics.ip...-1114064482.jpg

When I get the COA for the new batch, I'll upload it and post a link here. The following Sabinsa products shipped from the bottling facility: they won't be in stock for probably another week or so. I'll let you know as soon as they are available (ready to ship).

Forslean 10%
http://www.forslean.com/

Silbinol
http://www.silbinol.com/

Bacopin 50%
http://www.bacopin.com/

N-Acetyl-L-Cysteine

Curcumin C3 Complex
http://www.curcuminoids.com/

Grape Seed Extract

Shilajit 20%

Green Tea Extract 75% Decaf

Oh, and in case you are wondering if I am selling these out of my apartment -- NO! I am not. No more of that....I don't think I want any more problems with the goverment. I'm sure they are keeping a close eye on me anyways.

Peace.

Edited by nootropikamil, 10 May 2006 - 09:49 PM.

[tedsez]

What's the difference in price, dosage and effectiveness between taking one of these circumin supplements and adding, say, half a teaspoon of turmeric to your food every day?

[scottl]

FWIW the bioperine story is a lot more complicated as Zoolander tried to tell me...awhile back. I still think I'll pass, but judge for yourself:

http://www.mindandmu...showtopic=23700

[doug123]

That's good info, Scott; thank you for posting that. I'm interested in stellar and section8's viewpoint. Those cats know their stuff. I can't post there anymore -- they banned me for posting a link to a COA at a competitor site -- oh well.

Liorr is playing devil's advocate in that topic. He's good at that. It promotes more discussion.

[zoolander]

The response by AOR supports is good

[thumb]

Jarrow sell a curcumin supplement without bioperine in it

Supplement Facts
Serving Size: 1 Capsule
Servings per container: 60
                                Amount Per Serving  % Daily Value 
Curcumin                                    380 mg                          *
Demethoxycurcumin                      90 mg                            *
Bisdemethoxycurcumin                      15 mg                            *
Other Turmeric Substances            15 mg                          *

*Daily value not established.

Edited by zoolander, 11 May 2006 - 09:02 AM.

[doug123]

Jarrow is a great company -- they have been around for 30 years. I am 99.99% sure that they use Sabinsa's C3 as well in their formulas.

[xanadu]

What's the difference in price, dosage and effectiveness between taking one of these circumin supplements and adding, say, half a teaspoon of turmeric to your food every day?

That's a very good question, tedsez. I'm not so sure that extracts are always the best way to go. Mightn't one just buy tumeric and cap it up? It would take more to equal the extract but you would be getting all the goodies in the spice, not just what the solvents took out. It was the effects of the whole spice that caught the attention of health specialists. People in India don't use extracts. A solvent will tend to take out certain things and leave behind others. How can we be sure the solvent is taking out just what we want and not leaving behind something important?

[doug123]

Those are all keen observations, xanadu; however, proper standardization of an herbal extract basically concentrates the active constituents considered to be effective in producing whatever effect the herb itself is supposed to achieve. In this case, it's Tumeric's roots’ three main curcuminoids.
See the following page by this guy to see why it might be better to take the standardized extract: Also: besides having WHO and OU certification on their operation -- Sabinsa also has indepedent NSF testing performed on their C3 extract.

Here is a statement from Sabinsa's current president, Todd Norton -- he goes a bit into standardization here:

What are the major problems with quality control facing the natural products industry?
Todd Norton, president, Sabinsa Corp.: One--the lack of generally accepted assay methods and reporting of active ingredient percentages. There is a significant problem in this industry with companies buying ingredients and relying solely on what is reported on the product certificate of analysis to assure quality. Some ingredients report an assay based on HPLC, and others report it based on UV or gravimetric or something else. Either way, the results are bound to differ. Take guggul extract, for example. Sabinsa offers a minimum 2.5 percent Guggulsterone Z&E content in our Gugulipid product, as shown in clinical studies to be responsible for therapeutic benefits. We measure our guggulsterone content by HPLC to be precise. We compete against other generic guggul extracts that claim to offer 10 percent guggulsterones, yet when pressed on the method of analysis used to determine this percentage, the answer is either by UV, or "I don't know." So, what levels of guggulsterone Z&E do they really contain? And what is it exactly that constitutes the 10 percent assay? Now let's fast forward to the retail shelf. If two guggul products are side by side and one claims 10 percent while the other claims 2.5 percent guggulsterones, assuming they are similarly priced, which one will the consumer likely buy? Some manufacturers, when seeking the higher potency listed on a competitor's label then feel compelled to modify their product also. Does anybody along the way ask the question whether the jump to a higher assay is practical, necessary or possible in the first place? Sadly, the matter is best summed up by a comment made by industry consultant Jay Jacobowitz: "It's remarkable that in our industry it is 'news' when potency matches label claims."

Two--the lack of substantiated agreement on what actives are responsible and in what percentages for certain health benefits in botanicals. Look no further than to the media-beating this industry took over St. John's wort not long ago. After all, as long as it's St. John's wort, it's all the same, isn't it?

And third--too much downward pressure on pricing. I am a firm believer that in most instances you get what you pay for. The trend toward constantly chasing the lowest price is taking an adverse toll on product quality. What is basically happening is the barriers to entry to be a supplier of ingredients keep getting lowered, yet industry manufacturers increasingly expect suppliers to provide more documentation, product testing and marketing support. This is an inverse relationship, and it only can last for so long before something gives.

My father worked in the poultry industry for nearly 20 years. His company adopted the following motto and I think it is appropriate: "The bitterness of poor quality will remain long after the sweetness of low price is forgotten." Sound words of wisdom for any industry, especially one professing to transform the "snake oil" persona that shows up repeatedly in the mass media. Quality, or the lack thereof, does come with a price. It is up to the industry to decide where they will pay.

What types of QC certifications do you hold?
Sabinsa is the sales and marketing arm for our manufacturing operation SAMI Labs Inc., which is located outside the United States. SAMI Labs recently obtained World Health Organization (WHO) certification for its manufacturing operations.

How did you determine whether to hold a QC certification, and what does it offer you and your customers in the marketplace?

Sabinsa has a number of agents worldwide that represent our product line, many of which are affiliated with the European Union. We felt that WHO certification would best serve our diverse customer base and be universally recognized in the major international markets where we have a presence.

What do you do to ensure the quality of the raw materials you supply?

People need to remember that we are dealing with plant products that can, and do, change depending on which region they come from and the season in which the are harvested. The Sabinsa/SAMI operation is 100 percent vertically integrated. In some instances we control the cultivation of certain botanicals, and go so far as to provide our farmers with the seedling plants to ensure the right species is grown. When purchasing raw materials from outside sources, such as small villages or collection groups, we have a procurement team that travels with a portable testing equipment to quickly assess the identity and potency. If further testing is required we send the materials to our lab in the corporate office. Based on these results we either purchase or we dont.

What types of tests do you conduct on raw materials, and how do you determine the testing methods used?

The first thing to do is confirm with an identity test, usually thin layer chromatography (TLC), that you have the correct species of plant. Once confirmed, and before production begins on any of our standardized extracts, we first determine the assay value of our starting material. From here we can determine if any modifications are required to our manufacturing process. The whole idea of a standardized botanical extract is to provide the same percentage of active constituents from batch to batch. Testing the finished material varies depending on what the product is standardized for. Wherever possible an HPLC method of analysis is recommended due to the high degree of accuracy and reproducibility it offers. This is a good method to use when you want to identify a specific compound. Some products, however, contain a mixture of compounds that provide the activity. The methods generally used for testing in these instances are UV spectrophotometry or gravimetric. These methods identify compounds that are similar in chemical structure, thereby giving a cumulative percentage of their presence in the material. The methodology used is a function what you are testing for in the product. There are also other sophisticated methods and equipment available that can test for things like residual solvents and pesticide levels.

Edited by nootropikamil, 11 May 2006 - 05:57 PM.

[doug123]

Attached is a .pdf that is essentially a write up on Sabinsa's “Super Critical Fluid Extraction” plant. You should take a look at this technology they developed.

Attached Files

•  Sabinsa__s_SCFE_plant.pdf   110.96KB   83 downloads

[scottl]

It's an interesting argument, and I've said the same thing as xanadu...perhaps it was to AORsupport before. Standardized extracts ONLY WORK if you actually got all the good parts (which assumes you know what they are). OTOH if you don't use standardized extracts things vary more from batch to batch and company to company.

I would probably use the extract for this stuff. For published studies it is better if they use an extract..for a number of reasons. For myself and clients...depends on if I have a good source. If so, I'm liable to use the non-extract. GIngko comes to mind and an herbalist I know told me that the standardized extracts have most of the properties of the herb, but were missing one...I forget the details. Which gets back to my idea fixx (sp?) it's an art, however much we pretend it's a science.

[Shepard]

FWIW, Paul/Tom at MoreLife uses bioperine with his turmeric. I think he stated that turmeric was so important, he felt the benefits outweighed the risks. But, his situation is different from most of us.

[Pablo M]

An ND for a company I have sparred with says bioperine "enhances nutrient absorption by facillitating passage" through the stomach lining or some such. Studies suggest it may do this, but its more powerful and potentially damaging effects are in regaards to cytochrome P450. This company puts bioperine in EVERYTHING. The stupid motherf---ers.
http://www.progressivenutritional.com/

[scottl]

An ND for a company I have sparred with says bioperine "enhances nutrient absorption by facillitating passage" through the stomach lining

AFAIK no nutrients are absorbed through the stomach (alcohol and asprin I think are), only the small intestine, so that is...an interesting opinion.

And I think Paul from morelife did not for a long time.

Edited by scottl, 11 May 2006 - 11:22 PM.

[Shepard]

And I think Paul from morelife did not for a long time.

Maybe he saw some of the literature that trouble cited regarding bioperine. He seems to keep up to date on most things. I haven't read through all of what she posted yet, so I'm just assuming it was as credible as most of her posts.

[zoolander]

add this one to your list boys and girls

Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1.

Bae MK, Kim SH, Jeong JW, Lee YM, Kim HS, Kim SR, Yun I, Bae SK, Kim KW.

College of Dentistry, Pusan National University, Busan 602-739, Korea.

Hypoxia-inducible factor-1 (HIF-1) has a central role in cellular responses to hypoxia, including the transcriptional activation of a number of genes involved in angiogenesis in tumors. We found that curcumin, a natural, biologically active compound isolated from the commonly used spice turmeric, significantly decreases hypoxia-induced HIF-1alpha protein levels in HepG2 hepatocellular carcinoma cells. Moreover, curcumin suppressed the transcriptional activity of HIF-1 under hypoxia, leading to a decrease in the expression of vascular endothelial growth factor (VEGF), a major HIF-1 target angiogenic factor. Curcumin also blocked hypoxia-stimulated angiogenesis in vitro and down-regulated HIF-1alpha and VEGF expression in vascular endothelial cells. These findings suggest that curcumin may play pivotal roles in tumor suppression via the inhibition of HIF-1alpha-mediated angiogenesis.

PMID: 16685395 [PubMed - in process]

[stellar]

That's good info, Scott; thank you for posting that.  I'm interested in stellar and section8's viewpoint.  Those cats know their stuff.  I can't post there anymore -- they banned me for posting a link to a COA at a competitor site -- oh well.

Liorr is playing devil's advocate in that topic.  He's good at that.  It promotes more discussion.

Should you take a laundry list of supplements with piperine/bioperine? Definitely not.


But with Curcumin or Green Tea, I really dont see it as an issue. I usually mix my curcumin with some noodles and add 1/5 tsp black pepper (piperine makes up 5-7% of black pepper).

As I posted that chart over at M&M, there are a ton of things that inhibit/decrease CYP450. Bacopa, Silymarin, even Vitamin D.

[doug123]

I see what you are saying, stellar, dude.

But I just don't see the risk/return as favorable enough to mess with it. I can say I like your approach because it's more down to earth -- you just are taking black pepper itself-- and not piperine extract.

What AORsupport seems to suggest is that piperine is particularly powerful at messing with our critical detoxification enzymes -- which a lot of compounds may be affected by -- to various degrees. It's the degree of the effect he seems to be emphasizing may be a problem with respect to "letting too much in;" and as a life-extensionist, it's good to be careful to watch out for traps baited with hype. Miracle pills don't exist; so if something sounds too good to be true -- it probably isn't -- and might have an added nastiness you might not be aware of. It's good to be as speculative as possible when considering what compounds we take in hopes of an extended lifespan -- especially when they may open our "pores" to more potentially harmful environmental toxins. Of my all-time favorite MR quotes is this:

It would be one thing to take such a risk if you were (for instance) at short-term risk of massive AGE-related pathology, such as diabetic complications; it is quite another when one is essentially healthy and thus has relatively little to gain, and much to gamble away. (If you think about it, in fact, pharmaceutical standards are set precisely for people who do have life-threatening illness, and the presence of more than trace amounts of contaminants are still not considered to be an acceptable tradeoff for a few dollars saved). There would be little more bitter than to spend years pursuing extended youth, health, and longevity, only to discover that one has actually been poisoning oneself with the very substances which one has been swallowing in hopes of extended lifespan.

P.S. Stellar, dude:

Are you try to tease me -- when you say laundry list? [lol] Maybe I'm just paranoid. Peace.

[zoolander]

Some more research about curcumin for the social bunnies (rats) who drink and smoke

Mol Cell Biochem. 2006 May 12; [Epub ahead of print] 

Curcumin Combats Against Cigarette Smoke and Ethanol-Induced Lipid Alterationsin Rat Lung and Liver.

Vanisree AJ, Sudha N.

Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600033, Tamilnadu, India.

    Background: Human population, in spite of the medical and scientific achievements, still fall as a prey to the evils of habitual smoking and alcohol, thus necessitating safer counteracting measures. Objective: To evaluate the effect of cotreatment of curcumin (Curcuma longa) in rats subjected to acute exposure to cigarette smoke (CS) and ethanol (EtOH).  Methodology: Of the four groups of experimental rats, a set of rats was subjected to whole body exposure to cigarette smoke along with ethanol administration serving as a model of CS+EtOH injury. Curcumin treatment was given to two sets of rats: (i) one set receiving simultaneous CS+EtOH and (ii) one set of normal rats without any administration. The other group of rats served as control. Blood, liver and lung of rats were selected for assessment of CS+EtOH injury as well as curcumin treatment. Result: Altered lipid, lipoprotein profile and bile acid excretion were observed in CS+EtOH rats along with premalignant pathological state in tissues. In treated rats, the levels were maintained at near-normal levels along with near-normal histology. Conclusion: This biochemical picture on cotreatment with curcumin suggests that curcumin could counteract the injurious effects of combined CS and EtOH and thus might help to reduce the risk of hyperlipidemic disorders which develop due to smoking and drinking.

    PMID: 16691314 [PubMed - as supplied by publisher]

[Athanasios]

Zoolander,

How much are you planning to take, two or three grams?

[meatwad]

I'm not zoolander but why not a teaspoon with a curry or vindaloo once a day.

I have been adding a few sprinkles to my food for a few months now, I don't see myself capping this and eating it as a pill unless somebody pre-caps it and sells it for a reasonable price.

[Athanasios]

Because you need Curcumin that is an extract from tumeric. I believe it is about 3-5% the composition of the normal spice, and to get enough Curcumin that it is detectable in the blood stream, it is said, you must intake at least 2Gs. That is a lot of curry.

[zoolander]

Zoolander,

How much are you planning to take, two or three grams?

I am planning on taking and recommending 500-1000mg of an extract "Curcuma 95"

For example:

Turmeric (Curcuma longa Linn.) Extract (95% Curcuminoids) ....... 500 mg *
Typical Distribution/Distribution type:
Curcumin (diferuloylmethane) .......................................... 365 mg *
Demethoxycurcumin ........................................................ 80 mg *
Bis-Demethoxycurcumin ................................................... 10 mg *
Other curcuminoids ......................................................... 20 mg *

Cnorwood19, I have sent you a clinical plan trial paper re. curcumin. I have loosely based my decision from this paper. Research data with Humas is fairly hard to come by with curcumin.

[opales]

Research data with Humas is fairly hard to come by with curcumin.

You know, some people might consider that a reason not to take longterm supradietary amounts just yet. What do you think of this?:

http://www.imminst.o...94

[zoolander]

I am aware of curcumins prooxidant potential. Some suggest that curcumins prooxidant activity is beneficial

Anticancer Res. 2005 Nov-Dec;25(6B):4029-36. 

Induction of cytotoxicity and apoptosis and inhibition of cyclooxygenase-2 gene expression, by curcumin and its analog, alpha-diisoeugenol.

Atsumi T, Murakami Y, Shibuya K, Tonosaki K, Fujisawa S.

Department of Human Development and Fostering, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.

    Cytotoxici and alpha-diisoeugenol were investigated. The cytotoxicity of curcumin and a-diisoeugenol against human promyelocytic leukemia cells (HL-60 cells) and human submandibular cancer cells (HSG cells) was similar (CC50 1-3 microM). However, curcumin induced much more apoptosis, particularly in HL-60 cells compared with HSG cells, as revealed by measurement of the sub-G1/G0 DNA fraction in flow cytometric histograms. Treatment with 15 microM curcumin increased the number of cells with a sub-G1/G0 DNA fraction from control levels of <5% to 55% in HL-60 cells and 30% in HSG cells. Flow cytometry, after staining with annexin V-FITC/PI (the exposure of phosphatidylserine (PS) on the surface of apoptotic cells), showed a dose-dependent induction of early apoptosis by curcumin, which reached about 65% in HL-60 cells and about 20% in HSG cells after treatment with 10 microM curcumin. In contrast, alpha-diisoeugenol failed to induce apoptosis in either cell type. For both cell types, the proportion of late apoptotic/necrotic cells increased rapidly at concentrations of curcumin and a-diisoeugenol greater than 10 microM. The generation of intracellular reactive oxygen species (ROS) in curcumin-treated HL-60 cells was greater than that in HSG cells, as judged by CDFH-DA staining. In both cell types, ROS generation by a-diisoeugenol was at control levels. ROS generation by curcumin was suppressed by antioxidants such as N-acetyl-L-cysteine (NAC) and glutathione (GSH) and by scavengers of hydroxy radicals such as mannitol, but, conversely, was promoted by prooxidants such as the transition metal ions Cu(II) and Zn(II). ROS generation may play a part in the exposure of PS. Curcumin, but not a-diisoeugenol, at 10 microM inhibited LPS (lipopolysaccharide)-induced COX-2 gene expression in RAW 264.7 cells. Semiempirical PM 3 calculations suggested that this activity of curcumin, in which it behaves as a non-steroidal anti-inflammatory drug (NSAID)-like compound, is dependent on its phenolic function, which is more pronounced than that of alpha-diisoeugenol. Taken together, our results suggest that the bioactivity of curcumin is a result of its ability to act as both a prooxidant and an antioxidant.

    PMID: 16309195 [PubMed - indexed for MEDLINE]

Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity.

Fang J, Lu J, Holmgren A.

Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, SE-17177 Stockholm, Sweden.

The thioredoxin reductase (TrxR) isoenzymes, TrxR1 in cytosol or nucleus and TrxR2 in mitochondria, are essential mammalian selenocysteine (Sec)-containing flavoenzymes with a -Gly-Cys-Sec-Gly active site. TrxRs are the only enzymes catalyzing the NADPH-dependent reduction of the active site disulfide in thioredoxins (Trxs), which play essential roles in substrate reductions, defense against oxidative stress, and redox regulation by thiol redox control. TrxRs have been found to be overexpressed by a number of human tumors. Curcumin, which is consumed daily by millions of people, is a polyphenol derived from the plant Curcuma longa. This phytochemical has well known anticancer and antiangiogenic properties. In this study we report that rat TrxR1 activity in Trx-dependent disulfide reduction was inhibited by curcumin. The IC(50) value for the enzyme was 3.6 microM after incubation at room temperature for 2 h in vitro. The inhibition occurred with enzyme only in the presence of NADPH and persisted after removal of curcumin. By using mass spectrometry and blotting analysis, we proved that this irreversible inhibition by curcumin was caused by alkylation of both residues in the catalytically active site (Cys(496)/Sec(497)) of the enzyme. However, the curcumin-modified enzyme showed a strongly induced NADPH oxidase activity to produce reactive oxygen species. Inhibition of TrxR by curcumin added to cultured HeLa cells was also observed with an IC(50) of around 15 microM. Modification of TrxR by curcumin provides a possible mechanistic explanation for its cancer preventive activity, shifting the enzyme from an antioxidant to a prooxidant.

PMID: 15879598 [PubMed - indexed for MEDLINE]

Prooxidant activity and cellular effects of the phenoxyl radicals of dietary flavonoids and other polyphenolics.

Galati G, Sabzevari O, Wilson JX, O'Brien PJ.

Department of Pharmacology, Faculty of Pharmacy, University of Toronto, 19 Russell St., Toronto, Ontario, Canada M5S 2S2.

Dietary polyphenolics in fruits, vegetables, wines, spices and herbal medicines have beneficial antioxidant, anti-inflammatory and anticancer effects. However, we have observed that dietary polyphenolics with phenol rings were metabolized by peroxidase to form prooxidant phenoxyl radicals which, in some cases were sufficiently reactive to cooxidize GSH or NADH accompanied by extensive oxygen uptake and reactive oxygen species formation. The order of catalytic effectiveness found for oxygen activation when polyphenolics were metabolized by peroxidase in the presence of GSH was phloretin>phloridzin>4,2'-dihydroxy chalcone>p-coumaric acid>naringenin>apigenin>curcumin>resveratrol>isoliquiritigenin>capsaicin>kaempferol. Ascorbate was also cooxidized by the phenoxyl radicals but without oxygen activation. Polyphenolics with catechol rings also cooxidized ascorbate, likely mediated by semiquinone radicals. The order of catalytic effectiveness found for ascorbate cooxidation was fisetin luteolin, quercetin, >eriodictyol, caffeic acid, nordihydroguaiaretic acid>catechin>taxifolin, catechol. NADH was stoichiometrically oxidized without oxygen uptake which, suggests that o-quinone metabolites were responsible. GSH was not cooxidized and GSH conjugates were formed, likely mediated by the o-quinone metabolites. Incubation of hepatocytes with dietary polyphenolics containing phenol rings was found to partially oxidize hepatocyte GSH to GSSG while polyphenolics with a catechol ring were found to deplete GSH through formation of GSH conjugates. Dietary polyphenolics with phenol rings also oxidized human erythrocyte oxyhemoglobin and caused erythrocyte hemolysis more readily than polyphenolics with catechol rings. It is concluded that polyphenolics containing a phenol ring are generally more prooxidant than polyphenolics containing a catechol ring.

PMID: 12126798 [PubMed - indexed for MEDLINE]

Thank you for pointing this point out Opales. We have to weight up the benefits versus risks. When you look at Campisi's argument re. antioxidants and cancer.....it makes sense that chemopreventative agents have pro-oxidant activity. Here is an abstract from a Campisi paper

Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors.

Campisi J.

Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA. jcampisi@lbl.gov

Cells from organisms with renewable tissues can permanently withdraw from the cell cycle in response to diverse stress, including dysfunctional telomeres, DNA damage, strong mitogenic signals, and disrupted chromatin. This response, termed cellular senescence, is controlled by the p53 and RB tumor suppressor proteins and constitutes a potent anticancer mechanism. Nonetheless, senescent cells acquire phenotypic changes that may contribute to aging and certain age-related diseases, including late-life cancer. Thus, the senescence response may be antagonistically pleiotropic, promoting early-life survival by curtailing the development of cancer but eventually limiting longevity as dysfunctional senescent cells accumulate.

Publication Types:

    * Review


PMID: 15734683 [PubMed - indexed for MEDLINE]

The above paper is a great read. I highly recommend it to anyone. She is a very passionate about her work and if you ever get the chance to meet her you will see this.