Pomegranate Juice vs. extract
FunkOdyssey 27 May 2008
J Agric Food Chem. 2006 Feb 8;54(3):980-5.
Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells.
Adams LS, Seeram NP, Aggarwal BB, Takada Y, Sand D, Heber D.
Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA. ladams@mednet.ucla.edu
Phytochemicals from fruits such as the pomegranate (Punica granatum L) may inhibit cancer cell proliferation and apoptosis through the modulation of cellular transcription factors and signaling proteins. In previous studies, pomegranate juice (PJ) and its ellagitannins inhibited proliferation and induced apoptosis in HT-29 colon cancer cells. The present study examined the effects of PJ on inflammatory cell signaling proteins in the HT-29 human colon cancer cell line. At a concentration of 50 mg/L PJ significantly suppressed TNFalpha-induced COX-2 protein expression by 79% (SE = 0.042), total pomegranate tannin extract (TPT) 55% (SE = 0.049), and punicalagin 48% (SE = 0.022). Additionally, PJ reduced phosphorylation of the p65 subunit and binding to the NFkappaB response element 6.4-fold. TPT suppressed NFkappaB binding 10-fold, punicalagin 3.6-fold, whereas ellagic acid (EA) (another pomegranate polyphenol) was ineffective. PJ also abolished TNFalpha-induced AKT activation, needed for NFkappaB activity. Therefore, the polyphenolic phytochemicals in the pomegranate can play an important role in the modulation of inflammatory cell signaling in colon cancer cells.
J Nutr Biochem. 2005 Jun;16(6):360-7.
In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice.
Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, Heber D.
Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. nseeram@mednet.ucla.edu
Pomegranate (Punica granatum L.) fruits are widely consumed as juice (PJ). The potent antioxidant and anti-atherosclerotic activities of PJ are attributed to its polyphenols including punicalagin, the major fruit ellagitannin, and ellagic acid (EA). Punicalagin is the major antioxidant polyphenol ingredient in PJ. Punicalagin, EA, a standardized total pomegranate tannin (TPT) extract and PJ were evaluated for in vitro antiproliferative, apoptotic and antioxidant activities. Punicalagin, EA and TPT were evaluated for antiproliferative activity at 12.5-100 microg/ml on human oral (KB, CAL27), colon (HT-29, HCT116, SW480, SW620) and prostate (RWPE-1, 22Rv1) tumor cells. Punicalagin, EA and TPT were evaluated at 100 microg/ml concentrations for apoptotic effects and at 10 microg/ml concentrations for antioxidant properties. However, to evaluate the synergistic and/or additive contributions from other PJ phytochemicals, PJ was tested at concentrations normalized to deliver equivalent amounts of punicalagin (w/w). Apoptotic effects were evaluated against the HT-29 and HCT116 colon cancer cell lines. Antioxidant effects were evaluated using inhibition of lipid peroxidation and Trolox equivalent antioxidant capacity (TEAC) assays. Pomegranate juice showed greatest antiproliferative activity against all cell lines by inhibiting proliferation from 30% to 100%. At 100 microg/ml, PJ, EA, punicalagin and TPT induced apoptosis in HT-29 colon cells. However, in the HCT116 colon cells, EA, punicalagin and TPT but not PJ induced apoptosis. The trend in antioxidant activity was PJ>TPT>punicalagin>EA. The superior bioactivity of PJ compared to its purified polyphenols illustrated the multifactorial effects and chemical synergy of the action of multiple compounds compared to single purified active ingredients.
Additionally, all of the in-vivo human studies that I've seen use pomegranate juice (like the amazing reversal of atherosclerosis one).
Edited by FunkOdyssey, 27 May 2008 - 04:23 PM.
27 May 2008
The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats.
http://www.ncbi.nlm....entrez/17553710
FunkOdyssey 27 May 2008
http://www.pompills....duct_pills.aspx
http://www.pompills....uct_liquid.aspx
Edited by FunkOdyssey, 27 May 2008 - 06:00 PM.
Athanasios 27 May 2008
nameless 27 May 2008
Pomguard (Jarrow) or Cardiogranate might be good too, as they were developed by Ephraim Lansky (the guy who did much of the pom studies). Although for all we know he could have just sold his name to the products as a marketing tool. They also use peel and leaf extracts, which I'm not sure is good or not, due to pesticides and such.
I'm personally more concerned about possible drug interactions with pom, instead of the amount of sugar in the juice. If a person drinks a small amount, after consuming a meal (protein/fiber), I don't think it's a real problem.
27 May 2008
I'm personally more concerned about possible drug interactions with pom, instead of the amount of sugar in the juice.
Unlike grapefruit juice, pomegranate juice does not appear to have significant drug interaction:
Pomegranate Juice Does Not Impair Clearance of Oral or Intravenous Midazolam, a Probe for Cytochrome P450-3A Activity: Comparison With Grapefruit Juice
http://jcp.sagepub.c...stract/47/3/286
nameless 27 May 2008
I'm personally more concerned about possible drug interactions with pom, instead of the amount of sugar in the juice.
Unlike grapefruit juice, pomegranate juice does not appear to have significant drug interaction:
Pomegranate Juice Does Not Impair Clearance of Oral or Intravenous Midazolam, a Probe for Cytochrome P450-3A Activity: Comparison With Grapefruit Juice
http://jcp.sagepub.c...stract/47/3/286
Yeah, I've seen that before. But there is at least one study that contradicts that data - http://dmd.aspetjour...t/full/33/5/644 But that is a ratty study, so it may not apply to humans. It's the 3A4 and 2C9 drugs (which I take) I'm concerned about.
cyborgdreamer 27 May 2008
health_nutty 28 May 2008
mike250 28 May 2008
niner 28 May 2008
Statins seem to be the major problem, since so many people take them and getting too much statin may lead to rhabdomyolysis. I resurrected the following from an old post of mine. We talked about pomegranate / drug interactions here:Yeah, I've seen that before. But there is at least one study that contradicts that data - http://dmd.aspetjour...t/full/33/5/644 But that is a ratty study, so it may not apply to humans. It's the 3A4 and 2C9 drugs (which I take) I'm concerned about.I'm personally more concerned about possible drug interactions with pom, instead of the amount of sugar in the juice.
Unlike grapefruit juice, pomegranate juice does not appear to have significant drug interaction:
Pomegranate Juice Does Not Impair Clearance of Oral or Intravenous Midazolam, a Probe for Cytochrome P450-3A Activity: Comparison With Grapefruit Juice
http://jcp.sagepub.c...stract/47/3/286
I'm taking pomegranate extract daily, so I looked further into the p450 inhibition issue. It turns out that many fruit juices are p450 inhibitors, chiefly CYP3A. (CYP = CYtochrome P450) Pomegranate juice is also a 2C9 inhibitor (PMID: 17132763). The juices are 3A inhibitors in the following order: grapefruit > black mulberry > wild grape > pomegranate > black raspberry. (PMID: 16415112) Starfruit is also inhibitory, although I don't know where it fits in this scheme. Lime juice was seen to be an apparent 3A4 inhibitor in some subjects. (PMID: 12811362) Even red wine is a mild 3A4 inhibitor, and can lead to clinically relevant inhibition in some people. (PMID: 11452240)
The fruit juices all appear to act via a mechanism-based process. This means that they are covalently altering the p450 enzyme rather than just taking up space in the active site while they are present in high concentration. As such, the inhibition continues until the enzyme is recycled. After grapefruit juice consumption, it may take from 3 (PMID: 12891222) to 7 (PMID: 11061578) days for the metabolism of certain drugs to return to normal.
Several studies looked at fresh versus processed or heat treated juices, and saw no differences. This suggests that the inhibition is due to a reasonably robust small molecule, rather than a proteolytic activity.
The juices appear to affect only the enteric p450s. The hepatic p450s seem to be left alone, from my reading. Apparently some people have more p450 activity in the gut (and less in the liver?) than others, so the juices hit them harder.
Are these inhibitions clinically relevant? Yes, it appears that they are. "When simvastatin was taken with grapefruit juice, the mean peak serum concentration (Cmax) and the mean area under the serum concentration-time curve [AUC(0-infinity)] of simvastatin were increased 12.0-fold (P < .001) and 13.5-fold (P < .001), respectively, compared with control." (PMID: 11061578) "48-year-old man with possible underlying myopathy was successfully treated with ezetimibe 10 mg/day and rosuvastatin 5 mg every other day for 17 months. Three weeks before presentation, he began drinking pomegranate juice (200 ml twice weekly). He presented urgently with thigh pain and an elevated serum creatine kinase level (138,030 U/L, normal < 200 U/L). In conclusion, because both grapefruit and pomegranate juice are known to inhibit intestinal cytochrome P450 3A4, this report suggests that pomegranate juice may increase the risk of rhabdomyolysis during rosuvastatin treatment, despite the fact that rosuvastatin is not known to be metabolized by hepatic P450 3A4." (PMID: 16923466) This paper was published shortly before the paper that showed that pomegranate juice was a 2C9 inhibitor, and sure enough, rosuvastatin is metabolized by 2C9.
Opelousas Cajun 31 May 2008
What has been resolved regarding the benefits of Goji vs Pomegranate? I've been under the illusion of the following:
Food ORAC Score Grams Needed
Goji berries 25,300 20
Pomegranates 3,307 151
Blueberries 2,400 208
Noni fruit 1,506 332
Apples 218 2294
Spinach 1,770 282
Tomato 195 2564
Dk. chocolate 13,120 38.1
What is the real story??
Thanks in advance.
(excuse the format...I've tried to correct, but have been unsuccessful)
Edited by Opelousas Cajun, 31 May 2008 - 02:33 PM.
inawe 31 May 2008
It's not just the antioxidant power. I think there has been much more research on the positive healthNewbie here...
What has been resolved regarding the benefits of Goji vs Pomegranate? I've been under the illusion of the following:
Food ORAC Score Grams Needed
Goji berries 25,300 20
Pomegranates 3,307 151
Blueberries 2,400 208
Noni fruit 1,506 332
Apples 218 2294
Spinach 1,770 282
Tomato 195 2564
Dk. chocolate 13,120 38.1
What is the real story??
Thanks in advance.
(excuse the format...I've tried to correct, but have been unsuccessful)
effects of pomegranate than of goji. Pomegranate juice have been shown to
reduce carotid plaque. And there are like 10 clinical trials going on
checking pomegranate juice for cancer prevention.
DukeNukem 31 May 2008
Newbie here...
What has been resolved regarding the benefits of Goji vs Pomegranate? I've been under the illusion of the following:
Food ORAC Score Grams Needed
Goji berries 25,300 20
Pomegranates 3,307 151
Blueberries 2,400 208
Noni fruit 1,506 332
Apples 218 2294
Spinach 1,770 282
Tomato 195 2564
Dk. chocolate 13,120 38.1
What is the real story??
Thanks in advance.
(excuse the format...I've tried to correct, but have been unsuccessful)
You can almost ignore ORAC. Far more important is the specific benefits granted by unique polyphenols. Pomegranate appears to have a uniquely beneficial class of polyphenols. I've yet to hear anything specifically beneficial about wolfberry polyphenols.
Edited by DukeNukem, 31 May 2008 - 11:33 PM.
malbecman 01 Jun 2008
Newbie here...
What has been resolved regarding the benefits of Goji vs Pomegranate? I've been under the illusion of the following:
Food ORAC Score Grams Needed
Edited by Michael, 25 August 2009 - 04:11 PM.
Trim quotes
unbreakable 03 Aug 2008
Center for Human Nutrition, David Geffen School of Medicine, Los Angeles California, USA.
Pomegranate juice (PJ), a rich source of polyphenols including ellagitannins, has attracted much attention due to its reported health benefits. This has resulted in the consumption of liquid and powder pomegranate extracts as alternatives to PJ. Therefore establishing the bioavailability of polyphenols from these extract preparations is necessary. Sixteen healthy volunteers sequentially consumed, with a 1-week washout period between treatments, PJ (8 ounces, Wonderful fruit variety), a pomegranate polyphenol liquid extract (POMxl, 8 ounces), and a pomegranate polyphenol powder extract (POMxp, 1,000 mg). The three interventions provided 857, 776, and 755 mg of polyphenols as gallic acid equivalents, respectively. Plasma bioavailability, judged based on ellagic acid levels over a 6-hour period, did not show statistical differences in area under the curve for the three interventions: 0.14 +/- 0.05, 0.11 +/- 0.03, and 0.11 +/- 0.04 micromol . hour/L for PJ, POMxl, and POMxp, respectively. The time of maximum concentration was delayed for POMxp (2.58 +/- 0.42 hours) compared to PJ (0.65 +/- 0.23 hours) and POMxl (0.94 +/- 0.06 hours). Urolithin-A glucuronide, a urinary metabolite of ellagic acid, was not significantly different with the three interventions, reaching levels of approximately 1,000 ng/mL. This study demonstrates that ellagitannin metabolites, delivered from pomegranate fruits, as PJ, POMxl, and POMxp, reach equivalent levels with a delay in time of maximum concentration of POMxp compared to PJ and POMxl.
krillin 03 Aug 2008
VampIyer 03 Aug 2008
I've been using the BAC powder mixed in water for a little while, and it's going to get me yelled at by the dental hygienist next cleaning. It's staining the bejeebers out of my back teeth, even with twice-daily Sonicaring with whitening toothpaste.
I had a doctor look at my tongue after I had taken the p40p. It took a while for me to explain that I wasn't dying...
We should probably use our scales and start capping some of our extracts...
krillin 11 Aug 2008
http://www.lef.org/V...omegranate.html
krillin 11 Aug 2008
Blue 24 Aug 2009
http://jn.nutrition....ull/136/10/2481
Regardless of if ellagic acid or urolithin is the most important substance this would possible argue for using for example raspberries which has much higher concentration of ellagic acid than pomegranate.
Athanasios 24 Aug 2009
niner 24 Aug 2009
Blue 24 Aug 2009
Both those studies look at ellagic acid. Punicalagin is metabolized to ellagic acid. But is there any evidence that punicalagin itself is clinically relevant in humans? The paper I cited and the papers it cites (see the discussion section) find that punicalagin is not found in the blood in humans which is not surprising considering its large size.This paper argues in favor of extracts. So does this one. As far as I know, the idea that it's better to use an extract standardized on punicalagins as opposed to ellagic acid still stands. In consideration of the sugar and the cost, I'm using extracts. Cnorwood, I'll bet that the change in the LEF product is not the cause of your bp jump. The LEF extract got more like juice, rather than less from that change. There are all kinds of things that can cause bp to move a little. It's certainly not the case that punicalagins are ineffective in humans. They are the primary source of pomegranate polyphenols in fresh juice and fruit.
Edited by Blue, 24 August 2009 - 09:39 PM.
niner 24 Aug 2009
Here's an in vivo study looking at extract vs juice. I do think there is some evidence that punicalagin is superior to ellagic acid, but I don't have time to look for it now. I'll try later.Both those studies look at ellagic acid. Punicalagin is metabolized to ellagic acid. But is there any evidence that punicalagin itself is clinically relevant in humans? The paper I cited and the papers it cites (see the discussion section) find that punicalagin is not found in the blood in humans which is not surprising considering its large size.This paper argues in favor of extracts. So does this one. As far as I know, the idea that it's better to use an extract standardized on punicalagins as opposed to ellagic acid still stands. In consideration of the sugar and the cost, I'm using extracts. Cnorwood, I'll bet that the change in the LEF product is not the cause of your bp jump. The LEF extract got more like juice, rather than less from that change. There are all kinds of things that can cause bp to move a little. It's certainly not the case that punicalagins are ineffective in humans. They are the primary source of pomegranate polyphenols in fresh juice and fruit.
Nitric Oxide. 2007 Aug;17(1):50-4. Epub 2007 May 5.
The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats.
de Nigris F, Balestrieri ML, Williams-Ignarro S, D'Armiento FP, Fiorito C, Ignarro LJ, Napoli C.
Department of General Pathology and Excellence Research Center on Cardiovascular Diseases, Complesso S. Andrea delle Dame, Via de Crecchio 7, 1st School of Medicine, II University of Naples, Naples 80138, Italy.
Metabolic syndrome includes most widely distributed clinical conditions such as obesity, hypertension, dislipidemia, and diabetes. Pomegranate fruit extract (PFE), rich in polyphenolic antioxidants, reduces the expression of oxidation-sensitive genes at the sites of perturbed shear-stress. The aim of this study was to evaluate the effect of PFE in comparison to regular pomegranate juice (PJ) and seed oil on the biological actions of nitric oxide (NO) and the arterial function in obese Zucker rats, a model of metabolic syndrome. Our results indicated that supplementation with PFE or PJ significantly decreased the expression of vascular inflammation markers, thrombospondin (TSP), and cytokine TGFbeta1 (P<0.05), whereas seed oil supplementation had a significant effect only on TSP-1 expression (P <0.05). Plasma nitrate and nitrite (NO(x)) levels were significantly increased by PFE and PJ (P<0.05). Furthermore, the effect of PFE in increasing endothelial NO synthase (eNOS) expression was comparable to that of PJ. These data highlight possible clinical applications of PFE in metabolic syndrome.
PMID: 17553710
niner 25 Aug 2009
Punicalagins are tannins, large polyphenol compounds which are isomers of 2,3-(S)-hexahydroxydiphenoyl-4,6-(S,S)-gallagyl-D-glucose, hydrolysable tannins with a molecular weight of 1084. They are found in forms alpha and beta in pomegranates. Punicalagins are the largest molecule found intact in rat plasma after oral ingestion[1] and were found to show no toxic effects in rats who were given a 6% diet of punicalagins for 37 days.[2] Punicalagins are also found to be the major component responsible for pomegranate juice's antioxidant and health benefits.[3]
Punicalagins are water soluble and have high bioavailability. They are known to hydrolyze into smaller polyphenols such as ellagic acid in vivo where one potential mechanism is hydrolysis across the mitochondrial membrane of cultured human colon cells.[4][5]
A study in Taiwan showed that punicalagin alpha (1-alpha-O-galloylpunicalagin) induced nitric oxide production in a dose-dependent manner in endothelial cells[6] as well as inhibited ERK, JNK and Akt, all of which play roles in cancer growth, so their inhibition points to punicalagins' potential as strong cancer suppressors.[citation needed]
(continues...)
Here is some more in vivo work that finds extracts to be useful. It even finds ellagic acid to be useful, which is comforting given the large number of pomegranate extracts that are standardized against ellagic acid. I think we might be losing sight of the complexity of extracts; they aren't pure punicalagins or pure ellagic acid just because they are standardized to those compounds. Those compounds are just used as markers of overall concentration of polyphenols, and may be used to direct the blending of different extract feedstocks to generate a consistent final product.
J Agric Food Chem. 2008 Feb 13;56(3):1148-57. Epub 2008 Jan 4.
Pomegranate phenolics from the peels, arils, and flowers are antiatherogenic: studies in vivo in atherosclerotic apolipoprotein e-deficient (E 0) mice and in vitro in cultured macrophages and lipoproteins.
Aviram M, Volkova N, Coleman R, Dreher M, Reddy MK, Ferreira D, Rosenblat M.
The Lipid Research Laboratory, Rambam Medical Center, Haifa, Israel. aviram@tx.technion.ac.il
We have analyzed in vivo and in vitro the antiatherogenic properties and mechanisms of action of all pomegranate fruit parts: peels (POMxl, POMxp), arils (POMa), seeds (POMo), and flowers (POMf), in comparison to whole fruit juice (PJ). Atherosclerotic E 0 mice consumed POM extracts [200 microg of gallic acid equivalents (GAE)/mouse/day] for 3 months. Blood samples, peritoneal macrophages (MPM), and aortas were then collected. All POM extracts possess antioxidative properties in vitro. After consumption of PJ, POMxl, POMxp, POMa, or POMf by E (0) mice, the atherosclerotic lesion area was significantly decreased by 44, 38, 39, 6, or 70%, respectively, as compared to placebo-treated group, while POMo had no effect. POMf consumption reduced serum lipids, and glucose levels by 18-25%. PJ, POMxl, POMxp, POMf, or POMa consumption resulted in a significant decrement, by 53, 42, 35, 27, or 13%, respectively, in MPM total peroxides content, and increased cellular paraoxonase 2 (PON2) activity, as compared to placebo-treated mice. The uptake rates of oxidized-LDL by E (0)-MPM were significantly reduced by approximately 15% after consumption of PJ, POMxl, or POMxp. Similar results were obtained on using J774A.1 macrophage cell line. Finally, pomegranate phenolics (punicalagin, punicalin, gallic acid, and ellagic acid), as well as pomegranate unique complexed sugars, could mimic the antiatherogenic effects of pomegranate extracts. We conclude that attenuation of atherosclerosis development by some of the POM extracts and, in particular, POMf, could be related to the combined beneficial effects on serum lipids levels and on macrophage atherogenic properties.
PMID: 18173244
Blue 25 Aug 2009
Yes, there are several cell studies finding good effects from punicalagin. But if punicalagin is not absorbed intact then they irrelevant (unless they are intestinal cells).
Agree that we do not know what causes the very good effect seen from pomegranate juice in several studies but the above makes it likely it is not punicalagin itself.
The studies finding similar effects for extract and juice are good but they do not replicate the several years long studies on pomegranate juice. To be sure, one should really take exactly the same PJ as used in the studies. Really preferably the same year PJ. But I agree that there is a good chance that a similar effect will be seen from taking an extract. At least those extracts that have been studied. Not sure that all extracts preserve all ingredients equally.
Edited by Blue, 25 August 2009 - 01:39 PM.
Blue 29 Aug 2009
http://pubs.acs.org/....1021/jf9010017
kismet 29 Aug 2009
That's a tautology, but, yes, and more importantly, the biggest inter-species differences are, unfortunately, in the liver (IIRC). Making pharmacokinetic and absorption data from animals very difficult to interpret. I'm assuming punicalagin undergos hepatic clearance.But humans are not rats.
Edited by kismet, 29 August 2009 - 09:35 PM.
niner 30 Aug 2009
Nice Find, Blue. I've put in a request for full text via a friend with access, but it might take a while. I'd really like to know if they name names. I have one thought about punicalagins; given that they are polymers susceptible to hyrolysis in vivo, what about the presence of mixed oligomers in the blood? There might be dimers or trimers, for example, and they might have unique biological properties not held by ellagic acid. Just a hypothesis... If anyone has access to that paper and could put it in the resource sharing section, that would be great.