Special Research REPORT
FRENCH GRAPE SEED
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FRENCH GRAPE SEED Scientists and medical researchers have long known that grapes provided a wealth of health benefits. While anthocyanidin compounds in the skin of red grapes have been highly touted in the media, new findings show astonishing health benefits from oligomeric proanthocyanidin complexes (OPCs) found in the seeds of grapes. These naturally occurring plant compounds have been the subject of numerous studies over the past decade. This special report brings you cutting edge research on the most important findings to date.
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All rights reserved. No part of this booklet may be reproduced in any way, including print, digital, audio, or photocopying, without the express written permission of the publisher. We at Good Health Lifestyles would like to thank our advertiser for making this informative booklet possible. The statements in this publication have not been evaluated by the Food and Drug Administration. The information contained herein is provided for educational purposes only under Section 5 of the Dietary Supplement Health and Education Act of 1994 and is not intended to diagnose, treat, cure, or prevent any disease. Please consult with a licensed physician or other qualified healthcare professional for more in-depth information or prior to taking any dietary supplements.
The OPCs in grape seeds are a rich source of antioxidants that can protect against oxidative damage. In vivo studies have shown that the OPCs from grape seeds are a better free radical scavenger and inhibitor of oxidative tissue damage than vitamin C, vitamin E, or beta carotene. OPCs also provide anti-inflammatory properties and other physiological benefits that may lower the risk of many chronic illnesses. These findings provide an excellent reason to include a highly absorbable French grape seed extract to your daily preventive regimen. Turn the page to learn more. Ajay Goel, PhD, is a researcher at the Gastrointestinal Cancer Research Lab at Baylor University Medical Center in Dallas, TX. He is a member of the American Association for Cancer Research and the American Gastroenterology Association.
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POWERFUL PREVENTION with
Grape Seed Extract Nature’s answer to free-radical damage
C
urrent statistics on cancer are staggering. According to the American Cancer Society, more than 4,800 new cases of cancer will be identified each day in 2019. The chance of a person being diagnosed in their lifetime is now 1 in 3. The questions beg to be asked: Why is this devastating disease so widespread? And is there any hope for prevention?
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Research shows that cancer
can be attributed to a number of causes, but pinpointing a reason you or a family member may have developed the disease is nearly impossible. Tobacco use, toxic chemicals, obesity, hormone imbalances, radiation, viruses, chronic inflammation, and lack of exercise can all set the stage for the cellular damage that leads to cancer. An extremely complex disease, cancer doesn’t come with a onesize-fits-all cause—or solution. GOOD CELLS BEHAVING BADLY
All cancers can be traced back to an abnormal functioning of cells in the body. Ideally, each of your cells divides in an orderly fashion. During the typical life cycle, old or damaged cells die (a process known as apoptosis) and healthy new cells take their place. Cancer develops when the damaged cells don’t die, but continue to divide and grow. This overgrowth of damaged cells can eventually form tumors that may spread to other organs and tissues. But take heart—along with the sobering statistics on cancer comes some good news. For many years doctors believed that cancer was primarily a hereditary 5
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disease. Now we know that more than 95 percent of cancers have little to do with your genes, but may be caused by certain lifestyle and environmental factors. Why is this considered good news? While it can be nearly impossible to control things like toxins in the environment, it is possible to control some of the lifestyle factors that could lower your cancer risk in the first place. Also, treatment options are advancing. Screening techniques are becoming more effective. Best of all, cancer survival rates are on the rise. So while cancer remains extremely prevalent, people are beating it more than ever before in history. In the case of such a devastating illness, these small victories are cause for celebration. Another major contributor in the fight against cancer is the fact that people are becoming more educated in the many ways they can proactively help to prevent the disease in their own lives. While eating a healthy diet, participating 6
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in regular exercise, and avoiding tobacco products can provide a good start, science now tells us there are some powerful natural compounds that may have the ability to lessen the odds that the disease ever takes hold. One of the most effective weapons to have in your cancer prevention protocol is grape seed extract. AMAZING ANTIOXIDANT POWER
Grapes are abundantly rich in disease-fighting nutrients, including antioxidants that protect your cells from oxidative stress and inflammation. The skins and seeds of the grape contain high antioxidant concentrations that can benefit a number of health conditions, including heart disease, diabetes, and cancer. When it comes to disease-fighting botanicals, few have proven to be as powerful and versatile as grape seed extract.
Educational B O O K L E T Series Grape seed extract is so potent because it contains oligomeric proanthocyanidins, or OPCs. OPCs are compounds with great protective value, but to be beneficial, their molecular structure needs to be tiny and readily absorbable. The best OPCs are found in a French variety of grape seed extract called VX1. VX1 is tannin-free and has unique specifications that make it highly absorbable—and therefore more effective—in the body. STUDIES ON THE RISE
Impressively, French grape seed extract VX1 has a growing body of research backing its powerful cancer-prevention abilities. In a number of studies, OPCs have been shown to inhibit cancer cell proliferation and trigger cell death in colon, breast, prostate, and other cancers. They have also been shown to shrink the size of tumors, as well as target cancer stem cells that have become resistant to chemotherapy.
cancer cells. And when compared to other grape seed extracts in the study, VX1 was significantly more effective at a much lower dose than standard extracts. It’s also important to note that no healthy cells were harmed in this study. The OPCs pinpointed the cancer cells without destroying any healthy tissue. TARGETING STEM CELLS
Another impressive study shows the effectiveness of OPCs on cancer stem cells. You’ve heard it time and again. Someone is declared to be in remission or “cancer free,” only to have a reoccurrence in the future. Why does this happen? Because cancer cells are smart and resilient. Sometimes they can hide in the body and become resistant to chemotherapy treatment. While chemotherapy can cause cancer stem cells to become
One study appearing in the journal Carcinogenesis focused on colorectal cancer, one of the most deadly cancers in the United States. The research found that VX1 was able to boost levels of tumor-fighting genes, “turn off” the genes that promote tumor growth, and prevent the spread of 7
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chemo-resistant, the OPCs in French grape seed extract VX1 target a unique pathway called Hippo-YAP that is necessary for stem cell survival. After exposing colon cancer cells to this standardized extract, tumor growth was suppressed by as much as 90 percent. Additional findings published in Carcinogenesis reported that VX1 can stop DNA in cancer cells from replicating itself, which prevents the spread of cancer. ADULTERATION AWARENESS
To get the most cancerprevention potential from a grape seed extract supplement, look for French grape seed extract that is tanninfree with small OPCs for proven absorption. The best products have gone through a verification program to determine that the extract is authentic and hasn’t been adulterated.
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Mor e POWERHOUSE PROTECTION CURCUMIN This extremely potent antioxidant is the darling of the natural medicine world when it comes to inflammatory defense. Known for its unparalleled ability to stop the free radical cascades in the body that can lead to inflammation, curcumin also has the ability to enhance the beneficial effects of chemotherapy. BCM-95 curcumin (a proprietary ingredient also known as Curcugreen) is the subject of over 60 published studies for its health benefits. Preliminary research on its anti-cancer activity has found that it can suppress breast, prostate, liver, skin, oral, colon, and lung cancer cells. One study in particular researched the benefits of BCM-95 curcumin when combined with French grape seed extract VX1. Because these two botanicals target separate inflammatory pathways in the body, taking them simultaneously may pack an even bigger punch than taking either of them alone.
Educational B O O K L E T Series While grape seed extract has a great deal of anticancer properties, studies show that the following vitamins and botanicals can also set the stage for cells to exist cancer-free.
BOSWELLIA
VITAMIN D
Another of nature’s powerful antiinflammatory botanicals, boswellia stands out for its unique ability to target numerous inflammation pathways in the body, including an important one called 5-LOX. Not even curcumin and grape seed extract can touch 5-LOX, which is thought to contribute to serious health conditions like arthritis, Alzheimer’s, and inflammatory bowel disease.
Yes, the “sunshine vitamin” can do much more than keep your spirits up. Studies show it may prevent or slow the growth of some types of cancers, including breast, prostate, colon, and even pancreatic cancer. Vitamin D is unique in the way that it acts like a hormone in the body, helping to build healthy bones and regulate immune, muscle, and nervous system function.
In a cell study performed in Egypt, boswellia was found to be comparable to two chemotherapy drugs for inhibiting the growth of colon and liver cancer cells. Other preliminary work has shown that a primary compound in boswellia called AKBA was able to stop the growth of leukemia and prostate cancer cells by making the cancer cells unable to form blood vessels—their source of survival. When looking for an effective boswellia product, check the label to make sure it is standardized to 10 percent AKBA.
While the full benefits of vitamin D on cancer prevention still need to be explored, preliminary findings are promising. A recent study in PLOS ONE showed that postmenopausal women with higher amounts of vitamin D in their blood had a significantly lower risk of developing breast cancer than those with lower vitamin D counts. More research reflects that vitamin D has an influence on tumor growth and apoptosis. Remember that before you up your vitamin D intake, it’s important to get a blood test through your healthcare provider to check your levels. 9
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Research Roundup It’s our goal here at Good Health Lifestyles to bring you the latest in cutting-edge research for a variety of common health issues. Because we believe that knowledge is power— especially when it comes to health— we are digging deeper into the exciting new research from leading medical journals and breaking it down to help you get the most from today’s science.
SPECIAL FOCUS ON
Grape Seed Extract
French Grape Seed OPCs: Cancer-Preventive Compounds You’ve probably heard about grape seed extract, especially for heart related conditions. Unfortunately, many grape seed extracts on the market are adulterated with other ingredients. Others are composed primarily of tannins, which do contain oligomeric proanthocyanidins (OPCs), but the compounds are too large to be effectively absorbed and provide benefits. However, tannin-free grape seed extract provide only small, fully absorbable OPCs that can 10
readily enter into the cells most in need of healing attention. The studies highlighted here suggest the value of a French grape seed extract (VX1), standardized tannin-free OPCs in stopping colorectal cancer cells from growing and recurring. According to the Centers for Disease Control and Prevention (CDC), colorectal cancer has the second highest mortality rate in the United States. Fortunately, this latest research may provide insight and hope for the future.
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Stopping Stem-Like Cell “Seeds” with French Grape Seed OPCs
THE STUDY ABSTRACT:
Oligomeric proanthocyanidins (OPCs) target cancer stem-like cells and suppress tumor organoid formation in colorectal cancer. Proanthocyanidins are a heterogeneous group of flavan3-ol or flavan-3,4-diol oligomers present in various fruits and vegetables. In particular, the smaller oligomeric subset of proanthocyanidins, termed the oligomeric proanthocyanidins (OPCs) appear to have potent anti-tumorigenic properties, but the underlying mechanisms for their effectiveness remain unclear. Herein, we utilized a series of in vitro, in vivo and patientderived organoid approaches to systematically investigate the chemoprotective role of OPCs in colorectal cancer. OPCs exerted anti-tumorigenic effects through inhibition of cellular proliferation, and induced apoptosis and cell cycle arrest. Intriguingly, OPCs suppressed spheroid derived cancer stem-like cell formation and decreased the expression of intestinal cancer stem cell markers including LGR5, CD44 and CD133. Mechanistically, RNA-
sequencing results confirmed that OPCs prominently interfered with developmental and self-renewal pathways and identified several self-renewal associated oncogenes targeted by OPCs. Furthermore, OPCs inhibited Hippo pathway through downregulation of its key transcriptional regulators, YAP and TAZ. Finally, we confirmed anti-tumorigenic effects of OPCs using multiple xenograft experiments and recapitulated its protective effects using patient-derived colorectal tumor organoids. Collectively, we have comprehensively assessed anti-tumorigenic properties of OPCs and our data throws light on previously unrecognized chemopreventive mechanisms of OPCs highlighting its therapeutic potential. Source: Toden S, Ravindranathan P, Gu J, Cardenas J, Yuchang M, Goel A. Sci Rep. 2018 Feb 20;8(1):3335.
WHAT IT MEANS TO YOU:
Cancer stem cells, the “seeds” of recurring cancer, resist chemotherapy. They essentially hide in the body, remerging later—sometimes years following treatment. When this happens, the new cancer is even more resistant to treatment. 11
Researchers at Baylor found that French grape seed extract (VX1) stopped the regeneration of cancer stem cells by blocking a specific pathway in the body, abbreviated as HippoYAP. In studies, it actually prevented the ability of tumor cells to grow and spread, and eventually killed them altogether. This is an effect not seen with conventional drugs, so these results show the potential for OPCs from grape seed to do something completely unique. In this case, the viability of cancer cells exposed to the extract decreased by 70 percent. Further study using an animal model showed that the VX1 extract suppressed tumor growth by 90 percent. This study shows that the frontiers of natural cancer fighting are still being explored and that the potential for the right kind of grape seed extract—one that is tannin-free and specifically standardized for OPCs— is massive. According to the researchers, a human equivalent dose could be a small addition to a daily regimen—only about 300 mg to 600 mg per day.
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French Grape Seed OPCs
THE STUDY ABSTRACT:
Oligomeric proanthocyanidins (OPCs) from grape seed extract suppress the activity of ABC transporters in overcoming chemoresistance in colorectal cancer cells. Multidrug resistance is a major hindrance in managing cancer. By performing a series of experiments in chemoresistant colorectal cancer cell lines, we demonstrate that oligomeric proanthocyanidins (OPCs) from grape seed extracts can sensitize both acquired (HCT116-FOr cells) and innately chemoresistant (H716 cells) cancer cells to chemotherapeutic drugs, 5-fluorouracil (5FU) and oxaliplatin, by inhibiting ABC transporter proteins. When combined with chemotherapeutic drugs, OPCs significantly inhibited growth of the chemoresistant cells (p<0.05 to p<0.001), and decreased the expression of several key ABC transporters. Moreover, the activity of
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Improve the Effect of Some Chemotherapy Drugs the ABC transporters was also significantly decreased by OPCs in the cell lines (p<0.05). We further confirmed that cotreatment with OPCs sensitized the chemoresistant cells to 5FU and oxaliplatin, as observed by improvement in cell cycle arrest, double strand breaks and p53 accumulation in these cells. Additionally, we confirmed that co-administration of OPCs with chemotherapeutic drugs significantly decreased chemoresistant xenograft tumor growth in mice (p<0.05). Together, our study illuminates the downregulation of multiple ABC transporters as a mechanism by which OPCs overcome chemoresistance in cancer cells, and may serve as adjunctive treatments in patients with refractory colorectal cancer.
WHAT IT MEANS TO YOU:
One of the biggest barriers to conventional cancer treatment is that cancer cells become resistant to chemotherapy drugs. Trying to overcome that with higher dosages isn’t always an option because of the terrible side effects chemotherapy drugs can have on patients. This study found that the oligomeric proanthocyanidins (OPCs) from a French grape seed extract (VX1) inhibited the growth of resistant cancer cells and the proteins that would otherwise help them thrive. This means that the French grape seed OPCs could be part of an adjunct therapy—a beneficial add-on—to chemotherapy in patients with colorectal cancer.
Source: Ravindranathan P, Pasham D, Goel A. Carcinogenesis. 2018 Dec 29.
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For Results, Grape Seed OPCs Are the Critical Factor
THE STUDY ABSTRACT:
Mechanistic insights into anticancer properties of oligomeric proanthocyanidins from grape seeds in colorectal cancer. Although the anticancer properties of oligomeric proanthocyanidins (OPCs) from grape seeds have been well recognized, the molecular mechanisms by which they exert anticancer effects are poorly understood. In this study, through comprehensive RNAsequencing-based gene expression profiling in multiple colorectal cancer cell lines, we for the first time illuminate the genome-wide effects of OPCs from grape seeds in colorectal cancer. Our data revealed that OPCs affect several key cancer associated genes. In particular, genes involved in cell cycle and DNA replication were most significantly and consistently altered by OPCs across multiple cell lines. Intriguingly, our in vivo experiments showed that OPCs were significantly more potent at decreasing xenograft tumor growth compared with the unfractionated grape seed extract (GSE) that includes the larger polymers of proanthocyanidins. These findings were further confirmed in colorectal cancer patient-derived organoids, wherein OPCs more 14
potently inhibited the formation of organoids compared with GSE. Furthermore, we validated alteration of cell cycle and DNA replication-associated genes in cancer cell lines, mice xenografts as well as patient-derived organoids. Overall, this study provides an unbiased and comprehensive look at the mechanisms by which OPCs exert anticancer properties in colorectal cancer. Source: Ravindranathan P, Pasham D, Balaji U, Cardenas J, Gu J, Toden S, Goel A. Carcinogenesis. 2018 May 28;39(6):767-777.
WHAT IT MEANS TO YOU:
This study tested grape seed oligomeric proanthocyanidins (OPCs) against a plain, or unfractionated grape seed extract (GSE) that was not tannin-free, nor specifically standardized for the compounds. One of the insights garnered by this research was not just how the OPCs affect cancer-related genes and stop the cell growth cycle, but how much more effective the smaller-sized (low molecular weight) OPCs were in comparison with the larger proanthocyanidins from the regular grape seed extract. These OPCs target specific microRNAsâ&#x20AC;&#x201D;in this case the microscopic engineers that
replicate cancer cells—and prevent cancer by directly inducing apoptosis (the programmed death of damaged cells). It also boosted levels of tumor suppressor genes, downregulated tumor promoting genes, and prevented the migration of cancer cells. Although this research focused on colorectal cancer, there are similar types of activity across nearly all kinds of malignancies. In fact, the researchers found that the grape seed worked along so many tracks, they stated that “…no single clinical therapeutic has the ability to effectively block multiple oncogenic pathways…” That alone is an incredible breakthrough. But in vivo tests found something else even more applicable to everyday life. Because the tannin free OPCs from French grape seed VX1 were more absorbable than the tannin OPCs from unfractionated grape seed extract, the botanical ingredient was more effective at much lower dosages. For example, animal studies found that
even at smaller amounts, French grape seed VX1 was much more effective than a standard grape seed extract at reducing tumor size. In just 13 days, 100 mg of French grape seed VX1 reduced tumor size by 65 percent. Even a 50 mg level brought the tumor size down 40 percent. Compared to standard grape seed extract at only 13 percent and 8 percent, respectively, it shows how much of a difference it makes to get a tannin-free grape seed extract with absorbable OPCs that can reach their full potential. Additionally, there were no harmful effects on healthy cells—these actions were targeted to cancer cells only. Scaled up for human use, researchers determined that low daily dosages—just 240 mg per day—were sufficient. 15
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French Grape Seed OPCs Plus Curcumin Are Superior
THE STUDY ABSTRACT:
A combination of curcumin and oligomeric proanthocyanidins offer superior antitumorigenic properties in colorectal cancer. Combining anti-cancer agents in cancer therapies is becoming increasingly popular due to improved efficacy, reduced toxicity and decreased emergence of resistance. Here, we test the hypothesis that dietary agents such as oligomeric proanthocyanidins (OPCs) and curcumin cooperatively modulate cancer-associated cellular mechanisms to inhibit carcinogenesis. By a series of in vitro assays in colorectal cancer cell lines, we showed that the anti-tumorigenic properties of the OPCs-curcumin combination were superior to the effects of individual compounds. By RNA-sequencing based gene expression profiling in six colorectal cancer cell lines, we identified the cooperative modulation of key cancer-associated pathways such as DNA replication and cell cycle pathways. Moreover, several pathways, including protein export, glutathione metabolism and porphyrin metabolism were more effectively modulated by the combination of OPCs and curcumin. We validated genes belonging to these pathways, such as HSPA5, SEC61B, G6PD, HMOX1 16
and PDE3B to be cooperatively modulated by the OPCs-curcumin combination. We further confirmed that the OPCs-curcumin combination more potently suppresses colorectal carcinogenesis and modulated expression of genes identified by RNA-sequencing in mice xenografts and in colorectal cancer patient-derived organoids. Overall, by delineating the cooperative mechanisms of action of OPCs and curcumin, we make a case for the clinical coadministration of curcumin and OPCs as a treatment therapy for patients with colorectal cancer. Source: Ravindranathan P, Pasham D, Balaji U, Cardenas J, Gu J, Toden S, Goel A. Sci Rep. 2018 Sep 14;8(1):13869.
WHAT IT MEANS TO YOU:
Tannin-free French grape seed extract with highly absorbable OPCs has already shown strong antitumor effects in prior research. This study combined the OPCs from French grape seed extract with a curcumin from turmeric that is blended with turmeric essential oil containing ar-turmerone, a beneficial compound within the oil, for greater absorption. Both grape seed OPCs and curcumin work along multiple pathways in the body to reduce inflammatory damage to healthy DNA, help prevent cancer cells from replicating, and inhibit the
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Anti-Carcinogens growth and development of tumors. What’s interesting here is that these two botanical ingredients work along differing paths, and because of this, they can cover more ground in the battle against cancer than either one could separately. As in the other studies, an important key is the form of the ingredients used in the study. The grape seed (VX1) is tannin-free and specifically standardized for OPCs that can be absorbed in the digestive tract, enter the cells, and start repairing them (or triggering apoptosis, if they’re cancerous.) The curcumin, known as BCM-95/Curcugreen, shouldn’t be confused with plain turmeric or standard extracts. It uses turmeric essential oil, not piperine, to boost absorption and help it remain in the bloodstream longer. As the researchers note in their study, it has become increasingly popular to combine cancer-prevention therapies. Both French grape seed OPCs and curcumin represent a onetwo punch for reducing cancer risk. The French grape seed is water soluble—it absorbs quickly and works fast. The curcumin is fat soluble and remains in the body longer. This research suggests that this dynamic duo may be an excellent addition to standard therapies. 17
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SELECTED REFERENCES:
Buhrmann C. Curcumin suppresses crosstalk between colon cancer stem cells and stromal fibroblasts in the tumor microenvironment: potential role of EMT. PLoS One. 2014;9(9):e107514.
Satpathy R. Prediction of anticancer property of bowsellic acid derivatives by quantitative structure activity relationship analysis and molecular docking study. Pharm Bioallied Sci. 2015;7(1):21-5.
Derry M. Differential effects of grape seed extract against human colorectal cancer cell lines: The intricate role of death receptors and mitochondria. Cancer Lett. 2013;334(1):69-78.
Shakibaei M. Curcumin potentiates antitumor activity of 5-fluorouracil in a 3D alginate tumor microenvironment of colorectal cancer. BMC Cancer. 2015;15:250.
Dinicola S. Antiproliferative and apoptotic effects triggered by Grape Seed Extract (GSE) versus epigallocatechin and procyanidins on colon cancer cell lines. Int J Mol Sci. 2012;13(1):651-64.
Shakibaei M. Curcumin chemosensitizes 5-fluorouracil resistant MMR-deficient human colon cancer cells in high density cultures. PLoS One. 2014;9(1):e85397.
Goel A. Boswellia extracts induce DNA methylation changes in colon cancer cells. Poster presentation, International Meeting of American Gastroenterological Association, Chicago, IL, May 6-10, 2011. Hamidpour R. Frankincense (rĂť xiang; boswellia species): from the selection of traditional applications to the novel phytotherapy for the prevention and treatment of serious diseases. J Tradit Complement Med. 2013;3(4):221-6. McDonnell SL. Breast cancer risk markedly lower with serum 25-hydroxyvitamin D concentrations â&#x2030;Ľ60 vs <20 ng/ml (150 vs 50 nmol/L): Pooled analysis of two randomized trials and a prospective cohort. PLoS One. 2018;13(6): e0199265. Ravindranathan P. Oligomeric proanthocyanidins (OPCs) from grape seed extract suppress the activity of ABC transporters in overcoming chemoresistance in colorectal cancer cells. Carcinogenesis. 2019;40(3):412-421.
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Shehzad A. Molecular mechanisms of curcumin action: signal transduction. Biofactors. 2013;39(1):27-36. Shehzad A. Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Arch Pharm (Weinheim). 2010;343(9):489-99. Takada Y. Acetyl-11-keto-beta-boswellic acid potentiates apoptosis, inhibits invasion, and abolishes osteoclastogenesis by suppressing NF-kappa B and NF-kappa B-regulated gene expression. J Immunol. 2006;176(5):3127-40. Vuolo L. Vitamin D and cancer. Front Endocrinol (Lausanne). 2012;3:58.
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CONFIDENCE Helps maintain healthy heart and arteries*
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One of the reasons I use French is Grape Seed VX1 in my research ion. orpt abs its purity and increased
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’’
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While other grape seed products on the market can be adulterated with cheap ingredients that can fool those who don’t test carefully, Clinical OPC is the real deal. Our French grape seed extract VX1 is tested, verified, and NEVER adulterated—guaranteed. You can’t go wrong with Clinical OPC. EuroPharmaUSA.com MONEY-BACK GUARANTEE †Supports healthy levels already within normal range. ^Cellular protection from oxidative stress. ‡Member of the EuroPharma, Inc. Scientific Advisory Board. 19
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