One Year of Seal Oil Omega-3 Supplementation Stops the Progression of Diabetic Sensorimotor Polyneuropathy: Results from a Clinical Pilot Trial
Backgrounds: Diabetic sensorimotor peripheral neuropathy (DSP) is the leading complication in diabetes mellitus (DM) for which there are currently no intervention therapies. Corneal nerve fibre length (CNFL) measured by in vivo corneal confocal microscopy (IVCCM) is a biomarker for DSP onset and progression in T1DM. Longitudinal data shows an annual change of -1.6% in T!DM, while healthy controls change +5%. Omega-3 polyunsaturated fatty acids (N-3 PUFA) are essential for the development and maintenance of nerves, but have not yet been investigated for their ability to stop the progression of DSP.
Results: Forty participants (53% female), aged 48+14, BMI 28.1 +5.8 with diabetes duration of 27+18 years were enrolled in the trial. The finding show that 12 months of seal oil supplementation can stop the progression of DSP measured by CNFL N-3 supplementation could be a targeted nutritional therapy to address small nerve fibre damage in DSP.
Lewis, E., Perkins, B., Lovblom, E., et al. (2016) One Year of Seal Oil Omega-3 Supplementation Stops the Progression of Diabetic Sensorimotor Polyneuropathy: Results from a Clinical Pilot Trial. Canadian Journal of Diabetes.
Lutein, Zeaxanthin, and meso-Zeaxanthin in the Clinical Management of Eye Disease
Lutein, zeaxanthin, and meso-zeaxanthin are xanthophyll carotenoids found within the retina and throughout the visual system. The retina is one of the most metabolically active tissues in the body. The highest concentration of xanthophylls is found within the retina, and this selective presence has generated many theories regarding their role in supporting retinal function.
Subsequently, the effect of xanthophylls in the prevention and treatment of various eye diseases has been examined through epidemiological studies, animal studies, and clinical trials. This paper attempts to review the epidemiological studies and clinical trials investigating the effects of xanthophylls on the incidence and progression of various eye diseases.
Observational studies have reported that increased dietary intake and higher serum levels of lutein and zeaxanthin are associated with lower risk of age-related macular degeneration (AMD), especially late AMD.
Randomized, placebo-controlled clinical trials have demonstrated that xanthophyll supplementation increases macular pigment levels, improves visual function, and decreases the risk of progression to late AMD, especially neovascular AMD. Current publications on the preventive and therapeutic effects of lutein and zeaxanthin on cataracts, diabetic retinopathy, and retinopathy of prematurity have reported encouraging results.
Scripsema, N.K., Hu, D.N., Rosen, R.B. (2015). Lutein, Zeaxanthin, and meso-Zeaxanthin in the Clinical Management of Eye Disease. Journal Ophthalmol. doi: 10.1155/2015/865179.
Beneficial properties of Probiotics
This review has focused on several beneficial properties of probiotics. One of the most known health effects of probiotics is preventing and ameliorating bowel diseases by improving the immune system. Besides that, probiotics are found to exhibit hypocholesterolemic effects via cholesterol assimilation, binding of cholesterol to cellular surface, co-precipitation of cholesterol, interfering with the formation of micelle for intestinal absorption, deconjugation of bile acids by BSH, and improving the lipid profiles. Apart from these conventional beneficial effects, probiotics have been reported to improve atopic eczema, wound and scars healing, and possess skin-rejuvenating properties. It has been suggested that probiotics could exhibit beneficial dermal effects by producing bacterial compounds which evoke certain immune responses and improve skin barrier functions. Probiotics could also be used to prevent and treat oral diseases. They are found to improve/prevent dental caries and periodontal infection via growth inhibition of cariogenic bacteria and periodontopathogens. Additionally, they have been shown to reduce the production of nitric oxide, which subsequently suppresses the prostaglandin and matrix metalloproteinases levels in saliva. Moreover, the unpleasant odour from the oral cavity in halitosis could also be ameliorated by inhibiting the growth of volatile sulphide-producing species. On the other hand, improvement of stress-related psychiatric disorders such as anxiety and depression via modulation of gut-brain axis by probiotics has also further emphasised the importance of probiotics. However, more scientific developments are needed to establish the potential application of probiotics. There is no doubt that the application of probiotics for human health will expand to a greater degree with the current significant research progress.
Shi, H. Y., Balakrishnan, K., Ismail M., et al. (2016) Beneficial properties of probiotics. Tropical Life Science. Aug 27(2) 73-90.
Abstract
Recent studies suggest that lecithin-rich diet can modify cholesterol homeostasis and hepatic lipoprotein metabolism. Considering the phytotherapeutic impact of lecithin, this work hypothesizes that lecithin administration in hypercholesterolemic patients may reduce cholesterol concentrations by increasing biliary secretion. Total cholesterol and LDL were evaluated after soy lecithin administration in hypercholesterolemic patients. One soy lecithin capsule (500 mg/RP-Sherer) was administrated daily. One-two months before the treatment beginning, blood samples were collected for total lipids and cholesterol fractions analysis. The results showed a reduction of 40.66% and 42.00% in total cholesterol and of 42.05% and 56.15% in LDL cholesterol after treatment for one and two months, respectively. A significant reduction in total cholesterol and LDL-cholesterol concentrations was observed during the first month of treatment, suggesting that the administration of soy lecithin daily may be used as a supplemental treatment in hypercholesterolemia.
Conclusion
Lecithin-rich diets can stimulate the fatty acid secretion with high levels of cholesterol and phospholipids when compared with diets without lecithin, considering the lecithin performance as phytotherapic, with a large spectrum of activity. The results showed significant reduction in the concentration of total cholesterol and LDL-cholesterol during the first month, suggesting that the daily administration of lecithin capsule could be used as an adjuvant treatment in hypercholesterolemia, possibly by reducing the intestinal absorption or by the increased secretion of bile acids with high levels of cholesterol and phospholipids.
Amouni, M. M., Eder, C. P., Gava, P., Sabha. M., Moriel, P. (2010). Influence of Soy Lecithin administration on hypercholesterolemia. Cholesterol, doi: 10.1155/2010/824813
Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065734/
Research suggests seal oil could help people with Type 1 diabetes
TORONTO, June 13, 2017 – A research team at the Krembil Neuroscience Centre in Toronto has published a paper that suggests seal oil has the potential to help promote nerve regeneration in patients with Type 1 diabetes.
The study found that patients who ingested an omega-3 supplement derived from seal oil twice a day over a 12-month period reported an increase in corneal nerve fibre length. The paper entitled, "The effects of omega-3 supplementation on neuropathy in Type 1 diabetes," was published in the June, 2017 issue of Neurology, the medical journal of the American Academy of Neurology.
"Nothing like this has been attempted in humans before," says Dr. Evan Lewis, a neurologist and one of the study's authors. "Results from this trial are a very important step towards a clinical therapy for people with diabetic neuropathy."
Diabetic neuropathy is a form of nerve damage caused by diabetes. Symptoms vary from patient to patient, but can include tingling, numbness, loss of sensation, a feeling of burning in the hands and feet, constant pain and difficulty walking. There are currently no therapies available for patients that stop or reverse its effects.
"This study is the first to show that targeted nutritional invention can stop and reverse small fibre damage," says Dr. Vera Bril, head of the division of Neurology in the Department of Medicine, and Medical Director of the Ellen Prosserman Centre for Neuromuscular Diseases at UHN, and the study's principal investigator. Other members of the research team included Dr. Bruce Perkins of the Leadership Sinai Centre for Diabetes as well as Dr. Thomas Wolever and Dr. Richard Bazinet, both of the University of Toronto's Department of Nutritional Sciences.
Retrieved from :https://www.uhn.ca/corporate/News/PressReleases/Pages/research_suggests_seal_oil_could_help_people_Type1_diabetes.aspx
Omega-3, a polyunsaturated fatty acid, is an essential fatty acid necessary for human health, and it protects against cardiovascular disease, inflammation, autoimmune diseases, and cancer. In the present study, we investigated the effects of omega-3-rich harp seal oil (HSO) on the production of nitric oxide (NO) and cytokines, such as tumor necrosis factor (TNF)-α, interleukin-(IL)-1β, IL-6, and IL-12/IL-23 (p40) in peritoneal macrophages of mice. The culture supernatants of murine macrophages exposed to lipopolysaccharide (LPS), HSO, or HSO+LPS were harvested to assay IL-1β, TNF-α, IL-6, and IL-12/IL-23 (p40) cytokines and NO. TNF-α, IL-1 β, and IL-12/IL-23 (p40) levels, except IL-6, were lower in the culture supernatants of mouse peritoneal macrophages exposed to LPS plus HSO than those of the groups exposed to LPS alone. These observations demonstrate that omega-3-rich harp seal oil downregulates the production of the pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-12/IL-23 (p40). These results suggest that HSO could be potentially used as a preventive agent or as an adjunct in anti-inflammatory therapy, if more research results were accumulated.
In conclusion, we observed changes in the levels of expression of inflammatory cytokines, such as TNF-α, IL-1β, IL-6, IL-12/23A (p40), and NO using endotoxic LPS stimulation to observe the effects of HSO, which is known to be abundant in ω-3-polyunsaturated fatty acids. Administration of LPS to murine peritoneal macrophages led to a significant increase in TNF-α, IL-1β, IL-6, IL-12/23A (p40), and NO, and co-administration of HSO with LPS significantly reduced the formation of IL-1β, TNF-α, and IL-12/IL-23 (p40) with an increase in incubation time. The formation of NO was also reduced. Therefore, administration of ω-3-abundant HSO seemingly down-regulates the formation of pro-inflammatory cytokines. This is expected to be useful in the reduction of inflammation as well as in the management of immune diseases. We think that the molecular mechanism of the anti-inflammatory function of HSO needs to be investigated further. Also, additional experiments on the changes in IL-6 and NO levels by treatment with HSO alone may be required.
Retrieved from: Effects of Omega-3-Rich Harp Seal Oil on the Production of Pro-Inflammatory Cytokines in Mouse Peritoneal Macrophages (nih.gov)
Choi, M., Ju, J., Suh, S. J., Park, Y. K., Kim, H. K. (2015) Effects of Omega-3-Rich Harp Seal Oil on the production of pro-inflammatory cytokines in mouse peritoneal macrophages. Preventive Nutrition and Food Science, 20(2): 83-87
The rapid international spread of severe acute respiratory syndrome coronavirus 2 responsible for coronavirus disease 2019 (COVID-19) has posed a global health emergency in 2020. It has affected over 52 million people and led to over 1.29 million deaths worldwide, as of November 13th, 2020. Patients diagnosed with COVID-19 present with symptoms ranging from none to severe and include fever, shortness of breath, dry cough, anosmia, and gastrointestinal abnormalities. Severe complications are largely due to overdrive of the host immune system leading to “cytokine storm”. This results in disseminated intravascular coagulation, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Due to its highly infectious nature and concerning mortality rate, every effort has been focused on prevention and creating new medications or repurposing old treatment options to ameliorate the suffering of COVID-19 patients including the immune dysregulation. Omega-3 fatty acids are known to be incorporated throughout the body into the bi-phospholipid layer of the cell membrane leading to the production of less pro-inflammatory mediators compared to other fatty acids that are more prevalent in the Western diet. In this article, the benefits of omega-3 fatty acids, especially eicosapentaenoic acid and docosahexaenoic acid, including their anti-inflammatory, immunomodulating, and possible antiviral effects have been discussed.
In conclusion, the article stated that there are various benefits of omega 3 fatty acids. Taking it as a supplement might be associated with the prevention of the viral entry by changing the composition of fats in the bilipid membrane of cells. It also reduces the proinflammatory mediators thus decreasing inflammation of the lung by several processes such as reducing pulmonary neutrophils recruitment, increasing apoptosis by macrophages, and subsequently decreasing broncho-alveolar IL-6 production.
Hathaway, D.,Panday, K., Patel, M., Rodriguez, I., et. al. (2020). Omega 3 Fatty Acids and COVID 19: A comprehensive Review. Infection and chemotherapy. 52(4): 478-495
Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779984/
KEY POINTS
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Coenzyme Q10 (CoQ10) is an essential cofactor in oxidative phosphorylation in mitochondria and is fundamentally important to cellular energy (ATP) production. Additionally, CoQ10 has direct antioxidant effects.
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Cellular depletion of CoQ10 is hypothesized as one pathophysiologic cause of statin-associated myopathy syndrome (SAMS) and may be a contributing factor to myocardial dysfunction in patients with congestive heart failure (CHF).
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Although clinical trials of CoQ10 in SAMS have produced conflicting conclusions, meta-analysis supports the use of CoQ10 in patients with SAMS.
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In patients with chronic CHF, one randomized clinical trial, Q-SYMBIO, suggests a role for CoQ10 in improving symptoms and reducing major adverse clinical events, particularly in patients with milder left ventricular dysfunction.
Raizner, E. A. (2019). Coenzyme Q10. Methodist Debakey Cardiovasc Journal. 15(3): 185–191.doi: 10.14797/mdcj-15-3-185
Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822644/
Abstract
Lecithin is a complex mixture of phospholipids which compose lipid bilayer cell membranes. Lipid replacement therapy, or administration of phospholipids for the purpose of repairing the dmaged cell membranes, had been shown to alleviate fatigue. The present study aimed to investigate the effect of soy lecithin on fatigue in middle-aged women, as well as other menopausal symptoms and various health parameters.
Conclusions
High-dose (1200 mg/day) soy lecithin not only increases vigor, but also lowers the diastolic blood pressure and cardio-ankle vascular index in middle-aged women who present with fatigue.
Hirose, A., Terauchi, M., Osaka, Y., Akiyoshi, M., Kato, K., Miyasaka, N. (2018). Effect of soy lecithin on fatigue and menopausal symptoms in middle-aged women: a randomized, double-blind, placebo-controlled study. Nutrition Journal. doi: 10.1186/s12937-018-0314-5
Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757297/
Grape seed
Grapes (Vitis vinifera) have been heralded for their medicinal and nutritional value for thousands of years. Egyptians ate grapes at least 6,000 years ago, and several ancient Greek philosophers praised the healing power of grapes, usually in the form of wine. European folk healers made an ointment from the sap of grapevines to treat skin and eye diseases. Grape leaves were used to stop bleeding, inflammation, and pain, such as the kind brought on by hemorrhoids. Unripe grapes were used to treat sore throats, and dried grapes (raisins) were used for constipation and thirst. Round, ripe, sweet grapes were used to treat a range of health problems including cancer, cholera, smallpox, nausea, eye infections, and skin, kidney, and liver diseases.
But grapes, or the chemicals within them, especially oligomeric proanthocyanidin complexes (OPCs), have been touted as powerful antioxidants. Some people believe they could help treat a number of conditions, from heart disease to cancer to aging skin, although scientific evidence is mostly lacking for those conditions. However, there is good evidence that grape seed extract can help treat chronic venous insufficiency and edema.
A study of healthy volunteers found that taking grape seed extract substantially increased blood levels of antioxidants. Antioxidants are substances that destroy free radicals, which are harmful compounds in the body that damage DNA (genetic material) and even cause cell death. Scientists believe free radicals contribute to aging, as well as the development of a number of health problems, including heart disease and cancer.
Plant Description
Grapes are native to Asia near the Caspian Sea, but they were brought to North America and Europe. This plant's climbing vine has large, jagged leaves, and its stem bark tends to peel. The grapes may be green, red, or purple.
What is it Made Of?
Vitamin E, flavonoids, linoleic acid, and OPCs are highly concentrated in grape seeds. Lower concentrations of these compounds are also available in the skin of the grape, as well as grape juice and wine. Resveratrol is another compoud in grapes and grape skins that is related to OPCs. Resveratrol has become very popular as an antioxidant and is being studied in connection with a variety of diseases.
Medicinal Uses and Indications
Today, standardized extracts of grape seed may be used to treat a range of health problems related to free radical damage, including heart disease, diabetes, and cancer. Grape seed extract has also been shown to protect against bacterial infections, such as Staphylococcus aureus. Some studies, mostly in animals, support these uses.
Flavonoids found in red wine may help to protect the heart by lowering LDL ("bad") cholesterol. The so called "French paradox" is the belief that drinking wine protects people living in France from developing heart disease at the high rates seen in people living in the United States. So far, however, there is no clear evidence that taking grape seed extract helps reduce the risk of heart disease. Some researchers speculate that the alcohol in the wine, not the flavonoids, could be responsible for any healthful effects. Others think it could be the combination of alcohol and flavonoids.
Drinking alcohol to protect against heart disease is not advocated by the American Heart Association and other organizations because of the potential for addiction and other serious problems, such as car accidents and the increased risk of hypertension, liver disease, breast cancer, and weight gain. If you do drink red wine, you should have no more than 2 glasses (20 g ethanol) per day if you are a man, and no more than 1 glass per day if you are a woman.
Chronic venous insufficiency
In chronic venous insufficiency, blood pools in the legs, causing pain, swelling, fatigue, and visible veins. A number of high quality studies have shown that OPCs from grape seed can reduce symptoms.
Edema
Edema, swelling caused by surgery or an injury, seems to go away faster when people take grape seed extract. Edema is common after breast cancer surgery, and one double-blind, placebo-controlled study found that breast cancer patients who took 600 mg of grape seed extract daily after surgery for 6 months had less edema and pain than those who took placebo. Another study found that people who took grape seed extract after experiencing a sports injury had less swelling than those who took placebo.
High cholesterol
There is not enough evidence to say whether taking grape seed extract can lower cholesterol, although preliminary studies show promising results. A study of 40 people with high cholesterol looked at whether taking grape seed extract, chromium, a combination of both, or placebo for 2 months would lower cholesterol. The combination of grape seed extract and chromium was more effective than either grape seed alone or placebo in lowering total and LDL cholesterol.
Another study looked at the effects of a proprietary grape seed extract on lipid peroxidation (the breakdown of fats in the blood) in a group of heavy smokers. In the study, 24 healthy male smokers (aged 50 years or older) took either placebo or 2 capsules (75 mg of a grape procyanidin extracts and soy phosphatidalcholine), twice daily for 4 weeks. LDL cholesterol levels were lower in those taking the grape seed supplement than those taking placebo.
High blood pressure
Theoretically, grape seed extract might help treat hypertension or high blood pressure. Antioxidants, like the ones found in grape seed, help protect blood vessels from damage. Damaged blood vessels can lead to higher blood pressure. In several animal studies, grape seed extract substantially reduced blood pressure. More research is needed to determine whether grape seed extract helps people with high blood pressure.
Cancer
Studies have found that grape seed extracts may prevent the growth of breast, stomach, colon, prostate, and lung cancer cells in test tubes. However, there is no clear evidence whether it works in humans. Antioxidants, such as those found in grape seed extract, may help reduce the risk of developing cancer. Grape seed extract may also help prevent damage to human liver cells caused by chemotherapy medications. Talk to your doctor or pharmacist before combining antioxidants with any chemotherapy drugs to make sure they interact safely together, and that they do not interfere with effects of the chemotherapy medications.
Other conditions
Grape seed extract is sometimes suggested for the following, although evidence is slight:
- Alzheimer disease
- Diabetes (improving blood sugar control)
- Improving night vision
- Protecting collagen and elastin in skin (anti-aging)
- Treating hemorrhoids
- Protecting against oxidative rancidity and bacterial pathogens
Available Forms
Grape seed is available as a dietary supplement in capsules, tablets, and liquid extracts. Look for products that are standardized to 40 to 80% proanthocyanidins or an OPC content of not less than 95%.
How to Take It
Pediatric
Grape seed extracts are not recommended for children. Grapes, however, make a healthy and safe snack for children.
Adult
Grape seed often comes in standardized extracts with certain levels of proanthocyanidins. Speak to a knowledgeable provider to find the right dose for your issue.
Precautions
The use of herbs is a time-honored approach to strengthening the body and treating disease. Herbs, however, contain components that can trigger side effects and interact with other herbs, supplements, or medications. For these reasons, you should take herbs with care, under the supervision of a health care provider qualified in the field of botanical medicine. Common side effects include nausea, itching, dizziness, stomach upset, diarrhea, headache, sore throat, cough, and rash.
Pregnant or breastfeeding women should not take grape seed supplements.
Possible Interactions
Grape seed extract can potentially affect medications broken down by the liver. Numerous medications are broken down by the liver, so check with your physician. Also, OPCs in grape seed extract may interact with the following:
Anticoagulants (blood thinners): Grape seed extract may act as a blood thinner, and could increase the risk of bleeding if taken with other blood thinners such as warfarin (Coumadin), clopidogrel (Plavix), or aspirin. If you are taking blood-thinning medications, or have bleeding disorders, ask your doctor before taking grape seed extract.
Phenacetin: Drinking grape juice may increase how quickly the body breaks down Phenacetin to get rid of it. This may decrease the effectiveness of the Phenacetin you are taking.
Supporting Research
Al-Habib A. Bactericidal effect of grape seed extract on methicillin resistant Staphylococcus aureus (MRSA). J Toxicol Sci. 2010;35(3):357-64.
Anastasiadi M, Chorianopoulos NG, Nychas GJ, Haroutounian SA. Antilisterial activities of polyphenol-rich extracts of grapes and vinification byproducts. J Agric Food Chem. 2009;57(2):457-63.
Bagchi D, Sen CK, Ray SD, et al. Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. Mutat Res. 2003;523-524:87-97.
Banerjee B, Bagchi D. Beneficial effects of a novel IH636 grape seed proanthocyanidin extract in the treatment of chronic pancreatitis. Digestion. 2001;63(3):203-206.
Belleville J. The French paradox: possible involvement of ethanol in the protective effect against cardiovascular diseases. Nutrition. 2002;18(2):173-177.
Bernstein BJ, Grasso T. Prevalence of complementary and alternative medicine use in cancer patients. Oncology. 2001;15(10):1267-1272; discussion 1272-1278, 1283.
Bielory L. Complementary and alternative interventions in asthma, allergy, and immunology. Ann Allergy Asthma Immunol. 2004;93(2 Suppl 1):S45-54.
Brooker S, Martin S, Pearson A, et al. Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration. Radiother Oncol. 2006;79(1):45-51.
Busserolles J, Gueux E, Balasinska B, et al. In vivo antioxidant activity of procyanidin-rich extracts from grape seed and pine (Pinus maritima) bark in rats. Int J Vitam Nutr Res. 2006;76(1):22-7.
Carlson S, Peng N, Prasain JK, Wyss JM. Effects of botanical dietary supplements on cardiovascular, cognitive, and metabolic function in males and females. Gend Med. 2008;5 Suppl A:S76-90. Review.
Chan MM, Mattiacci JA, Hwang HS, et al. Synergy between ethanol and grape polyphenols, quercetin, and resveratrol, in the inhibition of the inducible nitric oxide synthase pathway. Biochem Pharmacol. 2000;60(10):1539-1548.
Chou EJ, Keevil JG, Aeschlimann S, et al. Effect of ingestion of purple grape juice on endothelial function in patients with coronary heart disease. Am J Cardiol. 2001;88(5):553-555.
Décordé K, Teissèdre PL, Sutra T, Ventura E, Cristol JP, Rouanet JM. Chardonnay grape seed procyanidin extract supplementation prevents high-fat diet-induced obesity in hamsters by improving adipokine imbalance and oxidative stress markers. Mol Nutr Food Res. 2008 Nov 26. [Epub ahead of print]
Faria A, Calhau C, de Freitas V, et al. Procyanidins as antioxidants and tumor cell growth modulators. J Agric Food Chem. 2006;54(6):2392-7.
Fitzpatrick DF, Bing B, Maggi DA, et al. Vasodilating procyanidins derived from grape seeds. Ann NY Acad Sci. 2002;957:78-89.
Freedman JE, Parker C 3rd, Li L, et al. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation. 2001;103(23):2792-2798.
Gruenwalkd J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 4th ed. Montvale, NJ: Thomson Healthcare; 2007:405-410.
Hsu CP, Lin YH, Chou CC, Zhou SP, Hsu YC, Liu CL, Ku FM, Chung YC. Mechanisms of grape seed procyanidin-induced apoptosis in colorectal carcinoma cells. Anticancer Res. 2009;29(1):283-9.
Hu H, Qin YM. Grape seed proanthocyanidin extract induced mitochondria-associated apoptosis in human acute myeloid leukemia 14.3D10 cells. Chin Med J (Engl). 2006;119(5):417-21.
Hung LM, Chen JK, Huang SS, et al. Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovasc Res. 2000;47(3):549-555.
Joshi SS, Kuszynski CA, Bagchi D. The cellular and molecular basis of health benefits of grape seed proanthocyanidin extract. Curr Pharm Biotechnol. 2001;2(2):187-200.
Kalin R, Righi A, Del Rosso A, et al., Activin, a grape seed-derived proanthocyanidin extract, reduces plasma levels of oxidative stress and adhesion molecules (ICAM-1, VCAM-1 and E-selectin) in systemic sclerosis. Free Radic Res. 2002;36(8):819-25.
Kar P, Laight D, Rooprai HK, Shaw KM, Cummings M. Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress, and insulin sensitivity. Diabet Med. 2009;26(5):526-31.
Kaur M, Agarwal R, Agarwal C. Grape seed extract induces anoikis and caspase-mediated apoptosis in human prostate carcinoma LNCaP cells: possible role of ataxia telangiectasia mutated-p53 activation. Mol Cancer Ther. 2006;5(5):1265-74.
Kaur M, Agarwal C, Argarwal R. Anticancer and cancer chemopreventive potential of grape seed extract and other grape-based products. J Nutr. 2009;139(9):1806S-12S.
Kaur M, Mandair R, Agarwal R, Agarwal C. Grape seed extract induces cell cycle arrest and apoptosis in human colon carcinoma cells. Nutr Cancer. 2008;60 Suppl 1:2-11.
LaValle JB, Krinsky DL, Hawkins EB, et al. Natural Therapeutics Pocket Guide. Hudson, OH: LexiComp; 2000:451-452.
Nassiri-Asl M, Hosseinzadeh H. Review of the pharmacological effects of Vitis vinifera (Grape) and its bioactive compounds. Phytother Res. 2009 Jan 12. [Epub ahead of print]
Natella F, Belelli F, Gentili V, et al. Grape seed proanthocyanidins prevent plasma postprandial oxidative stress in humans. J Agric Food Chem. 2002;50(26):7720-5.
Preuss HG, Wallerstedt D, Talpur N, et al. Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: a pilot study. J Med. 2000;31(5-6):227-246.
Preuss HG, Bagchi D, Bagchi M. Protective effects of a novel niacin-bound chromium complex and a grape seed proanthocyanidin extract on advancing age and various aspects of syndrome X. Ann NY Acad Sci. 2002;957:250-9.
Ramchandani AG, Karibasappa GS, Pakhale SS. Antitumor-promoting effects of polyphenolic extracts from seedless and seeded Indian grapes. J Environ Pathol Toxicol Oncol. 2008;27(4):321-31.
Vigna GB, Costantini F, Aldini G, et al. Effect of a standardized grape seed extract on low-density lipoprotein susceptibility to oxidation in heavy smokers. Metabolism. 2003;52(10):1250-7.
Vitseva O, Varghese S, Chakrabarti S, et al. Grape seed and skin extracts inhibit platelet function and release of reactive oxygen intermediates. J Cardiovasc Pharmacol. 2005;46(4):445-51.
Waffo-Teguo P, Hawthorne ME, Cuendet M, et al. Potential cancer-chemopreventive activities of wine stilbenoids and flavans extracted from grape (Vitis vinifera) cell cultures. Nutr Cancer. 2001;40(2):173-179.
Wang YJ, Thomas P, Zhong JH, Bi FF, Kosaraju S, Pollard A, Fenech M, Zhou XF. Consumption of grape seed extract prevents amyloid-beta deposition and attenuates inflammation in the brain of an Alzheimer's disease mouse. Neurotox Res. 2009;15(1):3-14.
Yamakoshi J, Saito M, Kataoka S, et al. Safety evaluation of proanthocyanidin-rich extract from grape seeds. Food Chem Toxicol. 2002;40(5):599-607.
Zhang HJ, Ji BP, Chen G, Zhou F, Luo YC, Yu HQ, Gao FY, Zhang ZP, Li HY. A combination of grape seed derived procyanidins and gypenosides alleviates insulin resistance in mice and HepG2 cells. J Food Sci. 2009;74(1):H1-7.
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