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ZAMU™ What America Thinks - MetLife Foundation Alzheimer's Survey Alzheimer's Disease Ranks As One of the Most Feared Diseases in the United States Study by: Harris Interactive for MetLife Foundation, February 2011 A new survey by MetLife Foundation finds that Alzheimer’s disease is the second most feared disease among American adults, behind only cancer. When asked which of five major diseases they are most afraid, 31 % said Alzheimer’s, while 41% said cancer. Heart disease and stroke were named by 8% each, while only 6% said they fear diabetes most. A majority of those polled (62%) admit they know little or nothing about Alzheimer’s disease, leading to the fact that few are planning for its possibility. Only 18%, fewer than one in five people, have developed any such plan, which may include care options, housing arrangements and/or financial planning. Currently, more than five million people have Alzheimer’s. That number is expected to rise sharply as the Baby Boom generation reaches retirement age. 44% of adults indicate they have family members or friends with Alzheimer’s. Read Full Article Tropical fruit camu-camu (Myrciaria dubia) has anti-oxidative and anti-inflammatory properties. Inoue T, Komoda H, Uchida T, Node K. Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan. BACKGROUND: Oxidative stress as well as inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Although, various anti-oxidative dietary supplements have been evaluated for their ability to prevent atherosclerosis, no effective ones have been determined at present. "Camu-camu" (Myrciaria dubia) is an Amazonian fruit that offers high vitamin C content. However, its anti-oxidative property has not been evaluated in vivo in humans. METHODS: To assess the anti-oxidative and anti-inflammatory properties of camu-camu in humans, 20 male smoking volunteers, considered to have an accelerated oxidative stress state, were recruited and randomly assigned to take daily 70ml of 100% camu-camu juice, corresponding to 1050mg of vitamin C (camu-camu group; n=10) or 1050mg of vitamin C tablets (vitamin C group; n=10) for 7 days. RESULTS: After 7 days, oxidative stress markers such as the levels of urinary 8-hydroxy-deoxyguanosine (P<0.05) and total reactive oxygen species (P<0.01) and inflammatory markers such as serum levels of high sensitivity C reactive protein (P<0.05), interleukin (IL)-6 (P<0.05), and IL-8 (P<0.01) decreased significantly in the camu-camu group, while there was no change in the vitamin C group. CONCLUSIONS: Our results suggest that camu-camu juice may have powerful anti-oxidative and anti-inflammatory properties, compared to vitamin C tablets containing equivalent vitamin C content. These effects may be due to the existence of unknown anti-oxidant substances besides vitamin C or unknown substances modulating in vivo vitamin C kinetics in camu-camu. PMID: 18922386 [PubMed - in process]

Camu-camu Myrciaria dubia (HBK) McVaugh: Chemical composition of fruit Abstract: The chemical composition of the Peruvian camu-camu fruit Myrciaria dubia(HBK) McVaugh was analysed at three stages of maturity (immature, midripe and ripe). As fruit matured, levels of ascorbic and dehydroascorbic acids, reducing sugars (fructose and glucose were the major sugars), amino acids (serine, valine and leucine) and soluble solids increased. Citric acid was the major acid (from 19.8 up to 29.8 g kg-1) and was responsible for the fruit's sour taste. Unlike citric acid, malic acid increased with maturation. Among the macronutrients, potassium was the most abundant mineral (711 mg kg-1) and could be considered, like vitamin C, nutritionally significant. During maturation, the fruit pulp colour turned from yellow-green to pink, presumably due to the migration of anthocyanin pigments from the peel. Sergio M Zapata, Jean-Pierre Dufour * Unité de Brasserie et des Industries Alimentaires, Catholic University of Louvain, Place Croix du Sud 2, Bte 7, B-1348 Louvain-la-Neuve, Belgium *Correspondence to Jean-Pierre Dufour, Unité de Brasserie et des Industries Alimentaires, Catholic University of Louvain, Place Croix du Sud 2, Bte 7, B-1348 Louvain-la-Neuve, Belgium. Keywords Myrciaria dubia (HBK) McVaugh • camu-camu • chemical composition • fruit maturation. http://www3.interscience.wiley.com/journal/113322680/abstract

Antioxidant compounds and antioxidant capacity of Peruvian camu camu (Myrciaria dubia (H.B.K.) McVaugh) fruit at different maturity stages The antioxidant capacities of ascorbic acid and phenolic compounds present in camu camu fruit were screened during ripening. Ascorbic acid decreased, and anthocyanin, flavonol and flavanol contents, and DPPH antioxidant capacity increased during ripening. Antioxidant compounds from camu camu were fractionated in two fractions: an ascorbic acid-rich fraction (F-I) and a phenolics-rich fraction (F-II). F-I was the major contributor to the DPPH antioxidant capacity (67.5–79.3%) and F-II played a minor role (20.7–32.5%). A total of 30 different phenolic compounds were detected by HPLC-PAD. The presence of catechin, delphinidin 3-glucoside, cyanidin 3-glucoside, ellagic acid and rutin was elucidated. Other phenolic compounds, such as flavan-3-ol, flavonol, flavanone and ellagic acid derivatives, were also present. For the three ripening stages the flavan-3-ols and ellagic acid group were the most representative phenolic compounds in this fruit. Acid hydrolysis of F-II revealed the presence mainly of gallic and ellagic acids, suggesting that camu camu fruit possesses important quantities of hydrolysed tannins (gallo- and/or ellagitannins). These results confirm that camu camu fruit is a promising source of antioxidant phenolics. Rosana Chirinos, Jorge Galarza, Indira Betalleluz-Pallardel, Romina Pedreschi and David Campos Instituto de Biotecnología (IBT), Universidad Nacional Agraria La Molina – UNALM, Av. La Molina s/n, Lima, Peru

Inhibition of liver fibrosis by ellagic acid. Chronic administration of carbon tetrachloride in liquid paraffin (1.7) ip; 0.15 ml, (20 doses) has been found to produce severe hepatotoxicity, as seen from the elevated levels of serum and liver glutamate-pyruvate transaminase, alkaline phosphatase and lipid peroxides. The chronic administration of carbon tetrachloride was also found to produce liver fibrosis as seen from pathological analysis as well as elevated liver-hydroxy proline. Oral administration of ellagic acid was found to significantly reduce the elevated levels of enzymes, lipid peroxide and liver hydroxy proline in these animals and rectified liver pathology. These results indicate that ellagic acid administration orally can circumvent the carbon tetrachloride toxicity and subsequent fibrosis. Thresiamma, K C : Kuttan, R Indian-J-Physiol-Pharmacol.

Effects of dietary ellagic acid on rat hepatic and esophageal mucosal cytochromes P450 and phase II enzymes Ellagic acid (EA), a naturally occurring plant polyphenol possesses broad chemoprotective properties. Dietary EA has been shown to reduce the incidence of N-2-fluorenyl acetamide-induced hepatocarcinogenesis in rats and N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumors. In this study changes in the expression and activities of specific rat hepatic and esophageal mucosal cytochromes P450 (P450) and phase II enzymes following dietary EA treatment were investigated. Liver and esophageal mucosal microsomes and cytosol were prepared from three groups of Fisher 344 rats which were fed an AIN-76 diet containing no EA or 0.4 or 4.0 g/kg EA for 23 days. In the liver total P450 content decreased by up to 25% and P450 2E1-catalyzed p-nitrophenol hydroxylation decreased by 15%. No changes were observed in P450 1A1, 2B1 or 3A1/2 expression or activities or cytochrome b5activity. P450 reductase activity decreased by up to 28%. Microsomal epoxide hydrolase (mEH) expression decreased by up to 85% after EA treatment, but mEH activities did not change. The hepatic phase II enzymes glutathione S-transferase (GST), NAD(P)H: quinone reductase (NAD(P)H: QR) and UDP glucuronosyltransferase (UDPGT) activities increased by up to 26, 17 and 75% respectively. Assays for specific forms of GST indicated marked increases in the activities of isozymes 2-2(190%), 4-4 (150%) and 5-5 (82%). In the rat esophageal mucosa only P450 1A1 could be detected by Western blot analysis and androstendione was the only P450 metabolite of testosterone detectable. However, there were no differences in the expression of P450 1A1, the formation of androstendione or NAD(P)H: QR activities between controland EA-fed rats in the esophagus. Although there was no significant decrease in overall GST activity, as measured with 1-chloro-2, 4-dinitrobenzene (CDNB), there was a significant decrease in the activity of the 2-2 isozyme (66% of control). In vitro incubations showed that EA at a concentration of 100 µM inhibited P450 2E1, 1A1 and 2B1 activities by 87, 55 and 18% respectively, but did not affect 3A1/2 activity. Using standard steady-state kinetic analyses, EA was shown to be a potent non-competitive inhibitor of both liver microsomal ethoxyresorufin O-deethylase and p-nitrophenol hydroxylase activities, with apparent K1 values of 55 and 14 µM respectively. In conclusion, these results demonstrate that EA causes a decrease in total hepatic P450 with a significant effect on hepatic P450 2E1, increases some hepatic phase II enzyme activities (GST, NAD(P)H: QR and UDPGT) and decreases hepatic mEH expression. It also inhibits the catalytic activity of some P450 isozymes in vitro. Thus the chemoprotective effect of EA against various chemically induced cancers may involve decreases in the rates of metabolism of these carcinogens by phase I enzymes, due to both direct inhibition of catalytic activity and modulation of gene expression, in addition to effects on the expression of phase II enzymes, thereby enhancing the ability of the target tissues to detoxify the reactive intermediates. Dean Ahn, David Putt, Laura Kresty, Gary D. Stoner, David Fromm and Paul F. Hollenberg 1Departments of Pharmacology and Surgery, Wayne State University Detroit, MI 48201 2Departments of Pharmacology and Laboratory of Cancer Chemoprevention and Etiology, Department of Preventive Medicine. The Ohio State University Columbus, OH 43210, USA

Quercetin Inhibits rhinovirus replication and subsequentchemokine response in Airway Epithelial Cells Rationale: Rhinovirus (RV), a single-stranded RNA virus from the picornaviridae family, is responsible for the majority of common colds. RV is an important trigger of COPD, asthma and CF exacerbations. Flavonoids with antioxidant and anti-inflammatory properties may be beneficial in the treatment of viral infections particularly in patients with underlying chronic lung diseases. Quercetin (3, 3’, 4’, 5, 7-pentahydroxyflavone) has potent antioxidant effects and inhibits various protein kinases by competing for ATP binding site. RV induces PI3 kinase-dependent chemkine responses and oxidative stressdependent disruption of barrier function in polarized airway epithelial cells. Therefore, we hypothesized that quercetin reduces RV-induced pro-inflammatory response and reduction in transepithelial resistence of polarized airway epithelial cells. Method: Polarized 16HBE14o- cells were infected with major or minor group RV or replication-deficient UV-irradiated virus (UV-RV) and incubated for 1 hour at 33°C to allow binding and endocytosis of RV. Infection media was then replaced with fresh media containing either quercetin; LY294002, a chemical inhibitor of PI3-kinase, or diphenyleneimidonium (DPI), an inhibitor of NADPH oxidase. After incubation for 8 or 24 hours, TER was measured and media was collected for IL-8 and IL-29 (IFN-l1) analysis, and the cells harvested for Western blot analysis and determination of viral titer. Results: Quercetin inhibited RV-induced reduction in TER, decreased RV-stimulated IL-8 expression. Surprisingly, we also observed reduction in interferon response, viral titer and complete abrogation of RV-triggered cleavage of eIF4GI, which is required for efficient translation of viral polypeptide. On the other hand, LY294002 although affected IL-8 response, had no effect on IL-29 response, viral titer or RV-induced cleavage of eIF4GI. DPI partially reduced viral titer and RV-induced effects in airway epithelial cells Conclusions: Our results suggest that quercetin may reduce RV-triggered cytokine response, and disruption of barrier function by inhibiting viral replication and virus induced cleavage of eIF4GI. Further, the observed effects of quercetin on viral replication may be attributed to its antioxidant effects and not on its effect on PI3-kinase activity. Therefore, quercetin may be beneficial in the treatment of viral infections, particularly in patients with underlying chronic lung disease. S. Ganesan, MS, S. Chattoraj, MS, A.N. Faris, Ph.D., A. Comstock, BS, U. Sajjan, PhD University of Michigan - Ann Arbor, MI/US Quercetin, a widely distributed bioflavonoid, has been shown to induce growth inhibition in certain cancer cell types. In the present study we have pursued the mechanism of growth inhibition in MCF-7 human breast cancer cells. Quercetin treatment resulted in the accumulation of cells specifically at G2/M phase of the cell cycle. Mitotic index measured by MPM2 staining clearly showed that cells were transiently accumulated in M phase, 24 h after treatment. The transient M phase accumulation was accompanied by a transient increase in the levels of cyclin B 1 and Cdc2 kinase activity. However, 24 h or longer treatment caused a marked accumulation of cells in G2 instead of M phase. Levels of cyclin Bl and cyclin B1-associated Cdc2 kinase activity were also decreased. We also found that quercetin markedly increased Cdk-inhibitor p21CIP1/WAF1 protein level after treatment for 48 h or longer, and the induction of p21CIP1/WAF1 increased its association with Cdc2-cyclin B1 complex, however, up-regulation of p53 by quercetin was not observed. Quercetin also induced significant apoptosis in MCF-7 cells in addition to cell cycle arrest, and the induction of apoptosis was markedly blocked by antisense p21CIP1/WAF1 expression. The present data, therefore, demonstrate that a flavonoid quercetin induces growth inhibition in the human breast carcinoma cell line MCF-7 through at least two different mechanisms; by inhibiting cell cycle progression through transient M phase accumulation and subsequent G2 arrest, and by inducing apoptosis. CHOI Jung-A (1) ; KIM Ja-Young (1) ; LEE Jeong-Yim (2) ; KANG Chang-Mo (1) ; KWON Ho-Jeong (3) ; YOO Young-Do (1) ; KIM Tae-Whan (1) ; LEE Yun-Sil (1) ; LEE Su-Jae (1) ; (1) Laboratory of Radiation Effect, Korea Cancer Center Hospital, Seoul 139-706, COREE, REPUBLIQUE DE (2) Department of Biological Sciences, Ajou University, Suwon 442-749, COREE, REPUBLIQUE DE (3) Department of Bioscience and Biothechnology, Sejong University, Seoul 143-747, COREE, REPUBLIQUE DE

Vitamin C and Cognition A high vitamin C intake may protect against both cognitive impairment and cerebrovascular disease. http://www.bmj.com/cgi/content/abstract/312/7031/608 Cognitive impairment and mortality in a cohort of elderly people Catharine R Gale, research student,a Christopher N Martyn, clinical scientist,a Cyrus Cooper, clinical scientist a a MRC Environmental Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton SO16 6YD Correspondence to: Dr Martyn.

Vitamins C/E and Dementia; Cognition These results suggest that vitamin E and C supplements may protect against vascular dementia and may improve cognitive function in late life. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men K. H. Masaki, MD, K. G. Losonczy, MA, G. Izmirlian, PhD, D. J. Foley, MS, G. W. Ross, MD, H. Petrovitch, MD, R. Havlik, MD and L. R. White, MD From the Honolulu–Asia Aging Study (Drs. Masaki, Petrovitch, and White), Kuakini Medical Center, Honolulu, HI; the Division of Geriatric Medicine (Drs. Masaki, Petrovitch, and Ross), University of Hawaii, John A. Burns School of Medicine, Honolulu, HI; the Epidemiology, Demography, and Biometry Program (Drs. Izmirlian, Havlik, and White, and K. Losonczy and D. Foley), National Institute on Aging, National Institutes of Health, Bethesda, MD; and the Department of Veteran’s Affairs (Dr. Ross), Honolulu, HI. Address correspondence and reprint requests to Dr. Kamal H. Masaki, The Honolulu Heart Program, 347 North Kuakini Street, HPM 9, Honolulu, HI 96817; e-mail: kamal@hhp2.hawaii-health.com http://www.neurology.org/cgi/content/abstract/54/6/1265

Vitamins C/E and Cognition Long-term, current users of vitamin E with vitamin C had significantly better mean performance, as judged by a global score that combined individual test scores, than did women who had never used vitamin E or C. High-dose antioxidant supplements and cognitive function in community-dwelling elderly women. Grodstein F, Chen J, Willett WC. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. fran.grodstein@channing.harvard.edu http://www.ncbi.nlm.nih.gov/pubmed/12663300?dopt=Abstract

Vitamins C/E/Carotene and Cognition/Delay High antioxidant intake from food and supplement sources of vitamin C, vitamin E, and carotene may delay cognitive decline in the elderly. Antioxidant intake and cognitive function of elderly men and women: the Cache County Study Alternative Medicine Review, Sept, 2007 by H.J. Wengreen, R.G. Munger, C.D. Corcoran Nutr Health Aging 2007;11:230-237. COPYRIGHT 2007 Thorne Research Inc. COPYRIGHT 2008 Gale, Cengage Learning http://findarticles.com/p/articles/mi_m0FDN/is_3_12/ai_n21066505

Flavonol and Dementia/Stroke/Cardio A pilot study evaluated the relationship between cerebral blood flow and a single acute dose (450 mg flavanols) of flavanol-rich cocoa and showed that flavanol-rich cocoa can increase the cerebral blood flow to gray matter, suggesting the potential of cocoa flavanols for treatment of vascular impairment, including dementia and strokes, and thus for maintaining cardiovascular health. fMRI = functional magnetic resonance imaging The Effect of Flavanol-rich Cocoa on the fMRI Response to a Cognitive Task in Healthy Young People Journal of Cardiovascular Pharmacology. 47 Supplement 2:S215-S220, June 2006. Francis, S. T. PhD *; Head, K. BSc(Hons) *; Morris, P. G. PhD *; Macdonald, I. A. PhD + http://www.cardiovascularpharm.com/pt/re/jcardiopharm/abstract.00005344-200606001-00018.htm;jsessionid=Lh1Vp56vbJQbLpYjQD3VZh67NFKKjr6ScpcS60Wq8tsnJdzK5Ttf!-1052912739!181195629!8091!-1

Flavonol and Dementia/Stroke/Cardio In summary, we show that dietary intake of FRC(flavonol rich cocoa) is associated with a significant increase in cerebral blood flow velocity in the MCA (middle cerebral artery) as measured by TCD (transcranial Doppler). Our data suggest a promising role for regular cocoa flavanol’s consumption in the treatment of cerebrovascular ischemic syndromes, including dementias and stroke. Neuropsychiatr Dis Treat. 2008 April; 4(2): 433–440. PMCID: PMC2518374 Published online 2008 April. Copyright © 2008 Sorond et al, publisher and licensee Dove Medical Press Ltd. Cerebral blood flow response to flavanol-rich cocoa in healthy elderly humans Farzaneh A Sorond,1,2 Lewis A Lipsitz,2,4 Norman K Hollenberg,3,5 and Naomi DL Fisher3 1Department of Neurology, Stroke Division, Boston, MA 2Institute for Aging Research, Hebrew SeniorLife, Boston, MA 3Department of Medicine, Endocrine-Hypertension Division, Boston, MA, USA 4Department of Medicine, Gerontology, Beth Israel Deaconess Medical Center, Boston, MA, USA 5Department of Radiology, Brigham and Women’s Hospital, Boston, MA Correspondence: Farzaneh A Sorond Brigham and Women’s Hospital, Neurology, Stroke Division, 45 Francis St, Boston, MA 02115, USA Tel +1 617 732 7432 Fax +1 617 278 6963 Email fsorond@partners.org http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2518374&rendertype=abstract

Cinnamon and insulin/anti-inflammatory response/anti-angiogenesis These results suggest that cinnamon exhibits the potential to increase the amount of proteins involved in insulin signaling, glucose transport, and anti-inflammatory/anti-angiogenesis response. Cinnamon extract and polyphenols affect the expression of tristetraprolin, insulin receptor, and glucose transporter 4 in mouse 3T3-L1 adipocytes Heping Cao, a, Marilyn M. Polanskya and Richard A. Anderson, a, aNutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Building 307C, BARC-East, 10300 Baltimore Avenue, Beltsville, MD 20705-2350, USA Received 8 November 2006; revised 20 December 2006. Available online 25 January 2007. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WB5-4MWY18K-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_version=1&_urlVersion=0&_userid=10&md5=21d95479a677c618a1fad8d9b584477b

Cinnamon and anti-inflammatory response The present results provided evidence that HCA, among cinnamaledhyde derivatives, has the most inhibitory effect on NO production through inhibition of NF-kappa B activation, and thus can be used as an anti-inflammatory agent. Biochem Pharmacol. 2005 Mar 1;69 (5):791-9 15710356 (P,S,G,E,B) Inhibitory effect of 2'-hydroxycinnamaldehyde on nitric oxide production through inhibition of NF-kappa B activation in RAW 264.7 cells. Seung Ho Lee, Sun Young Lee, Dong Ju Son, Heesoon Lee, Hwan Soo Yoo, Sukgil Song, Ki Wan Oh, Dong Cho Han, Byoung Mog Kwon, Jin Tae Hong College of Pharmacy, Chungbuk National University, Heungduk-gu, Cheongju 361-763, South Korea. http://lib.bioinfo.pl/pmid:15710356

Bromelain and anti-inflammatory response/anti-edema/anti-blood clotting Bromelain is a crude extract from the pineapple that contains, among other components, various closely related proteinases, demonstrating, in vitro and in vivo, antiedematous, antiinflammatory, antithrombotic and fibrinolytic activities. Bromelain: biochemistry, pharmacology and medical use. Maurer HR. Department of Biochemistry, Molecular Biology and Biotechnology, Institute of Pharmacy, Freie Universität Berlin, Germany. hrmaurer@zedat.fu-berlin.de http://www.ncbi.nlm.nih.gov/pubmed/11577981?dopt=Abstract

Bromelain and anti-inflammatory response/musculoskeletal In recent years, a number of clinical studies have appeared to substantiate one of the traditional therapeutic uses of extracts of bromelain, namely, in the treatment of inflammatory disorders of the musculoskeletal system. Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies Sarah Brien1,*, George Lewith1, Ann Walker2, Stephen M. Hicks2 and Dick Middleton3 1University of Southampton Southampton, UK, 2University of Reading Reading, UK, and 3Medic Herb UK Ltd UK http://ecam.oxfordjournals.org/cgi/content/full/1/3/251?maxtoshow=&HITS=60&hits=60&RESULTFORMAT=1&andorexacttitle=and&titleabstract=bromeline%2Cbromelain&andorexacttitleabs=or&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&tdate=//&resourcetype=HWCIT

Mango and bio-availability in juice A comparison between the three forms (juice, fresh and dried fruit) revealed that papaya and mangoes consumed in form of juice or fresh fruit are the best forms because they had higher bioavailability values. CONCLUSION: Association of these different forms of consumptions could lead to a better availability of these fruits throughout the year and therefore efficiently contribute to improve vitamin A status of the population. Systemic levels of carotenoids from mangoes and papaya consumed in three forms (juice, fresh and dry slice). Gouado I, Schweigert FJ, Ejoh RA, Tchouanguep MF, Camp JV. Faculty of Science, Department of Biochemistry, University of Douala, Douala, Cameroon. gouadoi@yahoo.fr http://www.ncbi.nlm.nih.gov/pubmed/17637601?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Antioxidants and their role in aging Therefore, since the immune system is an indicator of health and a longevity predictor, the protection of this system afforded by dietary antioxidant supplementation may play an important role in order to achieve a healthy ageing. Effects of antioxidants on immune system ageing M De la Fuente Departmento de Fisiología Animal, Facultad de Ciencias Biológicas, Universidad Complutense de Madrid, Madrid, Spain Correspondence to: M de la Fuente, Departmento de Fisiología Animal, Facultad de Ciencias Biológicas, Universidad Complutense, E-28040 Madrid, Spain European Journal of Clinical Nutrition (2002) 56, Suppl 3, S5-S8. doi:10.1038/sj.ejcn.1601476 http://www.nature.com/ejcn/journal/v56/n3s/abs/1601476a.html

Antioxidants and immune response Diets contain naturally occurring antioxidant compounds that can stabilize highly reactive, potentially harmful molecules called free radicals. Free radicals are generated during normal cellular metabolism and result from the metabolism of certain drugs or xenobiotics. Exposure to UV light, cigarette smoke, and other environmental pollutants also increases the body's free radical burden. The harmful activities of free radicals are associated with damage to membranes, enzymes, and DNA. The ability of antioxidants to destroy free radicals protects the structural integrity of cells and tissues. This review focuses on data indicating that the functions of the human immune system depend on the intake of micronutrients, which can act as antioxidants. Recent clinical trials have found that antioxidant supplementation can significantly improve certain immune responses. Specifically, supplementation with vitamins C, E, and A or ß-carotene increased the activation of cells involved in tumor immunity in the elderly. Supplementation with the antioxidant vitamins also protected immune responses in individuals exposed to certain environmental sources of free radicals. Physiological Role of Antioxidants in the Immune System Adrianne Bendich 1 1 Human Nutrition Research, Hoffmann-LaRoche Inc., Nutley, NJ 07110 http://jds.fass.org/cgi/content/abstract/76/9/2789

Cinnamon and glucose/triglyceride/cholesterol The results of this study demonstrate that intake of 1, 3, or 6 g of cinnamon per day reduces serum glucose, triglyceride, LDL cholesterol, and total cholesterol in people with type 2 diabetes and suggest that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases. Cinnamon Improves Glucose and Lipids of People With Type 2 Diabetes Alam Khan, MS, PHD1,2,3, Mahpara Safdar, MS1,2, Mohammad Muzaffar Ali Khan, MS, PHD1,2, Khan Nawaz Khattak, MS1,2 and Richard A. Anderson, PHD3 http://care.diabetesjournals.org/cgi/content/abstract/26/12/3215

Cinnamon Glucose These data illustrate that cinnamon spice supplementation may be important to in vivo glycaemic control and insulin sensitivity in humans, and not only are its effects immediate, they also appear to be sustained for 12 h. Solomon TP, Blannin AK. Diabetes Obes Metab. 2007 Nov;9(6):895-901 Effects of short-term cinnamon ingestion on in vivo glucose toleranceSchool of Sport and Exercise Sciences, University of Birmingham, Birmingham, UK. http://www.ncbi.nlm.nih.gov/pubmed/17924872?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Bromelain and anti-inflammatory response/non osteoperosis We conclude that bromelain may be effective in ameliorating physical symptoms and improving general well-being in otherwise healthy adults suffering from mild knee pain in a dose-dependant manner Note regarding this study: There is preliminary clinical evidence to support the contention that the anti-inflammatory and analgesic properties of bromelain help to reduce symptoms of osteo- and rheumatoid arthritis. However, there have been no controlled studies of its effects on joint health in healthy subjects who lack such diagnosis. The current study investigated the effects of bromelain on mild acute knee pain of less than 3 months duration in otherwise healthy adults. Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults. Walker AF, Bundy R, Hicks SM, Middleton RW. Hugh Sinclair Unit of Human Nutrition, The University of Reading, UK. a.f.walker@reading.ac.uk http://www.ncbi.nlm.nih.gov/pubmed/12587686?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Effects of chocolate consumption on enhancing cognitive performance We Rosanna Drake, Daniel Felbaum, Lauren Matthews, Alex Reed, & Bryan Raudenbush Previous research has found that the nutrient content of foods aids in glucose release and increased blood flow. These increases have subsequently been implicated in augmenting cognitive performance. The present study assessed the effects of various chocolate types on cognitive performance, mood, and task workload. In a within-subjects design, participants completed the protocol under four conditions: 85g milk chocolate (total fat 26g, saturated fat 18g, carbohydrates 50g, fiber 2g, sugar 44g, protein 6g), 85g dark chocolate (total fat 34g, saturated fat 20g, carbohydrates 46g, fiber 6g, sugar 34g, protein 4g), 85g carob (total fat 20g, saturated fat 14g, carbohydrates 45g, fiber 11g, sugar 40g, protein 11g), and a non-consumption control condition. After a 15 minute digestive period, participants completed a variety of computer-based neuropsychological tests assessing word discrimination, verbal memory, design memory, attention span, reaction time, problem solving, and response variability. Mood and task workload were assessed via the Profile of Mood States (POMS) and the NASA-Task Load Index (NASA-TLX). Gender and age served as co-variates for the analyses. Composite scores for verbal and visual memory were significantly higher for milk chocolate than the other conditions. Consumption of milk or dark chocolate showed improved impulse control and reaction time. These findings provide support for nutrient release via chocolate consumption to enhance cognitive performance. http://www.wju.edu/academics/psy/recentresearchs2006.asp

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Mark J. S. Miller^1,2, Wallace K. MacNaughton³, Xiao-Jing Zhang^1,2, Jane H. Thompson^1,2, Randi M. Charbonnet^1,2, Paul Bobrowski^1,2, Juan Lao⁴, Ann Marie Trentacosti⁵, and Manuel Sandoval<sup>1,2

1</sup> Department of Pediatrics and Center for Cardiovascular Sciences, Albany Medical College, Albany, New York 12208; ² Department of Pediatrics, Louisiana State University Medical Center, New Orleans, Louisiana 70112; ³ Department of Physiology and Biophysics, Gastrointestinal Research Group, University of Calgary, Calgary, Alberta, Canada T2N 4N1; ⁴ Universidad Nacional Agraria de la Selva, Tingo Maria, Peru; and ⁵ Rainforest Phytoceuticals, Delmar, New York 12054

Sangre de grado is an Amazonian herbal medicine used to facilitate the healing of gastric ulcers and to treat gastritis, diarrhea, skin lesions, and insect stings. This study was designed to evaluate the gastrointestinal applications. Gastric ulcers were induced in rats by brief serosal exposure of the fundus to acetic acid (80%). Sangre de grado was administered in drinking water at 1:1,000 and 1:10,000 dilutions from the postoperative period to day 7. Guinea pig ileum secretory responses to capsaicin, electrical field stimulation, and the neurokinin-1 (NK-1) agonist [Sar9,Met(O2)11]substance P were examined in Ussing chambers. Sangre de grado facilitated the healing of experimental gastric ulcer, reducing myeloperoxidase activity, ulcer size, and bacterial content of the ulcer. The expression of proinflammatory genes tumor necrosis factor-, inducible nitric oxide synthase (iNOS), interleukin (IL)-1, IL-6, and cyclooxygenase-2 was upregulated by ulcer induction but reduced by sangre de grado treatment, particularly iNOS and IL-6. In Ussing chambers, sangre de grado impaired the secretory response to capsaicin but not to electrical field stimulation or the NK-1 agonist. We conclude that sangre de grado is a potent, cost-effective treatment for gastrointestinal ulcers and distress via antimicrobial, anti-inflammatory, and sensory afferent-dependent actions.

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Chen ZP, Cai Y, Phillipson JD.


Three in-vitro assays have been adopted to examine the cytotoxicity and anti-bacterial activity of the blood-red sap of Croton lechleri from Ecuador, and to examine its effect upon the proliferation of endothelial cells. The sap was found not to be cytotoxic. Several simple phenolic compounds and diterpenes showed a potent anti-bacterial activity. The sap has little effect upon the proliferation of endothelial cells, and no single active ingredient was identified. A mechanism for the wound-healing property of the sap has been proposed.

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Author: Vaisberg, A J : Milla, M : Planas, M C : Cordova, J L : de : Agusti, E R : Ferreyra, R : Mustiga, M C : Carlin, L : Hammond, G B

Abstract: Sangre de Grado extract used by Peruvian natives as a cicatrizant agent, was collected from trees of the species Croton lechleri growing in the Peruvian jungle. The Sangre de Grado was found to contain one alkaloid identified as taspine and which was shown to be the active cicatrizant principle by an in vivo test in mice. This alkaloid exhibited a dose-related cicatrizant effect and an ED50 of 0.375 mg/kg. Experiments with taspine hydrochloride in order to study its mechanism of action in cell culture systems showed that the alkaloid was non-toxic to human foreskin fibroblasts at concentrations below 150 ng/ml and that it had no effect on cell proliferation. On the other hand, taspine hydrochloride was found to increase the migration of human foreskin fibroblasts. This effect on the migration of fibroblasts is probably the mechanism by which Sangre de Grado and taspine hydrochloride accelerate the wound healing process. Using the two-stage mouse skin carcinogenesis system, we have been able to show that neither Sangre de Grado nor taspine hydrochloride had carcinogenic or tumour promoter activity after 17 months of treatment.

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Zhu QY, Holt RR, Lazarus SA, Orozco TJ, Keen CL.


Excessive peroxidation of biomembranes is thought to contribute to the initiation and progression of numerous degenerative diseases. The present study examined the inhibitory effects of a cocoa extract, individual cocoa flavanols (-)-epicatechin and (+)-catechin, and procyanidin oligomers (dimer to decamer) isolated from cocoa on rat erythrocyte hemolysis. In vitro, the flavanols and the procyanidin oligomers exhibited dose-dependent protection against 2,2'-azo-bis (2-amidinopropane) dihydrochloride (AAPH)-induced erythrocyte hemolysis between concentrations of 2.5 and 40 microM. Dimer, trimer, and tetramer showed the strongest inhibitory effects at 10 microM, 59.4%, 66.2%, 70.9%; 20 microM, 84.1%, 87.6%, 81.0%; and 40 microM, 90.2%, 88.9%, 78.6%, respectively. In a subsequent experiment, male Sprague-Dawley rats (approximately 200 g; n = 5-6) were given a 100-mg intragastric dose of a cocoa extract. Blood was collected over a 4-hr time period. Epicatechin and catechin, and the dimers (-)-epicatechin-(4beta>8)-epicatechin (Dimer B2) and (-)-epicatechin-(4beta>6)-epicatechin (Dimer B5) were detected in the plasma with concentrations of 6.4 microM, and 217.6, 248.2, and 55.4 nM, respectively. Plasma antioxidant capacity (as measured by the total antioxidant potential [TRAP] assay) was elevated (P < 0.05) between 30 and 240 min following the cocoa extract feeding. Erythrocytes obtained from the cocoa extract-fed animals showed an enhanced resistance to hemolysis (P < 0.05). This enhanced resistance was also observed when erythrocytes from animals fed the cocoa extract were mixed with plasma obtained from animals given water only. Conversely, plasma obtained from rats given the cocoa extract improved the resistance of erythrocytes obtained from rats given water only. These results show cocoa flavanols and procyanidins can provide membrane protective effects.

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Schneider Y, Lazarus SA, Coehlo D, Raul F.


The effects of cocoa powder and extracts with different amounts of flavanols and related procyanidin oligomers were investigated on the growth of Caco-2 cells. Treatment of the cells with 50 microg/ml of procyanidin-enriched (PE) extracts caused a 70% growth inhibition with a blockade of the cell cycle at the G2/M phase. PE extracts caused a significant decrease of ornithine decarboxylase and S-adenosylmethionine decarboxylase activities, two key enzymes of polyamine biosynthesis. This led to a decrease in the intracellular pool of the polyamines. These observations indicate that polyamine metabolism might be an important target in the anti-proliferative effects of cocoa polyphenols.

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Hatano T, Miyatake H, Natsume M, Osakabe N, Takizawa T, Ito H, Yoshida T.


Purification of polar fractions from cacao liquor extracts gave 17 phenolics including four new compounds. The new compounds were characterized as a C-glycosidic flavan, an O-glycoside of a dimeric and two O-glycosides of trimeric A-linked proanthocyanidins, on the basis of spectroscopic data. Isolated polyphenols showed inhibitory effects on nicotinamide adenine dinucleotide phosphate-dependent lipid peroxidation in microsomes and on the autoxidation of linoleic acid. These effects were attributed to the radical-scavenging activity in the peroxidation chain reactions, based on the findings that the cacao polyphenols effectively scavenged the 1,1-diphenyl-2-picrylhydrazyl radical.

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Grodstein F, Kang JH, Glynn RJ, Cook NR, Gaziano JM.


BACKGROUND: Oxidative stress contributes to brain aging. Antioxidant treatment, especially over the long term, might confer cognitive benefits. METHODS: We added cognitive testing to the Physicians' Health Study II (PHSII), a randomized trial of beta carotene and other vitamin supplements for chronic disease prevention. The PHSII is a continuation of the Physicians' Health Study (PHS), which had randomized male participants to low-dose aspirin and beta carotene. Participants include those continuing their original beta carotene assignment from the PHS, begun in 1982, and newer recruits randomized as of 1998. The beta carotene arm (50 mg, alternate days) was terminated; follow-up is ongoing for the remaining arms. Near the close of the beta carotene arm, we interviewed 5956 participants older than 65 years to assess general cognition, verbal memory, and category fluency. The primary end point was a global score averaging all tests (using z scores); the secondary end point was a verbal memory score combining results of 4 tests. We compared mean cognition among those assigned to beta carotene vs placebo. We separately examined new recruits and continuing participants. RESULTS: Among 1904 newly recruited subjects (mean treatment duration, 1 year), cognition was similar across treatment assignments. Among 4052 continuing participants from the PHS (mean treatment duration, 18 years), the mean global score was significantly higher in the beta carotene group than in the placebo group (mean difference in z scores, 0.047 standard units; P = .03). On verbal memory, men receiving long-term beta carotene supplementation also performed significantly better than the placebo group (mean difference in z scores, 0.063; P = .007). CONCLUSION: We did not find an impact of short-term beta carotene supplementation on cognitive performance, but long-term supplementation may provide cognitive benefits.

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With over thirty years of experience working and researching for the United States Department of Agriculture, Dr. Duke is an expert in the field of holistic herbal healing. He has studied over 500 Rainforest botanicals in detail and has compiled extensive data on each species.

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