Dietary catechins and their potentially protective role in cardiovascular diseases and cancer

Catechins are polyphenolic compounds in plant foods that belong to the family of flavonoids. Due to their strong antioxidant activity and their capacity to influence mammalian enzyme systems, catechins were hypothesized to affect risk of cardiovascular diseases and cancer in humans. After optimizing the extraction and quantification of six major catechins from foods, a database containing catechin contents of more than 130 commonly consumed plant foods and beverages was created. Catechin levels varied between 5 and 610 mg/kg and were particularly high in tea, chocolate, fruits and red wine. Among 6,200 participants of the Dutch National Food Consumption Survey 1998, the average catechin intake was 50 mg/day. Catechin intake increased with age, and the intake was higher in women (60 mg/day) than in men (40 mg/day). Tea was the main catechin source in all age groups. The role of catechins in chronic disease prevention was studied in two prospective cohort studies: the Zutphen Elderly Study (~800 Dutch men, 65-84 years old, followed since 1985) and the Iowa Women's Health Study (~34,000 postmenopausal American women, 55-69 years old, followed since 1986). In Zutphen, a high intake of catechins was associated with a 51% lower risk of coronary heart disease (CHD) mortality, but not with myocardial infarction incidence or stroke. In Iowa, a 24% lower risk of CHD mortality was found in the highest quintile of intake of (+)-catechin and (-)-epicatechin, catechins typical of foods other than tea. Catechins derived from tea were not associated with CHD mortality. Lung cancer incidence was studied in both the Zutphen Elderly Study and the Iowa Women's Health Study. Whereas in Zutphen a borderline significant inverse association with lung cancer was found for catechins from foods other than tea, particularly apple, catechins were not associated with lung cancer in Iowa. The incidence of other cancers studied in Zutphen - total epithelial cancer and epithelial cancers other that those of the lung - was not associated with catechin intake. In Iowa, among several cancers studied, total catechin intake and the intake of catechins from tea were inversely associated with rectal cancer risk only. Thus, catechins are quantitatively important minor constituents of the diet. Major catechin sources in both the Netherlands and the USA are tea, apples, and chocolate. Overall, our data do not support a strong protective effect of the studied catechins against myocardial infarction, stroke and cancer incidence. However, certain catechins may lower the risk of CHD mortality and possibly certain cancers.</p

Deconjugation Kinetics of Glucuronidated Phase II Flavonoid Metabolites by B-glucuronidase from Neutrophils

Flavonoids are inactivated by phase II metabolism and occur in the body as glucuronides. Mammalian ß-glucuronidase released from neutrophils at inflammatory sites may be able to deconjugate and thus activate flavonoid glucuronides. We have studied deconjugation kinetics and pH optimum for four sources of ß-glucuronidase (human neutrophil, human recombinant, myeloid PLB-985 cells, Helix pomatia) with five flavonoid glucuronides (quercetin-3-glucuronide, quercetin-3'-glucuronide, quercetin-4'-glucuronide, quercetin-7-glucuronide, 3'-methylquercetin-3-glucuronide), 4-methylumbelliferyl-ß-D-glucuronide, and para-nitrophenol-glucuronide. All substrate-enzyme combinations tested exhibited first order kinetics. The optimum pH for hydrolysis was between 3.5-5, with appreciable hydrolysis activities up to pH 5.5. At pH 4, the Km ranged 44-fold from 22 µM for quercetin-4'-glucuronide with Helix pomatia ß-glucuronidase, to 981 µM for para-nitrophenol-glucuronide with recombinant ß-glucuronidase. Vmax (range: 0.735-24.012 µmol·min-1·unit-1 [1 unit is defined as the release of 1 µM 4-methylumbelliferyl-ß-D-glucuronide per min]) and the reaction rate constants at low substrate concentrations (k) (range: 0.002-0.062 min-1·(unit/L)-1 were similar for all substrates-enzyme combinations tested. In conclusion, we show that ß-glucuronidase from four different sources, including human neutrophils, is able to deconjugate flavonoid glucuronides and non-flavonoid substrates at fairly similar kinetic rates. At inflammatory sites in vivo the pH, neutrophil and flavonoid glucuronide concentrations seem favorable for deconjugation. However, it remains to be confirmed whether this is actually the case

Gut colonization with methanobrevibacter smithii is associated with childhood weight development

OBJECTIVE: To prospectively investigate the presence and counts of archaea in feces of 472 children in association with weight development from 6 to 10 years of age. METHODS: Within the KOALA Birth Cohort Study, a single fecal sample from each child was analyzed by quantitative polymerase chain reaction to quantify archaea (Methanobrevibacter smithii, Methanosphera stadtmanae). Anthropometric outcomes (overweight [body mass index {BMI} >/= 85th percentile], age- and sex-standardized BMI, weight, and height z-scores) were repeatedly measured at ages (mean +/- SD) of 6.2 +/- 0.5, 6.8 +/- 0.5, 7.8 +/- 0.5, and 8.8 +/- 0.5 years. Generalized estimating equation was used for statistical analysis while controlling for confounders. RESULTS: Methanobrevibacter smithii colonization was associated with an increased risk of overweight (adjusted odds ratio [OR] = 2.69; 95% confidence interval [CI] 0.96-7.54) from 6 to 10 years of age. Children with high levels (>7 log10 copies/g feces) of this archaeon were at highest risk for overweight (OR = 3.27; 95% CI 1.09-9.83). Moreover, M. smithii colonization was associated with higher weight z-scores (adj. beta 0.18; 95% CI 0.00-0.36), but not with height. For BMI z-scores, the interaction (P = 0.008) between M. smithii and age was statistically significant, implying children colonized with M. smithii had increasing BMI z-scores with age. CONCLUSIONS: Presence and higher counts of M. smithii in the gut of children are associated with higher weight z-scores, higher BMI z-scores, and overweight

Ассоциация аллельных полиморфизмов гена эндотелиальной NO-синтазы с развитием ишемической болезни сердца (литературный обзор)

Проведений аналіз вітчизняних та закордонних досліджень стосовно вивчення впливу Т-786С, G894T, 4a/b поліморфізмів гену eNOS на ризик розвитку ІХС у представників різних популяцій. Доведена роль Т-786 С поліморфізма гену eNOS у розвитку ІХС у представників японської, української, італійської популяції, причому в останніх він пов’язаний із багатосудинним ураженням. G894T поліморфізм гену eNOS пов’язаний із підвищеним ризиком розвитку ІХС, ішемічних інсультів в італійській, турецькій, азіатській популяціях, а в російській ─ із рестенозами стентів. Доведений зв’язок 4а/4b поліморфізму гену eNOS із виникненням ІХС у турецькій, японській, корейській, афро-американській, іранській, російській популяціях, а в японській популяції ─ гендерна специфіка даної асоціації. В окремих дослідженнях отримані суперечливі дані щодо впливу Т-786 С поліморфізму гену eNOS в турецькій популяції. Не виявлено асоціації 4а/4b поліморфізму гену eNOS у чоловіків Словенії, Фінляндії, G894T поліморфізму гену eNOS у корейській популяції, а у представників білої австралійської популяцій не виявлено асоціації генотипів 4а/4b, G894T, Т-786С поліморфізму гену eNOS із ризиком розвитку ІХС.В статье проведен анализ отечественных и зарубежных исследований, посвященных изучению влияния Т-786С, G894T, 4a/b полиморфизмов гена eNOS на риск развития ИБС у представителей различных популяций. Доказана роль Т-786 С полиморфизма гена eNOS в развитии ИБС у представителей японской, украинськой, итальянской популяции, причем у последних он связан с многососудистым поражением. G894T полиморфизм гена eNOS связан с повышеным риском развития ИХС, ишемических инсультов в итальянской, турецкой, азиатской популяциях, а в российской ─ с рестенозами стентов. Доказана связь 4а/4b полиморфизма гена eNOS с возникновением ИБС в турецкой, японской, корейской, афро-американской, иранськой, российской популяциях, а в японской популяции ─ гендерная специфика данной ассоциации. В отдельных исследованиях получены противоречивые данные о влиянии Т-786 С полиморфизма гена eNOS в турецкой популяции. Не выявлено ассоциации 4а/4b полиморфизма гена eNOS у мужчин Словении, Финляндии, G894T полиморфизма гена eNOS в корейской популяции, а у представителей белой австралийской популяции не выявлено ассоциации генотипов 4а/4b, G894T, Т-786С полиморфизму гену eNOS с риском развития ИБС.The article analyzed Ukrainian and foreign research on the impact study T-786С, G894T, 4a /b polymorphisms of the eNOS gene on the risk of coronary artery disease (CAD) among representatives of different populations. The role of T-786C polimorphism of the eNOS gene was proven in the development of CAD among Japanese, Ukrainian, Italian population, and in the past it is associated with multivessel disease. G894T polymorphism of the eNOS gene is associated with high risk of CAD, ischemic stroke in Italian, Turkish, Asian populations. In the Russian population this polymorphism assotiated with restenosis of stents. The 4a/4b polymorphism of the eNOS gene has significant influence on risk of CAD in Turkish, Japanese, Korean, AfricanAmerican, Iranian and Russian populations. Japanese population has gender specificity of the association. Conflicting data obtained in separate studies of the influence of T-786C polymorphism of the eNOS gene in the Turkish population. There was no association 4a /4b polymorphism of the eNOS gene in men Slovenia’s men and in Finland. Wasn’t identify association of G894T polymorphism of the eNOS gene in Korean population. Wasn’t detected association of genotypes 4a/4b, G894T, T-786S of the eNOS gene polymorphisms with risk of CAD in white Australians. Due to the existence of common pathogenetic mechanisms, involving NO, polymorphism eNOS gene presence may increases the risk of developing COPD. So perspective is study of polymorphisms eNOS gene in patients with COPD and CAD of Ukrainian population. Investigate their role as candidate genes can help to predict and prevent the appearance of comorbid disorders

Lignan contents of Dutch plant foods: a database including lariciresinol, pinoresinol, secoisolariciresinol and matairesinol

Enterolignans ( enterodiol and enterolactone) can potentially reduce the risk of certain cancers and cardiovascular diseases. Enterolignans are formed by the intestinal microflora after the consumption of plant lignans. Until recently, only secoisolariciresinol and matairesinol were considered enterolignan precursors, but now several new precursors have been identified, of which lariciresinol and pinoresinol have a high degree of conversion. Quantitative data on the contents in foods of these new enterolignan precursors are not available. Thus, the aim of this study was to compile a lignan database including all four major enterolignan precursors. Liquid chromatography-tandem mass spectrometry was used to quantify lariciresinol, pinoresinol, secoisolariciresinol and matairesinol in eighty-three solid foods and twenty-six beverages commonly consumed in The Netherlands. The richest source of lignans was flaxseed (301 129 μ g/100 g), which contained mainly secoisolariciresinol. Also, lignan concentrations in sesame seeds (29 331 μ g/100 g, mainly pinoresinol and lariciresinol) were relatively high. For grain products, which are known to be important sources of lignan, lignan concentrations ranged from 7 to 764 μ g/100 g. However, many vegetables and fruits had similar concentrations, because of the contribution of lariciresinol and pinoresinol. Brassica vegetables contained unexpectedly high levels of lignans (185-2321 μ g/100 g), mainly pinoresinol and lariciresinol. Lignan levels in beverages varied from 0 (cola) to 91 μ g/100 ml (red wine). Only four of the 109 foods did not contain a measurable amount of lignans, and in most cases the amount of lariciresinol and pinoresinol was larger than that of secoisolariciresinol and matairesinol. Thus, available databases largely underestimate the amount of enterolignan precursors in foods

Association between serum uric acid, aortic, carotid and femoral stiffness among adults aged 40-75 years without and with type 2 diabetes mellitus: The Maastricht Study

Objective: Arterial stiffness may be a mechanism to explain the association between uric acid and cardiovascular disease. We aimed to analyse associations between serum uric acid and regional and local arterial stiffness, and assess potential differences related to sex and glucose metabolism status. Methods: A cross-sectional study was performed in 614 adults [52.6% men; mean age 58.7 +/- 8.5 years; 23.2% type 2 diabetes mellitus (by design)] from The Maastricht Study. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV), distensibility, and compliance coefficient of the carotid and femoral artery, and carotid artery Young's elastic modulus. Results: Higher uric acid (per SD of 74 mu mol/l) was associated with greater stiffness indicated by a significantly higher cfPWV [beta = 0.216 (95% confidence interval 0.061, 0.372); P = 0.006] and lower carotid distensibility coefficient [beta = -0.633 (95% confidence interval -1.099, -0.166); P = 0.008] after adjustment for sex, age, and glucose metabolism status. Associations lost significance after adjusting for mean arterial pressure, BMI, waist, smoking status, heart rate, total : high-density lipoprotein cholesterol ratio, triglycerides, estimated glomerular filtration rate, use of lipid-lowering, antihypertensive, and diabetes medication, and use of secondary uricosurics. No associations were found between uric acid and carotid compliance coefficient, carotid Young's elastic modulus, or stiffness of the femoral artery. A significant interaction (P <0.10) with glucose metabolism status was found for cfPWV. However, none of the stratified associations were significant. There was no interaction with sex. Conclusion: Uric acid was not significantly associated with stiffness of the aorta, or the carotid or femoral artery among adults aged 40-75 years without and with type 2 diabetes mellitus

Determinants of the prevalence of gout in the general population: a systematic review and meta-regression

Studies on the occurrence of gout show a large range in estimates. However, a clear insight into the factors responsible for this variation in estimates is lacking. Therefore, our aim was to review the literature on the prevalence and incidence of gout systematically and to obtain insight into the degree of and factors contributing to the heterogeneity. We searched MEDLINE, EMBASE, and Web of Science (January 1962 to July 2012) to identify primary studies on the prevalence and incidence of gout in the general population. Data were extracted by two persons on sources of clinical heterogeneity, methodological heterogeneity, and variation in outcome reporting. Meta-analysis and meta-regression analysis were performed for the prevalence of gout. Of 1,466 articles screened, 77 articles were included, of which 71 reported the prevalence and 12 the incidence of gout. The pooled prevalence (67 studies; N = 12,226,425) based on a random effects model was 0.6 % (95 % CI 0.4; 0.7), however there was a high level of heterogeneity (I2 = 99.9 %). Results from a mixed-effects meta-regression model indicated that age (p = 0.019), sex (p < 0.001), continent (p < 0.001), response rate (p = 0.016), consistency in data collection (p = 0.002), and case definition (p < 0.001) were significantly associated with gout prevalence and jointly accounted for 88.7 % of the heterogeneity. The incidence in the total population ranged from 0.06 to 2.68 per 1,000 person-years. In conclusion, gout is a common disease and the large variation in the prevalence data on gout is explained by sex, continent on which the study was performed, and the case definition of gout