PMID: 

Am J Clin Nutr. 2012 Oct ;96(4):781-8. Epub 2012 Aug 22. PMID: 22914551

Abstract Title: 

Higher anthocyanin intake is associated with lower arterial stiffness and central blood pressure in women.

Abstract: 

BACKGROUND: Although a high intake of some flavonoid subclasses may reduce cardiovascular disease mortality, data regarding the in vivo mechanisms of action are limited.OBJECTIVE: We examined associations between habitual flavonoid intakes and direct measures of arterial stiffness, central blood pressure, and atherosclerosis.DESIGN: In a cross-sectional study of 1898 women aged 18-75 y from the TwinsUK registry, intakes of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, polymers, flavonols, and flavones) were calculated from validated food-frequency questionnaires by using an updated and extended USDA database. Direct measures of arterial stiffness and atherosclerosis included central systolic blood pressure (cSBP), central diastolic blood pressure, mean arterial pressure (MAP), augmentation index, pulse wave velocity (PWV), and intima-media thickness.RESULTS: In multivariate analyses, a higher anthocyanin intake was associated with significantly lower cSBP (mean± SE: -3.0 ± 1.4 mm Hg for quintile 5 compared with quintile 1; P-trend = 0.02), MAP (-2.3 ± 1.2 mm Hg for quintile 5 compared with quintile 1; P-trend = 0.04), and PWV (-0.4 ± 0.2 m/s for quintile 5 compared with quintile 1; P-trend = 0.04), whereas a higher flavone intake was associated with alower PWV (-0.4 ± 0.2 m/s for quintile 5 compared with quintile 1; P-trend = 0.04). Although a higher wine and berry intake was associated with a lower PWV, no associations were observed for total and other flavonoid subclasses.CONCLUSIONS: These data, which include direct measures of arterial stiffness and thickness, suggest that higher intake of anthocyanins and flavones are inversely associated with lower arterial stiffness. The intakes of anthocyanins associated with these findings could be incorporated into the diet by the consumption of 1-2 portions of berries daily and are, therefore, relevant for public health strategies to reduce cardiovascular disease risk.

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PMID: 

Am J Clin Nutr. 2008 May ;87(5):1439-45. PMID: 18469269

Abstract Title: 

Dietary flavonoid intake and non-Hodgkin lymphoma risk.

Abstract: 

BACKGROUND: The role of dietary factors in non-Hodgkin lymphoma (NHL) risk is not yet well understood. Dietary flavonoids are polyphenolic compounds proposed to be anticarcinogenic. Flavonoids are well-characterized antioxidants and metal chelators, and certain flavonoids exhibit antiproliferative and antiestrogenic effects.OBJECTIVE: We aimed to evaluate the hypothesis that higher flavonoid intake is associated with lower NHL risk.DESIGN: During 1998-2000, we identified incident NHL cases aged 20-74 y from 4 US Surveillance, Epidemiology, and End Results cancer registries. Controls without history of NHL were selected by random-digit dialing or from Medicare files and frequency-matched to cases by age, center, race, and sex. Using 3 recently developed US Department of Agriculture nutrient-specific databases, flavonoid intake was estimated from participant responses to a 117-item food-frequency questionnaire (n = 466 cases and 390 controls). NHL risk in relation to flavonoid intake in quartiles was evaluated after adjustment for age, sex, registry, education, NHL family history, and energy intake.RESULTS: Higher total flavonoid intake was significantly associated with lower risk of NHL (P for trend

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PMID: 

Food Nutr Res. 2015 ;59:29564. Epub 2015 Dec 11. PMID: 26652740

Abstract Title: 

Flavonoid intake and the risk of age-related cataract in China's Heilongjiang Province.

Abstract: 

BACKGROUND/OBJECTIVES: Epidemiological evidence suggests that diets rich in flavonoids may reduce the risk of developing age-related cataract (ARC). Flavonoids are widely distributed in foods of plant origin, and the objective of this study was to evaluate retrospectively the association between the intakes of the five flavonoid subclasses and the risk of ARC.SUBJECTS/METHODS: A population-based case-control study (249 cases and 66 controls) was carried out in Heilongjiang province, which is located in the northeast of China, and where intakes and availability of fresh vegetables and fruits can be limited. Dietary data gathered by food-frequency questionnaire (FFQ) were used to calculate flavonoid intake. Adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression.RESULTS: No linear associations between risk of developing ARC and intakes of total dietary flavonoids, anthocyanidins, flavon-3-ol, flavanone, total flavones or total flavonols were found, but quercetin and isorhamnetin intake was inversely associated with ARC risk (OR 11.78, 95% CI: 1.62-85.84, p

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PMID: 

Complement Ther Med. 2018 Aug ;39:14-18. Epub 2018 May 15. PMID: 30012385

Abstract Title: 

Association between dietary flavonoids intake and prostate cancer risk: A case-control study in Sicily.

Abstract: 

OBJECTIVES: The aim of this study is to test the association between dietary flavonoids intake and prostate cancer (PCa) in a sample of southern Italian individuals.DESIGN: A population-based case-control study on the association between PCa and dietary factors was conducted from January 2015 to December 2016, in a single institution.SETTING: Patients with elevated PSA (Prostate Specific Antigen) and/or suspicion of PCa underwent transperineal prostate biopsy (≥12 cores). A total of 118 histopathological-verified PCa cases were collected and matched with controls, which were selected from a sample of 2044 individuals randomly recruited among the same reference population. Finally, a total of 222 controls were selected.MAIN OUTCOME MEASURES: Prevalence of PCa.RESULTS: Consumption of certain groups of flavonoids significantly differed between controls and cases, in particular: flavonols (63.36 vs 37.14 mg/d, P 

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PMID: 

Cancer Causes Control. 2019 May ;30(5):527-535. Epub 2019 Mar 22. PMID: 30903485

Abstract Title: 

Flavonoids and bladder cancer risk.

Abstract: 

PURPOSE: Flavonoids have drawn attention because of their antioxidant capacity and anti-carcinogenic effect in various types of cancer. A limited number of studies has investigated their potential effect on the risk of bladder cancer, with inconsistent results.METHODS: We analyzed data from an Italian case-control study including 690 incident bladder cancer cases and 665 controls admitted to the same network of hospitals for acute, non-neoplastic, non tobacco-related diseases. Subjects were interviewed using a reproducible and validated food-frequency questionnaire. We applied data on food and beverage composition to estimate the intake of isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones and flavonols. We estimated odds ratios (ORs) through multiple logistic regression models, including terms for potential confounding factors, including tobacco smoking and total energy intake.RESULTS: We found an inverse association between isoflavones (OR for the highest compared to the lowest quintile of intake = 0.56, 95% CI 0.37-0.84) and flavones (OR = 0.64, 95% CI 0.44-0.95) and bladder cancer. Non-significant inverse association was found for flavan-3-ols (OR = 0.70), flavonols (OR = 0.85) and total flavonoids (OR = 0.76). The results were consistent for non-muscle-invasive and muscle-invasive bladder cancers.CONCLUSIONS: Our data indicate an inverse association between isoflavones and flavones with respect to bladder cancer risk.

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PMID: 

Ann Oncol. 2007 Jun ;18(6):1104-9. Epub 2007 Mar 19. PMID: 17372161

Abstract Title: 

Flavonoids and laryngeal cancer risk in Italy.

Abstract: 

BACKGROUND: Flavonoids may play an important role in explaining the protective effect of vegetables and fruit against cancer.PATIENTS AND METHODS: To investigate the relation between flavonoids and laryngeal cancer risk, we have applied data on the composition of foods and beverages in terms of six principal classes of flavonoids to a case-control study of laryngeal cancer conducted from 1992 to 2000 in Italy. Cases were 460 subjects with incident, histologically confirmed laryngeal cancer; controls were 1088 patients admitted for acute, non-neoplastic diseases. Odds ratios (OR) were estimated through multiple logistic regression models, including terms for sociodemographic and lifestyle factors, tobacco smoking, alcohol consumption and energy intake.RESULTS: Significant inverse relations were found for the highest versus the lowest quintile of intake for flavan-3-ols (OR = 0.64), flavanones (OR = 0.60), flavonols (OR = 0.32) and total flavonoids (OR = 0.60), although the overall trends in risk were significant only for flavanones and flavonols. No consistent associations were observed for isoflavones, anthocyanidins and flavones. The estimates did not differ substantially across strata of alcohol drinking, tobacco smoking, body mass index and education, and tended to persist even after controlling for vegetable and fruit intake.CONCLUSION: This study provides support for a beneficial effect of selected flavonoids on laryngeal cancer risk.

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PMID: 

Br J Nutr. 2007 Oct ;98(4):814-8. Epub 2007 Apr 30. PMID: 17466095

Abstract Title: 

The intake of flavonoids and carotid atherosclerosis: the Kuopio Ischaemic Heart Disease Risk Factor Study.

Abstract: 

The role of flavonoids in CVD is still unclear. In this cross-sectional study we assessed the relation between the intakes of twenty-six flavonoids from five subclasses: flavonols, flavones, flavanones, flavan-3-ols and anthocyanidins, and the mean common carotid artery intima-media thickness (CCA-IMT). The study population consisted of 1380 middle-aged eastern Finnish men for whom the mean CCA-IMT examinations were carried out as a part of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD). The mean intake of flavonoids was 128.5 (sd 206.7) mg/d and the mean CCA-IMT was 0.78 (sd 0.17) mm. In the lowest quartile of total flavonoid intake the non-adjusted mean CCA-IMT was 0.79 (sd 0.19) mm, while the mean CCA-IMT was 0.76 (sd 0.15) in the highest quartile (P

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PMID: 

Int J Cancer. 2008 Aug 1 ;123(3):664-71. PMID: 18491403

Abstract Title: 

Dietary flavonoid intake and risk of cancer in postmenopausal women: the Iowa Women's Health Study.

Abstract: 

Flavonoids, which are found in certain plant foods, are thought to lower cancer risk through their antioxidant, antiestrogenic and antiproliferative properties. We examined the association of intake of total flavonoids and 7 flavonoid subclasses with risk of lung, colorectal, breast, pancreatic and upper aerodigestive cancer among women in a large prospective cohort study. Study participants were 34,708 postmenopausal women in the Iowa Women's Health Study who completed a food frequency questionnaire and were followed for cancer occurrence from 1986 through 2004. Flavonoid intake was estimated from 3 databases developed by the USDA Nutrient Data Laboratory (NDL). Hazard ratios (HR) for cancer risk were calculated across total flavonoid and flavonoid subclass intake categories. Interactions between smoking history and flavonoid intake were also examined. After multivariable adjustment, lung cancer incidence was inversely associated with intakes of flavanones (HR = 0.68; 95% CI: 0.53-0.86, all results highest vs. lowest quintile) and proanthocyanidins (HR = 0.75; 95% CI: 0.57-0.97). Among current and past smokers, those with intakes in the highest quintile for flavanones (HR = 0.66; 95% CI: 0.50-0.86), and proanthocyanidins (HR = 0.66; 95% CI; 0.49-0.89) had significantly lower lung cancer incidence than those in the lowest quintile. Similar associations were not seen in never smokers. Isoflavone intake was inversely associated with overall cancer incidence (HR = 0.93, 95% CI: 0.86-1.00). This study provides further support for a beneficial effect of flavonoid intake on lung cancer risk, especially among current and past smokers.

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PMID: 

mBio. 2020 Jan 21 ;11(1). Epub 2020 Jan 21. PMID: 31964741

Abstract Title: 

Influenza Virus Infection Induces a Narrow Antibody Response in Children but a Broad Recall Response in Adults.

Abstract: 

In contrast to influenza virus vaccination, natural infection induces long-lived and relatively broad immune responses. However, many aspects of the antibody response to natural infection are not well understood. Here, we assessed the immune response after H1N1 influenza virus infection in children and adults in a Nicaraguan household transmission study using an influenza virus protein microarray (IVPM). This technology allows us to simultaneously measure IgG and IgA antibody responses to hemagglutinins of many different virus strains and subtypes quantitatively with a high throughput. We found that children under 6 years of age responded to natural infection with a relatively narrow response that targeted mostly the hemagglutinin of the strain that caused the infection. Adults, however, have a much broader response, including a boost in antibodies to many group 1 subtype hemagglutinins. Also, a strong recall response against historic H1 hemagglutinins that share the K133 epitope with the pandemic H1N1 virus was observed. Of note, some children, while responding narrowly within H1 and group 1 hemagglutinins, induced a boost to H3 and other group 2 hemagglutinins when infected with H1N1 when they had experienced an H3N2 infection earlier in life. This is an interesting phenomenon providing evidence for immune imprinting and a significant new insight which might be leveraged in future universal influenza virus vaccine strategies. Finally, preexisting immunity to pandemic H1 hemagglutinins was significantly associated with protection from infection in both children and adults. In adults, preexisting immunity to non-H1 group 1 hemagglutinins was also significantly associated with protection from infection.It is known since Thomas Francis, Jr. published his first paper on original antigenic sin in 1960 that the first infection(s) with influenza virus leaves a special immunological imprint which shapes immune responses to future infections with antigenically related influenza virus strains. Imprinting has been implicated in both protective effects as well as blunting of the immune response to vaccines. Despite the fact that this phenomenon was already described almost 60 years ago, we have very little detailed knowledge of the characteristics and breadth of the immune response to the first exposure(s) to influenza virus in life and how this compares to later exposure as adults. Here, we investigate these immune responses in detail using an influenza virus proteinmicroarray. While our findings are mostly descriptive in nature and based on a small sample size, they provide a strong basis for future large-scale studies to better understand imprinting effects.

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PMID: 

PLoS Pathog. 2019 Dec ;15(12):e1008109. Epub 2019 Dec 19. PMID: 31856206

Abstract Title: 

Childhood immune imprinting to influenza A shapes birth year-specific risk during seasonal H1N1 and H3N2 epidemics.

Abstract: 

Across decades of co-circulation in humans, influenza A subtypes H1N1 and H3N2 have caused seasonal epidemics characterized by different age distributions of cases and mortality. H3N2 causes the majority of severe, clinically attended cases in high-risk elderly cohorts, and the majority of overall deaths, whereas H1N1 causes fewer deaths overall, and cases shifted towards young and middle-aged adults. These contrasting age profiles may result from differences in childhood imprinting to H1N1 and H3N2 or from differences in evolutionary rate between subtypes. Here we analyze a large epidemiological surveillance dataset to test whether childhood immune imprinting shapes seasonal influenza epidemiology, and if so, whether it acts primarily via homosubtypic immune memory or via broader, heterosubtypic memory. We also test the impact of evolutionary differences between influenza subtypes on age distributions of cases. Likelihood-based model comparison shows that narrow, within-subtype imprinting shapes seasonal influenza risk alongside age-specific risk factors. The data do not support a strong effect of evolutionary rate, or of broadly protective imprinting that acts across subtypes. Our findings emphasize that childhood exposures can imprint a lifelong immunological bias toward particular influenza subtypes, and that these cohort-specific biases shape epidemic age distributions. As a consequence, newer and less"senior"antibody responses acquired later in life do not provide the same strength of protection as responses imprinted in childhood. Finally, we project that the relatively low mortality burden of H1N1 may increase in the coming decades, as cohorts that lack H1N1-specific imprinting eventually reach old age.

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