Martin Root

Combined Fruit and Vegetable Intake Is Correlated with Improved Inflammatory and Oxidant Status from a Cross-Sectional Study in a Community Setting

Previous studies have examined the relationship between specific nutrient and food intakes with limited markers of either inflammation or oxidant status. The objective of this study was to determine if an increase in combined self-reported fruit and vegetable (F&V) intake in a community setting was associated with improved multiple markers of inflammatory and oxidant status. A community group (N = 1000, age 18–85 years, 61% female) gave two fasted blood samples separated by 12 weeks. Blood inflammatory biomarkers included total leukocytes (WBC), plasma C-reactive protein (CRP), interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1, and granulocyte colony stimulating factor. Measured oxidant status markers were ferric reducing ability of plasma (FRAP), oxygen radical absorbance capacity (ORAC) and plasma F2-isoprostanes. The relation of markers across categories of F&V intake was examined. In analyses controlling for other important dietary and lifestyle factors, IL-6 and TNF-α were significantly lower across categories of increasing F&V intakes (p < 0.008). FRAP and ORAC were significantly higher (p < 0.0001 and p = 0.047 respectively) while F2-isoprostanes was significantly lower (p < 0.0001) across F&V categories. In a community study, several markers of both inflammation and oxidant status were associated in a putatively salutary direction by higher intake of combined F&V, supporting current guidelines suggesting increased F&V consumption for the prevention of chronic diseases.

Effects of carotenoid‐rich food extracts on the development of preneoplastic lesions in rat liver and on in vivo and in vitro antioxidant status

The effect of dietary carotenoid-rich extracts of carrots, tomatoes, and orange juice on rat liver gamma-glutamyl transpeptidase-positive preneoplastic foci induced by aflatoxin B1 was investigated. Organic extracts were prepared from the foods, dissolved in tricaprylin oil to equivalent concentrations of the major food-specific carotenoids, and fed by intubation to Fischer 344 male rats. The extracts were administered during the 2-week aflatoxin-dosing (initiation) period of the study or during the subsequent 12-week post-dosing (promotion) period. Vitamin status and antioxidant activities were measured in blood and liver. Extract feeding caused an accumulation of carotenoids in the liver, a substantial decrease in spontaneous erythrocyte hemolysis, and lowered plasma glutathione, blood superoxide dismutase, and blood catalase. Differences in foci development among the three extracts were not as consistent or profound as differences between initiation and promotion dosing. The number of gamma-glutamyl transpeptidase-positive foci was decreased by extract feeding during the initiation period, whereas extract feeding during the promotion period caused a decrease in the average diameter of the foci. The total volume of foci was markedly reduced by extract feeding during either period. Extracts were compared with purified carotenoids and alpha-tocopherol in their ability to affect in vitro antioxidation activity and were nearly as effective as the pure compounds. In summary, carotenoid-rich extracts of these three foods substantially inhibited biochemical and cellular events thought to play a role in the early stages of hepatocarcinogenesis.

Assessing risk for coronary heart disease: beyond Framingham☆

The Framingham Heart Study, initiated over 50 years ago, introduced the concept of risk factors for coronary heart disease (CHD) and has served as the standard for risk assessment over the years.1-4 Major risk factors identified by the Framingham HeartStudy, in- cluding age, sex, total cholesterol, high-density li- poprotein (HDL) cholesterol,smoking, and systolic blood pressure, have been incorporated into a scoring system thatidentifies subjects at high (>20%), interme- diate (10%–20%), and low ( 80% of the excess population risk for CHD.6-8 Recent clinical trials in high-risk subjectsdemonstrate dramatic reductions in risk (approximately 33%–50% in 5 y) with riskreduction therapies.9 This provides strong support for the concept that CHD and its sequela can be prevented by aggressive medical therapy and therapeutic lifestyle changes.Recent American Heart Association (AHA) guidelines (2002)4 for primary prevention ofcardiovascular disease and stroke recom- mend that risk-factor screening in adults shouldbegin at age 20 and should be repeated at least every 5 years in the absence of risk factors and every 2 years if risk factors are present. This panel recommends that global risk should be estimated in all adults >40 years of age. In this issue of the Journal, Cohn et al10 have proposed a method for risk assessment that focuses on measurements of early vasculardysfunction and disease markers rather than standard risk factors. Studies are ongoing intheir outpatient cardiovascular disease prevention clinic to validate the model by relating risk assessments to disease outcomes over time

DISSIMILARITY IN AFLATOXIN DOSE-RESPONSE RELATIONSHIPS BETWEEN DNA ADDUCT FORMATION AND DEVELOPMENT OF PRENEOPLASTIC FOCI IN RAT LIVER

Earlier work in this laboratory and that carried out by others demonstrated that after a single dose of aflatoxin B1 (AFB) the resulting liver AFB-DNA adduct levels were directly proportional to dose. Earlier work also showed that after ten daily doses the AFB dose-response relationship with gamma-glutamyl transpeptidase (GGT) positive preneoplastic foci measured at 3 months was sublinear, with a threshold at a dose of about 150 micrograms/kg body weight/day. The objective of this study is to determine the factors influencing the shift in AFB dose-response between AFB-DNA adducts and GGT foci. Male Fisher 344 weanling rats were orally administered one or ten doses of AFB ranging from 50 to 350 micrograms/kg body weight/day. The animals were killed 2 or 24 h after the first AFB dose, or after the tenth AFB dose. The first and tenth doses were tritiated in these animals and 3H-AFB-guanine adducts isolated from liver DNA were measured by HPLC. Another group was killed 3 months after receiving ten doses in order to measure GGT foci development. AFB-guanine adduct levels were directly proportional to dose after the first dose, but after the tenth dose were much lower in the 200-350 micrograms/kg groups than after a single dose. The GGT foci response confirmed earlier work concerning a sublinear response. Among the individual animals in the 200-350 micrograms/kg groups there was a positive relationship, after controlling for dose, between GGT foci development and weight gained both during dosing (P = 0.018) and also to a lesser extent during the early promotional period (P = 0.066). Enzyme activity levels of GGT in liver homogenates were higher in the highest dose groups and reflected biliary proliferation rather than histological GGT stained foci. Urinary levels of AFB metabolites changed proportions in the high dosage multiply dosed animals reflecting alteration in AFB metabolism or excretion. The differences between the linear adduct and the sublinear foci dose-response curves may be the result of non-adduct effects of higher multiple AFB doses on foci formation including acute cytotoxicity, altered AFB metabolism and disposition, enhanced weight gains, or shortened foci latency but not through enhanced guanine adduct levels. Other studies that showed a linear relationship between AFB dose and liver tumor development used continuous feeding of maximal doses an order of magnitude less than the lowest dose in this study and thus avoided acutely toxic effects. We hypothesize that liver tumor development may mirror foci response in a 10-dose AFB regimen with doses above 100 micrograms/kg due to acute toxicity effects.

Combining information from multiple data sources to create multivariable risk models: Illustration and preliminary assessment of a new method

A common practice of metanalysis is combining the results of numerous studies on the effects of a risk factor on a disease outcome. If several of these composite relative risks are estimated from the medical literature for a specific disease, they cannot be combined in a multivariate risk model, as is often done in individual studies, because methods are not available to overcome the issues of risk factor colinearity and heterogeneity of the different cohorts. We propose a solution to these problems for general linear regression of continuous outcomes using a simple example of combining two independent variables from two sources in estimating a joint outcome. We demonstrate that when explicitly modifying the underlying data characteristics (correlation coefficients, standard deviations, and univariate betas) over a wide range, the predicted outcomes remain reasonable estimates of empirically derived outcomes (gold standard). This method shows the most promise in situations where the primary interest is in generating predicted values as when identifying a high-risk group of individuals. The resulting partial regression coefficients are less robust than the predicted values.

Iron status of middle-aged women in five counties of rural China

Objective: To determine the relationships of dietary iron sources, other dietary factors, and lifestyle to iron status among premenopausal and recently postmenopausal Chinese women with widely varying regional dietary patterns.Design: Cross-sectional. Subjects were interviewed, blood samples were drawn, and dietary intakes were measured by a 3-day dietary survey for subjects in the five survey counties.Setting: Rural ChinaSubjects: About 80 randomly selected subjects per county among women aged 32–66 y.Main outcome measures: Blood hemoglobin, plasma ferritin, and plasma iron.Results: Total iron intake was relatively high (15–29 mg/d) compared to developed counties. Heme iron intake was negligible in two of the study counties. Overall levels of iron deficiency anemia were relatively low in these generally iron-stressed women. There was no clear statistical relationship between iron intake and physiological iron status. Although several measures of dietary intake (heme iron, dietary calcium, animal protein) were correlated with several measures of iron status before adjusting for survey county, only dietary animal protein was significantly positively correlated with plasma ferritin after adjusting for the possibly confounding factor of the survey county (r=0.15, P=0.009). Intakes of potential inhibitors of iron absorption, such as tea, even in very high amounts, were not correlated to iron status. Plasma ferritin was positively correlated with plasma retinol (P=0.024) and cholesterol (P=0.007). Systemic inflammatory response, as indicated by high plasma C-reactive protein levels, was shown to be raised in a group of subjects with apparently contradictory high levels of ferritin and low levels of hemoglobin (P=0.03).Conclusions: Iron nutriture in these areas of rural China seemed more related to physiological factors such as inflammatory response, menses, plasma vitamin A and cholesterol, than to dietary factors.Sponsors: NIH grant 5RO1 CA33638, Kellogg Co., Northeast Dairy Foods Research Center, American Institute for Cancer Research

Vitamin A and carotenoid status in rural China

Vitamin A status of 260 groups of twenty-five males or twenty-five females, aged 35-64 years, surveyed in twenty-four provinces of the Peoples Republic of China, was assessed by measuring plasma retinol. retinol-binding protein and beta-carotene concentrations. Direct measurements of food intake over a 3 d period and questionnaire data on the frequency of consumption of vegetables, fruits, animal products and other dietary items were also used. Vitamin A status appeared to be low only in specific counties but in general was satisfactory or only marginally deficient. Plasma beta-carotene levels were strikingly low in comparison with Western levels despite generous vegetable consumption suggesting that intake of vitamin A precursors may have been adequate but not abundant enough to maintain high circulating plasma levels of beta-carotene. Plasma beta-carotene, for both males and females, was significantly correlated with the frequency of consumption of green vegetables. Plasma retinol, for males, was highly correlated with meat, fish, oil and alcohol consumption expressed both in quantity or frequency of consumption. Higher levels of plasma retinol, together with lower levels of plasma beta-carotene in males compared with females, suggest that men consume more animal products or may have higher retinol requirements and therefore a higher rate of conversion of beta-carotene to retinol.

Healthy Eating Index 2005 and selected macronutrients are correlated with improved lung function in humans

A number of dietary components have been associated with lung function. However, a comprehensive measure of a healthy diet has not been compared with lung function. Herein, we test the hypothesis that a healthy overall diet, as assessed by the Healthy Eating Index 2005 (HEI-2005), will be associated with increased lung function. This is an investigation using the Atherosclerosis Risk in Communities Research Materials obtained from the National Heart Lung Blood Institute. The study surveyed dietary habits of 15 567 American subjects from 4 communities in 1987 to 1990. Spirometric measures of lung function were also taken at entry to the study and a second time 3 years later. Based on food and nutritional data collected by food frequency questionnaire, an HEI-2005 score was calculated for each subject. This total score, together with its 12 components scores and associated macronutrient, was compared with lung function results by linear regression. Models were controlled for smoking behavior, demographics, and other important covariates. The HEI-2005 total scores were positively associated with forced expiratory volume in 1 second per forced vital capacity (FEV(1)/FVC) at visit 1 (β = .101 per increase in 1 quintile of HEI-2005) and visit 2 (β = .140), and FEV(1) as percentage of the predicted FEV(1) at visit 2 (β = .215) (P < .05). In addition, HEI-2005 component scores that represented high intakes of whole grains (β = .127 and .096); saturated fats (β = -.091); and solid fats, alcohol, and added sugar (β = -.109 and -.131) were significantly associated with FEV(1)/FVC at either visit 1 or visit 2. Intakes of total calories (β =-.082 at visit 1) and saturated fatty acids (β = -.085 at visit 2) were negatively associated with FEV(1)/FVC. Dietary polyunsaturated fatty acids (β = .085 and .116) and long-chain omega-3 fatty acids (β = .109 and .103), animal protein (β = .132 and .093), and dietary fiber (β = .129) were positively associated with lung health. An overall healthy diet is associated with higher lung function.

Synthesis analysis of regression models with a continuous outcome

To estimate the multivariate regression model from multiple individual studies, it would be challenging to obtain results if the input from individual studies only provide univariate or incomplete multivariate regression information. Samsa et al. (J. Biomed. Biotechnol. 2005; 2:113-123) proposed a simple method to combine coefficients from univariate linear regression models into a multivariate linear regression model, a method known as synthesis analysis. However, the validity of this method relies on the normality assumption of the data, and it does not provide variance estimates. In this paper we propose a new synthesis method that improves on the existing synthesis method by eliminating the normality assumption, reducing bias, and allowing for the variance estimation of the estimated parameters.

Building prediction models for coronary heart disease by synthesizing multiple longitudinal research findings

Background No methodology is currently available to allow the combining of individual risk factor information derived from different longitudinal studies for a chronic disease in a multivariate fashion. This paper introduces such a methodology, named Synthesis Analysis, which is essentially a multivariate meta-analytic technique. Design The construction and validation of statistical models using available data sets. Methods and results Two analyses are presented. (1) With the same data, Synthesis Analysis produced a similar prediction model to the conventional regression approach when using the same risk variables. Synthesis Analysis produced better prediction models when additional risk variables were added. (2) A four-variable empirical logistic model for death from coronary heart disease was developed with data from the Framingham Heart Study. A synthesized prediction model with five new variables added to this empirical model was developed using Synthesis Analysis and literature information. This model was then compared with the four-variable empirical model using the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study data set. The synthesized model had significantly improved predictive power (x2 = 43.8, P < 0.00001). Conclusions Synthesis Analysis provides a new means of developing complex disease predictive models from the medical literature.