Use of the National Death Index in cancer studies.

The National Death Index (NDI) is a central file of identifying information on all deaths occurring in the United States since 1979. Potential uses of the NDI as a tool for both short-term and long-term follow-up in cancer treatment, prevention, and occupational studies are suggested. The various steps involved in using the NDI and interpreting the results are described, along with factors influencing the effectiveness of the matching process.

Does beta-carotene explain why reduced cancer risk is associated with vegetable and fruit intake?

Increased intake of vegetables, fruits, and carotenoids and elevated blood levels of beta-carotene are consistently associated with reduced risk of lung cancer in epidemiologic studies. Epidemiologic research also suggests that carotenoids may reduce the risk of other cancers, although the evidence is less extensive and consistent. The simplest explanation is that beta-carotene is protective. However, the possible roles of other carotenoids, other constituents of vegetables and fruits, and associated dietary patterns have not been adequately explored. To evaluate these alternative hypotheses, we are undertaking three lines of research. (a) With dietary data from the 1987 National Health Interview Survey and the 1982-1984 Epidemiologic Follow-up of the first National Health and Nutrition Examination Study, we have determined which food groups and nutrients are highly correlated with vegetable and fruit intake. (b) We have developed and characterized a liquid chromatography method for optimal recovery and resolution of the common carotenoids in blood, specifically lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and beta-carotene. (c) In a population-based case-control study of lung cancer in white men in New Jersey, we are assessing whether estimates of the intake of the individual carotenoids might produce stronger inverse associations than estimates of provitamin A carotenoids based on current food composition tables.

Human [74Se]selenomethionine metabolism: a kinetic model.

A study was undertaken to investigate the pharmacokinetics of an organically bound form of selenium. Six adults received a single oral 200-micrograms dose of 74Se as L-selenomethionine. A kinetic model was developed to simultaneously account for the appearance and disappearance of the tracer in plasma, urine, and feces. The model included absorption distributed along the gastrointestinal tract, uptake by the liver-pancreas subsystem, enterohepatic recirculation, distribution to two large tissue pools, and transport through four components of the plasma pool. Average turnover time of the plasma components varied from 0.01 to 1.1 d. The turnover time in the liver-pancreas subsystem ranged from 1.6 to 3.1 d. Turnover time ranged from 61 to 86 d in the peripheral tissues with the slowest turnover. The whole-body residence time was approximately five-fold greater than the turnover time of the tissue pool with the slowest turnover, reflecting substantial reutilization of labeled material.

Naturally occurring selenium compounds in cancer chemoprevention trials: a workshop summary.

Evidence from epidemiological studies and a human intervention trial indicates that selenium (Se) may have chemopreventive activity in humans. This report summarizes a workshop held by the National Cancer Institute to address the use of naturally occurring Se compounds in future cancer chemoprevention trials. Differences in the metabolism of inorganic and organic Se compounds can be seen both in the biochemical handling of these forms and in their kinetics in humans. Long-term supplementation could result in greater increases in muscle stores for organic rather than inorganic forms. Because of long half-lives, trials may have to be of long duration to assess efficacy and safety. The optimal size of dose for supplementation is controversial with respect to both efficacy and safety. In China, selenosis was observed in some individuals with a sustained intake of at least 750 micrograms/day but was not observed among others with intakes exceeding 1 mg. These levels exceed the reference dose, a measure of the maximal safe intake, which is 350 micrograms/day. A large-scale Se human intervention trial in the United States suggests no harm due to long-term Se intake of more than 200 micrograms/day. Se deficiency has been shown to have deleterious effects on the immune system, allowing, for example, a benign form of the Coxsackievirus to become virulent in mice. These recent results may provide an explanation of earlier findings showing a protective effect of elevated Se intakes against a mouse mammary tumor virus. Additional studies on the use of Se as a chemopreventive agent in man seem warranted.

Determinants of plasma vitamin E in healthy males.

Vitamin E or tocopherol, a known antioxidant, may play a role in the etiology of chronic diseases such as cancer and heart disease. This study examined both "internal" (lipids, lipoproteins, and apoproteins) and "external" (dietary components, physical activity, and body mass index) factors which may influence plasma alpha-tocopherol and gamma-tocopherol levels. Analyses were done using dietary questionnaires and plasma obtained from 65 nonsmoking male volunteers aged 30-59 years. Forty-six men did not take any supplements while 19 took supplements containing vitamin E. A positive correlation (r = 0.32; P < 0.01) between vitamin E intake and alpha-tocopherol status [(ratio of plasma alpha- or gamma-tocopherol/(total triglycerides + total cholesterol)] and a negative correlation (r = -0.33; P < 0.007) between intake and gamma-tocopherol status were observed. The main internal factors, or determinants, for plasma alpha-tocopherol for nonsupplement users were plasma triglycerides and apoproteins, apoA1 and apoB, but neither lipids nor apoproteins appeared to affect tocopherol levels in supplement users. External determinants of alpha-tocopherol status in nonsupplement users were vitamin E intake, total fat intake, and body mass index, while in supplement users only vitamin E intake was important. Both vitamin E intake and alcohol intake appeared to affect plasma gamma-tocopherol status in a negative manner.

Psychosocial factors associated with fruit and vegetable consumption.

PURPOSE: This study examined the relationship between various psychosocial factors and fruit and vegetable consumption. DESIGN: The 5 A Day Baseline Survey, conducted in August 1991, just before the initiation of the 5 A Day for Better Health Program, obtained data on adults' intakes of, and their knowledge, perceptions, and attitudes regarding, fruits and vegetables. SETTING: The survey was conducted by telephone. SUBJECTS: Subjects were 2811 adults (response rate, 43%) aged 18 years and older in the 48 coterminous United States. MEASURES: Fruit and vegetable intake was measured as self-reported frequency of use; most of the psychosocial variables were measured using Likert scales. RESULTS: This study estimates that only 8% of American adults thought that five or more servings of fruits and vegetables were needed for good health. Of the factors studied, the most important in determining someone's fruit and vegetable intake were the number of servings they thought they should have in a day, whether they liked the taste, and whether they had been in the habit of eating many fruits and vegetables since childhood. These few factors accounted for 15% more of the variation in fruit and vegetable consumption than did demographic variables alone (8%). CONCLUSIONS: Nutrition education should stress the need to eat five or more servings of fruits and vegetables per day because few adults are aware of this recommendation and such knowledge is strongly associated with increased intake. Furthermore, efforts to increase the palatability of fruits and vegetables, especially among children, should be promoted.

Fruit and vegetable intake in the United States: the baseline survey of the Five A Day for Better Health Program.

PURPOSE: The purpose of the Five A Day Baseline Survey was to assess fruit and vegetable intake and associated factors among US adults. DESIGN: Questionnaires querying frequency of intake of 33 fruits and vegetables, as well as demographics, attitudes, and knowledge related to fruits and vegetables were administered by telephone. SETTING: The study was a nationally representative random digit dial survey conducted by telephone in the summer of 1991; response rate was 42.8%. SUBJECTS: Respondents were 2811 US adults (including an oversample of African-Americans and Hispanics). MEASURES: Mean and median self-reported intakes of fruits and vegetables were calculated. Estimated servings per week were adjusted on the basis of responses to summary questions regarding overall fruit and vegetable intakes. RESULTS: Median intake of fruits and vegetables was 3.4 servings per day. Linear regressions (accounting for no more than 10% of the variation) showed that education, income, and smoking status were predictors of fruit and vegetable intake and that intake increased with education, income, and nonsmoking status. Women had higher intakes than men at all ages; these differences between men and women increased with age. Fruit and vegetable intakes increased with age for whites and Hispanics, but not for African-Americans. CONCLUSIONS: Fruit and vegetable intake among adults in the United States is lower than the recommended minimum of five daily servings. These data will be useful in targeting campaign efforts and in assessing progress of the Five A Day for Better Health Program.

The impact of screening and eliminating preexisting cases on sample size requirements for cancer prevention trials.

A cancer prevention trial may seek to test the effectiveness of an intervention in disease-free individuals, but the study population may include subjects with preexisting (but undiagnosed) disease. If sample size calculations assume all events are incident cases, the study will have less power than anticipated because preexisting cases cannot be expected to benefit from the intervention. Sample size can be increased appropriately by using revised event rates that include both preexisting and incident cases. These rates incorporate screening parameters and are applicable to the situation where subjects are screened before randomization. A simple cost model is given that permits examination of the tradeoffs involved in prescreening subjects versus increasing total sample size.

Food choices and the cancer guidelines.

Twenty-four hour dietary recall data from 11,658 adult respondents in the second National Health and Nutrition Examination Survey (NHANES II) (1976-80) were used to examine the American diet in relation to certain of the cancer dietary guidelines from the National Academy of Sciences and the American Cancer Society. The per cent who reported consuming any food in those food groups considered protective was small: cruciferous vegetables (18 per cent); fruits and vegetables high in vitamin A (21 per cent); high fiber breads and cereals (16 per cent). The per cent consuming foods potentially increasing cancer risk was high: red meat (55 per cent); bacon and lunch meats (43 per cent). Proportions of persons eating fruits and vegetables increased with income. Diets were closer to the guidelines for females than males, for Blacks than Whites, and for older than younger Americans.

Development of a model for selenite metabolism in humans.

The process of building a kinetic model for the metabolism of selenite in humans is described. Plasma, urine and fecal data from a selenium pharmacokinetics study are compared with an a priori model hypothesized before the study was conducted. The reasons for the rejection of the model are given. The iterative process of observing the fit of the model, modifying the model and testing the modification is illustrated by using as examples an intermediate model and a current working model. Several specific problems encountered in trying to fit the a priori and the intermediate model are described along with the approaches taken to resolve them. Finally, some uses of the current model are given, including checking an assumption underlying the pharmacokinetics study, making predictions about the effect of supplementation on plasma levels and developing research leads.

Regression analysis of grouped survival data: informative censoring and double sampling.

To analyze grouped survival data subject to informative censoring, we propose the following two-part model: a logistic regression model for the hazard for failure, given covariates and a logistic regression model for the hazard for informative censoring, given time of failure and covariates. We fit the model to survival data arising from a double sampling design: In a full follow-up (FF) sample subjects are followed after censoring, and in a partial follow-up (PF) sample subjects are not followed after censoring. We illustrate the methodology using data from a study of wound infection in which patients in the PF sample are censored by release from the hospital, whereas patients in the FF sample are followed after hospital release. We discuss identifiability when there is only a PF sample. We also consider how the allocation between the PF and FF samples affects the precision of estimates.

Calories, fat and cholesterol: intake patterns in the US population by race, sex and age.

Nutrient intakes were investigated for Blacks and Whites using data from the NHANES II survey (1976-80). Intake of energy, total fat, saturated fat, dietary cholesterol, P/S ratio, and per cent of calories derived from total and saturated fat are examined by sex and age, both in absolute terms and per unit of body weight. For most age and sex categories, Blacks are found to have a lower intake of energy and fats than Whites; however, Blacks have a consistently higher intake of dietary cholesterol. The ratio of polyunsaturated fats to saturated fats is higher in females than in males, but all age-sex groups are substantially below recommended levels. Per cent of calories from total and saturated fat are similar in most age-sex groups. Possible explanations of the observed patterns include activity level and metabolic differences.

Food choices of whites, blacks, and Hispanics: data from the 1987 National Health Interview Survey.

Dietary guidelines posit an association between diet and cancer. Different cancer mortality rates among whites, blacks, and Hispanics may be related to differences in diet. Food frequency data from the 1987 National Health Interview Survey on 20,143 adults were used to estimate the percentage of adults, by gender and race/ethnicity, who consume some 59 foods six or more times per year, median number of servings for consumers, and frequency of consumption of skin on poultry and fat on red meat. On the basis of percent consumption of these foods, women appear to have a more diverse diet than men. Women eat more fruits and vegetables, less meat, and fewer high-fat foods and drink fewer alcoholic beverages. Whites eat a more varied diet than blacks and Hispanics; blacks eat more fried and high-fat food; consumption of high-fat foods is lowest among Hispanics. Public health messages, especially those aimed at cancer prevention, should be targeted at increasing the overall consumption of fruits and vegetables, decreasing consumption of high-fat foods, especially among white and black men, and increasing consumption of those healthful foods already consumed by particular race/ethnicity groups.

Clinical metabolic studies in cancer research.

Clinical metabolic studies are being used increasingly to study the role of nutrition in cancer etiology and prevention. These studies have important applications in at least five areas. The kinetics and toxicity of potential chemoprevention agents can be investigated in preparation for intervention studies. Nutrient levels proposed as compliance markers in intervention studies can be assessed under rigorous control. Potential mechanisms of action of nutrients can be evaluated. And intermediate endpoints, markers of biologic damage, can be measured before and after controlled dietary manipulations. As a result of these contributions, clinical metabolic studies are taking on a new and important role in the interdisciplinary approach to cancer research.

Trends in food intake: the 1987 and 1992 National Health Interview Surveys.

To examine food intake trends in the US population, cross-sectional nationally representative food intake data were obtained from the 1987 and 1992 National Health Interview Survey Cancer Control Supplements. In each of these years, approximately 10,000 respondents completed methodologically consistent food frequency questionnaires containing the same 57 food items. Between 1987 and 1992, the proportion of Americans consuming high-fat foods, including fried fish, fried chicken, bacon, eggs, whole milk, and butter, decreased. The proportion of Americans drinking alcoholic beverages also decreased: fewer drank wine and hard liquor in 1992. The proportion of fruit and vegetable consumers remained stable over time. These results are similar to those obtained from more detailed national surveys. National guidelines urge Americans to avoid intake of high-fat foods, increase consumption of fruits and vegetables, and practice moderation when drinking alcoholic beverages to prevent cancer and other chronic diseases. The direction of Americans' apparent changes in food usage between 1987 and 1992, evaluated using limited data from food frequency questionnaires, suggests greater behavioral changes in the direction of guidelines recommending avoidance of foods that may increase the risk of cancer than in the direction of guidelines recommending increased consumption of foods that may confer protection.

Fruit and vegetables in the American diet: data from the NHANES II survey.

Twenty-four hour dietary recall data from the Second National Health and Nutrition Examination Survey (1976-80) were used to estimate the numbers of servings of fruit and vegetables consumed by Black and White adults, to examine the types of servings (e.g., potatoes, garden vegetables, fruit, and juice), and to estimate the mean intake of calories, fat, dietary fiber, and vitamins A and C by number of servings. An estimated 45 percent of the population had no servings of fruit or juice and 22 percent had no servings of a vegetable on the recall day. Only 27 percent consumed the three or more servings of vegetables and 29 percent had the two or more servings of fruit recommended by the US Departments of Agriculture and of Health and Human Services; 9 percent had both. Consumption was lower among Blacks than Whites. The choice of vegetables lacked variety. Diets including at least three servings of vegetables and two servings of fruit contained about 17 grams of dietary fiber. Although caloric and fat intake increased with increasing servings of fruit and vegetables, the percent of calories from fat remained relatively constant. Although these data are 10 years old, more recent surveys have shown similar results. The discrepancy between dietary guidelines and the actual diet suggests a need for extensive public education.

US dietary patterns associated with fat intake: the 1987 National Health Interview Survey.

OBJECTIVES: This research used food frequency data to investigate dietary patterns associated with fat intake. METHODS: Data from the 1987 National Health Interview Survey of 20,143 adults were used to determine correlations between fat (adjusted for kilocalories) and both nutrient and food group intakes. Median food and nutrient intakes were determined within quartiles of percentage of kilocalories from fat. RESULTS: Intakes of vegetables, fruits, cereals, fish/chicken, low-fat milk, alcoholic beverages, vitamin C, percentage of kilocalories from carbohydrates, carotenoids, folate, dietary fiber, carbohydrates, and vitamin A decreased as percentage of kilocalories from fat increased. Intakes of salty snacks, peanuts, processed and red meats, whole milk and cheese, desserts, eggs, fried potatoes, table fats, cholesterol, vitamin E, sodium, protein, and energy increased with percentage of kilocalories from fat. Results by demographic subgroups showed few differences from those found in the total population. CONCLUSIONS: Fat intake is consistently associated with specific dietary patterns. Such patterns need to be evaluated concurrently in studies of diet and chronic disease.

Body weight and prior depletion affect plasma ascorbate levels attained on identical vitamin C intake: a controlled-diet study.

PURPOSE: To evaluate the role of factors that may affect the level of plasma ascorbic acid (AA), including age, body weight, physical activity, minor illness and the impact of prior depletion and repletion. METHODS: After one month of stabilization on 60 mg vitamin C/day, subjects underwent two complete depletion-repletion cycles (one cycle=one month of vitamin C depletion with nine mg/day, followed by one month of repletion with 117 mg per day). Subjects (68 men, ages 30 to 59 years) did not smoke or drink alcohol during the study. All food was provided by the study. RESULTS: There was extreme individual variability in the plasma AA level achieved on an identical repletion dose: after four weeks at 117 mg/day of vitamin C, AA ranged from 26.8 micromol/L to 85.8 micromol/L. Body weight was inversely associated with plasma AA attained (p<0.0001). Regression analysis indicated that, compared to a 130-lb man, a 200-lb man reached 10 micromol/L lower AA after the first repletion and 18 micromol/L lower AA after the second repletion. One-third of the subjects did not reach a plasma plateau after the first repletion. Prior depletion and apparent repletion also had a major impact, and only 10% of subjects reached the same plasma AA on the second repletion as on the first repletion. CONCLUSIONS: Plasma AA attained on a given dose depends on body weight (or dose per kg of body weight) and on whether or not any prior depletions had been repleted adequately. The results have implications for nutrition recommendations and research design.

Ascorbic acid status and subsequent diastolic and systolic blood pressure.

Free radicals and oxidation are involved in several aspects of blood pressure physiology. We investigated the relationship between blood pressure and antioxidants, including plasma ascorbic acid (AscA), in a 17-week controlled-diet study. Study subjects included 68 men aged 30 to 59 years who had a mean diastolic blood pressure of 73.4 mm Hg and a mean systolic blood pressure of 122.2 mm Hg. One month of vitamin C depletion was followed by 1-month repletion with 117 mg/d, repeated twice. All food and drink were provided in the study. Subjects did not smoke or drink alcohol, all consumed fruits and vegetables, and body weight was maintained. Plasma was assayed periodically for AscA, alpha-tocopherol, carotenoids, and lipids. Plasma AscA was inversely related to diastolic blood pressure 1 month later (correlation -0.48, P:<0.0001). Persons in the bottom fourth of the plasma AscA distribution had >7 mm Hg higher diastolic blood pressure than did those in the top fourth of the plasma AscA distribution. Multivariate analysis with control for age, body mass index, other plasma antioxidants, and dietary energy, calcium, fiber, sodium, and potassium did not reduce the plasma AscA effect. One fourth of the variance in diastolic blood pressure was accounted for by plasma AscA alone. Plasma AscA was also significantly associated with systolic blood pressure in logistic regression. Vitamin C may be an important component of the effectiveness of fruits and vegetables in the reduction in blood pressure, and tissue AscA levels may be important in the maintenance of low blood pressure. Long-term intervention studies are warranted.

The bioavailability to humans of ascorbic acid from oranges, orange juice and cooked broccoli is similar to that of synthetic ascorbic acid.

The relative bioavailability of ascorbic acid from several sources was compared in 68 male non-smokers. Subjects underwent two 8-wk ascorbic acid depletion-repletion cycles. In repletion, subjects were randomized to receive 108 mg/d ascorbic acid as tablets with or without iron, as orange segments or juice, or as raw or cooked broccoli with a crossover within each major treatment group (e.g., cooked to raw broccoli) for the second repletion. Relative ascorbic acid bioavailability was estimated based on the slope obtained from linear regression of plasma ascorbic acid on time during each repletion. In the first repletion, slopes for all groups were similar except for the group consuming raw broccoli (20% lower response, P < 0.01). Second repletion responses were attenuated, but were similar to the first repletion. Ascorbic acid ingested as cooked broccoli, orange juice or fruit, or in synthetic form seems to be equally bioavailable. The lower relative bioavailability of ascorbic acid from raw broccoli is unlikely to be of practical importance in mixed diets.