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The relation between vegetable and fruit consumption and colorectal cancer risk was comprehensively assessed in the Netherlands Cohort Study on Diet and Cancer using a validated 150-item food frequency questionnaire. After 6.3 years of follow-up (1986-1992), over 1,000 incident cases of colorectal cancer were registered. Using case-cohort analysis, the authors calculated rate ratios and 95% confidence intervals adjusted for age, alcohol intake, and family history of colorectal cancer. For colon cancer, no statistically significant associations with total vegetable intake or total fruit intake were found. However, among women, an inverse association was observed with vegetables and fruits combined (for the highest quintile vs. the lowest, the rate ratio was 0.66 (95% confidence interval: 0.44, 1.01)). Brassica vegetables and cooked leafy vegetables showed inverse associations for both men and women. Among women and, to a lesser extent, among men, inverse associations were stronger for distal colonic tumors than for proximal colonic tumors. For rectal cancer, no statistically significant associations were found for vegetable consumption or fruit consumption or for specific groups of vegetables and fruits; only Brassica vegetables showed a positive association in women. As in other cohort studies, the observed inverse relation between vegetable and fruit consumption and occurrence of colorectal cancer was less strong than relations reported in case-control studies.

Many studies have reported inverse associations between vegetable and fruit consumption and lung cancer risk. The aim of the present study was to elucidate the role of several antioxidants and folate in this relationship. In the Netherlands Cohort Study on Diet and Cancer, 58,279 men of ages 55-69 years at baseline in 1986 returned a questionnaire including a 150-item food frequency questionnaire. After 6.3 years of follow-up, 939 male lung cancer cases were registered. A new Dutch carotenoid database was used to estimate intake of alpha-carotene, beta-carotene, lutein + zeaxanthin, beta-cryptoxanthin, and lycopene, completed with the antioxidant vitamins C and E and folate. Using case-cohort analysis, rate ratios were calculated, adjusted for age, smoking, educational level, and family history of lung cancer. Protective effects on lung cancer incidence were found for lutein + zeaxanthin, beta-cryptoxanthin, folate, and vitamin C. Other carotenoids (alpha-carotene, beta-carotene, and lycopene) and vitamin E did not show significant associations. After adjustment for vitamin C, only folate remained inversely associated, and after adjustment for folate, only beta-cryptoxanthin and vitamin C remained significantly associated. Inverse associations were strongest among current smokers and weaker for former smokers at baseline. Inverse associations with carotenes, lutein + zeaxanthin, and beta-cryptoxanthin seemed to be limited to small cell and squamous cell carcinomas. Only folate and vitamin C intake appeared to be inversely related to small cell and squamous cell carcinomas and adenocarcinomas. Folate, vitamin C, and beta-cryptoxanthin might be better protective agents against lung cancer in smokers than alpha-carotene, beta-carotene, lutein + zeaxanthin, and lycopene.

Objective: The purpose was to study the association between vegetable and fruit consumption and lung cancer incidence using 1074 cases after 6.3 years of follow-up in the Netherlands Cohort Study., Methods: Dietary intake was assessed using a 150-item food-frequency questionnaire. Multivariate models were used including age, sex, family history of lung cancer, highest educational level attained, and smoking history., Results: Statistically significant inverse associations were found with total vegetables and most vegetable groups. Rate ratios (RRs) based on consumption frequency showed the strongest effect of vegetables from the Brassica group (RR 0.5, 95% confidence interval (95% CI) 0.3-0.9, for consumption > or = 3 times per week versus < or = once a month). RR of highest versus lowest quintile of total vegetable consumption was 0.7 (95% CI 0.5-1.0, p-trend 0.001). Statistically significant inverse associations were found for all fruits listed in the questionnaire. RRs for quintiles of total fruit intake were 1.0, 0.7, 0.6, 0.6 and 0.8 respectively (p-trend < 0.0001). Protective effects of fruits and vegetables were stronger in current than in former smokers, and weaker for adenocarcinomas than for other types of tumors., Conclusions: Inverse associations with lung cancer are found for both vegetable and fruit intake, but no specific type of vegetable or fruit seems to be particularly responsible.

Objective: To discuss the approach of the US Food and Nutrition Board (FNB) to daily nutrient requirements and its relevance for Europe., Setting: A workshop for experts from academia and regulatory bodies, together with members from the FNB Dietary Reference Intakes Subcommittee on Upper Reference Levels of Intake, and from the B-vitamins Expert panel. The workshop was organised by the European Academy of Nutritional Sciences and TNO Nutrition and Food Research Institute (The Netherlands)., Conclusions: Classical approaches to recommended dietary allowances (RDA) are no longer satisfactory, because they do not take into account newly emerging science with regard to intakes beyond the RDA. There is an urgent need for global harmonisation of criteria used for assessing adequacy of intake and for harmonisation of terminology. For sound advice to consumers, the development of tolerable upper intake levels is necessary. The discussion of principal issues relating to criteria for nutrient adequacy should be pursued on an international level., Sponsorship: Roche Vitamins Europe Ltd, Birsfelden, Switzerland

Consumers increasingly use vitamin supplements. Also, since June 1996, foodstuffs enriched with vitamins are available on the Dutch market. These sources of extra vitamins may be useful for groups at risk for marginal vitamin deficiencies. These risk groups include the chronically ill (e.g. diabetics), people using medicaments, older people and pregnant women. Extra vitamins from low-dose supplements or enriched foodstuffs may also constitute a valuable and safe supplement to the diet of children, smokers, people eating unbalanced, people on slimming diets, vegetarians and people engaged in intensive sports. According to the advisory group Nutrition of the Health Council, addition of vitamins to foodstuffs causes no risks of any importance for public health, apart from vitamins A and D and of the trace elements selenium, copper and zinc. Consequently, these should only be added to reconstituted foodstuffs or in a substitution product, not in enriched foodstuffs.

This article is based on discussions of the lung cancer panel at the Hohenheim Consensus Meeting organized by the World Health Organization and the German Ministry of Health in November 1996. Panel members were international experts in the field of diet and cancer who discussed specific questions relating to lung cancer risk factors and prevention.

The calcium (Ca)-restricted diet of urolithiasis patients with absorptive hypercalciuria type II may decrease Ca excretion but increase biochemical markers of risk for osteopenia. We randomly allocated 25 patients from six hospitals into an experimental group (Ca restriction to 500 mg/day, oxalate-rich products discouraged and normalization of animal protein and sodium) and a control group (no restrictions) for one month. The urinary Ca excretion did not decrease significantly, but the oxalate excretion decreased, although not significantly. The hydroxyproline:creatinine ratio in fasting urine seemed to increase and the calcium:creatinine ratio to decrease. The deoxypyridinoline:creatinine ratio in fasting urine did not change. We conclude that our Ca-restricted diet, which is lower in Ca, animal protein and table salt due to the omission of dairy products, may be of benefit for absorptive hypercalciuria type II patients without enhancing the risk for osteopenia. However, a long-term clinical trial is required.

Objective: To describe the rationale, design and methods for a nutrition surveillance study with special reference to vitamin B6 and other micronutrients., Rationale and Design: Several studies in the Netherlands have shown that differences in dietary intake and in nutritional status indicators are relatively small among various socio-demographic groups, so that the relevance of this traditional risk group identification in terms of public health and nutrition policy is limited. Therefore, it was decided to use the diet itself as primary selection criterion for a study on the adequacy of the vitamin B6 supply. The first Dutch national food consumption survey in 1987/88 showed, among other things, that mean vitamin B6 intake (per gram of protein) was substantially below the adequate level for all age-gender groups studied. Since the potential impact on public health of this observation may be relatively large, intake of vitamin B6 was chosen as first selection criterion. A study design that creates the largest possible distinction in vitamin B6 intake would be most efficient to study the health risks as a consequence of a low vitamin B6 intake. Several arguments, such as the need to estimate the prevalence of an inadequate status of vitamin B6 and other micronutrients, led to the decision to use a random population sample as a reference group for comparison with the group with low habitual vitamin B6 intake. Other major arguments underlying the study design and the selection of the nutritional status indicators, as well as the framework of the Dutch Nutrition Surveillance System, are discussed. Finally, the design and methods of the study are described in detail (except food consumption methods).

Association between breast cancer risk and the intake of vitamins C and E, retinol, beta (beta)-carotene, dietary fibre, vegetables, fruit and potatoes was examined in The Netherlands Cohort Study, for 62,573 women aged 55-69 years. After 4.3 years of follow-up, 650 incident breast cancer cases were identified. After adjusting for traditional risk factors, breast cancer risk was not influenced by the intake of beta-carotene, vitamin E, dietary fibre, supplements with vitamin C, vegetables or potatoes. Fruit consumption showed a non-significant inverse association with breast cancer risk (RR highest/lowest quintile = 0.76, 95% CI 0.54-1.08). A small reduction in risk was also observed with increasing intake of dietary vitamin C (RR highest/lowest quintile = 0.77, 95% CI 0.55-1.08). For retinol, a weak positive association was observed (RR highest/lowest quintile = 1.24, 95% CI 0.83-1.83). Among subjects with a high intake of polyunsaturated fatty acids (PUFAs), both beta-carotene and vitamin C intake showed a non-significant inverse association with breast cancer risk (P-trend = 0.15 and 0.16 respectively). Our findings do not suggest a strong role, if any, for intake of vitamins C and E, beta-carotene, retinol, dietary fibre, vegetables, fruit and potatoes in the aetiology of breast cancer.

The intake of calcium (Ca) is negatively associated with colorectal cancer (crc) risk. The aim of this study was to investigate in a double-blind, placebo-controlled trial, the effects of the Ca-binder Calcisorb, which is given to kidney stone patients with hypercalciuria type I, on risk factors for crc risk, bile acids (BA), and long-chain fatty acids (LCFA) in fecal water. Results show that the concentration of BA and LCFA in fecal water did not change, although the urinary excretion of Ca and magnesium (Mg) and the concentration of Ca and magnesium in fecal water decreased. The daily excretion of BA and LCFA acids decreased significantly (p < 0.05) during the Calcisorb period. In conclusion, binding dietary Ca and Mg with Calcisorb from a diet with a relatively low amount of fat does not enhance the solubility of BA and LCFA in fecal water.

Objectives: In studies on diet and cancer, diet assessment should address long-term intake. Therefore, the authors determined the 5-year reproducibility of a self-administered 150-item food frequency questionnaire (FFQ) used to assess dietary habits in the Netherlands Cohort Study on diet and cancer. Since the FFQ was repeated more than once, the pure test-retest reliability of the FFQ could be distinguished from the intra-individual change in nutrient intake over time. These results were furthermore used to investigate the measurement error structure of the FFQ., Design: After baseline administration in 1986, the FFQ was annually repeated from 1987 to 1991 in independent random samples of the cohort (n = 400). Pearson correlation coefficients (r) between baseline and repeated measurements of nutrient intake, calculated for each time interval, were regressed on time interval to provide separate estimates of the test-retest correlation (intercept of regression line) and of the decline in correlation over time (slope). The proportion of correlated measurement error was derived from combining the test-retest results with those from a validation study, in which the FFQ was validated against three 3-day diet records., Results and Conclusions: Response was stable at 82%. The test-retest r ranged from 0.42 for selenium intake to 0.90 for alcohol intake. The slopes of the regression lines were relatively flat, but negative for most nutrients; on average, the decline in r amounted to 0.07 after 5 years, indicating that the potential of a single FFQ measurement to rank subjects according to nutrient intake dropped only slightly over time. This is important for studies on cancer since a long induction period may be involved. It was furthermore shown that the proportion of within-subject (error) variance of the FFQ method that could be attributed to correlated error ranged from 0 to 50%. This finding confirms that a reliability study may underestimate the measurement error of a method., Sponsorship: Dutch Cancer Society (grants CIVO 86-1 and CIVO 90-3).

For an evaluation of fat-soluble vitamin concentrations in adipose tissue as biomarkers of intake, estimates of usual intake of beta-carotene, total vitamin A, and vitamin E (assessed by food frequency questionnaire) were compared with plasma and adipose tissue concentrations of beta-carotene, retinol, and alpha-tocopherol, respectively. Data were collected in 1992 in the Netherlands for 85 healthy, nonsmoking volunteers aged 50-70 years (38 males and 47 females). For alpha-tocopherol, a significant age- and sex-adjusted partial correlation (r = 0.24, p < 0.05) was observed between adipose tissue levels and intake. For beta-carotene, the partial r was 0.20. Adipose tissue retinol did not reflect intake (partial r = 0.08). Correlations of adipose tissue vitamin levels with plasma vitamin levels were higher overall (r = 0.34 for alpha-tocopherol, r = 0.56 for beta-carotene, and r = 0.17 for retinol) than correlations with intake. Plasma concentrations of alpha-tocopherol, beta-carotene, and retinol were not associated with dietary intake (partial r's were 0.05, 0.17, and -0.12, respectively). Pearson correlations of repeated measurements in adipose tissue (after 4 months) were 0.24 for retinol, 0.50 for beta-carotene, and 0.78 for alpha-tocopherol. Adipose tissue beta-carotene was shown to increase sixfold after 6 months' supplementation with 30 mg of beta-carotene daily. It is concluded that adipose tissue vitamin concentrations are an acceptable alternative to plasma levels as relatively stable indicators of dietary intake. However, both plasma and adipose tissue levels are more useful as markers of internal dose, taking into account variations in absorption and metabolism, than of dietary intake.

To examine whether the consumption of fermented dairy products or the dietary intake of calcium decreases colon cancer risk, a case-control study was conducted in the The Netherlands. Dietary patterns were assessed in detail (for cases before diagnosis or symptoms occurred) using a structured dietary history questionnaire. After adjustment for potential confounding variables, consumption of fermented dairy products, hard cheese and unfermented dairy products was not significantly associated with risk of colon cancer: an odds ratio (OR) of 1.1 was found for individuals consuming more than one serving of fermented dairy products per day as compared to those consuming less than 10% of one serving a day. Adjustment for dietary calcium attenuated the associations. Total dietary calcium was positively but non-significantly associated with colon cancer risk after adjustment for age, gender, urbanization level and total energy intake. Additional adjustment for a positive family history of colorectal cancer, cholecystectomy and energy-adjusted intake of total fat, dietary fibre, vitamin C and alcohol increased the association. No differences were observed between calcium from fermented and from unfermented dairy sources. The observed associations for fermented dairy products and dietary calcium differed between men and women: positive significant associations were observed in men, while in women non-significant inverse associations were found. Our results do not support the hypothesis that an increased intake of commercially available, commonly used fermented dairy products or dietary calcium decreases the risk of colon cancer.

The association between toenail selenium and breast cancer was studied in a prospective study on diet and cancer among 62,573 Dutch women aged 55-69 years that started in September 1986. The analysis was based on 355 breast cancer cases, detected during 3.3 years of follow-up (1986-1989), for whom selenium data were available. Selenium levels were significantly lower among cases diagnosed early during follow-up. After exclusion of cases that occurred in the first year of follow-up, multivariable-adjusted rate ratios of breast cancer in increasing quintiles of selenium were 1.00, 0.90, 0.76, 0.86, and 0.91 (trend p = 0.618). The authors found no evidence for an inverse association between selenium status and breast cancer.

Objective: The study was conducted to assess the validity of a self-administered 150-item food frequency questionnaire (FFQ), used in a cohort study on diet and cancer (120,852 men and women, aged 55-69)., Design & Subjects: The study was carried out in a subgroup of the cohort (59 men and 50 women) 2 years after the baseline FFQ was completed. A dietary record, kept over three 3-day periods, 4-5 months apart, served as reference method. To evaluate the representativeness of the study population for the entire cohort, a comparison was made with the baseline questionnaire of a random sample of the cohort., Results: Pearson correlation coefficients between nutrient intakes assessed by the record and the FFQ that was completed afterwards ranged from 0.40 (95% CI: 0.22-0.54) for vitamin B1 to 0.86 (95% CI: 0.80-0.90) for alcohol intake, with correlations for most nutrients between 0.6 and 0.8. Adjustment for energy intake and sex did not materially affect these correlations, except the correlation for fat intake, which changed from 0.72 to 0.52. Correlation coefficients were only slightly modified when the results were extrapolated to the cohort at large. Correction of correlation coefficients for attenuation by day-to-day variance in the record data improved them by 0.07 on average., Conclusions: It is concluded that the FFQ is able to rank subjects according to intake of food groups and nutrients. Despite a better performance of validation study participants, this conclusion also applies to the cohort at large.

The association between alcohol consumption and cancer of the colon and rectum was investigated in a prospective cohort study, conducted in the Netherlands from 1986 onwards among 120,852 men and women, aged 55 to 69 years. During 3.3 years of follow-up, 312 and 166 cases of colon and rectal cancer had accumulated, respectively. After exclusion of cases diagnosed in the first year of follow-up, the analysis was based on 217 incident cases of colon cancer (107 men and 110 women) and 113 cases of rectal cancer (75 men and 38 women). For colon cancer, no association with total intake of alcohol nor with the consumption of beer and wine, specifically, could be demonstrated; for liquor intake, a significant (P = 0.04) decreasing risk with increasing consumption was observed. For rectal cancer in men, positive trends were observed for total alcohol intake (P = 0.04), beer (P = 0.05), and liquor (P = 0.06). Results for rectal cancer in women were consistent with those in men, but data were too sparse to provide stable estimates. Simultaneous adjustment for beverage type and quantity appeared to strengthen the association of rectal cancer with drinking beer (relative rate (yes/no) = 2.0, 95 percent confidence interval = 1.1-3.9), although a dose-response effect was not observed. When alcohol intake from beer, wine, and liquor were included as continuous variables, the association was somewhat stronger for liquor than for beer, but none of the associations were statistically significant. It is concluded that consumption of alcoholic beverages (beer, in particular) is associated with an increased risk for rectal but not colon cancer.

Objective: To study the relative validity of an open-ended question on the consumption of dietary supplements in the preceding five-year period, incorporated in a self-administered questionnaire used in the NLCS, The Netherlands Cohort Study on diet and cancer (120,852 men and women aged 55-69 years)., Design: Questionnaire data were compared with reference information from three personal interviews carried out within a period of 10 months., Setting and Subjects: A randomly selected subgroup (59 men and 50 women) of the cohort living in 12 municipalities in the eastern and western regions of The Netherlands., Results and Conclusions: The overall sensitivity of the questionnaire concerning the use of any dietary supplement was 65.9%, the specificity was 98.5%; kappa as measure of agreement was estimated at 0.69. A high percentage recall was observed among women, users of at least three types of dietary supplements, long-term supplement users and those in the oldest age group. Recall of intake of specific supplements ranged from 77.8% for garlic preparations to 11.8% for 'other' supplements. Estimates of consumption of specific supplements (garlic and vitamin preparations) may provide enough precision to correctly classify individuals as users or non-users of those supplements.

The high incidence of colon cancer in affluent societies has often been attributed to a high fat diet and, more in particular, the consumption of meat. The association of the consumption of meat and the intake of fat with risk of colon cancer was investigated in a prospective cohort study on diet and cancer, which is being conducted in the Netherlands since 1986 among 120,852 men and women, aged 55-69. The analysis was based on 215 incident cases of colon cancer (105 men and 110 women) accumulated in 3.3 years of follow-up, excluding cases diagnosed in the first year of follow-up. Dietary habits were assessed at baseline with a 150-item semiquantitative food frequency questionnaire. No trends in relative rates of colon cancer were detected for intake of energy or for the energy-adjusted intake of fats, protein, fat from meat, and protein from meat. Consumption of total fresh meat, beef, pork, minced meat, chicken, and fish was not associated with risk of colon cancer either. Processed meats, however, were associated with an increased risk in men and women (relative rate, 1.17 per increment of 15 g/day; 95% confidence interval, 1.03-1.33). The increased risk appeared to be attributable to one of the five questionnaire items on processed meat, which comprised mainly sausages. This study does not support a role of fresh meat and dietary fat in the etiology of colon cancer in this population. As an exception, some processed meats may increase the risk, but the mechanism is not yet clear.

Selenium has been suggested to be anticarcinogenic and to play a role in the cellular defense against oxidative stress. The association between toenail selenium (a marker of long-term selenium status) and lung cancer was investigated in a cohort study of diet and cancer that started in 1986 among 120,852 Dutch men and women aged 55-69 years. After 3.3 years of follow-up, 550 incident cases of lung carcinoma were detected. Toenail selenium data were available for 370 lung cancer cases and 2459 members of a randomly selected subcohort. The rate ratio of lung cancer for subjects in the highest compared to the lowest quintile of toenail selenium, after controlling for age, gender, smoking, and education, was 0.50 (95% confidence interval, 0.30-0.81), with a significant inverse trend across quintiles (P = 0.006). The protective effect of selenium was concentrated in subjects with a relatively low dietary intake of beta-carotene or vitamin C. The rate ratio in the highest compared to the lowest quintile of selenium was 0.45 in the low beta-carotene group (95% confidence interval, 0.22-0.92; trend P = 0.028) and 0.36 in the low vitamin C group (95% confidence interval, 0.17-0.75; trend P < 0.001). The results of this study support an inverse association between selenium status and lung cancer and suggest a modification of the effect of selenium by the antioxidants beta-carotene and vitamin C.

A continuous in vitro method for the estimation of the bioavailability of minerals and trace elements is presented. This in vitro method is believed to be more representative of in vivo physiological conditions than in vitro methods based on equilibrium dialysis, because dialysable components are continuously removed from the pancreatic digestion mixture. The continuous in vitro method is compared with the equilibrium in vitro method with respect to the dialysability of Ca, Mg, Fe, Cu and Zn from eight different types of bread (varying in phytic acid content). The results show a pronounced effect of continuous removal of dialysable components from the pancreatic digestion mixture on the dialysability of minerals and trace elements. Furthermore, removal of dialysable components influences the effect of phytic acid on the bioavailability of minerals and trace elements. For these two reasons the importance of removal of dialysable components in vitro for the estimation of bioavailability in vivo needs further investigation. The bioavailability of minerals and trace elements from bread samples is not related to the phytic acid content only. Therefore, the effect of phytic acid on the bioavailability of minerals and trace elements cannot be studied separately from the effects of other components on bioavailability.

In evaluating dietary data with reference to guidelines for a healthy diet, some potential pitfalls (i.e., method of food consumption assessment and calculation to include or exclude energy derived from alcohol) were investigated. The percentage of energy intake (en%) derived from total fat, saturated fatty acids (SFA), mono- and disaccharides (MD) and intake of cholesterol and dietary fiber per megajoule were calculated using 2-day records obtained in the Dutch National Food Consumption Survey of 1987-1988. Subjects (aged 4-85, n = 5595) were classified into age-sex groups. Mean values and intake distributions were calculated with and without adjustment for within-person variation. Except for the intake of cholesterol and MD, mean intake levels were not in accord with guidelines. About 20% of the women and 23% of the men met the goal for fat intake, 20% of the men and 27% of the women for dietary fiber, and about 60 and 70% for MD and cholesterol. Only 3% of subjects had SFA intake < or = 10 en%, whereas < 1% had a diet in accord with all criteria studied. After adjustment for within-person variation, percentages meeting the guidelines were generally lower for fat, SFA and dietary fiber and slightly higher for cholesterol and MD. Among elderly, unadjusted results were more in agreement with the prevalence estimates based on habitual dietary intake data than with adjusted ones. Fat intake (en%) was inversely related with intake of added MD and alcohol. Our data indicate that guidelines should state explicitly whether energy-related recommendations include energy derived from alcohol, and that the prevalence of a high-fat intake is more affected by the calculation method than by food consumption assessment.

The association between cholecystectomy and subsequent risk for colorectal carcinoma was investigated in a prospective cohort study on diet and cancer (n = 120,852), which is being conducted in the Netherlands from 1986 onwards among 120,852 men and women, aged 55 to 69. After a follow-up period of 3.3 years, 478 incident cases of colorectal cancer (258 men and 220 women) were identified in the cohort, 64 of whom reported at baseline to have undergone previous gall-bladder surgery (21 men and 43 women). After adjustment for age and familial history of large-bowel cancer, the relative rate (RR) for colorectal cancer in subjects who had undergone cholecystectomy compared with those who had not was 1.81 in men (p = 0.02) and 1.47 in women (p = 0.05). Additional adjustment for parity. Quetelet index, alcohol intake and other dietary variables resulted in a RR of 1.78 in men and 1.51 in women. In women, the highest RR was detected in the right colon (RR = 1.89), whereas in men, no site within the large bowel accounted specifically for the increased relative rate. In both men and women, the rate appeared to increase from approximately 6 years after cholecystectomy onward. According to the TNM stage of the disease, cholecystectomized patients were not detected at an earlier stage than the other patients. It is concluded that in this study the positive association between colorectal cancer and cholecystectomy cannot be explained by detection bias or ascertainment bias and is not confounded by risk factors for gallstone disease or dietary factors.

Potential predictors of toenail selenium levels were studied in 1211 men and 1248 women aged 55-69 years. These subjects were randomly selected cohort members without prevalent cancer (other than skin) participating in a prospective study on diet and cancer in the Netherlands. Information on the considered potential predictors (gender, age, smoking, intake of dietary selenium and alcohol, Quetelet index) was collected together with toenail specimens in 1986. The average toenail selenium concentration was significantly (P < 0.001) lower in men than in women: 0.547 +/- 0.126 microgram/g (mean +/- SD) and 0.575 +/- 0.109 microgram/g, respectively. The gender difference remained significant after adjustment for the other variables in multiple regression analyses. Age was not associated with toenail selenium levels in men or women. An inverse association was observed with current smoking but not with past smoking. The average toenail selenium values for male current smokers were 0.513 +/- 0.106 microgram/g (mean +/- SD) versus 0.571 +/- 0.133 microgram/g for male never- or ex-smokers (P < 0.001). For women these values were 0.548 +/- 0.101 and 0.581 +/- 0.109 microgram/g, respectively (P < 0.001). Dietary selenium intake was positively associated with toenail selenium levels in multivariate analyses (P < 0.001), but the association was weak (partial r = 0.09). Alcohol intake and Quetelet index were not significant independent predictors of toenail selenium. The observed associations had similar directions in men and women but were stronger in men.

Recently published results of epidemiologic case-control studies in China and Italy on gastric carcinoma in relation to diet suggest that consuming garlic may reduce the risk of gastric cancer. Chemical constituents of garlic have been tested for their inhibiting effect on carcinogenesis, using in vitro and in vivo models. In most experiments inhibition of tumour growth was established using fresh garlic extract, garlic compounds or synthetically prepared analogs. In this review the strengths and weaknesses of the experiments are discussed and the outcomes are evaluated to assess the possible significance of garlic or garlic compounds for the prevention of cancer in humans. It is concluded that evidence from laboratory experiments and epidemiologic studies is presently not conclusive as to the preventive activity of garlic. However, the available evidence warrants further research into the possible role of garlic in the prevention of cancer in humans.

Background: Various animal studies and ecologic studies suggest an inverse association between low dietary selenium intake and risk of various types of cancer., Purpose: The goal of this prospective cohort study was to investigate the association between toenail selenium levels and risks of stomach cancer and colorectal cancer., Methods: Our cohort study on diet and cancer started in The Netherlands in 1986 with enrollment of 120,852 subjects aged 55-69 years. Of this number, 58,279 were men and 62,573 were women. Following the case-cohort approach for analysis of the data, we randomly selected from the cohort a subcohort of 3500 subjects (1688 men and 1812 women). After 3.3 years of follow-up, 155 incident cases of microscopically confirmed stomach cancer, 313 cases of colon cancer, and 166 cases of rectal cancer had been detected in the cohort. Toenail selenium data were available for 104 patients with stomach cancer, 234 with colon cancer, and 113 with rectal cancer and for 2459 subjects from the subcohort., Results: In a multivariate analysis, the relative rates (RRs) of stomach cancer for subjects in increasing quintiles of toenail selenium level were 1.00, 0.44, 0.59, 0.84, and 0.64 (trend, P = .491). For men, there was some evidence for an inverse association between toenail selenium levels and stomach cancer: The RR for those in the highest compared with the lowest quintile of toenail selenium was 0.40 (95% confidence interval = 0.17-0.96), but the trend was not statistically significant (P = .136). For stomach cancer in women, there was no negative association with toenail selenium levels. Toenail selenium level was not associated with the risk of colon or rectal cancer. After exclusion of cases diagnosed in the 1st year of follow-up, the RRs of colon cancer for increasing quintiles of toenail selenium were 1.00, 1.27, 1.17, 0.75, and 1.07 (trend, P = .544); for rectal cancer, RR estimates were 1.00, 1.73, 0.83, 1.58, and 1.12 (trend, P = .890)., Conclusions: These data support a suggestive but inconsistent inverse association between selenium levels and risk of stomach cancer. Our findings, like those of other studies, do not suggest an inverse association with risk of colorectal cancer.

By means of a two-day dietary record, information on the use of dietary supplements has been collected in 1987 and 1988 in a representative sample of the Dutch population aged 1-75 years. More than 17 percent of the population had been using at least one dietary supplement on at least one day of the survey. Age, sex, season, social class, alternative food habits, smoking and diet were related to the use of supplements. In young persons mainly fluoride and vitamin AD preparations were used, while a shift towards other supplements, like garlic and brewer's yeast preparations, was observed as age progresses. The use of single vitamin C supplements was not related to the level of mean daily vitamin C intake by food consumption.

In 1986 a prospective cohort study on diet and cancer was started in the Netherlands among 62,573 women ages 55-69 years. Baseline information on diet and other risk factors was collected with a questionnaire. Cancer incidence was measured by record linkage with cancer registries and a pathology register. A case-cohort approach was used, in which the accumulated person time in the cohort was estimated by follow-up of a randomly selected subcohort (n = 1812). After 3.3 years of follow-up, 471 incident breast cancer cases were available for analysis. Questionnaire data for these cases and the 1716 female subcohort members without a history of cancer other than skin cancer were analyzed. In a multivariate analysis, controlling for traditional risk factors, the relative rates for breast cancer in increasing quintiles of energy-adjusted total fat intake were 1.00, 1.00, 1.34, 1.22, 1.08 (P-trend, 0.32). For saturated fat there was some evidence for a weak positive association when quintiles were used (relative rates in quintiles 1-5, 1.00, 1.22, 1.22, 1.38, 1.39; P-trend, 0.049). The 95% confidence interval (CI) for the top quintile was 0.94-2.06, however; and when saturated fat was used as a continuous variable, the effect was no longer significant (P = 0.20). Relative rate estimates for the highest versus lowest quintiles of monounsaturated fat, polyunsaturated fat, and cholesterol intake were 0.75 (95% CI, 0.50-1.12), 0.95 (95% CI, 0.64-1.40) and 1.09 (95% CI, 0.74-1.61), respectively, with no evidence for significant trends. This prospective study does not support a major role of dietary fat in the etiology of postmenopausal breast cancer.

beta-carotene has been hypothesised to reduce lung cancer risk. We studied the effect of 14 weeks of beta-carotene supplementation (20 mg d-1) on the frequency of micronuclei in sputum in 114 heavy smokers in a double-blind trial. Micronuclei reflect DNA damage in exfoliated cells and may thus provide a marker of early-stage carcinogenesis. Pre-treatment blood levels of cotinine, beta-carotene, retinol and vitamins C and E were similar in the placebo group (n = 61) and the treatment group (n = 53). Plasma beta-carotene levels increased 13-fold in the treatment group during intervention. Initial micronuclei counts (per 3,000 cells) were higher in the treatment group than in the placebo group (5.0 vs 4.0, P < 0.05). During intervention, the treatment group showed a 47% decrease, whereas the placebo group showed a non-significant decrease (16%). After adjustment for the initial levels, the treatment group had 27% lower micronuclei counts than the placebo group at the end of the trial (95% CI: 9-41%). These results indicate that beta-carotene may reduce lung cancer risk in man by preventing DNA damage in early-stage carcinogenesis.

Study Objective: The aim was to investigate whether dietary factors cluster in a favourable or unfavourable way and to characterise the groups identified by lifestyle and sociodemographic variables., Design and Setting: This cross sectional study was based on data of the 1987-1988 Dutch national food consumption survey (DNFCS), obtained from a panel by a stratified probability sample of the non-institutionalised Dutch population., Participants: 3781 adults (1802 males and 1979 females) of the DNFCS, aged 19 to 85 years, were studied., Measurements and Main Results: To estimate dietary intake two day food records were used. Lifestyle factors were collected by structured questionnaire and sociodemographic variables were available from panel information. Cluster analysis was used to classify subjects into groups based on similarities in dietary variables. Subsequently, these groups were characterised by sociodemographic and lifestyle factors as well as by the consumption of food groups. Eight clusters were found. In comparison with the guidelines, the dietary quality in four clusters was poor. The cluster with the poorest dietary intake (high intake of fat, cholesterol, and alcohol; low intake of dietary fibre) showed on average a high consumption of animal products (except milk), fats and oils, snacks, and alcoholic beverages, and a low consumption of fruit, potatoes, vegetables, and sugar rich products. Smoking, body mass index, dietary regimen on own initiative, hours of sleep, gender, age, socioeconomic status, and day of the week were found to discriminate among the clusters., Conclusions: Cluster analysis resulted in substantial differences in mean nutrient intake and seems useful for dietary risk group identification. Undesirable lifestyle habits were interrelated in some clusters, but an exclusive lifestyle for health risk has not been found.

Insight into the occurrence of and the association between certain socio-economic variables and life-style characteristics is necessary for preventive nutrition and health policy. The prevalence of and the interdependencies among these variables were examined in 1930 men and 2204 women aged 19 to 85 who participated in the Dutch National Food Consumption Survey 1987-1988. Dietary data were based on a two-day record. The associations among discrete variables were analysed using log-linear models. Analysis of covariance was used to explore the effects of the aggregate socio-economic status (SES) on dietary intake and anthropometry, whereas differences in food intake and SES were assessed by the non-parametric test of Kruskal and Wallis. In comparison to subjects with a high SES in people with a low SES a higher proportion of smokers (48 vs 32 per cent) was observed, a higher prevalence of obesity (39 vs 28 per cent), a higher percentage of heavy coffee drinkers (greater than six cups per day, 23 vs 17 per cent), and more subjects who skipped breakfast (19 vs 11 per cent). In the highest SES class more subjects used nutritional supplements (18 vs 11 per cent), more subjects followed a dietary rule (five vs two per cent), such as a vegetarian diet, and a higher proportion used more than three alcoholic drinks per day (19 vs 15 per cent). A higher SES was associated with a lower fat intake, but the differences (expressed as per cent of energy intake) were rather small and even absent among women when the contribution of alcohol to energy was not taken into account. In general, dietary intake among subjects in higher SES groups tended to be closer to dietary recommendations. The results indicate that a lower SES is accompanied by a higher prevalence of several indicators of an unhealthy life-style.

Combinations of dietary factors were studied in relation to breast-cancer occurrence among 133 breast cancer cases and 289 population controls in The Netherlands. Dietary factors were classified according to their possible mechanism of action, i.e., relating either to the intestinal microflora (total fat, fiber, fermented milk products) or to the anti-oxidant hypothesis (beta-carotene, selenium and polyunsaturated fatty acids). From 6 interactions evaluated, the combination of high fiber intake and high intake of fermented milk products was the only one suggesting synergistic protection (age-and-fat-adjusted OR for interaction = 0.48, 95% confidence interval (CI) = 0.21 - 1.13). In order to estimate the extent to which the above dietary factors together might be related to breast cancer, subjects with a supposedly favorable dietary pattern (low fat intake, high fiber intake, high intake of fermented milk products; high intake of beta-carotene and selenium, low intake of polyunsaturated fatty acids) were compared with subjects with an unfavorable dietary pattern. This resulted in an age-adjusted odds ratio of 0.40 (95% CI = 0.14 - 1.15), which was largely attributable to the combination of low intake of fat and high intake of fermented milk products and fiber (age-adjusted OR = 0.33, 95% CI = 0.15 - 0.73). The other factors did not appreciably affect the odds ratio. These analyses show in a quantitative way that a dietary pattern which combines low intake of fat and high intake of fiber and fermented milk products might provide substantial protection against breast cancer.

A double-blind study on the effects of vitamin C restriction on physical performance was executed with 12 healthy men. During seven weeks of low vitamin C intake six subjects were on a daily diet of regular food products, providing 20% of the Dutch Recommended Dietary Allowances (RDA) for vitamin C (Dutch RDA is 50 mg/day). Other vitamins were supplemented at twice the RDA level. After three weeks of low vitamin intake an additional vitamin C dose of 15 mg/day was provided, resulting in a total intake of 25 mg/day (50% of the Dutch RDA). Six control subjects consumed the same diet supplemented with twice the RDA for all vitamins. In the restriction group blood vitamin C levels decreased significantly (p less than 0.01). Vitamin C restriction had no harmful effects on health, aerobic power (VO2-max), and onset of blood lactate accumulation (OBLA). However, an increased heart rate at OBLA level was observed during the period of low vitamin C intake (p less than 0.05), possibly by interference with either catecholamine or carnitine metabolism. These results suggest that short-term marginal vitamin C deficiency does not affect physical performance in single bouts of intensive exercise.

The association between breast cancer and selenium, measured in the diet, plasma, erythrocytes, and toenails, was investigated in a case-control study in the Netherlands during 1985-1987. Dietary selenium intake was assessed by a structured dietary history technique among 133 breast cancer cases and 238 population controls. Absolute and energy-adjusted selenium intake and selenium concentrations in plasma, erythrocytes, and toenails were similar in cases and controls. The multivariate adjusted odds ratios of breast cancer for subjects in the lowest quartile compared with the highest quartile were 1.6 (95% confidence interval (CI) 0.8-3.4) for dietary selenium, 2.0 (95% CI 0.9-4.4) for plasma selenium, 0.9 (95% CI 0.4-1.9) for erythrocyte selenium, and 1.1 (95% CI 0.6-2.1) for toenail selenium. No statistically significant trend was observed in the odds ratios for any of the four indicators of selenium. These results do not suggest a substantial association between selenium and breast cancer for both short- and long-term markers of selenium status.

To study the association between dietary fiber, beta-carotene and breast cancer, the average daily intake of these dietary components was compared among 133 incident breast cancer cases and 238 population controls. Average daily intake of cereal products, fruit and vegetables was also studied. A statistically significant lower energy-adjusted intake of dietary fiber was observed in cases than in controls (mean +/- SD: 25.4 +/- 6.7 g vs. 27.7 +/- 7.4 g, 95% confidence interval (CI) of the age-adjusted difference = -3.8, -0.8). Intake of beta-carotene was similar for cases and controls. The multivariate adjusted odds ratio (OR) of breast cancer among women in the highest quartile of intake of cereal products, as compared to those in the lowest quartile, was 0.42 (95% CI = 0.19-0.92) and the trend was statistically significant (p = 0.03). The corresponding OR for intake of dietary fiber was 0.55 (95% CI = 0.26-1.17) but the trend was not significant. The OR for the highest quartile of intake of beta-carotene, fruit, vegetables, and all vegetable products combined was less than unity, but there was no significant inverse trend. These results suggest that a high intake of cereal products, especially those rich in fiber, may be inversely related to incidence of breast cancer.

Age-adjusted dietary fat intake of 133 incident Dutch breast cancer cases was significantly (p less than 0.01) higher than in 289 apparently healthy controls (mean and standard deviation: 102 +/- 36 g and 92 +/- 30 g, respectively). The age-adjusted relative odds of breast cancer showed a positive trend (p less than 0.05) with increasing fat intake. The multivariate adjusted relative odds was 3.5 (95% Cl = 1.6-7.6) for subjects in the highest quintile of fat intake (above 113 g) compared to those in the lowest quintile (below 65 g); this corresponds to a 30% increased risk per 10% of energy derived from fat. The association could not be attributed to energy intake, nor to the degree of saturation of the fat nor to any specific dietary source of fat.

In a nationwide survey the nutritional status was assessed of 539 apparently healthy, independently living elderly aged 65-79 years. Anthropometric data showed no energy deficits. The prevalence of anemia was 4 and 1% among men and women, respectively. Many elderly showed a low level of 25-hydroxyvitamin D in plasma (less than 31 nmol/L: men 35%; women 43%), indicating a marginal status. Although the prevalence of low blood levels of folate, pyridoxal-5'-phosphate, and total carotenoids was higher among the elderly than among younger adults, clear (clinical) signs of nutritional deficiencies were not observed. Prevalence of obesity (13%), hypercholesterolemia (38%), and hypertension (63%) was found to be high, the percentages being higher for women than for men. Several indicators of the nutritional status appeared to differ among age groups. It is concluded that few differences can be considered as being due to physiological aging, which finding should be reflected in reference values for elderly people.

In 1986, a prospective cohort study on diet and cancer was started in The Netherlands. The cohort (n = 120, 852) of 55-69 year old men (48.2%) and women (51.8%) originates from 204 computerized municipal population registries. At baseline, participants completed a self-administered questionnaire on diet and potential confounding variables. In addition, about 67% of the participants provided toenail clippings. Cancer follow-up consists of record linkage to a pathology registry and to cancer registries. The initial interest is in stomach, colorectal, breast and lung tumors. A case-cohort approach is applied, in which detailed follow-up information of a random subcohort (n = 5000) provides an estimate of the person-time experience of the cohort. Exposure data of the subcohort will be combined with those of incident cases, yielding exposure-specific incidence rate ratios. The intraindividual variation in determinants is estimated by annually repeated measurements (n = 250) within the subcohort. The rationale, efficiency aspects and study characteristics are discussed.

The fatty acid composition of the cholesteryl esters in serum was measured in 7- and 8-year-old boys in groups from 16 countries. The ratio of esterified cholesterol: total cholesterol was also measured. All sample collections and analyses were carried out under standardized conditions. The proportion of palmitic acid in the cholesteryl esters was high in the groups from Asia and Africa (0.17-0.26) compared with that in the groups from the U.S.A. and Europe (0.14-0.18). The proportion of linoleic acid in the cholesteryl esters was low in the groups from Asia and Africa (0.39-0.48) and high in the groups from the U.S.A. and Europe (0.45-0.58). The proportion of oleic acid, arachidonic acid, palmitoleic acid and stearic acid showed little variation between the groups. The proportion of linoleic acid in the cholesteryl esters was positively correlated with the concentration of total cholesterol (r = 0.75, n = 26, P < 0.005).

The dietary intake (assessed through dietary history) of 539 apparently healthy, independently living elderly aged 65-79 years, was evaluated in a nationwide random sample. Except for pyridoxine, the intake of vitamins, minerals, and water was adequate according to the Dutch recommended dietary allowances. Fat intake (40 energy%) as well as P/S ratio (0.41) was assessed as being unfavorable, whereas the intake of vitamin B6 was marginal. The prevalence of obesity was higher among the women, while food selection was healthier as reflected in the higher nutrient density than among the men. Food consumption of elderly men (26%) and women (33%) on a dietary regimen was more prudent and nutrient density higher than among the elderly not on a diet. Our results are in accordance with previous food consumption studies among elderly in The Netherlands, but differ substantially from dietary intake figures for American elderly. Although the intake of energy and nutrients was lower among elderly men than among younger men, we conclude that age per se is not an important determinant of dietary intake among Dutch apparently healthy elderly aged 65-79 years.

The effects of wheat bran and other sources of dietary fibre on serum total and high density lipoprotein(HDL)-cholesterol were investigated in a group of 62 subjects, with rigid control of dietary intake. It was found that a high-fibre diet with vegetables and fruits as well as a low-fibre diet, to which isolated citrus pectin had been added to the same level as present in the vegetables and fruits diet, caused a small decrease in the concentration of serum cholesterol after 5 weeks. Surprisingly, addition of bran (on average 38 g/day) to a low-fibre diet caused an increase in the level of serum cholesterol by on average 0.34 mmol/l (P less than or equal to 0.005). The amount and type of dietary fibre had no substantial effect on the HDL-cholesterol concentration.

The effects of casein and soy protein on serum cholesterol levels and lipoprotein composition were studied in 69 healthy volunteers (18 to 28 yr of age) under strict dietary control. Subjects were fed for 6 wk on diets containing 13% of energy as protein, 38% as fat (P/S ratio = 0.6) and about 380 mg cholesterol per day. Of the protein in the diets 65% consisted of casein or soy protein or a 2:1 mixture of casein and soy protein. After a control period of 10 days during which all the subjects received the casein-soy diet, 20 subjects continued on this diet for the next 4 wk as a base-line control, 25 subjects switched to the casein diet, and the remaining 24 subjects switched to the soy diet. Both food records and chemical analysis of double portions revealed that the diets were completely identical except for the type of protein. Average serum cholesterol levels at the end of the control period were 152 +/- 27 mg/dl (3.93 +/- 0.69 mmol/l) and 153 +/- 23 mg/dl (3.95 +/- 0.60 mmol/l) (mean +/- SD) for the casein and soy group, respectively. At the end of the test period the levels were 149 +/- 24 and 150 +/- 23 mg/dl, respectively; thus there was no significant change on either diet. On the casein diet there was no change in the low-density lipoprotein cholesterol concentration, and only a slight, nonsignificant increase in the high-density lipoprotein cholesterol concentration. On the soy diet, however, there was a significant decline in low-density lipoprotein-cholesterol (-6.6 mg/dl; -0.17 mmol/l) and a significant increase in high-density lipoprotein-cholesterol (+5.8 mg/dl; +0.15 mmol/l). The decline in low-density lipoprotein cholesterol in the soy group was significantly different from the small change in the casein group, but the difference in increase in high-density lipoprotein cholesterol in the soy and the casein group was only weakly significant. This suggest that soy protein could have a slight beneficial effect on the distribution of cholesterol over the various lipoprotein fractions, even at constant total cholesterol concentration.