Vegetable and fruit consumption and risks of colon and rectal cancer in a prospective cohort study: The Netherlands Cohort Study on Diet and Cancer.

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.

A prospective cohort study on antioxidant and folate intake and male lung cancer risk.

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.

Vegetable and fruit consumption and lung cancer risk in the Netherlands Cohort Study on diet and cancer.

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.

Approach of the US food and nutrition board to daily nutrient requirements: 'a useful basis for the European discussion on risk assessment of nutrients?' Report on a workshop organized by the European Academy of Nutritional Sciences (EANS) and TNO Food and Nutrition Research Institute, 11 December 1998, Brussels.

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

[Clinical significance of extra vitamin supplements and enriched food products]. / Klinische betekenis van extra vitaminen uit supplementen en verrijkte voedingsmiddelen.

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.

European Consensus Statement on Lung Cancer: risk factors and prevention. Lung Cancer Panel.

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 effects of the calcium-restricted diet of urolithiasis patients with absorptive hypercalciuria type II on risk factors for kidney stones and osteopenia.

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.

Vitamins C and E, retinol, beta-carotene and dietary fibre in relation to breast cancer risk: a prospective cohort study.

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.

Rationale, design and methods of a study on micronutrient status among adults.

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).

Effects of calcisorb on fecal bile acids and fatty acids in human volunteers.

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.

Reproducibility of a food frequency questionnaire and stability of dietary habits determined from five annually repeated measurements.

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).

Relations between antioxidant vitamins in adipose tissue, plasma, and diet.

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.

Fermented dairy products, dietary calcium and colon cancer: a case-control study in The Netherlands.

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.

Toenail selenium levels and the risk of breast 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.

Validation of a dietary questionnaire used in a large-scale prospective cohort study on diet and 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.

Prospective study on alcohol consumption and the risk of cancer of the colon and rectum in the Netherlands.

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.

Agreement between interview data and a self-administered questionnaire on dietary supplement use.

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.

A prospective cohort study on the relation between meat consumption and the risk of colon cancer.

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.

Bile acids and pH values in total feces and in fecal water from habitually omnivorous and vegetarian subjects.

Twenty habitually omnivorous subjects and 19 habitually lactoovovegetarian subjects aged 59-65 y collected feces during 4 consecutive days. The concentrations of bile acids in total feces did not differ between the omnivores and vegetarians, but the bile acid concentrations in fecal water were significantly lower in the vegetarians. The concentration of the colorectal cancer-predicting bile acid deoxycholic acid in fecal water was explained by the intake of saturated fat and the daily fecal wet weight (r2 = 0.50). Fecal pH did not differ between the omnivores and vegetarians. This variable was significantly (P < 0.05) explained by the intake of calcium (r2 = 0.30); 24-h fecal wet weight and defecation frequency were significantly higher in the vegetarians. In conclusion, our vegetarian subjects had a lower concentration of deoxycholic acid in fecal water, higher fecal wet weight, and higher defecation frequency than the omnivorous subjects.