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The objective of the present study was to investigate the influence of the single nucleotide polymorphism (rs17238540) at the 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene (HMGCR) on the relationship between serum lipids and dietary fat and fibre (NSP). FFQ and pyrosequencing were used to assess cross-sectional dietary intake and HMGCR genotype in a population study with data for serum lipids available. Genotype frequencies and allele distributions for 23 011 participants were: TT 95·65 %, TG 4·29 % and GG 0·06 %; T 97·8 % and G 2·2 %. In regression analyses, the TG+GG group showed a significant positive relationship between TAG and SFA intake (+0·11 (95 % CI 0·02, 0·20) mmol TAG/l; P = 0·017; per 3 % SFA energy increase) while the TT individuals showed no change in the TAG levels related to SFA intake ( − 0·0007 (95 % CI − 0·02, 0·02) mmol TAG/l; P = 0·99). TG+GG individuals showed an inverse relationship between TAG and fibre intake higher ( − 0·14 (95 % CI − 0·22, − 0·05) mmol TAG/l than the TT group ( − 0·04 (95 % CI − 0·06, − 0·02) mmol TAG/l). In both cases the respective coefficient regressions of TAG were different between the genotype groups (Z = 2·27, P = 0·023 for SFA intake; Z = 2·19, P = 0·029 for fibre intake). Individuals carrying the G allele may show a greater response in lower TAG levels with reduced SFA intake and increased fibre intake compared with those homozygous for the T allele. The effectiveness of different dietary interventions to control serum lipids may vary according to HMGCR genotype.
Evidence exists that a more acidic diet is detrimental to bone health. Although more precise methods exist for measurement of acid–base balance, urine pH reflects acid–base balance and is readily measurable but has not been related to habitual dietary intake in general populations. The present study investigated the relationship between urine pH and dietary acid–base load (potential renal acid load; PRAL) and its contributory food groups (fruit and vegetables, meats, cereal and dairy foods). There were 22 034 men and women aged 39–78 years living in Norfolk (UK) with casual urine samples and dietary intakes from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk FFQ. A sub-study (n 363) compared pH in casual samples and 24 h urine and intakes from a 7 d diary and the FFQ. A more alkaline diet (low PRAL), high fruit and vegetable intake and lower consumption of meat was significantly associated with a more alkaline urine pH before and after adjustment for age, BMI, physical activity and smoking habit and also after excluding for urinary protein, glucose, ketones, diagnosed high blood pressure and diuretic medication. In the sub-study the strongest relationship was found between the 24 h urine and the 7 d diary. In conclusion, a more alkaline diet, higher fruit and vegetable and lower meat intake were related to more alkaline urine with a magnitude similar to intervention studies. As urine pH relates to dietary acid–base load its use to monitor change in consumption of fruit and vegetables, in individuals, warrants further investigation.
To compare the average out-of-home (OH) consumption of foods and beverages, as well as energy intake, among populations from 10 European countries and to describe the characteristics of substantial OH eaters, as defined for the purpose of the present study, in comparison to other individuals.
Cross-sectional study. Dietary data were collected through single 24-hour dietary recalls, in which the place of consumption was recorded. For the present study, substantial OH eaters were defined as those who consumed more than 25% of total daily energy intake at locations other than the household premises. Mean dietary intakes and the proportion of substantial OH eaters are presented by food group and country. Logistic regression analyses were used to estimate the odds of being a substantial OH eater in comparison to not being one, using mutually adjusted possible non-dietary determinants.
Ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC).
The subjects were 34 270 individuals, 12 537 men and 21 733 women, aged 35–74 years.
The fraction of energy intake during OH eating was generally higher in northern European countries than in the southern ones. Among the food and beverage groups, those selectively consumed outside the home were coffee/tea/waters and sweets and, to a lesser extent, cereals, meats, added lipids and vegetables. Substantial OH eating was positively associated with energy intake and inversely associated with age and physical activity. Substantial OH eating was less common among the less educated compared with the more educated, and more common during weekdays in central and north Europe and during the weekend in south Europe.
Eating outside the home was associated with sedentary lifestyle and increased energy intake; it was more common among the young and concerned in particular coffee/tea/waters and sweets.
To investigate the association of a posteriori dietary patterns with overall survival of older Europeans.
Design and setting
This is a multi-centre cohort study. Cox regression analysis was used to investigate the association of the prevailing, a posteriori-derived, plant-based dietary pattern with all-cause mortality in a population of subjects who were 60 years or older at recruitment to the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort). Analyses controlled for all known potential risk factors.
In total, 74 607 men and women, 60 years or older at enrolment and without previous coronary heart disease, stroke or cancer, with complete information about dietary intakes and potentially confounding variables, and with known survival status as of December 2003, were included in the analysis.
An increase in the score which measures the adherence to the plant-based diet was associated with a lower overall mortality, a one standard deviation increment corresponding to a statistically significant reduction of 14% (95% confidence interval 5–23%). In country-specific analyses the apparent association was stronger in Greece, Spain, Denmark and The Netherlands, and absent in the UK and Germany.
Greater adherence to the plant-based diet that was defined a posteriori in this population of European elders is associated with lower all-cause mortality. This dietary score is moderately positively correlated with the Modified Mediterranean Diet Score that has been constructed a priori and was also shown to be beneficial for the survival of the same EPIC-Elderly cohort.
Intervention and prospective studies showing no effect of fibre in protection against colo-rectal cancer have challenged consensus recommendations that population intakes of fibre should be increased to reduce the risk of colo-rectal cancer. The European Prospective Investigation of Cancer and Nutrition (EPIC) of 519 978 individuals aged 25–70 years is the largest prospective study of diet and cancer to date worldwide. It incorporates ten different European countries in order to increase heterogeneity in dietary habits and calibration procedures to reduce measurement error. Data for 1065 reported cases of colo-rectal cancer were reported in 2003. There was a 40% reduction in risk for the highest quintile v. lowest quintile of fibre in food after calibration. It has been suggested that these effects were a result of confounding by folate and other factors. Although there are a number of hypotheses to explain why folate should be protective in colo-rectal cancer, a meta-analysis has shown that folate in food may be protective but there is no effect of total folate (i.e. food plus supplements). In a further analysis of 1826 cases in EPIC, identified in the latest follow-up, the inclusion of an additional 761 cases has confirmed the previously published results, with a strong and significant reduction in colo-rectal cancer of approximately 9% reduction in risk for each uncalibrated quintile increase in fibre (P<0·001 for linear trend) compared with an 8% reduction in the previous report, which had not been adjusted for folate. Inclusion of the other covariates (physical activity, alcohol, smoking and red and processed meat) with folate has confirmed this significant inverse association for colon cancer and strengthened the association with left-sided colon cancer (P<0·001).
Up to 80 % of breast, bowel and prostate cancers are attributed to dietary practices, and international comparisons show strong positive associations with meat consumption. Estimates of relative risk obtained from cohort investigations are in the same direction, although generally weak, and red and processed meats rather than white meat seem to be associated with elevated risk of colon cancer. In breast cancer, there are consistent associations with total meat intake and there is evidence of a dose response. Despite these associations with meat, existing studies suggest that vegetarians do not have reduced risk of breast, bowel or prostate cancer, but there are no quantitative estimates of amounts of meat consumed by meat eaters in these cohort studies. Possible mecha-nisms underlying epidemiological associations include the formation of heterocyclic amines in meat when it is cooked. These heterocyclic amines require acetylation by P450 enzymes, and individuals with the fast-acetylating genotype who eat high amounts of meat may be at increased risk of large-bowel cancer. NH3 and N-nitroso compounds (NOC) formed from residues by bacteria in the large bowel are probably also important. NH3 is a promotor of large-bowel tumours chemically induced by NOC, and some of the chromosomal mutations found in human colo-rectal cancer are consistent with effects of NOC and heterocyclic amines. However, the type, amount, and cooking method of meat or protein associated with increased risk are not certain. The effects of high levels of meat on NH3 and NOC output are not reduced by increasing the amount of fermenta-ble carbohydrate in the diet, but interaction between meat, NSP and vegetable intakes on the risk of cancer has not been studied comprehensively. The interaction between dietary low-penetrance genetic polymorphic and somatic mutation factors has also been investigated to a limited extent. Current Department of Health (1998) recommendations are that meat consumption should not rise, and that consumers at the top end of the distribution should consider a reduction in intakes.
In addition to their possible direct biological effects, plasma carotenoids can be used as biochemical markers of fruit and vegetable consumption for identifying diet–disease associations in epidemiological studies. Few studies have compared levels of these carotenoids between countries in Europe.
Our aim was to assess the variability of plasma carotenoid levels within the cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).
Plasma levels of six carotenoids – α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin – were measured cross-sectionally in 3043 study subjects from 16 regions in nine European countries. We investigated the relative influence of gender, season, age, body mass index (BMI), alcohol intake and smoking status on plasma levels of the carotenoids.
Mean plasma level of the sum of the six carotenoids varied twofold between regions (1.35μmoll−1 for men in Malmö, Sweden vs. 2.79μmoll−1 for men in Ragusa/Naples, Italy; 1.61μmoll−1 for women in The Netherlands vs. 3.52μmoll−1 in Ragusa/Naples, Italy). Mean levels of individual carotenoids varied up to fourfold (α-carotene: 0.06μmoll−1 for men in Murcia, Spain vs. 0.25μmoll−1 for vegetarian men living in the UK). In multivariate regression analyses, region was the most important predictor of total plasma carotenoid level (partial R2=27.3%), followed by BMI (partial R2=5.2%), gender (partial R2=2.7%) and smoking status (partial R2=2.8%). Females had higher total carotenoid levels than males across Europe.
Plasma levels of carotenoids vary substantially between 16 different regions in Italy, Greece, Spain, France, Germany, the UK, Sweden, Denmark and The Netherlands. Compared with region of residence, the other demographic and lifestyle factors and laboratory measurements have limited predictive value for plasma carotenoid levels in Europe.
To describe methods and dietary habits of a large population cohort.
Prospective assessment of diet using diet diaries and food-frequency questionnaires, and biomarkers of diet in 24-h urine collections and blood samples.
Free living individuals aged 45 to 75 years living in Norfolk, UK.
Food and nutrient intake from a food-frequency questionnaire on 23 003 men and women, and from a 7-day diet diary from 2117 men and women. Nitrogen, sodium and potassium excretion was obtained from single 24-h urine samples from 300 individuals in the EPIC cohort. Plasma vitamin C was measured for 20 846 men and women.
The food-frequency questionnaire (FFQ) and the food diary were able to determine differences in foods and nutrients between the sexes and were reliable as judged by repeated administrations of each method. Plasma vitamin C was significantly higher in women than men. There were significant (P<0.001) differences in mean intake of all nutrients measured by the two different methods in women but less so in men. The questionnaire overestimated dairy products and vegetables in both men and women when compared with intakes derived from the diary, but underestimated cereal and meat intake in men. There were some consistent trends with age in food and nutrient intakes assessed by both methods, particularly in men. Correlation coefficients between dietary intake assessed from the diary and excretion of nitrogen and potassium in a single 24-h urine sample ranged from 0.36 to 0.47. Those comparing urine excretion and intake assessed from the FFQ were 0.09 to 0.26. The correlations between plasma vitamin C and dietary intake from the first FFQ, 24-h recall or diary were 0.28, 0.35 and 0.40.
EPIC Norfolk is one of the largest epidemiological studies of nutrition in the UK and the largest on which plasma vitamin C has been obtained. Methods for obtaining food and nutrient intake are described in detail. The results shown here for food and nutrient intakes can be compared with results from other population studies utilising different methods of assessing dietary intake. The utility of different methods used in different settings within the main EPIC cohort is described. The FFQ is to be used particularly in pooled analyses of risk from diet in relation to cancer incidence within the larger European EPIC study, where measurement error is more likely to be overcome by large dietary heterogeneity on an international basis. Findings in the UK, where dietary variation between individuals is smaller and hence the need to use a more accurate individual method greater, will be derived from the 7-day diary information on a nested case–control basis. 24-h recalls can be used in the event that diary information should not be forthcoming from some eventual cases. Combinations of results utilising all dietary methods and biomarkers may also be possible.
To develop a method to make use of incomplete 24-hour urinary samples in nutritional epidemiology, especially when validating the dietary intake of nitrogen (protein), sodium and potassium.
Urinary data for men and women collected in three different studies were evaluated. The concentration of para-aminobenzoic acid (PABA) in one 24-hour urine sample per person was compared with the concentrations of nitrogen, sodium, potassium and creatinine.
Men and women living in Cambridge, UK and women living in the town of Varberg, Sweden.
In total, this study consists of data from 73 Swedish women (20–50 years of age), 165 UK women (50–65 years) and 75 UK men (55–88 years).
On average four out of 10 people in this study had a PABA recovery below 85%. The linear regression equations for urinary excretion of nitrogen, sodium and potassium in relation to PABA recovery were y = 2.3 + 0.088 * x (r = 0.99), y = 45 + 0.82 * x (r = 0.87) and y = 19 + 0.60 * x (r = 0.93), respectively.
The linear regression equations can be used for adjusting urinary nitrogen, sodium and potassium in urinary collections in cases where the PABA recovery is below 85%. Since it is common to obtain 24-hour urine collections with a PABA recovery below 85%, this method should increase the usefulness of biological markers of food intake in nutritional epidemiological studies and also increase the possibilities to study people that previously have been part of the drop-out group or the group with low motivation and cooperation. It is important to stress that we have not studied the relationship between PABA recovery and various urinary variables below the PABA recovery of 50%. Thus, in a case of PABA recovery below 50%, we do not recommend the use of this method to compensate for incomplete collections.
To examine the association between fish consumption and stroke risk.
Prospective population cohort study.
Norfolk, UK cohort of the European Prospective Investigation into Cancer (EPIC–Norfolk).
Subjects were 24 312 men and women aged 40–79 years who had no previous history of stroke at baseline.
Fish consumption was assessed using a food-frequency questionnaire at baseline in 1993–1997 and stroke incidence ascertained to 2004.
A total of 421 incident strokes were identified (mean follow-up=8.5 years, total person-years=209 238). There were no significant relationships between total fish, shellfish or fish roe consumption and risk of stroke in men and women after adjusting for age, systolic blood pressure, body mass index, smoking, cholesterol, diabetes, physical activity, alcohol consumption, fish oil supplement use and total energy intake using Cox regression analyses. Oily fish consumption was significantly lower in women who subsequently had a stroke (odds ratio (OR) for consumers vs. non-consumers=0.69, 95% confidence interval (CI) 0.51–0.94, P=0.02). The trend in men was similar but not significant (OR for consumers vs. non-consumers=0.88, 95% CI 0.65–1.19, P=0.41).
There was no consistent relationship between fish consumption and stroke in this British population. Inconsistencies in the observed health effects of fish consumption in different populations may reflect different patterns and type of fish consumed and preparation methods.
There is increasing evidence for a significant effect of processed meat (PM) intake on cancer risk. However, refined knowledge on how components of this heterogeneous food group are associated with cancer risk is still missing. Here, actual data on the intake of PM subcategories is given; within a food-based approach we considered preservation methods, cooking methods and nutrient content for stratification, in order to address most of the aetiologically relevant hypotheses.
Design and setting
Standardised computerised 24-hour diet recall interviews were collected within the framework of the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study in 27 centres across 10 European countries.
Subjects were 22 924 women and 13 031 men aged 35–74 years.
Except for the so-called ‘health-conscious’ cohort in the UK, energy-adjusted total PM intake ranged between 11.1 and 47.9 g day−1 in women and 18.8 and 88.5 g day−1 in men. Ham, salami-type sausages and heated sausages contributed most to the overall PM intake. The intake of cured (addition of nitrate/nitrite) PM was highest in the German, Dutch and northern European EPIC centres, with up to 68.8 g day−1 in men. The same was true for smoked PM (up to 51.8 g day−1). However, due to the different manufacturing practice, the highest average intake of NaNO2 through PM consumption was found for the Spanish centres (5.4 mg day−1 in men) as compared with German and British centres. Spanish centres also showed the highest intake of NaCl-rich types of PM; most cholesterol- and iron-rich PM was consumed in central and northern European centres. Possibly hazardous cooking methods were more often used for PM preparation in central and northern European centres.
We applied a food-based categorisation of PM that addresses aetiologically relevant mechanisms for cancer development and found distinct differences in dietary intake of these categories of PM across European cohorts. This predisposes EPIC to further investigate the role of PM in cancer aetiology.
To investigate the association between fruit and vegetable consumption and self-reported physical and mental functional health measured by an anglicised short-form 36-item questionnaire (UK SF-36).
Population-based cross-sectional study.
General community in Norfolk, UK.
A total of 16 792 men and women aged 40–79 years recruited from general practice population registers as part of the European Prospective Investigation into Cancer (EPIC)–Norfolk study, who completed food-frequency questionnaires in 1993–1997 and Health and Life Experiences Questionnaires 18 months later, were enrolled in the study.
Mean SF-36 physical component summary scores increased significantly with increasing total fruit and vegetable consumption in both men and women (P < 0.0001 for trend). Men and women in the top quartile of consumption compared with the bottom quartile had a significantly higher likelihood of reporting good physical health (defined as a score ≥ 55); odds ratio (OR) 1.30, 95% confidence interval (CI) 1.11–1.53 for men and OR 1.28, 95% CI 1.11–1.48 for women, after controlling for age, body mass index, smoking, education, social class, prevalent illness and total energy intake. Exclusion of current smokers and people with prevalent illness did not alter the associations.
Higher fruit and vegetable consumption is associated with better self-reported physical functional health within a general population. Increasing daily intake by two portions of fruit and vegetables was associated with an 11% higher likelihood of good functional health. Since the current average consumption of fruit and vegetables in the UK is about three portions, the recommended ‘five a day’ strategy may have additional benefit for functional as well as other health outcomes in the population.
To evaluate measurement error structure in dietary assessment instruments and to investigate its implications for nutritional studies, using urinary nitrogen excretion as a reference biomarker for protein intake.
The dietary assessment methods included different food-frequency questionnaires (FFQs) and such conventional dietary-report reference instruments as a series of 24-hour recalls, 4-day weighed food records or 7-day diaries.
Six original pilot validation studies within the European Prospective Investigation of Cancer (EPIC), and two validation studies conducted by the British Medical Research Council (MRC) within the Norfolk cohort that later joined as a collaborative component cohort of EPIC.
A sample of approximately 100 to 200 women and men, aged 35–74 years, from each of eight validation studies.
In assessing protein intake, all conventional dietary-report reference methods violated the critical requirements for a valid reference instrument for evaluating, and adjusting for, dietary measurement error in an FFQ. They displayed systematic bias that depended partly on true intake and partly was person-specific, correlated with person-specific bias in the FFQ. Using the dietary-report methods as reference instruments produced substantial overestimation (up to 230%) of the FFQ correlation with true usual intake and serious underestimation (up to 240%) of the degree of attenuation of FFQ-based log relative risks.
The impact of measurement error in dietary assessment instruments on the design, analysis and interpretation of nutritional studies may be much greater than has been previously estimated, at least regarding protein intake.
To illustrate biomarkers of diet that can be used to validate estimates of dietary intake in the study of gene–environment interactions in complex diseases.
Prospective cohort studies, studies of biomarkers where diet is carefully controlled.
Free–living individuals, volunteers in metabolic suites.
Male and female human volunteers.
Recent studies using biomarkers have demonstrated substantial differences in the extent of measurement error from those derived by comparison with other methods of dietary assessment. The interaction between nutritional and genetic factors has so far largely gone uninvestigated, but can be studied in epidemiological trials that include collections of biological material. Large sample sizes are required to study interactions, and these are made larger in the presence of measurement errors.
Diet is of key importance in affecting the risk of most chronic diseases in man. Nutritional epidemiology provides the only direct approach to the quantification of risks. The introduction of biomarkers to calibrate the measurement error in dietary reports, and as additional measures of exposure, is a significant development in the effort to improve estimates of the magnitude of the contribution of diet in affecting individual disease risk within populations. The extent of measurement error has important implications for correction for regression dilution and for sample size. The collection of biological samples to improve and validate estimates of exposure, enhance the pursuit of scientific hypotheses, and enable gene–nutrient interactions to be studied, should become the routine in nutritional epidemiology.
Tree nuts, peanuts and seeds are nutrient dense foods whose intake has been shown to be associated with reduced risk of some chronic diseases. They are regularly consumed in European diets either as whole, in spreads or from hidden sources (e.g. commercial products). However, little is known about their intake profiles or differences in consumption between European countries or geographic regions. The objective of this study was to analyse the population mean intake and average portion sizes in subjects reporting intake of nuts and seeds consumed as whole, derived from hidden sources or from spreads. Data was obtained from standardised 24-hour dietary recalls collected from 36 994 subjects in 10 different countries that are part of the European Prospective Investigation into Cancer and Nutrition (EPIC). Overall, for nuts and seeds consumed as whole, the percentage of subjects reporting intake on the day of the recall was: tree nuts = 4·4%, peanuts = 2·3% and seeds = 1·3%. The data show a clear northern (Sweden: mean intake = 0·15 g/d, average portion size = 15·1 g/d) to southern (Spain: mean intake = 2·99 g/d, average portion size = 34·7 g/d) European gradient of whole tree nut intake. The three most popular tree nuts were walnuts, almonds and hazelnuts, respectively. In general, tree nuts were more widely consumed than peanuts or seeds. In subjects reporting intake, men consumed a significantly higher average portion size of tree nuts (28·5 v. 23·1 g/d, P<0·01) and peanuts (46·1 v. 35·1 g/d, P<0·01) per day than women. These data may be useful in devising research initiatives and health policy strategies based on the intake of this food group.
Overall dietary patterns have been associated with health and longevity. We used principal component (PC) and cluster analyses to identify the prevailing dietary patterns of 99 744 participants, aged 60 years or older, living in nine European countries and participating in the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort) and to examine their socio-demographic and lifestyle correlates. Two PC were identified: PC1 reflects a ‘vegetable-based’ diet with an emphasis on foods of plant origin, rice, pasta and other grain rather than on margarine, potatoes and non-alcoholic beverages. PC2 indicates a ‘sweet- and fat-dominated’ diet with a preference for sweets, added fat and dairy products but not meat, alcohol, bread and eggs. PC1 was associated with a younger age, a higher level of education, physical activity, a higher BMI, a lower waist:hip ratio and never and past smoking. PC2 was associated with older age, less education, never having smoked, a lower BMI and waist:hip ratio and lower levels of physical activity. Elderly individuals in southern Europe scored positively on PC1 and about zero on PC2, whereas the elderly in northern Europe scored negatively on PC1 and variably on PC2. The results of cluster analysis were compatible with the indicated dietary patterns. ‘Vegetable-based’ and a ‘sweet- and fat-dominated’ diets are prevalent among the elderly across Europe, and there is a north–south gradient regarding their dietary choices. Our study contributes to the identification of groups of elderly who are likely to have different prospects for long-term disease occurrence and survival.