Gender-stratified analysis of DLG5 R30Q in 4707 patients with Crohn disease and 4973 controls from 12 Caucasian cohorts.

BACKGROUND: DLG5 p.R30Q has been reported to be associated with Crohn disease (CD), but this association has not been replicated in most studies. A recent analysis of gender-stratified data from two case-control studies and two population cohorts found an association of DLG5 30Q with increased risk of CD in men but not in women and found differences between 30Q population frequencies for males and females. Male-female differences in population allele frequencies and male-specific risk could explain the difficulty in replicating the association with CD. METHODS: DLG5 R30Q genotype data were collected for patients with CD and controls from 11 studies that did not include gender-stratified allele counts in their published reports and tested for male-female frequency differences in controls and for case-control frequency differences in men and in women. RESULTS: The data showed no male-female allele frequency differences in controls. An exact conditional test gave marginal evidence that 30Q is associated with decreased risk of CD in women (p = 0.049, OR = 0.87, 95% CI 0.77 to 1.00). There was also a trend towards reduced 30Q frequencies in male patients with CD compared with male controls, but this was not significant at the 0.05 level (p = 0.058, OR = 0.87, 95% CI 0.74 to 1.01). When data from this study were combined with previously published, gender-stratified data, the 30Q allele was found to be associated with decreased risk of CD in women (p = 0.010, OR = 0.86, 95% CI 0.76 to 0.97), but not in men. CONCLUSION: DLG5 30Q is associated with a small reduction in risk of CD in women.

Urinary sucrose and fructose as biomarkers of sugar consumption: comparison of normal weight and obese volunteers.

Using urinary sugars as a biomarker of consumption, we have previously shown that obese people consume significantly more sugars than individuals of normal weight. However, there is concern that recovery of this biomarker may differ between normal weight and obese individuals. A total of 19 subjects, divided into two groups according to their body mass index (BMI) (normal weight BMI < or = 25 kg/m(2), n=10; obese BMI > or = 30 kg/m(2), n=9), participated in a randomized crossover dietary intervention study of three diets providing 13, 30 and 50% of energy from sugars for 4 days each while living in a volunteer suite. The mean urinary sucrose and fructose excretions in 24-h urine increased with increasing sugar consumption over the three dietary periods in both BMI groups and were significantly different between the diets (P < 0.01). There was no significant interaction effect of BMI class on the mean urinary excretions of these sugars with different sugar intakes, either as absolute values or expressed as a percentage of total sugar intake. In conclusion, BMI does not affect the validity of sucrose and fructose excretions in 24-h urine collections used as biomarkers to estimate total sugar consumption.

Twenty-four-hour urinary thiamine as a biomarker for the assessment of thiamine intake.

OBJECTIVE: To investigate 24-h urinary thiamine as a potential biomarker for thiamine intake for use in validation studies to assess the validity of dietary intake data collected by self-reporting dietary methods. SUBJECTS: Seven male and six female healthy participants living for 30 days in a metabolic suite under strictly controlled conditions consuming their usual diet as assessed beforehand from four consecutive 7-day food diaries kept at home. During the 30-day study, all 24-h urine specimens were collected, validated for their completeness and analysed for thiamine. RESULTS: Thirty-day mean (+/-s.d.) calculated thiamine intake was 2.22+/-0.55 mg/day. Thirty-day mean (+/-s.d.) urinary excretion of thiamine was 526.5+/-193.0 microg/day (24.7+/-8.10% of intake). There was a highly significant correlation between individuals' 30-day means of thiamine intake and their mean excretion level (r=0.720; P=0.006), where 1 mg of thiamine intake predicted 268.2 microg of thiamine in urine. The correlations between intake and excretion remained significant when measurement from a single 24-h urine collection was used (r=0.56). CONCLUSION: Twenty-four-hour urinary thiamine can be used as a concentration biomarker for thiamine intake in dietary validation studies.

Differential leucocyte count and the risk of future coronary artery disease in healthy men and women: the EPIC-Norfolk Prospective Population Study.

BACKGROUND: We examined the relationship between granulocyte, lymphocyte and monocyte counts and risk of coronary heart disease (CHD) and cardiovascular disease (CVD) in men and women. There is paucity of data on the differential leucocyte count and its relationship with the risk of CHD and CVD. METHODS: This prospective study comprised 7073 men and 9035 women who were 45-79 years of age and were residents of Norfolk. United Kingdom. RESULTS: During an average of 8 years of follow-up we identified 857 incident CHD events and 2581 CVD incident events. Increased total leucocyte count was associated with increased risk for both CHD and CVD. The highest quartile of granulocyte count was associated with increased risk when compared to lowest quartile for CHD (men HR 1.70 95% CI: 1.30-2.21; women HR 1.24 95% CI: 0.91-1.69) and for CVD (men HR 1.46 95% CI: 1.24-1.71; women HR 1.20 95% CI: 1.02-1.42). The association remained unchanged when the analyses were restricted to nonsmokers and when risk was assessed for every 1000 cells L(-1) increase in cell count. In multivariable models, despite adjusting for C-reactive protein (CRP), the granulocyte count remained an independent predictor of CHD and CVD risk, especially amongst men. Lymphocyte or monocyte counts were not significantly associated with increased risk. In all analyses, additionally adjusting for CRP did not affect the results materially. CONCLUSIONS: In conclusion, we found that the higher risk for CHD and CVD associated with increased total leucocyte count seems to be accounted for by the increased granulocyte count.

Intakes and sources of soya foods and isoflavones in a UK population cohort study (EPIC-Norfolk).

BACKGROUND: It has been suggested that the consumption of a diet rich in phytoestrogens might protect against a variety of diseases common in Western societies. However, there are little available data on the food sources or distribution of intake in the UK diet. OBJECTIVE: To estimate the average intake and range of soya foods and isoflavones in a population-based cohort and to provide data on isoflavone consumption by food group. SUBJECTS: Men and women (11,843) from the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Dietary daidzein and genistein intakes were obtained from 7-day food diaries, completed by participants between 1993 and 1998 and calculated from an in-house food composition database. Energy and anthropometric measurements were also carried out. RESULTS: Average daily isoflavone intakes for both men and women were less than 1 mg (interquartile range (IQR) men: 0.39-0.82 mg; women: 0.30-0.64 mg). However, in soya-consumers, average daily intakes were higher: 8.6 mg in women (IQR: 2.28-10.72 mg) and 7.5 mg in men (IQR: 2.22-9.17 mg). In both men and women, bread and bread rolls made the highest contribution to isoflavone intake - 62.5 and 53.0%, respectively. In soya-consuming men and women, vegetable dishes and milks were the main contributors - 25.0 and 38.5% in men and 38.5% and 26.0% in women, respectively. CONCLUSIONS: Isoflavone intake is low in the UK but may be an underestimate due to soya added to commercial products. Future analyses of the isoflavone and lignan content of basic ingredient foods and commercial items commonly consumed in the UK diet will enable more accurate estimates of phytoestrogen intake to be made. The ability to estimate isoflavone intake in Western populations more accurately will enable investigations to be conducted into the suggested beneficial effects of phytoestrogens on health.

Tissue factor serum levels and the risk of future coronary artery disease in apparently healthy men and women: the EPIC-Norfolk prospective population study.

INTRODUCTION: Tissue factor (TF) has been implicated in coronary artery disease (CAD). High levels of circulating TF are found in patients with acute atherothrombotic events. Whether high serum TF levels predict risk of future CAD independent of known risk factors remains unknown. METHODS: We conducted a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population study. Cases (n=1037) were apparently healthy men and women, aged 45-79 years, who developed fatal or non-fatal CAD during follow-up. Controls (n=2005) were matched by age, sex, and enrolment time. Serum TF levels were measured using high-affinity antibodies. RESULTS: In men, median TF levels were not significant higher in cases than in controls (59.0 pg mL-1, range: 16.7-370.4 vs. 54.9 pg mL-1, range: 16.2-452.4). In women, median TF levels were not significant higher in controls than in cases (73.4 pg mL-1, range: 16.7-492.3 vs. 50.5 pg mL-1, range: 16.5-376.7). The incidence of smoking was about double in the lowest compared with the highest TF quartile. Correcting for sex, age, body mass index, smoking, diabetes, systolic blood pressure, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and C-reactive protein levels, the risk of future CAD was 1.05 (95% CI: 0.81-1.36) for people in the highest TF quartile, compared with those in the lowest (P-value for linearity=0.8). CONCLUSION: High levels of serum TF were not independently associated with an increased risk of future CAD in apparently healthy individuals.

Meat, starch, and nonstarch polysaccharides and large bowel cancer.

Starch and nonstarch polysaccharides enter the large gut where they are available for fermentation by the bacterial flora. The effect of fermentation on nitrogen metabolism, the supply of nutrients to the mucosa, and the carcinogen production is discussed in relation to epidemiological associations between dietary intake and large bowel cancer incidence.

The use of 24-h urine samples and energy expenditure to validate dietary assessments.

The doubly labeled-water technique can be used as a noninvasive measure of energy expenditure, and, with no gains or losses in weight, expenditure should equal intake. Provided sufficiently complete urine collections are obtained, urine nitrogen is an accurate measure of protein intake in individuals in nitrogen balance. Validations of dietary surveys by using estimates of energy expenditure and the 24-h urine nitrogen technique show that inaccurate reports of food intake occur in a proportion of individuals within a group, leading to bias in overall average intakes for some nutrients, if only one method of dietary assessment is used. Errors between methods however are not usually correlated, so that improved estimates can be obtained from a combination of two or more methods of dietary assessment. All future dietary surveys should require independent evidence of their validity.

Using biochemical markers to assess the validity of prospective dietary assessment methods and the effect of energy adjustment.

The validity of dietary assessment methods in a group of women aged 50-65 y was evaluated with use of biochemical markers. Estimates of nitrogen, potassium, and carotene intakes from weighed-food and estimated records yielded higher correlations with urinary nitrogen, urinary potassium, and serum concentrations of carotenoids than did estimates from food-frequency questionnaires and 24-h recalls. When the residuals method of energy adjustment was used, the correlations between intakes of nitrogen and potassium estimated from food-frequency questionnaires and 24-h recalls and intakes derived from weighed-food records improved, and the high correlations between biochemical markers and estimates from weighed-food records were maintained. In addition, with use of this method, estimates for nitrogen and potassium intakes from food-frequency questionnaires showed the most improvement in comparison with the biochemical markers; however, the correlations of crude nitrogen and potassium with crude energy intake were highest. Carotene intake was not related to energy intake, so that correlations between the intake of carotene assessed by any method and the plasma beta-carotene concentration did not improve with energy adjustment and between-person variability was not reduced. Energy adjustment with either the energy density or residuals method did not alter the ranking of accuracy of various dietary assessment methods in comparison with weighed-food records or biochemical markers in either the total group of subjects or those who were identified as having provided valid weighed-food records.

Urine nitrogen as an independent validatory measure of dietary intake: a study of nitrogen balance in individuals consuming their normal diet.

In order to determine the value of 24 h urine nitrogen (N) excretion as a way of validating dietary methods of measuring protein intake in individuals, daily N intake and excretion has been measured in eight healthy subjects while consuming their usual, varying, diets for 28 days. Daily duplicates of all food eaten were obtained and consecutive 24 h collections of urine and feces were made throughout and analyzed for N by the Kjeldahl method. The completeness of the 24 h urine collections was verified by the use of PABA and of feces by radiopaque pellets. N losses in blood and from the skin were measured. The within person variation in dietary intake ranged from 14 to 26% (coefficient of variation, CV) while urine N was more constant, varying from 11 to 18% (CV) within individuals. In these subjects eight 24 h urine collections, verified for their completeness, were sufficient to estimate dietary N intake to within 81 +/- 5% (SD) as assessed by 18 day dietary records.

Use of biological markers to validate self-reported dietary intake in a random sample of the European Prospective Investigation into Cancer United Kingdom Norfolk cohort.

BACKGROUND: The validity of dietary assessment methods should be established before diet-disease associations are reported. OBJECTIVE: Our objective was to validate a 7-d food diary and a food-frequency questionnaire (FFQ) against independent biomarkers of intake in urine (nitrogen, potassium, and sodium) and blood (plasma ascorbic acid). DESIGN: A total of 146 healthy middle-aged men and women were recruited from the European Prospective Investigation into Cancer UK Norfolk cohort, a free-living cohort of approximately 25000 persons. Over a 9-mo period, urinary nitrogen, potassium, and sodium were estimated from 2-6 complete 24-h urine collections in 134 subjects and plasma ascorbic acid was estimated from 2-3 fasting blood samples in 118 subjects. Subjects completed 2 FFQs and two 7-d food diaries. RESULTS: In men and women combined, correlations between 24-h urinary nitrogen excretion and dietary intake from the 7-d food diary were high (r = 0.57-0.67) compared with those for the FFQ (r = 0.21-0.29). Similarly, correlations between urinary potassium and dietary potassium were higher for the 7-d food diary (r = 0.51-0.55) than for the FFQ (r = 0.32-0.34). There was no overall difference in correlations between plasma ascorbic acid and dietary vitamin C between the 7-d food diary (r = 0.40-0.52) and the FFQ (r = 0.44-0.45). CONCLUSIONS: These data indicate that, despite increased subject burden, the 7-d food diary provided a better estimate of nitrogen and potassium intakes than did the FFQ in this study population. However, with respect to plasma ascorbic acid, both the FFQ and 7-d food diary provided a similar ranking of subjects according to vitamin C intake.

Mammographic patterns as a predictive biomarker of breast cancer risk: effect of tamoxifen.

Mammographic breast density has been shown to be associated with up to a 4- to 6-fold increase in risk of breast cancer, whereas tamoxifen therapy increases disease-free survival and reduces mortality. We have therefore investigated whether these effects are related. To determine the effects of tamoxifen on mammographic density, mammograms from 94 women who had received tamoxifen for breast cancer and 188 women (without breast cancer) who had not received tamoxifen were visually classified according to the criteria of Wolfe. Two controls were age-matched to each case. All of the women were postmenopausal (ages, 50-64 years), neither group was taking hormone replacement therapy, and none of the cases had received chemotherapy. There were significant differences in breast density between cases and controls at the initial mammogram (P = 0.0001) but no significant differences at the follow-up mammogram (P = 0.51). A significant change to a more lucent pattern had occurred among the case group (P = 0.0001). The odds ratio for cancer that was associated with the more dense (P2 and DY) patterns with respect to the more lucent (N1 and P1) patterns was 3.6 (95% confidence interval, 2.11-6.18) at the initial mammogram. This was significantly reduced to 1.5 (95% confidence interval, 1.32-1.70) after treatment with tamoxifen (P = 0.019; chi2 = 5.52). The substantial reduction in breast density with tamoxifen provides evidence that tamoxifen has the capacity to favorably alter postmenopausal breast density toward a more lucent pattern, which is associated with reduced risk of breast cancer. Mammographic pattern is, thus, a potential biomarker of breast cancer risk.

Apolipoprotein E and methylenetetrahydrofolate reductase genetic polymorphisms in relation to other risk factors for cardiovascular disease in UK Caucasians and Black South Africans.

Genetic polymorphisms for apolipoprotein E (apo E) and methylenetetrahydrofolate reductase (MTHFR) are believed to modulate risk of coronary heart disease (CHD) acting through regulation of lipid and homocysteine metabolism, respectively. The distributions of apo E and MTHFR alleles in Black South Africans, a population with a low CHD incidence, and UK Caucasians from the Cambridge area, with a higher CHD incidence, were therefore compared. Clinically healthy volunteers (207), including 107 UK Caucasians from the Cambridge area and 100 Black South Africans, participated in the study. Apo E and MTHFR genotypes were determined in all of them. Analyses for serum total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and plasma fibrinogen were carried out in 65 UK Caucasians and 60 Black South Africans. The apo E epsilon4 allele, which is associated with elevated CHD risk, was present in 48% of Black South Africans compared to 20.8% of Caucasians (P < 0.0001); however, both total and LDL cholesterol levels in Black South Africans were 18-32% lower than in Caucasians with similar apo E genotypes. Hyperhomocysteinemia-causing MTHFR 677T variant was detected in only 20% of Black South Africans (no homozygotes) versus 56% of Caucasians with 12% homozygotes (P<0.0001). Our findings suggest that the potentially unfavourable pattern of apo E allele distribution in Black South Africans does not result in increased CHD incidence due to protection by dietary and/or other life style related factors. The exceptionally low frequency of MTHFR mutant homozygotes in this population suggests that this polymorphism should not be regarded as an important CHD risk factor among Black South Africans.

Comparison of metabolic effects of vegetables and teas with colorectal proliferation and with tumour development in DMH-treated F344 rats.

The aim of this study was to screen potentially chemopreventive vegetables and teas for their effects as human dietary components for the colorectal epithelium and also to seek biomarkers of preventive efficacy. Groups of F344 rats were adapted to a human basal diet supplemented with vegetables or teas, having known contents of glucosinolates, polyphenols and anti-oxidants. Both inductions and suppressions were found for overall glutathione S-transferase (GST) and quinone reductase activities. The mitotic index (MI) showed a three-fold range between groups, with substantial reductions by black tea, spinach, petit pois and peppers. Changes to PCNA labelling index and proliferation zone were marginal. No correlation was found between colonic and hepatic enzyme activities, nor with glucosinolate intake. Colonic MI was associated with the activity ratio GST(hepatic)/GST(colonic) (r = 0.49, P < 0.002), possibly reflecting a need for direct induction rather than exposure to products of hepatic conjugation.

Magnetic microcapsules as novel biomonitors of cross-linking agents and diet-dependent reactive oxygen species in the human gastrointestinal tract.

Six healthy, scientifically informed human volunteers were given 14C-labeled polyethyleneimine (PEI) microcapsules by mouth. Fecal 14C recovery was inversely related to mean gut transit time (r = -0.66), and the extent of cross-linking between the membrane and core PEI was inversely related to total fecal output (r = -0.81). Cross-linking of PEI microcapsules may be a biomonitor of endogenous cross-linking agents within the human gastrointestinal tract. Extensive loss of [14C]CH3 label occurred from the microcapsules during human transit and in in vitro fermentations with human fecal flora. A mechanism whereby reactive oxygen species could arise in the iron-rich core of these microcapsules, leading to loss of [14C]CH3 label, is proposed.

Validation of dietary assessment methods in the UK arm of EPIC using weighed records, and 24-hour urinary nitrogen and potassium and serum vitamin C and carotenoids as biomarkers.

BACKGROUND: In the UK EPIC validation studies, the accuracy of several methods was assessed by comparison with to-day weighed records and the biomarkers, 24-hour urine nitrogen (N) and potassium (K), plasma carotenoids and plasma vitamin C. METHODS: Comparisons between methods were made on 156 women, studied over 1 year at 3-monthly intervals at home. On each of four occasions, volunteers completed 4 days of weighed records and provided two 24-hour urine collections and a fasting blood sample. RESULTS: In comparison with the 16 days of weighed records, a food frequency questionnaire (FFQ) yielded higher values mainly due to greater reported consumption of milk and of vegetables. A 24-hour recall was as good as the FFQ in placing individuals in the distribution of habitual diet from weighed records. Results obtained from a 7-day estimated record were closest to those obtained from the weighed record. Correlations between 24-hour urine excretion and dietary N intake from weighed records were high (0.78-0.87) as were those with estimated food diaries (0.60-0.70). Correlations between urine N and the FFQ and 24-hour recall were lower (0.10 to 0.27), but improved by energy adjustment using residuals for N and K which are correlated with total energy intake. Comparisons between dietary estimates and urinary K and serum carotenoids and vitamin C showed broadly similar results. Limited biomarker information amongst 200 UK EPIC participants supported the findings of the validation study. CONCLUSIONS: UK EPIC uses three methods (the 7-day diary, an improved FFQ, and the 24-hour recall) to assess diet. 93% of first food diaries are returned completed by participants. Repeated diaries are the main dietary assessment method for nested case-control analyses.

Dietary assessments in the European prospective study of diet and cancer (EPIC).

Biomarkers of nutrition intake were used to validate the dietary assessments proposed for use in the European prospective study of diet and cancer (EPIC). In the UK validation studies, the accuracy of several tested methods was assessed with weighed food records and biomarkers, 24 h urine nitrogen, potassium and plasma carotenoids and vitamin C. Correlations between dietary nitrogen intake from weighed food records and 24 h urine excretion were high (0.78-0.87). The correlations between nitrogen from estimated food diaries and urinary nitrogen were r = 0.60-0.70. Correlations with other methods were lower, but improved by energy adjustment, using residuals for those nutrients correlated with total energy, such as nitrogen and potassium, but not for nutrients not correlated with energy intake--for example, beta-carotene. Hence, the correlation between urinary nitrogen and unadjusted nitrogen from a food frequency questionnaire (FFQ) was 0.24 but improved with energy adjustment to 0.49. UK EPIC uses three methods (diary, improved FFQ and 24 h recall) to assess diet, with repeated measures from the food diary at 18 months and four years. Ninety-three percent of first food diaries are returned completed by participants. Results from 200 subjects randomly selected from the first 2,000 recruits suggest that differences between methods with improved FFQ design are less obvious than in the initial validation study. Results from the diary are more closely correlated with plasma carotenoids and vitamin C than other methods, although supplements of vitamin C are the main determinant of the magnitude of correlations. More detailed biomarker studies are in progress among EPIC participants.

Daidzein and genistein content of fruits and nuts.

Dietary phytoestrogens such as the isoflavones daidzein and genistein are thought to protect against chronic diseases that are common in Western societies, such as cancer, osteoporosis, and ischemic heart disease. In addition, there are concerns regarding the deleterious effects of hormone-like compounds, especially with respect to the development of infants. However, there is little information regarding the phytoestrogen content of foods, and therefore epidemiologic investigations of phytoestrogens are limited. As part of a study quantifying the consumption of phytoestrogens, the objective of this work was to assess the daidzein and genistein content of fruits and nuts commonly eaten in Europe. Eighty different fruits and nuts were sampled, prepared for eating, and freeze-dried. Daidzein and genistein were extracted from the dried foods, and the two isoflavones were quantified after hydrolytic removal of any conjugated carbohydrate. Completeness of extraction and any procedural losses of the isoflavones were accounted for using synthetic daidzin (7-O-glucosyl-4'-hydroxyisoflavone) and genistin (7-O-glucosyl-4'5-dihydroxyisoflavone) as internal standards. Of the 80 foods assayed, 43 contained no detectable daidzein or genistein, at a limit of quantification of 1 microg/kg dry weight of food. Nine foods contained more than 100 microg of the two isoflavones combined per kilogram wet weight, and 28 contained less than this amount. Currants and raisins were the richest sources of the isoflavones, containing 2,250 microg and 1,840 microg of the two isoflavones combined per kilogram of wet weight of food. Although fruits and nuts are not as rich in isoflavone phytoestrogens as are soy and other legumes, this is the first documentation of levels of daidzein and genistein occurring in these foods.

Measurements of total energy expenditure provide insights into the validity of dietary measurements of energy intake.

The quantification of errors inherent in methods of measuring dietary intake has been handicapped by the absence of independent markers for testing their validity. The doubly labeled water technique permits a precise measure of energy expenditure in free-living persons. Because energy expenditure must equal energy intake in populations in energy balance, this technique may be used to validate the assessment of energy intake. A series of studies demonstrated good agreement between mean energy intake and mean energy expenditure when food intake was recorded by observers or when it was self-reported by normal-weight, self-selected, highly motivated volunteer subjects using weighed records. However, in randomly recruited men and women, energy intake by weighed records was 82% and 81%, of energy expenditure, respectively, indicating underestimation of habitual intake. Men and women in the lowest third of reported intake recorded energy expenditure of only 69% and 61%, respectively. Reported intake of obese and previously obese women was only 73% and 64% of expenditure, whether measured by weighed record or by diet history, confirming suspicions that these subjects misrepresented their intake. Acceptable weighed records were obtained from 7- and 9-year-olds whereas 15- and 18-year-olds underestimated intake. Diet histories taken from the same children tended to overestimate intake. These studies suggest that, ideally, all dietary studies should include independent measures of validity.

Validation of dietary intakes of protein and energy against 24 hour urinary N and DLW energy expenditure in middle-aged women, retired men and post-obese subjects: comparisons with validation against presumed energy requirements.

OBJECTIVES: To compare validation of reported dietary intakes from weighed records against urinary nitrogen excretion and energy expenditure measured by DLW, and to examine the utility of the Goldberg cut-off for EI:BMR in the identification of under-reporters. DESIGN: Energy (EI) and nitrogen (protein) intake (NI) were measured by 16 d of weighed diet records collected over 1 y. They were validated against urinary nitrogen excretion in 5-8 (mean 6.0) 24 h urine collections and total energy expenditure (EE) measured by doubly labelled water (DLW). Basal metabolic rate (BMR) as measured by whole body calorimetry in women or bedside ventilated hood (Deltatrac) in men. Individual subjects were identified as under-reporters if Urine N:NI was > 1.00 or if EI:EE was < 0.79. The agreement between the two ratios in detecting under-reporting was examined. The results from the direct validation by DLW were also compared with validation using the Goldberg cut-off for EI:BMR (Goldberg et al, 1991). SUBJECTS: Eighteen women aged 50-65 y and 27 men aged 55-87 y were selected from participants in two larger dietary surveys as representing the full range of dietary reporting as measured by Urine N:NI. Data from a previous study of 11 post-obese subjects were also included. RESULTS: The two ratios, Urine N:NI and EI:EE, were significantly related (r = -0.48, P < 0.01). Using the above cut-offs, seven (4F, 3M) subjects were identified as under-reporters by both methods, one (1M) by Urine N:NI only and 8 (3F, 5M) by EI:EE only. There was close agreement in post-obese subjects where 6 subjects showed a substantial degree of under-reporting by both methods (r = -0.87, P < 0.001). The correlation between direct validation by DLW and EI:BMRest was 0.65 (P < 0.001). Some limitations of the Goldberg cut-off for identifying individual under-reporters were demonstrated. CONCLUSIONS: EI:EE provides an estimate of the degree of under-reporting of energy at the group and individual level. Urine N:NI identifies under-reporting of protein intake and the most obvious under-reporters of energy, but is probably of lesser value in estimating the overall degree of under-reporting of energy at group level. Good validation by EI:BMR depends on knowledge of physical activity at both group and individual level. However, the correlation of 0.65 between EI:EE and EI:BMRest suggests that EI:BMR could be usefully incorporated into analysis of data from epidemiological studies. Validation measures consisting of at least predicted EI:BMR ratios and urinary measures should be incorporated into dietary surveys. SPONSORSHIP: This work was funded by the Ministry of Agriculture Fisheries and Food, the Medical Research Council, the Cancer Research Council and the Swedish Medical Research Council and the Henning and Johan Throne-Holst Foundation.