Intake of dietary fats and colorectal cancer risk: Prospective findings from the UK Dietary Cohort Consortium

Introduction: Epidemiologic evidence for an association between colorectal cancer (CRC) risk and total dietary fat, saturated fat (SF), monounsaturated fat (MUFA) and polyunsaturated fat (PUFA) is inconsistent. Previous studies have used food frequency questionnaires (FFQ) to assess diet, but data from food diaries may be less prone to severe measurement error than data from FFQ. Methods: We conducted a case–control study nested within seven prospective UK cohort studies, comprising 579 cases of incident CRC and 1996 matched controls. Standardized dietary data from 4- to 7-day food diaries and from FFQ were used to estimate odds ratios for CRC risk associated with intake of fat and subtypes of fat using conditional logistic regression. We also calculated multivariate measurement error corrected odds ratios for CRC using repeated food diary measurements. Results: We observed no associations between intakes of total dietary fat or types of fat and CRC risk, irrespective of whether dietary data were obtained using food diaries or FFQ. Conclusion: Our results do not support the hypothesis that intakes of total dietary fat, SF, MUFA or PUFA are linked to risk of CRC.     

Estimation of the correlation between nutrient intake measures under restricted sampling

Food frequency questionnaires (FFQs) are commonly used to assess dietary intake in epidemiologic research. To evaluate the FFQ reliability, the commonly used approach is to estimate the correlation coefficient between the data given in FFQ and those in food records (for example, 4-day food records [4DFR]) for nutrients of interest. However, in a dietary intervention study, a criterion for eligibility may be to select participants who have baseline FFQ-measured dietary intake of percent energy from fat above a prespecified quantity. Other instruments, such as the 4DFR, may be subsequently administrated only to eligible participants. Under these circumstances, analysis without adjusting for the restricted population will usually lead to biased estimation of correlation coefficients and other parameters of interest. In this paper, we apply likelihood-based and multiple imputation (MI) methods to accommodate such incomplete data obtained as a result of the study design. A simulation study is conducted to examine finite sample performance of various estimators. We note that both the MI estimate and the maximum likelihood (ML) estimate based on a bivariate-normal model are not sensitive to departures from this normality assumption. This led us to investigate robustness properties of the ML estimator analytically. We present some data analyses from a dietary assessment study from the Women's Health Initiative to illustrate the methods.     

Energy Intake and Physical Activity in Pima Indians: Comparison with Energy Expenditure Measured by Doubly-Labeled Water

To test the validity of survey techniques for measuring diet and activity patterns of Pima Indians, sequential 24-hour recalls, a food frequency ques tionnaire (FFQ), and an activity questionnaire were compared to free-living energy expenditure. Total energy expenditure (TEE) measured by doubly labeled water was 13.27 ± 2.95 MJ/d for the 12 males (mean±SD: 35 ± 14 yr; 97 ± 35 kg; 32 + 9% body fat) and 11.67 ± 1.85 MJ/d for the 9 females (31 ± 13 yr; 106 ± 32 kg; 49 ± 6% body fat). Energy intake assessed by 24-hour recall was 13.59 ± 7.81 MJ/d for men and 9.29 ± 2.77 MJ/d for women, compared to 12.84 ± 2.85 and 9.40 ± 2.61 MJ/d for men and women, respectively, by FFQ. Both dietary methods indicated significant underreporting by women when compared to TEE. Energy intake assessed by FFQ was significantly correlated with TEE (r=0.48, p=0.03). This was true with 24-hour recall energy intake only when data from two extremely large alcohol consumers were eliminated (r=0.64, p=0.03, N=19). Although a low level of activity was apparent, the activity questionnaire produced significant correlations with measurements of energy expenditure and therefore represents an important tool for examining the relationship between physical activity and diseases.     

Validity of a self-administered food frequency questionnaire in the assessment of heterocyclic amine intake using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) levels in hair

Several case-control studies have reported possible associations between heterocyclic amine (HCA) intake and the risk of cancer. The validity of questionnaires used to assess HCA intake has hardly been examined, however; in particular, no biomarker able to serve as an independent measure of habitual HCA intake has been established. In this study, we examined the validity of HCA intake estimated from a food frequency questionnaire (FFQ) using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) level in hair as a reference method. Study subjects were 20 volunteers (7 men and 13 women) aged 25-57 years residing in Tokyo or neighboring cities in Japan. The subjects completed the FFQ, and gave 3-5g of hair twice at an interval of 1-3 months for use in establishing validity. Results showed that intakes of PhIP, MeIQ, Trp-P-1, and total HCA by the FFQ were significantly correlated with PhIP levels in hair when adjustment was made for melanin content (r=0.47, r=0.50, r=0.55, and r=0.51, respectively). The present study indicates that HCA intake estimated from this FFQ provides a reasonable ranking of individuals to allow the analysis of associations between HCA intake and risk of cancer in large-scale epidemiological studies.     

Vitamin D Intake,Month the Mammogram Was Taken and Mammographic Density in Norwegian Women Aged 50–69

BackgroundThe role of vitamin D in breast cancer etiology is unclear. There is some, but inconsistent, evidence that vitamin D is associated with both breast cancer risk and mammographic density (MD). We evaluated the associations of MD with month the mammogram was taken, and with vitamin D intake, in a population of women from Norway—a country with limited sunlight exposure for a large part of the year.Methods3114 women aged 50–69, who participated in the Norwegian Breast Cancer Screening Program (NBCSP) in 2004 or 2006/07, completed risk factor and food frequency (FFQ) questionnaires. Dietary and total (dietary plus supplements) vitamin D, calcium and energy intakes were estimated by the FFQ. Month when the mammogram was taken was recorded on the mammogram. Percent MD was assessed using a computer assisted method (Madena, University of Southern California) after digitization of the films. Linear regression models were used to investigate percent MD associations with month the mammogram was taken, and vitamin D and calcium intakes, adjusting for age, body mass index (BMI), study year, estrogen and progestin therapy (EPT), education, parity, calcium intakes and energy intakes.ResultsThere was no statistical significant association between the month the mammogram was taken and percent MD. Overall, there was no association between percent MD and quartiles of total or dietary vitamin D intakes, or of calcium intake. However, analysis restricted to women aged <55 years revealed a suggestive inverse association between total vitamin D intake and percent MD (p for trend = 0.03).ConclusionOverall, we found no strong evidence that month the mammogram was taken was associated with percent MD. We found no inverse association between vitamin D intake and percent MD overall, but observed a suggestive inverse association between dietary vitamin D and MD for women less than 55 years old.     

Peripheral oestrogen metabolism in postmenopausal women with or without breast cancer: the role of dietary lipids and growth factors

Studies we have carried out have revealed significant differences in oestrogen production and metabolism between normal women and postmenopausal women with breast cancer. The free, biologically available fraction of oestradiol is elevated in plasma from women with breast cancer and we have found that metabolic clearance rates and production rates of oestradiol are also increased. In vitro studies have suggested that lipids can influence the distribution of sex steroids in plasma and we have therefore examined the effect of dietary lipids on the distribution of sex steroids in plasma in vivo. Consumption of a meal with a high saturated fat content or the oral or i.v. administration of "Intralipid", a stabilised emulsion of soya bean oil that is high in unsaturated free fatty acids, had little effect on the available fractions of oestradiol in plasma. However, results from a preliminary study suggest that long-term changes in dietary fat intake can alter the distribution of steroids in plasma. It is concluded that dietary lipids may influence the availability of sex steroids to tissues. Such a mechanism could account for the significant correlation that has been found between dietary fat consumption and the incidence of breast cancer on a world-wide basis.     

A zero‐augmented generalized gamma regression calibration to adjust for covariate measurement error: A case of an episodically consumed dietary intake

Measurement error in exposure variables is a serious impediment in epidemiological studies that relate exposures to health outcomes. In nutritional studies, interest could be in the association between long‐term dietary intake and disease occurrence. Long‐term intake is usually assessed with food frequency questionnaire (FFQ), which is prone to recall bias. Measurement error in FFQ‐reported intakes leads to bias in parameter estimate that quantifies the association. To adjust for bias in the association, a calibration study is required to obtain unbiased intake measurements using a short‐term instrument such as 24‐hour recall (24HR). The 24HR intakes are used as response in regression calibration to adjust for bias in the association. For foods not consumed daily, 24HR‐reported intakes are usually characterized by excess zeroes, right skewness, and heteroscedasticity posing serious challenge in regression calibration modeling. We proposed a zero‐augmented calibration model to adjust for measurement error in reported intake, while handling excess zeroes, skewness, and heteroscedasticity simultaneously without transforming 24HR intake values. We compared the proposed calibration method with the standard method and with methods that ignore measurement error by estimating long‐term intake with 24HR and FFQ‐reported intakes. The comparison was done in real and simulated datasets. With the 24HR, the mean increase in mercury level per ounce fish intake was about 0.4; with the FFQ intake, the increase was about 1.2. With both calibration methods, the mean increase was about 2.0. Similar trend was observed in the simulation study. In conclusion, the proposed calibration method performs at least as good as the standard method.     

Validity of a self-administered food frequency questionnaire in the assessment of heterocyclic amine intake using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) levels in hair

Several case-control studies have reported possible associations between heterocyclic amine (HCA) intake and the risk of cancer. The validity of questionnaires used to assess HCA intake has hardly been examined, however; in particular, no biomarker able to serve as an independent measure of habitual HCA intake has been established. In this study, we examined the validity of HCA intake estimated from a food frequency questionnaire (FFQ) using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) level in hair as a reference method. Study subjects were 20 volunteers (7 men and 13 women) aged 25–57 years residing in Tokyo or neighboring cities in Japan. The subjects completed the FFQ, and gave 3–5 g of hair twice at an interval of 1–3 months for use in establishing validity. Results showed that intakes of PhIP, MeIQ, Trp-P-1, and total HCA by the FFQ were significantly correlated with PhIP levels in hair when adjustment was made for melanin content (r = 0.47, r = 0.50, r = 0.55, and r = 0.51, respectively). The present study indicates that HCA intake estimated from this FFQ provides a reasonable ranking of individuals to allow the analysis of associations between HCA intake and risk of cancer in large-scale epidemiological studies.     

The lipidome as a composite biomarker of the modifiable part of the risk of breast cancer

The potential for dietary fat to prevent breast cancer makes identification of defined molecules a mandatory step. In order to circumvent the limitations and/or bias of dietary exposure assessment tools, we have used the fatty acid composition of white adipose tissue as biomarker of past lipid intake. When considered separately, candidate fatty acids identified as favourable on the basis of their association with breast cancer risk have usually led to inconsistent results in dietary intervention studies carried out in rats. This inconsistency indicates that any approach based on a single fatty acid should be abandoned for an integrated view over the complex lipid interactions, which finally determines the lipidome, the lipid profile that is found in individuals. We reappraised the role of the complete lipid profile through a comprehensive study of adipose tissue fatty acids obtained in patients with benign or malignant breast tumors. Rather than a single fatty acid, a composite indicator combining elevated monounsaturates and low n-6/n-3 fatty acid ratio was associated with decreased breast cancer risk. The lipidome may provide the opportunity to quantify the modifiable part of the risk of breast cancer. The lipidome may be used as a template for designing proper dietary modifications in order to delay the occurrence of breast cancer. Which dietary modifications should be undertaken in order to bring a pertinent change to the lipidome with respect to the risk of breast cancer is currently unknown. The lipidome may allow the individualization of a high risk population of women, who may be targeted for a dietary prevention of breast cancer. The setting and validation of a high-throughput lipidomic station with analytical capabilities fitted to the need of mass screening is required. These two locks must be resolved before a primary prevention of breast cancer by diet could be contemplated.     

Development of a culturally sensitive food frequency questionnaire for use in the Southern Community Cohort Study.

A food frequency questionnaire (FFQ) was developed to assess long-term habitual dietary intake in a cohort of approximately 100,000 40 to 79 year-old men and women living in the Southeastern US. Using the NHANES-III database for the southem region for specific race and sex subgroups, a list of 262 food categories was developed, coded and reduced to 102 food items that could discriminate between racial groups and account for large portions of cancer-relevant nutrients. The developed FFQ was tested in a pilot study in three southeastern states involving 239 African Americans and Whites, aged 56.9 +/- 12.2 years. The frequencies of consumption and portion sizes of the 102 foods were determined and intakes of various nutrients were estimated and compared with the NHANES-III data. African Americans reported higher total energy intakes and higher consumption of macronutrients and several micronutrients, compared to Whites. Estimated nutrient indices were higher among pilot study than among NHANES-III participants, although adjustment for total energy essentially eliminated the differences. Analysis of the frequency distribution of individual foods shows that the questionnaire includes commonly eaten foods that can discriminate between African Americans and Whites. The FFQ is currently being calibrated within the cohort study population.     

随机限食与重喂食小鼠的能量代谢和行为的可塑性

分别测定了随机限食和重喂食驯化的雌性KM小鼠的体重、摄食量、基础代谢率(BMR)、行为活动、身体脂肪和性腺重量.随机限食使摄食量增加、BMR和活动行为降低,生长发育迟缓,但对身体脂肪无显著影响.重喂食后上述指标均恢复到对照组水平,表现出显著的可塑性变化.结果表明,动物通过能量摄入和支出的权衡策略适应难以预测的食物资源变化,能量代谢和活动行为的可塑性调节在能量代谢的权衡策略中发挥重要作用.     

The role of leptin in striped hamsters subjected to food restriction and refeeding

Food restriction(FR) and refeeding(Re) have been suggested to impair body mass regulation and thereby making it easier to regain the lost weight and develop over-weight when FR ends. However, it is unclear if this is the case in small mammals showing seasonal forging behaviors. In the present study, energy budget, body fat and serum leptin level were measured in striped hamsters that were exposed to FR-Re. The effects of leptin on food intake, body fat and genes expressions of several hypothalamus neuropeptides were determined. Body mass, fat content and serum leptin level decreased during FR and then increased during Re. Leptin supplement significantly attenuated the increase in food intake during Re, decreased genes expressions of neuropepetide Y(NPY) and agouti-related protein(AgRP) of hypothalamus and leptin of white adipose tissue(WAT). Hormone-sensitive lipase(HSL) gene expression of WAT increased in leptin-treated hamsters that were fed ad libitum, but decreased in FR-Re hamsters. This indicates that the adaptive regulation of WAT HSL gene expression may be involved in the mobilization of fat storage during Re, which partly contributes to the resistance to FR-Re-induced overweight. Leptin may be involved in the down regulations of hypothalamus orexigenic peptides gene expression and consequently plays a crucial role in controlling food intake when FR ends.     

Linear measurement error models with restricted sampling

The relationship between nutrient consumption and chronic disease risk is the focus of a large number of epidemiological studies where food frequency questionnaires (FFQ) and food records are commonly used to assess dietary intake. However, these self-assessment tools are known to involve substantial random error for most nutrients, and probably important systematic error as well. Study subject selection in dietary intervention studies is sometimes conducted in two stages. At the first stage, FFQ-measured dietary intakes are observed and at the second stage another instrument, such as a 4-day food record, is administered only to participants who have fulfilled a prespecified criterion that is based on the baseline FFQ-measured dietary intake (e.g., only those reporting percent energy intake from fat above a prespecified quantity). Performing analysis without adjusting for this truncated sample design and for the measurement error in the nutrient consumption assessments will usually provide biased estimates for the population parameters. In this work we provide a general statistical analysis technique for such data with the classical additive measurement error that corrects for the two sources of bias. The proposed technique is based on multiple imputation for longitudinal data. Results of a simulation study along with a sensitivity analysis are presented, showing the performance of the proposed method under a simple linear regression model.     

Dietary fat and carcinogenesis.

Epidemiologic investigations have suggested a relationship between dietary fat intake and various types of cancer incidences. Furthermore, epidemiologic studies as well as studies with animal models have demonstrated that not only the amount but also the type of fat consumed is important. At present, the mechanism by which dietary fat modulates carcinogenesis has not been elucidated. The effects of dietary fat on the development of tumours have been summarized in the present review with emphasis on colorectal, pancreas, breast and prostate cancer. It is concluded that influence on synthesis of prostaglandins and leukotrienes may be the universal mechanism by which dietary fats modulate carcinogenesis.     

Weighted normality-based estimator in correcting correlation coefficient estimation between incomplete nutrient measurements

Consider the problem of estimating the correlation between two nutrient measurements, such as the percent energy from fat obtained from a food frequency questionnaire (FFQ) and that from repeated food records or 24-hour recalls. Under a classical additive model for repeated food records, it is known that there is an attenuation effect on the correlation estimation if the sample average of repeated food records for each subject is used to estimate the underlying long-term average. This paper considers the case in which the selection probability of a subject for participation in the calibration study, in which repeated food records are measured, depends on the corresponding FFQ value, and the repeated longitudinal measurement errors have an autoregressive structure. This paper investigates a normality-based estimator and compares it with a simple method of moments. Both methods are consistent if the first two moments of nutrient measurements exist. Furthermore, joint estimating equations are applied to estimate the correlation coefficient and related nuisance parameters simultaneously. This approach provides a simple sandwich formula for the covariance estimation of the estimator. Finite sample performance is examined via a simulation study, and the proposed weighted normality-based estimator performs well under various distributional assumptions. The methods are applied to real data from a dietary assessment study.     

High Dietary Magnesium Intake Is Associated with Low Insulin Resistance in the Newfoundland Population

Background

Magnesium plays a role in glucose and insulin homeostasis and evidence suggests that magnesium intake is associated with insulin resistance (IR). However, data is inconsistent and most studies have not adequately controlled for critical confounding factors.

Objective

The study investigated the association between magnesium intake and IR in normal-weight (NW), overweight (OW) and obese (OB) along with pre- and post- menopausal women.

Design

A total of 2295 subjects (590 men and 1705 women) were recruited from the CODING study. Dietary magnesium intake was computed from the Willett Food Frequency Questionnaire (FFQ). Adiposity (NW, OW and OB) was classified by body fat percentage (%BF) measured by Dual-energy X-ray absorptiometry according to the Bray criteria. Multiple regression analyses were used to test adiposity-specific associations of dietary magnesium intake on insulin resistance adjusting for caloric intake, physical activity, medication use and menopausal status.

Results

Subjects with the highest intakes of dietary magnesium had the lowest levels of circulating insulin, HOMA-IR, and HOMA-ß and subjects with the lowest intake of dietary magnesium had the highest levels of these measures, suggesting a dose effect. Multiple regression analysis revealed a strong inverse association between dietary magnesium with IR. In addition, adiposity and menopausal status were found to be critical factors revealing that the association between dietary magnesium and IR was stronger in OW and OB along with Pre-menopausal women.

Conclusion

The results of this study indicate that higher dietary magnesium intake is strongly associated with the attenuation of insulin resistance and is more beneficial for overweight and obese individuals in the general population and pre-menopausal women. Moreover, the inverse correlation between insulin resistance and dietary magnesium intake is stronger when adjusting for %BF than BMI.     

Is Dietary Fat Intake Related to Liking or Household Availability of High‐ and Low‐Fat Foods?

Objectives : Despite the increasing availability of low‐ and reduced‐fat foods, Americans continue to consume more fat than recommended, which may be a contributing factor to the obesity epidemic. This investigation examined relationships between liking and household availability of high‐ and low‐fat foods and their association with dietary fat intake. Research Methods and Procedures : A food frequency questionnaire assessed percent calories from fat consumed over the past year in 85 men and 80 women. Participants reported their degree of liking 22 “high‐fat foods” (>45% calories from fat) and 22 “low‐fat foods” (<18% calories from fat), and the number and percentage (number of high‐ or low‐fat foods/total number of foods × 100) of these high‐ and low‐fat foods in their homes. Results : Hierarchical regression analyses examined the ability of liking and household availability of low‐ and high‐fat foods to predict percent dietary fat intake. After controlling for age, sex, and BMI, liking ratings for high‐ and low‐fat foods and the interaction of liking for low‐fat foods by the percentage of low‐fat foods in the household were significant predictors of percent dietary fat consumed. Greater liking of high‐fat foods and lower liking of low‐fat foods, both alone and combined with a lower percentage of low‐fat foods in the home, were predictive of higher dietary fat intake. Discussion : Interventions designed to reduce dietary fat intake should target both decreasing liking for high‐fat foods and increasing liking for low‐fat foods, along with increasing the proportion of low‐fat foods in the household.     

Validation of overweight children's fruit and vegetable intake using plasma carotenoids

Assessing dietary intake in children is difficult and limited validated tools exist. Plasma carotenoids are nutritional biomarkers of fruit and vegetable intake and therefore suitable to validate reported dietary intakes. The aim of this study was to examine the comparative validity of a food frequency questionnaire (FFQ), completed by parents reporting child fruit and vegetable intake compared to plasma carotenoid concentrations. A sample of children aged 5-12 years (n = 93) from a range of weight categories were assessed. Dietary intake was measured using a 137-item semi-quantitative FFQ. Plasma carotenoids were measured using reverse phase high-performance liquid chromatography. Pearson correlation coefficients between reported dietary intake of carotenoids and plasma carotenoid concentrations were strongest after adjustment for BMI (beta-carotene (r = 0.56, P < 0.05), alpha-carotene (r = 0.51, P < 0.001), cryptoxanthin (r = 0.32, P < 0.001)). Significantly lower levels (P < 0.05) of all plasma carotenoids, except lutein, were found among overweight and obese children when compared to healthy weight children. Parental report of children's carotenoid intakes, using a FFQ can be used to provide a relative validation of fruit and vegetable intake. The lower plasma carotenoid concentrations found in overweight and obese children requires further investigation.     

A maternal high n-6 fat diet with fish oil supplementation during pregnancy and lactation in rats decreases breast cancer risk in the female offspring

The timing of dietary fat intake may modify breast cancer risk. In addition, n-3 fatty acids reduce, and n-6 fatty acids increase, the risk of breast cancer and a maternal high n-6 fat diet results in a greater risk of breast cancer in the female offspring. We hypothesized that the timing of n-3 fatty acid-enriched fish oil supplementation would be important for reducing the risk of breast cancer. Female rats were fed to a high n-6 fat diet containing 20% of the sunflower oil by weight during pregnancy and lactation, and the female offspring were exposed to fish oil by oral gavage either during the perinatal period via maternal intake or during puberty or adulthood. Exposure during the perinatal period to a maternal high n-6 fat diet with fish oil supplementation significantly reduced the incidence of carcinogen-induced mammary tumors in the female offspring compared to a maternal high n-6 fat diet with no fish oil supplementation or fish oil supplementation later in life (P=.0228 by Cox proportional hazards model). We found that a maternal high n-6 fat diet during pregnancy is more important in increasing the risk of mammary tumors in the female offspring than a maternal high n-6 fat diet during lactation. This study suggests that fish oil supplementation during the perinatal period decreases the effect of a maternal high n-6 fat diet on subsequent carcinogen-induced mammary tumor risk, whereas fish oil supplementation during puberty or adulthood does not.