Statistical analysis of a dynamic model for dietary contaminant exposure

This paper is devoted to the statistical analysis of a stochastic model introduced in [P. Bertail, S. Clémen?on, and J. Tressou, A storage model with random release rate for modelling exposure to food contaminants, Math. Biosci. Eng. 35 (1) (2008), pp. 35-60] for describing the phenomenon of exposure to a certain food contaminant. In this modelling, the temporal evolution of the contamination exposure is entirely determined by the accumulation phenomenon due to successive dietary intakes and the pharmacokinetics governing the elimination process inbetween intakes, in such a way that the exposure dynamic through time is described as a piecewise deterministic Markov process. Paths of the contamination exposure process are scarcely observable in practice, therefore intensive computer simulation methods are crucial for estimating the time-dependent or steady-state features of the process. Here we consider simulation estimators based on consumption and contamination data and investigate how to construct accurate bootstrap confidence intervals (CI) for certain quantities of considerable importance from the epidemiology viewpoint. Special attention is also paid to the problem of computing the probability of certain rare events related to the exposure process path arising in dietary risk analysis using multilevel splitting or importance sampling (IS) techniques. Applications of these statistical methods to a collection of data sets related to dietary methyl mercury contamination are discussed thoroughly.     

Association of habitual dietary intake with morningness-eveningness and rotating shift work in Japanese female nurses

Rotating shift workers are associated with imbalanced dietary intakes. Rotating shift workers and dietary intakes in adults who do not engage in night work have also been shown to be associated with chronotype. However, no studies have examined associations between morningness-eveningness (i.e., the degree to which people prefer to be active in the morning or the evening), rotating shift work and dietary intakes. Therefore, our first purpose was to elucidate the association between morningness-eveningness and habitual food group intakes in rotating shift workers. The second purpose was to elucidate the association of morningness-eveningness and rotating shift work with food group intakes, considering habitual sleep durations. Japanese nurses (1095 day workers and 1464 rotating shift workers) were studied using a self-administered questionnaire. The questionnaire covered habitual dietary intakes, morningness-eveningness and demographic characteristics of the participants. A Japanese version of the Morningness-Eveningness Questionnaire (MEQ) was used to measure self-rated morningness-eveningness. Dietary intakes over the previous 1 month were evaluated using a semi-quantitative food frequency questionnaire. Intakes of pulses, green/yellow vegetables, white vegetables, fruits, algae, eggs, confectioneries/savory snacks and sugar-sweetened beverages were significantly (p < 0.05) associated with the MEQ score in rotating shift workers. Among these food groups, intakes of green/yellow vegetables, white vegetables, fruits and algae were significantly (p < 0.05) lower in rotating shift workers than in day workers, and intakes of confectioneries/savory snacks and sugar-sweetened beverages were significantly (p < 0.05) higher in rotating shift workers than in day workers. Intakes of these food groups were also significantly (p < 0.05) associated with the MEQ score in day workers. In addition, the MEQ score was significantly (p < 0.05) lower in rotating shift workers than in day workers, indicating greater eveningness among rotating shift workers. Multivariate linear regression revealed that the MEQ scores were significantly (p < 0.05) associated with intakes of these food groups, while rotating shift work was associated only with confectioneries/savory snacks. These results suggest that morningness-eveningness is associated with unbalanced dietary intakes in rotating shift workers as well as day workers, which may partially explain associations between rotating shift work and unfavorable dietary intakes. These findings have important implications for the development of novel strategies for preventing poor health caused by imbalanced dietary intakes in rotating shift workers.     

Dietary recommendations to meet both endocrine and autocrine needs of Vitamin D

In the most recent revision of the dietary recommendations for Americans and Canadians in 1997, a recommended intake for Vitamin D was set in the absence of an estimation of mean requirements. There are now new data to estimate average requirements; however, there must be consideration of factors affecting need in populations and of total body tissue needs including the prevention and treatment of cancer. A recent study provides dietary dose-response data in the absence of sun exposure, and a mean requirement of 12.5microg (500IU) was found for Caucasian men. A seasonal build up (summer) and waning (winter) of Vitamin D stores implies that the requirement of Vitamin D in complete absence of yearly summertime sun exposure would approach levels of intake that mimic Vitamin D gained from sun exposure. High prevalence of Vitamin D insufficiency and the re-emergence of rickets have been observed worldwide. For many countries without mandatory staple food fortification, Vitamin D intake is often too low to sustain healthy circulating levels of 25 hydroxyvitamin D. Even in some countries that require (mandatory) or allow fortification (optional), Vitamin D intakes are low in some groups due to their unique dietary patterns, such as low milk consumption, vegetarian diet, limited or no use of dietary supplements, or changes away from traditional food consumption. Supplement use can significantly increase Vitamin D intakes across all age and gender groups but the benefit is primarily gained in persons whose intakes are close to adequate. African American men and women have greater prevalence of Vitamin D insufficiency, which may be a factor in their susceptibility to certain cancers. New recommendations for Vitamin D should be made for the otherwise healthy populations in greatest need of dietary Vitamin D due to lack of adequate sun exposure.     

Dietary exposure and risk assessment to cadmium of the adult population of Jiangsu province,China: Comparing between semi-probabilistic and fully probabilistic approaches

With rapid industrialization and modernization in China, long-term dietary exposure to cadmium (Cd) has the potential to cause health risks. The traditional probabilistic approach for long-term dietary assessment was a semi-probabilistic method that had limitations in qualifying the variation in concentration data. Thus, this article estimated the long-term dietary exposure to Cd of the adults of Jiangsu province using semi-probabilistic and fully probabilistic approaches, and compared the two models. Cd concentration data were obtained from the national food contamination monitoring program 2001–2009. Food consumption data were gathered from the National Diet and Nutrition Survey conducted in 2002. The provisional tolerable daily intakes (PTDI) of 0.8 μg kg^–1 bw for Cd was applied in the risk assessment. The estimates of semi-probabilistic approach were within the provisional tolerable daily intakes (PTDI) at mean and all percentiles. However, the P95 of exposure with fully probabilistic approach for all population groups were above PTDI. Rice and rice products followed by wheat flour and wheat flour products, crustaceans, pak-choi, beans, and bean products contributed most to the Cd intake for adults. The fully probabilistic estimates could indicate a possible public health concern on Cd for adults in Jiangsu province.     

Methods for Assessment of Dietary Lead Exposure of the Inner-City Population

Abstract

Assessment of dietary lead exposure of individuals begins with the determination of food and beverage intake by the individuals, and concludes with an evaluation of the lead content of the foods and beverages consumed. Of several techniques available for assessment of dietary intake, the 24-hour food recall is recommended as the method of choice for assessing current dietary lead intakes in inner-city populations. The three-day food record can be used among cooperative and motivated subjects, while the dietary history method is available for assessing long-term intakes in the past. The unavailability of lead content values of a large number of foods will to a large extent restrict the use of these methods in large-scale dietary lead exposure studies. Until the time that such data becomes available, the most accurate estimates of lead intake can be provided by chemical analysis of duplicate samples of foods consumed, as is currently done. However, this method is feasible only for small samples.     

N‐6 From Different Sources Protect From Metabolic Alterations to Obese Patients: A Factor Analysis

First, to analyze the interactions among fatty acids (FAs) from diet, plasma and subcutaneous and visceral adipose tissue (AT), and second, the relationship among FAs from these different sources and obesity‐related alterations in extreme obesity. We studied 20 extreme obese subjects. A food‐frequency questionnaire was used to determine the FA intakes. Serum and AT (subcutaneous and visceral) FA concentrations were determined by gas chromatography. Cardiometabolic risk parameters were assessed. Principal factor analysis was performed to define specific FA factors in the metabolic alterations. We found important associations among diet, plasma, and AT FA and cardiometabolic parameters. In this regard, it is interesting to highlight the negative associations between plasma cholesterol and dietary n‐3 FA. In the subcutaneous depot, as occurred in plasma, n‐6 and polyunsaturated FAs (PUFA) were negatively associated with triacylglycerols (TGs). Factor analysis revealed TGs as the unique cardiovascular risk parameter appearing in the first factor (F1), together with n‐6 (load factor = 0.94) and PUFA (0.91). Besides, n‐3 from diet and plasma appeared in the third factor inversely related to cholesterol, low‐density lipoprotein cholesterol (LDL‐c), and insulin. In an opposite way, dietary and AT trans FAs and saturated FA (SFA) were associated to an increase of the metabolic risk. We have shown, for the first time, the importance of n‐6 and PUFAs composition as protective factors against metabolic alterations in extreme obese subjects. These findings support current dietary recommendations to increase PUFA intakes and restrict saturated and trans FA intakes even in extreme obesity.     

Dietary Exposure to PCDD/Fs Through Animal Products in a Highly Polluted Area in Turkey

We present an estimation of dietary exposure to PCDD/Fs by animal products in Kocaeli, a highly polluted area in Turkey, based on current food data consumption. The calculation of the PCDD/F intakes by an exposure methodology concerning consumption habits of different receptor groups in Kocaeli was included. The data relate to the PCDD/F levels in food groups of animal origin (milk, egg, meat, chicken, and fish), food consumption rates, and the fractions of locally grown foods in total consumption were statistically assessed. Monte Carlo simulation was used to estimate the ranges of PCDD/F doses through the consumption of animal products. The PCDD/F intakes through the consumption of animal products were calculated to average between 0.4–1.8 pg WHO-TEQ.kg^?1 bodyweight (bw).day^?1. The results are within the range of 1–4 pg WHO-TEQ.kg^?1 bw.day^?1, proposed as the tolerable daily intake by the World Health Organization. On the other hand, contributions of the consumption of different foods to the total PCDD/F intake and the results of sensitivity analysis showed that the PCDD/F intake in semi-urban and rural settings was determined primarily by the consumption of milk products, while consumption of meat and fish had a greater importance in urban settings.     

Factors determining dietary intakes of heterocyclic amines in cooked foods.

The identification of heterocyclic amines (HCAs) in cooked foods has focused attention on the potential health effects from their consumption in the diet. Recent studies have estimated daily dietary intakes of HCAs that vary 10-fold and implicated different cooked meats as the prime source of HCAs in the diet. These varied estimates can be attributed to the different dietary assessment methods used in these studies, as well as the different levels of HCAs ascribed to the most commonly consumed cooked meats. Epidemiological studies utilizing information on dietary practice and food intake have found higher risks for several cancers among individuals consuming the highest levels of HCAs. These studies have highlighted the importance of using information on cooking methods in addition to food intake to accurately estimate dietary exposure to HCAs.     

EPA and DHA--protein, not fat is "where it's at"?

Guidelines and recommendations for the dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are topics of debate. Recently, EPA and DHA intakes have been demonstrated to be associated with dietary protein intakes and not dietary fat intakes that are distinct from α-linolenic acid. We presently confirm these observations in a secondary analysis of baseline dietary intake data for the validation of a food frequency questionnaire (n=99). DHA intakes measured by both 3 d dietary record and food frequency questionnaire and EPA intakes measured by food frequency questionnaire were positively correlated with protein intakes. EPA and DHA were not associated with fat intakes in either assessment, while ?-linolenic acid was positively correlated with fat intakes. Future recommendations regarding the intake of omega-3 polyunsaturated fatty acids, and EPA and DHA specifically, should consider these associations that provide insight on dietary sources of EPA and DHA in the food supply.     

Correlation Between Dietary Zinc Intakes and Its Serum Levels with Depression Scales in Young Female Students

It has been suggested that mood disorders and depressive status may be accompanied by lowered zinc status in the body, and adequate consumption of zinc increases a general perceived well-being. The main objective of this study was to assess the correlation between serum zinc concentrations and dietary zinc intakes with depression scores in university female students. In the first phase, Beck's depression questionnaire was applied in a random sampling of 308 selected 20–25-year-old female students (one third of total students in Ahvaz Jondi-Shapour University of Medical Sciences Golestan dormitories) to assess the major depressive disorder (MDD) scales. Then, in the second phase, 23 students who identified as having moderate and severe depression were selected as the case group, and 23 healthy age matched were chosen as the controls. Each of them completed a 12-item semiquantitative food frequency questionnaire containing the main food sources of zinc in the usual dietary patterns and also a 24-h food recall questionnaire to assure the daily zinc intakes. Daily zinc intakes were obtained by multiplying each portion size by its zinc content using food tables. A 5-ml blood sample was taken for further serum zinc status using flame atomic absorption spectrophotometry technique. Pearson's r was used to show the correlation between quantitative variables. Both daily zinc intake and serum zinc concentrations of MDD group were about two thirds of healthy index (p < 0.01). Depressed individuals used to eat lower servings of red meats and chicken as the main food sources of zinc in students' usual diets (p < 0.001). Consumption of other foods as the sources of zinc was not significantly different in two groups. A linear significant correlation between dietary zinc intakes and its serum levels was seen in samples (r = 0.62; p < 0.001) and MDD students (r = 0.55; p < 0.001). There was a linear inverse correlation between Beck questionnaire scores and serum zinc concentrations in all of the investigated students(r = -0.65; p < 0.001) and MDD girls (r = −0.71; p < 0.001). Beck questionnaire scores and diatary zinc intakes were also inversly correlated (r = −0.58; p < 0.001). However, no statistical correlation was seen between these two variables in MDD cases. In depressed female students, dietary zinc intake is correlated to its serum concentrations; however, the serum zinc levels are inversely correlated to depression scales. Consumption of the main dietary sources of zinc such as red meats and chicken should be encouraged in young depressed girls.     

Measurement of dietary exposure: a challenging problem which may be overcome thanks to metabolomics?

The diet is an important environmental exposure, and its measurement is an essential component of much health-related research. However, conventional tools for measuring dietary exposure have significant limitations being subject to an unknown degree of misreporting and dependent upon food composition tables to allow estimation of intakes of energy, nutrients and non-nutrient food constituents. In addition, such tools may be inappropriate for use with certain groups of people. As an alternative approach, the recent techniques of metabolite profiling or fingerprinting, which allows simultaneous monitoring of multiple and dynamic components of biological fluids, may provide metabolic signals indicative of food intake. Samples can be analysed through numerous analytical platforms, followed by multivariate data analysis. In humans, metabolomics has been applied successfully in pharmacology, toxicology and medical screening, but nutritional metabolomics is still in its infancy. Biomarkers of a small number of specific foods and nutrients have been developed successfully but less targeted and more high-throughput methods, that do not need prior knowledge of which signals might be discriminatory, and which may allow a more global characterisation of dietary intake, remain to be tested. A proof a principle project (the MEDE Study) is currently underway in our laboratories to test the hypothesis that high-throughput, non-targeted metabolite fingerprinting using flow injection electrospray mass spectrometry can be applied to human biofluids (blood and urine) to characterise dietary exposure in humans.     

Plasticity of olfactory orientation to foods in the snailAchatina fulica

Summary Snails were tested in an olfactometer for their orientation to food odours. Measures of odour choice, latency to make a choice and percentage of upwind orientations were obtained after experimental manipulations of dietary experience and hunger motivation. Juvenile snails, given an exclusive diet of a certain food for 12 h or less, oriented preferentially toward the odour of that food when subsequently presented with a choice between it and a novel food odour (Fig. 2). A 48 h period of exposure to a food resulted in a 21 day retention of the odour preference (Fig. 3). There was no evidence for an especially sensitive period for conditioning during the first 50 days of age (Fig. 4); however, adult snails (minimum 1 year old) required longer periods of dietary exposure to establish equivalent food odour memories (Fig. 5). Measures of latency and percentage of upwind orientations confirmed the choice data in demonstrating an effect of dietary experiences on olfactory orientation. Hunger motivation increased the selection for familiar food odours, and reduced the latency (Fig. 6 and Tables 3 and 4). Sensory adaptation appears inadequate to explain the conditioning phenomenon since formation of the preferences was contingent upon ingestion of the foods; exposure to the food odours alone was insufficient (Table 2). The data suggest that orientation preferences derive from a learned association between the odour of a food and its nutritional value.We thank Dr. Donald Kramer for helpful criticism throughout the course of this work. The research was supported financially by the National Research Council of Canada and le Ministère de l'Education du Québec.     

Dietary generalists and nutritional specialists: Feeding strategies of adult female blue monkeys (Cercopithecus mitis) in the Kakamega Forest,Kenya

Generalist primates eat many food types and shift their diet with changes in food availability. Variation in foods eaten may not, however, match variation in nutrient intake. We examined dietary variation in a generalist‐feeder, the blue monkey (Cercopithecus mitis), to see how dietary food intake related to variation in available food and nutrient intake. We used 371 all‐day focal follows from 24 adult females (three groups) in a wild rainforest population to quantify daily diet over 9 months. We measured food availability using vegetation surveys and phenology monitoring. We analyzed >700 food and fecal samples for macronutrient content. Subjects included 445 food items (species‐specific plant parts and insect morphotypes) in their diet. Variation in fruit consumption (percentage of diet and total kcal) tracked variation in availability, suggesting fruit was a preferred food type. Fruits also constituted the majority of the diet (by calories) and some fruit species were eaten more than expected based on relative availability. In contrast, few species of young leaves were eaten more than expected. Also, subjects ate fewer young leaves (based on calories consumed) when fruit or young leaves were more available, suggesting that young leaves served as fallback foods. Despite the broad range of foods in the diet, group differences in fiber digestibility, and variation that reflected food availability, subjects and groups converged on similar nutrient intakes (grand mean ± SD: 637.1 ± 104.7 kcal overall energy intake, 293.3 ± 46.9 kcal nonstructural carbohydrate, 147.8 ± 72.4 kcal lipid, 107.8 ± 12.9 kcal available protein, and 88.1 ± 17.5 kcal structural carbohydrate; N = 24 subjects). Thus, blue monkeys appear to be food composition generalists and nutrient intake specialists, using flexible feeding strategies to regulate nutrient intake. Findings highlight the importance of simultaneously examining dietary composition at both levels of foods and nutrients to understand primate feeding ecology.     

Associations between copper and zinc intakes from diet and mortality from cardiovascular disease in a large population-based prospective cohort study

Several studies have related cardiovascular disease (CVD) to serum concentrations of copper and zinc but not to their dietary intakes. We thought to examine the association between dietary intakes of copper and zinc with risk of mortality from CVD in a prospective study encompassing 58,646 healthy Japanese men and women aged 40-79 years. The intakes of copper and zinc were determined by a validated self-administered food frequency questionnaire, and their associations with risk of mortality from CVD were evaluated by Cox proportional hazard modelling. During 965, 970 person-years of follow-up between 1989-2009, we documented 3,388 CVD deaths [1,514 from stroke, 702 from coronary heart disease (CHD) and 1,172 from other CVD]. Copper intake was not associated with CHD mortality; however, the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) for mortality from stroke, other CVD and total CVD in the highest versus the lowest quintiles of copper intake among men were 1.78 (1.16-2.77; P-trend=0.007), 1.61 (1.01-2.81; P-trend =0.03) and 1.63 (1.21-2.33; P-trend=0.001), respectively, and those among women were 1.49 (1.00-2.19; P-trend=0.04), 1.59 (1.09-2.55; P-trend =0.02) and 1.36 (1.06-1.69; P-trend=0.01), respectively. Higher intakes of zinc was inversely associated with mortality from CHD in men; 0.68 (0.58-1.03; P-trend=0.05) but not women; 1.13 (0.71- 1.49; P-trend=0.61). No associations were observed with other mortality endpoints. In conclusion, dietary copper intake was positively associated with mortality from CVD in both genders; whereas, higher dietary zinc intake was inversely associated with mortality from CHD in men but not women.     

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.     

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 Intake of Arsenic, Cadmium, Mercury, and Lead by the Population of Catalonia, Spain

The concentrations of arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) were determined in samples of food items widely consumed by the population of Catalonia, Spain. All samples were randomly acquired in 12 cities of Catalonia between March and June of 2006 and analyzed by inductively coupled plasma mass spectrometry. The dietary intake of these elements was estimated for various age–gender groups of population: children, adolescents, adults, and seniors. In order to determine the temporal trend on the dietary exposure to As, Cd, Hg, and Pb, the current results were compared with those of a previous survey (2000). In the present market basket study, for a standard male adult of 70-kg body weight living in Catalonia, the dietary intakes of As, Cd, Hg, and Pb were 261.01, 9.80, 12.61, and 45.13 μg/day, respectively, while in the 2000 survey, these intakes were 223.59, 15.73, 21.22, and 28.37 μg/day, for As, Cd, Hg, and Pb, respectively. For As, the only food groups currently contributing with measurable amounts to intake of total As were fish and shellfish and cereals, while for Cd the highest contribution to total intake corresponded to pulses, tubers, and cereals. For Hg, the contribution was only due to fish and shellfish, while cereals were the group with the highest contribution to total Pb intake. The estimated intakes of As, Cd, Hg, and Pb are notably lower than the respective provisional tolerable weekly intakes, which indicate that these intakes should not mean additional health risks for the consumers.     

风险矩阵分级模型在哈尔滨市食品安全风险评估中的建立与应用

目的:建立哈尔滨市风险矩阵分级模型,并应用该模型探索食品污染的风险。方法:采用风险矩阵、文献综述及专家判断法对某年食品安全风险监测中位列化学污染物及微生物污染超标率首位的食品-项目组合,即动物肝脏-克伦特罗组合、水产品-副溶血性弧菌组合进行模型评估。结果:参照风险矩阵,动物肝脏-克伦特罗组合的健康风险分值为6,可以判断哈尔滨市人群由于食用动物肝脏而导致克伦特罗膳食暴露的健康风险等级为"中风险",水产品-副溶血性弧菌组合的健康风险分值为2,可以判断哈尔滨市人群每餐由于食用水产品而导致副溶血性弧菌膳食暴露的健康风险等级为"极低风险"。结论:哈尔滨市该年食品安全总体情况较好,风险等级较低,但部分监测项目存在食品安全风险隐患,应予以关注。     

Effect of dietary intake and lifestyle factors on in vivo mutant frequency at the HPRT gene locus in healthy human subjects

This paper describes the results of a study designed to assess the effects of a variety of dietary and lifestyle factors on background levels of mutant frequency (MF) at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene locus in humans. Eighty-three healthy and free-living subjects (aged 20–80 yr; 61 males and 22 females; mean age of 63.07±14.71 yr) were recruited. Background levels of MF were determined for each subject using a cloning assay. The mean MF/10⁶ clonable cells (MF) for the study subjects was 4.63±2.20. An interview-administered questionnaire was completed by each study subject in order to assess details of dietary history, physical activity, health and potential genotoxin exposure history. A 7-day estimated dietary record method with a food frequency questionnaire was used to determine average intakes of energy and macronutrients (including alcohol), and a range of micronutrients (including vitamin and mineral supplement usage). The relationships between individual dietary and lifestyle factors and HPRT MF were investigated by univariate and multivariate analysis (data was adjusted for age, lymphocyte plating efficiency [PE] and energy intake [EI]). Univariate analysis revealed a significant positive correlation between EI and MF and multivariate analysis revealed significant positive correlations between, body mass index (BMI), % energy intake from total carbohydrate, starch, fat and MF. These findings suggest that a reduction in EI may be a useful preventative measure against the onset of carcinogenesis in humans. No correlations were found between alcohol intake and MF or between estimated antioxidant intake and MF. Thus, estimated intakes of antioxidants may not reflect their bioavailability and functional capacity in vivo and it may be more useful to examine actual plasma/cell levels vs. MF to establish if any significant relationship exists.     

Reconciling nutritional geometry with classical dietary restriction: Effects of nutrient intake,not calories,on survival and reproduction

Dietary restriction (DR) is one of the main experimental paradigms to investigate the mechanisms that determine lifespan and aging. Yet, the exact nutritional parameters responsible for DR remain unclear. Recently, the advent of the geometric framework of nutrition (GF) has refocussed interest from calories to dietary macronutrients. However, GF experiments focus on invertebrates, with the importance of macronutrients in vertebrates still widely debated. This has led to the suggestion of a fundamental difference in the mode of action of DR between vertebrates and invertebrates, questioning the suggestion of an evolutionarily conserved mechanism. The use of dietary dilution rather than restriction in GF studies makes comparison with traditional DR studies difficult. Here, using a novel nonmodel vertebrate system (the stickleback fish, Gasterosteus aculeatus), we test the effect of macronutrient versus calorie intake on key fitness‐related traits, both using the GF and avoiding dietary dilution. We find that the intake of macronutrients rather than calories determines both mortality risk and reproduction. Male mortality risk was lowest on intermediate lipid intakes, and female risk was generally reduced by low protein intakes. The effect of macronutrient intake on reproduction was similar between the sexes, with high protein intakes maximizing reproduction. Our results provide, to our knowledge, the first evidence that macronutrient, not caloric, intake predicts changes in mortality and reproduction in the absence of dietary dilution. This supports the suggestion of evolutionary conservation in the effect of diet on lifespan, but via variation in macronutrient intake rather than calories.