The Use of Three-Dimensional Images and Food Descriptions from a Smartphone Device Is Feasible and Accurate for Dietary Assessment.

Technology-assisted dietary assessment has the potential to improve the accuracy of self-reported dietary intake. This study evaluates MealScan3D (MS3D), a mobile device-based food recording system, which uses three-dimensional images to obtain food volumes and an application to capture algorithm-driven food intake data. Participants (n = 179) were randomly assigned and trained to record three meals using either MS3D or a written food record (WFR). Generous amounts of standardized meals were provided, and participants self-selected portions for each food. The weights of provided and uneaten/leftover foods were used to determine true intake. For total energy intake (three meals combined), validity (Pearson correlation) was significantly higher for MS3D vs. the WFR (p < 0.001); when interpreted as the percentage of variance in energy intake explained, MS3D explained 84.6% of true variance, a 25.3% absolute and 42.6% relative increase over the 59.3% explained by the WFR. For 9 of 15 individual foods, the Pearson correlations between true and reported portion size estimates were significantly larger for MS3D than the WFR. Bias was smaller (intercepts were closer to the means) for 9 of 15 foods and the regression coefficients for 10 of 15 foods were significantly closer to 1.0 in the MS3D arm. MS3D is feasible for dietary assessment and may provide improvements in accuracy compared to WFRs.

A practical method for collecting food record data in a prospective cohort study of breast cancer survivors.

Multiple-day diet records can be unsuitable for cohort studies because of high administrative and analytical costs. Costs could be reduced if a subsample of participants were analyzed in a nested case-control study. However, completed records are usually reviewed ("documented") with participants to correct errors and omissions before analysis. The authors evaluated the suitability of using undocumented 3-day food records in 2 samples of women in a Northern California cohort study of breast cancer survivorship (2006-2009). One group of participants (n = 130) received an introduction to the food record at enrollment, while another (n = 70) received more comprehensive instruction. Food records were mailed to participants 6 months later for follow-up and were analyzed as received and after phone documentation. Error rates for adequate completion were high in the first group but substantially lower among persons receiving instruction; prevalences of missing data on serving size and incomplete food descriptions changed from 30% to 4% and from 32% to 6%, respectively (P < 0.0001). Correlations between nutrient intakes calculated from undocumented and documented records were 0.72-0.93 in the first group and were significantly stronger (0.84-0.99) among persons receiving instruction. Documentation had little effect on intraclass correlation coefficients across days, but training increased the coefficients for many nutrients. When participants receive proper instruction, undocumented food records can be satisfactory for large epidemiologic studies.

Serum leptin concentrations and markers of immune function in overweight or obese postmenopausal women.

Experimental studies and case reports suggest a multifunctional role of leptin in immune function. However, clinical studies of leptin in healthy individuals with a comprehensive assessment of immunity are lacking. This study investigated associations between serum leptin concentrations and multiple biomarkers of cellular immunity and inflammation among 114 healthy postmenopausal, overweight, or obese women. Leptin was measured by RIA. C-reactive protein (CRP) and serum amyloid A (SAA) were measured by nephelometry. Flow cytometry was used to measure natural killer (NK) cell cytotoxicity and to enumerate and phenotype lymphocyte subsets. T-lymphocyte proliferation was assessed in response to phytohemagluttinin, as well as to anti-CD3 antibodies by the flow cytometric cell division tracking method. Multiple linear regression analysis with adjustment for confounding factors and log transformation, where appropriate, was used. Serum leptin concentrations were positively associated with serum CRP, SAA, and interleukin 6 (IL6) (P<0.0001, P=0.01, and P=0.04 respectively), more strongly among women with a body mass index (BMI) <30 kg/m(2). The associations were attenuated after adjustment for measured body composition, yet remained significant for CRP and SAA. No statistically significant associations were observed between leptin and NK cytotoxicity, lymphocyte subpopulations, or T-lymphocyte proliferation. This study fills an important gap in knowledge about the relationship between leptin concentrations and immune function in healthy individuals. Findings support an association between serum leptin and the inflammatory proteins CRP and SAA, which appears to be mediated only partly by adipose tissue. Our study does not support a link between leptin and other immune parameters among overweight or obese, but otherwise healthy postmenopausal women, perhaps because such effects are only present at low or deficient leptin concentrations.

Mathematical modeling of folate metabolism: predicted effects of genetic polymorphisms on mechanisms and biomarkers relevant to carcinogenesis.

Low-folate status and genetic polymorphisms in folate metabolism have been linked to several cancers. Possible biological mechanisms for this association include effects on purine and thymidine synthesis, DNA methylation, or homocysteine concentrations. The influence of genetic variation in folate metabolism on these putative mechanisms or biomarkers of cancer risk has been largely unexplored. We used a mathematical model that simulates folate metabolism biochemistry to predict (a) the effects of polymorphisms with defined effects on enzyme function (MTHFR and TS) and (b) the effects of potential, as-of-yet-unidentified polymorphisms in a comprehensive set of folate-metabolizing enzymes on biomarkers and mechanisms related to cancer risk. The model suggests that there is substantial robustness in the pathway. Our predictions were consistent with measured effects of known polymorphisms in MTHFR and TS on biomarkers. Polymorphisms that alter enzyme function of FTD, FTS, and MTCH are expected to affect purine synthesis, FTS more so under a low-folate status. In addition, MTCH polymorphisms are predicted to influence thymidine synthesis. Polymorphisms in methyltransferases should affect both methylation rates and thymidylate synthesis. Combinations of polymorphisms in MTHFR, TS, and SHMT are expected to affect nucleotide synthesis in a nonlinear fashion. These investigations provide information on effects of genetic polymorphisms on biomarkers, including those that cannot be measured well, and highlight robustness and sensitivity in this complex biological system with regard to genetic variability. Although the proportional changes in biomarkers of risk with individual polymorphisms are frequently small, they may be quite relevant if present over an individual's lifetime.

Does folic acid supplementation prevent or promote colorectal cancer? Results from model-based predictions.

Folate is essential for nucleotide synthesis, DNA replication, and methyl group supply. Low-folate status has been associated with increased risks of several cancer types, suggesting a chemopreventive role of folate. However, recent findings on giving folic acid to patients with a history of colorectal polyps raise concerns about the efficacy and safety of folate supplementation and the long-term health effects of folate fortification. Results suggest that undetected precursor lesions may progress under folic acid supplementation, consistent with the role of folate role in nucleotide synthesis and cell proliferation. To better understand the possible trade-offs between the protective effects due to decreased mutation rates and possibly concomitant detrimental effects due to increased cell proliferation of folic acid, we used a biologically based mathematical model of colorectal carcinogenesis. We predict changes in cancer risk based on timing of treatment start and the potential effect of folic acid on cell proliferation and mutation rates. Changes in colorectal cancer risk in response to folic acid supplementation are likely a complex function of treatment start, duration, and effect on cell proliferation and mutations rates. Predicted colorectal cancer incidence rates under supplementation are mostly higher than rates without folic acid supplementation unless supplementation is initiated early in life (before age 20 years). To the extent to which this model predicts reality, it indicates that the effect on cancer risk when starting folic acid supplementation late in life is small, yet mostly detrimental. Experimental studies are needed to provide direct evidence for this dual role of folate in colorectal cancer and to validate and improve the model predictions.

Predictors of diet quality among overweight and obese postmenopausal women.

Previous studies have shown that sociodemographic characteristics can be determinants of healthful eating. However, health characteristics such as smoking status have not been well studied. The objective of this research, therefore, was to determine predictors of diet quality in postmenopausal women. We included 164 overweight or obese postmenopausal women aged 50 to 75 years living in and around Seattle, WA, and intake, measured by food frequency questionnaire, was used to calculate scores for the Diet Quality Index and Healthy Eating Index. Information on sociodemographic factors and health behaviors was collected by self-administered questionnaire. Body mass index was computed using duplicate measures of height and weight. Percent body fat was measured by dual-energy x-ray absorptiometry. Following data collection, one-way analysis of variance, chi(2), and Pearson correlations were used to compare means of diet quality scores across participant characteristics. We found that predictors of better diet quality in this study population were higher education and former smoking history (compared to never-smokers); there was no evidence for a relationship with income level. Individuals with higher-quality diets were more likely to have lower body mass index or percent body fat. Based on the results of this study, education level and smoking history are predictors of diet quality among overweight and obese postmenopausal women. These findings add to the increasing evidence for targeting public health interventions to individuals with lower education because this group stands to benefit from improved dietary intake. In addition, these results suggest that the timing of smoking cessation is a possible teachable moment for food and nutrition professionals.

Associations between healthy eating patterns and immune function or inflammation in overweight or obese postmenopausal women.

BACKGROUND: The link between poor nutritional status and impaired immune function is well established; however, most studies have focused on individual nutrients instead of overall dietary patterns. OBJECTIVE: Our objective was to investigate associations between 3 indexes of overall diet quality [the Diet Quality Index (DQI), the DQI including supplementary calcium (DQI-Ca), and the Healthy Eating Index (HEI)] and biomarkers of inflammation and immunity. DESIGN: This cross-sectional study included 110 overweight or obese postmenopausal women. Dietary intake measured by food-frequency questionnaire was used to calculate diet quality scores. C-reactive protein (CRP) and serum amyloid A (SAA) were measured by latex-enhanced nephelometry. Flow cytometry was used to measure natural killer (NK) cell cytotoxicity and to enumerate and phenotype lymphocyte subsets. T lymphocyte proliferation was assessed by (3)H-thymidine incorporation as well as by the carboxyfluorescein-succinimidyl ester method of cell division tracking. Multivariable-adjusted linear regression analysis was used to investigate associations between diet quality scores and markers of inflammation and immune function. RESULTS: Higher diet quality was associated with increased proportions of cytotoxic and decreased proportions of helper T lymphocytes. CRP and SAA concentrations were higher among women with a lower-quality diet; these associations became nonsignificant after adjustment for body mass index or percentage body fat. We observed limited evidence for an association between healthy eating patterns and greater lymphocyte proliferation and no evidence for an association with NK cell cytotoxicity. CONCLUSION: Our results provide limited evidence that healthy eating patterns contribute to enhanced immune function and reduced inflammation in overweight and obese postmenopausal women.

A mathematical model gives insights into nutritional and genetic aspects of folate-mediated one-carbon metabolism.

Impaired folate-mediated 1-carbon metabolism has been linked to multiple disease outcomes. A better understanding of the nutritional and genetic influences on this complex biochemical pathway is needed to comprehend their impact on human health. To this end, we created a mathematical model of folate-mediated 1-carbon metabolism. The model uses published data on folate enzyme kinetics and regulatory mechanisms to simulate the impact of genetic and nutritional variation on critical aspects of the pathway. We found that the model predictions match experimental data, while providing novel insights into pathway kinetics. Our primary observations were as follows: 1) the inverse association between folate and homocysteine is strongest at very low folate concentrations, but there is no association at high folate concentrations; 2) the DNA methylation reaction rate is relatively insensitive to changes in folate pool size; and 3) as folate concentrations become very high, enzyme velocities decrease. With regard to polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR), the modeling predicts that decrease MTHFR activity reduces concentrations of S-adenosylmethionine and 5-methyltetrahydrofolate, as well as DNA methylation, while modestly increasing S-adenosylhomocysteine and homocysteine concentrations and thymidine or purine synthesis. Decreased folate together with a simulated vitamin B-12 deficiency results in decreases in DNA methylation and purine and thymidine synthesis. Decreased MTHFR activity superimposed on the B-12 deficiency appears to reverse the declines in purine and thymidine synthesis. These mathematical simulations of folate-mediated 1-carbon metabolism provide a cost-efficient approach to in silico experimentation that can complement and help guide laboratory studies.

Pharmacogenetics of folate-related drug targets in cancer treatment.

Folate metabolism is the target of two major drug groups: folate antagonists (for example, methotrexate) and thymidylate synthase inhibitors (for example, 5-fluorouracil). These agents are used in the treatment of cancer, as well as for other conditions, such as rheumatoid arthritis. High-dose cancer treatment protocols can induce a state of acute folate depletion which may lead to significant treatment-related toxicity. Polymorphisms in folate-metabolizing enzymes may modify the therapeutic effectiveness and toxicity of these drugs. This review briefly summarizes the drugs targeting the folate pathway and describes common polymorphisms in folate-metabolizing enzymes and transport proteins. Pharmacogenetic studies investigating folate-related drug targets in the treatment of colorectal cancers and hematologic malignancies will subsequently be discussed. Findings to date illustrate a potential for targeting therapy based on patients' genotypes, in order to improve outcomes and reduce toxicity. However, larger, well-designed studies are needed to confirm these early findings.