Health Disparities in Calorie Knowledge and Confidence Among the U.S. Adult Population.

PURPOSE: Obesity prevalence has reached an all-time high in the US, affecting >40% of the population. This study's objective was to evaluate associations between demographics and self-reported calorie knowledge and self-perceived confidence in calorie knowledge ("calorie confidence"). The relationships between body mass index (BMI) and calorie knowledge and confidence were also explored. METHODS: We analyzed data from participants (n = 2171) in the crosssectional, nationally representative 2019 FDA Food Safety and Nutrition Survey using logistic regression to estimate adjusted odds ratios (AORs) and confidence intervals (95% CIs) for associations between BMI and calorie knowledge (correct/incorrect), calorie confidence (confident/not confident), and demographic characteristics, and the Wald chi square test to evaluate relationships between BMI and both calorie knowledge and confidence. RESULTS: Many of the same subgroups were more likely than others to report lack of calorie knowledge and lack of confidence in knowing the typical daily calorie intake needed to maintain a healthy weight [respective AORs (95% CIs): age (years), >60 vs 51-60, 1.7 (1.1-2.5), and 1.4 (1.0-2.0); sex, male vs female, 1.7 (1.3-2.3), and 1.7 (1.3-2.1); race/ethnicity, non-Hispanic Black vs non-Hispanic white, 3.4 (2.1-5.5), and 2.4 (1.6-3.8); education, ≤high school vs college grad, 1.5 (1.0- 2.3), and 1.9 (1.3-2.7)]. BMI was significantly correlated with calorie confidence (P = .047), such that those reporting less confidence were more likely overweight or obese [underweight/healthy (BMI < 25): 29%, overweight (25 ≤ BMI < 30): 34%, obese (BMI ≥ 30): 37%]. CONCLUSION: In certain demographic subgroups associations between calorie knowledge and confidence differed. Tailored education and outreach for these groups may help to address these disparities.

Reported Knowledge of Typical Daily Calorie Requirements: Relationship to Demographic Characteristics in US Adults.

BACKGROUND: US obesity rates are at historically high levels, increasing the risk of negative health and economic outcomes at individual and population levels. Findings from earlier studies indicate that many consumers lack a clear understanding of calorie needs, potentially affecting their ability to manage caloric intake. OBJECTIVE: Our aim was to determine the knowledge of typical daily calorie needs of US adults by demographic and other characteristics, using a nationally representative sample. DESIGN: Data were analyzed from 6,267 respondents to the 2007-2008 and 2009-2010 National Health and Nutrition Examination Survey and its supplemental data source, the Flexible Consumer Behavior Survey, to assess reported knowledge of typical daily calorie requirements and associations with demographic and other characteristics of interest. STATISTICAL ANALYSES PERFORMED: Logistic regression for complex sample surveys was used to estimate associations between self-reported daily calorie needs for men and women aged 21 years and older and participant characteristics. RESULTS: Most respondents accurately reported typical daily calorie needs for a person of their sex, age group, and physical activity level, however, distinct differences emerged between demographic groups. Women, non-Hispanic whites, and those with higher income and education levels were more likely to estimate typical daily calorie needs accurately; men were almost four times more likely than women to indicate a lack of knowledge of daily calorie needs. CONCLUSIONS: Knowledge of typical daily calorie requirements is a foundational concept of nutrition literacy. Educational efforts to increase awareness, knowledge, and use of calorie information for certain groups may be helpful to refine interventions and ultimately improve public health in the United States.

Evaluation of CYP3A4 inhibition and hepatotoxicity using DMSO-treated human hepatoma HuH-7 cells.

A human hepatoma cell line (HuH-7) was evaluated as a metabolically competent cell model to investigate cytochrome P450 3A4 (CYP3A4) inhibition, induction, and hepatotoxicity. First, CYP3A4 gene expression and activity were determined in HuH-7 cells under three culture conditions: 1-week culture, 3-week culture, or 1 % dimethyl sulfoxide (DMSO) treatment. HuH-7 cells treated with DMSO for 2 weeks after confluence expressed the highest CYP3A4 gene expression and activity compared to the other two culture conditions. Furthermore, CYP3A4 activity in DMSO-treated HuH-7 cells was compared to that in a human hepatoma cell line (HepG2/C3A) and human bipotent progenitor cell line (HepaRG), which yielded the following ranking: HepaRG > DMSO-treated HuH-7 >> HepG2/C3A cells. The effects of three known CYP3A4 inhibitors were evaluated using DMSO-treated HuH-7 cells. CYP3A4 enzyme inhibition in HuH-7 cells was further compared to human recombinant CYP3A4, indicating similar potency for reversible inhibitors (IC 50 within 2.5-fold), but different potency for the irreversible inhibitor. Next, induction of CYP3A4 activity was compared between DMSO-treated HuH-7 and HepaRG cells using two known inducers. DMSO-treated HuH-7 cells yielded minimal CYP3A4 induction compared to that in the HepaRG cells after 48-h treatments. Finally, the cytotoxicity of five known hepatotoxicants was evaluated in DMSO-treated HuH-7, HepG2/C3A, and HepaRG cells, and significant differences in cytotoxic sensitivity were observed. Overall, DMSO-treated HuH-7 cells are a valuable model for medium- or high-throughput screening of chemicals for CYP3A4 inhibition and hepatotoxicity.

Sex hormone modulation of both induction and inhibition of CYP1A by genistein in HepG2/C3A cells.

Genistein is a widely consumed phytoestrogen in dietary supplements and has been reported to play roles in both cancer prevention and promotion. These conflicting effects may be complicated by sex differences. Cytochrome P450 1A (CYP1A) participates in carcinogen activation and detoxification, and the enzyme may interact with genistein. Therefore, modulation of CYP1A by a combination of genistein and sex hormones could be responsible for sex differences related to cancer prevention and promotion. In the current study, a human liver cell line, HepG2/C3A, cultured in sex hormone-supplemented media was used to investigate the modulatory effect of genistein on CYP1A gene expression and activity. Genistein exerted both long-term (72 h) induction and short-term (immediate) inhibition of CYP1A activity in HepG2/C3A cells. In the long-term study, CYP1A gene expression and enzyme activity were induced to a greater extent in male hormone-supplemented cells than female ones. In the short-term study, CYP1A activity was inhibited more strongly by genistein in the male hormone-supplemented cells than in the female hormone-supplemented cells. These significant differences suggest that male hormones can modulate the effects of genistein on CYP1A gene expression and activity.

Use of the Combination Index to determine interactions between plant-derived phenolic acids on hepatotoxicity endpoints in human and rat hepatoma cells.

The beneficial or adverse effects of isolated phytochemicals are not always concordant with effects of the botanical dietary supplements from which they were derived. This disparity could be due to interactions between the various phytochemicals present in the whole plant. The phenolic acids, rosmarinic acid (RA), caffeic acid (CA) and ferulic acid (FA) are widely present in foods and dietary supplements, and they are assumed to exert various beneficial biological effects. However, there is little data on the potential biological interactions of these three phenolic acids which commonly occur together and are linked metabolically. In the present study, liver toxicity of the three phenolic acids was assessed on the three compounds singly and in various binary and one ternary combinations. A series of in vitro endpoints relevant to liver toxicity were evaluated in both a human (HepG2/C3A) and rat (MH1C1) hepatocyte cell line. The Combination Index (CI) was calculated for each endpoint from both the concentration responses of the single compounds and the responses of the various binary and ternary mixtures. Both synergistic and antagonistic interactions were observed for some endpoints and some combinations of test agents. Interactions were most prevalent in measures of oxidative stress and cytochrome P450 activities in both cell types. There was only a 53% concordance between the rat and human cells which may be suggestive of species differences. The data suggest an approach for better characterizing the beneficial or adverse effects of complex botanical products through evaluation of interactions between individual phytochemical components.

Effects of dietary phenolics and botanical extracts on hepatotoxicity-related endpoints in human and rat hepatoma cells and statistical models for prediction of hepatotoxicity.

Toxicity assessment of botanical materials is difficult because they are typically complex mixtures of phytochemicals. In the present study, 16 phenolics were tested in both human (HepG2/C3A) and rat (MH1C1) hepatoma cells using a battery of eight toxicity endpoints. Cluster analysis was used to group the phenolics into four clusters for each cell type. Comparison of overall and individual liver activity of phenolics on both human and rat hepatoma cell lines showed significant differences for some endpoints. However, the cluster membership was similar across both cell types with the majority of phenolics clustering with the solvent control group (cluster 1). Each cell type produced a cluster of compounds with reported in vivo liver toxicity (cluster 2). Five herbal extracts were prepared and then tested as above. Using the cluster model developed with the phenolics, in the HepG2/C3A cells green tea was assigned to cluster 2 and the remaining four extracts to cluster 1. In the MH1C1 cells, green tea and thyme were assigned to cluster 2, cinnamon to cluster 4, and juniper berry and peppermint to cluster 1. The data suggest that this in vitro model may be useful for identifying hepatotoxic phenolics and botanical preparations rich in phenolics.

An in vitro system for studying potential biological mechanisms of human sex differences in susceptibility to acute liver injury.

Women are more susceptible than men to acute liver injury from drugs and other xenobiotics. The biological mechanisms for this sex difference are unknown, but known sex differences in steroid hormone levels and immune response could play a role. A human hepatocyte cell line, HepG2, was cultured for 8 days in either a male hormone, female hormone, or sex hormone-free medium. The cells were then exposed to a mixture of pro-inflammatory cytokines (interleukin (IL)-1beta, IL-6, TNFalpha) for 72h to simulate acute inflammation. Cell viability (total DNA) and various metabolic functions (reactive oxygen species (ROS), neutral and polar lipid (PL) accumulation, mitochondrial membrane potential, cytochrome P450 (CYP) activities) were measured fluorometrically. Acute phase proteins (albumin, IL-1ra) were measured in the culture medium by ELISA. This model gave both significant hormone only effects (ROS, PL accumulation) and cytokine only effects (total DNA, CYP1A, neutral and PL accumulation, albumin, IL-1ra) consistent with known biological responses. Significant hormone-cytokine interactions were observed for several endpoints (total DNA, ROS, neutral and PL accumulation, albumin). These findings suggest that sex hormones and pro-inflammatory cytokines can interact to alter liver metabolism in ways that may contribute to the marked sex difference in susceptibility to chemical-induced acute liver injury.

Multiendpoint mechanistic profiling of hepatotoxicants in HepG2/C3A human hepatoma cells and novel statistical approaches for development of a prediction model for acute hepatotoxicity.

HepG2/C3A human hepatoma cells were exposed to serial concentrations of seven known hepatotoxicants for 48h. Six endpoint assays were selected to model different mechanisms of acute hepatotoxicity. Each compound produced a unique concentration-response pattern across all endpoints. The endpoints did not correlate strongly, suggesting that each endpoint monitored an independent cellular process. Prediction models were developed using five statistical methods. The models used only known hepatotoxicants for the training set. The zero concentration (control) and all concentrations not significantly different from control were programmed as non-toxic levels and concentrations significantly different from control as toxic levels. So, rather than a binary classification of each compound (i.e., toxic or non-toxic), the models gave a prediction of the concentration, if any, at which a compound showed behavior similar to liver toxicants at their toxic concentrations. The discriminant analysis model gave the best overall performance with positive and negative predictive values of 1.00 and 0.83, respectively. Ten additional compounds were tested using this prediction model. The model predicted liver active concentrations for each compound that were consistent with their known biologically active concentrations. This model system may be useful for predicting concentration levels at which unknown compounds would display undesirable liver activity.