Christopher J. Cifelli

Multiple cytochrome P-450 genes are concomitantly regulated by vitamin A under steady-state conditions and by retinoic acid during hepatic first-pass metabolism

Vitamin A (retinol) is an essential precursor for the production of retinoic acid (RA), which in turn is a major regulator of gene expression, affecting cell differentiation throughout the body. Understanding how vitamin A nutritional status, as well as therapeutic retinoid treatment, regulates the expression of retinoid homeostatic genes is important for improvement of dietary recommendations and therapeutic strategies using retinoids. This study investigated genes central to processes of retinoid uptake and storage, release to plasma, and oxidation in the liver of rats under steady-state conditions after different exposures to dietary vitamin A (deficient, marginal, adequate, and supplemented) and acutely after administration of a therapeutic dose of all-trans-RA. Over a very wide range of dietary vitamin A, lecithin:retinol acyltransferase (LRAT) as well as multiple cytochrome P-450s (CYP26A1, CYP26B1, and CYP2C22) differed by diet and were highly correlated with one another and with vitamin A status assessed by liver retinol concentration (all correlations, P < 0.05). After acute treatment with RA, the same genes were rapidly and concomitantly induced, preceding retinoic acid receptor (RAR)β, a classical direct target of RA. CYP26A1 mRNA exhibited the greatest dynamic range (change of log 2(6) in 3 h). Moreover, CYP26A1 increased more rapidly in the liver of RA-primed rats than naive rats, evidenced by increased CYP26A1 gene expression and increased conversion of [(3)H]RA to polar metabolites. By in situ hybridization, CYP26A1 mRNA was strongly regulated within hepatocytes, closely resembling retinol-binding protein (RBP)4 in location. Overall, whether RA is produced endogenously from retinol or administered exogenously, changes in retinoid homeostatic gene expression simultaneously favor both retinol esterification and RA oxidation, with CYP26A1 exhibiting the greatest dynamic change.

Use of Model‐Based Compartmental Analysis to Study Vitamin A Kinetics and Metabolism

We discuss the use of mathematical modeling, and specifically model-based compartmental analysis, to analyze vitamin A kinetic data obtained in rat and human studies over the past 25 years. Following an overview of whole-body vitamin A metabolism, a review of early kinetic studies, and an introduction to the approach and terminology of compartmental analysis, we summarize studies done in this laboratory to develop models of whole-body vitamin A metabolism in rats at varying levels of vitamin A status. Highlights of the results of these studies include the extensive recycling of vitamin A among plasma and tissues before irreversible utilization and the existence of significant extrahepatic pools of the vitamin. Our studies also document important differences in vitamin A kinetics as a function of vitamin A status and the importance of plasma retinol pool size in vitamin A utilization rate. Later we describe vitamin A kinetics and models developed for specific organs including the liver, eyes, kidneys, small intestine, lungs, testes, adrenals, and remaining carcass, and we discuss the effects of various exogenous factors (e.g., 4-HPR, dioxin, iron deficiency, dietary retinoic acid, and inflammation) on vitamin A dynamics. We also briefly review the retrospective application of model-based compartmental analysis to human vitamin A kinetic data. Overall, we conclude that the application of model-based compartmental analysis to vitamin A kinetic data provides unique insights into both quantitative and descriptive aspects of vitamin A metabolism and homeostasis in the intact animal.

Increasing Plant Based Foods or Dairy Foods Differentially Affects Nutrient Intakes: Dietary Scenarios Using NHANES 2007–2010

Diets rich in plant foods and lower in animal-based products have garnered increased attention among researchers, dietitians and health professionals in recent years for their potential to, not only improve health, but also to lessen the environmental impact. However, the potential effects of increasing plant-based foods at the expense of animal-based foods on macro- and micronutrient nutrient adequacy in the U.S. diet is unknown. In addition, dairy foods are consistently under consumed, thus the impact of increased dairy on nutrient adequacy is important to measure. Accordingly, the objective of this study was to use national survey data to model three different dietary scenarios to assess the effects of increasing plant-based foods or dairy foods on macronutrient intake and nutrient adequacy. Data from the National Health and Nutrition Examination Survey (NHANES) 2007–2010 for persons two years and older (n = 17,387) were used in all the analyses. Comparisons were made of usual intake of macronutrients and shortfall nutrients of three dietary scenarios that increased intakes by 100%: (i) plant-based foods; (ii) protein-rich plant-based foods (i.e., legumes, nuts, seeds, soy); and (iii) milk, cheese and yogurt. Scenarios (i) and (ii) had commensurate reductions in animal product intake. In both children (2–18 years) and adults (≥19 years), the percent not meeting the Estimated Average Requirement (EAR) decreased for vitamin C, magnesium, vitamin E, folate and iron when plant-based foods were increased. However the percent not meeting the EAR increased for calcium, protein, vitamin A, and vitamin D in this scenario. Doubling protein-rich plant-based foods had no effect on nutrient intake because they were consumed in very low quantities in the baseline diet. The dairy model reduced the percent not meeting the EAR for calcium, vitamin A, vitamin D, magnesium, and protein, while sodium and saturated fat levels increased. Our modeling shows that increasing plant-based foods could lead to unintended dietary outcomes without simultaneous changes in the types and amounts of plant foods currently consumed. Increasing dairy foods, which are currently under-consumed, could assist in improving the intakes of many nutrients of concern.

Diet modeling in older Americans: The impact of increasing plant-based foods or dairy products on protein intake

ObjectivesTo determine the effects of increasing plant-based foods or dairy products on protein intake in older Americans by performing diet modeling.DesignData from What We Eat in America (WWEIA), the dietary component of the National Health and Nutrition Examination Survey (NHANES), 2007-2010 for Americans aged 51 years and older (n=5,389), divided as 51-70 years (n=3,513) and 71 years and older (n=1,876) were used.MeasurementsUsual protein intake was compared among three dietary models that increased intakes by 100%: (1) plant-based foods; (2) higher protein plant-based foods (i.e., legumes, nuts, seeds, soy); and (3) dairy products (milk, cheese, and yogurt). Models (1) and (2) had commensurate reductions in animal-based protein intake.ResultsDoubling intake of plant-based foods (as currently consumed) resulted in a drop of protein intake by approximately 22% for males and females aged 51+ years. For older males and females, aged 71+ years, doubling intake of plant-based foods (as currently consumed) resulted in an estimated usual intake of 0.83±0.02 g/kg ideal body weight (iBW))/day and 0.78±0.01 g/kg iBW/day, respectively. In this model, 33% of females aged 71+ years did not meet the estimated average requirement for protein. Doubling dairy product consumption achieved current protein intake recommendations.ConclusionThese data illustrate that increasing plant-based foods and reducing animal-based products could have unintended consequences on protein intake of older Americans. Doubling dairy product intake can help older adults get to an intake level of approximately 1.2 g/kg iBW/day, consistent with the growing consensus that older adults need to consume higher levels of protein for health.

The Pattern of Complementary Foods in American Infants and Children Aged 0–5 Years Old—A Cross-Sectional Analysis of Data from the NHANES 2011–2014

Proper nutrition early in life can influence children’s present and future health. While several authoritative sources provide eating/food recommendations, only a few studies have assessed whether these recommendations are followed. The goal of this paper was to examine food and nutrient intakes on any given day during infancy and early childhood among various ethnicities. Twenty-four-hour dietary recall data of 0–5 years-old children (n = 2431) from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 was used to estimate intakes of nutrients and food groups and prevalence of inadequate intake. Data was analyzed separately for various age groups and ethnicities, and differences in means by age and or race/ethnicity were determined by t-tests with p < 0.05 as significant. The results indicate that intakes of all food groups were expectedly low at 0–11 months, increased with age, and were influenced by race/ethnicity. Mixed dish consumption, which also increased with age, made substantial contributions to children’s food group intakes. However, there was a substantial percentage of the population among all age and race/ethnic groups who did not consume the recommended amounts for each food group and had inadequate intakes of key nutrients, such as calcium, vitamin D, and vitamin E. Non-Hispanic black children consumed less dairy and more protein foods, and a significantly greater proportion of these children had inadequate intakes of calcium and vitamin D compared to their peers. In conclusion, the results from this study suggest that a substantial population of American infants and children from 0 to five years of age did not meet food group recommendations and had inadequate intakes of key nutrients such as calcium, vitamin D, and vitamin E from foods.

The impact of doubling dairy or plant-based foods on consumption of nutrients of concern and proper bone health for adolescent females.

Objective To determine the effects of increasing plant-based foods v. dairy foods on energy and nutrients of concern in adolescent females via diet modelling exercises. Design Data from the National Health and Nutrition Examination Survey (NHANES) were used to compare nutrient intakes from usual diet with those from three dietary scenarios that increased current intakes by 100 % of the following: (i) plant-based foods; (ii) protein-rich plant-based foods; and (iii) milk, cheese and yoghurt. The first two scenarios had commensurate reductions in animal products. Setting What We Eat in America, NHANES 2007–2010. Subjects Female adolescents (n 1594) aged 9–18 years. Results When currently consumed plant-based foods were increased by 100 %, there were increases in dietary fibre, added sugar, vitamin E, Fe and folate intakes. These increases were accompanied by decreases in total fat, saturated fat, Zn, vitamin D, Ca and protein intakes. Protein-rich plant foods are consumed in very low quantities in this population such that doubling their intake resulted in no real nutritional impact. When dairy products were increased by 100 % there were increases in intakes of vitamin D, Mg, Zn, Ca, K, energy, saturated fat and protein. Conclusions Non-specific recommendations to increase plant foods can lead to unintended nutritional consequences. For adolescent girls, meeting the dietary recommendation of three daily servings of dairy improved the intake of the identified nutrients of concern while simultaneously providing adequate nutrients essential for proper growth and bone health critical during the adolescent phase.