Joanna K. Hodges

Catechins in green tea extract (GTE) (epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin (EC), epicatechin gallate (ECG)) vary in bioactivity. We developed a physiologically relevant mathematical model of catechin metabolism to test the hypothesis that fractional catabolic rates of catechins would be differentially affected by their structural attributes. Pharmacokinetic data of plasma and urine catechin concentrations were used from healthy adults (n = 19) who ingested confections containing 0.5 g GTE (290 mg EGCG, 87 mg EGC, 39 mg EC, 28 mg ECG). A 7-compartmental model of catechin metabolism comprised of the gastrointestinal tract (stomach, small and large intestine), liver, plasma, extravascular tissues, and kidneys was developed using a mean fraction dose of EGCG, ECG, EGC, and EC. Fitting was by iterative least squares regression analysis, and goodness of fit was ascertained by the estimated variability of parameters (FSD < 0.5). The interaction of gallation and B-ring dihydroxylation most greatly extended plasma residence time such that EGC > EC = EGCG > EGC. The interaction between gallation and B-ring dihydroxylation accelerated the transfer from the upper gastrointestinal tract to the small intestine but delayed subsequent transfers from the small intestine through the liver to plasma and from kidneys to urine. Gallation and B-ring dihydroxylation independently delayed the transfer from plasma to extravascular tissues, except the uptake to kidneys, which was slowed by gallation only. This multi-compartment model, to be validated in a future study, suggests that gallation and B-ring dihydroxylation affect catechin catabolism in a tissue-specific manner and thus their potential bioactivity.

Full-fat dairy milk may protect against cardiometabolic disorders, due to the milk fat globule membrane (MFGM), through anti-inflammatory and gut-health-promoting activities. We hypothesized that a MFGM-enriched milk beverage (MEB) would alleviate metabolic endotoxemia in metabolic syndrome (MetS) persons by improving gut barrier function and glucose tolerance. In a randomized crossover trial, MetS persons consumed for two-week period a controlled diet with MEB (2.3 g/d milk phospholipids) or a comparator beverage (COMP) formulated with soy phospholipid and palm/coconut oil. They then provided fasting blood and completed a high-fat/high-carbohydrate test meal challenge for evaluating postprandial metabolism and intestinal permeability. Participants had no adverse effects and achieved high compliance, and there were no between-trial differences in dietary intakes. Compared with COMP, fasting endotoxin, glucose, incretins, and triglyceride were unaffected by MEB. The meal challenge increased postprandial endotoxin, triglyceride, and incretins, but were unaffected by MEB. Insulin sensitivity; fecal calprotectin, myeloperoxidase, and short-chain fatty acids; and small intestinal and colonic permeability were also unaffected by MEB. This short-term study demonstrates that controlled administration of MEB in MetS persons does not affect gut barrier function, glucose tolerance, and other cardiometabolic health biomarkers, which contradicts observational evidence that full-fat milk heightens cardiometabolic risk. Registered at ClinicalTrials.gov (NCT03860584).

Poor diet quality influences cardiometabolic risk. Although potatoes are suggested to adversely affect cardiometabolic health, controlled trials that can establish causality are limited. Consistent with potatoes being rich in micronutrients and resistant starch, we hypothesized that their inclusion in a Dietary Guidelines for Americans (DGA)-based dietary pattern would improve cardiometabolic and gut health in metabolic syndrome (MetS) persons. In a randomized cross-over trial, MetS persons (n = 27; 32.5 ± 1.3 year) consumed a DGA-based diet for 2 weeks containing potatoes (DGA + POTATO; 17.5 g/day resistant starch) or bagels (DGA + BAGEL; 0 g/day resistant starch) prior to completing oral glucose and gut permeability tests. Blood pressure, fasting glucose and insulin, and insulin resistance decreased (p < 0.05) from baseline regardless of treatment without any change in body mass. Oral glucose-induced changes in brachial artery flow-mediated dilation, nitric oxide homeostasis, and lipid peroxidation did not differ between treatment arms. Serum endotoxin AUC_{0–120 min} and urinary lactulose/mannitol, but not urinary sucralose/erythritol, were lower in DGA + POTATO. Fecal microbiome showed limited between-treatment differences, but the proportion of acetate was higher in DGA + POTATO. Thus, short-term consumption of a DGA-based diet decreases cardiometabolic risk, and the incorporation of resistant starch-containing potatoes into a healthy diet reduces small intestinal permeability and postprandial endotoxemia.

Preclinical studies suggest that blueberry consumption is associated with improved bone health. This study quantified changes in urinary excretion of the long-lived calcium radioisotope ⁴¹Ca to assess the dose-response effect of blueberries on bone loss in postmenopausal women. We hypothesized that blueberry consumption would reduce bone loss in a dose-dependent manner. Healthy women at least 4 years past menopause were dosed with 50 nCi of ⁴¹Ca and completed a 5-mo equilibration period for ⁴¹Ca deposition in bone followed by a 6-wk control period. Subsequently, participants were assigned to a random sequence of 3 intervention periods, each corresponding to a low (17.5 g/d), medium (35 g/d), or high (70 g/d) dose of freeze-dried blueberry powder equivalent to 0.75, 1.5, or 3 cups of fresh blueberries. The blueberry powder was incorporated into granola bars, spread, and drinks consumed daily for 6 wk, followed by a 6-wk washout period. Urinary ⁴¹Ca: Ca ratio was measured by accelerator mass spectrometry in 24-h urine collected weekly during intervention and every 3 wk during washout. Serum 25-hydroxyvitamin D and calcium concentrations were assessed prior to each intervention. Serum bone resorption biomarkers and urinary polyphenols were measured at the end of each control and intervention period. Data were analyzed using a linear mixed model and repeated measures ANOVA. Fourteen healthy, non-osteoporotic (mean bone mineral density t-score: −1.33) women completed the study. Net bone calcium retention increased by 6% in the low (P < 0.01) and 4% in the medium (P < 0.05) dose intervention compared with the control and washout periods. The high dose had no significant effect on net bone calcium retention (P = 0.19). Urinary excretion of hippuric acid increased dose-dependently with blueberry consumption. No significant relationships were found between bone resorption biomarkers, 25-hydroxyvitamin D, or calcium and any of the interventions. A hormetic response was observed to blueberry intake, whereby daily consumption of foods containing 17.5–35 g, but not 70 g, of freeze-dried blueberry powder increased net bone calcium retention. Moderate consumption of blueberries may be an effective strategy to attenuate bone loss in healthy postmenopausal women. NIH/NCCIH, Project Development Team within the ICTSI NIH/NCRR.

Magnesium (Mg), a cofactor in 300 enzymes, is essential for energy transfer and adequate vitamin D status and plays an important structural role with 60% of bodily reserves residing in bone. The Food and Nutrition Board recommendations for dietary intake of Mg, the Dietary Reference Intakes, have not been updated since 1997. Current recommendations for children were set based on an intake producing positive Mg balance. Population-based studies showed that the average intakes in children are suboptimal relative to the current recommendation. Newer evidence suggests Mg requirement should be related to body size. Other potential modifying factors of Mg requirements include calcium and sodium intake and chronic disease state. Future research is needed to refine public health recommendations for Mg and to establish the new Dietary Reference Intakes category of Chronic Disease Risk Reduction level for Mg, especially for children.

Quantifying the long-term effects of nutritional or drug treatments on bone is challenging due to the delay in time between treatment and changes in bone mass. The objective of this study was to develop a dynamic (non-steady state) mathematical model of calcium metabolism in young growing rats as an analogue for human adolescents and to use that model to predict the effects of treatments on calcium mass in bone. A dynamic model of calcium metabolism was developed using kinetic data collected from Sprague-Dawley male rats (n = 54) dosed intraperitoneally with 50 μCi of ⁴⁵Ca at 4 wk of age. Total calcium and ⁴⁵Ca levels measured in serum and 24-h urine samples collected periodically for 45 d after treatment were analyzed by compartmental modeling using WinSAAM software. Concurrently, tracer (⁴⁵Ca) and tracee (total calcium) models, together called the ‘dynamic model’, were developed. Growth of the rats was modeled using a formula based on body weight. Calcium absorption was decreased by about 50% at wk 6 to account for the reduction in bone mineral accretion in late puberty. During the first 40 d after weaning, the model included a 4-fold decrease in bone resorption and a 20-fold decrease in bone formation, consistent with previous findings of studies conducted in growing rats. Data were fitted by iterative least squares regression analysis. To mimic the effects of dietary and drug interventions during adolescence, the absorption efficiency was manipulated in terms of degree, timing, and duration and the subsequent changes in bone mass were quantified. The dynamic model predicted that, if absorption decreased by 25% instead of 50% during growth, the rate of bone accretion would be 32% higher and the bone mineral mass at d 50 would be 24% larger, suggesting that a dietary or drug intervention that minimizes the drop in absorption, would result in a higher bone mineral mass. A dynamic model of calcium metabolism during growth was developed and used to predict the effect of interventions on bone mass. These predictions would be tested in future studies. Purdue University Graduate School and Amgen, Inc., Thousand Oaks, CA.