Identifying Gut Microbiome Features that Predict Responsiveness Toward a Prebiotic Capable of Increasing Calcium Absorption: A Pilot Study.

Previously, we demonstrated that prebiotics may provide a complementary strategy for increasing calcium (Ca) absorption in adolescents which may improve long-term bone health. However, not all children responded to prebiotic intervention. We determine if certain baseline characteristics of gut microbiome composition predict prebiotic responsiveness. In this secondary analysis, we compared differences in relative microbiota taxa abundance between responders (greater than or equal to 3% increase in Ca absorption) and non-responders (less than 3% increase). Dual stable isotope methodologies were used to assess fractional Ca absorption at the end of crossover treatments with placebo, 10, and 20 g/day of soluble corn fiber (SCF). Microbial DNA was obtained from stool samples collected before and after each intervention. Sequencing of the 16S rRNA gene was used to taxonomically characterize the gut microbiome. Machine learning techniques were used to build a predictive model for identifying responders based on baseline relative taxa abundances. Model output was used to infer which features contributed most to prediction accuracy. We identified 19 microbial features out of the 221 observed that predicted responsiveness with 96.0% average accuracy. The results suggest a simplified prescreening can be performed to determine if a subject's bone health may benefit from a prebiotic. Additionally, the findings provide insight and prompt further investigation into the metabolic and genetic underpinnings affecting calcium absorption during pubertal bone development.

Iodine Intake Trends in United States Girls and Women between 2011 and 2020.

BACKGROUND: Usual intakes of iodine in United States girls and women, including pregnant and lactating women have not been adequately studied. Adequate intake of iodine is critical for neurodevelopment of girls, thyroid functions, and reproductive health of women. OBJECTIVES: This study aimed to examine the adequacy and trends of iodine intake of United States girls and women between 2011 and 2020. METHODS: We mapped the sources of United States girls and women's iodine intake from the 29 food groups between 2011 and 2020 using United States Department of Agriculture's iodine data release 2. The total food intakes from 2 d of dietary recall of the United States National Health and Nutritional Examination Survey and estimated iodine concentrations of the food groups were used to calculate the usual iodine intakes of female participants. Trends of usual intakes, urinary iodine concentrations (UIC), and estimated intake adequacy were calculated. RESULTS: Median usual intakes of iodine estimated from diet and supplements and UIC of United States girls and nonpregnant, nonlactating women declined between 2011 and 2020 in all 3 age groups: ≤14 y, 15-49 y old, and ≥50 y. Median usual intakes of iodine for pregnant and lactating United States women declined as well. Inadequacy levels of usual iodine intake were 9.9% for nonpregnant, nonlactating women of reproductive age 15-49 y old, 40.3% for lactating, and 10.2% for pregnant women in the 2017-2020 period. Intake insufficiencies estimated from UIC were 48.8%, 63.2%, and 31.3% for nonpregnant, nonlactating women of reproductive age 15-49 y old, pregnant and lactating women, respectively, in the 2017-2020 period. A significant decline in milk consumption might be one of the major contributors to the dietary iodine decline in United States women. CONCLUSIONS: Iodine intake of United States girls and women were on the decline between 2011 and 2020 and the increased inadequacy of iodine intake deserves public health attention.

Including calcium-fortified water or flour in modeled diets based on local foods could improve calcium intake for women, adolescent girls, and young children in Bangladesh, Uganda, and Guatemala.

Adequate calcium intake is essential for health, especially for infants, children, adolescents, and women, yet is difficult to achieve with local foods in many low- and middle-income countries. Previous analysis found it was not always possible to identify food-based recommendations (FBRs) that reached the calcium population recommended intake (PRI) for these groups in Bangladesh, Guatemala, and Uganda. We have modeled the potential contribution of calcium-fortified drinking water or wheat flour to FBR sets, to fill the remaining intake gaps. Optimized diets containing fortified products, with calcium-rich local foods, achieved the calcium PRI for all target groups. Combining fortified water or flour with FBRs met dietary intake targets for adolescent girls in all geographies and allowed a reduction from 3-4 to the more feasible 1-2 FBRs. Water with a calcium concentration of 100 mg/L with FBRs was sufficient to meet calcium targets in Uganda, but higher concentrations (400-500 mg/L) were mostly required in Guatemala and Bangladesh. Combining calcium-fortified wheat flour at 400 mg/100 g of flour and the FBR for small fish resulted in diets meeting the calcium PRI in Bangladesh. Calcium-fortified water or flour could improve calcium intake for vulnerable populations, especially when combined with FBRs based on locally available foods.

Moderate consumption of freeze-dried blueberry powder increased net bone calcium retention compared with no treatment in healthy postmenopausal women: a randomized crossover trial.

BACKGROUND: Preclinical studies suggest that blueberry consumption is associated with improved bone health. OBJECTIVES: We conducted a blueberry dose-response study in ovariectomized (OVX)-rats that informed a study in postmenopausal women using the urinary appearance of calcium (Ca) tracers from prelabeled bone to reflect changes in bone balance. We hypothesized that blueberry consumption would reduce bone loss in a dose-dependent manner compared with no treatment. METHODS: OVX rats were fed 4 doses of blueberry powder (2.5%, 5%, 10%, and 15%) in randomized order to determine bone 45Ca retention. Fourteen healthy, nonosteoporotic women ≥4 y past menopause were dosed with 50 nCi of 41Ca, a long-lived radioisotope, and equilibrated for 5 mo to allow 41Ca deposition in bone. Following a 6-wk baseline period, participants were assigned to a random sequence of 3 6-wk interventions, 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 incorporated into food and beverage products. Urinary 41Ca:Ca ratio was measured by accelerator mass spectrometry. 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 analysis of variance. RESULTS: In both OVX rats and postmenopausal women, blueberry interventions benefited net bone calcium balance at lower but not at higher doses. In women, net bone calcium retention increased by 6% with the low (95% CI: 2.50, 8.60; P < 0.01) and 4% with the medium (95% CI: 0.96, 7.90; P < 0.05) dose compared with no treatment. Urinary excretion of hippuric acid increased dose-dependently with blueberry consumption. No significant relationships were found between bone resorption biomarkers, 25-hydroxyvitamin D, and interventions. CONCLUSIONS: Moderate consumption (<1 cup/d) of blueberries may be an effective strategy to attenuate bone loss in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT02630797.

Trends in Diet Quality and Increasing Inadequacies of Micronutrients Vitamin C, Vitamin B12, Iron and Potassium in US Type 2 Diabetic Adults.

BACKGROUND: Prevalence of diabetes was high and rose significantly in the US between 1999 and 2018. A healthy dietary pattern that provides micronutrient adequacy is one of the most important lifestyle choices for battling the progress of diabetes. Yet, the patterns and trends of diet quality of the US type 2 diabetes are understudied. OBJECTIVES: We aim to examine the patterns and trends of diet quality and major food sources of macronutrients of US type 2 diabetic adults. METHODS: The 24 h dietary recalls of 7789 type 2 diabetic adults, comprising 94.3% of total adults with diabetes from the US National Health and Nutrition Examination Survey cycles (1999-2018), were analyzed. Diet quality was measured by the total Healthy Eating Index (HEI)-2015 scores and 13 individual components. Trends of usual intakes of vitamin C (VC), vitamin B12 (VB12), iron, and potassium and supplements from two 24 h recalls were also examined for type 2 diabetic population. RESULTS: Diet quality of type 2 diabetic adults worsened between 1999 and 2018 while that of US adults of general population improved based on the total HEI 2015 scores. For people with type 2 diabetes, consumption of saturated fat and added sugar increased while consumption of vegetables and fruits declined significantly, although consumption of refined grain declined and consumption of seafood and plant protein increased significantly. In addition, usual intakes of micronutrients VC, VB12, iron, and potassium from food sources declined significantly during this period. CONCLUSIONS: Diet quality generally worsened for US type 2 diabetic adults between 1999 and 2018. Declining consumptions of fruits, vegetables, and non-poultry meat may have contributed to the increasing inadequacies of VC, VB12, iron, and potassium in the US type 2 diabetic adults.

Effect of soluble corn fibre and calcium supplementation on bone mineral content and bone mineral density in preadolescent Malaysian children-a double-blind randomised controlled trial (PREBONE-Kids Study).

Soluble corn fibre (SCF) with calcium did not improve bone indices after 1 year in preadolescent children. INTRODUCTION: SCF has been reported to improve calcium absorption. We investigated the long-term effect of SCF and calcium on bone indices of healthy preadolescent children aged 9-11 years old. METHODS: In a double-blind, randomised, parallel arm study, 243 participants were randomised into four groups: placebo, 12-g SCF, 600-mg calcium lactate gluconate (Ca) and 12-g SCF + 600-mg calcium lactate gluconate (SCF + Ca). Total body bone mineral content (TBBMC) and total body bone mineral density (TBBMD) were measured using dual-energy X-ray absorptiometry at baseline, 6 and 12 months. RESULTS: At 6 months, SCF + Ca had a significant increase in TBBMC from baseline (27.14 ± 6.10 g, p = 0.001). At 12 months, there was a significant increase in TBBMC from baseline in the SCF + Ca (40.28 ± 9.03 g, p = 0.001) and SCF groups (27.34 ± 7.93 g, p = 0.037). At 6 months, the change in TBBMD in the SCF + Ca (0.019 ± 0.003 g/cm2) and Ca (0.014 ± 0.003 g/cm2) groups was significantly different (p < 0.05) from SCF (0.004 ± 0.002 g/cm2) and placebo (0.002 ± 0.003 g/cm2). However, the changes in TBBMD and TBBMC were not significantly different among groups at 12 months. CONCLUSION: SCF did not increase TBBMC and TBBMD in Malaysian children after 1 year although calcium supplementation increased TBBMD at 6 months. Further work is needed to fully understand the mechanism and health benefits of prebiotics in this study population. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03864172.

Decreasing Vitamin C Intake, Low Serum Vitamin C Level and Risk for US Adults with Diabetes.

Vitamin C (VC) intakes, serum VC, fasting plasma glucose, and A1c levels of 25,206 adult men and 26,944 adult women with 6807 type 2 and 428 type 1 diabetes from the NHANES database between 1999 and 2018 were analyzed. Our hypothesis is that low VC intake and serum VC level may be a health risk for US adults with diabetes. Analyses revealed total VC intake below the estimated average requirement (EAR) increased from 38.1% to 46.5% between 1999-2018. VC intake and serum VC levels were inversely associated with markers of pre-diabetes and type 2 diabetes, namely, fasting plasma glucose and A1c levels. Risks of type 2 diabetes increased in adults with VC intake below the EAR and with no VC supplement (odds ratio 1.20, 95% CI 1.1-1.3 and 1.28, 95% CI 1.18-1.40, respectively). Median survivor years of diabetic adults with lower and deficient serum VC were shorter than that of diabetic adults with normal serum VC. Mortality risks of type 2 diabetes with low VC intake and/or deficient serum VC levels were elevated compared to those with adequate VC intake and normal serum VC (HR 1.25, 95% CI 1.05-1.49 and 1.84, 95% CI 1.10-3.08, respectively). Observation of declining VC intake and deleterious consequences of low serum VC in US adults with diabetes suggests encouragement of VC intake, including VC supplementation of 500-1000 mg/day, may be beneficial for pre-diabetic and diabetic US adults.

Calcium status assessment at the population level: Candidate approaches and challenges.

Inadequate dietary calcium intake is a global public health problem that disproportionately affects low- and middle-income countries. However, the calcium status of a population is challenging to measure, and there are no standard methods to identify high-risk communities even in settings with an elevated prevalence of a disease caused or exacerbated by low calcium intake (e.g., rickets). The calcium status of a population depends on numerous factors, including intake of calcium-rich foods; the bioavailability of the types of calcium consumed in foods and supplements; and population characteristics, including age, sex, vitamin D status, and genetic attributes that influence calcium retention and absorption. The aim of this narrative review was to assess candidate indicators of population-level calcium status based on a range of biomarkers and measurement methods, including dietary assessment, calcium balance studies, hormonal factors related to calcium, and health outcomes associated with low calcium status. Several promising approaches were identified, but there was insufficient evidence of the suitability of any single indicator to assess population calcium status. Further research is required to develop and validate specific indicators of calcium status that could be derived from the analysis of data or samples that are feasibly collected in population-based surveys.

Interventions to improve calcium intake through foods in populations with low intake.

Calcium intake remains inadequate in many low- and middle-income countries, especially in Africa and South Asia, where average intakes can be below 400 mg/day. Given the vital role of calcium in bone health, metabolism, and cell signaling, countries with low calcium intake may want to consider food-based approaches to improve calcium consumption and bioavailability within their population. This is especially true for those with low calcium intake who would benefit the most, including pregnant women (by reducing the risk of preeclampsia) and children (by reducing calcium-deficiency rickets). Specifically, some animal-source foods that are naturally high in bioavailable calcium and plant foods that can contribute to calcium intake could be promoted either through policies or educational materials. Some food processing techniques can improve the calcium content in food or increase calcium bioavailability. Staple-food fortification with calcium can also be a cost-effective method to increase intake with minimal behavior change required. Lastly, biofortification is currently being investigated to improve calcium content, either through genetic screening and breeding of high-calcium varieties or through the application of calcium-rich fertilizers. These mechanisms can be used alone or in combination based on the local context to improve calcium intake within a population.

Blueberry Polyphenols do not Improve Bone Mineral Density or Mechanical Properties in Ovariectomized Rats.

Osteoporosis-related bone fragility fractures are a major public health concern. Given the potential for adverse side effects of pharmacological treatment, many have sought alternative treatments, including dietary changes. Based on recent evidence that polyphenol-rich foods, like blueberries, increase calcium absorption and bone mineral density (BMD), we hypothesized that blueberry polyphenols would improve bone biomechanical properties. To test this, 5-month-old ovariectomized Sprague-Dawley rats (n = 10/gp) were orally gavaged for 90 days with either a purified extract of blueberry polyphenols (0-1000 mg total polyphenols/kg bw/day) or lyophilized blueberries (50 mg total polyphenols/kg bw/day). Upon completion of the dosing regimen, right femur, right tibia, and L1-L4 vertebrae were harvested and assessed for bone mineral density (BMD), with femurs being further analyzed for biomechanical properties via three-point bending. There were no differences in BMD at any of the sites analyzed. For bone mechanical properties, the only statistically significant difference was the high dose group having greater ultimate stress than the medium dose, although in the absence of differences in other measures of bone mechanical properties, we concluded that this result, while statistically significant, had little biological significance. Our results indicate that blueberry polyphenols had little impact on BMD or bone mechanical properties in an animal model of estrogen deficiency-induced bone loss.

(Poly)phenol toxicity in vivo following oral administration: A targeted narrative review of (poly)phenols from green tea, grape, and anthocyanin-rich extracts.

Fruit- and vegetable-derived (poly)phenols are secondary plant metabolites that may have beneficial effects on human health when consumed regularly. Recent years have seen rapid growth in both consumer demand for and research interest in (poly)phenol-rich dietary supplements, natural colorants, and functional foods. As these products continue to enter the marketplace and (poly)phenol intake patterns change from traditional food products to these sources, attention must be paid to the potential for toxicity from consuming elevated doses of (poly)phenols. To date, much remains unknown regarding the safety of high doses of (poly)phenols, especially in vivo. In this targeted narrative review, we summarize evidence from in vivo investigations of (poly)phenol toxicity after oral administration of green tea extracts, grape-derived phenolics, and anthocyanin-rich extracts. There is limited evidence of overt toxicity from oral ingestion of these (poly)phenol-rich sources, though more research on the safety of high doses-as well as defining what constitutes a "high" dose of both individual and complex mixtures of (poly)phenols-is needed before these observations can be used to create dietary guidance for consumers.

Short-Term Supplemental Dietary Potassium from Potato and Potassium Gluconate: Effect on Calcium Retention and Urinary pH in Pre-Hypertensive-to-Hypertensive Adults.

Potassium supplementation has been associated with reduced urinary calcium (Ca) excretion and increased Ca balance. Dietary interventions assessing the impact of potassium on bone are lacking. In this secondary analysis of a study designed primarily to determine blood pressure effects, we assessed the effects of potassium intake from potato sources and a potassium supplement on urinary Ca, urine pH, and Ca balance. Thirty men (n = 15) and women (n = 15) with a mean ± SD age and BMI of 48.2 ± 15 years and 31.4 ± 6.1 kg/m2, respectively, were enrolled in a cross-over, randomized control feeding trial. Participants were assigned to a random order of four 16-day dietary potassium interventions including a basal diet (control) of 2300 mg/day (~60 mmol/day) of potassium, and three phases of an additional 1000 mg/day (3300 mg/day(~85 mmol/day) total) of potassium in the form of potatoes (baked, boiled, or pan-heated), French fries (FF), or a potassium (K)-gluconate supplement. Calcium intake for all diets was approximately 700-800 mg/day. Using a mixed model ANOVA there was a significantly lower urinary Ca excretion in the K-gluconate phase (96 ± 10 mg/day) compared to the control (115 ± 10 mg/day; p = 0.027) and potato (114 ± 10 mg/day; p = 0.033). In addition, there was a significant difference in urinary pH between the supplement and control phases (6.54 ± 0.16 vs. 6.08 ± 0.18; p = 0.0036). There were no significant differences in Ca retention. An increased potassium intake via K-gluconate supplementation may favorably influence urinary Ca excretion and urine pH. This trial was registered at ClinicalTrials.gov as NCT02697708.

Short-Term RCT of Increased Dietary Potassium from Potato or Potassium Gluconate: Effect on Blood Pressure, Microcirculation, and Potassium and Sodium Retention in Pre-Hypertensive-to-Hypertensive Adults.

Increased potassium intake has been linked to improvements in cardiovascular and other health outcomes. We assessed increasing potassium intake through food or supplements as part of a controlled diet on blood pressure (BP), microcirculation (endothelial function), and potassium and sodium retention in thirty pre-hypertensive-to-hypertensive men and women. Participants were randomly assigned to a sequence of four 17 day dietary potassium treatments: a basal diet (control) of 60 mmol/d and three phases of 85 mmol/d added as potatoes, French fries, or a potassium gluconate supplement. Blood pressure was measured by manual auscultation, cutaneous microvascular and endothelial function by thermal hyperemia, utilizing laser Doppler flowmetry, and mineral retention by metabolic balance. There were no significant differences among treatments for end-of-treatment BP, change in BP over time, or endothelial function using a mixed-model ANOVA. However, there was a greater change in systolic blood pressure (SBP) over time by feeding baked/boiled potatoes compared with control (-6.0 mmHg vs. -2.6 mmHg; p = 0.011) using contrast analysis. Potassium retention was highest with supplements. Individuals with a higher cardiometabolic risk may benefit by increasing potassium intake. This trial was registered at ClinicalTrials.gov as NCT02697708.

Perspective: Framework for Developing Recommended Intakes of Bioactive Dietary Substances.

Dietary bioactives are food substances that promote health but are not essential to prevent typical deficiency conditions. Examples include lutein and zeaxanthin, omega-3 fatty acids, and flavonoids. When quality evidence is available, quantified intake recommendations linking dietary bioactives with specific health benefits will enable health professionals to provide evidence-based information to consumers. Without evidence-based recommendations, consumers use information from available sources that often lack standards and rigor. This article describes a framework to develop guidance based on quality evidence fully vetted for efficacy and safety by qualified experts, and designed to communicate the amounts of specific dietary bioactive compounds with identified health benefits. The 4-step Framework described here can be adapted by credible health organizations to work within their guideline development process. Standards of practice used in clinical guidelines are adapted to quantify dietary bioactive intake recommendations from foods consumed by the general public, by taking into account that side effects and trade-offs are often needed for medical treatments but are not acceptable for dietary bioactives. In quantifying dietary bioactive recommendations, this Framework establishes 4 decision-making steps: 1) characterize the bioactive, determine amounts in specific food sources, and quantify intakes; 2) evaluate safety; 3) quantify the causal relation between the specific bioactive and accepted markers of health or normal function via systematic evidence reviews; and 4) translate the evidence into a quantified bioactive intake statement. This Framework provides a working model that can be updated as new approaches are advanced.

Blueberry polyphenols alter gut microbiota & phenolic metabolism in rats.

Consuming polyphenol-rich fruits and vegetables, including blueberries, is associated with beneficial health outcomes. Interest in enhancing polyphenol intakes via dietary supplements has grown, though differences in fruit versus supplement matrix on gut microbiota and ultimate phenolic metabolism to bioactive metabolites are unknown. To evaluate this, 5-month-old, ovariectomized, Sprague-Dawley rats were gavaged for 90 d with a purified extract of blueberry polyphenols (0, 50, 250, or 1000 mg total polyphenols per kg bw per d) or lyophilized blueberries (50 mg total polyphenols per kg bw per d, equivalent to 150 g fresh blueberries per day in humans). Urine, feces, and tissues were assessed for gut microbiota and phenolic metabolism. Significant dose- and food matrix-dependent effects were observed at all endpoints measured. Gut microbial populations showed increased diversity at moderate doses but decreased diversity at high doses. Urinary phenolic metabolites were primarily observed as microbially derived metabolites and underwent extensive host xenobiotic phase II metabolism. Thus, blueberry polyphenols in fruit and supplements induce differences in gut microbial communities and phenolic metabolism, which may alter intended health effects.

Circulating Ionized Magnesium as a Measure of Supplement Bioavailability: Results from a Pilot Study for Randomized Clinical Trial.

Oral supplementation may improve the dietary intake of magnesium, which has been identified as a shortfall nutrient. We conducted a pilot study to evaluate appropriate methods for assessing responses to the ingestion of oral magnesium supplements, including ionized magnesium in whole blood (iMg2+) concentration, serum total magnesium concentration, and total urinary magnesium content. In a single-blinded crossover study, 17 healthy adults were randomly assigned to consume 300 mg of magnesium from MgCl2 (ReMag®, a picosized magnesium formulation) or placebo, while having a low-magnesium breakfast. Blood and urine samples were obtained for the measurement of iMg2+, serum total magnesium, and total urine magnesium, during 24 h following the magnesium supplement or placebo dosing. Bioavailability was assessed using area-under-the-curve (AUC) as well as maximum (Cmax) and time-to-maximum (Tmax) concentration. Depending on normality, data were expressed as the mean ± standard deviation or median (range), and differences between responses to MgCl2 or placebo were measured using the paired t-test or Wilcoxon signed-rank test. Following MgCl2 administration versus placebo administration, we observed significantly greater increases in iMg2+ concentrations (AUC = 1.51 ± 0.96 vs. 0.84 ± 0.82 mg/dL·24h; Cmax = 1.38 ± 0.13 vs. 1.32 ± 0.07 mg/dL, respectively; both p < 0.05) but not in serum total magnesium (AUC = 27.00 [0, 172.93] vs. 14.55 [0, 91.18] mg/dL·24h; Cmax = 2.38 [1.97, 4.01] vs. 2.24 [1.98, 4.31] mg/dL) or in urinary magnesium (AUC = 201.74 ± 161.63 vs. 139.30 ± 92.84 mg·24h; Cmax = 26.12 [12.91, 88.63] vs. 24.38 [13.51, 81.51] mg/dL; p > 0.05). Whole blood iMg2+ may be a more sensitive measure of acute oral intake of magnesium compared to serum and urinary magnesium and may be preferred for assessing supplement bioavailability.

Increasing Doses of Blueberry Polyphenols Alters Colonic Metabolism and Calcium Absorption in Ovariectomized Rats.

SCOPE: Blueberries are rich sources of bioactive polyphenols that may provide health benefits when consumed regularly, leading to their increased marketing as dietary supplements. However, the metabolic changes associated with consuming concentrated doses of purified polyphenols, as may be present in dietary supplements, are unknown, especially when considering the colonic metabolites formed. This study aimed to evaluate the pharmacokinetics of high doses of purified blueberry polyphenols. METHODS AND RESULTS: 5-month old, ovariectomized Sprague-Dawley rats are acutely dosed with purified blueberry polyphenols (0, 75, 350, and 1000 mg total polyphenols per kg body weight (bw)) and 45 Ca to measure calcium absorption. Blood and urine are collected for 48 h after dosing and phenolic metabolites measured via ultra high-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The most prominent metabolites are colonically generated cinnamic and hippuric acids. Smaller amounts of other phenolic acids, flavonols, and anthocyanins are also detected. Most metabolites follow a dose-response relationship, though several show saturated absorption. Maximal metabolite concentrations are reached within 12 h for a majority of compounds measured, while some (e.g., hippuric acid) peaked up to 24 h post-dosing. Calcium absorption is significantly increased in the highest dose group (p = 0.03). CONCLUSION: These results indicate that increased doses of blueberry polyphenols induce changes in intestinal phenolic metabolism and increase calcium absorption.

Use of Calcium Isotopic Tracers To Determine Factors That Perturb Calcium Metabolism.

Calcium plays an important role in maintaining bone health. Ensuring adequate calcium intake throughout life is essential for reaching greater peak bone mass in young adulthood and lowering osteoporotic fracture risk when aging. Calcium homeostasis involves a complex interaction between three organ systems: intestine, kidney, and bone. Metabolic balance plus kinetic studies using calcium isotopic tracers can estimate calcium metabolism parameters and pinpoint how organs and processes are perturbed by internal and external modifiers. Both modifiable factors (e.g., vitamin D supplementations and dietary bioactives) and non-modifiable factors (e.g., age, sex, and race) influence calcium utilization. Current evidence suggests that prebiotic fibers may offer an alternative approach to enhance calcium absorption through altering gut microbiota to ultimately improve bone health.

A 90 day oral toxicity study of blueberry polyphenols in ovariectomized sprague-dawley rats.

Regular consumption of polyphenol-rich fruits and vegetables is associated with beneficial health outcomes. To increase polyphenol intakes, consumers are increasingly using herbal and botanical dietary supplements containing concentrated polyphenol extracts. However, the safety of this consumption modality has not been vetted. To address this, ovariectomized Sprague-Dawley (OVX-SD) rats were orally gavaged with purified blueberry polyphenols at 0-1000 mg total polyphenols/kg bw/d for 90d. No differences in behavior, body weight, or food consumption were observed. No tumors or macroscopic changes were observed, and histopathological analyses showed no differences among groups. Although several statistically significant differences between treatment and control groups were observed in urine (color and pH) and blood (monocyte count, total cholesterol, and chloride ion concentration) analyses, these parameters were within normal ranges and not considered biologically significant. Intestinal permeability assessed via FITC-dextran showed increased intestinal permeability in the highest dose, though no morphological differences were found throughout the gastrointestinal tract. Given the lack of other systemic changes, this finding is likely of minimal physiological importance. These results indicate a NOAEL for blueberry polyphenols in OVX-SD rats is ≥ 1000 mg total polyphenols/kg bw/d, which translates to a 70 kg human consuming ~10 g polyphenols. Keywords: Blueberry, Polyphenol, Sub-chronic toxicity.

Calcium Supplement Use Is Associated With Less Bone Mineral Density Loss, But Does Not Lessen the Risk of Bone Fracture Across the Menopause Transition: Data From the Study of Women's Health Across the Nation.

Diet is a modifiable factor that is related to bone mass and risk for fractures; however, the use of calcium supplements for bone health is controversial, with little scientific agreement. The purpose of this analysis was to estimate the change in lumbar spine and femoral neck BMD and the risk of bone fracture by the use of calcium supplements among the Study of Women's Health Across the Nation (SWAN) participants. SWAN is a multicenter, multiethnic, community-based longitudinal cohort designed to examine the health of women across the menopause transition (n = 1490; aged 42 to 52 years at baseline in 1996 to 1997 and followed annually until 2006 to 2008). A mixed-effect model for repeated measures was used to estimate annualized BMD change across time between supplement users and nonusers, unadjusted or fully adjusted (age, race, height, weight, menopausal status [pre-, early peri-, late peri-, and postmenopausal], DXA scanner mode, alcohol intake, vitamin D supplement use, smoking, and physical activity) and a log-linear model with repeated measures was used to estimate the relative risk of fracture by calcium supplement use. All models were also stratified by baseline menopausal status. In fully adjusted models, calcium supplement use was associated with less annualized loss of femoral neck BMD (-0.0032 versus -0.0040 g/cm2/year; p < .001) and lumbar spine BMD (-0.0046 versus -0.0053 g/cm2/year, p = 0.021) in the complete cohort. However, this protective association of calcium supplement use with BMD loss was significant only among premenopausal women (femoral neck: -0.0032 versus -0.0042 g/cm2/year; p = 0.002; lumbar spine: -0.0038 versus -0.0050 g/cm2/year, p = 0.001); no significant differences in BMD were observed among women who were early perimenopausal by calcium supplement use at baseline. No significant differences in the relative risk of fracture were observed, regardless of baseline menopausal status. The use of calcium supplements was associated with less BMD loss over more than a decade, but was not related to the risk of incident bone fracture across the menopause transition. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.