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.

Crop, Host, and Gut Microbiome Variation Influence Precision Nutrition: An Example of Blueberries.

Epidemiological studies have shown associations between polyphenol-rich fruit intake and bone health, and preclinical studies have shown that blueberries improve bone health. To determine the genotype and dose of blueberries that are effective in ameliorating age-related bone loss, a multi-institutional team of investigators performed in vitro, preclinical, and clinical studies on blueberry varieties that differed in flavonoid profiles. Principal component analysis was used to select blueberry genotypes that varied in anthocyanin profiles. Total phenolic content did not predict the bioavailability of polyphenolic compounds in rats. A range in bioavailability was observed in individual polyphenolic compounds across genotypes. Both alpha and beta diversity analyses indicated that gut microbiome profiles varied with blueberry dose in rats. Additionally, the identification of specific taxa, such as Prevotellaceae_UCG-001 and Coriobacteriales, increasing after blueberry consumption adds to the mounting evidence of their role in polyphenol metabolism. All of the sources of variation can inform blueberry breeding practices to influence precision nutrition.

Effects of Plant-Based Protein Consumption on Kidney Function and Mineral Bone Disorder Outcomes in Adults With Stage 3-5 Chronic Kidney Disease: A Systematic Review.

INTRODUCTION: Plant-based protein is of growing interest for dietary management of chronic kidney disease (CKD) and is hypothesized to preserve kidney function and reduce CKD-mineral bone disorder (MBD) complications, among other benefits. This systematic review aimed to summarize the available clinical trial evidence for the effect of plant-based protein on kidney function and CKD-MBD outcomes in adults with stage 3-5 CKD not on dialysis. METHODS: Searches of Medline, Embase, Agricola, CAB abstracts, Web of Science, Scopus, and hand searching were performed. Clinical trials with ≥8 participants ≥18 years of age with an estimated glomerular filtration rate <60 mL/min/1.73 m2 but not on dialysis were included. Additionally, only clinical trials with ≥1-week interventions with ≥50% dietary protein from plant-based sources and reported at least one outcome for both kidney function and CKD-MBD outcomes were included. Of the 10,962 identified abstracts, 32 met inclusion criteria and were assessed for risk of bias. RESULTS: Results for kidney function and CKD-MBD outcomes were heterogenous, with most studies having suboptimal methodological quality. In most of the studies (27/32), protein source was altered only secondarily to low-protein diet interventions. Thus, data synthesis and interpretation were focused on a subset of five studies that investigated a change in protein source only (i.e., animal vs. plant). Of this subset, four studies reported no change in kidney function, while one study reported a decrease. Three studies reported no change in serum phosphorus, and one study reported lower serum phosphorus following a vegetarian diet. Further, limited data and inconclusive results were observed for phosphaturic hormones, parathyroid hormone, and fibroblast growth factor-23. CONCLUSION: Current clinical trial evidence on plant-based protein interventions for preserving kidney function and preventing CKD-MBD is limited to inform clinical guidelines at this time. This systematic review emphasizes the ongoing need to research the effects of plant-based protein on kidney function and CKD-MBD outcomes.

Acute High Dietary Phosphorus Following Low-Phosphorus Diet Acclimation Does Not Enhance Intestinal Fractional Phosphorus Absorption in Nephrectomized Male Rats.

Dietary phosphorus restriction and phosphorus binders are commonly prescribed for patients with chronic kidney disease (CKD). However, occurrences of non-adherence to these interventions are common. As low-phosphorus (LP) diets have been consistently experimentally shown in vitro to increase intestinal phosphorus absorption efficiency, a bout of non-adherence to diet or binders may cause an unintended consequence of enhanced intestinal phosphorus absorption. Thus, we aimed to determine the effect of a single bout of high-phosphorus (HP) intake after acclimation to a LP diet. Male Sprague Dawley rats with 5/6 nephrectomy (n = 36) or sham operation (n = 36) were block-randomized to 1 of 3 diets: LP (0.1% P w/w), HP (1.2%), or LP followed by acute HP (LPHP 0.1% then 1.2%). Phosphorus absorption tests were conducted using 33P radioisotope administrated by oral gavage or intravenously (iv). Although the overall two-way ANCOVA model for intestinal fractional phosphorus absorption was non-significant, exploratory comparisons showed intestinal fractional phosphorus absorption efficiency tended to be higher in rats in the LP compared with HP or LPHP groups. Rats in the HP or LPHP groups had higher plasma phosphorus compared with rats in the LP group, but the LPHP group was not different from the HP group. Gene expression of the major intestinal phosphate transporter, NaPi-2b, was lower in the jejunum of rats in the LPHP group compared with rats in the HP group but not different in the duodenum. These results demonstrate that an acute HP load after acclimation to a LP diet does not lead to enhanced intestinal fractional phosphorus absorption efficiency in 5/6 nephrectomized male rats. These data provide evidence against the notion that dietary phosphorus restriction or binder use adversely increases absorption efficiency after a single instance of dietary or binder non-adherence. However, other adverse consequences of fluctuating dietary phosphorus intake cannot be ruled out. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

(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.

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.

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.

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.

Lactose Intolerance and Bone Health: The Challenge of Ensuring Adequate Calcium Intake.

Calcium is an important nutrient with impact upon many biological systems, most notably bone. Ensuring adequate calcium intake throughout the lifespan is essential to building and maintaining bone. Lactose intolerance may predispose individuals to low calcium intake as the number of lactose-free, calcium-rich food sources is limited. In this review, we summarize data from human and animal studies on the influence of lactose and lactase deficiency on calcium absorption and bone health. Based on the available evidence, neither dietary lactose nor lactase deficiency have a significant impact on calcium absorption in adult humans. However, lactose intolerance may lead to reduced bone density and fragility fractures when accompanied by decreased intake or avoidance of dairy. Recently published human trials and meta-analyses suggest a weak but significant association between dairy consumption and bone health, particularly in children. Given the availability of simple dietary approaches to building lactose tolerance and the nutritional deficiencies associated with dairy avoidance, multiple public health organizations recommend that all individuals-including those that are lactose intolerant-consume three servings of dairy per day to ensure adequate nutrient intakes and optimal bone health.

What Is the Evidence Base for a Potassium Requirement?

Increased intake of potassium should be promoted to reduce the risk of cardiovascular disease and stroke and to protect against bone loss, but confidence in recommended intakes depends on the strength of the evidence. All public health recommendations are considerably higher than current average intakes. Evidence on which current potassium intake recommendations for the United States, Europe, and globally have limitations. More recent evidence reviewed by the Agency for Healthcare Research and Quality affirms that more evidence is needed to define specific values for optimal potassium intakes. Potassium requirements undoubtedly vary with a number of factors including energy needs, race, and intake of sodium.

Changes in phenolic content of commercial potato varieties through industrial processing and fresh preparation.

Reported content and process stability of phenolics in potato products is inconsistent. Changes in phenolic content of select varieties through fresh and industrial preparation/reconstitution were assessed. Total chlorogenic acids (CQAs) ranged from 43 to 953mg/100g dw and were more concentrated in pigmented compared to white/yellow-fleshed potatoes. Anthocyanin (ANC) content ranged from 18.6 to 22.9mg/100g dw and were mainly present in the flesh of pigmented potatoes. Retention of phenolics through commercial processing ranged from 49 to 85% for pigmented varieties and 32-55% for white/yellow. CQA levels were reduced through processing but to a greater extent in white relative to pigmented potatoes. ANCs were well retained through industrial processing of pigmented potatoes (79-129%). Levels of CQA were significantly (p<0.05) lower in some industrially versus freshly processed products but not for all products. While some differences exist, overall, industrially processed potato products compare favorably to fresh preparation in levels and recovery of phenolics.

Synthesis, Characterization, and Stoichiometric U-O Bond Scission in Uranyl Species Supported by Pyridine(diimine) Ligand Radicals.

Two uranium(VI) uranyl compounds, Cp*UO2((Mes)PDI(Me)) (3) and Cp*UO2((t)Bu-(Mes)PDI(Me)) (3-(t)Bu) (Cp* = 1,2,3,4,5-pentamethylcyclopentadienide; (Mes)PDI(Me) = 2,6-((Mes)N=CMe)2C5H3N; (t)Bu-(Mes)PDI(Me) = 2,6-((Mes)N=CMe)2-p-C(CH3)3C5H2N; Mes = 2,4,6-trimethylphenyl), have been synthesized by addition of N-methylmorpholine N-oxide to trianionic pyridine(diimine) uranium(IV) precursors, Cp*U((Mes)PDI(Me))(THF) (1), Cp*U((Mes)PDI(Me))(HMPA) (1-HMPA), and Cp*U((t)Bu-(Mes)PDI(Me))(THF) (1-(t)Bu). These uranyl complexes contain singly reduced pyridine(diimine) ligands suggesting formation occurs via cooperative ligand/metal oxidation. Treating 3 or 3-(t)Bu with stoichiometric equivalents of Me3SiI results in stepwise oxo silylation to form (Me3SiO)2UI2((Mes)PDI(Me)) (5) or (Me3SiO)UI2((t)Bu-(Mes)PDI(Me)) (5-(t)Bu), respectively. Additional equivalents result in full uranium-oxo bond scission and formation of UI4(1,4-dioxane)2 with extrusion of hexamethyldisiloxane. The uranium complexes have been characterized via multinuclear NMR, vibrational, and electronic absorption spectroscopies and, in some cases, X-ray crystallography.

Postharvest correlation between swordfish (Xiphius gladius) size and mercury concentration in edible tissues.

Total mercury was measured via thermal decomposition amalgamation atomic absorption spectroscopy in the muscle tissue of 82 swordfish originating in the Pacific Ocean and was found to range from 228 to 2,090 ppb. The relationships between total mercury concentration and the size of the fish (i.e., length and weight) were analyzed. It was found that dressed weight (DW) was a better predictor of mercury concentration than cleithrum-to-caudal keel length in a single variable model, and DW was the only significant predictor of mercury concentration in a multivariable model. Based on these relationships, swordfish with a DW greater than 96.4 kg (213 lb; 95% confidence interval, 88 to 107 kg [195 to 235 lb]) will exceed 1,000 ppb of mercury-the action level in the United States, Canada, and Europe-and should not be sold in commercial markets. Additionally, a logistic regression model was created to illustrate the probability of a swordfish at any DW being unsafe to consume (i.e., containing more than 1,000 ppb of mercury). In this model, the probability of a swordfish being unsafe exceeds the probability of being safe at 94.6 kg (209 lb). Taken together, the models presented in this report give regulators valuable postharvest tools to use for rapid determination of the safety of swordfish intended for sale in commercial markets.

A comparison of actual versus stated label amounts of EPA and DHA in commercial omega-3 dietary supplements in the United States.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with health benefits throughout life and are obtained primarily through fish and fish oil supplements. Due to the growing popularity of dietary supplements, 47 commercial fish, krill, and algal oil supplements were analyzed for EPA, DHA, and other fatty acids. RESULTS: For fish- and krill-based supplements, the range of EPA was 81.8 to 454.6 mg g(-1) oil and DHA was 51.6 to 220.4 mg g(-1) oil. For algal oil supplements, EPA ranged from 7.7 to 151.1 mg g(-1) oil and DHA ranged from 237.8 to 423.5 mg g(-1) oil. The percentage of the stated label amount for EPA and DHA ranged from 66 to 184% and 62 to 184%, respectively. Only 10 supplements (21% of those tested) had at least 100% of the stated label amount of EPA, while 12 supplements (25% of those tested) had at least 100% of the stated amount of DHA. Over 70% of the supplements tested did not contain the stated label amount of EPA or DHA. CONCLUSIONS: These results indicate that the quality of fish oil supplements is not being adequately monitored by manufacturers or government agencies and increased testing is needed to ensure regulatory compliance.

Mercury content in commercially available finfish in the United States.

Seventy-seven finfish species (300 composites of three fish) were obtained from commercial vendors in six regions of the United States: Great Lakes, mid-Atlantic, New England, northwest, southeast, and southwest. Total mercury in fish muscle tissue ranged from 1 ppb (channel catfish) to 1,425 ppb (king mackerel). Of the top 10 most commonly consumed seafoods in the United States, all finfish species, including salmon species (13 to 62 ppb), Alaskan pollock (11 ppb), tilapia (16 ppb), channel catfish (1 ppb), Atlantic cod (82 ppb), and pangasius (swai) (2 ppb), had low total mercury concentrations. However, two large predatory species, king mackerel and swordfish (1,107 ppb), contained mercury concentrations above the current U.S. Food and Drug Administration action level of 1,000 ppb, indicating that consumers may be unaware that species that are high in mercury are being sold in the marketplace.

Fatty acid profiles of commercially available finfish fillets in the United States.

Fillets of 76 finfish species (293 composites of three fish) were obtained from commercial seafood vendors in six regions of the United States (i.e., Great Lakes, Mid-Atlantic, New England, Northwest, Southeast, and Southwest). Full fatty acid profiles were determined for each species and are presented here. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been associated with many health benefits. Thus, fillets of each species were compared for total EPA plus DHA content, which ranged from 17 mg/100 g (pangasius/swai) to 2430 mg/100 g (Chilean sea bass). Of the top ten most popularly consumed seafoods in the US, finfish, including salmon species (717-1533 mg/100 g), Alaskan pollock (236 mg/100 g), tilapia (76 mg/100 g), channel catfish (44 mg/100 g), Atlantic cod (253 mg/100 g), and pangasius/swai (17 mg/100 g), exhibited a wide concentration range of EPA plus DHA. Large variances were found within many of the farmed species analyzed, which likely stems from dietary differences in the farm-fed diet. The results of this study provide current information on a broad range of species and will help nutritionists and the public make informed decisions regarding seafood consumption.

Multi-electron reduction facilitated by a trianionic pyridine(diimine) ligand.

Reduction of Cp*2UI(THF) with KC8 in the presence of a pyridine(diimine) ligand ((Mes)PDI(Me)) results in the formation of Cp*U(PDI)(THF), which features a triply reduced PDI ligand. This species performs four electron cleavage of azobenzene to generate the uranium bis(imido), Cp*(PDI)U(NPh)2.

Reductive heterocoupling mediated by Cp*2U(2,2'-bpy).

Trivalent Cp*(2)U(2,2'-bpy) (2) (Cp* = C(5)Me(5), 2,2'-bpy = 2,2'-bipyridine), which has a monoanionic bipyridine, was treated with p-tolualdehyde (a), furfuraldehyde (b), acetone (c), and benzophenone (d). Reduction of the C[double bond, length as m-dash]O bond followed by radical coupling with bipyridine forms the U(iv) derivatives [Cp*(2)U(2,2'-bpy)(OCRR')] (3a-d).