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Objectives: Brain-derived neurotrophic factor (BDNF) plays an essential role in brain and metabolic health. The fact that higher concentrations are associated with improved cognitive performance has resulted in numerous intervention trials that aim at elevating BDNF levels. This systematic review provides an overview of the relation between various nutritional factors and BDNF concentrations in controlled human intervention studies. Methods: A systematic search in May 2020 identified 48 articles that examined the effects of dietary patterns or foods (n = 3), diets based on energy intake (n = 7), vitamins and minerals (n = 7), polyphenols (n = 11), long-chain omega-3 polyunsaturated fatty acids (n = 5), probiotics (n = 8), and miscellaneous food supplements (n = 7). Results: In particular, studies with dietary patterns or foods showed increased peripheral BDNF concentrations. There are also strong indications that polyphenols tend to have a positive effect on BDNF concentrations. Four of the 11 included studies with a polyphenol intervention showed a significant increase in BDNF concentrations, one study showed an increase but this was not statistically analyzed, and two studies showed a trend to an increase. Discussion: The two polyphenol classes, phenolic acids, and other phenolic compounds were responsible for the significant effects. No clear effect was found for the other dietary factors, which might also be related to whether serum or plasma was used for BDNF analysis. More work is needed to understand the relation between peripheral and central BDNF concentrations.

Objectives: Brain-derived neurotrophic factor (BDNF) plays an essential role in brain and metabolic health. The fact that higher concentrations are associated with improved cognitive performance has resulted in numerous intervention trials that aim at elevating BDNF levels. This systematic review provides an overview of the relation between various nutritional factors and BDNF concentrations in controlled human intervention studies. Methods: A systematic search in May 2020 identified 48 articles that examined the effects of dietary patterns or foods (n = 3), diets based on energy intake (n = 7), vitamins and minerals (n = 7), polyphenols (n = 11), long-chain omega-3 polyunsaturated fatty acids (n = 5), probiotics (n = 8), and miscellaneous food supplements (n = 7). Results: In particular, studies with dietary patterns or foods showed increased peripheral BDNF concentrations. There are also strong indications that polyphenols tend to have a positive effect on BDNF concentrations. Four of the 11 included studies with a polyphenol intervention showed a significant increase in BDNF concentrations, one study showed an increase but this was not statistically analyzed, and two studies showed a trend to an increase. Discussion: The two polyphenol classes, phenolic acids, and other phenolic compounds were responsible for the significant effects. No clear effect was found for the other dietary factors, which might also be related to whether serum or plasma was used for BDNF analysis. More work is needed to understand the relation between peripheral and central BDNF concentrations.

The coronavirus disease 2019 (COVID-19) pandemic is the largest health crisis ever faced worldwide. It has resulted in great health and economic costs because no effective treatment is currently available. Since infected persons vary in presentation from healthy asymptomatic mild symptoms to those who need intensive care support and eventually succumb to the disease, this illness is considered to depend primarily on individual immunity. Demographic distribution and disease severity in several regions of the world vary; therefore, it is believed that natural inherent immunity provided through dietary sources and traditional medicines could play an important role in infection prevention and disease progression. People can boost their immunity to prevent them from infection after COVID-19 exposure and can reduce their inflammatory reactions to protect their organ deterioration in case suffering from the disease. Some drugs with in-situ immunomodulatory and anti-inflammatory activity are also identified as adjunctive therapy in the COVID-19 era. This review discusses the importance of COVID-19 interactions with immune cells and inflammatory cells; and further emphasizes the possible pathways related with traditional herbs, medications and nutritional products. We believe that such pathophysiological pathway approach treatment is rational and important for future development of new therapeutic agents for prevention or cure of COVID-19 infection.

Several studies have shown that diets containing lower vitamin D than in the AIN-93G diet do not compromise bone structure, bone mineral density (BMD), and/or bone strength in male and female mice. This study determined if a diet containing low vitamin D from prepregnancy through to the end of lactation maintained these bone outcomes to a similar extent as a high vitamin D diet. Mice were fed an AIN-93G diet with 25 (LD diet) or 5000 (HD diet) IU vitamin D/kg diet from premating through to lactation (n = 15/group). Of the major structure outcomes, only cortical area fraction of the distal femur was lower (P, The study findings suggest that the level of bone-supporting nutrients such as vitamin D should be part of the conversation regarding a potential revision of the AIN-93 diets.

OBJECTIVES: The purpose of this study was to investigate the relationship between dietary Mg intake and concentrations of ionized magnesium (iMg(+2)) in whole blood and total Mg in serum. METHODS: We evaluated blood iMg(+2) concentration, the physiological active measure of Mg, as well as serum Mg concentration which is a more commonly used measure of body's status. The data study population were healthy participants (18–52 years; n = 23) who participated in three clinical visits in a magnesium supplement bioavailability study. All study participants were not taking Mg supplements within two weeks of study screening. Dietary Mg intake obtained from 3-day food records was compared with iMg(+2) in whole blood and total Mg in serum concentrations using Pearson's correlations. Ionized magnesium was measured with NOVA 8 (NOVA Biochemical, Waltham, MA), serum Mg was measured with atomic absorption spectroscopy, and dietary intake of Mg was assessed using the Nutrition Data System for Research (NDSR; University of Minnesota, MN). Results were reported as means (standard deviations) and percentages for continuous and categorical data, respectively. RESULTS: Mean iMg(+2) and serum Mg concentrations, and dietary Mg intake were 1.27 (0.07) mg/dL, 2.20 (5.0) mg/dL and 304.05 (128.77) mg/day, respectively. Results from the Pearson's correlation coefficient showed no significant association between dietary Mg intake vs. and serum Mg (r = −0.30, p = 0.23), nor was there a significant association between dietary Mg intake and iMg(+2) (r = −0.08, p = 0.74). CONCLUSIONS: Our findings suggest that iMg(+2) and serum Mg concentrations may not reflect dietary Mg intake in a significant manner. Further research is needed to identify objective and accurate biomarkers that reflect dietary Mg intake, which will enable a better understanding of Mg deficiency and its association with conditions such as cardiovascular diseases, hypertension, diabetes, and chronic kidney disease. FUNDING SOURCES: An unrestricted educational grant from New Capstone Inc., the manufacturer of ReMag®.

OBJECTIVES: Investigate the impact of variable vitamin K (VK) intakes on the coagulation activities of four VK-dependent factors and clotting times, in warfarin-treated rats. METHODS: Male Wistar rats were randomly allocated to a AIN-93 based diet containing low (L: 80 mcg/kg/d), adequate (A: 750 mcg/kg/d) or enriched (E: 2000 mcg/kg/d) phylloquinone (K1) containing diet (n = 24/diet group). After one week, half the animals from each diet group were randomly allocated to receive 0.2 mg warfarin/kg/d through drinking water (W gp) or plain water (C gp), for 10 weeks. Coagulation activity (%) was assessed for factors II, VII, IX and X, and clotting times were based on prothrombin [PT (sec)] and activated thromboplastin times [APTT (sec)]. Measures were obtained at the end of the study and were conducted in the hospital clinical laboratory using standard procedures. Diet effects within C and W groups were investigated using one-way ANOVA and uncorrected Fisher post-hoc tests. RESULTS: Warfarin treatment resulted in significantly higher clotting times (PT and APTT) in all diet groups when compared to corresponding C groups (p

OBJECTIVES: Iron deficiency is one of the most common nutrient deficiencies worldwide. Adaptive thermogenesis plays a critical role for maintaining energy homeostasis. Currently, the role of dietary iron deficiency on adaptive thermogenesis is unknown. We hypothesized that dietary iron deficiency attenuates adaptive thermogenesis via dysfunctional iron metabolism in adipose tissue. METHODS: C57BL/6 male mice were fed a diet containing either adequate-iron (Cont: 35ppm) or deficient-iron (ID: 3ppm) throughout for 14 weeks and the last 10 weeks were fed a high-fat diet to induce obesity. Systemic iron status was evaluated by measuring serum ferritin, hemoglobin (Hb), and hematocrit (HCt). The iron content of adipose tissue was determined by ICP-MS spectrometer. The protein and gene expressions related to iron-handling and thermogenesis were measured in adipose tissue by Western blot analysis and qPCR. To assess adaptive thermogenic function, mice were exposed to cold temperature acutely (3 hour) or administrated with β3-adrenoceptor agonist (CL) for 5 days. The core body temperature and thermogenesis were determined by a rectal thermometer and infrared camera, respectively. RESULTS: The ID mice displayed a non-anemic iron deficiency with reduced serum ferritin (p

OBJECTIVES: To investigate the effects of vitamin K2 supplementation on the prevention and treatment of rheumatoid arthritis(RA). METHODS: Vitamin K2 and rheumatoid arthritis were searched in Pubmed from inception until December 2020. RESULTS: Study 1: Vitamin K2 inhibited the proliferation of mitogen-activated PBMCs of RA patients with an IC50 value of 3,288.47 ± 4,910.02 ng/mL. There was a significant correlation between IC50 values of vitamin K2 and patient-related factors of RA patients (p

OBJECTIVES: While the replacement of folic acid (FA) with the bioactive folate form 5-methyltetrahydrofolate (MTHF) is gaining popularity, a comparison of their effects during pregnancy is limited. In a comparison of maternal intakes of FA and MTHF at recommended or high (5X) doses in Wistar rat dams, we found that dams fed 5X MTHF gained > 70% more weight and ate 8% more food to 19-weeks post weaning (PW) than those fed the high FA diet (Nutrients. 2021;13:48). However, both high dose diets resulted in dysregulation of leptin and central energy regulatory systems. The objective of this study was to compare the effect of gestational FA and MTHF diets on metabolic response and leptin-dependent hypothalamic energy-regulatory genes in the brain of their female offspring. METHODS: Pregnant Wistar rats were fed an AIN-93G diet with 1X recommended (2mg/kg diet) or 5X FA or equimolar MTHF. At weaning, female offspring were fed a high-fat diet until 19-weeks PW. Body weight, food intake, adiposity, plasma leptin, and gene expression of leptin signaling and related candidate genes in the hypothalamus were measured. RESULTS: Similar to the mothers, the 5X-MTHF gestational diet resulted in offspring with higher weight (>15%, P 1.5-fold, P

OBJECTIVES: Thiamine acts as a coenzyme (prosthetic group) after converting to thiamine pyrophosphate in crucial metabolic enzymes of pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and transketolase. Theoretically, thiamine should not be consumed by an increase in the number of substrates for those enzymes. However, thiamine is often described to be consumed by excessive carbohydrate intake. Such a possible misunderstanding is assessed in the relevant literature. METHODS: The original paper (Elmadfa, et al. Int J Vitam Nutr Res 2001), which seems to mislead the reader into considering an increase in thiamine requirement for excessive carbohydrate intake, and the relevant papers were reviewed. RESULTS: The original paper demonstrated that increases in carbohydrate intake from 55% to 65% and 75% of total energy caused decreases in plasma and urine concentrations of thiamine, while erythrocyte transketolase activity remained unchanged. This seems to misleadingly support the idea that excessive carbohydrate intake increases the thiamine requirement for carbohydrate metabolism. It could be interpreted as the decreases of thiamine concentrations were observed only during an adaptation period. It was reported that diabetic patients had low plasma thiamine levels in association with increased renal clearance and fractional excretion of thiamine, without a decrease in erythrocyte transketolase activity (Thornalley, et al. Diabetologia 2007). As a similar case of possible misinterpretation, a case report (Watson, et al. Ir J Med Sci 1981) demonstrated that glucose loading precipitated thiamine deficiency in malnourished patients with latent thiamine deficiency. CONCLUSIONS: From the relevant literature, it is inferred that excessive carbohydrate intake in people without hyperglycemia could lead to a small increase, if any, in urinary thiamine excretion, but not to an increase in thiamine requirement for glucose metabolism. Even in the academic field, it seems that thiamine is often misunderstood to be consumed by excessive carbohydrate intake. FUNDING SOURCES: None.

OBJECTIVES: High folic acid (FA) intake may be associated with adverse health outcomes, including colon cancer promotion. 5-methyltetrahydrofolate (5MTHF) has been proposed as a safer alternative form of folate supplementation. We compared the effects of FA and 5MTHF supplementation on the progression of aberrant crypt foci (ACF; earliest colon cancer precursor). METHODS: Male Sprague Dawley rats (n = 120) received a control diet (1mg FA or equimolar 5MTHF) at weaning and ACF were induced by azoxymethane. Six weeks post-induction, rats were randomized to the control or supplemental (10mg FA or equimolar 5MTHF) diets for 18 weeks. Plasma folate concentrations were assessed using microbiological assay and compared. Colorectal tumor incidence, multiplicity and burden (sum of tumor diameters) were determined and compared. RESULTS: 5MTHF resulted in higher plasma folate concentration compared to FA (p

OBJECTIVES: Cognitive decline is a major public health issue among older adults. Dietary supplement use is common among older adults, and a concern has been raised about high folic acid intake among those with vitamin B12 (vB12) deficiency and exacerbation of cognitive decline. We evaluated supplement intake and folate and vB12 concentrations among older adults with measured cognitive function. METHODS: We used NHANES 2011–2014 data on adults aged 60 + years (n = 3266) and estimated folic acid and vB12 intake from dietary supplements. We defined vB12 insufficiency as serum vB12 concentration ≤ 258 pmol/L and high folate concentrations as either serum folate ≥ 59 nmol/L or RBC folate ≥ 1609 nmol/L. Cognitive impairment was defined as a test score

OBJECTIVES: Calcium (Ca(2+)) is a vital micronutrient for many physiological functions with the greatest rate of accumulation occurring during the critical period of infancy. Previous work has demonstrated that molecular mechanisms of intestinal Ca(2+) absorption across the small intestine are significantly different in animal models of infants and adults to permit greater absorption early in life. The colon contributes to overall Ca(2+) balance in adults via transcellular, TRPV6 mediated and paracellular claudin-2 and -12 mediated pathways. Whether these same colonic pathways contribute to overall Ca(2+) absorption in infants is not known. Here we aimed to investigate the molecular details of Ca(2+) absorption across the large intestine in murine models of infancy relative to older mice. METHODS: Mice at 14 days (P14) were used as a model of suckling infants and mice at 2 months were employed to represent adult physiology. Wildtype and mutant mice with a non-functioning Trpv6 or deletions of Cldn2 or Cldn12 were used. Net (45)Ca(2+) flux (J(Ca)) and Ca(2+) permeability (P(Ca)) were measured in Ussing chambers. Gene expression was determined by real-time PCR. RESULTS: J(Ca) indicates net absorption across the colon at both P14 and 2 months. While gene expression of Trpv6 and S100g suggest greater cellular uptake of Ca(2+) into colonocytes at P14, net J(Ca) in vitro was not different than at 2 months. In contrast to previous work in mice at 2 months, TRPV6 does not mediate J(Ca) at P14. P(Ca) was 20% greater at P14 than 2 months, suggesting greater capacity for bidirectional diffusion of Ca(2+) down an electrochemical gradient in younger mice. In contrast to previous work in mice at 2 months, claudin-2 and claudin-12 do not mediate P(Ca) at P14 and, expression of Cldn2 and Cldn12 were significantly reduced in younger mice. CONCLUSIONS: These results improve our understanding of intestinal Ca(2+) handling during a critical age early in life. Future work is required to delineate molecular details under in vivo conditions of colonic Ca(2+) transport in infants. FUNDING SOURCES: This work was funded by grants from the Women and Children's Health Research Institute, which is supported by the Stollery Children's Hospital Foundation, and the National Sciences and Engineering Research Council to RTA, who is the Canada Research Chair in Renal Epithelial Transport Physiology.

OBJECTIVES: Zinc is an essential nutrient for diverse biological processes in the body. Cellular zinc homeostasis is established through differential expressions of the transmembrane zinc transporter proteins, ZnTs and ZIPs. The aims of the current studies were to elucidate the roles of cellular zinc in erythrocyte maturation, and to determine the zinc transporters essential to erythroid zinc homeostasis. METHODS: G1E-ER4 mouse cells were employed as an in vitro study model of terminal erythroid differentiation. A cell-impermeable zinc chelator, diethylenetriamine pentaacetate (DTPA), was used to limit extracellular zinc availability. For gene silencing, gene-specific siRNAs were introduced to cells via Nucleofection. Functional impacts of zinc and gene deficiency were assessed via ICP-MS-based metal quantitation, heme assays, and gene expression assays using RNA-seq, qPCR, and western analyses. RESULTS: G1E-ER4 cells featured a 1.7-fold increase in total cellular zinc contents after 48 h of differentiation. Restriction of zinc import by 50 µM of DTPA led to less red coloration and lower increases in mean corpuscular hemoglobin contents by development. The heme deficiency by DTPA was fully restored by the addition of equimolar zinc, and was not due to changes in cellular iron contents. Zinc-deficient G1E-ER4 cells differentiated with normal Alas2 and Hbb-b1 transcript responses, but less Alad and alpha-globin expressions. Among the 24 zinc transporter genes, Zip10 produced the most prominent response to zinc restriction in differentiating erythroid cells. ZIP10-deficient G1E-ER4 cells were less efficient than control cells in hemoglobin production under zinc restriction. ZIP10 deficiency alone had no effects on the molecular indices of red cell hemoglobinization. CONCLUSIONS: Our studies characterize zinc as a nutrient essential to normal erythroid maturation and heme synthesis. Moreover, we have identified a compensatory role of ZIP10 for erythroid zinc homeostasis during zinc restriction. Thus, poor zinc status and ZIP10 mutations might serve as potential risk factors and thus new therapeutic targets for anemia and other erythrocyte-related disorders. FUNDING SOURCES: Supported by CFANS Graduate Fellowship to JK, and the Allen Foundation, Inc. and USDA NIFA Hatch Funds to M-SR.

OBJECTIVES: The purpose of this secondary outcome analysis is to investigate whether small-quantity lipid-based nutrient supplements (SQ-LNS) alters lipid, protein or glycan composition, or the cholesterol efflux capacity (CEC), of high-density lipoprotein (HDL) particles in children in the International Lipid-Based Nutrient Supplements (iLiNS) DYAD trial in Ghana. METHODS: Plasma samples were obtained from a subcohort of 80 children at 18 months of age from the iLiNS-DYAD-Ghana trial. Mothers were randomized to either iron and folic acid (IFA) in pregnancy and 200 mg/d calcium for 6 months postpartum or SQ-LNS (pregnancy and 6 months postpartum). Children in the SQ-LNS group received SQ-LNS from 6 to 18 months while children in the IFA group did not receive supplements. HDL was isolated from plasma by sequential ultracentrifugation followed by size-exclusion chromatography. Assay of cholesterol efflux was performed in vitro, and glycoproteomic and lipidomic composition were analyzed by mass spectrometry. The primary analysis was a comparison of the effects of intervention groups on HDL lipidome, proteome, and CEC. In the exploratory analysis, we compared the enrichment of glycopeptides in measured HDL-associated proteins between groups. RESULTS: Mean (±SD) HDL CEC was higher among children in the SQ-LNS vs. IFA group (20.9 ± 4.1% vs. 19.4 ± 3.3%; one-tailed p = 0.038). We found no differences in HDL lipidomic or proteomic composition between groups. CONCLUSIONS: Prenatal and postnatal SQ-LNS may improve the CEC of child HDL particles. These improvements may have a potential impact on child health outcomes. FUNDING SOURCES: Supported by Bill & Melinda Gates Foundation grant to the University of California, Davis.

OBJECTIVES: The work was carried out to compare the quantity of vitamin C in two commonly consumed species of pineapple in Nigeria; Honey Queen Pineapple (indigenous) and Brazza imported from Republic of Benin. This is expedient because complaints of gastro-intestinal tract problems often emerge after consumption of Brazza specie. METHODS: Seven of both species were cleaned, peeled, flesh separated from hard core making seven flesh portions, seven hard core each. All flesh portions of each specie were blended separately into paste as well as the core. Four portions were the end result Brazza Pineapple Core (BRPC); Brazza Pineapple Flesh (BRPF); Honey Queen Pineapple Core (HQPC) and Honey Queen Pineapple Flesh (HQPF). Standard solutions of ascorbic acid was prepared by weighing 0.5g of standard ascorbic acid and dissolved in 10ml of 0.1 molar phosphoric acid solution to obtain a concentration. Hundred millimeters of each sample was poured in sterile tubes and centrifuged at 6000rpm for five minutes, poured into sterile sample bottles and filtered with muslin cloth to have clearer sample and stored in sterile sample bottles. 20ml of each prepared fruit juice samples solution was injected into the HPLC machine in triplicates. The flow rate was 0.8ml/min. The ascorbic acid was detected at 245nm using Agilent Variable Wavelength Detector. Linear curve was done by plotting concentration versus average detector response. RESULTS: The quantity of vitamin C in each sample was estimated from the standard curve calibration from the HPLC using the formular- Quantity = Curve Area-324.26 34.79. Vitamin C content in BRPC was 2.8ug/ml; BRPF 16ug/ml; HQPC 1.10ug/ml and HQPF 1.17ug/ml. Vitamin C concentration was derived by multiplying these results by 50. Amount of vitamin C per gram was 126.75 ug/g; 726.61 ug/g; 76.96 ug/g and 53.13 ug/g respectively. CONCLUSIONS: It has been proven that the Brazza specie from the neighbouring country contains more than 10 times higher than the Nigeria local specie. Nutritionist/dietitian advice should be sought before individuals who react negatively to high doses of vitamin C consume Brazza pineapple specie. FUNDING SOURCES: It is a self funded project.

OBJECTIVES: In vitro dissolution tests are valuable first-step tools in the development of bioavailable delivery systems, making it possible to assess the performance of novel technologies in releasing active ingredients through the amount dissolved in a dissolution medium. The objective of this study was to evaluate whether phosphatidyl choline-enriched lipid encapsulation releases the majority of vitamin C as ascorbic acid past the stomach in a standard in vitro dissolution procedure and to assess the release profile. METHODS: A novel phosphatidyl choline-enriched lipid encapsulation that is solid at room temperature was tested for dissolution in a standard dissolution apparatus according to compendial United States Pharmacopeia methods, as per Good Manufacturing Practices for dietary supplements. One serving (included 1000 mg ascorbic acid) was placed into vessels containing simulated gastric fluid (0.1 M HCl) for 120 minutes then changed to simulated intestinal fluid (buffered 2% sodium lauryl sulfate, pH 6.8) for an additional 360 minutes. Aliquots were tested for ascorbic acid concentration at 8 time points by titration. The data was compared with 1000 mg of regular ascorbic acid in a capsule format. RESULTS: The phosphatidyl choline-enriched lipid encapsulation released 36% of the vitamin C at 2 hours in the acid phase and released 56% at 3 hours, 67% at 4 hours, 85% at 6 hours and 98% at 8 hours in the intestinal phase. Regular vitamin C filled capsules released 100% of the vitamin C at 30 minutes. CONCLUSIONS: The dissolution results indicated that phosphatidyl choline-enriched lipid encapsulation can pass the stomach and release the majority of vitamin C in the small intestine. The encapsulation demonstrated a sustained and prolonged release of vitamin C over an 8 hour period. The release profile observed in this in vitro study suggests phosphatidyl choline-enriched lipid encapsulation may improve nutrient absorption and bioavailability which requires further testing including human clinical trials. FUNDING SOURCES: This study was supported by Lonza (Greenwood, SC) and Ritual (Natals Inc, Los Angeles, CA).

OBJECTIVES: To develop a compartmental model which describes vitamin B-6 metabolism in the blood and tissues of the mouse under a variety of circumstances and to develop a computer application which can utilize the data to display the movement of tracer through the various compartments. METHODS: A circulation model was developed. Literature data from vitamin B-6 feeding studies and tracer experiments were used to develop an appropriate compartmental model using the SAAM II program (The Epsilon Group, Charlottesville, VA). A web-based application transforms the mass and flux data into intuitive and interactive graphical illustrations. RESULTS: Describing the interconversions between pyridoxine, pyridoxine 5’-phosphate, pyridoxal, pyridoxal 5’-phosphate, pyridoxamine, pyridoxamine 5’-phosphate and 4-pyridoxic acid in multiple tissues required 231 compartments. The largest amount of data deals with liver and brain. The model includes less detailed information on plasma, erythrocytes, gut, bone, muscle, heart, kidney, skin, adipose tissue and lung. The model includes adjustments to food intake, water intake, cardiac output, binding sites and Vmax values for enzymes based on the specified body weight of experimental animals. We did not include growth curves at this time. The model uses two parallel systems to monitor the steady state of endogenous metabolites as well as following tracer administration. Binding mechanisms are included to provide conservation of vitamin B-6 when intake is reduced. The model provides reasonable agreement with literature data on various vitamin B-6 intakes as well as oral and intravenous administration of tracer. It also reveals some areas which need clarification. For example, we have not found any detailed analysis of vitamin B-6 metabolites in mouse urine. There is little pyridoxic acid in plasma or urine suggesting that pyridoxic acid may not be the primary end product for vitamin B-6 in the mouse. The visualization application shows changes in the content of all 231 compartments over time illustrating the value of such computer applications in the interpretation of large, complex models. CONCLUSIONS: This model facilitates the simulation of various dietary and physiological conditions on vitamin B-6 metabolism in mice. We hope to adapt it to rats, pigs and humans. FUNDING SOURCES: Purdue University Fort Wayne.

OBJECTIVES: Gestational diabetes (GDM) is associated with adverse outcomes in both mother and child. Women with diabetes and obesity (BMI ≥ 30kg/m(2)) are recommended to take more folic acid than recommended for healthy women, to prevent birth defects. However, little is known about the effects of high folic acid supplementation in GDM. The objective of this study was to determine if folic acid supplementation in a mouse model of GDM affects maternal and fetal metabolic health. METHODS: Female (C57BL/6J) mice were fed from weaning a control diet (10% kcal fat; control dams) or western diet (45% kcal fat; western dams; model of GDM) with (10mg/kg diet) or without (2mg/kg diet) supplemental folic acid (SFA). Dams were fed for 13 weeks prior to breeding. Physiological assessments of glucose homeostasis were conducted before breeding. Tissues were collected at gestational day 18.5 RESULTS: Western dams had greater adiposity (p

OBJECTIVES: The prenatal period is a critical time for fetal development, programming the offspring's later-life health in response to the postnatal environment. We have shown that a high maternal choline diet programs long-term energy regulation leading to higher food intake and weight-gain in mature rat offspring fed a normal fat diet. However, the offspring's response to an obesogenic post-weaning diet has not been described. We aim to elucidate the interaction between the choline content of the gestational diet (GD) and fat content of the post-weaning diet (PWD) on male Wistar rat offspring's long-term metabolic phenotype. METHODS: Pregnant Wistar rats were fed an AIN-93G diet with either recommended choline (RC, 1g/kg diet choline bitartrate) or high choline (HC, 2.5-fold). Male pups were weaned to either a normal (10%) fat (RC-NF and HC-NF) or a high (45%) fat (RC-HF and HC-HF) diet for 17 weeks. Dependent measures were body weight, food intake, visceral adiposity, plasma glucoregulatory hormones and triglycerides, and plasma and hepatic free fatty acids (FFAs). Data were analyzed with 2-way ANOVA for main effects of GD and PWD and their interaction. Measures with significant interaction effects were followed by a Student's T-test comparing groups stratified by PWD. RESULTS: HC-HF offspring had lower body weight (7%, P

OBJECTIVES: Chronic inflammation and selenium deficiency are common in persons infected with the human immunodeficiency virus (HIV). Both C-reactive protein, a pro-inflammatory biomarker, and selenium deficiency have been associated with accelerated disease progression and poorer survival among persons infected with HIV-infection. However, research on the role of serum selenium levels in inflammation is limited. We assessed the association between serum selenium levels and C-reactive protein (CRP) concentrations in a cohort of persons infected with HIV. METHODS: A cross-sectional survey was conducted among 233 HIV-infected persons (124 men and 109 women) aged 18–60 years who were residing in Kathmandu, Nepal. Regular serum CRP and selenium concentrations were measured by the latex agglutination turbidimetric and the atomic absorption method, respectively. Relationships were assessed using multiple linear regression analysis to adjust for potential confounding factors including sociodemographic, smoking, body mass index, chronic diseases, CD4(+) T-cell count, and anti-retroviral therapy. RESULTS: The geometric means of serum selenium and CRP concentrations were 9.65 µg/dL and 1.43 mg/L, respectively. Mean serum CRP concentration was significantly decreased with increasing serum selenium concentration across selenium tertiles (P for trend = 0.019), with mean serum CRP concentration in the highest tertile of serum selenium concentration was 40.8% lower than that in the lowest tertile. We found a significant inverse relation between log selenium and log CRP concentrations (beta for 1 unit change in log selenium; β = −1.01, p = 0.06). CONCLUSIONS: Serum selenium levels may be inversely associated with serum CRP concentrations in persons infected with HIV. Further prospective study to confirm the role of serum selenium levels in inflammation among persons infected with HIV is warranted. FUNDING SOURCES: University of Massachusetts Amherst.

OBJECTIVES: Bioequivalence of vitamin E and folate in a single oral dose multivitamin (MVI) gummy or tablet. METHODS: This crossover clinical trial involved healthy adults randomized to either gummy or tablet MVI containing vitamin E (VE – 279 IU gummy; 239 IU tablet) and folate (1860 µg gummy; 1877 µg tablet) as a single dose in Phase 1 with blood samples collected at pre-dose and 0.5-, 1-, 2-, 4-, 6-, 8-, 9-, 10-, 24-, and 48-hours after dosing, followed by a 2-week washout period. In Phase 2, participants crossed over to receive MVI in the form not previously given, with blood draws at the same timepoints. Maximum Concentration (Cmax), Time of Maximum Concentration (Tmax), and Area Under the Curve (AUC) were calculated for each subject for both vitamin forms. Bioequivalence for AUC, Tmax, and Cmax was defined as a 90% confidence interval (CI) for the gummy to tablet comparator ratio of the geometric mean between 80% and 125%. RESULTS: Nineteen participants completed the study. Both gummy and tablet demonstrated absorption for both vitamins. The ratio of geometric means demonstrated bioequivalence between gummy and tablet for both VE and folate with both AUC and Cmax. While bioequivalence was also demonstrated for VE with Tmax, folate absorption peaked earlier in the gummy group (Tmax 1.89 hrs) than the tablet group (Tmax 4.00 hrs), shifting Cmax values in the gummy group to earlier timepoints than in the tablet group without affecting total absorption AUC. These results were consistent with a previous pilot study. CONCLUSIONS: Overall, under the conditions of this study, both gummy and tablet showed similar absorption of vitamin E and folate. FUNDING SOURCES: Church & Dwight Co., Inc.

OBJECTIVES: The 2013 Palestinian Micronutrient Survey(1) reported high and comparable 1(st) trimester prevalences of micronutrient deficiencies in the Gaza Strip and West Bank: 23.6% and 21.3% for iron, 67.9% and 49.6% for zinc, 11.4% and 8.8% for vitamin A, 27.9% and 19.1% for B(12), 78.6% and 66.7% for vitamin D and 17.5% and 13.2% for vitamin E, respectively. Rates were generally higher among gravida in their 2(nd)-3(rd) trimesters. Interim, clinic-based, anemia rates(2) in the Gaza Strip and West Bank of 32% and 19% in the first trimester and 71% and 38% in the 2(nd) and 3(rd) trimesters, respectively, coupled with food insecurity, dietary inadequacy, civil conflict and stresses from the COVID-19 pandemic, suggest micronutrient deficiencies persist as a public health burden in the State of Palestine. To replace current iron-folic acid (IFA) with a multiple micronutrient supplement (MMS) providing a Recommended Dietary Allowance of 15 essential vitamins and minerals as standard of antenatal care (ANC) in UNWRA clinics and hot spots serving pregnant women in the Gaza (n = 22) in 2021–2 and West Bank (n = 44) in 2022–3. METHODS: MMS is planned to start in Gaza in the Fall of 2021, where UNRWA antenatal services reach ∼38,000 pregnant women with IFA each year; ∼97% of whom attended ANC ≥ 4 times(2). Implementation will follow a randomized, step-wedge procedure whereby MMS will start in the 1(st) 11 clinics, and six months later, the 2(nd) group of 11 clinics, providing a design for monitoring and comparing the new MMS to existing IFA programs during an initial 6–8 month period. RESULTS: Outcomes will include indicators of adoption, acceptability, coverage, adherence, fidelity, cost-efficiencies and, as a routine clinical outcome, late pregnancy anemia. CONCLUSIONS: Maternal micronutrient deficiencies are common in Palestine(3), meriting replacing IFA with MMS. This research protocol will evaluate implementation in the Gaza Strip to provide guidance for launching and improving antenatal MMS delivery throughout the UNRWA health system. FUNDING SOURCES: UNWRA, Sight and Life, Kirk Humanitarian, Vitamin Angels Alliance, Ministry of Foreign Affairs of Japan, Palestine Ministry of Health.

OBJECTIVES: Prebiotic galacto-oligosaccharides (GOS) have shown promising results in enhancing the absorption of oral supplemental iron in form of ferrous fumarate (FeFum) in iron depleted adults. The mechanism behind this effect is unknown. We aimed to assess the absorption profile of FeFum given with and without GOS using stable isotope appearance curves (SIACs). METHODS: We conducted a controlled, single-center, prospective cross-over trial in iron depleted women between Sept and Nov 2019 at the Laboratory of Human Nutrition, ETH Zurich, Switzerland. All women (n = 11; median SF = 15.2 µg/L) received two supplemental iron doses of 14 mg in form of FeFum containing 6 mg of isotopic tracers ((57)Fe or (58)Fe). The supplemental iron doses were administered in random order on d 1 and 15 after an overnight fast. The supplement combinations were: 1) (57)FeFum + 300 ml water; and 2) (58)FeFum + 15 g GOS + 300 ml water. Eleven blood samples were collected up to 24 h after administration of the iron supplements to determine serum iron appearance. Fractional iron absorption (FIA) of the isotopic tracers was calculated in whole blood collected 14 days after administration of each of the supplemental iron doses on the basis of the shift in iron isotope ratios according to the principle of isotope dilution. RESULTS: There was a trend towards increased FIA and total absolute AUC of the SIAC from FeFum given with 15 g GOS compared to without (P = 0.064; P = 0.080 respectively). Estimated timepoints of the peak serum isotope concentration were not different (P = 0.096). Relative SF and relative bioavailability correlated significantly (P = 0.037). In subjects with a lower SF the increase in bioavailability of iron when given with GOS was more pronounced compared to participants with higher SF. CONCLUSIONS: Adding 15 g GOS to FeFum did not result in a different absorption profile compared to without GOS. The enhancing effect of GOS seems to depend on iron status, even though overall the improvement of iron absorption when given with 15 g GOS did not reach significance, probably due to the small sample size. Since women with a low iron status can benefit the most from an increase in iron bioavailability, the use of GOS for the improvement of iron bioavailability from FeFum in women with very low iron stores is promising. FUNDING SOURCES: Innosuisse, Swiss Innovation Agency, in collaboration with Antistress AG - Burgerstein Vitamine.