Office Of Dietary Supplements Research Articles

Evolution and impact of Standard Reference Materials (SRMs) for determining vitamin D metabolites.

The National Institute of Standards and Technology (NIST), in collaboration with the National Institutes of Health, Office of Dietary Supplements (NIH ODS), introduced the first Standard Reference Material® (SRM) for determining vitamin D metabolites in 2009 motivated by significant concerns about the comparability and accuracy of different assays to assess vitamin D status. After 14years, a suite of five serum matrix SRMs and three calibration solution SRMs are available. Values were also assigned for vitamin D metabolites in five additional SRMs intended primarily to support measurements of other clinical diagnostic markers. Both the SRMs and the certification approach have evolved from significant exogenous serum content to primarily endogenous content and from value assignment by combining the results of multiple analytical methods to the use of measurements exclusively from reference measurement procedures (RMPs). The impact of the availability of these SRMs can be assessed by both the distribution information (sales) and by reports in the scientific literature describing their use for method validation, quality control, and research. In this review, we describe the development of these SRMs, the evolution in design and value assignment, the expansion of information reported, and SRM use in validating analytical methods and providing quality assurance within the vitamin D measurement community.

PartII: Interactive case:Drug‐inducedendocrine disorders

Part<scp>II</scp>: Interactive case:<scp>Drug‐induced</scp>endocrine disorders

Establishing a Rat Model of Intestinal Heme-iron Absorption

Heme iron, derived from hemoglobin and myoglobin of animal products, is efficiently absorbed and utilized by humans. Despite extensive investigation over the last several decades, the exact mechanism(s) of heme-iron absorption and tissue utilization of absorbed heme are unclear. Mice are frequently used for investigation of iron biology; however, mice do not efficiently utilize dietary iron derived from heme, so development of alternative models is warranted. Rats could more efficiently utilize dietary heme iron, but this has not been rigorously tested. Our initial studies demonstrated that dietary heme (derived from porcine RBCs) could partially correct iron-deficiency anemia (IDA) in rats of one strain (rat strain 1), but not in 2 others. We hypothesized that a heme-iron diet would fully replete strain 1 rats with IDA, at a similar rate to a non-heme iron (NHI) diet. We utilized repletion diets containing 50, 75 or 100 ppm heme iron; a control diet contained 50 ppm NHI. Forty-two, three-week-old, female strain 1 rats were weaned onto a low-iron diet with 3-4 ppm NHI, and then after 2 weeks, rats were repleted with the different diets for 8 days. Rats were housed in overhanging wire bottom stainless steel cages during the low-iron feeding period to prevent coprophagia. Blood was collected from the tail vein at baseline and every 4 days thereafter to track correction of anemia. Outcomes showed that repletion of IDA rats with the 50-ppm heme-iron diet resolved the anemia; however, tissue iron depletion indicated that the rats remained iron deficient. Also, the rate of repletion was slightly slower as compared to rats repleted with the control (50 ppm NHI) diet. With higher dietary heme-iron levels, repletion was as fast, or even faster, than in control rats suggesting that a rat strain was identified that can efficiently assimilate dietary heme iron. Our studies support a role for rats as a genetic model to preferentially mimic human nutritional studies of iron and heme absorption. This investigation was funded by grant DK074867 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (JFC, PI), and grant DK109717 from NIDDK and the Office of Dietary Supplements (to JFC, PI). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Immune Supplements Under the Magnifying Glass: An Expert Panel Develops Priorities and Evidence-Based Recommendations for Future Research Regarding Dietary Supplements.

Immune Supplements Under the Magnifying Glass: An Expert Panel Develops Priorities and Evidence-Based Recommendations for Future Research Regarding Dietary Supplements.

1123-P: Racial Differences in Glycemia and A1C in the Vitamin D and Diabetes (D2d) Study

Understanding the association between glycemia and A1c by race can improve screening for prediabetes and type 2 diabetes (T2D) . This association was examined cross-sectionally in 1016 Black and 2658 White persons screened for D2d (mean age 60; fasting glucose [FG] 1mg/dL; A1c 5.9%) . Of these, 22with at least 2-of-3 ADA glycemic criteria for prediabetes (mean age 60, FG 1mg/dL, A1c 5.9%, 28% Black) were followed longitudinally for median 2.5 years with annual OGTT and semi-annual FG and A1c. Numerical integration methods were used for the estimation of area under the OGTT-derived glucose curve (AUC) . Mean A1c was estimated for a given AUC quintile using linear regression for Whites, Blacks, and Asians. Adjusting for covariates, the A1c was higher by 0.2-0.25% among Black vs. White participants with similar glycemia in all AUC quintiles. During follow-up, Black participants were more likely to be diagnosed with T2D based on A1c; White participants were more likely to be diagnosed by FG. The absolute increase in A1c over time according to baseline AUC-glucose quintiles differed by race. Compared to White participants, Black participants in lower baseline AUC quintiles had greater increases in A1c over time, while A1c increased similarly in White and Black persons in the two highest baseline AUC quintiles. In summary, Black participants had higher A1c than White participants for similar degree of glycemia defined by AUC; the glycemic criteria contributing to the diagnosis of T2D differed by race; and there were AUC by racial interactions in A1c increase over time. Disclosure E.S.Leblanc: n/a. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck &amp; Co., Inc., Sanofi. J.P.Nelson: None. D.S.Hsia: None. D2d research group: n/a. A.G.Pittas: None. R.Chatterjee montgomery: Research Support; Bristol-Myers Squibb Company, Epigenomics AG. N.Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Allergan, Eli Lilly and Company, Novo Nordisk. M.K.Rhee: Research Support; Kowa Company, Ltd. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck &amp; Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. C.Desouza: Advisory Panel; AstraZeneca, Bayer AG, Novo Nordisk A/S, Consultant; Asahi Kasei Corporation. L.M.Neff: Employee; Eli Lilly and Company, Research Support; Amryt Pharma Plc, Novo Nordisk, Stock/Shareholder; Eli Lilly and Company. A.L.Peters: Advisory Panel; Abbott Diabetes, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Shouti, Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Other Relationship; Omada Health, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Leona M. and Harry B. Helmsley Charitable Trust, Stock/Shareholder; Teladoc Health. Funding American Diabetes Association (1-14-D2d-01) ; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases and Office of Dietary Supplements (U01DK098245)

30-OR: Effects of Vitamin D Supplementation by Race and Weight Status on Serum Vitamin D Measures and Diabetes Risk in the D2d Study

Higher blood 25 (OH) D is associated with lower risk of type 2 diabetes (T2D) in people with prediabetes. Blood 25 (OH) D can vary due to skin color and weight. It is not known if blood 25 (OH) D levels have similar impact on T2D risk for people of color or higher weight. The vitamin D and type 2 diabetes (D2d) study is a randomized clinical trial of participants with high-risk prediabetes and overweight/obesity who were randomized to vitamin D3 4000 IU daily vs. placebo and followed for 2.5 years for the primary outcome of T2D. We compared baseline and intra-trial (mean achieved) serum 25 (OH) D among race-weight groups. We used Cox models to determine the associations between intra-trial serum 25 (OH) D and T2D risk by race-weight groups; we additionally tested for interactions between intra-trial serum 25 (OH) D and race or weight. Of 2362 D2d participants with self-reported race, Black (n = 616) and White (n = 1616) participants were included in analyses. Baseline serum 25 (OH) D was lower in Black (24.2 ng/mL ± 10.9) compared to White (29.6 ng/mL ± 9.5) participants (P&amp;lt;0.001) ; and were lower in those with higher vs. lower BMI in both races. Intra-trial serum 25 (OH) D was lower in Black participants (P&amp;lt;0.001) overall and those with higher baseline BMI. Both Black and White participants with intra-trial serum 25 (OH) D ≥ 40 ng/mL had significantly reduced risk of T2D [HR (95% CI) ]; Black: 0.51 (0.29, 0.92) ; White 0.42 (0.30, 0.60) ] with no significant race*BMI interaction. Participants with baseline BMI ≤ 40 kg/m2 who achieved intra-trial serum 25 (OH) D levels ≥ 40 ng/mL had significantly reduced risks of T2D but not those with a BMI &amp;gt; 40 kg/m2 with no significant BMI*race interaction. Conclusions: An intra-trial mean serum 25 (OH) D level ≥ 40 ng/mL was associated with significantly reduced risk of T2D in Black and White D2d participants, but only among those with BMI &amp;lt; 40 kg/m2. Targeting a serum 25 (OH) D level ≥ 40 ng/mL would optimize T2D prevention efforts among people with high-risk prediabetes. Disclosure R.Chatterjee montgomery: Research Support; Bristol-Myers Squibb Company, Epigenomics AG. B.Dawson-hughes: None. D2d research group: n/a. C.A.Davenport: None. K.C.Johnson: None. S.Kashyap: Advisory Panel; Fractyl Health, Inc., GI Dynamics, Research Support; Janssen Pharmaceuticals, Inc. E.S.Leblanc: n/a. J.P.Nelson: None. E.Vickery: None. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck &amp; Co., Inc., Sanofi. A.G.Pittas: None. Funding American Diabetes Association (1-14-D2d-01) ; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases and Office of Dietary Supplements (U01DK098245)

854-P: Statin Use and New-Onset Diabetes in People with Prediabetes

Statins lower the risk of cardiovascular disease, yet may adversely affect glucose metabolism. In the D2d study, which evaluated the effect of vitamin D versus placebo in a contemporary cohort of people with high-risk prediabetes (n=2,423) , we evaluated the association between statin use at baseline and progression to diabetes. In the D2d study, 1396 participants (58%) were on statin at baseline. Kaplan Meier curves of incident diabetes over 2.5 years by baseline status of statin use and adjusted hazard ratio (95%CI) of the difference in incident diabetes between statin and no statin use were estimated. We tested for a statin use * D2d assignment (vitamin D or placebo) interaction on incident diabetes. Mean age (SD) was 57±years and 64±8 for those not on vs. on statin; baseline HbA1c was 5.9 ± 0.2% in both groups. 27% of statin users developed diabetes vs. 24% of non-statin users (adjusted HR [95%CI] 1.23 [1.04-1.46]) (Figure) . There was no significant interaction (p=0.67) with vitamin D treatment assignment; therefore, subgroup analyses by D2d treatment assignment are not presented. Conclusions: In this observational analysis among people at high risk for diabetes, baseline statin use was associated with a 23% higher risk of progression to diabetes after 2.5 years compared to no use. Increased risk of diabetes progression should be considered along with the cardiovascular benefits of statin therapy and diabetes prevention measures re-enforced. Disclosure J.Y.Park: None. A.Ghazi: None. A.G.Pittas: None. E.Vickery: None. J.P.Nelson: None. V.R.Aroda: Consultant; Applied Therapeutics, Fractyl Health, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Other Relationship; Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Research Support; Applied Therapeutics, Fractyl Health, Inc., Novo Nordisk, Sanofi. D2d research group: n/a. Funding American Diabetes Association (1-14-D2d-01) ; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases and Office of Dietary Supplements (U01DK098245)

1174-P: A Posteriori Dietary Patterns and Insulin-Resistance Status and Diabetes Risk by Hispanic/Latino Heritage in HCHS/SOL

We examined links among dietary patterns (DPs) , insulin resistance (IR) , and diabetes risk by heritage (Cuban, Dominican, Mexican, Puerto Rican, and Central and South American) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) . HCHS/SOL is a population-based cohort of 16,415 Hispanics/Latinos aged 18-74 y living in 4 US cities. At both visits, questionnaires and clinical examinations were administered, including two 24-hr diet recalls conducted at baseline only (2008-11) . Among 7,774 participants with 2nd-visit data (2014-17) and without diabetes at baseline, we performed heritage-specific principal factor analyses and characterized overarching DPs based on high-loading foods shared by ≥ 2 heritage groups. We classified 6-yr IR status (improved, unchanged, worsened) using a SD-change in fasting insulin. We defined incident diabetes using self-report, self-reported diabetes medication, or labs (fasting glucose (≥126 mg/dL) , post-OGTT (≥200 mg/dL) , or HbA1C (≥6.5%)) . We identified 5 overarching DPs: Burger, Fries, &amp; Soft Drinks; White Rice, Beans, &amp; Red Meats; Fish &amp; Whole Grains; Cheese &amp; Sweets; and Stew &amp; Corn. Comparing highest to lowest quintiles, the Burger, Fries, &amp; Soft Drinks DP in Dominicans (log-odds: 2.35, 95% CI: 1.02, 3.68, P trend=0.037) and White Rice, Beans, &amp; Red Meats DP in Cubans (log-odds: 1.27, 95% CI: 0.49, 2.06, P trend =0.009) were associated with worsened (vs. unchanged) 6-year IR status. The Burger, Fries, &amp; Soft Drinks DP in Puerto Ricans (OR: 3.00, 95% CI:1.50, 5.99, P trend=0.003) and the White Rice, Beans, &amp; Red Meats DP in Central Americans (OR: 2.41, 95% CI: 1.05, 5.50, P trend=0.032) were associated with greater diabetes risk. In sum, dietary interventions for diabetes prevention should be tailored by Hispanic/Latino heritage. Disclosure L.E.Maldonado: None. L.Gallo: None. S.Albrecht: None. D.Sotres-alvarez: None. J.Mattei: None. M.L.Daviglus: None. G.A.Talavera: None. K.M.Perreira: None. L.Van horn: None. Y.Mossavar-rahmani: None. M.N.Lecroy: None. Funding The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233) , University of Miami (N01-HC65234) , Albert Einstein College of Medicine (N01-HC65235) , Northwestern University (N01-HC65236) , and San Diego State University (N01-HC65237) . The following Institutes/Centers/Offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: National Center on Minority Health and Health Disparities, the National Institute of Deafness and Other Communications Disorders, the National Institute of Dental and Craniofacial Research, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the Office of Dietary Supplements. This research received support from the National Heart, Lung, and Blood Institute Global Cardiometabolic Disease Training Grant (1T32HL129969-01A1) , the National Institute of Diabetes and Digestive and Kidney Diseases (K01DK107791) ,and from the Population Research Infrastructure Program (R24 HD050924) awarded to the Carolina Population Center at The University of North Carolina at Chapel Hill by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

558-P: Effect of Vitamin D Supplementation on Regression to Normal Glucose Regulation from Prediabetes in the D2d Study

Regression to normal glucose regulation (NGR) has been reported in response to lifestyle modification and medications. In this secondary analysis of the D2d study, a randomized trial of 4,000 IU/d of vitamin D3 vs. placebo, we determined whether vitamin D increased regression to NGR in people with prediabetes. Eligible participants met at least 2-of-3 ADA glycemic criteria for prediabetes (n=2423) and the two groups were similar at baseline. During follow-up, glycemic status was assessed semi-annually with FG and HbA1c and annually with 2-hour glucose after 75-g glucose load (2hPG) . In exploratory analyses that censored follow up at initiation of diabetes/weight-loss medication, stopping trial pills, taking vitamin D above the trial limit, death or withdrawal, we tested for an effect of vitamin D on new-onset NGR, which was defined as the first occurrence of 2 or 3 glycemic criteria in the normal range and none in the diabetes range. Over a median follow-up of 2.5 years, the NGR outcome occurred in 343/12 participants in the vitamin D group and 295/1212 in the placebo group; hazard ratio (95%CI) for time-to-NGR for vitamin D was 1.16 (0.99-1.36) . Among those who never met NGR during follow-up (n=1785) , 29% developed diabetes compared to 8.2% among those who met NGR at some point during the study (p&amp;lt;0.01) . At the last encounter, the NGR outcome was observed in 133/1069 participants in the vitamin D group and 102/1050 in the placebo group; incidence rate ratio (95%CI) for vitamin D was 1.26 (0.97-1.63) . When we used the NGR definition from other studies to include only those with normal FG and 2hPG regardless of HbA1c, 90/1037 participants in the vitamin D group and 63/1050 in the placebo group at the last encounter had NGR; incidence rate ratio (95%CI) for vitamin D 1.39 (1.01-1.91) . In conclusion, vitamin D supplementation increased the likelihood of regression to NGR at the last visit, and those who met NGR during the study were less likely to subsequently develop diabetes. Disclosure D.S.Hsia: None. A.G.Pittas: None. D2d research group: n/a. J.P.Nelson: None. E.Vickery: None. N.Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Allergan, Eli Lilly and Company, Novo Nordisk. E.S.Leblanc: n/a. S.H.Kim: Advisory Panel; GI Dynamics, Consultant; Aligos, Research Support; Fractyl Health, Inc. I.Brodsky: None. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck &amp; Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. B.Dawson-hughes: None. Funding American Diabetes Association (1-14-D2d-01) ; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases and Office of Dietary Supplements (U01DK098245)

0030 Development and Validation of a Metabolomic Risk Score for Obstructive Sleep Apnea across Race/Ethnicities

Abstract Introduction Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent episodes of upper airway obstruction during sleep resulting in oxygen desaturation and sleep fragmentation, and associated with increased risk of adverse health outcomes. Metabolites are being increasingly used for biomarker discovery and evaluation of disease processes and progression. We aimed to develop a metabolomic risk score (MRS) for OSA and identify individual metabolites associated with OSA to provide insights into the pathogenesis of OSA. Methods We studied 219 metabolites and their associations the apnea hypopnea index (AHI) and with OSA, defined as AHI , in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (n=3507) using two methods: (1) association analysis of individual metabolites, and (2) least absolute shrinkage and selection operator (LASSO) regression to identify a subset of metabolites that are jointly associated with OSA, and develop an MRS. We then validated the results in Multi-Ethnic Study of Atherosclerosis (MESA) (n=475), an independent dataset. Results HCHS/SOL participants were 41.72 years old on average, 50.7% female, and 10.2% had OSA. MESA individuals were 68.45 years old on average, 56.2% females, and 46.7% had OSA. When assessing the associations between OSA/AHI and individual metabolites, we identified seven metabolites significantly and positively associated with OSA in HCHS/SOL (FDR p&amp;lt;0.05), of which four associations - glutamate, oleoyl-linoleoyl-glycerol (18:1/18:2) (DAG(36:3)), linoleoyl-linoleoyl-glycerol (18:2/18:2) (DAG(36:4)) and phenylalanine, replicated in MESA (one sided-p value&amp;lt;0.05). The OSA-MRS, composed of 14 metabolites, was associated with 52% increase of risk for moderate to severe OSA (OR=1.52 [95% CI: 1.23-1.87] per 1 SD of OSA-MRS, p&amp;lt;.001) in the discovery dataset of HCHS/SOL and 44% increased risk (OR=1.44 [95% CI: 1.03-2.03] per 1 SD of OSA-MRS, p=0.034) in the validation dataset of MESA, both adjusted for demographic, lifestyle, and comorbidities. Similar albeit less significant associations were observed for AHI modeled continuously. Conclusion We developed an MRS that replicated in an independent multi-ethnic dataset, demonstrating the robustness of metabolomic-based OSA risk score to population heterogeneity. Replicated metabolite associations may provide insights into OSA-related molecular and metabolic mechanisms. Support (If Any) Support for metabolomics data was graciously provided by the JLH Foundation (Houston, Texas). The Hispanic Community Health Study/Study of Latinos was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: National Center on Minority Health and Health Disparities, the National Institute of Deafness and Other Communications Disorders, the National Institute of Dental and Craniofacial Research, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the Office of Dietary Supplements. The authors thank the staff and participants of HCHS/SOL for their important contributions. MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420. MESA Family is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support is provided by grants and contracts R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071258, R01HL071259, and by the National Center for Research Resources, Grant UL1RR033176. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. Molecular data for the Trans-Omics in Precision Medicine (TOPMed) program was supported by the National Heart, Lung and Blood Institute (NHLBI). ). Metabolomics for “NHLBI TOPMed: Multi-Ethnic Study of Atherosclerosis (MESA)” (phs001416) was performed at Broad Institute and Beth Israel Metabolomics Platform (HHSN268201600038I). Core support including centralized genomic read mapping and genotype calling, along with variant quality metrics and filtering were provided by the TOPMed Informatics Research Center (3R01HL-117626-02S1; contract HHSN268201800002I). Core support including phenotype harmonization, data management, sample-identity QC, and general program coordination were provided by the TOPMed Data Coordinating Center (R01HL-120393; U01HL-120393; contract HHSN268201800001I). We gratefully acknowledge the studies and participants who provided biological samples and data for TOPMed. This study was supported by NHLBI grant R35HL135818.

The Importance of Vitamin D in Long-Term Care Residents

The Importance of Vitamin D in Long-Term Care Residents

Development of Kudzu (Pueraria Montana var. lobata) Reference Materials for the Determination of Isoflavones and Toxic Elements.

In collaboration with the Office of Dietary Supplements at the National Institutes of Health, the National Institute of Standards and Technology issued a suite of botanical matrix reference materials (RMs) and Standard Reference Material® (SRM) for determination of isoflavones and toxic elements in kudzu dietary supplement ingredients. RM 8650 Pueraria montana var. lobata (Kudzu) Rhizome, SRM 3268 Pueraria montana var. lobata (Kudzu) Extract, and RM 8652 Kudzu-Containing Solid Oral Dosage Form were issued with values assigned for isoflavones (puerarin, daidzin, and daidzein), toxic elements (arsenic, cadmium, and lead), and selenium. Isoflavone values were assigned using liquid chromatography with UV absorbance or mass spectrometry detection. Element values were assigned using inductively coupled plasma mass spectrometry and results from an interlaboratory comparison exercise. Mass fractions for puerarin were 32.2 ± 3.2 mg/g, 128 ± 13 mg/g, and 68.2 ± 6.9 mg/g in RM 8650, SRM 3268, and RM 8652, respectively. Arsenic increases from 156 ± 14 ng/g to 849 ± 83 ng/g and cadmium decreases from 348 ± 14 ng/g to 82.1 ± 4.9 ng/g from rhizome to extract. The kudzu RM/SRM suite complements previously issued soy-related SRMs with values assigned for isoflavones, which have been studied for their potential health benefits, and expands the analytical resource by providing values for puerarin, an isoflavone not found in soy. The three new kudzurmaterials are for use in the determination of isoflavones, toxic elements, and selenium. For the isoflavones, these new kudzu materials provide higher levels of daidzin and daidzein than existing soy-related SRMs, and they provide a value for an isoflavone not in existing SRMs (puerarin). Toxic elements in RM 8650 and SRM 3268 provide new botanical matrixes for use by dietary supplement manufacturers for the verification of the safety of their raw materials.

Rise in Blood Pressure Observed Among US Adults During the COVID-19 Pandemic

Rise in Blood Pressure Observed Among US Adults During the COVID-19 Pandemic

Academy of Breastfeeding Medicine Position Statement and Guideline: Infant Feeding and Lactation-Related Language and Gender.

Academy of Breastfeeding Medicine Position Statement and Guideline: Infant Feeding and Lactation-Related Language and Gender.

301-OR: Effect of Vitamin D Supplementation on Insulin Sensitivity and Beta-Cell Function in Prediabetes

Vitamin D is believed to regulate pathways in glucose homeostasis, but effects of vitamin D supplementation on insulin sensitivity and β-cell function in humans remain uncertain. We completed a secondary analysis of the Vitamin D and type 2 diabetes (D2d) study to investigate the effects of vitamin D supplementation on insulin sensitivity and β-cell function. Participants at high risk for type 2 diabetes, meeting at least 2-out-of-3 ADA criteria for prediabetes, were randomly assigned to 4000 IU/day of vitamin D3 or placebo. Insulin sensitivity and β-cell function were estimated using data from 75-gram oral glucose tolerance tests (OGTT). We used the University of Oxford HOMA2 Calculator to estimate insulin sensitivity from simultaneously measured fasting plasma glucose and C-peptide values. Early C-peptide and insulin responses were calculated as the ratio of C-peptide or insulin increment to glucose level changes during the first 30 minutes of the OGTT. The disposition index (DI) as an estimate of β-cell function was calculated as the product of C-peptide response and HOMA2%S. The response to vitamin D3 was evaluated in 1,774 participants over 24 months. Baseline characteristics [mean age 60.5±9.8 years, BMI 31.9±4.4 kg/m2, 56.4% male, 69.1% white, 25-hydroxyvitamin D (25-OH D) 28.2±10.2 ng/ml, HbA1c 5.9%±0.2, FPG 107.7±7.2 mg/dl, 2hrOGTT glucose 137.1±34.1 mg/dl] were similar between the vitamin D and placebo groups. Serum 25-OH D increased from 27.9±10.3 ng/ml to 54.9±14.4 ng/ml at 24 months in the vitamin D group and remained unchanged with placebo (p&amp;lt;0.05 between group changes from baseline). There were no significant differences in changes in HOMA2%S, C-peptide or insulin responses and DI between the two groups. In conclusion, in this pre-specified analysis from the D2d study, supplementation with vitamin D for 24 months did not alter insulin sensitivity or β-cell function in people with prediabetes who were not selected based on their baseline vitamin D levels. Disclosure N. Rasouli: Consultant; Self; Novo Nordisk, Research Support; Self; Allergan plc, Lilly Diabetes, Novo Nordisk. I. Brodsky: None. R. Chatterjee: Research Support; Self; Bristol-Myers Squibb Company, Epigenomics AG, Verily Life Sciences. S. H. Kim: Advisory Panel; Self; Bayer U. S., GI Dynamics, Stock/Shareholder; Spouse/Partner; Dexcom, Inc. R. E. Pratley: Other Relationship; Self; Hanmi Pharmaceutical, Merck Sharp &amp; Dohme Corp., Metavention, Monster Energy Company, Inc., Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. M. Staten: None. J. P. Nelson: None. A. G. Pittas: None. D2d research group: n/a. Funding American Diabetes Association (1-14-D2d-01 to A.G.P.); National Institute of Diabetes and Digestive and Kidney Diseases (U34DK091958); Office of Dietary Supplements (U01DK098245)

Quality Assessment of Online Complementary and Alternative Medicine Information Resources Relevant to Cancer.

Background:Complementary and alternative medicine (CAM) is often used by cancer patients and survivors in the US. Many people turn to the internet as their first source of information. Health information seeking through the internet can be useful for patients to gain a better understanding of specific CAM treatments to discuss with their healthcare team, but only if the information is comprehensive, high quality, and reliable. The aim of this article is to examine the content, writing/vetting processes, and visibility of cancer CAM online informational resources.Methods:Online CAM resources were identified by Google and PubMed searches, literature reviews, and through sources listed on various websites. The websites were analyzed through a modified online health information evaluation tool, DISCERN (score range = 1-5). The website’s features relevant to the quality assessment were described.Results:Eleven CAM websites were chosen for analysis. The DISCERN analysis showed a range of quality scores from 3.6 to 4.9. Lower DISCERN scores were generally due to deficiencies in describing the writing, editing, and updating processes. A lack of transparency with authorship and references was commonly present.Conclusion:Cancer patients interested in CAM need unbiased, evidence-based, reliable, high-quality, easily accessible educational materials. Individuals should use the guidelines followed in this analysis (including DISCERN and Medline Plus) to find reliable sources. Website developers can use CAM Cancer (NAFKAM), Beyond Conventional Cancer Therapies, Memorial Sloan Kettering Cancer Center, breastcancer.org, Office of Dietary Supplements, National Center for Complementary and Integrative Health, and Cancer.gov as models for trustworthy content.

Vitamin D3 Found Ineffective at Preventing Depression

Back to table of contents Previous article Next article Clinical & ResearchFull AccessVitamin D3 Found Ineffective at Preventing DepressionNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:15 Sep 2020https://doi.org/10.1176/appi.pn.2020.9a25AbstractThe trial involved over 18,000 middle-aged and older adults from across the country who took a high dose of vitamin D supplements or placebo daily for over five years.iStock/Helin Loik-TomsonHigh-dose vitamin D3 supplements do not appear to be effective at preventing depression in older adults, according to a large, placebo-controlled study published August 4 in JAMA.Observational studies have suggested that people with lower blood levels of vitamin D are at higher risk of late-life depression, while other research has found that vitamin D deficiency may be involved in seasonal depressive disorder. But to date prospective studies of people taking vitamin D supplements have yielded little evidence that adding vitamin D protects against depression.It is possible that previous supplement studies examined vitamin D doses that were too low and/or the studies were too short in duration. This new study addressed previous shortcomings by evaluating over 18,000 older adults across the United States for over five years.The adults were participants in the Vitamin D and Omega-3 Trial (VITAL), a randomized study examining the effects of daily vitamin D3 and/or fish oil supplements on the prevention of cancer and cardiovascular disease. As an ancillary part of the study (VITAL-DEP), participants were also given the eight-item Patient Health Questionnaire (PHQ-8) during their periodic assessments to screen for depressive symptoms. Participants who were currently receiving treatment for depression or had another psychiatric or neurological condition were excluded from this ancillary analysis.The final sample included 9,181 adults who took 2,000 IU/d of vitamin D3 daily for an average of 5.3 years and 9,172 adults who took placebo for the same average time. By the end of the study, 609 adults taking vitamin D3 and 625 taking placebo received a diagnosis of depression or developed clinically relevant depressive symptoms (a PHQ-8 score of ≥10)—which the authors noted was not a significant difference between the groups.There was also no significant difference between the two groups in overall mood over time; average PHQ-8 scores rose by 0.20 points in the vitamin D3 group and 0.16 points in the placebo group.“By no means is this study a verdict on vitamin D as a supplement in general,” said study author Olivia Okereke, M.D., the director of geriatric psychiatry at Massachusetts General Hospital and an associate professor of psychiatry and epidemiology at Harvard Medical School. “This vitamin is important for bone health and immune health and potentially other conditions.”She continued, “The findings indicate that for an average adult, taking vitamin D3 supplements for the purpose of improving mood will provide no benefit.”Okereke and colleagues also looked at data on various subgroups in the study to see whether there might be a population that experienced a positive effect from vitamin D3. However, vitamin D3 did not appear to prevent depression in any of the tested subgroups, including grouping by sex, ethnicity, age group, and depression history.“Now, there was one interesting signal that showed adults with normal body weight [body mass index score of 25 or less] might be gaining some protection from depression,” Okereke noted. This signal mirrored some data seen in the main VITAL study, which was published last year in the New England Journal of Medicine. This study found that while vitamin D3 supplements did not prevent cancer or major cardiovascular events in the general population, the supplements did appear to reduce the risk of cancer in adults with low body mass index.Okereke cautioned that the findings on obesity are still preliminary, but if there was one variable worth pursuing with further research, that would be it.The VITAL-DEP researchers are reviewing data related to fish oil and depression and hope to release those findings soon.VITAL-DEP was supported by a grant from the National Institute of Mental Health. The main VITAL study was supported by grants from the National Cancer Institute; the National Heart, Lung, and Blood Institute; the National Institute of Neurological Disorders and Stroke; the National Center for Complementary and Integrative Health; and the Office of Dietary Supplements. Pharmavite LLC and Pronova BioPharma/ BASF donated the vitamin D3 and fish oil for the study, respectively. ■“Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial” is posted here.The parent VITAL study, “Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease” is posted here. ISSUES NewArchived

Elimination of the Variance Between Individuals Is Necessary to Evaluate the Impact of Garlic on the Metabolic Profile of Human Urine

Abstract Objectives To determine the impact of garlic on the metabolic profile of urine. Methods On the first day 17 fasting subjects were fed a breakfast of bread and butter. Urines were collected before and 3 hours after the meal. On a second day, the same 17 fasting subjects were fed a meal of bread, butter, and garlic. Urines were again collected before and 3 hours after the meal. Samples were analyzed by metabolomics using liquid chromatography-mass spectrometry (LC-MS) and data were subjected to analysis of variance-principal component analysis (ANOVA-PCA). Results 637 compounds were found in the urines and 277 were identified. PCA of urine profiles were dominated by variation between individual. Removal of individual variance by ANOVA allowed differentiation of fasting urines from bread and butter urines from bread, butter, and garlic urines. PCA loadings identified compounds that led to discrimination between treatments. Influence of the loading identified compounds were verified by examination of the LC-MS data for individual compounds. Three unique sulfur containing compounds were identified. Loadings showed, however, that a change in the metabolite profiles (ratios of compounds) and not the unique compounds) were most informative. Conclusions Removal of variance between individuals is essential to properly analyze the data. Changes in the patterns of compounds routinely observed in urine were the major result of the garlic meal. ANOVA-PCA is an excellent tool for isolating experimental factors. Funding Sources Agricultural Research Service, US Department of Agriculture and Office of Dietary Supplements, National Institutes of Health.

Gpr44 Mediates the Selenium-Dependent Anti-Leukemic Effect in Acute Myeloid Leukemia

Abstract Objectives The relapse of acute myeloid leukemia (AML) remains a significant concern due to persistent leukemia stem cells (LSCs) that are not targeted by existing therapies. LSCs show sensitivity to endogenous cyclopentenone prostaglandin J (CyPG) metabolites that are increased by dietary trace element selenium (Se), which is significantly decreased in AML patients. We investigated the anti-leukemic effect of Se supplementation in AML via mechanisms involving the activation of the membrane-bound G-protein coupled receptor 44 (Gpr44) and the intracellular receptor, peroxisome proliferator-activated receptor gamma (PPARγ), by endogenous CyPGs. Methods A murine model of AML generated by transplantation of hematopoietic stem cells (HSCs- WT or Gpr44−/−) expressing human MLL-AF9 fusion oncoprotein, in the following experiments: To investigate the effect of Se supplementation on the outcome of AML, donor mice were maintained on either Se-adequate (Se-A; 0.08–0.1 ppm Se) or Se-supplemented (Se-S; 0.4 ppm Se) diets. Complete cell counts in peripheral blood were analyzed by hemavet. LSCs in bone marrow and spleen were analyzed by flow cytometry. To determine the role of Gpr44 activation in AML, mice were treated with Gpr44 agonists, CyPGs. LSCs in bone marrow and spleen were analyzed. Mice transplanted with Gpr44−/- AML cells were compared with mice transplanted with wild type AML cells and the progression of the disease was followed as above. To determine the role of PPARγ activation in AML, PPARγ agonist (Rosiglitazone, 6 mg/kg, i.p, 14 d) and antagonist (GW9662, 1 mg/kg, i.p. once every other day, 7 injections) were applied to Se-S mice transplanted with Gpr44−/- AML cells and disease progression was followed. Results Se supplementation at supraphysiological levels alleviated the disease via the elimination of LSCs in a murine model of AML. CyPGs induced by Se supplementation mediate the apoptosis in LSCs via the activation of Gpr44 and PPARγ. Conclusions Endogenous CyPGs produced upon supplementation with Se at supraphysiological levels improved the outcome of AML by targeting LSCs to apoptosis via the activation of two receptors, Gpr44 and PPARg. Funding Sources NIH DK 07,7152; CA 175,576; CA 162,665. Office of Dietary Supplements, USDA Hatch funds PEN04605, Accession # 1,010,021 (KSP, RFP).

1920-P: Coingestion of Glucose and Fructose Has Synergistic Effects on Lipoprotein Risk Factors for Cardiovascular Disease in Healthy Young Adults

Global sugar consumption is at an all-time high. In previous studies, we and others have demonstrated that, compared with glucose (Gluc), consumption of fructose (Fruc) increases risk factors for cardiovascular disease (CVD), diabetes and metabolic syndrome. However, humans almost exclusively consume Fruc in combination with Gluc. Our aim was to study effects of Gluc, Fruc and their combination - high fructose corn syrup (HFCS) - and identify effects on metabolic risk factors. We performed a parallel-armed, double blinded intervention study wherein the subjects consumed beverages sweetened with 25% of their energy requirement (Ereq) as Gluc, Fruc or HFCS, or 17.5% Ereq as Fruc or HFCS, or Aspartame (ASP) for two weeks with their usual diet. Procedures, which included fasting and postprandial blood draws, were conducted over a 48-h period at baseline and at the end of intervention while subjects consumed standardized meals containing 30% Ereq as fat, 15% protein, 55% carbohydrate (mainly complex during baseline; complex + sweetened beverage during intervention). As expected, the increases for 24h triglyceride area under the curve (AUC), 24h uric acid AUC, and postprandial apoCIII were highest in both Fruc groups (all P&amp;lt;0.01 versus ASP), next highest in both HFCS groups (all P&amp;lt;0.05 25% Ereq HFCS versus ASP), and lowest in the Gluc group (all P&amp;gt;0.05 versus ASP). Unexpectedly, the increases of LDL- and non-HDL-cholesterol (C) and ApoB were highest in the HFCS groups (all P&amp;lt;0.001 25% HFCS versus ASP, P&amp;lt;0.01 versus Gluc). Re-analyzing the outcomes based on the amounts of Fruc and Gluc contained in the beverages revealed significant interactions between Fruc and Gluc on fasting and postprandial concentrations of LDL-C, non-HDL-C and ApoB (all P&amp;lt;0.01). While sole consumption of Fruc leads to increases of metabolic risk factors, those increases are exacerbated for several risk factors when Fruc is co-ingested with Gluc as HFCS. Disclosure B. Hieronimus: None. V. Medici: None. V. Lee: None. M. Nunez: None. P.J. Havel: Research Support; Self; Arrowhead Research, Bristol-Myers Squibb Company, Magnamosis Inc. K.L. Stanhope: None. Funding National Heart, Lung, and Blood Institute (1R01HL09133, 1R01HL107256); National Center for Research Resources (UL1RR024146); Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD051958); Office of Research on Women’s Health; Office of Dietary Supplements; National Institute on Aging (to K.L.S.)