Research Project: Improving Public Health by Understanding Metabolic and Bio-Behavioral Effects of Following Recommendations in the Dietary Guidelines for Americans

Location: Obesity and Metabolism Research

2020 Annual Report

Objectives
The following research project addresses a key unmet need of the USDA Human Nutrition Program, namely to test the metabolic impact of the Dietary Guidelines for Americans (DGA) --which has immediate nutrition policy implications. To achieve this goal, project scientists have designed an interdisciplinary effort leveraging tools from analytical chemistry, biochemistry, clinical nutrition, endocrinology, exercise biology, genetics, molecular biology, physiology, and psychological/CNS-based assessments - applying cutting edge phenotyping tools alongside complementary basic research experiments. Objective 1: Determine if achieving and maintaining a healthy body weight is the key health promoting recommendation of the Dietary Guidelines for Americans (DGA). Sub-objective 1A: Determine if achieving and maintaining a healthy body weight improves cardiometabolic risk in persons at-risk for metabolic disease. Sub-objective 1B: Determine if chronic stress, stress system responsiveness, and diet quality interact to influence metabolic responses and if these responses can be sustained over time. Sub-objective 1C: Determine the eating behavior characteristics, including dietary restraint, food cravings and preferences, motivation for food choice, and satiety response to a meal challenge to evaluate a) how diet interventions affect these variables b) which behavioral variables are associated with adherence to prescribed diet during the fully controlled interventions (mos 1 & 2) and during the partially controlled interventions (mos 3-6) c) and body weight changes during the follow-up period. Sub-objective 1D: Determine how weight loss and diet interact to influence lipoprotein particle metabolomic structure and their association with cardiometabolic risk factors. Objective 2: Identify hepatic gene polymorphisms associated with metabolic response to diets. This objective complements and integrates with Objective 1, which systematically tests the effect of the DGA. Objective 2 studies are designed to identify genetic sources of variation and their impact on metabolism in response to diet using a population of mice with defined genetic diversity to answer the following sub-objectives: Sub-objective 2A: Identify gene-diet interactions affecting adiposity and hepatic fat accumulation. Sub-objective 2B: Identify changes in gut microbiome composition associated with resistance to weight loss. Sub-objective 2C: Determine how atherogenic risk mechanisms alter lipoprotein particle lipidomic structure in cardiometabolic disease models. Objective 3: Develop Reference Values for mineral and vitamin concentrations in human milk, which will improve estimates of recommended nutrient intakes for breastfeeding infants and their mothers.

Approach
Objective 1 Hypotheses: 1A1: Consuming a DGA diet pattern for 8 wk will improve cardiometabolic risk factors, primarily insulin sensitivity and lipid profiles, compared to a typical American diet (TAD); 1A2: Cardiometabolic improvements resulting from the DGA diet will be greater in overweight/obese women when energy intake is restricted to result in weight loss; 1B: Phenotypic differences in psychological stress will partly explain variation in metabolic responses to a healthy diet; 1C1: Hunger, circulating ghrelin, and snack selection following a meal challenge will be greater with energy-restricted diets; 1C2: Adherence to the DGA diets will be better than adherence to the TAD diets when controlled for eating behavior, cognitive function, and subjective satiety; 1C3: Body weight changes in the follow-up period will associate with endocannabinoid tone, craving, and increased palatable food intake independent of intervention group; 1D1: Weight loss-induced metabolomic changes in plasma particles will decrease LDL region pro-atherogenic character, while increasing HDL anti-atherogenic character; 1D2: Diets rich in fruits, vegetables, and omega-3 fatty acids will reduce the 8 wk concentrations of non-enzymatically generated oxygenated lipids in LDL region lipoproteins. Objective 2 Hypotheses: 2A: Reduction in adiposity associated with dietary change is due to both genetic and dietary interactions; 2B: Gut microbial diversity will affect the weight loss response in a genetically diverse mouse population; 2C: Dietary manipulations will differentially change the lipoprotein oxylipins and ceramide composition in atherosclerosis prone vs. resistant cardiometabolic disease mouse models. A Randomized Control Trial will address hypotheses under Objective 1. This trial will be an intervention with human volunteers randomized to one of four parallel diet groups: 1. participants will consume a diet based on the Dietary Guidelines for Americans (DGA) and maintain energy balance; 2. participants will consume a control diet based on the typical American diet (TAD) and maintain energy balance; 3. participants will consume a DGA diet, restricted in calories to stimulate body weight loss; and 4. participants will consume a TAD, restricted in calories in order to stimulate body weight loss. A complementary mouse experiment will address Objective 2 hypotheses. This study will use diets formulated to match the diet types used in Objective 1 for the TAD and DGA. Four experimental groups will be tested: Ad libitum DGA diet; energy restricted DGA diet; ad libitum TAD diet; and energy restricted TAD diet. This study utilizes a systems genetic approach using genetic reference panels to assess gene x diet interactions that affect both the susceptibility to obesity and the resistance to weight loss. Objective 3 Hypothesis: Reference Values for vitamins and minerals in human milk can be established by measuring the range of concentrations in milk from well-nourished women who are not consuming additional micronutrients through supplements or fortified foods.

Progress Report
In support of Objective 1, ARS researchers at Davis, California, finalized, submitted, and received approval of the University of California, Davis (UCD) Institutional Review Board application to conduct the Objective 1 human intervention. The study team also developed and finalized the intervention diet menus. Substantial progress was made in the design and experimental methods for conducting the Objective 1 post-intervention follow up study. In support of Objective 2, ARS researchers completed study plans and received Institutional Animal Care and Use Committee (IACUC) approval for conducting mouse studies under this Objective. Additionally, the underlying analysis infrastructure has been developed on SciNet, the high-speed computing resource for ARS. These analyses include implementation of microbiome processing protocols and analysis of 16S microbiome sequence results. The analytic structure for genetic analysis of pending results from Objective 2 have been completed and validated on two independent datasets. In support of Objective 3, investigators in the four study sites completed collection of human milk samples from 700 participants at Visit 1 (2-3 days postpartum) which is 70% of the planned total and 60% of Visit 2 (at 1 to 3.5 months postpartum); 589 participants or 60% of Visit 3 (3.5 to 6 months postpartum); and 508 participants or 50% of the fourth visit (at 6 to 8.5 months) postpartum. In the same visits, blood is drawn from the mother and her infant for assessment of nutritional status biomarkers, hormones and immunity factors. Saliva is sampled from the mother and infant after dosing with deuterated water, to measure milk volume over a 14-day period. Feces from mothers and infants are collected for evaluation of the fecal microbiome. The USDA ARS facility in Davis, California, has received all of the samples from the Danish study, which has been completed: 46% of total anticipated samples from Rio de Janeiro; 45% from The Gambia, but none yet from Bangladesh. Laboratory analyses were completed on 400 milk samples for macronutrient content and 839 plasma samples for vitamin B12, folate, vitamin D and ferritin. Additionally, vitamin B12 was measured in 500 milk samples. All data are being entered into the Research Electronic Data Capture (REDCap) database, at the Medical Research Council site in The Gambia, to which the ARS researchers have access. ARS researchers submitted a new grant to the collaborator for additional funding to expand analyses, acquire equipment and service contracts, support data analysis and publication meetings, and add a new study on milk composition during the first month postpartum in the same four field sites. In a subordinate project with the French National Institute for Agricultural Research (INRA) (2032-51530-025-07N) investigating bioactive lipid mediators in plasma lipids as nutrition-sensitive biomarkers of cardiometabolic health, ARS researchers participated in an international intercalibration study with researchers in France and Germany to evaluate the comparability of data generated in different laboratories using harmonized methods and standards. Methods were found to be generally reproducible by trained personnel, but critical factors influencing data quality were identified. These results have been presented to the scientific community. Findings suggest that with appropriate control, total oxylipins are viable analytical targets for clinical assessments. Progress on this project supports the parent Sub-objectives 1D and 2C validating tools to be used to evaluate the key health promoting recommendations of the Dietary Guidelines for Americans. In a subordinate project (2032-51530-025-10N) on analytical capabilities, ARS researchers, in collaboration with researchers at UCD, West Coast Central Comprehensive Metabolomics Resource Core (WC3MRC) have developed novel and efficient methods for the analysis of fecal short chain fatty acids and bile acids, and expanded the coverage of quantitative metabolomics. These tools will be used to support the research efforts in project Objectives 1 and 2, and have been used to support research regionally throughout California, nationally in Alabama, Georgia, Nebraska, New York, North Carolina, Ohio and Illinois, and internationally in India and South Korea. In a subordinate project with the Washington State Fruit Commission (2032-51530-025-09R) on the cardiometabolic and cognitive effects of consuming sweet cherry juice, progress includes approval of the intervention by the UCD Institutional Review Board for conducting human studies. Sufficient levels of bioactive substances, such as anthocyanins, in the cherry juice were confirmed by biochemical analysis. All study standard operating procedures were completed, and recruitment and screening began. Three participants completed this 12-week placebo controlled intervention where they were tested on 6 test days to determine the effects of cherry juice consumption on blood pressure, vascular function, inflammatory and metabolic responses, glucose and insulin status, cognitive function, and cardiovascular reactivity to a mental stress test. Progress on this project supports the parent project Sub-objectives 1A and 1B to understand the relationship between diet, mental stress, and cardiometabolic function. Progress on a subordinate project with the Almond Board of California (2032-51530-025-16T) on satiety and eating behavior associated with a randomized intervention of almond or cereal mix snacks, included continuing approval of the intervention by the Institutional Review Board for conducting human studies, completion of data management plan, detailed standard operating procedures, and targeted recruitment. Eleven qualified participants were randomized to one of the two interventions, and two participants completed the full intervention before the study was suspended. Progress on this project expands the research on satiety that supports the parent Sub-objective 1C to determine eating behavior characteristics and satiety response to a meal challenge protocol. In a subordinate project (2032-51530-025-14S) on thiamine metabolism, ARS researchers in Davis, California, in collaboration with ARS researchers in Boston, Massachusetts, and researchers at the University of California, San Francisco, are investigating the impact of common pharmacological drugs on thiamine status and metabolism, with a focus on one of two thiamine specific transporters (SLC19A3). Initial results suggest that the antimicrobial drug trimethoprim increases plasma thiamine levels in healthy humans, but impacts on tissues are unknown. A mouse model expressing the human SLC19A3 generated by ARS researchers in Boston, Massachusetts, has been shown to rescue thiamine levels in the knockout mouse SLC19A3 by the ARS researchers in Davis, California. This novel mouse model will be used to explore the impact of SLC19A3 on tissue specific thiamine-dependent metabolism and the impacts of SLC19A3 transported drugs on these phenomena and it represents an expansion of the parent project Sub-objective 2. In a subordinate project with National Institutes of Health (2032-51530-025-03I), ARS researchers are investigating the genetic regulation of the composition of the gut microbiome and a microbiome derived metabolite- trimethylamine N-Oxide (TMAO). These studies utilize 472 mice derived from a novel population of mice called the Diversity Outbred (DO) bred with mice harboring transgenes for two hyperlipidemia-inducing mutations: human cholesteryl ester transfer protein (CETP) and apolipoprotein E-Leiden (APOE-Leiden). These studies have identified a number of bacteria altered by diet, under genetic regulation and associated with TMAO. Experiments to validate the associated bacteria and underlying mechanisms are planned. Progress on this project supports Sub-objective 2B to determine alterations in the microbiome associated with disease risk.

Accomplishments
1. Benefits of lower sodium and more vegetables in a whole food diet based on the Dietary Guidelines for Americans. Psychological stress is a growing public health concern. Nutritional habits may affect vulnerability or resilience to stress-related disease risk. Stress and how one reacts to stress are linked to increased risk for developing chronic diseases, such as diabetes, cardiovascular diseases, and neurological conditions and diseases. However, the factors that connect increased stress and disease risk remain unknown. In an eight-week randomized control trial that compared effects of a healthy Dietary Guidelines for Americans (DGA)-based diet and a relatively unhealthy diet (based on the typical American diet), ARS researchers in Davis, California, learned that adopting and adhering to a diet of higher quality (DGA) for eight weeks was shown to be generally more stressful in the absence of improvements in vegetable or sodium consumption. These study findings, which were published in the journal, “Nutrients”, supplies further evidence for the mental health benefits of maximizing vegetable and minimizing sodium consumption.

2. Behavioral importance of dietary carbohydrate as part of a Dietary Guidelines for Americans based diet. Vulnerability to mental stress is linked to chronic disease risk and exacerbation of chronic disease status. In an eight-week randomized control trial that compared effects of a healthy Dietary Guidelines for Americans (DGA)-based diet and relatively more unhealthy diet (based on the typical American diet), ARS researchers in Davis, California, learned that increasing dietary carbohydrate as part of the DGA-based diet reduced concentrations of a key stress response hormone, cortisol, and dampened psychological stress-induced cortisol reactions. These novel findings provide new evidence suggesting that, in the context of a healthy whole food diet, carbohydrate consumption may provide some protection from stress-related disease risk in some people. Furthermore, this apparent stress and cortisol dampening effect could reduce stress-related eating and improve the ability to sustain a healthier diet based on the DGA.

3. Omega-3 supplement doses to reduce cardiovascular risk. The omega-3 index is a simple status marker of long-chain omega-3 fatty acid consumption that is negatively associated with cardiovascular risk. From a clinical research study of long chain omega-3 fatty acid supplementation, predictive algorithms were developed by ARS researchers in Davis, California, using factors that influence how omega-3 supplementation influences the omega-3 fatty index. It was determined that body mass index, supplement dose, and the baseline omega-3 index explained over 60% of the variability in individual responses, and that consuming omega-3 fatty acids as triglycerides was approximately one and a half times more efficient than consuming phospholipids. The models generated can be used by clinicians to recommend efficacious omega-3 fatty acid doses and by researchers to estimate appropriate doses to reach beneficial omega-3 index levels in their study population. These findings, which were reported in the journal, “Nutrients”, provide important tools to both understand and improve cardiovascular health through the use of dietary supplements.

4. ALA-enriched butter reduces insulin resistance and supports omega-3 rich food consumption. Consuming butter enriched with the plant derived omega-3 fatty acid, alpha-linolenic acid (ALA), can reduce obesity and insulin resistance, which may decrease the risk for diabetes and cardiovascular diseases in overweight individuals. ALA cannot be synthesized in the human body and must be obtained from the diet to produce long chain omega-3 fatty acids which have diverse beneficial roles in human health. In collaboration with researchers at the University of Nebraska, ARS researchers in Davis, California, conducted experiments to determine if consuming ALA-enriched butter would reduce diet-induced obesity and its associated inflammation in a rodent model. ALA feeding reduced liver triglyceride accumulation and inflammation in body fat tissue and reduced insulin resistance. These findings suggest that consuming ALA-enriched butter conferred metabolic benefits against obesity-induced inflammation. These results also further support the cardioprotective benefits of consuming plant-based omega-3 fatty acids, and will be valuable to biomedical researchers, health care providers, and food manufacturers.

5. Blood lipid lowering effects of consuming chardonnay grape pomace powder. Grape pomace, a byproduct of winemaking, is a valuable, nutrient-rich agricultural resource that is underutilized, used mainly as landfill, animal feed, or recycled as compost. A study of healthy adults by ARS researchers in Davis, California, showed that consuming chardonnay grape pomace mixed with soluble extracts of the grape altered the blood lipid response after participants were challenged with a mixed breakfast meal. The pomace blend with higher fiber content produced lower triglycerides in the circulation following the meal, compared to the blend with higher extract content or the control. The significance of this finding is that circulating triglyceride concentrations are recognized as an important risk factor for cardiovascular disease. The higher fiber blend has greater nutritional complexity as it also contains essential micronutrient minerals, flavonoids, essential fatty acids, sterols, and stanols, making it a potentially important food ingredient to be used in heart-healthy food products.

6. Efficient analysis of multiple nutrients in human milk. Human milk composition, including its nutrient content, is now recognized to be affected by maternal diet and/or nutritional status. To provide Reference Values for the usual range of nutrients in milk from well-nourished women, ARS investigators in Davis, California, have developed and validated analytical methods that measure multiple nutrients simultaneously in small volumes of sample. Novel analytical methods have been developed, which now allow the accurate measurement of milk vitamins and minerals using lowest sample volumes to date, and providing accurate data in less time, including for concentrations of the many micronutrients and metabolites in milk previously not analyzable or measured with inaccurate methods. The new methods include ultra performance liquid chromatography (UPLC)-mass spectrometry, high pressure liquid chromatography coupled to fluorescence or ultraviolet detection, immunoassays, inductively coupled plasma mass spectrometry, and targeted metabolomics. These analytical methods are being used to measure milk composition in a four-country research project supervised by the ARS researchers in Davis, California.

7. Methods and protocols to validate the genetic regulation of the microbiome. The gut microbiome consists of a diverse number of microbial organisms, which can have detrimental and beneficial effects on health-related functions in the body. ARS investigators in Davis, California, developed and validated fecal microbiota transplantation (FMT), which is a procedure for implanting intestinal microbiota from a donor animal to the gastrointestinal tract of another animal. The microbiota from two types of mice (C57BL/6J and WSB/EiJ) differing in body fat and glucose tolerance were collected and transplanted into C57BL/6J mice previously treated with antibiotics to remove the microbiota. Unexpectedly, mice receiving WSB/EiJ microbiota had increased body fat, but improved glucose sensitivity. Large scale profiling and detailed analysis of the metabolites and microbiota in these mice indicated broad metabolic changes during and after FMT, which may explain the study results and provide novel pathways of disease susceptibility.

Review Publications
Fan, R., Kim, J., You, M., Giraud, D., Toney, A.M., Shin, S., Kim, S., Borkowski, K., Newman, J.W., Chung, S. 2019. Alpha-Linolenic acid-enriched butter attenuated high fat diet-induced insulin resistance and inflammation by promoting bioconversion of n-3 PUFA and subsequent oxylipin formation. Journal of Nutritional Biochemistry. 76. https://doi.org/10.1016/j.jnutbio.2019.108285.
Hughes, C.H., Bosviel, R., Newman, J.W., Pate, J.L. 2019. Luteal lipids regulate progesterone production and may modulate immune cell function during the estrous cycle and pregnancy. Frontiers in Endocrinology. 10. https://doi.org/10.3389/fendo.2019.00662.
Perrin, M.T., Pawlak, R., Allen, L.H., Hampel, D. 2019. Total water-soluble choline concentration does not differ in milk from vegan, vegetarian, and nonvegetarian lactating women. Journal of Nutrition. 150(3):512-517. https://doi.org/10.1093/jn/nxz257.
Soltani, H., Keim, N.L., Laugero, K.D. 2019. Increasing dietary carbohydrate as part of a healthy whole food diet intervention dampens eight week changes in salivary cortisol and cortisol responsiveness. Nutrients. 11(11). https://doi.org/10.3390/nu11112563.
Maeda-Smithies, N., Hiller, S., Dong, S., Suk Kim, H., Bennett, B.J., Kayashima, Y. 2020. Ectopic expression of the Stabilin2 gene triggered by an intracisternal A particle (IAP) element in DBA/2J strain of mice. Mammalian Genome. 31:2-16. https://doi.org/10.1007/s00335-019-09824-1.
Huda, N.M., Winnike, J., Crowell, J., O'Connor, A., Bennett, B.J. 2020. Microbial modulation of host body composition and plasma metabolic profile. Scientific Reports. 10. https://doi.org/10.1038/s41598-020-63214-1.
Walker, R.E., Harris Jackson, K., Tintle, N.L., Shearer, G.C., Bernasconi, A., Masson, S., Latini, R., Heydari, B., Kwong, R.Y., Flock, M., Kris-Etherton, P., Nedergaard Hedengran, A., Carney, R.M., Skulas-Ray, A., Gidding, S.S., Dewell, A., Gardner, C., Grenon, M.S., Sarter, B., Newman, J.W., Pedersen, T.L., Larson, M., Harris, W.S. 2019. Predicting the effects of supplemental EPA and DHA on the omega-3 index. American Journal of Clinical Nutrition. 110(4):1034-1040. https://doi.org/10.1093/ajcn/nqz161.
Foolad, N., Vaughn, A.R., Rybak, I., Burney, W., Chodur, G., Newman, J.W., Steinberg, F.M., Sivamani, R.K. 2019. Prospective randomized controlled pilot study on the effects of almond consumption on skin lipids and wrinkles. Phytotherapy Research. 33(12):3212-3217. https://doi.org/10.1002/ptr.6495.
Rajan, M., Sotak, M., Barrenas, F., Shen, T., Borkowski, K., Ashton, N., Biorserud, C., Lindahl, T.L., Ramstrom, S., Scholl, M., Lindahl, P., Fiehn, O., Newman, J.W., Perkins, R., Wallenius, V., Lange, S., Borgeson, E. 2019. Comparative analysis of obesity-related cardiometabolic and renal biomarkers in human plasma and serum. Scientific Reports. 9. https://doi.org/10.1038/s41598-019-51673-0.
La Frano, M.R., Brito, A., Johnson, C.M., Wilhelmson, B., Gannon, B., Fanter, R.K., Pedersen, T.L., Tanumihardjo, S.A., Newman, J.W. 2020. Metabolomics reveals altered hepatic bile acids, gut microbiome metabolites, and cell membrane lipids associated with marginal vitamin A deficiency in a Mongolian gerbil model. Molecular Nutrition and Food Research. 64(13). https://doi.org/10.1002/mnfr.201901319.
De Leon, A., Burnett, D.J., Rust, B.M., Casperson, S.L., Horn, W.F., Keim, N.L. 2020. Liking and acceptability of whole grains increases with a six-week exposure but preferences for foods varying in taste and fat content are not altered: a randomized controlled trial. Current Developments in Nutrition. 4(3). https://doi.org/10.1093/cdn/nzaa023.
Krishnan, S., Lee, F., Burnett, D.J., Kan, A., Bonnel, E.L., Allen, L.H., Adams, S.H., Keim, N.L. 2020. Challenges in designing and delivering diets and assessing adherence: A randomized controlled trial evaluating the 2010 Dietary Guidelines for Americans. Current Developments in Nutrition. 4(3). https://doi.org/10.1093/cdn/nzaa022.
Otoki, Y., Metherel, A.H., Pedersen, T., Yang, J., Hammock, B.D., Bazinet, R.P., Newman, J.W., Taha, A.Y. 2019. Acute hypercapnia/ischemia alters the esterification of arachidonic acid and docosahexaenoic acid epoxide metabolites in rat brain neutral lipids. Lipids. 55(1):7-22. https://doi.org/10.1002/lipd.12197.
Devi, S.K., Varkey, A., Dharmar, M., Holt, R.R., Allen, L.H., Sheshshayee, M.S., Preston, T., Keen, K.L., Kurpad, A. 2020. Amino acid digestibility of extruded chickpea and yellow pea protein is high and comparable in moderately stunted South Indian children with use of a dual stable isotope tracer method. Journal of Nutrition. 150(5):1178-1185. https://doi.org/10.1093/jn/nxaa004.
Perrin, M.T., Pawlak, R., Allen, L.H., Hampel, D. 2019. Total water-soluble choline concentration does not differ in milk from vegan, vegetarian, and non-vegetarian lactating women. Journal of Nutrition. 150(3):512-517. https://doi.org/10.1093/jn/nxz257.
Varkey, A., Devi, S., Mukhopadhyay, A., Kamat, N.G., Pauline, M., Dharmar, M., Holt, R., Allen, L.H., Thomas, T., Keen, C.I., Kurpad, A. 2020. Metabolome and microbiome alterations related to short-term feeding of a micronutrient-fortified, high-quality legume protein-based food product to stunted school age children: A randomized controlled pilot trial. Clinical Nutrition. https://doi.org/10.1016/j.clnu.2020.02.018.
Raiten, D.J., Allen, L.H., Slavin, J.L., Mitloehner, F.M., Thoma, G.J., Haggerty, P.A., Finley, J.W. 2020. Understanding the intersection of climate/environmental change, health, agriculture and improved nutrition: a case study on micronutrient nutrition and animal source foods. Current Developments in Nutrition. 4(7). https://doi.org/10.1093/cdn/nzaa087.
Yaktine, A.L., King, J.C., Allen, L.H. 2020. Why the derivation of nutrient reference values should be harmonized and how it can be accomplished. Advances in Nutrition. https://doi.org/10.1093/advances/nmaa048.
Henjum, S., Manger, M., Hampel, D., Brantsæter, A.L., Shahab-Ferdows, S., Bastani, N.E., Strand, T.A., Refsum, H., Allen, L.H. 2020. Vitamin B12 concentrations in milk from Norwegian women during the six first months of lactation. European Journal of Clinical Nutrition. 74:749-756. https://doi.org/10.1038/s41430-020-0567-x.
Anaya-Loyola, M.A., Brito, A., Vergara-Castaneda, H., Sosa, C., Rosado, J., Allen, L.H. 2019. Low serum B12 concentrations are associated with low B12 dietary intake but not with Helicobacter pylori infection or abnormal gastric function in rural Mexican women. Nutrients. 11(12):2922. https://doi.org/10.3390/nu11122922.
Williams, A.M., Ladva, C.N., Leon, J.S., Lopman, B.A., Tangpricha, V., Whitehead, R.D., Armitage, A.E., Wray, K., Morovat, A., Pasricha, S., Thurnham, D., Tanumihardjo, S.A., Shahab-Ferdows, S., Allen, L.H., Flores-Ayala, R.C., Suchdev, P.S. 2019. Changes in micronutrient and inflammation serum biomarker concentrations after a norovirus human challenge. Journal of Nutrition. 110(6):1456-1464. https://doi.org/10.1093/ajcn/nqz201.
Lweno, O.N., Sudfeld, C.R., Hertzmark, E., Manji, K.P., Aboud, S., Noor, R.A., Masanja, H., Salim, N., Shahab-Ferdows, S., Allen, L.H., Fawzi, W. 2020. Vitamin B12 is low in milk of early postpartum women in urban Tanzania, and was not significantly increased by high dose supplementation. Nutrients. 12(4). https://doi.org/10.3390/nu12040963.
Huda, N.M., Verhague, M., Albright, J., Smallwood, T., Bell, T., Que, E., Miller, D., Roshanravan, B., Allayee, H., Manuel De Villena, F., Bennett, B.J. 2020. Dissecting the genetic architecture of cystatin C in diversity outbred mice. Genes, Genomes, and Genomics. 10(7):2529-2541. https://doi.org/10.1534/g3.120.401275.