Research Project: Nutritional Epidemiology

Location: Jean Mayer Human Nutrition Research Center On Aging

2019 Annual Report

Objectives
LAB NAME: Nutritional Epidemiology 1. Using an epidemiologic approach, investigate the role of foods and food components such as carbohydrates sources (e.g., whole grains, sugar sweetened beverages), selected nutrients (e.g., folate, vitamin B12, magnesium), other bioactive food components (e.g., flavonoids, carotenoids), healthy dietary patterns (Dietary Guidelines for Americans, Mediterranean Diet) and gene-diet interactions in preventing age-related conditions such as weight gain, inflammation, insulin resistance and type 2 diabetes mellitus, cardiovascular disease, cancer, cognitive decline, musculoskeletal disorders, vision disorders and kidney disease. 1.A. Determine if higher sugar consumption is associated with cardiometabolic risk factors such as abdominal obesity, ectopic fat accumulation in liver and visceral depots, and inflammation and insulin resistance. 1.B. Determine the role that vitamin B6 plays in chronic inflammation and if modulation of vitamin B6 status can influence risk of inflammation. 1.C. Determine if inadequate vitamin B12 status is associated with reduced muscle power in older adults. 1.D. Determine if consumption of diets consistent with the 2010 Dietary Guidelines for Americans recommendations is associated with maintenance of healthy weight, normal metabolic function, and reduced risk of age-related chronic diseases. 1.E. Determine if lower dietary choline intake is related to accelerated brain aging and increased risk for dementia, and whether omega-3 fatty acids modifies these relationships. 1.F. Determine if specific flavonoids may reduce the risk of age-related chronic disease, including CVD, type 2 diabetes, and dementia. 1.G. Determine if dairy foods or components of dairy foods may help to prevent the development of age-related chronic disease. 2. Using an epidemiologic approach, examine the health effects of high folic acid intakes and the interaction between high folic acid intake and vitamin B12 status to investigate safe upper limits for intake of folic acid in older individuals (in collaboration with the HNRCA Vitamin and Metabolism Laboratory). 3. Using an experimental approach, conduct separate food-based intervention studies to examine the impact of dietary modification with individual foods (including whole grain, dietary fiber, added sugar, and fermented dairy) on weight change and ectopic fat depots (in collaboration with the HNRCA Energy Metabolism Laboratory), microbiota or intermediate metabolic markers of disease risk.

Approach
LAB NAME: Nutritional Epidemiology Many age-related conditions that result in disability and premature death, such as weight gain, type 2 diabetes, cardiovascular disease, cancer, cognitive decline, and musculoskeletal disorders, appear to have strong nutritional connections. However, the development of nutritional recommendations and public health interventions requires a greater understanding of the presumptive role that nutrition plays in healthy aging. Our project objectives will be achieved through the application of observational epidemiologic methods in community-based aging population samples to identify dietary patterns, foods and food components associated with age-related health outcomes and testing of these candidate foods and food components in intervention trials of intermediate markers of age-related disease risk.

Progress Report
This is the final report for the project 8050-51530-013-00D. Researchers in the Nutritional Epidemiology Program have had substantial success on a number of projects under Objective 1. The research program on carbohydrate nutrition and metabolic health, which includes projects under Objectives 1.A (added sugars), 1.H (dietary fiber), 1.N (whole grains and carbohydrate quality) and 1.O (sugar and branched chain amino acids), represents a major focus of the lab’s research. The lab has successfully completed projects demonstrating that greater sugar-sweetened beverage consumption among middle-aged and older adults was associated with a higher risk of fatty liver disease, greater increases in visceral adipose tissue with aging, higher risk of dyslipidemia, and greater progression of insulin resistance and higher risk of prediabetes (Objectives 1.A). In collaboration with investigators from Boston University, researchers in the Nutritional Epidemiology Program observed that higher sugar-sweetened beverage intake was associated with preclinical Alzheimer’s disease; however, sugar-sweetened beverages were not associated with ischemic stroke, all-cause dementia, or incidence of Alzheimer’s disease. Artificially sweetened beverage consumption was associated with an increased risk of all three of these outcomes. The research program on dietary fiber continues with great success (Objective 1.H). The Nutritional Epidemiology Program’s publicly available, comprehensive dietary fiber database linking fiber to health outcomes (Dietary Fiber and Human Health Outcomes database) has continued to grow to version 5.0, was published in 2019 and updated with literature through May 2018. A searchable interface researchers in the lab helped to create is accessible at the following link: https://ilsina.org/fiberdb/. Researchers in the Nutritional Epidemiology Program continued their whole grain research with the development of a database of published human intervention studies on whole grain intake and health outcomes, similar to our fiber database. Members of the research team also collaborated with investigators from the HNRCA (Human Nutrition Research Center on Aging) Antioxidants Research Laboratory to examine phytochemical and bioactive properties of two whole grains, oats and barley, and in collaboration with investigators from Boston University, researchers in the lab observed that higher dietary fiber intake was associated with a reduced incidence of knee osteoarthritis and knee pain worsening with age and that any effect of fiber may be partially mediated through reduced body weight. The projects examining healthy dietary pattern fall under three objectives. As part of the work on the health benefits of adherence to the Dietary Guidelines for Americans (Objective 1.D), researchers in the Nutritional Epidemiology Program demonstrated that higher overall diet quality was associated with a decreased risk of developing a low estimated glomerular filtration rate. Work also progressed with the finalization of the 2015 Dietary Guidelines Adherence Index, which was used to examine the impact of a healthy diet on gene expression. Researchers conducted a transcriptome-wide association study (transcriptome referring to all RNA molecules expressed from all genes) with the Dietary Guidelines Adherence Index score and observed that the Dietary Guidelines Adherence Index was significantly associated with the expression of 19 genes, and the expression profile of these genes was associated with several metabolic traits (e.g., glucose levels, metabolic syndrome, type 2 diabetes risk). Researchers also observed that increasing diet quality was associated with reduced risk for new-onset fatty liver disease. As part of another aspect of our ongoing research efforts on healthy dietary patterns, researchers have developed an index to simultaneously assess the dietary quality and environmental impact for a wide range of foods commonly consumed in the U.S. so that researchers can identify sustainable diet patterns that maximize diet quality and minimize environmental impact (Objective 1.I). Findings from early applications of this Dietary Environmental Index indicate that plant-based foods on average provide a better combination of higher nutritional quality and lower environmental impact. However, the range of index scores within categories of foods is quite broad such that the ranges of Dietary Environmental Index scores for fruits and vegetables overlaps substantially with scores for the dairy, meat and fish categories. The Program’s focus on dietary patterns and healthy aging continues with progress on the Adhering to Dietary Approaches for Personal Taste study (Objective 1.L). The Adhering to Dietary Approaches for Personal Taste study was initiated in 2015, as a feasibility survey to determine whether online data collection among followers of popular diets could be achieved and willingness of participants to be involved in future, more comprehensive research. In a subsequent pilot study, researchers from the Nutritional Epidemiology Program have shown that whole-food, plant-based followers often emphasized health-related motivations, while vegans and vegetarians/pescatarians tended to emphasize ethical motivations, such as environmental concern and animal welfare. As part of the lab’s research program on the health benefits of dietary flavonoids (Objective 1.F), researchers observed that higher anthocyanin and flavonol intakes are associated with a lower overall index of inflammation biomarkers and higher intakes of flavan-3-ols and their polymers were associated with a reduction in oxidative stress biomarkers. In another study researchers found that higher intake of flavonols, flavan-3-ols, anthocyanins, polymeric flavonoids and total flavonoids were associated with a lower incidence of prediabetes. Scientists from the lab also observed that flavonol intake was significantly associated with lower risk of cardiovascular disease incidence. Research from the lab on dairy food consumption and cardiometabolic health (Objective 1.G) resulted in a paper showing that higher consumption of skim/low-fat milk and yogurt could delay the onset of hypertension. As part of the ongoing research on dairy food consumption and cardiometabolic health, the lab demonstrated that associations of dairy with incident prediabetes or diabetes varied both by dairy product and type and by baseline glycemic status. Researchers from the Nutritional Epidemiology Program are currently using a metabolomics approach to identify metabolic signatures associated with consumption of different dairy foods. As part of this project, researchers continue to update the examination of the trends in dairy consumption from 1999 to 2014 among a representative sample of Americans using data from the National Health and Nutrition Examination Survey. Researchers continued research on the lab’s objective to examine the relationship between protein intake in middle aged and older adults and healthy aging (Objective 1.J), as characterized by maintenance metabolic health and physical performance and prevention of physical disability with aging. As part of this project, researchers from the lab demonstrated that higher, long-term protein intakes, based on 5 dietary assessments over 20 years of follow-up, were favorably associated with changes in markers of cardiometabolic health. Scientists also observed that higher protein intake was strongly associated with a 30% lower risk of developing functional disabilities at over 20 years of follow-up. Scientists also examined the role of protein intake in mitigating “inflammaging” (i.e., the low-grade chronic systemic inflammation that occurs with physiological aging). In an effort to better understand the role of water intake and hydration in healthy aging (Objective 1.M), researchers from the Nutritional Epidemiology Program recently initiated a study to assess the relationship between hydration status and fluid intake in a large cohort of older Americans to determine their role in maintenance of metabolic health in older individuals. The lab’s examination of associations between hydration/ fluid intake and cardiometabolic risk factors found that higher total fluid and plain water intake were associated with higher high-density lipoprotein cholesterol levels, higher water intake was associated with lower triglyceride concentration and higher total fluid intake was associated with lower systolic blood pressure. The Nutritional Epidemiology Program has two objectives examining the relationship between B vitamins and healthy aging, Objective 1.C (vitamin B12 and muscle power) and Objective 2 (modification of vitamin B12 associations on health outcomes by high folate status). Based on preliminary findings from the National Health and Nutrition Examination Survey III that support a relationship between vitamin B12 deficiency and lower muscle power, researchers from the lab undertook a study of vitamin B12 status and its relationship to muscle power in a sample of 80 men and women (age 70-85 yrs) at risk for mobility-related disability. Researchers failed to observe any relationship between vitamin B12 status and muscle power. As part of the lab's program on B vitamins (Objective 2), researchers assessed, in collaboration with investigators from the Neuroscience and Aging Laboratory and Hebrew University of Jerusalem, whether supplementing with a high dose of B vitamins for up to five years could decrease cognitive decline in a group of stable kidney transplant recipients. Researchers found that, while nearly all of the participants were already B vitamin sufficient before the study intervention, further B vitamin supplementation modestly improved performance on tests of memory and information processing speed, suggesting that B vitamin supplementation in patients who had poor nutritional status may have greater impact on cognitive function.

Accomplishments
1. High protein intake helps preserve physical function. Research around the role of protein in preventing frailty, disability, and physical dysfunction is limited. Thus, the aim of ARS funded researchers in Boston, Massachusetts, was to examine associations between protein intake and maintenance of physical function and prevention of physical disability. The researchers hypothesized that higher protein intake would be associated with maintenance of function and used data from nearly 3,000 participants from the Framingham Heart Study Offspring cohort over a 20-year timeframe. The investigators observed better physical function that correlated with lower odds of falls, fractures, and frailty in the highest protein intake group. These results suggest that optimizing protein intake may play a role in helping to preserve muscle mass and strength, protect against frailty and falls, and maintain independence among aging adults.

Review Publications
Hruby, A., Jacques, P.F. 2019. Dietary protein and changes in biomarkers of inflammation and oxidative stress in the Framingham Heart Study Offspring cohort. Current Developments in Nutrition. https://doi.org/10.1093/cdn/nzz019.
Hennein, R., Liu, C., McKeown, N.M., Hoffman, U., Long, M.T., Levy, D., Ma, J. 2019. Increased diet quality is associated with long-term reduction of abdominal and pericardial fat. Obesity. 27(4):670-677. https://doi.org/10.1002/oby.22427.
Shams-White, M.M., Chui, K., Deuster, P.A., McKeown, N.M., Must, A. 2019. Investigating items to improve the validity of the five-item Healthy Eating Score compared with the 2015 Healthy Eating Index in a military population. Nutrients. 11(2):251. https://doi.org/10.3390/nu11020251.
Dai, Z., Jafarzadeh, S., Niu, J., Felson, D.T., Jacques, P.F., Li, S., Zhang, Y. 2018. Body mass index mediates the association between dietary fiber and symptomatic knee osteoarthritis in the Osteoarthritis Initiative and the Framingham Osteoarthritis Study. Journal of Nutrition. 148:1961-1967. https://doi.org/10.1093/jn/nxy231.
Hurby, A., Guasch-Ferre, M., Bhupathiraju, S.N., Manson, J.E., Willett, W.C., McKeown, N.M., Hu, F.B. 2017. Magnesium intake, quality of carbohydrates, and risk of type 2 diabetes: results from three U.S. cohorts. Diabetes Care. https://doi.org/10.2337/dc17-1143.
Hurby, A., Sahni, S., Bolster, D., Jacques, P.F. 2018. Protein intake and functional integrity in aging: the Framingham Heart Study offspring. Journal of Gerontology Medical Science. https://doi.org/10.1093/gerona/gly201.
Hruby, A., Jacques, P.F. 2018. Dietary protein and changes in markers of cardiometabolic health across 20 years of follow-up in middle-aged Americans. Public Health Nutrition. 21(16):2998-3010. https://doi.org/10.1017/S1368980018001854.
Zhang, X., Xia, J., Del Gobbo, L.C., Hruby, A., Dai, Q. 2017. Serum magnesium concentrations and all-cause, cardiovascular, and cancer mortality among U.S. adults: results from the NHANES I Epidemiologic Follow-up Study. Clinical Nutrition. 37(5):1541-1549. https://doi.org/10.1016/j.clnu.2017.08.021.
Sawicki, C., Livingston, K.A., Ross, A.B., Jacques, P.F., Koecher, K., McKeown, N.M. 2018. Evaluating whole grain intervention study designs and reporting practices using evidence mapping methodology. Nutrients. 10(8). https://doi.org/10.3390/nu10081052.
Karlsen, M.C., Rogers, G., Miki, A., Lichtenstein, A.H., Folta, S.C., Economos, C.D., Jacques, P.F., Livingston, K.A., McKeown, N.M. 2019. Theoretical food and nutrient composition of whole-food plant-based and vegan diets compared to current dietary recommendations. Nutrients. 11(3):625. https://doi.org/10.3390/nu11030625.
Dashti, H.S., Merino, J., Lane, J.M., Song, Y., Smith, C.E., Tanaka, T., McKeown, N.M., Tucker, C., Sun, D., Bartz, T.M., Li-Gao, R., Nisa, H., Reutrakul, S., Lemaitre, R.N., Alshehr, T.M., de Mutsert, R., Bazzano, L., Qi, L., Knutson, K.L., Psaty, B.M., Mook-Kanamori, D.O., Perica, V.B., Neuhouser, M.L., Scheer, F.A., Rutter, M.K., Garaulet, M., Saxena, R. 2019. Genome-wide association study of breakfast skipping links clock regulation with food timing. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqz076.
Maki, K.C., Palacios, O.M., Koecher, K., Sawicki, C., Livingston, K.A., Bell, M., Cortes, H.N., McKeown, N.M. 2019. The relationship between whole grain intake and body weight: results of meta-analyses of observational studies and randomized controlled trials. Nutrients. 11(6):1245. https://doi.org/10.3390/nu11061245.
Sawicki, C.M., Livingston, K.A., Obin, M., Roberts, S.B., Chung, M., McKeown, N.M. 2017. Dietary fiber and the human gut microbiota: application of evidence mapping methodology. Nutrients. 9(2). https://doi.org/10.3390/nu9020125.
Koecher, K., McKeown, N.M., Sawicki, C.M., Menon, R., Slavin, J.L. 2019. Effect of whole-grain consumption on changes in fecal microbiota: a review of human intervention trials. Nutrition Reviews. 77(7):487-497. https://doi.org/10.1093/nutrit/nuz008.
Makarem, N., Bandera, E.V., Lin, Y., Jacques, P.F., Hayes, R.B., Parekh, N. 2018. Consumption of sugars, sugary foods, and sugary beverages in relation to adiposity-related cancer risk in the Framingham Offspring Cohort (1991-2013). Cancer Prevention Research. 11(6). https://doi.org/10.1158/1940-6207.CAPR-17-0218.
McKeown, N.M., Griffin, T. 2019. Whole grains, health, and sustainability. Cereal Foods World. 64(3):0029. https://doi.org/10.1094/CFW-64-3-0029.
Sawicki, C., Livingston, K.A., McKeown, N.M. 2019. Whole grains and cardiovascular health. Cereal Foods World. 64(3):0031. https://doi.org/10.1094/CFW-64-3-0031.