Skip to main content
ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Research Project #426848

Research Project: Nutritional Epidemiology

Location: Jean Mayer Human Nutrition Research Center On Aging

2018 Annual Report

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.

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
We have substantial progress to report on a number of projects that fall under Objective 1. As part of Objective 1.A, we observed that sugar-sweetened beverages (SSB) intake among 6000 individuals was significantly associated with higher total cholesterol, LDL-cholesterol, and triglyceride and lower HDL-cholesterol. We also initiated a study of SSB consumption and HDL and LDL particle size. We are also examining whether gene variants (i.e., single-nucleotide polymorphisms or SNPs) in the carbohydrate-responsive element-binding protein pathway, which is involved in sugar and lipid metabolism, modify associations between SSB and metabolic traits (Objective 1.A). We identified 19 SNPs significantly associated with HDL levels and 127 SNPs significantly associated with triglyceride levels, and are now examining this association with a meta-analysis using six Cohorts for Heart & Aging Research in Genomic Epidemiology (CHARGE) Consortium cohorts (n=36,905) for our discovery analyses. Our research program on dietary fiber continues with great success (Objective 1.H). Our publicly available, comprehensive Dietary Fiber and Human Health Outcomes (v.4.0) database linking fiber to health outcomes ( has been updated with literature through May 2017, capturing 1,044 studies. It has been utilized by researchers in government, industry, and academia. We used the database for a publication that identified 188 distinct studies reporting on at least one outcome related to modulation of the colonic microflora or colonic fermentation/short-chain fatty acid production. Characteristics of these studies and a sub-analysis of oligosaccharides and bacterial composition of the gut were described in this publication. In a second publication we discussed misconceptions of the health benefits of isolated fibers, focusing on three health outcomes, (cholesterol lowering, glycemic control, and stool form [constipation and diarrhea]). As dietary carbohydrates consist of a diverse compounds (starch, fibers, and sugars) with a wide range of physiological properties, we initiated analyses examining novel indices of carbohydrate quality, which may better capture multiple aspects of carbohydrate quality, in relation to markers of cardiometabolic risk, such as serum lipids, blood pressure, glycemic traits, adiposity (including fat depots), and inflammation (Objective 1.N). The novel measures of carbohydrate quality we will examine include a carbohydrate quality index score and ratios of total carbohydrate to total fiber and total carbohydrate to cereal fiber intakes. Our Program’s focus on dietary patterns and healthy aging continues with progress on the Adhering to Dietary Approaches for Personal Taste (ADAPT) study (Objective 1.L). A 2015 ADAPT Feasibility Survey (FS) enrolled 9726 participants. Self-reported dietary patterns in the FS included the following groups: whole-food, plant-based (25%); vegan and raw vegan (19%); Paleo (14%); try to eat healthy (11%); vegetarian and pescatarian (9%); whole food (8%); Weston A. Price (5%); and low-carbohydrate (low-carb) (4%). Based on the success of the FS, we designed a larger ADAPT Pilot Study that included 18 study questionnaires over the 6-week study period with the aim of streamlining and improving the participant experience and incorporating longitudinal data collection. Approximately 7,300 ADAPT FS participants and approximately 2,400 of these participants enrolled and participated in the 6 week ADAPT Pilot Study. We also completed two manuscript using data from ADAPT: one describing the best practices for web-based recruitment and survey methodology suitable to capture followers of popular diets and a second examining weight status among followers of a diet pattern for 1-5 yrs (n=4,067), which showed that body mass index (BMI) was lower among individuals who reported making a conscious decision to adhere to a specific diet for 1-5 years compared to those without a specific pattern but trying to eat healthy. Other ongoing Adapt projects include analyzing data on motivations for choosing to adhere to a specific dietary pattern, comparing food and nutrient levels estimated from MyPlate meal recommendations to those of vegan and paleo meal plans derived from popular diet sources, and examine how factors, including motivation, self-efficacy, convenience and access to food, and social support, are associated with self-reported long-term adherence to specific dietary patterns, specifically intake patterns that are healthier than the standard American diet. As part of another aspect of our ongoing research efforts on healthy dietary patterns, we have developed an index to simultaneously assess the dietary quality versus environmental impact for a wide range of foods commonly consumed in the U.S. so that we can identify sustainable diet patterns that maximize diet quality and minimize environmental impact (Objective 1.I). Preliminary findings from early applications of this index indicate that, as expected, 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 index scores for fruits and vegetables overlaps substantially with scores for the dairy, meat and fish categories. We also continue to make progress on our research related to benefits of healthy aging for selected nutrients and dietary components. We have initiated a study examining the relationship between usual flavonoid intake and brain aging (Objective 1.F). Data analyses initiated for the first phase of this project will examine the relationship between flavonoid intake and cognitive function based on a series of neuropsychological tests administered three times of a period of approximately 15 years. Our work on protein intake in middle-aged and older adults and healthy aging over a 20+ years of follow-up demonstrated higher protein intakes were favorably associated with annual rate of increase in systolic blood pressure and decrease of estimated glomerular filtration rate with age but an unfavorable association was also noted for fasting glucose levels, which rose faster with age among those with the highest protein intakes (Objective 1.J). We are currently assessing the relationship between protein intake and maintenance of functional integrity with aging. We also initiated a study to assess the importance of hydration in healthy aging. Preliminary analyses from our work on examining associations between hydration and healthy aging showed that lower hydration status/fluid intake are associated with higher circulating triglyceride concentrations and lower HDL cholesterol concentrations (Objective 1.M).

1. Dietary Index developed to maximize nutrition value and minimize environmental impact of foods. Integrating sustainability into healthy dietary patterns is hindered by the lack of a standard method to simultaneously evaluate the nutritional quality and ecological effects of food choices. To help people make healthy food choices that are good for the environment ARS-funded researchers in Boston, Massachusetts developed the Dietary Environmental Index (DEX), a standardized method that ranks foods based on the ratio of a nutrient density score and environmental impact score that reflects the impact each food has on land use, climate change and the use and quality of water. The DEX has ranked more than 7700 foods consumed by participants from the 2007-2008 National Health and Nutrition Examination Survey (NHANES). Foods with higher DEX scores have greater nutrient density and less environmental impact and include most fruit, vegetable, legume, and nut categories. Cereals, pasta, and grain products ranged predominantly around the median DEX. Among dairy, milk and cheeses generally ranked 25th–50th percentile. Meat-based dishes fluctuated around the 25th percentile, with higher DEX generally for poultry and egg products and lower scores for beef and pork. Within each food group DEX scores vary widely so knowledge of the index will allow people to select a variety of foods from all categories. This index could become a powerful tool for making food choices that are good for the health of individuals and the environment while supporting a more sustainable food system.

Review Publications
McKeown, N.M., Dashti, H.S., Ma, J., Haslam, D., Kiefte-De Jong, J.C., Smith, C.E., Tanaka, T., Graff, M., Lemaitre, R.N., Rybin, D., Sonestedt, E., Frazier-Wood, A., Mook-Kanamori, D.O., Li, Y., Wang, C.A., Leermakers, E.T., Mikkila, V., Young, K.L., Mukamal, K.J., Cupples, L.A., Schulz, C.A., Chen, T., Li-Gao, R., Huang, T., Oddy, W.H., Raitakari, O., Rice, K., Meigs, J., Ericson, U., Steffen, L., Rosendaal, F.R., Hofman, A., Kahonen, M., Psaty, B.M., Brunkwall, L., Uitterlinden, A.G., Viikari, J., Siscovick, D.S., Seppala, I., North, K.E., Mozaffarian, D., Dupius, J., Orho-Melander, M., Rich, S.S., De Mutsert, R., Qi, L., Pennell, C.E., Franco, O.H., Lehtimaki, T., Herman, M. 2017. Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway: a meta-analysis. Diabetologia.
Hannou, S., Haslam, D.E., McKeown, N.M., Herman, M. 2018. Fructose metabolism and metabolic disease. Journal of Clinical Investigation. 128(2):545-555.
Markarem, N., Bandera, E.V., Lin, Y., Jacques, P.F., Richard, H.B., Parekh, N. 2017. Carbohydrate nutrition and risk of adiposity-related cancers: results from the Framingham Offspring cohort (1991-2013). British Journal of Nutrition. 117:1603-1614.
Foster, M.C., Hwang, S., Massaro, J.M., Jacques, P.F., Fox, C.S., Chu, A.Y. 2015. Lifestyle factors and indices of kidney function in the Framingham Heart Study. The American Journal of Nephrology. 41:267-274.
Hruby, A., Ma, J., Rogers, G., Meigs, J.B., Jacques, P.F. 2017. Associations of dairy intake with incident prediabetes or diabetes in middle-aged adults vary by both dairy type and glycemic status. Journal of Nutrition.
Pase, M.P., Himali, J.J., Jacques, P.F., DeCarli, C., Satizabal, C.L., Aparicio, H., Vasan, R.S., Beiser, A.S., Seshadri, S. 2017. Sugary beverage intake and preclinical Alzheimer's disease in the community. Alzheimer's & Dementia. 13(9):955-964.
Cassidy, A., Rogers, G., Peterson, J.J., Dwyer, J.T., Lin, H., Jacques, P.F. 2015. Higher dietary anthocyanin and flavonol intakes are associated with anti-inflammatory effects in a population of US adults. American Journal of Clinical Nutrition. 102:172-181.
Ruiz-Canela, M., Hruby, A., Clish, C., Liang, L., Martinez-Gonzalez, M.A., Hu, F.B. 2017. Comprehensive metabolomic profiling and incident cardiovascular disease: a systematic review. Journal of the American Heart Association. 6(10):e005705.
Ikezaki, H., Furusyo, N., Jacques, P.F., Shimizu, M., Murata, M., Schaefer, E.J., Urita, Y., Hayashi, J. 2017. Higher dietary cholesterol and omega-3 fatty acid intakes are associated with a lower success rate of Helicobacter pylori eradication therapy in Japan. American Journal of Clinical Nutrition. 106(2):581-588.
Ikezaki, H., Ai, M., Schaefer, E.J., Otokozawa, S., Asztalos, B.F., Nakajima, K., Zhou, Y., Liu, C., Jacques, P.F., Cupples, L., Furusyo, N. 2017. Cardiovascular disease prevalence and insulin resistance in the Kyushu-Okinawa Population Study and the Framingham Offspring Study. Journal of Clinical Lipidology. 11:348-356.
Ma, J., McKeown, N.M., Hwang, S., Hoffman, U., Jacques, P.F., Fox, C.S. 2016. Sugar-sweetened beverage consumption is associated with change of visceral adipose tissue over 6 years of follow-up. Circulation. 133:370-377.
Mozaffarian, D., Dashti, H.S., Wojczynski, M.K., Chu, A.Y., Nettleton, J.A., Mannisto, S., Kristiansson, K., Reedik, M., Lahti, J., Houston, D.K., Cornelis, M.C., Van Rooij, F.J., Dimitriou, M., Kanoni, S., Mikkila, V., Steffen, L.M., De Oliveira Otto, M.C., Qi, L., Psaty, B., Djousse, L., Rotter, J.I., Harald, K., Perola, M., Rissanen, H., Jula, A., Fischer, K., Mihailov, E., Feitosa, M.F., Ngwa, J.S., Xue, L., Jacques, P.F., Perala, M., Palotie, A., Liu, Y., Nalls, M.A., Ferrrucci, L., Hernandez, D., Manichaikul, A., Tsai, M.Y., Kiefte-De Jong, J.C., Hofman, A., Uitterlinden, A.G., Rallidis, L., Ridker, P.M., Rose, L.M., Buring, J., Lehtimaki, T., Kahonen, M., Viikari, J., Lemaitre, R., Salomaa, V., Knekt, P., Metspalu, A., Borecki, I.B., Cupples, L., Eriksson, J.G., Kritchevsky, S.B., Bandinelli, S., Siscovick, D., Franco, O.H., Deloukas, P., Dedoussis, G., Chasman, D.I., Raitakari, O., Toshiko, T. 2017. Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts. PLoS One. 12(12):e0186456.
Izezaki, H., Ai, M., Schaefer, E., Otokozawa, S., Asztlos, B.F., Nakajima, K., Zhou, Y., Liu, C., Jacques, P.F., Cupples, L.A., Furusyo, N. 2016. Ethnic differences in glucose homeostasis markers between the Kyushu-Okinawa Population Study and the Framingham Offspring Study. Scientific Reports. 6:36725.
Karlsen, M.C., Lichtenstein, A.H., Economos, C., Folta, S., Rogers, G.T., Jacques, P.F., Livingston, K., Rancano, K., McKeown, N.M. 2018. Web-based recruitment and survey methodology to maximize response rates from followers of popular diets: the Adhering to Dietary Approaches for Personal Taste (ADAPT) feasibility survey. Current Developments in Nutrition. 2(5).
Haslam, D., McKeown, N.M., Herman, M.A., Lichtenstein, A.H., Dashti, H.S. 2018. Interactions between genetics and sugar-sweetened beverage consumption on health outcomes: a review of gene-diet interaction studies. Frontiers in Endocrinology. 8:368.