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

2017 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 made substantial progress on a number of projects that are part of our research program on carbohydrate nutrition and metabolic health (Objective 1.) We have continued our research program on the relationship between added sugars and cardiometabolic health (Subobjective 1.A). We have demonstrated that sugar-sweetened beverage (SSB) consumption is associated with the progression of insulin resistance and prediabetes. Another ongoing project examines the possible genetic modification of the cardiometabolic consequence of added sugar intake by Carbohydrate Responsive Element Binding Protein (ChREBP) in which we have demonstrated that consumption of SSB differentially influences insulin sensitivity in persons with underlying genetic differences in the ChREBP gene. We recently initiated a new study to examine the association between SSB intake and metabolic traits (HDL and triglycerides). We also extended our work on added sugars to examine their potential role in stroke and dementia. In collaboration with investigators from Boston University, we observed that higher intake of sugar-sweetened beverages was associated with markers of Alzheimer’s disease, including lower total brain volume and poorer performance on tests of episodic memory. However, in a second study that examined the role of sugar sweetened and artificially sweetened beverages in the incidence of stroke and dementia, we observed that artificially sweetened soft drink consumption was associated with an increased risk of ischemic stroke, all-cause dementia, and Alzheimer’s disease, but sugar-sweetened beverages were not associated with any of these outcomes. Our research program on whole grains and dietary fiber continues with great success. Our publicly available, comprehensive dietary fiber database linking fiber to health outcomes ( has continued to grow to version 3.1, capturing 991 studies, and is currently in the process of being updated for 2017. In addition to the database, we have created a detailed corresponding user manual and web tutorial on accessing and using the database. We developed a similar database of published human intervention studies on whole grain intake and health outcomes. This database contains data on 283 papers, and we have used it to capture and summarize the current body of literature and methodological variability in dietary whole grain interventions, allowing us to evaluate study design, report practices, and highlight issues that could be better addressed in future research. Members of our research team also collaborated with investigators from the Human Nutrition Research Center of Aging (HNRCA) Antioxidants Research Laboratory to examine phytochemical and bioactive properties of two whole grains, oats and barley, and in collaboration with investigators from Boston University, we 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 final research based on our carbohydrate nutrition program was a study examining the role of carbohydrate intake and other aspects of carbohydrate quality on cancer risk. To address the contradictory findings between carbohydrate and cancer risk, we collaborated with investigators at New York University and Rutgers University to examine the role of carbohydrate nutrition on risk of the three most common adiposity-related cancers in the United States: breast, prostate, and colorectal cancers. Our results indicated that the amount of carbohydrate, glycemic index, and intake of whole or refined grains were not associated with combined incidence of adiposity-related cancers, although higher carbohydrate intake and higher whole grain intake were associated with about a 40% lower breast cancer risk. Our work on the health benefits of adherence to the Dietary Guidelines for Americans (Subobjective 1.D) has progressed with the finalization of the 2015 Dietary Guidelines Adherence Index (DGAI). As part of our research program on the health benefits of dietary flavonoids (Objective 1.F) we have initiated a study to examine the relationship between flavonoid intake and maintenance of brain health at older ages. Our ongoing research on dairy food consumption and cardiometabolic health (Objective 1.G) involves examining the role of dairy in development of prediabetes and progression of prediabetes to diabetes. We are also using a metabolomics approach to identify metabolic signatures associated with consumption of different dairy foods. As part of this project, we continue to update our 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 (NHANES). As part of our work on nutrition and cardiometabolic risk (Objective 1,) one of our investigators examined the use of metabolomics as a tool for cardiovascular biomarker discovery based on a systematic review, reporting that the number of longitudinal studies assessing associations between comprehensive metabolomic profiles and cardiovascular disease (CVD) risk is very limited and summarizing the literature is challenging owing to the widely varying analytical tools and diversity of methodological and statistical approaches. A project on ethnic differences in cardiometabolic risk, performed in collaboration with investigators from the HNRCA Cardiovascular Nutrition Laboratory, Boston University and various universities and hospitals in Japan, examined glucose homeostasis and insulin resistance and their relationship with cardiovascular risk in Japanese and American populations. The project demonstrated that there is significantly less impaired fasting glucose and insulin resistance but higher diabetes prevalence in men from Fukuoka, Japan than in men from Framingham, Massachusetts, indicating that insulin deficiency may be an important cause of diabetes in Japan. We went on to show that while CVD prevalence rates were more than 6-fold higher in Framingham men and women than their Fukuoka counterparts, none of the traditional risk factors explained these large differences in CVD risk, but the ethnic differences we observed in insulin levels may explain some differences in CVD risk. We continued our project examining the relationship between protein intake in middle age and healthy aging (Objective 1) as characterized by maintenance metabolic health and physical performance and prevention of physical disability. Preliminary findings indicate that usually protein intake from mid-life through older ages has little effect on changes in cardiometabolic risk factors, but higher protein intake was strongly associated with a lower risk of developing functional disabilities at older ages. We also completed a feasibility phase of a study, the Adhering to Dietary Approaches for Personal Taste (ADAPT) study, during which we identified consumers of popular diets with the intention of conducting a larger, long-term study in the future. This research initiative was designed to identify consumers of popular diets including Paleo, low-carb, vegetarian, vegan, raw, Mediterranean, gluten-free, low-fat, and others to examine how nutrient intakes differ between diets, determine what factors affect adherence to these different diets, and compare the relative metabolic impacts of the various diets (Objective 1). During the past year, we identified, tested, and revised questionnaires for study inclusion, programmed all questionnaires into Qualtrics for electronic completion, set up email management software for communicating with participants, communicated periodic updates to keep feasibility study participants engaged, developed all study communications (i.e. recruitment, weekly questionnaire emails, etc.), and tested a participant portal which will allow for a more streamlined participant experience to maximize retention. The portal and study communications have all been pilot-tested, and we plan to begin study recruitment in early July of 2017. Using data from the feasibility phase of the ADAPT survey, we also initiated an evaluation of responses to queries on individuals perceptions of dietary environmental impact and whether environmental concerns influence their food purchases. This evaluation will help us better understand the sustainability considerations influencing dietary choice. As part of our program on B vitamins and cognitive function (Objective 2), we assessed in collaboration with the Hebrew University of Jerusalem and the HNRCA Neuroscience and Aging Laboratory, 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. We 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.

1. Drinking sugar-sweetened beverages increases risk of diabetes. Evidence suggests that consumption of sugar-sweetened beverages (SSB), such as soda and fruit-flavored drinks, is associated with increased risk of type 2 diabetes and may contribute to weight gain. Using a meta-analysis of 22 large cohorts within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium, ARS-funded researchers in Boston, Massachusetts found a significant association between long-term sugar-sweetened beverage consumption and higher fasting glucose and insulin levels related to increased risk for type 2 diabetes and heart disease. These findings may lead to greater awareness of the dangers of SSBs and new dietary recommendations which may reduce diabetes and other cardiovascular disease.

2. Dairy foods are differentially associated with incidence of prediabetes and progression to type 2 diabetes. Dairy intake in relation to chronic diseases, such as type 2 diabetes, has been a topic of interest for nutrition researchers for many years, but the evidence about dairy's relationship with health and disease remains inconsistent. With this mixed evidence in mind, ARS-funded researchers in Boston, Massachusetts, undertook a study to see whether consumption of different dairy (from cows’ milk only) foods was related to risk of developing type 2 diabetes, a chronic disease that affects an estimated 1 in 3 Americans. In both participants with and without prediabetes, intake of dairy products was associated with a decreased risk of developing diabetes or prediabetes, respectively. Researchers also found that the type of dairy most beneficial in lowering risk of prediabetes or diabetes may depend on an individual's metabolic health status. These findings could inform diet recommendations for individuals at high risk for developing prediabetes.

Review Publications
Ma, J., Jacques, P.F., Meigs, J.B., Fox, C.S., Rogers, G., Smith, C.E., Hurby, A., Saltzman, E., Mckeown, N. 2016. Sugar-sweetened beverage but not diet soda consumption is positively associated with progression of insulin resistance and prediabetes. Journal of Nutrition. doi: 10.3945/jn.116.234047.
Costello, R.B., Elin, R.J., Rosanoff, A., Wallace, T.C., Guerrero-Romero, F., Hruby, A., Lutsey, P.L., Nielsen, F.H., Rodgriguez-Moran, M., Song, Y., Van Horn, L.V. 2016. The case for an evidence based reference interval for serum magnesium - The time has come. Advances in Nutrition. doi: 10.3945/an.116.012765.
Karakis, I., Pase, M.P., Beiser, A., Booth, S.L., Jacques, P.F., Rogers, G., Decarli, C., Vasan, R.S., Wang, T.J., Himali, J., Annweiler, C., Seshadri, S. 2016. Association of serum vitamin D with the risk of incident dementia and subclinical indices of brain aging the framingham heart study. Journal of Alzheimer's Disease. doi: 10.3233/JAD-150991.
Perry III, C.S., Thomas, A.K., Taylor, H.A., Jacques, P.F., Kanarek, R.B. 2016. The impact of caffeine use across the lifespan on cognitive performance in elderly women. Appetite. doi: 10.1016/j.appet.2016.07.028.
Staffier, K.L., Chung, M., Sawicki, C., Lyle, B.J., Wang, D., Roberts, S., McKeown, N.M. 2016. Development of a publicly available, comprehensive database of fiber and health outcomes: rationale and methods. PLoS One. doi: 10.1371/journal.pone.0156961.
Ma, J., Jacques, P.F., Hwang, S., Troy, L.M., McKeown, N.M., Chu, A.Y., Fox, C.S. 2016. Dietary guideline adherence index and kidney measures in the framingham heart study. American Journal of Kidney Diseases. doi: 10.1053/j.ajkd.2016.04.015.
Makarem, N., Lin, Y., Bandera, E.V., Jacques, P.F., Parekh, N. 2015. Concordance with World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines for cancer prevention and obesity-related cancer risk in the Framingham Offspring cohort (1991-2008). Cancer Causes and Control. 26(2):277-286.
Jarolim, P., Claggett, B., Conrad, M.J., Carpenter, M.A., Invanova, A., Bostom, A.G., Kusek, J.W., Hunsicker, H.G., Jacques, P.F., Gravens-Mueller, L., Finn, P., Solomon, S.D., Weiner, D.E., Levey, A.S., Pfeffer, M.A. 2016. B-type natriuretic peptide and cardiac troponin I are associated with adverse outcomes in stable kidney transplant recipients. Transplantation. doi: 10.1097/TP.0000000000001080.
Dai, Z., Niu, J., Zhang, Y., Jacques, P.F., Felson, D.T. 2017. Dietary intake of fiber and risk of knee osteoarthritis in two U.S. prospective cohorts. Annals of the Rheumatic Diseases. doi: 10.1136/annrheumdis-2016-210810.
McRorie, J.W., McKeown, N.M. 2017. Understanding the physics of functional fibers in the gastrointestinal tract: an evidence-based approach to resolving enduring misconceptions about insoluble and soluble fiber. Journal of the Academy of Nutrition and Dietetics. doi: 10.1016/j.jand.2016.09.021.