Research Project: Nutrition, Epidemiology, and Healthy Aging

Location: Jean Mayer Human Nutrition Research Center On Aging

2023 Annual Report

Objectives
Objective 1: Characterize diet to determine patterns that associate with healthy aging, and construct models of the various components of these dietary patterns to determine the contribution that each component of the pattern provides to overall associations, while concurrently considering the joint associations of different dietary components. Subobjective 1.A: Form a new cohort composed of participants adhering to more plant-based dietary patterns to identify factors associated with long-term adherence to healthier dietary patterns and to examine the health benefits of adherence to these dietary patterns. Subobjective 1.B: Describe the relationship between water intake, hydration and age, and examine the relationships between water intake and hydration and healthy aging. Objective 2: Determine the relationships between specific foods, nutrients, and other bioactive dietary components of dietary patterns and healthy aging and key elements of healthy aging, such as physical, metabolic, musculoskeletal, vision, and cognitive function. Subobjective 2.A: Examine the relationship between inadequate vitamin B12 status and accelerated brain aging and explore potential exacerbation of this relationship by high folate status. Objective 3: Examine the potential genetic modification of the relationships between dietary patterns and their constituents associated with healthy aging, and employ metabolomic and transcriptomic “signatures” of optimal dietary patterns and of healthy aging to detect pathways that may link diet and healthy aging. Subobjective 3.A: Examine the association between sugar-sweetened beverage (SSB) consumption and dyslipidemia and determine if single nucleotide polymorphisms (SNPs) in the CHREBP locus affect this association.

Approach
Diet plays a critical role in maintaining health across the lifespan, but questions remain about the relationship between nutrition and healthy aging, including physical, cardiometabolic, and cognitive health. Using an epidemiological approach applied to community-based, aging populations, we will study diet patterns and provide the evidence needed to create interventions to foster healthy aging. Most of our research will focus on the impact of the entire diet and dietary behaviors, a departure from the more traditional approach of isolating single nutrients. This approach, broadly referred to as dietary pattern analysis, is more predictive of health outcomes and more reflective of the way people eat. We will link this approach with genetics, metabolomics, and transcriptomics in the context of large community-based aging cohorts so we can characterize not just healthy aging phenomena, but make an impact by identifying optimal dietary and behavior patterns at both the individual and population levels. The dietary pattern methodology allows us to capture the complexity of diet and the interactions of different dietary components. In addition to conventional diets, we will include alternative diets such as whole food and plant-based (e.g., vegan diets). We will identify factors associated with adherence to such diets; examine potential mechanisms by which bioactive dietary components affect health outcomes (e.g., B vitamins and dementia); and identify factors, such as genetic variation, responsible for differences in response to dietary patterns and food components (such as sugar intake). Results of this research will allow us to translate the science of nutrition and healthy aging into guidance for the public.

Progress Report
a) We continue our progress on the online Adhering to Dietary Approaches for Personal Tast (ADAPT) project, a longitudinal study of healthy dietary patterns and psychobiological, cultural, social, and environmental predictors of long-term dietary adherence to popular dietary patterns in adults (subobjective 1.A). Based on a sample of 1291 ADAPT participants [355 vegans, 90 vegetarians, 710 whole food plant-based (WFPB), and 136 paleo], we demonstrated that WFPB and vegan diets had the highest diet quality; all four diet patterns had higher mean HEI than the reported average for U.S. adults. In a subsample (n=214) of ADAPT participants, 3-day electronic food records were collected to examine intake of four designated nutrients of public concern identified by the Dietary Guidelines for Americans 2020-2025 (dietary fiber, vitamin D, calcium, and potassium). Among WFBP and vegan followers, over 94% and 82% achieved adequate dietary fiber and potassium intake, compared to vegetarians (68%, 45%) and paleo (34%, 51%). However, even with supplement use, less than 25% of all diet followers met calcium recommendations, and those meeting vitamin D recommendations ranged from 28% of vegetarian to 56% of paleo followers. b) As part of our research examining the role of dietary patterns in healthy aging (Objective 1), we observed, in collaboration with the Tufts Friedman School of Nutrition Science and Policy, Boston University and the Framingham Heart Study, that higher scores for the Alternative Healthy Eating Index, which is an index of Adherence to the Dietary Guidelines for Americans, were associated with better platelet function in the Framingham Heart Study cohort. In collaboration with investigators from Boston University, National Heart, Lung and Blood Institute (NHLBI) and universities across the U.S., we observed that three healthy dietary patterns were associated with a lower risk of liver fat and fibrosis, which are risk factors for cirrhosis and liver failure. As part of Objective 1, we also demonstrated in a recently completed study that participants consuming diet patterns characterized by lower carbohydrate, higher protein and fat that maintained higher quality carbohydrate foods showed beneficial changes over more than 16 years of follow-up for HDL cholesterol and lower triglycerides whereas lower carbohydrate diet patterns that did not include high quality carbohydrates were associated with increasing plasma glucose concentrations. Irrespective of carbohydrate quality, long-term consumption of lower carbohydrate diet patterns was associated with lower systolic blood pressure but were also associated with greater increases in waist circumference. c) Our research on the role of specific foods on healthy aging (Objective 2) demonstrated that consumption of 100% fruit juice was associated with fewer days per month of anxiety compared to non-consumers. Preliminary findings from a collaborative study with investigators from Boston University that is examining the role of flavonoid-rich fruits on dementia risk suggest that greater consumption of flavonoid-rich fruits in midlife appear to be more strongly associated with reduced dementia risk than similar consumption in late-life. d) We also showed in collaboration with investigators from Hebrew SeniorLife and Harvard University that yogurt consumption was modestly associated with reduced frailty onset, but other dairy food intakes showed no association with frailty in this study of healthy adults. e) As part of our research on food components as part of Objective 2, we demonstrated, in collaboration with investigators from Framingham and Boston University, that lower dietary choline was associated with increased risks of Alzheimer’s disease and related dementia. f) In a collaborative project with investigators from the National Center for Health Statistics (CDC), Johns Hopkins University, and George Washington University, we observed that lower vitamin D status was significantly associated with metabolic syndrome among U.S. adults and that this finding was noted across all race and Hispanic origin groups. g) We continued to maintain our long-running program on carbohydrates and healthy aging. To clarify the quantity and quality of available evidence relating whole grain consumption to prevention of age-related cognitive decline, we conducted a systematic review with investigators from the Tufts Friedman School of Nutrition, Boston University and New Zealand to synthesize all available observational and interventional studies evaluating the association between whole-grain intake and cognitive outcomes – focusing on cognitive decline and function (including dementia) and measured changes to brain structure and function), or measures of mood (including depression) and anxiety. Our examination of existing studies indicated that the limited evidence for whole grains reducing age-related cognitive decline is inconclusive, indicating the need for additional high-quality research in this area. h) As part of our examination of the potential genetic modification of the relationships between diet and healthy aging (Objective 3), we were able to demonstrate, in collaboration with investigators from across the US and internationally, that intake of vitamin C and vitamin E is associated with DNA methylation, which plays a critical role in the regulation of cellular mechanisms involved in the immune response, highlighting the importance of the intake of vitamins C and E through consumption of fruit, vegetables, nuts, seeds, and oils in overall health and the reduction of burden from inflammatory processes.

Accomplishments
1. Choline shows promise in reducing risk of dementia. Dementia is one of the biggest global public health and social care challenges for which there are no major medical treatments. Therefore, prevention is critical, and diet has shown promise as a potential modifiable method to reduce the risk of dementia. ARS-funded researchers in Boston, Massachusetts, examined the relationship of choline, an essential dietary nutrient closely related to brain development and maintaining nerve cell membranes, to the progression of Alzheimer's Disease (AD) and other dementia. Studying data from participants from the Framingham Offspring cohort who were followed for about 16 years, the researchers demonstrated that low choline intake was significantly associated with a greater risk of developing dementia. These results suggest that adequate intake of choline in conjunction with a healthy diet may be one means to lower the risk of age-related cognitive decline and development of AD and other forms of dementia.

Review Publications
Agarwal, S., Fulgoni, V.L., Jacques, P.F. 2022. Association of 100% fruit juice consumption with cognitive measures, anxiety, and depression in US adults. Nutrients. https://doi.org/10.3390/nu14224827.
Ahluwalia, N., Ramkripa, R., Guangya, Z., Talegawkar, S., Jacques, P.F. 2022. Vitamin D status and prevalence of metabolic syndrome by race and Hispanic origin in US adults: findings from the 2007-2014 NHANES. The American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqac234.
Siefkas, A., Courtney, M.L., Dufour, A.B., Kiel, D., Jacques, P.F., Hannan, M.T., Shivani, S. 2022. Dairy food intake is not associated with frailty in adults from the Framingham Heart Study. Journal of the Academy of Nutrition and Dietetics. https://doi.org/10.1016/j.jand.2022.09.012.
Karlsen, M.C., Staffier, K.L., Agoulnik, D.S., Miki, A., Lichtenstein, A.H., Gilhooly, C., Folta, S.C., Economos, C.D., McKeown, N.M. 2021. Part 2: Theoretical intakes of modern-day Paleo diets: Comparison to dietary reference intakes and MyPlate recommendations. Nutrition Today. 56(4):158-168. https://doi.org/10.1097/NT.0000000000000490.
Sawicki, C., Jacques, P.F., Lichtenstein, A.H., Rogers, G., Ma, J., Saltzman, E., McKeown, N.M. 2021. Whole- and refined-grain consumption and longitudinal changes in cardiometabolic risk factors in the Framingham Offspring Cohort. Journal of Nutrition. 151(9):2790-2799. https://doi.org/10.1093/jn/nxab177.
Gao, V., Long, M.T., Singh, S.R., Youjin, K., Xuehong, Z., Rogers, G., Jacques, P.F., Levy, D., Ma, J. 2023. Healthy diet is associated with lower risk of hepatic fibrosis. Journal of Nutrition. https://doi.org/10.1016/j.tjnut.2023.03.038.
Igho-Osagie, E., Kelly, C., Wang, D.D., Yao, Q., Penkert, L.P., Cassidy, A., Ferruzzi, M., Jacques, P.F., Johnson, E.J., Chung, M., Wallace, T.C. 2020. Short-Term tea consumption is not associated with a reduction in blood lipids or pressure: A systematic review and meta-analysis of randomized controlled trials. Journal of Nutrition. 150(12):3269-3279. https://doi.org/10.1093/jn/ nxaa295.
Haslam, D.E., Chasman, D.I., Peloso, G.M., Herman, M.A., Dupuis, J., Lichtenstein, A.H., Smith, C.E., Ridker, P.M., Jacques, P.F., Mora, S., McKeown, N. 2022. Sugar-sweetened beverage consumption and plasma lipoprotein cholesterol, apolipoprotein, and lipoprotein particle size concentrations in U.S. adults. Journal of Nutrition. https://doi.org/10.1093/jn/nxac166.
Miller, C.L., Costa, E., Jacques, P.F., Dufour, A.B., Kiel, D., Hannan, M.T., Sahni, S. 2023. Adherence to the Mediterranean-style diet and high intake of total carotenoids reduces the odds of frailty over 11 years in older adults: results from the Framingham offspring study. The American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqac130.