Research Project: Nutrition, Epidemiology, and Healthy Aging

Location: Jean Mayer Human Nutrition Research Center On Aging

2020 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
We have made significant progress for all objectives; however, progress on some subobjectives (1.A and 2.A) has been affected by the COVID-19 pandemic, as described below. For our online Adhering to Dietary Approaches for Personal Taste (ADAPT) project, a study of healthy dietary patterns and psycho-biological, cultural, social, and environmental predictors of long-term dietary adherence to dietary patterns in adults (subobjective 1.A), progress was seen in many areas, including improvement of our online data collection procedures, recruitment, and data collection and cleaning. We have spent the past year working to grow and strengthen the research platform, specifically the ADAPT Dashboard in preparation for continued large-scale recruitment and longitudinal data collection. With respect to recruitment, we have recruited approximately 50 percent of the proposed target sample and completed baseline data on approximately one-third of these participants. We had planned to expand our recruitment in spring 2020 by engaging a number of reputable scientists in the field with large social media followings to share recruitment ads. However, this effort was put on hold due to COVID-19, as we felt that the time was not ideal with respect to (1) recruiting participants and (2) capturing data on ‘usual’ diet and lifestyle behaviors. The ADAPT baseline data collection includes 17 questionnaires, and we are currently approximately 50 percent of the way through formal cleaning of this data, coding of qualitative data, and creation of analytic codebook and datasets. In an effort to inform our future work on dietary pattern adherence (hypothesis 1.A.4), we completed a full-scale literature search and review culminating in a formal written report examining how dietary adherence is defined and methods used for capturing dietary adherence in nutrition studies. We also made significant progress for three of our hypotheses for Subobjective 1.B. We have completed the analyses for examining water intake and hydration status in older adults and the effects of age on assessing hydration status (hypothesis 1.B.1). We demonstrated that total water intake, and water intake from beverages and plain water, but not water from foods, is reduced with aging. We also demonstrated that water intake from total water, beverages, plain water and food were all inversely associated with hydration as measured by 24-hour urine creatinine concentrations. However, these associations did not weaken with age, indicating that the value of urinary measures of hydration may not diminish with age as had been hypothesized. Preliminary analyses for our examination of beverage consumption patterns and hydration status in older adults (hypothesis 1.B.2) demonstrate five unique beverage consumption patterns in our older adult sample from the Framingham Heart Study cohort, including patterns characterized by consumption of alcoholic beverages, sweet beverages, skim/low-fat milk, plain water and tea. We are nearing completion of data analyses for examination of water intake, hydration and cardiometabolic risk in older adults (hypothesis 1.B.3). Our findings to date suggest that low water intake and under-hydration can increase risk of dyslipidemia in older adults as see in younger adults, but we are not observing higher glucose and elevated hemoglobin A1c levels with low water and under-hydration in our older sample as has been previously reported in younger adults. Our study of the role B vitamins in brain aging and Alzheimer’s disease (Subobjective 2.A) is currently at the stage of measuring blood levels of various B vitamins for characterizing long-term B vitamin status, but our progress over this past year has been limited because the COVID-19 pandemic has temporarily shut down our core laboratory. We recently completed a project examining the relationship of consumption of plant metabolites (phytonutrients) called flavonoids and brain aging. This project resulted in the publication of three papers showing that higher intakes of certain types of flavonoids were associated with slower age-related declines in cognitive function and healthier brain tissues due to less small vessel disease as determined MRI, and a lower risk of developing Alzheimer’s disease and related dementias. Also, as part of Objective 2, we continue to maintain and update a publicly available, comprehensive dietary fiber database linking fiber to health outcomes (Dietary Fiber and Human Health Outcomes database). Version 5 of the database, published in 2019, contains 1,156 publications. We are currently in the process of creating version 6, having completed reviews of 1,181 abstracts based on a comprehensive Medline search and identifying 142 potentially relevant articles, which we are currently in the process of closely reviewing. As part of Objective 3, we have examined the association between sugar-sweetened beverages (SSB), genetic variants, and dyslipidemia (Subobjective 3.A). We observed that increased consumption of SSBs contribute to development of dyslipidemia. We then conducted a cross-sectional analysis of data from 11 Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium cohorts (N=63,599). Our results showed that high SSB consumption may modify the association between genetic variants and HDL and triglyceride concentrations. Next, we conducted a replication analysis using data from the UK Biobank cohort, which yielded results consistent with our earlier analysis, suggesting that adults with a specific genetic variation may be protected against SSB-inducted low HDL concentrations. These results highlight the importance of understanding the complex role of dietary intake, and in particularly beverage consumption patterns, and genetics in disease risk.

Accomplishments
1. Sugar sweetened beverages contribute to heart disease risk. Almost one-half of adults suffer from abnormal cholesterol levels, a significant risk factor for cardiovascular disease. ARS-funded researchers in Boston, Massachusetts, in a study of more than 6,000 adults from the Framingham Heart Study found that regular consumption of sugar-sweetened beverages produces adverse changes in lipoprotein concentrations, including increased cholesterol levels, triglyceride, and lower HDL-C levels. The researchers also observed there was no significant relationship between long-term consumption of low-calorie sweetened beverages and the incidence of adverse changes in triglycerides or HDL cholesterol. The results also show that people who adopt dietary patterns that include beverages low in sugar-sweetened drinks and limited amounts of 100 percent fruit juice had more favorable plasma lipoprotein profiles. These results support recommendations to limit sugar-sweetened beverage intake to decrease the risk of cardiovascular disease.

2. Certain foods decrease risk of Alzheimer’s disease. Currently 5.8 million Americans are living with Alzheimer’s disease, representing some 60 to 80% of dementia cases, making this is one of the most significant public health challenges affecting adults over 65 years that does not have any effective drug treatment. ARS-funded researchers in Boston, Massachusetts, have identified that certain fruits and vegetables rich in plant metabolites known as flavonoids reduce the risk of developing dementia. The researchers followed for an average 20 years some 2,809 men and women over 50 years in the Framingham Heart Study and found those with higher intakes of four specific types of flavonoids had significantly lower risk of Alzheimer’s. Foods identified with lowest risk for Alzheimer’s included blueberries, strawberries, red wine with apples, pears, oranges, bananas and tea also proving beneficial. This study suggests that by adding certain fruits into their diet, people can reduce the risk of developing Alzheimer’s disease.

Review Publications
Mandaviya, P.R., Joehanes, R., Brody, J., Castillo-Fernandez, J., Dekkers, K.F., Do, A.N., Graff, M., Hanninen, I.K., Tanaka, T., De Jonge, E.A., Kiefte-De Jong, J.C., Absher, D.M., Aslibekyan, S., De Rijke, Y.B., Fornage, M., Hernandez, D.G., Hurme, M.A., Ikram, M.A., Jacques, P.F., Justice, A.E., Kiel, D.P., Lemaitre, R.N., Mendelson, M.M., Mikkila, V., Moore, A.Z., Pallister, T., Raitakari, O.T., Schalkwijk, C.G., Sha, J., Slagboom, E.P., Smith, C.E., Stehouwer, C.D., Tsai, P., Uitterlinden, A.G., Van Der Kallen, C.J., Van Heemst, D., Arnett, D.K., Bandinelli, S., Bell, J.T., Heijmans, B.T., Lehtimaki, T., Levy, D., North, K.E., Sotoodehnia, N., Van Grevenbroek, M.M., Van Meurs, J.B., Heil, S.G. 2019. Association of dietary folate and vitamin B-12 intake with genome-wide DNA methylation in blood: a large-scale epigenome-wide association analysis in 5841 individuals. American Journal of Clinical Nutrition. 110(2):437-450. https://doi.org/10.1093/ajcn/nqz031.
Marklund, M., Wu, J.H., Imamura, F., Del Gobbo, L.C., Fretts, A., De Goede, J., Shi, P., Tintle, N., Wennberg, M., Aslibekyan, S., Chen, T., De Oliveira Otto, M.C., Hirakawa, Y., Eriksen, H.H., Kroger, J., Laguzzi, F., Lankinen, M., Murphy, R.A., Prem, K., Samieri, C., Virtanen, J., Wood, A.C., Wong, K., Yang, W., Zhou, X., Baylin, A., Boer, J.M., Brouwer, I.A., Campos, H., Chaves, P.H., Chien, K., De Faire, U., Djousse, L., Eiriksdottir, G., El-Abbadi, N., Forouhi, N.G., Gaziano, J., Geleijnse, J.M., Gigante, B., Giles, G., Guallar, E., Gudnason, V., Harris, T., Harris, W.S., Helmer, C., Hellenius, M., Hodge, A., Hu, F.B., Jacques, P.F., Jansson, J., Kalsbeek, A., Khaw, K., Koh, W., Laakso, M., Leander, K., Lin, H., Lind, L., Luben, R., Luo, J., Mcknight, B., Mursu, J., Ninomiya, T., Overvad, K., Psaty, B.M., Rimm, E., Schulze, M.B., Siscovick, D., Skjelbo Nielsen, M., Smith, A.V., Steffen, B.T., Steffen, L., Sun, Q., Sundstrom, J., Tsai, M.Y., Tunstall-Pedoe, H., Uusitupa, M.I., Van Dam, R.M., Veenstra, J., Verschuren, W.M., Wareham, N., Willett, W., Woodward, M., Yuan, J., Micha, R., Lemaitre, R.N., Mozaffarian, D., Riserus, U. 2019. Biomarkers of dietary omega-6 fatty acids and incident cardiovascular disease and mortality: an individual-level pooled analysis of 30 cohort studies. Circulation. 139(21):2422-2436. https://doi.org/10.1161/CIRCULATIONAHA.118.038908.
Weiner, D.E., Park, M., Tighiouart, H., Joseph, A.A., Carpenter, M.A., Goyal, N., House, A.A., Hsu, C., Ix, J.H., Jacques, P.F., Kew, C.E., Kim, S.J., Kusek, J.W., Pesavento, T.E., Pfeffer, M.A., Smith, S.R., Weir, M.R., Levey, A.S., Bostom, A.G. 2018. Albuminuria and allograft failure, cardiovascular disease events, and all-cause death in stable kidney transplant recipients: a cohort analysis of the FAVORIT trial. American Journal of Kidney Diseases. 73(1):51-61. https://doi.org/10.1053/j.ajkd.2018.05.015.
Chung, M., Zhao, N., Wang, D., Shams-White, M., Karlsen, M., Cassidy, A., Ferruzzi, M., Jacques, P.F., Johnson, E.J., Wallace, T.C. 2020. Dose-response relationship between tea consumption and risk of cardiovascular disease and all-cause mortality: a systematic review and meta-analysis of population-based studies. Advances in Nutrition. https://doi.org/10.1093/advances/nmaa010.
Walker, M.E., Xanthakis, V., Moore, L.L., Vasan, R.S., Jacques, P.F. 2019. Cumulative sugar-sweetened beverage consumption is associated with higher concentrations of circulating ceramides in the Framingham Offspring Cohort. American Journal of Clinical Nutrition. 111:420-428. https://doi.org/10.1093/ajcn/nqz257.
Kummel Duarte, C., Bocardi, V.B., Andrade, P.A., Lopes, A.S., Jacques, P.F. 2020. Dairy versus other saturated fats source and cardiometabolic risk markers: systematic review of randomized controlled trials. Critical Reviews in Food Science and Nutrition. https://doi.org/10.1080/10408398.2020.1736509.
Shishtar, E., Rogers, G.T., Blumberg, J.B., Au, R., DeCarli, C., Jacques, P.F. 2020. Flavonoid intake and MRI markers of brain health in the Framingham Offspring Cohort. Journal of Nutrition. https://doi.org/10.1093/jn/nxaa068.
Haslam, D.E., Peloso, G.M., Herman, M.A., Dupuis, J., Lichtenstein, A.H., Smith, C.E., McKeown, N.M. 2020. Beverage consumption and longitudinal changes in lipoprotein concentrations and incident dyslipidemia in U.S. adults: the Framingham Heart Study. Journal of the American Heart Association. 9(5). https://doi.org/10.1161/JAHA.119.014083.
Shishtar, E.A., Rogers, G.T., Blumberg, J.B., Au, R., Jacques, P.F. 2020. Long-term dietary flavonoid intake and risk of Alzheimer's disease and related dementias in the Framingham Offspring Cohort. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqaa079.
Shishtar, E., Rogers, G., Blumberg, J.B., Au, R., Jacques, P.F. 2020. Long-term dietary flavonoid intake and change in cognitive function in the Framingham Offspring cohort. Public Health Nutrition. 23(9):1576-1588. https://doi.org/10.1017/S136898001900394X.
Haslam, D.E., Ma, J., McKeown, N.M. 2019. Potential link between sugar consumption and ectopic fat. In: Patel, V.B., editor. Molecular Nutrition: Carbohydrates. Amsterdam, Netherlands: Elsevier. p. 73-90.
Lin, H., Rogers, G.T., Lunetta, K.L., Levy, D., Miao, X., Troy, L.M., Jacques, P.F., Murabito, J.M. 2020. Healthy diet is associated with gene expression in blood: the Framingham Heart Study. American Journal of Clinical Nutrition. 110(3):742-749. https://doi.org/10.1093/ajcn/nqz060.
Walker, M.E., Song, R.J., Xu, X., Gerszten, R.E., Ngo, D., Clish, C.B., Corlin, L., Ma, J., Xanthankis, V., Jacques, P.F., Vasan, R.S. 2020. Proteomic and metabolomic correlates of healthy dietary patterns: the Framingham Heart Study. Nutrients. 12(5):1476. https://doi.org/10.3390/nu12051476.
Shan, Z., Rehm, C.D., Rogers, G., Ruan, M., Wang, D.D., Hu, F.B., Mozaffarian, D., Zhang, F., Bhupathiraju, S.N. 2019. Trends in dietary carbohydrate, protein, and fat intake and diet quality among US adults, 1999-2016. Journal of the American Medical Association. 322(12):1178-1187. https://doi.org/10.1001/jama.2019.13771.
Hruby, A., Dennis, C., Jacques, P.F. 2020. Dairy intake in two American cohorts associates with novel and known targeted and untargeted circulating metabolites. Journal of Nutrition. https://doi.org/10.1093/jn/nxaa021.
Chen, F., Du, M., Blumberg, J.B., Chui, K.K., Ruan, M., Rogers, G., Shan, Z., Zeng, L., Zhang, F. 2019. Association among dietary supplement use, nutrient intake, and mortality among U.S. adults: a cohort study. Annals Of Internal Medicine. 170(9):604-613. https://doi.org/10.7326/M18-2478.
Miki, A.J., Livingston, K.A., Karlsen, M.C., Folta, S.C., Mckeown, N.M. 2020. Using evidence mapping to examine motivations for following plant-based diets. Current Developments in Nutrition. https://doi.org/10.1093/cdn/nzaa013.