2007 Annual Report 1a.Objectives (from AD-416) LAB:Nutritional Epidemiology Determine, using epidemiologic approaches, the independent influence of different aspects of nutrition on the prevention of insulin resistance, metabolic syndrome, type 2 diabetes mellitus and CVD. Test with epidemiologic methods whether age-related cataract and maculopathy can be prevented or delayed with higher intake of antioxidant nutrients, healthier dietary patterns and higher intakes of polyunsaturated fatty acids. Examine the effect of homocysteine lowering with B vitamin therapy on change in cognitive function. Identify the causes and consequences of mild hyperhomocysteinemia to test whether. 1)homocysteine, nutrients and genetic mutations related to one-carbon metabolism affect risk of cardiovascular disease and dementia; . 2)homocysteine and vitamin B12 levels have a high degree of heritability; and. 3)homocysteine concentrations of adult offspring can predict risk of CVD and dementia in their parents. Measure the amount of folic acid in enriched grain products to determine the amount provided by fortification and assess the safety by examining the relation of folic acid intake to a) circulating unmetabolized folic acid, b) vitamin B12 status, and c) cognitive function. Assess the prevalence of high vitamin E levels and examine the use of vitamin E supplements is associated with risk of CVD to exmine the hypothesis that vitamin E supplements are associated with a reduced incidence of CVD among individuals free of CVD and diabetes, but CVD events, including death, is not associated with vitamin E supplement use among individuals with existing CVD or diabetes. Develop an index to assess adherence to the 2005 Dietary Guidelines for Americans and test the hypothesis that adherences to the Dietary Guidelines is associated with less age-related chronic disease. Examine the role of diet, starting with both data-defined and policy-based dietary patterns and working from foods to nutrients, in development of cardiovascular diseases using intermediate markers of CVD risk including brachial artery flow-mediated dilation and biomarkers of inflammation and oxidative stress. LAB:Dietary Assessment To determine if low micronutrient intakes and poor dietary patterns increase bone loss and fracture risk with aging. To determine if specific vitamin of fatty acid intakes protect against depression and loss of cognitive function. To identify subgroups of older adults in the United States (US) with inadequate dietary intakes, and the extent to which inadequate intakes are associated with poor nutritional status. To determine the relationship between dietary patterns and heart disease risk factors, including obesity, among older adults. To determine how genetic polymorphisms modify dietary effects on risk of heart disease, cognitive function and bone status. To determine whether cumulative environmental stress is modified by nutritional factors to affect risk of obesity, diabetes, depression, cognitive decline and physical disability. 1b.Approach (from AD-416) LAB:Nutritional Epidemiology Development of public health nutrition guidelines and interventions to reduce economic and societal costs associated with age-related disabilities and premature death from chronic disease requires a greater understanding of the presumptive role that nutrition plays in delaying the development of these conditions. This project will focus on two major two overall goals to address these issues:. 1)to identify environmental, lifestyle and genetic factors that influence the nutritional status and requirements of the elderly, and. 2)to determine the role of nutritional status in healthy aging and the development of chronic disease and age-related impairments such as cardiovascular disease, dementia, type 2 diabetes mellitus, cataract and maculopathy. These goals will be achieved through the application of epidemiological methods and community-based investigation of aging population samples. Our approach will provide knowledge on the role of nutrition in preventing a number of age-related disabilities that can be readily applied to the development of nutrition guidelines and interventions. LAB:Dietary Assessment Establish a longitudinal cohort of Puerto Rican adults and assess dietary intake and nutritional status, along with stress measures and genetic markers and relate to the development and progression of chronic health conditions . Conduct intervention studies with Puerto Rican adults. Analyze data from the Baltimore Longitudinal Study of Aging to assess relationships between dietary patterns and metabolic syndrome. Analyze data from the Normative Aging Study to assess relationships between dietary intake, vitamin status and cognitive decline. Compare dietary intake measured by food frequency with serum biomarkers in the Jackson Heart Study. Analyze data from the Framingham Osteoporosis study to assess relationships between dietary pattern and bone mineral density and fracture. 4.Accomplishments LAB:NUTRITIONAL EPIDEMIOLOGY 1) Folate and vitamin B-12 status in relation to anemia and cognitive impairment in older Americans in the age of folic acid fortification. Historic reports on the treatment of pernicious anemia with folic acid suggest that high-level folic acid fortification delays the diagnosis of or exacerbates the effects of vitamin B-12 deficiency, which affects many seniors. This idea is controversial, however, because data are few and inconclusive. We examined the relations between serum folate and vitamin B-12 status relative to anemia, macrocytosis, and cognitive impairment (ie, Digit Symbol-Coding score <34) in 1459 senior participants in the 1999–2002 US National Health and Nutrition Examination Survey. We defined low vitamin B-12 status as a serum vitamin B-12 concentration <148 pmol/L or a serum methylmalonic acid concentration >210 nmol/L—the maximum of the reference range for serum vitamin B-12–replete participants with normal creatinine. In the group with a low vitamin B-12 status, higher serum folate (>59 nmol/L, the 80th percentile) was associated with a 3-fold increased risk of anemia and a 2.5-fold increased risk of cognitive impairment. In the normal vitamin B-12 group, higher serum folate was associated with a reduced risk cognitive impairment. In seniors with low vitamin B-12 status, high serum folate was associated with anemia and cognitive impairment. When vitamin B-12 status was normal, however, high serum folate was associated with protection against cognitive impairment. Increasing the vitamin B12 status of older Americans may have an important impact on the prevalence of age-related cognitive decline. NP107 Human Nutrition Component 4-Nutrient Requirements. 2) Dietary choline in relation to cognitive performance and total cerebral brain volume. Age-related cognitive impairments prevalent in non-demented older persons are frequently related to alterations in brain neurotransmission systems, mainly cholinergic deficits. Choline is an essential nutrient that acts as a precursor to acetylcholine, which is a fundamental component of the cholinergic neural networks associated with memory. Animal studies have demonstrated that supplementation of choline improves memory function. Age-related brain atrophy as measured by total cerebral brain volume has been associated with cognitive impairment and dementia. We examined the relationship between dietary choline intake and cognition and total cerebral brain volume in 1820 non-demented, stroke-free participants from the community-based Framingham Offspring cohort. Choline intake was positively related to three neuropsychological factors verbal memory (p<0.0001), visuospatial memory and organization (p = 0.002), and visual scanning and motor speed (p = 0.01), but was unrelated to brain volume in this non-demented, community-based population. These results suggest that increased dietary choline levels may slow the development of age-related cognitive impairment in non-demented individuals. NP107 Human Nutrition Component 4-Nutrient Requirements. 3) Dietary Quality Predicts Adult Weight Gain. It is proposed, based on the science behind the Dietary Guidelines for Americans (DGA), that adherence to these dietary recommendations is believed to limit age-related weight gain; however, there are few actual data that have evaluated the effect of adherence to these guidelines on weight gain. We tested the hypothesis that adherence to the DGA as assessed by the Diet Quality Index (DQI) was related to weight change in adults. Dietary intake was assessed among 2245 adult men and women in the Framingham Offspring cohort. Men and women with higher DQI scores gained less weight during follow-up (p < 0.05). Average gain over 8 years was 3 pounds among those with highest scores, compared with 5 to 8 pounds among those with lower scores. A high-quality diet that is consistent with the DGA may help curb rising rates of obesity at the population level. Poor compliance with the Guidelines, rather than the guidelines themselves, is likely responsible for the weight gain observed in the American population. Adoption of an eating pattern consistent with the DGA should facilitate population weight control if sustained long term. NP107 Human Nutrition Component 6-Prevention of Obesity and Disease: Relationship between Diet, Genetics and Lifestyle. 4) The 2005 Dietary Guidelines for Americans (DGA) and risk of hip fracture in elderly men and women. The 2005 Dietary Guidelines for Americans (DGA) is a government-promulgated healthy dietary pattern developed to reduce risk of age-related chronic diseases related to diet including osteoporosis. We examined whether a diet consistent with the DGA was associated with decreased hip fracture risk in 386 older men and 617 postmenopausal women (67-95y) from the Framingham Heart Study. We developed a 20-item DGA index (DGAI) to measure dietary recommendations of the 2005 DGA. Hip fractures (n=102) were assessed over 15 years (1988 to 2003). There was no significant association between DGAI and hip fracture (p-trend=0.55). A modest reduction of hip fracture risk was observed with increased intakes of dark green vegetables and alcohol. This study assessed the adherence to many of the DGA recommendations and observed no impact of consuming a health dietary pattern on fracture risk for elderly Americans. These results do not suggest that individual dietary factors, such as calcium and vitamin D, may not affect fracture risk in elderly individuals nor does it address the impact of a healthy diet pattern consumed as younger and middle aged adults on later risk of fracture. However, these results do suggest that adherence to an overall health diet pattern in elderly do not have any substantial affect on their risk of hip fractures. NP107 Human Nutrition Component 4-Nutrient Requirements. 5) Dietary carbohydrates and cardiovascular disease risk factors. The quality of carbohydrate in the diet can be measured using the dietary glycemic index. Blood glucose levels increase after consuming carbohydrate foods. The higher the glycemic index of a food, the greater the increase in glucose, indicating a poorer the quality of the carbohydrate. In a healthy group of men and women, we divided people into 5 groups based on their reported dietary glycemic index. A fasting blood sample was taken for each person and we found that people with the highest dietary glycemic index had higher triglcyerides and lower HDL-cholesterol. Also, people who had higher glycemic index diets had a higher degree of insulin resistance compared to those with lower glycemic index diets. Low levels of HDL cholesterol and high triglyceride blood levels increase a person’s risk of developing heart disease. Also, the more insulin resistant a person is the more likely they will develop heart disease and diabetes. Dietary recommendations encourage people to eat a diet rich in vegetables, legumes, and fruits and these foods generally have a low glycemic index. Incorporating these foods into the diet may improve cardiovascular disease risk factors and reduce an individual’s risk of developing heart disease. NP107 Human Nutrition Component 6-Prevention of Obesity and Disease: Relationship between Diet, Genetics and Lifestyle. 6)Magnesium intake is related to improved insulin homeostasis. The number of Americans with type 2 Diabetes Mellitus (DM) is rapidly increasing. Impaired insulin sensitivity is a key risk factor in the etiology of type 2 DM. Low magnesium status may be a factor in development of insulin sensitivity and type 2 DM risk. Magnesium, an intracellular metal cation, acts as a cofactor in several important enzymatic reactions that affect glucose and insulin homeostasis. The aim of this study was to examine the association between dietary magnesium intake and metabolic risk factors for impaired insulin sensitivity and type 2 DM, including fasting glucose and insulin, 2-hour post-challenge plasma glucose and insulin, and insulin resistance assessed by the homeostasis model (HOMA-IR). The study was performed in 1223 men and 1485 women without diabetes from the Framingham Offspring cohort. Magnesium intake was inversely associated with fasting insulin (P trend <0.001), post-glucose challenge plasma insulin (P trend <0.001), and HOMA-IR (P trend <0.001). No significant association was found between magnesium intake and fasting glucose or 2-hour post challenge glucose. Higher dietary magnesium intake may reduce the risk of developing type 2 DM through beneficial effects on insulin sensitivity. NP107 Human Nutrition Component 6-Prevention of Obesity and Disease: Relationship between Diet, Genetics and Lifestyle. 7)Magnesium intake and prevalence of metabolic syndrome in older adults. Metabolic Syndrome (MS), a clustering of risk factors including, abdominal adiposity, dyslipidemia, glucose intolerance and hypertension, affects over 40% of people older than 60 years. The prevalence rate of this syndrome increases with age, predisposing more individuals to type 2 diabetes mellitus (DM) and CVD risk. Magnesium (Mg) is an essential cofactor for enzymes involved in glucose and insulin metabolism. The objective of this study was to examine the association between dietary Mg intake and metabolic syndrome in elderly men and women. Mg intake was inversely associated with the MS; those with the highest intake of Mg had significantly approximately 60% lower risk of having MS compared to those with the lowest intake. A significant inverse relationship was also observed between Mg intake and fasting glucose. Our study demonstrates that Mg intake is inversely associated with prevalence of the MS in older adults. Higher dietary magnesium intake may reduce the risk of developing type 2 Diabetes mellitus (DM)and Cardiovascular Disease (CVD) through beneficial effects on prevalence of metabolic syndrome and glucose homeostasis. NP107 Human Nutrition Component 6-Prevention of Obesity and Disease: Relationship between Diet, Genetics and Lifestyle. 8) Use of the Affinity/HPLC Method for Quantitative Estimation of Folic Acid in Enriched Cereal-Grain Products. In 1998, the United States introduced mandatory fortification of enriched cereal-grain products with folic acid to reduce the incidence of neural tube defects. As a consequence, substantial amounts of folic acid, the synthetic form of folate, were added to the American diet, and the ability to assess folic acid intake took on greater importance. The purpose of the current study was to separate and quantify folic acid and 5-methyltetrahydrofolate, the most prominent naturally occurring folate in fortified foods, with a reliable and robust method. An HPLC method was developed for this purpose. The coefficient of variation (CV) of the peak areas of folic acid and 5-methyltetrahydrofolate for 5 commercial wheat flour samples extracted and run separately on the same day was 2.0 and 5.7% and, run over 5 consecutive days, was 7.2 and 7.3%, respectively. Total folate values in 45 samples of fortified food measured by HPLC and by the traditional microbiological assay demonstrated a high correlation (r-squared =0.99). This method will allow for the development of food databases for folic acid. Such databases are critical for the assessment of dietary folate intake in the presence of high dietary folic acid levels in the post-fortification era and for the determination of dietary folate equivalents (DFE), which is the current recommended approach for assessing total folate intake. NP107 Human Nutrition Component 1 Composition of Foods. LAB:DIETARY ASSESSMENT 1)Cola consumption is associated with lower bone mineral density. Soft drink consumption may have adverse effects on bone mineral density (BMD), but studies have shown mixed results. In addition to displacing healthier beverages, colas contain caffeine and phosphoric acid, which may adversely affect bone. BMD was measured at the spine and three hip sites for 1413 women and 1125 men in the Framingham Offspring Study. Dietary intake was assessed by food frequency questionnaire. After adjusting for BMI, height, age, energy intake, physical activity score, smoking, alcohol use, total calcium intake, total vitamin D intake, caffeine from non-cola sources, season of measurement and, for women, menopausal status and estrogen use, cola intake was associated with significantly lower BMD at each hip site in women. Relative to those consuming <1 serving/month, mean hip BMD of those with daily cola intake was up to 5% lower. Similar results were seen for diet cola, and although weaker, for decaffeinated cola. Although further research is needed, these findings advise caution against daily cola consumption for women concerned about bone mineral density. NP107 Human Nutrition Component 6-Prevention of Obesity and Disease: Relationship between Diet, Genetics and Lifestyle. 2)Advanced dietary patterns research shows associations with obesity and vitamin E status and validates methods. Most research on diet and health has historically focused on single nutrients or foods and their effect on disease outcomes. In recent years, this focus has shifted to include the total dietary pattern, or combinations of foods and nutrients, as a risk factor in epidemiologic studies. We studied obesity in relation to dietary patterns in a large population of Swedish women and determined that changes in eating patterns were significantly related to changes in BMI over 9 years. We also determined that a large proportion (>90%) of Hispanic and non-Hispanic elders in Massachusetts have inadequate intake of vitamin E, and their vitamin E status was associated with dietary intake patterns. In addition, we validated a diet screening tool to measure dietary patterns and presented commentary on the methods used in dietary patterns research and the need to establish a consensus in order to better validate results. This research is important to better understand potential interactions among nutrients and to better guide dietary recommendations in relation to disease outcomes. NP107 Human Nutrition Component 6-Prevention of Obesity and Disease: Relationship between Diet, Genetics and Lifestyle. 3) TV viewing is associated with prevalence of metabolic syndrome in Hispanic adults. The metabolic syndrome, a cluster of abnormalities including abdominal obesity, insulin resistance, glucose intolerance, dyslipidemia and high blood pressure, is associated with diabetes, cardiovascular disease, and mortality. It affects up to 25% of adults and more than 40% of elders in the United States, with even higher prevalence shown in Mexican Americans, but little information is available for other Hispanic subgroups. Prolonged television viewing, a major sedentary behavior in the U.S., has been identified as a risk factor for diabetes and obesity, and has been associated with components of the metabolic syndrome. We examined a representative sample of 350 Puerto Rican and 105 Dominican elders living in Massachusetts and found that 50.1% of the Puerto Ricans and 56.9% of the Dominicans had metabolic syndrome. 82.6% of subjects had high blood pressure, and 61.4% had high fasting glucose. Prevalence of the syndrome was significantly associated with television viewing with each additional hour of television viewing associated with a 16% greater likelihood of having the metabolic syndrome. We concluded that a high prevalence of the metabolic syndrome in this representative sample of Caribbean origin Hispanic elders was associated with prolonged television viewing, independent of physical activity and energy intake. These results are important for policy makers in addressing health disparities. NP107 Human Nutrition Component 6-Prevention of Obesity and disease: Relationship between Diet, Genetics, and Lifestyle. 4)Iron deficiency anemia is prevalent in Hispanic elders. Dietary sources of iron status have not been well described in Hispanic elders. We examined intake of various dietary factors in relation to iron status in a representative sample of 605 Hispanic (mainly Puerto Rican) adults (age 59-91 y) living in Massachusetts and a neighborhood sample of non-Hispanic white subjects. Hispanic elders had significantly lower mean serum ferritin, and mean hemoglobin concentrations, and showed a higher prevalence of anemia compared to non-Hispanic whites. Hispanic elders had lower mean dietary intake of total iron, nonheme iron, total vitamin C, supplemental vitamin C, total calcium, and dietary calcium, as compared to non-Hispanic white elders. After adjusting for age, sex, BMI, alcohol use, smoking, total energy intake, inflammation, diabetes, and liver disease, intake of heme iron from red meat was positively associated, and dietary calcium was negatively associated with serum ferritin concentrations. Cultural variation in dietary intake appears to influence body iron stores and to contribute to an increased risk for iron deficiency anemia among Hispanic elders. These results are important for policy makers in addressing health disparities. NP107 Human Nutrition Component 4-Nutrient Requirements. 5.Significant Activities that Support Special Target Populations We are currently conducting The Boston Puerto Rican Health Study as part of the Boston Center on Population Health and Health Disparities. The Center aims to gain a better understanding of the factors that lead to poor health outcomes, and to determine how these processes link to the health disparities observed in minority communities, with a focus on sources of stress as modified by diet and nutritional status. We have completed more than 1200 baseline interviews and more than 400 2 year follow-up interviews at this time. Preliminary data show very high prevalence of metabolic syndrome, diabetes, depression and physical disability in this population, as well as high levels of "allostatic load" (a physiologic measure of accumulated stress) and psychosocial stress. Genetic analyses also show high prevalence of polymorphisms that have been associated with disease risk. Analyses are underway to determine gene-environment interactions that may explain some of the contribution to these health disparities. 6.Technology Transfer Number of non-peer reviewed presentations and proceedings 28 Number of newspaper articles and other presentations for non-science audiences 129 Review Publications Morris, M.S., Jacques, P., Rosenberg, I., Selhub, J. 2007. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. American Journal of Clinical Nutrition. 85(1):193-200. Dietrich, M., Traber, M.G., Jacques, P., Cross, C.E., Hu, Y., Block, G. 2006. Does gamma-tocopherol play a role in the primary prevention of heart disease and cancer? A review. Journal of the American College of Nutrition. 25(4): 292-299. Fogli-Cawley, J.J., Dwyer, J.T., Saltzman, E., Mccullough, M.L., Troy, L.M., Jacques, P. 2006. The 2005 dietary guidelines for americans adherence index: development and application. Journal of Nutrition. 136:2908-2915. Fogli-Cawley, J., Dwyer, J., Saltzman, E., Mccollough, M., Troy, L.M., Meigs, J., Jacques, P. 2007. The 2005 Dietary Guidelines for Americans & Insulin Resistance in the Framingham Offspring Cohort. Diabetes Care. 304(4):817-822. Feldeisen, S.E., Tucker, K. 2007. Nutritional Strategies in the Prevention and Treatment of Metabolic Syndrome. Applied Physiology, Nutrition, and Metabolism. 32(1):46-60. Tucker, K. 2007. Assessment of usual dietary intake in population studies of gene-diet interaction. Nutrition Metabolism and Cardiovascular Disease. 17(2): 74-81. Sahni, S., Forrester, J.E., Tucker, K. 2007. Assessing dietary intake of drug abusing Hispanic adults with and without HIV infection. Journal Of The American Dietetic Association. 107: 968-976. Gao, X., Nelson, M.E., Tucker, K. 2007. Television viewing is associated with prevalence of metabolic syndrome in Hispanic elders. Diabetes Care. 30:694-700. Gao, X., Wilde, P., Lichtenstein, A.H., Tucker, K.L. 2006. Meeting adequate intake for dietary calcium without dairy foods in adolescents, aged 9-18 years (nhanes 2001-2002). Journal Of The American Dietetic Association. 106(11):1759-65. Tucker, K.L., Morita, K., Qiao, N., Hannan, M.T., Cupples, L.A., Kiel, D.P. 2006. Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: The Framingham Osteoporosis Study. American Journal of Clinical Nutrition. 84(4):936-42. Gao, X., Martin, A., Lin, H., Bermudez, O.I., Tucker, K.L. 2006. Alpha-tocopherol intake and plasma status of Hispanic and non-Hispanic white elders is associated with dietary intake pattern. Journal of Nutrition. 136(10):2574-2579. Newby, P.K., Weismayer, C., Akesson, A., Tucker, K., Wolk, A. 2006. Longitudinal changes in food patterns predict changes in weight and body mass index and the effects are greatest in obese women. Journal of Nutrition. 136:2580-2587. Ho, G.Y., Qian, H., Kim, M.Y., Melnik, T.A., Tucker, K.L., Jimenez-Velazquez, I.Z., Kaplan, R.C., Lee-Rey, E.T., Stein, D.T., Rivera, W., Rohan, T.E. 2006. Health disparities between island and mainland Puerto Ricans. Review Article. 19(5):331-339. Moeller, S.M., Reedy, J., Millen, A.E., Dixon, L.B., Newby, P.K., Tucker, K., Krebs-Smith, S.M., Guenther, P.M. 2007. Dietary Patterns: Challenges and Opportunities in Dietary Patterns Research. Journal Of The American Dietetic Association. 107(7):1233-1239.