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 adherence 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. 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. 4.Accomplishments 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 folic acid treatment of pernicious anemia, a disease caused by severe vitamin B-12 deficiency, suggested that high-level folic acid fortification might result in delayed diagnosis or exacerbated 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 and cognitive function in senior participants in the 1999–2002 US National Health and Nutrition Examination Survey. The study found that, though higher folate status was associated with less anemia and better cognition in seniors with normal vitamin B-12 status, it was associated with worse anemia and worse cognition in seniors with low vitamin B-12 status. The study suggests that increasing the vitamin B-12 status of older Americans will reduce the prevalence of age-related cognitive decline in the age of folic acid fortification. 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 healthy dietary pattern on fracture risk for elderly Americans. Nor did the results suggest that individual dietary factors, such as calcium and vitamin D, affect fracture risk in elderly individuals. The study did not address the impact of a healthy diet pattern consumed as younger and middle aged adults on later risk of fracture. 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 DM and 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. 5.Significant Activities that Support Special Target Populations None. 6.Technology Transfer Number of non-peer reviewed presentations and proceedings 16 Number of newspaper articles and other presentations for non-science audiences 14