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United States Department of Agriculture

Agricultural Research Service

Research Project: MACRO- AND MICRONUTRIENT MODULATION OF BIOMARKERS OF CHRONIC DISEASE AND INDICATORS OF NUTRITIONAL ADEQUACY

Location: Food Components and Health Laboratory

2013 Annual Report


1a.Objectives (from AD-416):
Objective 1: Investigate macronutrient modulation of biomarkers of chronic disease. Sub-objective 1.A.: Investigate the role of individual fatty acids (such as alphalinolenic, stearic, conjugated linoleic, and/or vaccenic acids) on markers of inflammation and oxidation related to chronic disease. Delineate their metabolic pathways. Sub-objective 1.B.: Determine the differential effects of protein sources and macronutrient profiles on post-prandial oxidation, oxidative stress, insulin signaling,and blood pressure regulation. Objective 2: Improve biomarkers and indicators of nutritional adequacy through investigation of micronutrient metabolism. Sub-objective 2.A.: Investigate the differential in vivo metabolism of various forms of micronutrients (such as tocopherol and/or folate) through mathematical modeling.


1b.Approach (from AD-416):
Appropriate macro- and micronutrient intake is fundamental to a diet that will maintain health and reduce risk of chronic, degenerative diseases. For many nutrients or classes of nutrients, qualitative and quantitative estimates of intake to maintain health are available. However, for other nutrients, where there are a variety of dietary sources, specific sources may offer additional health benefits as compared to others. Many observations of the health effects of specific sources of food are based on epidemiologic data and therefore do not provide an opportunity to show a cause and effect. For example, epidemiologic data suggest that there is no association between consumption of naturally occurring trans fatty acids and risk for coronary heart disease whereas trans fatty acids from partially hydrogenated vegetable sources do increase risk for coronary heart disease and death. Epidemiologic data suggest that a decrease in body weight is associated with low-fat dairy food consumption but identification of the specific component(s) (such as proteins) found in low-fat dairy foods that may be responsible for this effect is needed. This five-year project will investigate the effects of different sources of trans fatty acids and protein on risk factors associated with cardiovascular disease, and diabetes in humans and will assess the relative bioavailability of synthetic and natural sources of vitamin E in humans using mathematical modeling. This research will fill knowledge gaps in macro and micronutrient metabolism and provide a scientific basis for dietary recommendations and nutrition policy.


3.Progress Report:
Progress was made for both objectives of this National Program 107 plan, focusing on Component II and III to provide a Scientific Basis for Dietary Guidance for Health Promotion and Disease Prevention and for the Prevention of Obesity and Related Diseases. Progress has been made addressing Problem Statement 2A: Identify Roles of Food, Nutrients, Food Components, and Physical Activity in Promoting Health and Preventing Disease through studies on nuts, avocados, advanced glycation end-products, and vitamin E.

Research with tree nuts continues with progress being made on understanding how almonds alter risk factors for cardiovascular disease, specifically the mechanism by which almonds lower LDL cholesterol. Using new analytical platforms, the metabolites of cholesterol were observed to increase when almonds were consumed. This change in these cholesterol metabolites suggests that almonds increase the excretion of cholesterol and thus reduce circulating concentration of LDL cholesterol.

In a study of healthy volunteers, a feeding study was conducted to investigate the role of avocados in improving heart health. Avocados are expected to provide benefit by promoting healthy blood vessels. Researchers provided 60 volunteers with controlled diets, one diet being comprised of typical American foods, and the other diet containing avocado in place of foods high in saturated fat. At the beginning and end of the intervention, blood and urine were collected for analysis of markers of cardiovascular disease. ARS researchers also administered a specialized blood pressure test to determine potential improvements in the ability of blood vessels to relax when necessary, thus maintaining healthy blood pressure. In these volunteers, blood pressure tended to be reduced in the group consuming avocados compared to the control group. Despite the reduction in saturated fat and the increase in monounsaturated fat, inflammatory markers were increased in the group consuming avocado.

Advanced glycation end-products (AGEs) are compounds that occur in food when it is browned or cooked. These AGE products are thought to increase risk for a number of chronic diseases. After analysis of the diets, researchers found that indeed, using different methods of food processing, one can increase intake of dietary AGE products. There was no detrimental effect of AGE products on health outcomes studied.

Research continues on a study of vitamin E requirement to improve scientific basis for dietary guidelines. The dietary recommendation for vitamin E is based on sparse data and a loose association between the purported function of vitamin E in the body and a test meant to reflect a small portion of that function. ARS researchers used kinetic modeling to determine that target blood values for vitamin E can be maintained with a daily intake much lower than the current recommended daily intake. Further, progress has been made in analyzing vitamin E concentration of different carriers of vitamin E. These data are being used to model transport and metabolism of vitamin E. This information is expected to impact future dietary intake recommendations.


4.Accomplishments
1. Specific genes were identified whose variability predicts HDL cholesterol (good cholesterol) concentration. Higher concentration of HDL cholesterol is associated with decreased risk of coronary heart disease. Exercise, saturated fatty acids, and alcohol can increase HDL cholesterol concentrations. In addition to these environmental factors, we identified genetic factors that predict HDL cholesterol concentration. Using data from two populations, we found that there are seven genes that can predict HDL cholesterol concentration. Some of these genes are also involved with folate (a B-vitamin) and carotenoid metabolism. Other identified genes are involved more directly with lipoprotein (the carriers of cholesterol) and cholesterol metabolism. These results provide new insight into understanding individual variability and risk for coronary heart disease. Moreover, these data will target dietary and other interventions that may increase HDL cholesterol concentration.

2. Dietary stearic acid, a saturated fatty acid, does not detrimentally impact blood clotting. Blood clot formation and breakdown is a highly controlled biological process. Factors that increase blood clotting may increase risk for coronary heart disease. Evidence suggests that stearic acid, a saturated fatty acid, effects LDL cholesterol differently than other saturated fatty acids – consumption of stearic acid does not increase LDL cholesterol whereas consumption of other saturated fatty acids typically raises LDL cholesterol. Since stearic acid does not raise LDL cholesterol, its use as an alternative for trans fatty acids in foods is possible since stearic acid can provide some of the same functional properties as trans fatty acids without the negative effect on LDL cholesterol. However, the effect of stearic acid on other markers of cardiovascular disease risk, such as markers of hemostasis (blood clotting), is unclear. Using data from a highly-controlled dietary intervention, there were no differences in several markers of hemostasis when comparing a diet enriched in stearic acid to a carbohydrate control diet, whereas a diet enriched in oleic acid diet increased these markers when compared to the carbohydrate control diet. Stearic acid and oleic acid had similar effects on these factors involved in hemostasis in healthy men, within the context of a highly-controlled diet. These data fill a void in knowledge as identified by the US Dietary Guideline Advisory Committee and are of interest to food manufacturers and those involved in establishing food labeling policy.


Review Publications
Novotny Dura, J., Gebauer, S.K., Baer, D.J. 2012. Discrepancy between Atwater factor predicted and empirically measured energy value of almonds in human diets. American Journal of Clinical Nutrition. 96:296-301.

Novotny Dura, J., Fadel, J.G., Holstege, D.M., Furr, H.C., Clifford, A.J. 2012. Kinetics, bioavailability, and metabolism of RRR-alpha-tocopherol in humans supports lower requirement for vitamin E. Journal of Nutrition. 142:2105-2111.

Andrew, C.J., Gonzalo, R., Janel, O., Juan, M., Moshfegh, A.J., Baer, D.J., Novotny Dura, J. 2013. Single nucleotide polymorphisms in CETP, SLC46A1, SLC19A1, CD36, BCOM1, APOA5, and ABCA1 are significant predictors of plasma HDL in healthy adults. Lipids in Health and Disease. 12:66-75.

Gribok, A., Reed, H., Buller, M., Rumpler, W.V. 2013. On the accuracy of instantaneous gas exchange rates, energy expenditure, and respiratory quotient calculations obtained in indirect whole room calorimetry. Physiological Measurement. 34:737-755.

Last Modified: 8/27/2014
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