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ARS Home » Northeast Area » Beltsville, Maryland (BHNRC) » Beltsville Human Nutrition Research Center » Food Components and Health Laboratory » Research » Research Project #426314

Research Project: Metabolism and Molecular Targets of Macro and Micro Food Components in the Development and Management of Obesity and Chronic Diseases

Location: Food Components and Health Laboratory

2016 Annual Report

Diet is a modifiable factor that can influence the multitude of chronic health disorders that face the U.S. adult population, including type 2 diabetes, cardiovascular disease, some cancers, arthritis, endothelial dysfunction, and others. Through the experiments planned for this project, we will attempt to improve the understanding of the influence of diet on chronic disease. We will investigate direct effects of diet on cardiometabolic profile and additionally factors that influence weight gain, which increases risk for chronic disease. Objective 1. Determine the energy content of specific foods in the context of a mixed diet, and the absorption, metabolism and impact on biomarkers for health promotion of these foods or their macro and micro components. Objective 2. Determine the influence and interaction of the composition of food intake and exercise on glucoregulation, cardiometabolic profile, and metabolic flexibility (fuel management). Objective 3. Determine the extent to which the day-to-day variation in daily voluntary food intake, measured over at least 3 months, is related to diet composition, physical activity, and changes in physiological and metabolic markers related to energy balance, satiety and hunger.

Diet is a modifiable lifestyle factor that can influence the multitude of chronic diseases faced by an increasing proportion of the U.S. population, including type 2 diabetes, hypertension, vascular dysfunction, cardiovascular disease, cancer, and arthritis. Moreover, the widespread global prevalence of these diseases threatens the quality of life and places additional stresses on an already overburdened health care system. This project, through highly controlled human feeding studies, will target specific factors which influence risk for and development of chronic disease. First, research will be conducted to improve accuracy of the energy value of foods, which can impact weight gain, a risk factor for chronic disease. Second, research will be conducted to investigate dietary factors that can influence cardiometabolic profile, i.e. risk for cardiovascular disease, stroke, or diabetes. Third, we will study how diet influences voluntary food intake, again impacting weight gain, a risk factor for chronic disease. The outcomes of this research will provide a better understanding of 1) the energy content of specific foods in the context of a mixed diet, and the absorption, metabolism and impact on biomarkers for health promotion of these foods or their components, 2) dietary and lifestyle influences on diabetes and cardiovascular disease risk, and 3) the extent to which the day-to-day variation in daily voluntary food intake is related to diet composition. This research will fill knowledge gaps in the metabolism of macro and micro food components related to the development and management of obesity and chronic diseases, and provide a scientific basis for dietary recommendations and nutrition policy.

Progress Report
Progress was made for two objectives of this project plan linked to National Program 107 Plan, focusing on Component 3 to provide a Scientific Basis for Dietary Guidance. Progress has been made addressing Problem Statement 3B: Identify Roles of Food, Food Components and Physical Activity in Promoting Health and Preventing Disease through studies on tree nuts and energy metabolism. A controlled dietary intervention of cashew nuts was conducted with two objectives: 1) to determine the effect of cashew nut consumption on biochemical and physiological biomarkers of cardiovascular disease and 2) to empirically measure the energy content of a serving of cashew nuts. Cardiovascular disease is the leading cause of death worldwide, accounting for over 4 million deaths annually in Europe and almost 930,000 deaths annually in the United States. Tree nuts are a dietary component that appears to have beneficial effects on biomarkers of cardiovascular disease risk, though data relating cashew nuts to cardiovascular disease risk is limited to one study. Moreover, cashew nuts are excluded from the Food and Drug Administration’s qualified health claim for tree nuts and cardiovascular disease (due to the limited data to evaluate cashew nuts and their slightly higher saturated fat content). Despite the potential role of cashew nuts in improving heart health, consumers may be wary to consume nuts due to their high energy density, thus missing the opportunity to improve their diet quality and health by consuming this dietary component. The study was conducted in a crossover design with two four-week treatment arms: 1) a base Western-style diet with cashew nuts, and 2) a base Western-style diet without cashew nuts. Biomarkers of cardiovascular disease risk were assessed at the beginning of the study and at the end of each intervention period. Complete urine and fecal collections in the third week of the study were conducted to allow empirical measurement of the metabolizable energy content of cashew nuts. A large double-blind dietary intervention study (n=60) of soybean oils was conducted in individuals at-risk for coronary heart disease. In 2013, the U.S. Food & Drug Administration made a preliminary determination that partially hydrogenated oils are no longer “generally recognized as safe” due to the presence of trans fatty acids. Plant and food scientists have worked to develop oil alternatives to trans fatty acids that are low in saturated fatty acids but still provide the functionality of trans fatty acids, such as taste, texture, and increased shelf life, without the need for partial hydrogenation. Newer plant breeding techniques have made it possible to modify the fatty acid composition of vegetable oils in order to increase monounsaturated fatty acids, such as oleic acid, and decrease saturated and polyunsaturated fatty acids, thus producing a potentially healthier and more shelf-stable trans fatty acids alternative. The aim of this study is to investigate the effect of a high-oleic soybean oil and a blend of high-oleic soybean oil and fully hydrogenated soybean oil on the risk factors used to define metabolic syndrome which includes biomarkers of diabetes and cardiovascular disease. A study was conducted to improve the understanding of pre-analytical sample handling methods on metabolomic profiling. The two objectives were to determine how distinct sample handling conditions affect estimated concentrations of ~1,000 serum metabolites, and to quantify the degree of attenuation and/or potential bias in epidemiologic associations that may result from less than optimal sample handling conditions. Metabolomics, the simultaneous quantification of concentrations of 100s or 1000s of metabolites simultaneously in a biological matrix, is a versatile analytical technique capable of accelerating biomarker-based discoveries in nutritional science. Recently, metabolomics has been applied to samples collected in feeding studies and epidemiologic studies to identify dozens of novel potential dietary biomarkers. A crucial but incompletely understood factor in metabolomics analyses is how pre-analytical sample handling may affect results. Very few studies have examined pre-analytical sample handling such as time to process samples after collection, the number of freeze-thaw cycles, and the time and method used to defrost samples. The results of this study have not been published, but it is expected that they will be valuable in interpreting existing studies, guiding meta-analyses of existing datasets, and guiding the conduct of future studies.

1. The predominant naturally occurring trans fatty isomer, vaccenic acid, raises LDL cholesterol. In addition to food products produced using partially hydrogenated vegetable oils, dietary trans fatty acids are found naturally in products from ruminant animals (for example, milk, beef, lamb). Evidence of the adverse effects of industrially-produced trans fatty acids on risk of cardiovascular disease is consistent and well-documented in the scientific literature; however, the cardiovascular effects of naturally-occurring trans fatty acids synthesized in ruminant animals, such as vaccenic acid and specific conjugated linolenic acid, are less clear. ARS researchers at the Beltsville Human Nutrition Research Center, Beltsville, Maryland, conducted a double-blind, randomized crossover feeding trial in healthy adults to determine whether different isomers differentially affect lipoprotein risk factors compared to a control diet. Both naturally occurring and industrially produced trans fatty acid isomers increased total cholesterol and LDL-cholesterol (“bad” cholesterol) when compared with the control diet. With respect to risk of cardiovascular disease, the results of our study are consistent with current nutrition labeling guidelines, with the requirement of trans fatty acids, but not conjugated linoleic acids, to be listed under the trans fatty acid listing on the Nutrition Facts Panel.

2. Moderate alcohol consumption decreases markers of inflammation. Moderate alcohol consumption has previously been associated with a decreased risk for cardiovascular disease. Inflammation and the balance between blood clot formation and breakdown (hemostasis) contribute to the development of cardiovascular disease, especially coronary heart disease; further, beneficial changes in cholesterol, alcohol may reduce risk for cardiovascular disease risk through its effect on the inflammatory and blood clotting (hemostatic) processes. The objective of this study was to evaluate the effect of moderate alcohol consumption on biomarkers of inflammation and hemostasis in postmenopausal women. Researchers at the Beltsville Human Nutrition Research Center, Beltsville, Maryland, conducted a controlled dietary intervention study with postmenopausal women who each consumed a weight-maintaining diet plus no drinks per day, 1 drink per day, and 2 drinks per day of alcohol for eight weeks. Moderate alcohol consumption decreased several markers of inflammation; however, one inhibitor of blood clot breakdown (plasminogen activator inhibitor-1) did increase with moderate alcohol intake. These data suggest that moderate alcohol consumption may have beneficial effects on inflammation and hemostasis in postmenopausal women, which may be mitigated by an increase in plasminogen activator inhibitor-1. These data are important to consumers interested in the relationship between diet and risk for disease and allied health and medical professionals involved with making dietary recommendations.

3. Personalized nutrition is important to determining who might benefit from consuming plant sterols. Plant sterols lower LDL-cholesterol (“bad” cholesterol), but there is large variability in the response among individuals. Researchers at the Beltsville Human Nutrition Research Center, Beltsville, Maryland, studied the effect of selected genetic profiles on blood cholesterol response to plant sterols in a study which recruited individuals who were classified as either having a high or low ability to synthesize their own cholesterol. LDL-cholesterol lowering in response to plant sterol consumption was associated with individuals’ genotypes. Some genetic profiles showed no LDL-cholesterol lowering, while the presence of specific genetic profiles was associated with LDL-cholesterol response in a dose dependent fashion. Similarly, individuals with the presence of certain lipoprotein profiles (ApoE e3) responded less than individuals with other ApoE profiles (ApoE e4) and a certain gene combination was associated with non-responsiveness to the diet. Specific genetic profile and ApoE isoform are associated with the extent of reduction in circulating LDL-cholesterol in response to plant sterol consumption and could serve as potential predictive genetic markers to identify individuals who would derive maximum LDL-cholesterol lowering with plant sterol consumption.

Review Publications
Stote, K.S., Tracy, R.P., Taylor, P.R., Baer, D.J. 2016. The effect of moderate alcohol consumption on biomarkers of inflammation and hemostatic factors in postmenopausal women. European Journal of Clinical Nutrition. 70:470-474.
Mackay, D.S., Eck, P.K., Gebauer, S.K., Baer, D.J., Jones, P.J. 2015. CYP7A1-rs3808607 and APOE isoform associate with LDL cholesterol lowering after plant sterol consumption in a randomized clinical trial. American Journal of Clinical Nutrition. 102:951-957.
Gebauer, S.K., Destaillats, F., Dionisi, F., Krauss, R.M., Baer, D.J. 2015. Vaccenic acid and trans fatty acid isomers from partially hydrogenated oil both adversely affect LDL cholesterol: a double-blind, randomized controlled trial. American Journal of Clinical Nutrition. 102:1339-1346.
Baer, D.J., Gebauer, S.K., Novotny Dura, J. 2016. Walnuts consumed by healthy adults provide less available energy than predicted by the Atwater factors. Journal of Nutrition. 146:9-13.
Paul, D., Kramer, M.H., Stote, K., Baer, D.J. 2015. Determinants of variance in the habitual physical activity of overweight adults. Journal of Physical Activity and Health. 12:680-685.