We have developed a beverage targeting the elderly consumer with elevations in circulating lipids. The formulation contains a unique blend of components that independently have been shown to lower plasma concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, circulating triglycerides (TGs), and liver fat. The blend consists of a specific formulation of essential amino acids (EAAs) and the amino acid arginine that have been shown to lower circulating TGs and liver fat, and plant sterols that have been shown to lower total and LDL cholesterol. The cholesterol-lowering effect of plant sterols has been previously proven. In the current proposal we will focus on the action of the EAAs plus arginine to lower circulating TGs and liver fat. The specific hypotheses to be tested are as follows: 1. Ingestion of the EAA formulation will reduce circulating TGs and liver fat in elderly individuals who are receiving drug therapy with statins but still have a significant elevation in triglycerides, or in whom statin therapy has failed due to myopathies. 2. EAAs will lower circulating and liver TGs principally by stimulating peripheral clearance of VLDL-TG. We propose that greater VLDL-TG clearance will lower plasma concentrations of TGs, thereby enabling more VLDL-TG to be secreted by the liver without increasing plasma concentrations. Greater VLDL-TG secretion, coupled with no change in delivery of free fatty acids to the liver as a result of peripheral lipolysis, will reduce TG in the liver. 3. Reduction of liver fat will be related to improved glucose tolerance and insulin sensitivity. Stable isotope tracer methodology will be used to quantify VLDL-TG secretion and clearance, and peripheral free fatty acid release. Magnetic resonance spectroscopy will be used to measure liver fat. Glucose tolerance and insulin sensitivity will be estimated from an oral glucose tolerance test. PUBLIC HEALTH RELEVANCE Elevations in plasma triglycerides and liver fat are common in the elderly. These responses are a prominent component of the metabolic syndrome, and are risk factors for cardiovascular disease. In this project we will investigate a new dietary supplement that we propose will reduce both circulating TGs and liver fat in elderly individuals. The formulation avoids the cost and potential adverse side effects of existing medications that are commonly used to lower plasma lipids.
Thesaurus Terms: Adverse Effects; Aged 65 And Over; Amino Acids; Amino Acids, Essential; Arginine; Arginine, L-Isomer; Beverages; Blood Plasma; Blood Pressure; Cardiovascular Diseases; Cholest-5-En-3-Ol (3beta)-; Cholesterol; Clinical Trials, Phase I; Clinical Trials, Phase Ii; Communities; Coupled; D-Glucose; Data; Development; Dextrose; Diabetes Mellitus; Diet Supplement; Dietary Supplements; Dietary Intake; Disorder Of Muscle, Unspecified; Drug Formulations; Drug Therapy; Drugs; Dyslipidemias; Early-Stage Clinical Trials; Effectiveness; Elderly; Elderly, Over 65; Essential Amino Acids; Flr; Failure (Biologic Function); Fasting; Fats; Fatty Acids, Nonesterified; Fatty Acid Glycerol Esters; Formulation; Formulations, Drug; Free Fatty Acids; Glucose; Glucose Plasma Concentration; Glycohemoglobin A; Glycosylated Hemoglobin A; Goals; Hb A1; Hb A1a+B; Hb A1c; Hba1; Hba1c; Hemoglobin A(1); Hour; Individual; Ingestion; Insulin Resistance; Intellectual Property; L-Arginine; Ldl Cholesterol; Ldl Cholesterol Lipoproteins; Link; Lipids; Lipolysis; Liver; Low Density Lipoprotein Cholesterol; Mr Spectroscopy; Mrs; Mrsi; Magnetic Resonance Spectroscopy; Measures; Medication; Metabolic Syndrome; Method Loinc Axis 6; Methodology; Monitor; Muscle; Muscle Disease; Muscle Disorders; Muscle Tissue; Muscle Disease Or Syndrome; Muscular Diseases; Myopathic Conditions; Myopathic Diseases And Syndromes; Myopathic Disease Or Syndrome; Myopathy; Myopathy, Unspecified; Nonesterified Fatty Acids; Nutritional Supplement; Ogtt; Oral; Oral Glucose Tolerance; Oral Glucose Tolerance Test; Peripheral; Pharmaceutic Preparations; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phase 1 Clinical Trials; Phase 2 Clinical Trials; Phase I Clinical Trials; Phase I Study; Phase Ii Clinical Trials; Phytosterols; Plant Sterols; Plasma; Protocol; Protocols Documentation; Reticuloendothelial System, Serum, Plasma; Risk Factors; Serum, Plasma; Tag; Testing; Time; Tracer; Treatment Side Effects; Triacylglycerol; Triglycerides; Vldl Triacylglycerol; Vldl Triglyceride; Advanced Age; Aminoacid; Base; Beta-Lipoprotein Cholesterol; Body System, Hepatic; Cardiovascular Disease Risk; Cardiovascular Disorder; Cardiovascular Disorder Risk; Cost; Diabetes; Drug/Agent; Elders; Essential Amino Acid; Essential Aminoacid; Failure; Fasted; Fasts; Geriatric; Glucose Tolerance; Hemoglobin A1c; Improved; Insulin Resistant; Insulin Sensitivity; Late Life; Later Life; Lipoprotein, Vldl Triglyceride; Muscular Disorder; Older Adult; Older Person; Organ System, Hepatic; Phase 1 Study; Phase 1 Trial; Phase 2 Study; Phase 2 Trial; Phase I Trial; Phase Ii Trial; Protocol, Phase I; Protocol, Phase Ii; Public Health Relevance; Response; Senior Citizen; Side Effect; Stable Isotope; Study, Phase Ii; Success; Therapy Adverse Effect; Treatment Adverse Effect; Very Low Density Lipoprotein Triglyceride
