Effects of Amino Acids on Regional Lipid Metabolism

Sponsor

University of Arkansas (Other)

Overall Status

Completed

CT.gov ID

NCT01150188

Collaborator

National Institute on Aging (NIA) (NIH)

125

Enrollment

Location

Arms

Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Elevated fat level in blood is a risk factor for coronary heart disease, a major cause of death in America. The overall goal of this project is to test a novel treatment using nutrient (amino acid) supplementation against this condition in men and women, and to understand how this treatment works.

Condition or Disease	Intervention/Treatment	Phase
Hypertriglyceridemia	Dietary Supplement: Amino acids Dietary Supplement: Placebo	N/A

Detailed Description

Coronary heart disease (CHD) remains the single largest killer of American men and women (45). Hyper¬triglyceridemia (elevated triglyceride [TG] concentration in the blood) has been shown to be a significant independent risk factor for CHD (7;8;25), accordingly, treatment for hypertriglyceridemia has been included in the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program (36). In a meta-analysis of 21 population-based prospective studies including a total of 65,863 men and 11,089 women, each increase of 89 mg/dl (1 mmol/l) in TG concentration was associated with a 32% increase in CHD risk in men and 76% increase in women (3). Thus, hypertriglyceridemia is an even stronger risk factor for CHD in women than in men.

The prevalence of hypertriglyceridemia is high. It is a common finding with aging, and is also associated with overweight, obesity, diabetes, and renal disease (39). With the aging of the US population and ongoing epidemics of obesity and type 2-diabetes, the number of individuals with conditions associated with elevated TG levels is likely to grow.

4.1.2 Effect of Amino Acids on Plasma Triglyceride Concentration In an effort to clarify the potential independent effect of protein on plasma and tissue lipids, we supplemented a normal weight-maintaining diet with a relatively small amount of amino acids (~90 kcal/day) between meals. We measured tissue lipids in addition to plasma lipids since the increase in insulin resistance with aging has been linked to increased fat accumulation in muscle and liver tissue (20;63). Also, it has repeatedly been shown that amino acid intake stimulates muscle protein synthesis and improves muscle protein net balance (86). Our hypothesis was that supplementation of the normal diet with a mixture of amino acids will reduce circulating and tissue TG concentrations and improve insulin sensitivity in elderly subjects with impaired glucose tolerance. Twelve impaired glucose tolerant elderly ingested 11 g of essential amino acids (EAA) + arginine twice a day for 16 weeks, after a 7 week control run in. Diet and activity were not otherwise modified. We found individuals consuming the EAA supplement had improved physical function. Further, these individuals had lower plasma and liver TG concentrations than before supplementation, and total cholesterol and VLDL-cholesterol concentrations were also lower after supplementations (12). In the present study, we will investigate this by supplementing the diet of older subjects shown to have hypertriglyceridemia.

Study Design

Study Type:

Interventional

Actual Enrollment :

125 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

Effects of Amino Acids on Regional Lipid Metabolism

Study Start Date :

Jun 1, 2010

Actual Primary Completion Date :

Aug 1, 2016

Actual Study Completion Date :

Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Amino acids Amino acid supplementation between meals for eight weeks	Dietary Supplement: Amino acids 11 g amino acids two times per day for eight weeks
Placebo Comparator: Placebo Supplementation of placebo (inert components) between meals for eight weeks	Dietary Supplement: Placebo Placebo of inert compounds, 11 g two times per day for eight weeks

Arm

Intervention/Treatment

Active Comparator: Amino acids

Amino acid supplementation between meals for eight weeks

Dietary Supplement: Amino acids

11 g amino acids two times per day for eight weeks

Placebo Comparator: Placebo

Supplementation of placebo (inert components) between meals for eight weeks

Dietary Supplement: Placebo

Placebo of inert compounds, 11 g two times per day for eight weeks

Outcome Measures

Primary Outcome Measures

Very low density lipoprotein (VLDL) turnover [Eight weeks]
Turnover rates of VLDL-triglycerides and VLDL-ApoB-100, including synthesis and breakdown rates, measured before and after eight weeks of amino acid supplementation

Secondary Outcome Measures

Fat oxidation [8 weeks]
Fat oxidation measured before and after eight weeks of amino acid supplementation
Lipolysis [8 weeks]
Lipolysis measured before and after eight weeks of amino acid supplementation
Triglyceride uptake in muscle and adipose tissue [Eight weeks]
Triglyceride uptake in muscle and adipose tissue measured before and after eight weeks of amino acid supplementation

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age 50-75 years.
Men and Women (Women postmenopausal).
Ability to sign informed consent, including ≥26 Mini-Mental State Exam.
Plasma triglyceride concentration between 130-500 mg/dl.

Exclusion Criteria:

Diabetes (plasma glucose: fasting ≥126 mg/dl or ≥200 mg/dl at 2 hr after 75 g glucose load).
On diabetes medication or lipid altering agents, including over the counter fish oil/omega 3 fatty acids.
Kidney/renal or liver disease.
Bleeding disorders or anemia.
Endocrine disease.
Positive hepatitis or HIV screens.
Alcohol abuse or drug abuse
Score of <26 on the Mini-Mental State Exam.
Allergy to iodine or fish products.
Subjects with cerebral aneurysm clips, internal transistorized devices (e.g., neural stimulators), or cardiac pacemakers.