Effects of Amino Acids on Regional Lipid Metabolism



Status:Recruiting
Conditions:High Cholesterol, Metabolic
Therapuetic Areas:Cardiology / Vascular Diseases, Pharmacology / Toxicology
Healthy:No
Age Range:50 - 75
Updated:7/22/2016
Start Date:June 2010
End Date:December 2016
Contact:Elisabet Borsheim, PhD
Email:EBorsheim@uams.edu
Phone:(501)-364-3053

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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.

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.

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.
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Little Rock, Arkansas 72205
Phone: 501-364-3053
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