Differential Metabolism of Dietary Fatty Acids

Differences in how diet fats are converted to energy could explain some of the reported differences in health effects among different classes of dietary fat (e.g. monounsaturated vs. saturated). Recently, this laboratory showed that monounsaturated fats are turned into energy more readily than saturated fats. These results may mean that if one feeds more monounsaturated fatty acids (MUFA) and less saturated fatty acids (SFA) in the diet, body fat might accumulate at a lower rate. This could affect the risk of obesity and Type 2 Diabetes. This project has two principal Specific Aims which will be assessed in healthy young adults who are fed liquid formulas containing either an approximately equal amount of MUFA and SFA (controls) or a much greater amount of MUFA and much less SFA:

1. To determine if a higher intake of MUFA and a reciprocally lower intake of SFA is associated with a higher rate of fat oxidation. We hypothesize that the rate of fat oxidation after eating will be higher in those subjects randomized to the MUFA-enriched diet compared to controls.
2. To measure energy intake required to maintain constant body weight during each diet and to measure fat-free mass and fat mass, before and after each dietary change. We hypothesize that those on the high MUFA diet will need a higher energy intake required to maintain constant body weight.

Study Overview

• Status: Completed
• Conditions: Obesity; Diabetes; Hyperlipidemia
• Intervention / Treatment: Dietary supplement: Oleic acid (OA); Dietary supplement: Palmitic Acid (PA)

Detailed Description

Our Preliminary Data indicate that the rate of oleic acid (OA) oxidation (amount/unit time) is 21% increased compared to palmitic acid (PA) when both fatty acids are fed to the same person at the same intake. We hypothesize that if the ratio of OA to PA in the diet were to increase, the rate of total fatty acid oxidation in the fed state also would increase under the same metabolic conditions. If our principal hypothesis is correct, overall daily fat balance might be decreased in humans fed diets enriched in OA. This would have potential significance to the treatment and prevention of obesity.

In order to address this hypothesis, we propose the following double-masked, randomized control trial. Indirect calorimetry will be performed in the fed and fasting state in young, healthy adults who will be studied under two conditions: after a 30-day, supervised, solid food diet and then again after a 30-day formula diet. The subjects will be randomized to receive either a Control Formula Diet of the same macronutrient and fatty acid composition as the solid food diet (OA=PA=16.4% total kcal) or a High Oleic Acid Formula Diet (OA=31.4% total kcal and PA=1.7% total kcal). The Control Diets (solid and liquid) provide amounts (per kcal) of total fat, saturated fat, and OA that are similar to the to the 50-75th percentile of intake of young adult Americans but above the intake of total fat and saturated fat that is recommended for optimal long-term health. The High OA Formula Diet is designed to simulate the fat source of the Mediterranean Diet. The High OA diet will result in a 167% increase in the intake/kcal of OA in the sn-1 and sn-3 positions of the dietary triacylglycerol. Using dual-energy x-ray absorptiometry (DEXA), we will monitor body composition before and after each diet, while adjusting energy intake to maintain constant body weight. The following Specific Aims will be addressed:

1. To determine if a higher intake of oleic acid (and a reciprocally lower intake of palmitic acid) is associated with a higher rate of fat oxidation. We hypothesize that the rate of fat oxidation (g/hr) in the fed state, adjusted for the covariate effect of the rate of fat oxidation on the solid food diet, will be higher (>30%) in those subjects randomized to the OA-enriched diet compared to controls. Furthermore, we hypothesize that fat oxidation will not be higher when expressed as a proportion of energy expenditure in the OA-enriched formula group. That is, we expect energy expenditure in the fed state to be higher in those fed the OA-enriched diet.
2. To measure energy intake required to maintain constant body weight during each diet and to measure fat-free mass and fat mass, before and after each dietary change. We hypothesize that a higher rate of fat oxidation on the high OA diet will be associated with a higher energy intake required to maintain constant body weight.
3. To compare fat oxidation on the liquid formula diet with that observed on the solid food diet. We hypothesize that fat oxidation will increase in those fed the OA-enriched diet.
4. To measure the thermic effect of feeding during both the solid food and formula diet periods. We hypothesize that the high OA feeding will be associated with a higher thermic effect of feeding.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Galveston, Texas, United States, 77555
      • Utmb Gcrc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

• Healthy young adults, ages 18-35 yr. .: Generally, this means that the subject is not being continually treated with medication (possible exceptions include thyroid replacement therapy and some allergy treatments).
• Must avoid pregnancy during the study duration (we will test for this as part of the protocol).
• Must avoid use of drugs that may affect lipid metabolism, including caffeine and nicotine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oleic acid (OA)	Dietary supplement: Oleic acid (OA); OA-enriched (HI OA; fat, 40%; PA, 1.7%; OA, 31.4%)
Experimental: Palmitic acid (PA)	Dietary supplement: Palmitic Acid (PA); PA-enriched (HI PA; fat, 40% of energy; PA, 16.8%; OA, 16.4%)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Oxygen consumption	Day 29

Secondary Outcome Measures

Outcome Measure	Time Frame
Carbon dioxide production	Day 29
Respiratory quotient	Day 29
excess Post exercise oxygen consumption (EPOC)	Day 29

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: The University of Texas Medical Branch, Galveston
• Investigators: Principal Investigator: Craig L Kein, MD, PhD, The University of Texas Medical Branch, Galveston

Publications and helpful links

General Publications

• Schmidt DE, Allred JB, Kien CL. Fractional oxidation of chylomicron-derived oleate is greater than that of palmitate in healthy adults fed frequent small meals. J Lipid Res. 1999 Dec;40(12):2322-32.
• Borsheim E, Kien CL, Pearl WM. Differential effects of dietary intake of palmitic acid and oleic acid on oxygen consumption during and after exercise. Metabolism. 2006 Sep;55(9):1215-21. doi: 10.1016/j.metabol.2006.05.005.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2000
• Primary Completion (Actual): April 1, 2005
• Study Completion (Actual): April 1, 2005

Study Registration Dates

• First Submitted: April 22, 2003
• First Submitted That Met QC Criteria: April 22, 2003
• First Posted (Estimate): April 23, 2003

Study Record Updates

• Last Update Posted (Actual): October 12, 2017
• Last Update Submitted That Met QC Criteria: October 11, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: body composition; human; energy expenditure; fat oxidation; fatty acids; monounsaturated fat; palmitic acid; oleic acid
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Palmitic Acid
• Other Study ID Numbers: DMDFA (COMPLETED); R01DK055384 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No