Clinical trial NCT00728338: Docosahexenoic Acid (DHA) Supplementation and Cardiovascular Disease in Men With High Triglycerides
Official title: Effect of Docosahexenoic Acid (22:6n-3, DHA) Supplementation on Risk Factors for Cardiovascular Disease in Hyperlipidemic Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertriglyceridemia
Keywords: docosahexenoic acid (DHA)
dietary supplement
n-3 polyunsaturated fatty acid
cardiovascular disease
Lead sponsor: USDA, Western Human Nutrition Research Center
Sponsor class: FED
Collaborators: name: VA Northern California Health Care System
name: DSM Nutritional Products, Inc.
First posted: 2008-08-05
Enrollment: 40
Sex: MALE
Minimum age (years): 39
Maximum age (years): 66
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the effects of supplementing diets of hyperlipidemic men with DHA (docosahexenoic acid) on risk factors for cardiovascular disease. We hypothesize that supplementing diets of hyperlipidemic men with DHA will decrease the plasma concentrations of CRP (C-reactive protein), inflammatory cytokines, and soluble adhesion molecules. We further hypothesize that DHA supplementation will decrease serum triglyceride concentrations and increase HDL concentration.

Detailed description: Cardiovascular disease (CVD) and stroke are the leading causes of mortality in the United States, accounting for more than 38% of all deaths. Elevated total- and LDL- cholesterol, number of total and small dense LDL particles, triacylglycerols, and low HDL-C are established independent risk factors for the development of CVD. Additional novel blood lipid markers used as risk factors for CVD include, increased plasma concentration of remnant like particle-cholesterol (RLP-C), decreased ratio between plasma eicosapentaenoic acid (EPA) and arachidonic acd (AA), and decreased omega-3 index (sum of EPA and DHA as a percentage of total fatty acid content) of the red blood cells.

Diets rich in omega-3 fatty acids have been shown to be cardio-protective; these diets decreased inflammation, platelet aggregation, cardiac arrhythmias, triglycerides, number of total LDL and small dense LDL particles, and increased omega-3 index, endothelial relaxation and atherosclerotic plaque stability. Most of the earlier studies regarding the effects of long chain n-3 PUFA on blood lipids were conducted with fish oils which contain a mixture of EPA and DHA. Recently a number of studies have been conducted with EPA and DHA individually. Results from studies with individual fatty acids show that EPA and DHA have similar effects on some of the lipid parameters, but they are assimilated to a different concentration in tissues and have different effects on lipoprotein particle size, heart rate and blood pressure. The main purpose of this study is to examine the effects of DHA supplementation on the above three risk factors.

Eligibility criteria: Inclusion Criteria:

* fasting serum triglyceride values of 150-400 mg/dL
* total cholesterol \< 300 mg/dL
* LDL-cholesterol \< 220 mg/dL
* BMI between 22 and 35 Kg/m2

Exclusion Criteria:

* anti-inflammatory medications including steroids
* antihypertensives
* non sulfonyl urea medications for diabetes mellitus
* drugs that alter serum triacylglycerols and HDL-C levels (i.e. fibrates)
* niacin supplements
* consumers of illegal substances
* consumers of more than 5 drinks of alcohol per week
* more than one fish meal per week
* dietary supplements of fish oil, flaxseed oil or vitamin C or E

Primary outcomes:
measure: Plasma biomarkers of inflammation
timeFrame: 0, 45, and 90 days
Secondary outcomes:
measure: Granulocyte maturation
timeFrame: 0, 45, and 90 dyas
measure: fasting and post-prandial serum lipids and lipoproteins
timeFrame: 0, 45, and 90 days
measure: blood pressure and blood clotting
timeFrame: 0, 45, and 90 days
measure: plasma biomarkers for diabetes
timeFrame: 0, 45, and 90 days
Other outcomes:
Locations:
city: Davis
country: United States
facility: Usda, Ars, Whnrc
state: California
Study officials:
affiliation: USDA, ARS, WHNRC
name: Darshan S Kelley, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kelley DS, Siegel D, Vemuri M, Mackey BE. Docosahexaenoic acid supplementation improves fasting and postprandial lipid profiles in hypertriglyceridemic men. Am J Clin Nutr. 2007 Aug;86(2):324-33. doi: 10.1093/ajcn/86.2.324.
citation: Kelley DS, Siegel D, Vemuri M, Chung GH, Mackey BE. Docosahexaenoic acid supplementation decreases remnant-like particle-cholesterol and increases the (n-3) index in hypertriglyceridemic men. J Nutr. 2008 Jan;138(1):30-5. doi: 10.1093/jn/138.1.30.
citation: Kelley DS, Adkins Y, Woodhouse LR, Swislocki A, Mackey BE, Siegel D. Docosahexaenoic acid supplementation improved lipocentric but not glucocentric markers of insulin sensitivity in hypertriglyceridemic men. Metab Syndr Relat Disord. 2012 Feb;10(1):32-8. doi: 10.1089/met.2011.0081. Epub 2011 Oct 14.
citation: Dawson K, Zhao L, Adkins Y, Vemuri M, Rodriguez RL, Gregg JP, Kelley DS, Hwang DH. Modulation of blood cell gene expression by DHA supplementation in hypertriglyceridemic men. J Nutr Biochem. 2012 Jun;23(6):616-21. doi: 10.1016/j.jnutbio.2011.03.004. Epub 2011 Jul 19.