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United States Department of Agriculture

Agricultural Research Service


item Ferretti, Aldo
item Nelson, Gary
item Schmidt, Perla
item Kelley, Darshan
item Bartolini, Giovanni
item Flanagan, Vincent

Submitted to: Lipids
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/26/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: Coronary heart disease (CHD) causes more than 600,000 deaths in the United States each year. It is estimated that total direct and indirect cost of CHD is over $80 billion/year. Decades of research produced a consensus among investigators that the diet exerts a significant influence on the atherosclerotic process and on the level of risk of life-threatening events ssuch as heart attacks and strokes. Fat is the dietary component that most directly influences the development of such events. Important mediators of these effects are certain metabolic products of arachidonic acid called eicosanoids. To develop dietary guidelines, it is important to know direction and magnitude of diet-induced alterations in the production of those mediators. Thus, systematic studies are underway to assess the effects of specific fatty acids. The present study focuses on the effect of arachidonic acid on indices of risk for CHD. We found that a five-fold increase of this fatty acid above the level of a reference diet results in an average 41% increase in the synthetic rate of the prothrombotic TXA2 and an increase of 25% in the synthesis of the antithrombotic PGI2. The effect of dietary manipulations on the production of those two eicosanoids is an important criterion in the development of nutritional guidelines for the general public.

Technical Abstract: Data on the effect of dietary arachidonic acid (20:4n-6) on the synthesis of thromboxane (TXA2) and prostacyclin (PGI2) in the human are lacking. We measured the effect of 1.5 g/d (ca. 0.5 en%) of 20:4n-6 added isocalorically to a stabilization (S) diet on the excretion of 11-dehydro- thromboxane B2 (11-DTXB2) and 2,3-dinor-6-oxo-PGF1alpha(PGI2-M). In a crossover design, ten healthy men, living in a metabolic unit, were fed low-fat diet (S) containing 340 mg of 20:4n-6 for 65 days and an identical diet (AA) that contained 1.5 g/d of additional 20:4n-6 for 50 days. Three- day urine pools were collected at the end of each dietary period and analyzed for eicosanoids by gas chromatography-electron capture negative ion-tandem mass spectrometry (GC-ECNI-MS-MS). Mean excretion of 11-DTXB2 was 493 + 49 ng/d (SE; n=10) with the S diet and 696 + 45 ng/d with the AA diet (41% increase, P=0.0037); mean excretion of PGI2-M was 151 + 11 ng/d (SE; n=10) and 192 + 17 ng/d with the S and the AA diets, respectively (27 increase, P=0.0143). Thus, both the metabolites of TXA2 and PGI2 increase on the AA diet. Furthermore, both indicated changes in metabolite excretion may have measurable effects on several physiologically significant cellular functions, such as platelet aggregation in vivo and inflammation in response to immune challenges.

Last Modified: 06/22/2017
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