A human dietary arachidonic acid supplementation study conducted in a metabolic research unit: rationale and design.
While there are many reports of studies that fed arachidonic acid (AA) to animals, there are very few reports of AA feeding to humans under controlled conditions. This 130-d study was conceived as a controlled, symmetrical crossover design with healthy, adult male volunteers. They lived in the metabolic research unit (MRU) of the Western Human Nutrition Research (WHNRC) for the entire study. All food was prepared by the WHNRC kitchen. The basal (low-AA) diet consisted of natural foods (30 en% fat, 15 en% protein, and 55 en% carbohydrate), containing 210 mg/d of AA, and met the recommended daily allowance for all nutrients. The high-AA (intervention) diet was similar except that 1.5 g/d of AA in the form of a triglyceride containing 50% AA replaced an equal amount of high-oleic safflower oil in the basal diet. The subjects (ages 20 to 39) were within -10 to +20% of ideal body weight, nonsmoking, and not allowed alcohol in the MRU. Their exercise level was constant, and their body weights were maintained within 2% of entry level. Subjects were initially fed the low-AA diet for 15 d. On day 16, half of the subjects (group A) wee placed on the high-AA diet, and the other group (B) remained on the low-AA diets. On day 65, the two groups switched diets. On day 115, group B returned to the low-AA diet. This design, assuming no carryover effect, allowed us to merge the data from the two groups, with the data comparison days being 65 (low-AA) and 115 (high-AA) for group B and 130 (low-AA) and 65 (high-AA) for group A. The main indices studied were the fatty acid composition of the plasma, red blood cells, platelets, and adipose tissue; in vitro platelet aggregation, bleeding times, clotting factors; immune response as measured by delayed hypersensitivity skin tests, cellular proliferation of peripheral blood mononuclear cells in response to various mitogens and antigens, natural killer cell activity, and response to measles/mumps/rubella and influenza vaccines; the metabolic conversion of deuterated linoleic acid to AA and the metabolic fate of deuterated AA in the subjects on and off the high-AA diet; and the production of eicosanoids as measured by excretion of 11-DTXB2 and PGI2-M in urine. The results of these studies will be presented in the next five papers from this symposium.
Nelson
G J
GJ
Western Human Nutrition Research Center, ARS, USDA, San Francisco, California 94129, USA.
Kelley
D S
DS
Emken
E A
EA
Phinney
S D
SD
Kyle
D
D
Ferretti
A
A
D000328:Adult; D000917:Antibody Formation; D016718:Arachidonic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000494:pharmacology*; D011464:Epoprostenol / Q000652:urine; D005227:Fatty Acids / Q000737:chemistry; D005527:Food, Fortified; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D013931:Thromboxanes / Q000652:urine; D014280:Triglycerides / Q000378:metabolism / Q000494:pharmacology*
D004041:Dietary Fats; D005227:Fatty Acids; D008055:Lipids; D013931:Thromboxanes; D014280:Triglycerides; D016718:Arachidonic Acid; D011464:Epoprostenol