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LETTER

Potential Risk of Prolonged Gamma-linolenic Acid Use

right arrow Stephen Phinney, MD, PhD

15 April 1994 | Volume 120 Issue 8 | Page 692


TO THE EDITOR:

The report by Leventhal and colleagues [1] did not address the potential risk of arachidonate accretion associated with prolonged use of {gamma}-linolenic acid. Because elongase is more active than delta-5-desaturase, the dihomo-{gamma}-linolenic acid content of tissue lipids is increased during administration of borage oil, and some of this is metabolized further to arachidonate. We found that 2 g/d of {gamma}-linolenic acid given to previously obese women increased the arachidonate content of their serum phospholipids [2]. Gamma-linolenic acid given to obese Zucker rats increased adipose triglyceride arachidonate fivefold compared with controls and reduced their food intake [3]. Elevated dihomo-{gamma}-linolenic acid in muscle phospholipids is associated with insulin resistance [4]. During relatively short periods of borage oil administration, the initial effects result from the increase in dihomo-{gamma}-linolenic acid. With prolonged administration (for example, >1 year), slow accumulation of arachidonate will eventually enhance the tissue content of this inflammatory mediator, which could counteract the early therapeutic effects of borage oil. After {gamma}-linolenic acid treatment is discontinued, the production of extra dihomo-{gamma}-linolenic acid ceases, and the residual effects of enhanced tissue arachidonate could include exacerbation of the arthritis. Thus, it would be important to have data on serum or tissue fatty acids and to know whether symptoms rebounded in study patients after drug discontinuation and in its absence. Physicians and patients should be alerted that a tissue buildup of arachidonate might promote subsequent inflammation, thrombosis, and immunosuppression [5].


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University of California, Davis; School of Medicine; Davis, CA 95616


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1. Leventhal LJ, Boyce EG, Zurler RB. Treatment of rheumatoid arthritis with gammalinolenic acid. Ann Intern Med. 1993; 119:867-73.

2. Phinney SD, Davis PG, Johnson SB, Holman RT. Phospholipid arachidonate deficiency in human obesity responds to {gamma}-linolenate supplementation. Int J Obesity. 1989; 13:402.

3. Phinney SD, Tang AB, Thurmond DC, Nakamura MT, Stern JS. Abnormal polyunsaturated lipid metabolism in the obese Zucker rat with partial metaboic correction by {gamma}-linolenate supplementation. Metabolism. 1993; 42:1340-50.

4. Borkman M, Storlien LH, Pan DA, Jenkins AB, Chisholm DJ, Campbell LV. The relation between insulin sensitivity and fatty acid composition of skeletal muscle phospholipids. N Engl J Med. 1993; 328:238-44.

5. Kinsella JE. Lipids, membranee receptors, and enzymes: effects of dietary fatty acids. J Parenteral Enteral Nutr. 1990; 14:200s-17s.

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