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Abstract
In the pathogenesis of hypercalciuria and hyperoxaluria, n-6 polyunsaturated fatty acids (PUFAs) have been implicated by virtue of their metabolic links with arachidonic acid (AA) and prostaglandin PGE2. Studies have also shown that n-3 PUFAs, particularly those in fish oil—eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—can serve as competitive substrates for AA in the n-6 series and can be incorporated into cell membrane phospholipids in the latter’s place, thereby reducing urinary excretions of calcium and oxalate. The present review interrogates several different types of study which address the question of the potential roles played by dietary PUFAs in modulating stone formation. Included among these are human trials that have investigated the effects of dietary PUFA interventions. We identified 16 such trials. Besides fish oil (EPA+DHA), other supplements such as evening primrose oil containing n-6 FAs linoleic acid (LA) and γ-linolenic acid (GLA) were tested. Urinary excretion of calcium or oxalate or both decreased in most trials. However, these decreases were most prominent in the fish oil trials. We recommend the administration of fish oil containing EPA and DHA in the management of calcium oxalate urolithiasis.
Highlights
During the past 30 years, studies have claimed that the dietary intake of n-3 polyunsaturated fatty acids, those occurring in marine fish and fish oils, reduces the risk of urinary stone formation [1,2,3,4,5,6,7]
Studies suggesting a lithogenic role for n-6 polyunsaturated fatty acids (PUFAs) have based their claims on arachidonic acid (AA) being a precursor of the pro-inflammatory and pro-aggregatory dienoic metabolite prostaglandin PGE2 [1], which is thought to affect calcium excretion by influencing renal tubular function and possibly by increasing intestinal calcium absorption [1,3,11]
In order to appreciate the role played by various PUFAs in possible stone formation and prevention, it is helpful to refer to established metabolic pathways of n-3 and n-6 metabolism
Summary
During the past 30 years, studies have claimed that the dietary intake of n-3 polyunsaturated fatty acids, those occurring in marine fish and fish oils, reduces the risk of urinary stone formation [1,2,3,4,5,6,7]. The study by Taylor and co-workers involving over 230,000 subjects in 3 three large national US cohorts showed that an increased intake of dietary n-3 PUFAs is highly unlikely to reduce the risk for kidney stone formation [13]. The process of renal parenchymal calcification is triggered, which itself is likely to be etiologically significant in the pathogenesis of calcium oxalate stone formation. In view of these contradictory findings, an assessment of the potential protective role of polyunsaturated fatty acids in stone formation and the mechanisms by which these fatty acids achieve these effects is warranted. Our review shows that the ingestion of fish oil, a rich source of n-3 fatty acids, reduces important physicochemical risk factors for calcium oxalate kidney stones
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