Different effects of γ-linolenic acid (GLA) supplementation on plasma and red blood cell phospholipid fatty acid composition and calcium oxalate kidney stone risk factors in healthy subjects from two race groups with different risk profiles pose questions about the GLA-arachidonic acid-oxaluria metabolic pathway: pilot study

Abstract

Fatty acid (FA) composition of phospholipids in plasma and red blood cells (RBC) can influence calciuria, oxaluria and renal stone formation. In this regard, the ratio of arachidonic acid (AA) and its precursor linoleic acid (LA) appears to be important. Administration of γ-linolenic acid (GLA) has been shown to increase the concentration of dihomo-gamma linoleic acid (DGLA) relative to AA indicating that it may attenuate biosynthesis of the latter. Such effects have not been investigated in race groups having difference stone occurrence rates. Black (B) and white (W) healthy males ingested capsules containing linoleic acid (LA) and GLA, for 30 days. Plasma and RBC total phospholipid (TPL) FA profiles, serum and 24 h urine biomarkers of hypercalciuria and urinary stone risk factors were determined on days 0 and 30. Data were tested for statistical significance using GraphPadInstat version 3.02. Concentration and percentage content of DGLA in plasma TPL increased in W but not in B. Arachidonic acid (AA) did not change in either group. There was no change in calcium excretion in either group but oxalate and citrate excretion increased in W. We suggest that elongation of GLA to DGLA may occur more rapidly than desaturation of DGLA to AA in W and that depressed activity of the enzyme elongase may occur in B. Calciuric and citraturic effects may be dependent on the quantity of LA or on the mass ratio of LA/GLA in the FA supplement. Questions about the mooted DGLA-AA-oxaluria pathway arise. We speculate that there exists a potential for using GLA as a conservative treatment for hypocitraturia. The observation of different responses in B and W indicates that such differences may play a role in stone formation and prevention.

The Efficacy of Polyunsaturated Fatty Acids as Protectors against Calcium Oxalate Renal Stone Formation: A Review

“…They suggested that this inconsistency might be due to differences in their respective patient cohorts as their earlier study involved hypercalciuric patients while their subsequent study did not [5]. Interestingly, Table 1 shows that four of the other studies in which no decrease in urinary Ca occurred used healthy subjects as their test group as opposed to stone-formers [6,10,14,25] lending support to the notion that PUFA-induced reduction of Ca excretion is possibly restricted to stone-forming patients. Indeed, Buck and co-workers commented in an earlier paper that the normalizing effect of fish oil with respect to urinary calcium and oxalate levels was more pronounced in patients in whom these parameters were markedly raised [1].…”

“…Finally, Rodgers et al argued that the significantly lower occurrence of stones in South Africa's black population relative to that in the white population presented them with an ideal opportunity to test whether PUFAs might play a role in this anomaly. They examined PUFA plasma and urinary profiles in their low-and high-risk groups B and W, respectively [15,25], and reported findings that were also counterintuitive relative to the Baggio model [11]. The concentration of AA was significantly higher in the low-risk B group, and there was no difference between the groups in AA/LA ratios [15].…”

“…We note that a total of 16 studies is listed. PUFAs which were tested are EPA (2 studies) [1,5], EPA+DHA (8 studies) [1,2,[6][7][8][9]11,14], LA+GLA (5 studies) [2,10,25], and EPA+DHA+GLA+LA (one study) [2]. These have been delivered as fish oil or as isolated supplements (EPA, GLA, evening primrose oil).…”

“…Table 1 shows that urinary oxalate was measured in thirteen studies after the administration of the PUFA test substance. It decreased in four of these [1,6,7,11] but remained unchanged in eight studies [2,8,10,14,25]. (Reference 2 describes three studies; reference 10 describes 2 studies; reference 25 also describes 2 studies, but an unchanged urinary oxalate was recorded in only one of them).…”

“…One study found that it increased [25]. Of importance is that the supplement that was administered in the four studies in which urinary Ox decreased was fish oil.…”