Arachidonic acid concentrations in patients with Crohn disease.

We read with interest the work by Jeppesen et al (1) examining the fatty acid content of plasma phospholipids in patients with malabsorption and patients receiving home parenteral nutrition (HPN). In that article, patients with fat malabsorption were subgrouped according to the severity of malabsorption (fat malabsorption ≤50% and fat malabsorption >50%), whereas patients receiving HPN were grouped according to whether they received parenteral lipid. The control subjects were healthy volunteers. Most of the patients in the non-HPN groups (17 of 20) had Crohn disease and 11 of 20 patients in the HPN groups had Crohn disease. We would like to draw attention to the significant differences, not discussed in the text, in percentage plasma phospholipid arachidonic acid (AA; 20:4n26) among the groups. AA, along with eicosopentaenoic acid (20:5n23), serves as an eicosanoid precursor; its deficiency is responsible for many of the clinical consequences of essential fatty acid deficiency. Non-HPN patients without major fat malabsorption and HPN patients receiving lipid had strikingly higher AA concentrations than did control subjects (7.8%, 10.4%, and 11.7%, respectively; both P < 0.05). Patients with short-gut syndrome and severe malabsorption and HPN patients not receiving lipid had values similar to those of control subjects (8.1% and 8.3%, respectively), presumably reflecting relative dietary deficiency of the essential fatty acid precursor, linoleic acid. Generally, AA concentrations are tightly controlled and stable across a wide range of linoleic acid intakes above a maintenance intake. AA concentrations are reduced only in a limited number of conditions, including classic essential fatty acid deficiency, prematurity or end-stage liver disease (in which hepatic enzyme immaturity or pathologic damage, respectively, prevents elongation and desaturation to AA), and increased dietary intake of eicosopentaenoic acid, which inhibits formation of AA from precursors and competes with AA for tissue incorporation (2). Elevated AA relative to linoleic acid is rarely found to be related to diet because AA, which can enter phospholipids directly (3), is usually such a small dietary component. We wonder whether this elevation in AA might represent a proinflammatory state and question whether provision of lipid to HPN patients as a means of normalizing linoleic acid concentrations might exacerbate the inflammation underlying Crohn disease. It would be interesting to consider patients with Crohn disease stratified for extent of malabsorption separately from other patients with fat malabsorption; such stratification has never been performed stringently. The presence of a relative increase in the ratio of AA to linoleic acid in the intestinal mucosa of patients with Crohn disease has been documented and the etiologic importance of this finding in the development of local inflammation considered (4). Thus, this parallel finding of Jeppesen et al is a potentially important observation. If it can be confirmed that patients with Crohn disease who are not deficient in essential fatty acids (either because of only mild-to-moderate malabsorption or because of parenteral fat therapy) have an overabundance of plasma phospholipid AA, we must consider the possibility that abnormal fatty acid regulation might play an important role in the pathology of Crohn disease. This hypothesis is strengthened by the finding that fish oil, possibly by inhibiting AA formation and altering eicosanoid production, can maintain clinical remission in patients with Crohn disease (5).