Abnormalities in plasma composition of essential fatty acids (EFAs) may be associated with the etiology of pruritus and other skin problems in patients undergoing hemodialysis. To study whether an oral supplementation with ω–6 (n–6) EFAs would restore deranged plasma EFAs and ameliorate skin symptoms, 9 and 7 dialysis patients were randomly assigned to receive either γ-linolenic acid (GLA)-rich evening primrose oil (EPO) or linoleic acid (LA) (2 g/day each) for 6 weeks. Plasma concentrations of EFA were analyzed by gas chromatography and uremic skin symptoms were assessed for dryness, pruritus and erythema by questionnaire and visual inspection in a double-blind manner. The patients given EPO exhibited a significant (p < 0.05) increase in plasma dihomo-γ-linolenic acid (a precursor of anti-inflammatory prostaglandin E1) with no concomitant change in plasma arachidonic acid (a precursor of pro-inflammatory prostaglandin E2 and leukotriene B4). In contrast, those given LA exhibited a significant (p < 0.05) increase in LA but not in any other n–6 EFAs, whereas they exhibited a significant (p < 0.05) decrease in plasma docosahexaenoic acid. The patients given EPO showed a significant (p < 0.05) improvement in the skin scores for the three different uremic skin symptoms over the baseline values and a trend toward a greater improvement (0.05 < p < 0.1) in pruritus scores than those given LA. Results indicate that GLA-rich EPO would be a more favorable supplemental source than LA in terms of shifting eicosanoid metabolism toward a less inflammation status through modifying plasma concentrations of their precursor n–6 EFAs. Further studies are required to confirm the efficacy and safety of EPO therapy for the treatment of uremic pruritus.

Keywords:
Essential fatty acids, Evening primrose oil, γ-Linolenic acid, Linoleic acid, Hemodialysis, Uremic skin symptoms, Randomized double-blind trial
1.
Rosen T: Uremic pruritus: A review. Cutis 1979;23:790–792.
2.
Bencini PL, Montagnino G, Citterio A, Graziani G, Crosti C, Ponticelli C: Cutaneous abnormalities in uremic patients. Nephron 1985;40:316–320.
3.
Ponticelli C, Bencini PL: Uremic pruritus: A review. Nephron 1992;60:1–5.
4.
Nielsen T, Andersen KE, Kristiansen J: Pruritus and xerosis in patients with chronic renal failure. Dan Med Bull 1980;27:269–271.
5.
Hampers CL, Katz AI, Wilson RE, Merrill JP: Disappearance of ‘uremic’ itching after subtotal parathyroidectomy. N Engl J Med 1968;279:695–697.
6.
Matsumoto M, Ichikawa K, Horie A: Pruritus and mast cell proliferation of the skin in end-stage renal failure. Clin Nephrol 1985;23:285–288.
7.
Francos GC, Kauh YC, Gittlen SD, Shulman ES, Besarab A, Goyal S, Burke JF Jr: Elevated plasma histamine in chronic uremia. Int J Dermatol 1991;30:884–889.
8.
Hartop PJ, Prottey C: Changes in trans-epidermal water loss and the composition of epidermal lecithin after applications of pure fatty acid triglycerides to the skin of essential fatty acid deficient rats. Br J Dermatol 1976;95:255–264.
9.
Wene JD, Connor WE, den Besten L: Development of essential fatty acid deficiency in healthy men fed fat-free diets intravenously and orally. J Clin Invest 1975;56:127–134.
10.
Ahmad S, Dasgupta A, Kenny M: Fatty acid abnormalities in hemodialysis patients: Effects of L-carnitine administration. Kidney Int 1989;36(suppl 27):243–246.
11.
Dasgupta A, Kenny MA, Ahmad S: Abnormal fatty acid profiles in chronic hemodialysis patients: Possible deficiency of essential fatty acids. Clin Physiol Biochem 1990;8:238–243.
12.
Bowser PA, White RJ: Isolation, barrier properties and lipid analysis of the stratum compactum, a discrete layer of the stratum corneum. Br J Dermatol 1985;112:1–14.
13.
Lovell CR, Burton PA, Duncan EH, Burton JL: Prostaglandins and pruritus. Br J Dermatol 1976;94:273–275.
14.
Fantone JC, Kunkel SL, Zurier RB: Effects of prostaglandins on in vivo immune and inflammatory reactions; in Goodwin JS (ed): Prostaglandins and Immunity. Boston, Nijhoff, 1985, pp 123–146.
15.
Miller CC, Ziboh VA, Jones AD: Guinea pig epidermis synthesis 15-hydroxy-8,11,13-eicosatrienoic acid (15-OH 20:3n-6) from dihomo-gamma-linolenic acid: A potent lipoxygenase inhibitor derived from dietary primrose oil. J Invest Dermatol 1987;88:507.
16.
Brenner RR: Nutritional and hormonal factors influencing desaturation of essential fatty acids. Prog Lipid Res 1982;20:41–48.
17.
Daugirdas JT, Depner TA: A nomogram approach to hemodialysis urea modeling. Am J Kidney Dis 1994;23:33–40.
18.
Lowrier EG, Lazarus JM, Hampers CL, Merrill JP: Some statistical methods for use in assessing the adequacy of hemodialysis. Kidney Int 1975;2(suppl):231–242.
19.
Shalin-Karrila M, Mattila L, Jansen CT, Uotila P: Evening primrose oil in the treatment of atopic eczema: Effect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins. Br J Dermatol 1987;117:11–19.
20.
Manku MS, Morse-Fisher N, Horrobin DF: Changes in human plasma essential fatty acid levels at a result of administration of linoleic acid and gamma-linolenic acid. Eur J Clin Nutr 1988;42:55–60.
21.
Lasserre M, Mendy F, Spielman D: Effects of different dietary intakes of essential fatty acids on 20:3n-6 and 20:4n-6 serum levels of human adults. Lipids 1985;20:227–233.
22.
Manku MS, Horrobin DF, Morse N, Wright S, Burton JL: Reduced levels of prostaglandin precursors in the blood of atopic patients: Defective delta-6-desaturase function as a biochemical basis for atopy. Prostaglandins Leukot Med 1982;9:1–13.
23.
Horrobin DF, Manku MS: Clinical biochemistry of essential fatty acids; in Horrobin DF (ed): Omega-6-Essential Fatty Acids: Pathophysiology and Roles in Clinical Medicine. New York, Liss, 1990, pp 21–54.
24.
Burr ML, Gilbert JF, Holliday RM, Elwood PC, Fehily AM, Rogers S, Sweetnam PM, Deadman NM: Effects of changes of fat, fish, and fiber intakes on death and myocardial reinfarction: Diet and reinfarction trial (DART). Lancet 1989;ii:757–761.
25.
Rostand SG, Gretes JC, Kirk KA, Rutsky EA, Andreoli TE: Ischemic heart disease in patients with uremia undergoing maintenance hemodialysis. Kidney Int 1979;16:600–611.
26.
Peck LW, Monsen ER, Ahmad S: Effect of three sources of long-chain fatty acids on the plasma fatty acid profile, plasma prostaglandin E2 concentrations, and pruritus symptoms in hemodialysis patients. Am J Clin Nutr 1996;64:210–214.
27.
Wright S: Essential fatty acids and the skin. Br J Dermatol 1991;125:503–515.
28.
Bamford JTM, Reiner RW, Gibson CM: Atopic eczema unresponsive to evening primrose oil. J Am Acad Dermatol 1985;13:959–963.
29.
Callegari P, Zurier RB: Botanical lipids: Potential role in modulation of immunologic responses and inflammatory reactions. Rheum Dis Clin North Am 1991;17:415–425.
30.
Pullman-Mooar S, Laposata M, Lem D, Holman RT, Levental IJ, DeMarco D, Zurier RB: Alteration of the cellular fatty acid profile and the production of eicosanoids in human monocytes by gamma-linolenic acid. Arthritis Rheum 1990;33:1526–1533.
31.
Tate G, Mandell BF, Laposata M, Ohliger D, Baker DG, Schumacher HR et al: Suppression of acute and chronic inflammation by dietary gamma-linoenic acid. J Rheumatol 1989;16:729–734.
32.
Leventhal LJ, Boyce EG, Zurier RB: Treatment of rheumatoid arthritis with gamma-linolenic acid. Ann Intern Med 1993;119:867–873.
1999
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