Omega-3 Studien: Hautkrankheiten, Neurodermitis, Psoriasis

Omega-3: Fakten - Therapie und Dosierung

Hautkrankheiten: 1,88g oder 6,0g/Tag EPA & DHA
In Fachzeitschriften wurden folgende Artikel über Omega-3 publiziert. Die Liste dieser Publikationen wurde im April 2003 kompiliert und erhebt keinen Anspruch auf Vollständigkeit. Quelle: MEDLINE.
Die Daten dienen als Referenz für Ärzte und Therapeuten, damit eine therapeutische Dosis für Hautkrankheiten; Psoriasis und Neurodermitis festgelegt werden kann.

Human milk polyunsaturated long-chain fatty acids and secretory immunoglobulin A antibodies and early childhood allergy.
Duchén K: Department of Health and Environment, Linköping University Hospital, Sweden; Casas R, Fagerås-Böttcher M, Yu G, Björkstén B
Pediatr Allergy Immunol 2000 Feb 11:29-39
The possible protective effect of breast milk against atopic manifestations in infancy, i.e. atopic eczema and food allergy, has been controversial for the last decades. Besides the methodological problems, differences in the composition of human milk could explain these controversies. The aim of this study was to investigate the composition of polyunsaturated fatty acids (PUFA) and secretory immunoglobulin A (S-IgA) levels to food proteins (ovalbumin and beta-lactoglobulin) and an inhalant allergen (cat) in milk from mothers of allergic and non-allergic children. Blood samples were obtained at birth and at 3 months from 120 children. Skin prick tests were performed at 6, 12 and 18 months, and the development of atopic diseases was assessed in the children. Breast milk samples were collected from their mothers at birth and monthly during the lactation period. Milk PUFA composition was measured by gas chromatography, and enzyme-linked immunosorbent assay (ELISA) was used to measure total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-beta-lactoglobulin S-IgA. Allergic disease developed in 44/120 children (22/63 children of allergic mothers and 22/57 children of non-allergic mothers). Lower levels of eicosapentaenoic acid, C20:5 n-3 (EPA), docosapentaenoic acid C22:5 n-3 (DPA), and docosatetraenoic acid C22:4 n-6 (DHA) (p < 0.05 for all) were found in mature milk from mothers of allergic as compared to milk from mothers of non-allergic children. The total n-6:total n-3 and the arachidonic acid, C20:4 n-6 (AA):EPA ratios were significantly lower in transitional and mature milk from mothers of allergic children, as compared to milk from mothers of non-allergic children. The PUFA levels in serum of allergic and non-allergic children were largely similar, except for higher levels of C22:4 n-6 and C22:5 n-6 (p < 0.05 for both) and a higher AA:EPA ratio in serum phospholipids in the former group (p < 0.05). Changes in the levels of milk PUFA were reflected in changes in PUFA serum phospholipids, particularly for the n-6 PUFA. The AA: EPA ratio in maternal milk was related, however, to the AA:EPA only in serum from non-allergic children, while this was not the case in allergic children. The levels of total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-beta-lactoglobulin S-IgA in milk from mothers of allergic, as compared to non-allergic, children were similar through the first 3 months of lactation. Low levels of n-3 PUFA in human milk, and particularly a high AA:EPA ratio in maternal milk and serum phospholipids in the infants, were related to the development of symptoms of allergic disease at 18 months of age. The milk PUFA composition influenced the composition of PUFA in serum phospholipids of the children. We also showed that the lower levels of colostral anti-ovalbumin S-IgA and lower total S-IgA in mature milk from atopic mothers did not influence the development of allergic disease in the children up to 18 months of age. The findings indicate that low alpha-linolenic acid, C18:3 n-3 (LNA) and n-3 long-chain polyunsaturated fatty acids (LCP) 20-22 carbon chains, but not the levels of S-IgA antibodies to allergens, are related to the development of atopy in children.

Atopic sensitization during the first year of life in relation to long chain polyunsaturated fatty acid levels in human milk.
Duchén K: Department of Paediatrics, Linköping University, Sweden; Yu G, Björkstén B
Pediatr Res 1998 Oct 44:478-84
The levels of the long chain polyunsaturated n-6 and n-3 fatty acids (PUFA) were studied in colostrum and mature milk of 29 atopic and 29 nonatopic mothers and related to sensitization in their babies during the first 12 mo of life. The levels of alpha-linolenic acid (LNA) were lower (0.96 versus 1.23 weight percentage, p < 0.01) and the levels of dihomo-gamma-linoleic acid were higher (0.36 versus 0.31 weight percentage, p < 0.05) in mature milk from mothers of atopic babies (n = 24) compared with mothers of nonatopic babies (n = 34). The total n-3 levels and the ratio of n-6 PUFA/n-3 PUFA were similar in colostrum of all mothers and then decreased significantly in mature milk (p < 0.001), particularly in milk given to atopic babies. The levels of the n-6 fatty acids arachidonic acid, C22:4, and C22:5 n-6 correlated in milk samples from nonatopic mothers (r = 0.61-0.97, p < 0.05 to p < 0.001) but were largely absent in colostrum and mature milk from atopic mothers. In contrast, LNA and eicosapentaenoic levels correlated in colostrum from the atopic mothers (r = 0.61-0.88) regardless of atopic sensitization in the infants, whereas LNA correlated to C20:4 n-3 in colostrum from nonatopic mothers of nonatopic infants. Furthermore, the levels of the n-3 fatty acid C20:4 n-3 correlated significantly to all n-6 fatty acids, except linoleic acid (r = 0.64-0.79, all p < 0.01) in mature milk from nonatopic mothers of nonsensitized children. Low levels of LNA and total n-3 long chain polyunsaturated fatty acids, in mature milk from the mothers, appear to be associated with atopic sensitization early in life, as well as disturbed relationships between the n-3 fatty acid 20:4 and the n-6 fatty acids particularly in mature milk. On the other hand, disturbed relationships within the individual fatty acids in the n-6 series in human milk reflected the atopic status in the mothers. The variations in the lipid composition of human milk could in part explain some of the controversies regarding the protective effects of breast-feeding against allergy.

Identification of a fatty acid delta6-desaturase deficiency in human skin fibroblasts.
Williard DE: Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA; Nwankwo JO, Kaduce TL, Harmon SD, Irons M, Moser HW, Raymond GV, Spector AA
J Lipid Res 2001 Apr 42:501-8
Polyunsaturated fatty acid (PUFA) utilization was investigated in skin fibroblasts cultured from a female patient with an inherited abnormality in lipid metabolism. These deficient human skin fibroblasts (DF) converted 85;-95% less [1-14C]linoleic acid (18:2n-6) to arachidonic acid (20:4n-6), 95% less [3-14C]tetracosatetraenoic acid (24:4n-6) to docosapentaenoic acid (22:5n-6), and 95% less [1-14C]-linolenic acid (18:3n-3) and [3-14C]tetracosapentaenoic acid (24:5n-3) to docosahexaenoic acid (22:6n-3) than did normal human skin fibroblasts (NF). The only product formed by the DF cultures from [1-14C]tetradecadienoic acid (14:2n-6) was 18:2n-6. However, they produced 50;-90% as much 20:4n-6 as the NF cultures from [1-14C]hexadecatrienoic acid (16:3n-6), [1-14C]gamma-linolenic acid (18:3n-6), and [1-14C]dihomo-gamma-linolenic acid (20:3n-6), PUFA substrates that contain Delta6 double bonds. DF also contained 80% more 18:2n-6 and 25% less 20:4n-6. These results suggested that DF are deficient in Delta6 desaturation. This was confirmed by Northern blots demonstrating an 81;-94% decrease in Delta6-desaturase mRNA content in the DF cultures, whereas the Delta5-desaturase mRNA content was reduced by only 14%. This is the first inherited abnormality in human PUFA metabolism shown to be associated with a Delta6-desaturase deficiency. Furthermore, the finding that the 18- and 24-carbon substrates are equally affected suggests that a single enzyme carries out both Delta6 desaturation reactions in human PUFA metabolism.

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Polyunsaturated fatty acids in school children in relation to allergy and serum IgE levels.
Yu G: Department of Health and Environment, Linköping University, Sweden; Björkstén B
Pediatr Allergy Immunol 1998 Aug 9:133-8
Altered composition of polyunsaturated fatty acids (PUFA) has been observed in allergic individuals and it has been proposed that this is due to an impairment of delta-6-desaturase activity. We have studied the composition of PUFA in serum phospholipids in twenty-two 12-15 year old children with asthma and/or allergic dermatitis and 23 non-atopic controls of similar age. The relative levels of docosahexaenoic acid (DHA, C22:6n-3) and total n-3 long-chain polyunsaturated fatty acids (LCP) were lower (1.46% +/- 0.54 vs. 1.90% +/- 0.58, P = 0.01 for DHA and 2.34% +/- 0.67 vs. 2.80% +/- 0.77, P < 0.05 for total n-3 LCP) and the ratio of total n-6 to n-3 LCP was higher (P < 0.01) in the allergic children than in the controls. In addition to these differences, the relative levels of docosapentaenoic acid (DPA, C22:5n-3) and the ratio of arachidonic acid (AA, C20:4n-6) to dihomo-gamma-linolenic acid (DHGLA, C20:3n-6) were also lower in the 12 allergic children with positive skin prick test, as compared with the SPT negative children (both P < 0.05). In non-allergic children, the levels of total n-3 correlated with n-6 LCP (r = 0.76, p < 0.001). Furthermore, the n-3 LCP, i.e. EPA, DPA and DHA, correlated significantly with each other (r = 0.52-0.78, all p < 0.01) and correlated with n-6 LCP, i.e. C20:2, DHGLA and AA respectively (r = 0.56-0.83, all P < 0.01). Most of these correlations were absent in allergic children. Higher levels of C20:2n-6 and lower levels of eicosapentaenoic acid (EPA, C20:5n-3) were recorded in 11 allergic children with serum IgE above the median level (56 kU/l), as compared to 11 with lower IgE levels (both P < 0.05). Furthermore, the levels of C20:2n-6 correlated with the IgE levels in the children (r = 0.65, P = 0.001). The findings could not confirm an impaired delta-6-desaturase activity in allergic school children and suggest that a disturbance of LCP metabolism is associated with allergic diseases.

The changes of lymphocyte membrane receptors in bronchial asthma and atopic dermatitis in pediatric patients receiving treatment with polyenic fatty acids.
Gorelova JYu: Institute of Nutrition, Moscow, Russia; Semikina EM
Z Ernahrungswiss 1998 37 Suppl 1:142-3
The influence of a diet supplemented with n-3 PUFA on the immune status of children with atopic dermatitis and asthma was investigated. The results of the investigation have shown the improvement of cell immunity along with a decrease in the clinical manifestation of the disease. n-3 PUFA could be used as immunocorrectors in combination with pathogenic treatment of children with allergic diseases.

A double-blind, randomized, placebo-controlled trial of n-3 versus n-6 fatty acid-based lipid infusion in atopic dermatitis.
Mayser P: Department of Dermatology, Center for Dermatology and Andrology, Justus-Liebig-University, Giessen, Germany; Mayer K, Mahloudjian M, Benzing S, Krämer HJ, Schill WB, Seeger W, Grimminger F
JPEN J Parenter Enteral Nutr 2002 May-Jun 26:151-8
BACKGROUND: In the involved epidermis of patients with atopic dermatitis, changes in the metabolism of eicosanoids with increased quantities of the arachidonic acid (AA)-derived lipoxygenase products have been observed. Free eicosapentaenoic acid (EPA), a fish oil-derived alternative (n-3) fatty acid, may compete with AA, resulting in an anti-inflammatory effect. METHODS: In a 10-day double-blind, randomized, placebo-controlled trial, 22 patients hospitalized for moderate-to-severe atopic dermatitis were randomly assigned to receive daily infusions of either a n-3 fatty acid-based lipid emulsion (fish oil, 10%; 200 mL/d) or a conventional n-6-lipid emulsion (soybean oil, 10%; 200 mL/d). Topical treatment was restricted to emollients. The severity of disease was evaluated daily with scoring of erythema, infiltration, and desquamation and by subjective patient scoring of clinical manifestations. In addition, plasma-free and total-bound fatty acids and the composition of membrane fatty acids in blood cells (thrombocytes, granulocytes, and erythrocytes), lipid mediators from isolated neutrophils and platelets, and lymphocyte-activation parameters were determined. RESULTS: Twenty patients completed the trial. Marked improvement from baseline was seen in both groups. On days 6, 7, 8, and 10, disease severity score-defined as the sum of all scores-was more pronounced (p < .05) in the n-3 group compared with the n-6 group. Free arachidonic acid in plasma did not change substantially in both groups, whereas plasma-free EPA, total-bound EPA, and the membrane EPA/AA ratio markedly increased in response to n-3-lipid infusion. In parallel, EPA-derived lipid mediators appeared, whereas lymphocyte functions were unaffected. In the post-treatment period (2/4 weeks), relapse was observed in some patients after n-3 psoralene-ultraviolet A (PUVA) infusion, whereas there was a marked long-term improvement in the n-6 group. CONCLUSIONS: IV n-3-fatty acid administration is effective in acutely improving the severity of atopic dermatitis, paralleled by changes in plasma and membrane fatty acid composition and lipid mediator synthesis. The long-term beneficial effects of IV n-6 fatty acids should be evaluated further.

Dietary supplementation with very long-chain n-3 fatty acids in man decreases expression of the interleukin-2 receptor (CD25) on mitogen-stimulated lymphocytes from patients with inflammatory skin diseases.
Søyland E: Section for Dietary Reasearch, University of Oslo, Norway; Lea T, Sandstad B, Drevon A
Eur J Clin Invest 1994 Apr 24:236-42
T-cell activation and cytokine production play an important role in several chronic inflammatory diseases. Because n-3 fatty acids exert beneficial effects on the clinical state of some of these diseases, we examined the effect of dietary supplementation of n-3 fatty acids on T-cell proliferation, expression of CD25 (interleukin-2 receptor alpha-chain), secretion of interleukin-2, interleukin-6 and tumour necrosis factor from T-cells from patients with psoriasis and atopic dermatitis. During 4 months, 21 patients supplied 6 g of highly concentrated ethyl esters of EPA and DHA in gelatin capsules daily to their diet. In the control group 20 patients supplied 6 g per day of corn oil in gelatin capsules to their diet. Eicosapentaenoic acid (20:5, n-3) of serum phospholipids increased from 14 (min 4-max 42) to 81 (min 59-max 144) mg l-1 (P < 0.01) in patients with atopic dermatitis receiving n-3 fatty acids, and from 25 (min 7-max 66) to 74 (min 46-max 142) mg l-1 (P < 0.01) in patients with psoriasis, whereas docosahexaenoic acid (22:6, n-3) increased from 65 (min 46-max 120) to 92 (min 54-max 121) mg l-1 (P < 0.05) and from 81 (min 38-max 122) to 92 (min 63-max 169) mg l-1 (NS) in atopic and psoriatic patients, respectively. The changes in the serum phospholipid fatty acid profile in the groups receiving n-3 fatty acids, correlate to the dietary intake of corresponding fatty acids.

Effects of dietary supplementation of fish oil on neutrophil and epidermal fatty acids. Modulation of clinical course of psoriatic subjects.
Ziboh VA, Cohen KA, Ellis CN, Miller C, Hamilton TA, Kragballe K, Hydrick CR, Voorhees JJ
Arch Dermatol 1986 Nov 122:1277-82
Findings from an eight-week fish oil-supplemented diet given to 13 psoriatic patients demonstrated that eicosapentaenoic acid (20:5,n3 [EPA]) and docosahexaenoic acid (22:6,n3 [DCHA]) are rapidly incorporated into the sera, neutrophils, and epidermis of participating patients, and that the incorporation of EPA and DCHA into epidermal lipids increased with weeks of supplementation with minimal alteration of arachidonic acid (AA) in the epidermal lipids. Global clinical evaluation showed that eight patients demonstrated mild to moderate improvement in their psoriatic lesions. Improved clinical response correlated with high EPA/DCHA ratios attained in epidermal tissue specimens. These findings underscore the need for further investigations into the role of dietary n3 fatty acids, particularly the possibility of pentaenoic acid as a potential protective agent and/or therapeutic adjunct for the clinical management of psoriasis.

n-3 fatty acids in psoriasis.
Mayser P: Department of Dermatology and Andrology, Justus Liebig University, Giessen, Germany; Grimm H, Grimminger F
Br J Nutr 2002 Jan 87 Suppl 1:S77-82

Increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. Replacement of arachidonic acid by alternative precursor polyunsaturated fatty acids (PUFA), especially eicosapentaenoic acid (EPA), which can be metabolized via the same enzymatic pathways as AA, might be a therapeutic option in psoriasis. However the results of studies evaluating the therapeutic benefit of dietary fish oil have been conflicting and not clearly dose-dependent. To overcome the slow kinetics and limited availability of oral supplementation, we have performed three studies to assess the efficacy and safety of an intravenously administered fish oil derived lipid emulsion on different forms of psoriasis. Patients received daily infusions of either an n-3 fatty acid-based lipid emulsion (Omegaven) or a conventional n-6 lipid emulsion (Lipoven) in different time and dose regimens. In addition to an overall assessment of the clinical course of psoriasis, EPA- and AA-derived neutrophil 5-lipoxygenase (LO)--products, thromboxane (TX) B2/B3, PAF and plasma free fatty acids were investigated. Treatment with n-3 fatty acids resulted in a considerably higher response rate than infusion of n-6 lipids. A more than 10-fold increase in neutrophil EPA-derived 5-LO product formation was noted in the n-3 group, accompanied by a rapid increase in plasma-free EPA within the first days. In conclusion, intravenous n-3-fatty acid administration causes reduction of psoriasis, which may be related to changes in inflammatory eicosanoid generation. The rapidity of the response to intravenous n-3 lipids exceeds by orders of magnitude the hitherto reported kinetics of improvement of psoriatic lesions upon use of oral supplementation.

Effects of dietary supplementation with polyunsaturated ethyl ester lipids (Angiosan) in patients with psoriasis and psoriatic arthritis.
Lassus A: Department of Dermatology, University Central Hospital, Helsinki, Finland; Dahlgren AL, Halpern MJ, Santalahti J, Happonen HP
J Int Med Res 1990 Jan-Feb 18:68-73
A total of 80 patients with chronic, stable psoriasis, 34 of whom also had psoriatic arthritis, were treated with 1122 mg/day eicosapentaenoic acid ethyl ester and 756 mg/day docosahexaenoic acid ethyl ester. Before the study and after 4 and 8 weeks of treatment a Psoriatic Association scoring index (PASI) score was assessed. Before treatment the mean PASI score was 3.56, after 4 weeks 1.98 and after 8 weeks 1.24; the decrease in the score was highly significant (P less than 0.001). The degree of pruritis decreased most rapidly, followed by scaling and induration of the plaques, and erythema was most persistent. At the end of the trial, seven patients were completely healed and in 13 other patients more than 75% healing was observed but in 14 patients the result was poor. The majority of patients with psoriatic arthritis reported a subjective improvement in joint pain during the study. It is concluded that polyunsaturated ethyl ester lipids may be useful for the treatment of psoriasis and psoriatic arthritis and may provide an important adjuvant to standard therapy of both conditions.

Effect of regular consumption of oily fish compared with white fish on chronic plaque psoriasis.
Collier PM: Department of Dermatology, Westminster Hospital, London, UK; Ursell A, Zaremba K, Payne CM, Staughton RC, Sanders T
Eur J Clin Nutr 1993 Apr 47:251-4
The influence of dietary advice on the severity of chronic plaque psoriasis was studied in 18 patients. Medication was standardized in all patients who were advised to eat 170 g white fish daily for a 4 week run-in period. Then the patients were randomized either to continue with the white fish diet or to substitute 170 g oily fish daily for 6 weeks. At the end of this second period the diets were reversed for a further 6 weeks. The oily fish but not the white fish diet led to a modest clinical improvement (11% and 15%, P < 0.01) which was accompanied by a rise in plasma eicosapentaenoic acid (20:5n-3) concentrations. It is concluded that dietary advice to increase the daily intake of oily fish is a useful adjunct in the treatment of psoriasis. The fish that should be recommended include mackerel, sardine, salmon, pilchard, kipper and herring.