Functional textiles for atopic dermatitis: a systematic review and meta-analysis.

Atopic dermatitis (AD) is a relapsing inflammatory skin disease with a considerable social and economic burden. Functional textiles may have antimicrobial and antipruritic properties and have been used as complementary treatment in AD. We aimed to assess their effectiveness and safety in this setting. We carried out a systematic review of three large biomedical databases. GRADE approach was used to rate the levels of evidence and grade of recommendation. Meta-analyses of comparable studies were carried out. Thirteen studies (eight randomized controlled trials and five observational studies) met the eligibility criteria. Interventions were limited to silk (six studies), silver-coated cotton (five studies), borage oil, and ethylene vinyl alcohol (EVOH) fiber (one study each). Silver textiles were associated with improvement in SCORAD (2 of 4), fewer symptoms, a lower need for rescue medication (1 of 2), no difference in quality of life, decreased Staphyloccosus aureus colonization (2 of 3), and improvement of trans-epidermal water loss (1 of 2), with no safety concerns. Silk textile use was associated with improvement in SCORAD and symptoms (2 of 4), with no differences in quality of life or need for rescue medication. With borage oil use only skin erythema showed improvement, and with EVOH fiber, an improvement in eczema severity was reported. Recommendation for the use of functional textiles in AD treatment is weak, supported by low quality of evidence regarding effectiveness in AD symptoms and severity, with no evidence of hazardous consequences with their use. More studies with better methodology and longer follow-up are needed.

Nutritional immunomodulation in critically ill children with acute lung injury: feasibility and impact on circulating biomarkers.

OBJECTIVE: Respiratory failure caused by acute lung injury or acute respiratory distress syndrome is associated with significant morbidity in children. Enteral nutrition enriched with eicosapentaenoic acid, γ-linolenic acid and antioxidants (eicosapentaenoic acid + γ-linolenic acid) can safely modulate plasma phospholipid fatty acid profiles, reduce inflammation, and improve clinical outcomes in adults. There is little information regarding the use of enteral eicosapentaenoic acid + γ-linolenic acid to modulate plasma phospholipid fatty acid profiles in children. We sought to determine if continuous feeding of enteral nutrition containing eicosapentaenoic acid, γ-linolenic acid, and antioxidants was feasible in critically ill children with acute lung injury or acute respiratory distress syndrome. We further evaluated the impact of such an approach on the alteration of plasma phospholipid fatty acid concentrations. DESIGN: Prospective, blinded, randomized, controlled, multicenter trial. SETTING: PICU. PATIENTS: Twenty-six critically ill children (age 6.2 ± 0.9 yr, PaO2/FIO2 185 ± 15) with the diagnosis of acute lung injury or acute respiratory distress syndrome. INTERVENTIONS: Mechanically ventilated children received either eicosapentaenoic acid + γ-linolenic acid or a standard pediatric enteral formula. Clinical, biochemical, plasma fatty acid, and safety data were assessed at baseline, study days 4 and 7. MEASUREMENTS AND MAIN RESULTS: At baseline, there were no significant differences in the two study groups. Both groups met enteral feeding goals within 30 hrs and had similar caloric delivery. There were no differences in formula tolerance as measured by serum chemistries, liver and renal function, and hematology studies after 7 days of feeding either eicosapentaenoic acid + γ-linolenic acid or pediatric enteral formula. On study day 4 and 7, plasma phospholipid fatty acid profiles in the eicosapentaenoic acid + γ-linolenic acid group showed a significant increase in anti-inflammatory circulating markers. CONCLUSIONS: Providing enteral nutrition with eicosapentaenoic acid + γ-linolenic acid to critically ill children with lung injury was feasible and caloric goals were met within 30 hrs. This feeding protocol effectively modulated plasma phospholipid fatty acid concentrations to reflect an anti-inflammatory profile. This study provides data to inform future outcome studies using enteral eicosapentaenoic acid + γ-linolenic acid in children with lung injury.

Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury.

CONTEXT: The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with γ-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury. OBJECTIVE: To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28. DESIGN, SETTING, AND PARTICIPANTS: The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. All participants had complete follow-up. INTERVENTIONS: Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement. MAIN OUTCOME MEASURE: Ventilator-free days to study day 28. RESULTS: The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P = .02) (difference, -3.2 [95% CI, -5.8 to -0.7]) and intensive care unit-free days (14.0 vs 16.7; P = .04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P = .02). Sixty-day hospital mortality was 26.6% in the n-3 group vs 16.3% in the control group (P = .054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P = .11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P = .001). CONCLUSIONS: Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00609180.

The safety of evening primrose oil in epilepsy.

The concern that evening primrose oil might cause epilepsy or seizures, or reduce the threshold for seizures, originated from two papers published in the early 1980s. These original reports are re-examined, and the association of evening primrose oil with seizures is shown to be spurious. Not only are linoleic acid and gamma-linolenic acid safe in epilepsy, with prolonged oral administration of linoleic acid and alpha-linolenic acid (in a 4:1 mixture) protecting rats from having seizures in four different epilepsy models, but the evening primrose oil-derived omega-6 fatty acid arachidonic acid inhibits sodium ion currents and synaptic transmission, while the evening primrose oil-derived eicosanoid prostaglandin E(1) appears to have anticonvulsant activity. In light of these findings, it is suggested that formularies should now remove seizures or epilepsy as a side-effect of evening primrose oil, and should remove a history of seizures or epilepsy as a contraindication to taking evening primrose oil.

Comparative efficacy of alpha-linolenic acid and gamma-linolenic acid to attenuate valproic acid-induced autism-like features.

The present study was undertaken to elucidate the effect of alpha-linolenic acid (ALA, 18:3, ω-3) and gamma-linolenic acid (GLA, 18:3, ω-6) on experimental autism features induced by early prenatal exposure to valproic acid (VPA) in albino wistar pups. The pups were scrutinized on the accounts of behavioral, biochemical, and inflammatory markers, and the results suggested that the GLA can impart significant protection in comparison to ALA against VPA-induced autism features. When scrutinized histopathologically, the cerebellum of the GLA-treated animals was evident for more marked protection toward neuronal degeneration and neuronal loss in comparison to ALA. Concomitant administration of ALA and GLA with VPA demonstrated a marked cutdown in the Pgp 9.5 expression with GLA having more pronounced effect. Henceforth, it can be concluded that ALA and GLA can impart favorable protection against the VPA-induced autism-like features with GLA having pronounced effect.

Trophic effects of essential fatty acids on pig skin.

The daily oral administration of 3 ml of two oils (So-5407 and So-1129) containing essential fatty acids (EFAs) for 16 weeks resulted in a transient increase in cell proliferative activity in the skin of female Large White pigs. The So-5407 oil contained 7% gamma-linolenic acid (GLA) whereas So-1129 was an oil of similar composition, but with no GLA. Hyperplasia of the epidermis was observed after the administration of both oils, and this was characterized by an increase in the size of the rete pegs. The maximum effect occurred at 4 weeks after the start of oil administration, at which time the number of viable cell layers had increased by a factor of approximately 1.5, and mean epidermal thickness (excluding the stratum corneum) was approximately 40% greater than that of the epidermis prior to oil administration. There was a marked increase in the labelling index (LI) of the basal cell layer of the epidermis in pigs receiving So-5407. Maximum LIs were quantified at 4 weeks after the start of administration and were 18.8 +/- 1.3% and 13.1 +/- 1.7% for pigs receiving So-5407 and So-1129, respectively. After this time the LI declined progressively and had returned to values within normal limits (P > 0.1) by 8 weeks after the start of administration of both oils. A similar pattern of change in the LI was seen in the follicular epithelium, although the peak values at 4 weeks after the start of oil administration of 12.2 +/- 1.8% and 10.8 +/- 0.9 for the groups receiving So-5407 and So-1129, respectively, were lower than in the epidermis. Labelled cells were also counted in the papillary dermis and maximum values were again seen at 4 weeks after the start of oil administration. Of the two oils, So-1129 had the greatest effect, with the number of labelled cells in the papillary dermis being a factor of three to four-fold higher than in skin prior to oil administration, between 2 and 12 weeks after the start of administration.

An open-label phase I/II dose escalation study of the treatment of pancreatic cancer using lithium gammalinolenate.

There are currently no satisfactory treatments for inoperable pancreatic cancer. Median survivals for untreated patients are of the order of 100 days and, with one exception, no chemotherapy or radiotherapy regime has been found to produce a worthwhile extension of life with reasonably tolerable side effects. Gamma-linolenic acid (GLA) has been found to kill about 40 different human cancer cell lines in vitro without harming normal cells. The lithium salt of GLA (LiGLA) can be administered intravenously and a dose escalation study of a 10 day infusion followed by oral therapy in patients with inoperable pancreatic cancer was carried out in 48 patients in two centres. Peripheral venous infusion caused thrombophlebitis but this could be avoided by infusing via a central vein with appropriate heparinisation. Too rapid infusion caused haemolysis which could be avoided by slow dose escalation in the first few days and maintenance of plasma lithium below 0.8 mmol/l. Doses ranged from 7 to 77g/patient cumulatively delivered over 2-12 days. Other than the above described events there were no important side effects and patients felt well during the infusions. A Kaplan-Meier analysis showed that survival was not significantly influenced by which centre the patients were treated in, the sex of the patients or the presence or absence of histological confirmation. The presence or absence of liver metastases, the patients' Karnofsky scores and the-dose of LiGLA had significant effects on survival from treatment. A Cox proportional hazards model revealed similar results: in both centres, in both sexes, and in patients with and without liver metastases according to the model the highest doses of LiGLA were associated with longer survival times as compared with the lowest doses. LiGLA deserves investigation in a randomised prospective study.

Efficacy of gamma-linolenic acid in the treatment of patients with atopic dermatitis.

Of 60 patients with atopic dermatitis (30 males and 30 females, 15-30 years old) 30 were treated with gamma-linolenic acid of (C18:3 n-6) at a dosage of 274 mg twice a day; the other 30 patients were given placebo. The patients were treated for 12 weeks, during which their symptoms were assessed on a linear scale both by a dermatologist and by themselves every 4 weeks. The patients who received gamma-linolenic acid, showed gradual improvements in pruritus, erythema, vesiculation and oozing, which were statistically significant compared with the control group (P < 0.001). Only one patient had presented with scaling at the beginning of the study and this symptom appeared to be less influenced by the effects of gamma-linolenic acid. The assessments of symptoms made by the dermatologist were generally consistent with those made by the patients themselves. gamma-linolenic acid was found to be effective and without side-effects for the treatment of atopic dermatitis.

The efficacy and safety of gamma-linolenic acid in the treatment of infantile atopic dermatitis.

The efficacy and safety of gamma-linolenic acid in the treatment of atopic dermatitis was evaluated. The children (mean age, 11.4 months) with atopic dermatitis (mean duration, 8.56 months) were openly treated with 3 g/day gamma-linolenic acid, for 28 days. Clinical evaluations were carried out every 7 days, and parents were asked to keep a diary, recording details of symptoms of eczema every day. Blood chemistry and immunological tests were done before and after treatment. None of the children showed complete recovery of symptoms. A gradual improvement in erythema, excoriations and lichenification was seen; significant differences were shown for itching (P < 0.01), and the use of antihistamines (P < 0.01). A significant rise in the percentage of circulating CD8 was found. No side-effects were recorded. Dietetic and pharmacological approaches are the basis of the treatment of atopic dermatitis and gamma-linolenic acid appears to be a safe and efficient additional therapy for infants and young children.

Long-term Supplementation With n-6 and n-3 PUFAs Improves Moderate-to-Severe Keratoconjunctivitis Sicca: A Randomized Double-Blind Clinical Trial.

PURPOSE: Supplementation with gamma-linolenic acid (GLA) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) has been found to decrease the production of disease-relevant inflammatory mediators that are implicated in the pathogenesis of chronic dry eye. This study evaluated the effect of a supplement containing both GLA and n-3 PUFAs on signs and symptoms of moderate-to-severe keratoconjunctivitis sicca in postmenopausal patients. METHODS: This multicenter, double-masked placebo-controlled clinical trial enrolled 38 patients (both eyes) with tear dysfunction who were randomized to supplemental GLA + n-3 PUFAs or placebo for 6 months. Disease parameters, including Ocular Surface Disease Index, Schirmer test, tear breakup time, conjunctival fluorescein and lissamine green staining, and topographic corneal smoothness indexes (surface asymmetry index and surface regularity index), were assessed at baseline and at 4, 12, and 24 weeks. The intensity of dendritic cell CD11c integrin and HLA-DR expression was measured in conjunctival impression cytologies. RESULTS: The Ocular Surface Disease Index score improved with supplementation and was significantly lower than placebo (21 ± 4 vs. 34 ± 5) after 24 weeks (P = 0.05, n = 19 per group). The surface asymmetry index was significantly lower in supplement-treated subjects (0.37 ± 0.03, n = 15) than placebo (0.51 ± 0.03, n = 16) at 24 weeks (P = 0.005). Placebo treatment also significantly increased HLA-DR intensity by 36% ± 9% and CD11c by 34% ± 7% when compared with supplement treatment (n = 19 per group, P = 0.001, 24 weeks). Neither treatment had any effect on tear production, tear breakup time, or corneal or conjunctival staining. CONCLUSIONS: Supplemental GLA and n-3 PUFAs for 6 months improved ocular irritation symptoms, maintained corneal surface smoothness, and inhibited conjunctival dendritic cell maturation in patients with postmenopausal keratoconjunctivitis sicca.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00883649.

Clinical study of the effects on asthma-related QOL and asthma management of a medical food in adult asthma patients.

BACKGROUND: Asthma can have a negative impact on quality of life although this is not well correlated with objective evaluations of pulmonary function. A medical food, EFF1009, containing the fatty acids gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA) decreases leukotriene B(4) synthesis in patients with asthma. Two previous clinical studies with EFF1009 provided preliminary evidence that the medical food improves asthma-related quality of life (ARQOL) and asthma management. OBJECTIVE: To evaluate the impact on ARQOL of EFF1009 in adults with asthma. RESEARCH DESIGN AND METHODS: The study was a randomized, prospective, double-blind, placebo-controlled, parallel group study in twenty-one (N = 21 evaluable) subjects with mild to moderate persistent asthma who consumed the medical food emulsion or placebo emulsion daily for 28 days. All participants continued their asthma medications throughout the study. ARQOL, including asthma signs and symptoms, and asthma control were measured using the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) and the Asthma Control Questionnaire (ACQ), administered at baseline, Day 14 and Day 28. Safety and tolerability parameters, including adverse events, were monitored. RESULTS: Baseline ARQOL scores, forced expiratory volume in one second (FEV(1)) and other characteristics were balanced between both groups. Mean (standard error) total MiniAQLQ scores changed by 0.73 (0.38) and -0.22 (0.36) in the EFF1009 and placebo groups, respectively, (p < 0.05). The MiniAQLQ symptom domain score was improved in the EFF1009 group (p < 0.05). Total scores for the ACQ were not significantly improved in either group. Levels of the fatty acid EPA in plasma increased in the EFF1009 group but not the placebo group (p < 0.03). The medical food was well tolerated and no safety concerns were identified. CONCLUSIONS: The dietary addition of the medical food EFF1009 to asthma management regimens can improve patient perceived, ARQOL and can also improve asthma management as evidenced by reduced asthma symptoms. An additional study of the medical food, with larger subject population and longer treatment duration, is warranted to confirm these findings.

Co-supplementation of healthy women with fish oil and evening primrose oil increases plasma docosahexaenoic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid levels without reducing arachidonic acid concentrations.

Fish oil supplementation during pregnancy not only improves maternal and neonatal DHA status, but often reduces gamma-linolenic acid (GLA), dihomo-GLA (DGLA), and arachidonic acid (ARA) levels also, which may compromise foetal and infant development. The present study investigated the effects of a fish oil/evening primrose oil (FSO/EPO) blend (456 mg DHA/d and 353 mg GLA/d) compared to a placebo (mixture of habitual dietary fatty acids) on the plasma fatty acid (FA) composition in two groups of twenty non-pregnant women using a randomised, double-blind, placebo-controlled parallel design. FA were quantified in plasma total lipids, phospholipids, cholesterol esters, and TAG at weeks 0, 4, 6 and 8. After 8 weeks of intervention, percentage changes from baseline values of plasma total lipid FA were significantly different between FSO/EPO and placebo for GLA (+49.9 % v. +2.1 %, means), DGLA (+13.8 % v. +0.7 %) and DHA (+59.6 % v. +5.5 %), while there was no significant difference for ARA ( - 2.2 % v. - 5.9 %). FA changes were largely comparable between plasma lipid fractions. In both groups three subjects reported mild adverse effects. As compared with placebo, FSO/EPO supplementation did not result in any physiologically relevant changes of safety parameters (blood cell count, liver enzymes). In women of childbearing age the tested FSO/EPO blend was well tolerated and appears safe. It increases plasma GLA, DGLA, and DHA levels without impairing ARA status. These data provide a basis for testing this FSO/EPO blend in pregnant women for its effects on maternal and neonatal FA status and infant development.

The toxicities of a polyunsaturated fatty acid and a microcystin to Daphnia magna.

Polyunsaturated fatty acids (PUFAs) are essential components of zooplankton diets. However, studies with PUFAs from cyanobacteria indicate toxic properties. We investigated the toxicity of the PUFA gamma-linolenic acid and the cyanobacterial peptide toxin microcystin-LR to Daphnia. The PUFA was acutely toxic at a concentration of 9 micrograms ml-1. The effect of microcystin-LR was not statistically significant at the concentration used (3 micrograms ml-1), but an additive effect with the PUFA was observed. Relative to LC50-values of well-known pollutants, the PUFA was intermediately toxic. The activity equaled that of microcystin-LR, which is commonly treated as one of the most potent cyanobacterial toxins. Our results suggest that the toxic properties of PUFAs deserve more attention.

Treatment of rheumatoid arthritis with gammalinolenic acid.

OBJECTIVE: To assess the clinical efficacy and side effects of gammalinolenic acid, a plant-seed-derived essential fatty acid that suppresses inflammation and joint tissue injury in animal models. DESIGN: A randomized, double-blind, placebo-controlled, 24-week trial. SETTING: Rheumatology clinic of a university hospital. PATIENTS: Thirty-seven patients with rheumatoid arthritis and active synovitis. INTERVENTION: Treatment with 1.4 g/d gammalinolenic acid in borage seed oil or cotton seed oil (placebo). MEASUREMENTS: Physicians' and patients' global assessment of disease activity; joint tenderness, joint swelling, morning stiffness, grip strength, and ability to do daily activities. RESULTS: Treatment with gammalinolenic acid resulted in clinically important reduction in the signs and symptoms of disease activity in patients with rheumatoid arthritis (P < 0.05). In contrast, patients given a placebo showed no change or showed worsening of disease. Gammalinolenic acid reduced the number of tender joints by 36%, the tender joint score by 45%, swollen joint count by 28%, and the swollen joint score by 41%, whereas the placebo group did not show significant improvement in any measure. Overall clinical responses (significant change in four measures) were also better in the treatment group (P < 0.05). No patients withdrew from gammalinolenic acid treatment because of adverse reactions. CONCLUSION: Gammalinolenic acid in doses used in this study is a well-tolerated and effective treatment for active rheumatoid arthritis. Gammalinolenic acid is available worldwide as a component of evening primrose and borage seed oils. It is usually taken in far lower doses than used in this trial. It is not approved in the United States for the treatment of any condition and should not be viewed as therapy for any disease. Further controlled studies of its use in rheumatoid arthritis are warranted.