linoleic-acid and Dermatitis--Atopic

Active rebuilding, stabilizing, and maintaining the lipid barrier of the skin is an encouraging disease management and care concept for dry skin, atopic dermatitis (eczema, neurodermatitis), and psoriasis. For decades, corticosteroids have been the mainstay of topical therapy for atopic dermatitis; however, innovations within the scope of basic therapy are rare. In (extremely) dry, irritated, or inflammatory skin, as well as in lesions, an altered (sphingo)lipid profile is present. Recovery of a balanced (sphingo)lipid profile is a promising target for topical and personalized treatment and prophylaxis. New approaches for adults and small children are still lacking. With an ingenious combination of commonly used active ingredients, it is possible to restore and reinforce the dermal lipid barrier and maintain refractivity. Lysosomes and ceramide de novo synthesis play a key role in attenuation of the dermal lipid barrier. Linoleic acid in combination with amitriptyline in topical medication offers the possibility to relieve patients affected by dry and itchy skin, mild to moderate atopic dermatitis lesions, and eczemas without the commonly occurring serious adverse effects of topical corticosteroids or systemic antibody administration.

Topics: Amitriptyline; Animals; Antioxidants; Apoptosis; Ceramides; Dermatitis, Atopic; Humans; Linoleic Acid; Sphingolipids

Atopic dermatitis (AD) is a common pruritic chronic skin disease. AD pathogenesis remains elusive, but may involve complex interplays among skin barrier dysfunction, Th2 inflammation, and pruritus. Current treatments for AD are still limited to symptomatic therapies. We previously showed that HR-1 hairless mice fed a special diet (HR-AD) develop AD-like symptoms; however, the ingredient(s) causing dermatitis remain unclear. In this study, we examined whether the deficiency of certain polyunsaturated fatty acids (PUFAs) was involved in the diet-induced AD pathogenesis. In the serum of HR-AD-fed mice, levels of linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3), as well as their metabolites, were markedly decreased. HR-AD-induced AD symptoms were significantly ameliorated by LA supplementation, and to a lesser extent by ALA supplementation. In addition, LA metabolites, such as γ-linolenic acid and arachidonic acid, had effects similar to those of LA. Further, using semi-purified custom diets, we attempted to reproduce HR-AD-induced AD symptoms. Unexpectedly, a deficiency in unsaturated fatty acids (UFAs) alone caused mild symptoms. However, several modifications of fat and carbohydrate components in the diet revealed that dietary deficiencies of UFA and cornstarch were required to fully induce severe AD symptoms. Furthermore, we examined the influence of genetic background on the development of diet-induced AD and found that a hypomorphic mutation in the hairless gene Hr, encoding a nuclear receptor (NR) corepressor, was essential for the complete development of diet-induced pruritic atopic skin. Thus, our findings suggest that certain PUFAs and NRs are new, potential therapeutic targets for treating AD.

Topics: Animals; Co-Repressor Proteins; Dermatitis, Atopic; Diet; Disease Models, Animal; Fatty Acids, Unsaturated; Humans; Linoleic Acid; Mice, Hairless; Molecular Targeted Therapy; Mutation; Starch; Transcription Factors

Research from the 1930s to the 1950s established that a deficit of n-6 essential fatty acids (EFAs) leads to an inflammatory skin condition in both animals and humans. In a common inherited skin condition, atopic dermatitis (eczema), there was evidence of low blood EFA concentrations and of a therapeutic response to exceptionally high doses of linoleic acid. More recently, it has been established that there is no deficit of linoleic acid in atopic eczema. Concentrations of linoleic acid instead tend to be elevated in blood, milk, and adipose tissue of patients with atopic eczema, whereas concentrations of linoleic acid metabolites are substantially reduced. This suggests reduced conversion of linoleic acid to gamma-linolenic acid (GLA). In most but not all studies, administration of GLA has been found to improve the clinically assessed skin condition, the objectively assessed skin roughness, and the elevated blood catecholamine concentrations of patients with atopic eczema. Atopic eczema may be a minor inherited abnormality of EFA metabolism.

Topics: Adipose Tissue; Adolescent; Adult; alpha-Linolenic Acid; Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Dermatitis, Atopic; Fatty Acids, Essential; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Infant; Linoleic Acid; Linoleic Acids; Milk, Human; Oenothera biennis; Plant Oils

Linoleic acid is the main dietary essential fatty acid (EFA). To be fully utilized by the body, it must be metabolized to a range of other substances. The first step in this pathway is delta-6-desaturation to gamma-linolenic acid (GLA). This step is slow and rate-limiting, particularly in humans. If delta-6-desaturation is impaired for any reason, the supply of further metabolites may be inadequate for normal function. If the consumption of further metabolites is excessive, then a normal rate of delta-6-desaturation may be inadequate. In these circumstances the direct supply of GLA or further metabolites may be of value. This concept is illustrated by atopic eczema and diabetes, which may represent inherited and acquired examples of inadequate delta-6-desaturation.

Topics: Dermatitis, Atopic; Diabetes Mellitus; Diabetic Neuropathies; Fatty Acid Desaturases; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Linoleic Acid; Linoleic Acids; Linolenic Acids; Linoleoyl-CoA Desaturase

The breakdown of the epidermal barrier and consequent loss of skin hydration is a feature of skin aging and eczematous dermatitis. Few treatments, however, resolve these underlying processes to provide full symptomatic relief. In this study, we evaluated isosorbide di-(linoleate/oleate) (IDL), which was generated by esterifying isosorbide with sunflower fatty acids. Topical effects of IDL in skin were compared with those of ethyl linoleate/oleate, which has previously been shown to improve skin barrier function. Both IDL and ethyl linoleate/oleate downregulated inflammatory gene expression, but IDL more effectively upregulated the expression of genes associated with keratinocyte differentiation (e.g., KRT1, GRHL2, SPRR4). Consistent with this, IDL increased the abundance of epidermal barrier proteins (FLG and involucrin) and prevented cytokine-mediated stratum corneum degradation. IDL also downregulated the expression of unhealthy skin signature genes linked to the loss of epidermal homeostasis and uniquely repressed an IFN-inducible coexpression module activated in multiple skin diseases, including psoriasis. In a double-blind, placebo-controlled trial enrolling females with dry skin, 2% IDL lotion applied over 2 weeks significantly improved skin hydration and decreased transepidermal water loss (NCT04253704). These results demonstrate mechanisms by which IDL improves skin hydration and epidermal barrier function, supporting IDL as an effective intervention for the treatment of xerotic pruritic skin.

Topics: Adult; Cell Differentiation; Dermatitis, Atopic; Double-Blind Method; Emollients; Epidermis; Female; Filaggrin Proteins; Follow-Up Studies; Gene Expression Profiling; Gene Expression Regulation; Humans; Isosorbide; Keratinocytes; Linoleic Acid; Middle Aged; Oleic Acid; Skin Cream; Treatment Outcome; Water Loss, Insensible

Atopic dermatitis (AD), chronic eczema, and pruritus hiemalis are a set of prevalent chronic xerotic skin disorders that share clinical features such as dryness, scales, and pruritus. A ceramide deficiency and defective epidermal functions are common in these diseases. This study was designed to assess the effect of ceramide-linoleic acid (LA-Cer)-containing moisturizer as an adjunctive therapy in the treatment of AD, chronic eczema, and pruritus hiemalis. In a 2-month study, patients with one of these three diseases were divided into two groups. The control group was treated with mometasone furoate (0.1%) cream (MF), whereas the treatment group received 0.1% MF in combination with an LA-Cer-containing moisturizer. Capacitance and transepidermal water loss were measured in normal and lesional skin, along with Eczema Assessment Severity Index and pruritus scores at Weeks 0, 2, 4, and 8. The results showed that tropical applications of an LA-Cer-containing moisturizer in combination with a topical glucocorticoid accelerated the reestablishment of epidermal permeability barrier and the amelioration of pruritus in patients with AD and pruritus hiemalis. However, it did not provide the same effect for chronic eczema. Thus, the efficacy of this combination therapy for this set of xerotic disorders requires further evaluation.

Topics: Administration, Cutaneous; Ceramides; Dermatitis, Atopic; Dermatologic Agents; Eczema; Electric Capacitance; Emollients; Glucocorticoids; Humans; Linoleic Acid; Mometasone Furoate; Pruritus; Severity of Illness Index; Treatment Outcome; Water Loss, Insensible

Topics: Adult; Dermatitis, Atopic; Dietary Supplements; Double-Blind Method; Eczema; Epidermis; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Humans; Hydroxyeicosatetraenoic Acids; Linoleic Acid; Linoleic Acids; Male; Pilot Projects; Placebos; Skin

We have measured all the essential fatty acids (EFA) in plasma phospholipids in forty-one adults with atopic eczema and fifty normal controls. The major dietary n-6 EFA, linoleic acid, was significantly elevated, but all its metabolites, 18:3n-6, 20:3n-6, 20:4n-6, 22:4n-6, and 22:5n-6 were significantly reduced. The major dietary n-3 EFA, alpha-linolenic acid, was also elevated, though not significantly, while all its metabolites were also significantly reduced. These observations suggest that atopic eczema is associated not with any defect of EFA intake, but with abnormal metabolism, possibly involving the enzyme delta-6-desaturase. Treatment with oral evening primrose oil produced partial correction of the n-6 EFA abnormality, but had no effect on the n-3 EFAs.

Topics: Adult; alpha-Linolenic Acid; Dermatitis, Atopic; Dermatologic Agents; Fatty Acids, Essential; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Hypolipidemic Agents; Linoleic Acid; Linoleic Acids; Linolenic Acids; Male; Oenothera biennis; Phospholipids; Plant Oils

Topics: Allergens; Animals; Dermatitis, Atopic; Egg White; Food Hypersensitivity; Humans; Infant; Linoleic Acid; Milk

Rebuilding, stabilizing and maintaining the dermal lipid barrier is an encouraging disease management concept (relief and care) in the treatment and prevention of atopic dermatitis. Prevention and topical treatment, however, lack a simple, safe, effective and modular approach. For decades, the mainstay of topical therapy of atopic dermatitis has been corticosteroids, with innovations being rare. Our case report demonstrates the struggle of a patient with little relief of itchy dermal lesions and the recurrence of skin lesions following current therapeutic guidelines which proved to be ineffective. Therefore we decided to try an advanced C

Topics: Administration, Cutaneous; Amitriptyline; Ceramides; Child; Dermatitis, Atopic; Dermatologic Agents; Female; Humans; Linoleic Acid; Treatment Outcome

The present study investigated the antiallergic and anti-inflammatory effects of 10-hydroxy-cis-12-octadecenoic acid (HYA), a novel gut microbial metabolite of linoleic acid, in NC/Nga mice, a model of atopic dermatitis (AD). Feeding HYA decreased the plasma immunoglobulin E level and skin infiltration of mast cells with a concomitant decrease in dermatitis score. HYA feeding decreased TNF-α and increased claudin-1, a tight junction protein, levels in the mouse skin. Cytokine expression levels in the skin and intestinal Peyer's patches cells suggested that HYA improved the Th1/Th2 balance in mice. Immunoglobulin A concentration in the feces of the HYA-fed mice was approximately four times higher than that in the control mice. Finally, denaturing gradient gel electrophoresis of the PCR-amplified 16 S rRNA gene of fecal microbes indicated the modification of microbiota by HYA. Taken together, the alterations in the intestinal microbiota might be, at least in part, associated with the antiallergic effect of HYA.

Topics: Animal Feed; Animals; Behavior, Animal; Cytokines; Dermatitis, Atopic; Diet; Dietary Supplements; Feces; Gastrointestinal Microbiome; Gene Expression Regulation; Immunoglobulin A; Inflammation; Linoleic Acid; Mice; Molecular Structure; Oleic Acids; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction

Hairless mice fed a special diet, HR-AD, develop atopic dermatitis (AD)-like skin inflammation with skin barrier defects and itch-related scratching; however, the ingredient(s) causing the dermatitis remains unclear. In this study, we examined whether deficiency of certain polyunsaturated fatty acids (PUFAs) is involved in HR-AD-induced AD. High-purity PUFAs were given to HR-AD-fed mice by dietary supplementation or gavage. Fatty acid levels in the serum and skin were determined by using gas chromatography-mass spectrometry. In serum from HR-AD-fed mice, linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3), as well as their metabolites, were markedly decreased. When mice were fed HR-AD supplemented with LA or ALA in an amount equal to that contained in a normal diet, the development of AD-like symptoms was completely prevented by supplementation with LA but not with ALA. Relatively high dose of ALA slightly alleviated skin barrier defects, but did neither itch-related scratching nor skin inflammation. On the other hand, gavage administration of LA metabolites, such as γ-linolenic acid and arachidonic acid (AA), significantly ameliorated established dermatitis without increasing LA in the serum and skin. Moreover, AA-induced amelioration of dermatitis was not affected by pharmacological blockade of 5-lipoxygenase (5-LOX) and cyclooxygenase (COX), suggesting no involvement of 5-LOX- or COX-mediated AA metabolites in the amelioration. In conclusion, our results indicate that deficiency of n-6 PUFAs is mainly responsible for AD-like symptoms by HR-AD feeding. Thus, this model could be useful for studying the pathomechanisms associated with deficiency of n-6 PUFAs in AD.

Topics: Animals; Arachidonic Acid; Dermatitis, Atopic; Diet; Dietary Fats, Unsaturated; Disease Models, Animal; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Linoleic Acid; Mice; Mice, Hairless; Pruritus; Skin

It has been suggested that atopic dermatitis (AD) is associated with impaired delta-6 desaturase activity and the subsequent altered composition of n-6 essential fatty acids (EFAs).. To investigate whether n-6 EFA deficiency accounts for AD by affecting transepidermal water loss or the immune response.. Serum levels of n-6 EFAs were measured using gas chromatography-mass spectrometry in a well-defined group of 35 children with AD (IgE level >150 U/mL); 35 age-matched children with allergic rhinitis, asthma, or both (IgE level >150 U/mL); and 31 nonatopic controls (IgE level <100 U/mL). Skin barrier function was evaluated by measuring transepidermal water loss and severity of AD by computing the Scoring Atopic Dermatitis (SCORAD) index.. Atopic children had higher levels of linoleic acid (LA) and lower levels of its metabolites. Furthermore, gamma-linolenic acid to LA and dihommo-gamma-linolenic acid to LA ratios were significantly reduced in atopic patients. Transepidermal water loss and the SCORAD index were negatively correlated with serum levels of LA metabolites. There was no correlation between the SCORAD index and IgE level (P = .51) or between n-6 EFA concentrations and IgE level (P > .10).. Deficits in n-6 EFAs were correlated with the severity of AD by affecting skin barrier function and cutaneous inflammation. The link between impaired n-6 EFA metabolism and IgE level could not be defined.

Topics: 8,11,14-Eicosatrienoic Acid; Adolescent; Arachidonic Acid; Asthma; Child; Child, Preschool; Dermatitis, Atopic; Epidermis; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Immunoglobulin E; Linoleic Acid; Lipids; Male; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Water; Water Loss, Insensible

Topics: Adolescent; Adult; alpha-Linolenic Acid; Arachidonic Acid; Child; Child, Preschool; Dermatitis, Atopic; Fatty Acids, Essential; Humans; Infant; Infant, Newborn; Linoleic Acid; T-Lymphocytes

The major theory implicating diet with allergic diseases is associated with altered food consumption and subsequent changes in fatty acid composition.. To investigate fatty acid compositions among infants with atopic and non-atopic eczema and healthy infants and to evaluate the expediency of non-invasive cheek cell phospholipid fatty acid composition as a marker in patients with eczema.. Diagnosis of eczema in infants was confirmed clinically and by positive (atopic eczema, n=6) or negative (non-atopic eczema, n=6) skin prick testing in comparison with controls (n=19). The fatty acid compositions of infant cheek cell and serum phospholipids and breast milk total lipids were analysed by gas chromatography.. The distinction between atopic and non-atopic eczema was manifested in cheek cell phospholipids as linoleic acid (14.69 (13.67-15.53)% of total fatty acids; the median (interquartile range)), the sum of n-6 fatty acids (19.94 (19.06-20.53)%) and the sum of polyunsaturated fatty acids (22.70 (21.31-23.28)%) were higher in infants with atopic eczema compared with non-atopic eczema (12.69 (10.87-13.93); 17.72 (15.63-18.91) and 19.90 (17.64-21.06), respectively; P<0.05) and controls (12.50 (12.16-13.42); 18.19 (17.43-18.70) and 20.32 (19.32-21.03), respectively; P<0.05). Serum phospholipid gamma-linolenic acid was lower in both atopic and non-atopic eczema compared with controls (P<0.05) and additionally eicosapentaenoic acid was higher in atopic eczema compared with controls (P<0.05).. These preliminary results suggest differences in fatty acid compositions between the two types of eczema, calling for further evaluation in a larger setting. The two types of eczema may be regulated by different immunological processes, and fatty acids may have a more profound role in the atopic type.

Topics: alpha-Linolenic Acid; Case-Control Studies; Cheek; Chromatography, Gas; Dermatitis, Atopic; Eczema; Fatty Acids; Humans; Infant; Infant, Newborn; Linoleic Acid; Lipids; Milk, Human; Mouth Mucosa; Phospholipids; Statistics, Nonparametric

The proportions of linoleic acid in total plasma lipids and phospholipids were significantly greater and those of oleic acid were lower in pre-puberal and puberal atopic patients as compared with age-matched healthy controls. The n-3/n-6 fatty acid ratio of the triacylglycerol fraction was also lower in atopic patients. However, no significant decreases in the proportions of dihomo-gamma-linolenic acid and arachidonic acid were observed in plasma lipids of atopic patients, suggesting that delta 6-desaturase activity is not impaired in atopic patients. We provide an explanation for the beneficial effects of raising the n-3/n-6 ratio of dietary oils in the context of suppressing allergic hyper-reactivity in humans.

Topics: Adolescent; Asthma; Child; Dermatitis, Atopic; Fatty Acids; Fatty Acids, Omega-3; Humans; Linoleic Acid; Linoleic Acids; Lipids; Oleic Acid; Oleic Acids; Phospholipids; Triglycerides

Topics: Arachidonic Acid; Child; Child, Preschool; Dermatitis, Atopic; Erythrocyte Membrane; Fatty Acids, Unsaturated; Female; Humans; Immunoglobulin E; Linoleic Acid; Linoleic Acids; Male; Matched-Pair Analysis; Radioallergosorbent Test; Skin Tests

Thirty-five dogs with non-seasonal atopic dermatitis were used in a double-blind, placebo-controlled crossover study of the effects of evening primrose (Oenothera biennis) oil. There was a significant treatment effect (P less than 0.05) on erythema. An analysis of the changes in plasma phospholipid levels of essential fatty acids revealed a significant (P less than 0.05) rise in linoleic acid concentration above that in the placebo group. Arachidonic acid levels in the treated group increased significantly (P less than 0.005) in the first phase and also in the second phase (P less than 0.05). In the second phase the levels of arachidonic acid in the active and placebo groups differed significantly (P less than 0.05) and there was a significant treatment effect (P less than 0.05).

Topics: Animals; Arachidonic Acid; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Double-Blind Method; Fatty Acids, Essential; gamma-Linolenic Acid; Linoleic Acid; Linoleic Acids; Oenothera biennis; Phospholipids; Plant Oils

We have measured adipose tissue total lipid and plasma phospholipid essential fatty acid composition by capillary column gas chromatography in patients with atopic eczema. In both adipose tissue and plasma phospholipids there was a significant elevation of linoleic acid in patients compared to a control group (adipose tissue P less than 0.05; plasma P less than 0.001), and a substantially higher ratio of linoleic acid to the sum of its longer chain highly unsaturated derived fatty acids, dihomogamma linolenic acid and arachidonic acid. These findings add support to the proposition that patients with atopic eczema have a defect in the conversion of linoleic acid.

Topics: Adipose Tissue; Adolescent; Adult; Dermatitis, Atopic; Evaluation Studies as Topic; Fatty Acids, Essential; Female; Humans; Linoleic Acid; Linoleic Acids; Male; Phospholipids

The metabolism of essential unsaturated fatty acids seems to show changes in patients with atopic dermatitis (AD). A defect or a deficiency of a Delta-6-Desaturase, which transforms cis-linoleic acid into gamma-linolenic-acid will be discussed. We examined the influence of a treatment with unsaturated fatty acids on clinical phenotype and the surface antigens of lymphocytes in peripheral blood. Prolonged recurrence free intervals as well as a faster ability to control relapse were established. Dysbalance in the lymphocytic system was able to be positively influenced. We found an increase of Leu 2 a-antigen carrying T-suppressor-lymphocytes and of the Leu 3+8+- antigen carrying subpopulation of T-helper-lymphocytes, which are responsible for activation of precursor T-suppressor cells into.

Topics: Adolescent; Adult; Dermatitis, Atopic; Dietary Fats, Unsaturated; Female; gamma-Linolenic Acid; Humans; Immunity, Cellular; Immunocompetence; Linoleic Acid; Linoleic Acids; Linolenic Acids; Male; T-Lymphocytes

The fatty acid composition of serum lecithin from children with atopic dermatitis (AD) was found to be abnormal, characterized by significantly increased proportion of linoleic acid and reduced levels of metabolites of this fatty acid. The levels of linoleic acid in umbilical cord serum lecithin were significantly higher in babies with high serum IgE than in those with low or non-demonstrable serum IgE. Since elevated cord serum IgE is strongly associated with development of atopic disease the results suggest that fatty acid changes may be a basic feature of AD. Immunologic dysfunction in patients with AD may possibly partly be a consequence of the fatty acid abnormality.

Topics: Child; Dermatitis, Atopic; Fatty Acids, Essential; Fetal Blood; Humans; Immunoglobulin E; Infant, Newborn; Linoleic Acid; Linoleic Acids; Phosphatidylcholines

Topics: Adolescent; Adult; Dermatitis, Atopic; Female; gamma-Linolenic Acid; Humans; Linoleic Acid; Linoleic Acids; Linolenic Acids; Male

Topics: Arachidonic Acid; Child; Dermatitis, Atopic; Eczema; Humans; Infant; Linoleic Acid