Borage Oil in the Treatment of Atopic Dermatitis
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See discussions, stats, and author profiles for this publication at: http://www.researchgate.net/publication/44801514 Borage oil in the treatment of atopic dermatitis ARTICLE in NUTRITION · JULY 2010 Impact Factor: 3.05 · DOI: 10.1016/j.nut.2009.10.014 · Source: PubMed CITATIONS DOWNLOADS VIEWS 17 183 194 3 AUTHORS: Rachel Foster Gil Hardy University of Otago University of Auckland 60 PUBLICATIONS 1,417 CITATIONS 127 PUBLICATIONS 1,114 CITATIONS SEE PROFILE SEE PROFILE Raid G Alany Kingston University London 94 PUBLICATIONS 649 CITATIONS SEE PROFILE Available from: Raid G Alany Retrieved on: 16 September 2015 ARTICLE IN PRESS NUT8304_proof 6 December 2009 1/11 Nutrition xxx (2010) 1–11 Contents lists available at ScienceDirect Nutrition journal homepage: www.nutritionjrnl.com 53 Review 1 54 2 A review of borage oil in the treatment of atopic dermatitis 55 3 56 4 57 a a b,* 5 Rachel H. Foster B.Pharm. , Gil Hardy Ph.D. , Raid G. Alany Ph.D., M.P.S., Reg. Pharm. NZ, FNZCP 58 6 a School of Pharmacy, The University of Auckland, Auckland, New Zealand 59 7 b Drug Delivery Research Unit (DDRU), School of Pharmacy, The University of Auckland, Auckland, New Zealand 60 8 61 9 62 10 article info abstract 63 11 64 12 Article history: Nutritional supplementation with omega-6 essential fatty acids (u-6 EFAs) is of potential interest 65 13 Received 1 April 2009 in the treatment of atopic dermatitis. EFAs play a vital role in skin structure and physiology. EFA 66 Accepted 28 October 2009 14 deficiency replicates the symptoms of atopic dermatitis, and patients with atopic dermatitis have 67 15 been reported to have imbalances in EFA levels. Although direct proof is lacking, it has been 68 Keywords: hypothesized that patients with atopic dermatitis have impaired activity of the delta-6 desaturase 16 69 Borage oil enzyme, affecting metabolism of linoleic acid to gamma-linolenic acid (GLA). However, to date, 17 Atopic dermatitis 70 studies of EFA supplementation in atopicPROOF dermatitis, most commonly using evening primrose oil, Essential fatty acids 71 18 have produced conflicting results. Borage oil is of interest because it contains two to three times 72 19 more GLA than evening primrose oil. This review identified 12 clinical trials of oral or topical 20 borage oil for treatment of atopic dermatitis and one preventive trial. All studies were controlled 73 21 and most were randomized and double-blind, but many were small and had other methodological 74 22 limitations. The results of studies of borage oil for the treatment of atopic dermatitis were highly 75 23 variable, with the effect reported to be significant in five studies, insignificant in five studies, and 76 24 mixed in two studies. Borage oil given to at-risk neonates did not prevent development of atopic 77 25 dermatitis. However, the majority of studies showed at least a small degree of efficacy or were not 78 26 able to exclude the possibility that the oil produces a small benefit. Overall, the data suggest that 79 nutritional supplementation with borage oil is unlikely to have a major clinical effect but may be 27 80 useful in some individual patients with less severe atopic dermatitis who are seeking an alternative 28 81 treatment. Which patients are likely to respond cannot yet be identified. Borage oil is well tolerated 82 29 in the short term but no long-term tolerability data are available. 30 Ó 2010 Elsevier Inc. All rights reserved. 83 31 84 32 85 33 86 34 Introduction various cytokines and chemokines play an essential role. Most, 87 35 but not all, cases are IgE-mediated. Atopic dermatitis often co- 88 36 Atopic dermatitis (atopic eczema) is a chronic-relapsing occurs with other atopic conditions such as asthma and hayfever. 89 37 inflammatory skin condition that can be distressing, and when The condition has been linked to various regulatorygenes, and it is 90 38 Q1 severe, can be functionally and socially disabling [1]. It affects up strongly linked to a family history of atopy. The pathophysiology 91 39 to 15–20% of children in developed countries, and the incidence of atopic dermatitis includes skin barrier defects causing 92 40 is increasing [2,6]. The condition improves or resolves with age increased transepidermal water loss (TEWL) and increased 93 41 in most patients. However, many patients will require intermit- permeability to irritants and allergens. There is increased 94 42 tent treatment for exacerbations through to early adulthood or susceptibility to infection, and colonization of the skin with 95 43 beyond with agents such as topical corticosteroids that have Staphylococcus aureus contributes to inflammation of the skin. 96 44 significant adverse effects (Table 1) [2,6,15]. It has been proposed that atopic dermatitis is associated with 97 45 The pathogenesis of atopic dermatitis is multifactorial and an abnormality in essential fatty acid (EFA) metabolism, in 98 46 involves a complex interaction between environmental, immu- particular, affecting production of GLA, and possibly also 99 47 nological, and genetic factors [1,3].UNCORRECTED It is associated with hyperre- impaired incorporation of EFAs into membrane phospholipids 100 48 activity to environmental triggers. T-cell-mediated processes and [7–9]. In the body, EFAs and their products, particularly those of 101 49 the omega-6 (u-6) series, are important for skin structure and 102 50 physiology. EFAs play a crucial role in cell membrane fluidity and 103 * Corresponding author. Tel.: þ64 9 373 7599, ext: 86967; fax: þ64 9 367 104 51 7192. flexibility and affect activity of membrane-associated proteins 52 E-mail address: [email protected] (R. G. Alany). such as receptors and enzymes. Notably, EFAs are key 105 0899-9007/$ – see front matter Ó 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.nut.2009.10.014 Please cite this article in press as: Foster RH, et al., A review of borage oil in the treatment of atopic dermatitis, Nutrition (2010), doi:10.1016/j.nut.2009.10.014 ARTICLE IN PRESS NUT8304_proof 6 December 2009 2/11 2 R. H. Foster et al. / Nutrition xxx (2010) 1–11 106 components in the membrane systems that maintain the struc- Key 170 Essential fatty acid 107 tural integrity of the skin and epidermal function as a perme- Metabolic enzyme 171 108 ability barrier. Furthermore, EFAs are metabolized to highly Impaired in atopic eczema 172 13-HODE Linoleic acid 109 active eicosanoid products, such as prostaglandins and leuko- 173 110 trienes, that modulate inflammatory, immunologic, and prolif- 174 111 erative responses including those of the skin cells [7,8,14,16]. Δ-6 desaturase 175 112 In states of EFA deficiency, skin changes similar to those of 176 113 atopic dermatitis are replicated [7,8]. The skin becomes inflamed 177 Gamma-linolenic 114 178 with dry, scaly, red, and weeping lesions. There is an increased acid 115 rate of proliferation of epidermal cells, metabolic activity, and 179 116 formation of sterol esters and abnormal keratinocytes. The skin’s 180 Elongase 117 normal function as a barrier to water loss becomes markedly 181 PG1s 118 impaired [7,8]. There is increased colonization with S. aureus [5]. 182 TxA1 119 This atopic dermatitis-like skin disorder is reversed by treatment Dihomo-gamma- 183 LT3s linolenic acid 120 with u-6 EFAs [14]. 15-HETrE 184 121 There remains controversy over the exact importance of EFA 185 122 disturbances as a pathophysiological factor in atopic dermatitis, Δ-5 desaturase 186 123 and current data fall short of direct proof. Nevertheless, the PG2s 187 124 finding that EFA abnormalities can be detected prior to the TxA2 Arachidonic acid 188 125 development of atopic dermatitis does support a causative role LT4s 189 15-HETE 126 [10]. EFA abnormalities could contribute to atopic dermatitis in 190 127 two ways: first, through a direct effect on the skin structure and Fig. 1. Pathways of omega-6 essential fatty acid metabolism of interest in the 191 128 function, and, second, by affecting maturation and sensitization treatment of atopic eczema. The black box indicates the metabolic step believed to 192 129 of the immune system affecting the skin [7]. The abnormalities in be impaired in atopic eczema. This potentially affects production of all metabolites 193 beyond this point. Supplementation with gamma-linolenic acid in borage oil is 130 EFA metabolism could potentially reduce levels of the prosta- 194 believed to shiftPROOF metabolism of dihomo-gamma-linolenic acid toward anti- 131 glandin PGE1, resulting in reduced levels of cyclic AMP, and inflammatory products such as PGE1 and 15-HETrE (shown by the black block 195 132 thereby affecting parts of the immune system causing selective arrow) rather than toward arachidonic acid and production of pro-inflammatory 196 133 Q2 hyperactivity. mediators such as LTB4 [7,8,14,16]. 13-HODE, 13-hydroxyoctadecadienoic acid; 15- 197 HETE, 15-hydroxyeicosatetraenoic acid; 15-HETrE, 15-hydroxyeicosatrienoic acid; 134 Such data have stimulated interest in whether EFA-containing 198 LT, leukotriene; PG, prostaglandin; Tx, thromboxane. 135 oils, particularly oils such as evening primrose oil that are rich in 199 136 the u-6 EFAs, are of value in the treatment of atopic dermatitis. present as unesterified fatty acids or as components of choles- 200 137 More recently, borage oil (also known as starflower oil) has terol esters, triacylglycerols, and phospholipids. For simplicity, 201 138 become of interest because of its high GLA content, which is two such distinctions will not be made in this article except where 202 139 to three times higher than that of evening primrose oil [11,12]. specifically necessary.) For both u-6 and u-3 EFAs, metabolism 203 140 While there have been a number of reviews on the use of involves alternating steps of desaturation and elongation.