A nutritional approach to managing skin conditions

Common inflammatory ailments:A nutritional approach to managing skin conditions

Sophie TullyBSc (Hons) MSc

• Igennus is the only independent manufacturer of specialist Fatty Acid in the UK. Based in Cambridge the medical innovation hub for the UK:

- Seven Seas Merck Pharma Germany- Minami Atrium Pharma Canada- Biocare Elder Pharma India- Eskimo 3 Bringwell Pharma Sweden- Equizen Vifor Pharma Swiss

Introduction

• Skin is the biggest ‘organ’ of the body

• Physical barrier, protects against: injury, infection, water and electrolyte loss

• Plays an important role in the immune system

• Multi-layered, consisting of: • Epidermis • Dermis• Hypodermis



Skin and inflammation

• The epidermis and dermis ‘host’ numerous immune cells including: fibroblasts, mast cells, leukocytes

• Inflammation involved in skin healing and repair post injury

• Inflammation plays a prominent role in acute and chronic skin conditions, including psoriasis and atopic dermatitis, sunburn and skin cancer

• Skin cell eicosanoids are involved in many pathways underpinning these conditions

• Respiratory allergic diseases often present with skin symptoms (asthma and eczema)




• Phospholipase – key enzyme for eicosanoid production

• Activity is linked to many skin conditions including sunburn and psoriasis

• COX and LOX inflammatory pathways are highly active in skin

• Most human skin cells produce prostaglandins, thromboxanes and hydroxy fatty acids which are essential for skin cell turnover

• Free-radical damage results in lipid peroxidation and pro-inflammatory eicosanoid production

Nicolaou., 2013






Inflammatory skin conditions:

• Over 40 listed online

• Most common: atopic dermatitis (eczema) psoriasis acne rosacea

• Sunburn and skin cancer



Inflammation in specific skin conditions



Psoriasis:

• Common, chronic

• Inflammatory and proliferative

• Genetic and environmental aetiology

• Abnormal skin lipids and increased inflammatory products

• Increased: phospholipase activity eicosanoids LOX reactionsoxidative stress



Atopic dermatitis (eczema)

• Common, chronic, allergic (IgE), inflammatory

• Genetic and environmental aetiology

• Abnormal skin barrier function

• Increased: phospholipase activity COX derived inflammatory eicosanoids



Acne vulgaris

• Common, complex, inflammatory

• Increased: activated leukocytes release inflammatory mediatorsexcess sebum production by sebaceous glandsproliferation of propionobacterium acnes

• Potential role for increased IGF-1 and androgen hormones

• Sex hormones and insulin also a factor



Sunburn

• Inflammation occurs as a result of UV exposure

• COX and LOX pathways are activated resulting in increased eicosanoids

• UVB and UVA generate reactive oxygen species and oxidative stress

• Subsequently stimulates phospholipase



Skin and Fatty acids • Skin structure and function reliant on fatty acids

• Linoleic acid = 12% fatty acids in skin, AA, DHA and EPA = <5%

• Eicosanoids derived from these PUFAs are important for skin physiology and homeostasis

• PUFA metabolism is highly active in the epidermis and dietary deficiency results in scaly dry skin disorders

• Balance and ratio of PUFAs in cell membranes is heavily involved in inflammatory regulation

• AA:EPA ratio is a highly accurate marker of inflammation

Ziboh et al, 2000



Anti-inflammatory eicosanoids

Anti-inflammatory eicosanoids

Anti-inflammatory docosanoids

Inflammatoryeicosanoids

Series-3 prostaglandinsSeries-3 thromboxanesSeries-5 leukotrienesHydroxy fatty acids

Series-1 prostaglandinsSeries-1 thromboxanes

Series-2 prostaglandinsSeries-2 thromboxanesSeries-4 leukotrienesHydroxy fatty acids

Resolvins Protectins

DGLA

EPA

DHA

AA

Omega-6

Omega-3



Fatty acid intervention studiesPsoriasis



• 20 hospitalised guttate psoriasis sufferers given daily lipid emulsion enriched with EPA and DHA (23g) or omega-6

• After 10 days, symptom severity in both groups had improved • Only significant in the EPA+DHA group (45-76%) • Improvements were noted from day 4 Grimminger et al., 1993

• 9 chronic psoriasis patients were given 3.6g pure EPA (no DHA) for 3, 6 or 12 months

• Clinical improvement in skin lesions was noted at 2-3 months• EPA and DPA levels increased whilst AA and DHA remained stable• Lower AA:EPA ratio correlated with improvements in inflammatory profile

although changes were not significant (very low participants) Kojima et al., 1991



• 1998 double blind, randomised, placebo-controlled trial including 83 patients across 8 centres

• 14 days intravenous infusion of omega-3 enriched lipid emulsion (4.2g of EPA and DHA)

• Significant improvement in psoriasis severity score versus omega-6 emulsion, as well as greater improvements in area of psoriasis, skin redness, scaling and perception of severity in investigators and patients

• A 50% or greater reduction in condition severity was achieved in 37% of the omega-3 group versus 23% in the omega-6 group

• Increased EPA levels and subsequent changes in inflammatory profile were evident after a few days with omega-3 but not omega-6 only infusion

Mayser et al., 1998



• 2 earlier RCTs showed no significant improvements in condition severity • Both used 1.8g EPA for a maximum of 12 weeks

Bjorneboe et al., 1988 and Bittiner et al., 1988

• Henneicke-von Zeplin et al., 1993 found that topical application of fish oil (15% EPA 10% DHA) versus liquid paraffin (standard topical treatment) for 4 weeks resulted in significantly greater improvements in scaling but not redness

• Dose, treatment type (oral/intravenous/topical) and length of treatment all play an important role in clinical outcome



Other nutritional considerationsPsoriasis



• Alcohol intake has been linked to increased occurrence and severity

• Body weight and metabolic syndrome may also correlate with psoriasis • Therapeutic interventions to improve metabolic comorbidities often result in

improved psoriasis severity• Likely due to anti-inflammatory actions of the drugs used

• Gluten sensitivity may predispose to psoriasis • Gluten-free diet often results in symptom resolve in subjects displaying

increased antibody response to gluten



• Antioxidant supplementation in the form of selenium, CoQ10 and vitamin E may help to reduce severity of plaques

• Selenium may only be effective in those with a low baseline selenium status

• Low vitamin A status is often noted in psoriatic cohorts • Topical or oral administration has established results • Dose is important due to potential toxicity

Ricketts et al., 2010 Review

• Ala et al, 2013 found a link between psoriasis and elevated copper levels suggesting potential need to reduce dietary and environmental copper exposure



Fatty acid intervention studiesAtopic Dermatitis (AD)



• 20 hospitalised patients were randomly assigned to receive either omega-3 (fish oil) or omega-6 (soybean oil) enriched fatty acid lipid emulsion for 10 days

• Improvements were seen in both groups but were more pronounced in the omega-3 group

• Free and bound EPA levels and membrane AA:EPA ratio markedly increased in omega-3 group, together with increased EPA lipid mediators

• Relapse post intervention was greater in omega-3 group

Mayser et al., 2002



• In an open trial, 17 patients were given either omega-3 and 6 or 3,6 and 9 in combination with vitamin C, E and zinc for 16 weeks

• Severity score improved throughout the study in both groups and was significant at 8 and 16 weeks compared to baseline

• 14 patients reported greater than 50% improvement

Eriksen and Kare, 2006



Very early studies have found:

• Low long-chain PUFA levels correlate with skin dryness, redness and abnormal cell structure

• Children given cow’s milk formula, low in PUFAs, have been shown to display skin lesions

• LA deficiency causes redness, dryness and itching – leading to skin conditions

• Decreased AA concentration is common in serum of children with atopic dermatitis

• Abnormal fatty acid profiles and poor delta-6 desaturase activity observed

• Poor conversion of LA to its metabolites has been found in several subsequent studies with GLA and AA levels particularly affected



• Numerous intervention studies show LA & GLA has positive reduction in condition severity, allergic disease and AD risk

• 2004 Meta-analysis failed to show significant benefits of GLA on AD severity but a positive association with fish oil intake was seen

• Topical application of steroids has been shown to be lower in children taking evening primrose oil versus placebo

• Oral supplementation of fish oil during pregnancy reduced severity of AD in children of AD mothers and correlated with increased EPA and DHA levels in the breast milk

• Sustained GLA and evening primrose oil may be beneficial to reduce AD incidence when taken for sustained periods

Kaczmarski et al., 2013 review



Other nutritional considerationsAtopic Dermatitis



• Studies have shown AD patients to have higher levels of oxidative stress and reduced enzymatically produced and total antioxidant levels when compared with healthy controls Sivaranjani et al., 2013

• Food allergy may correlate with symptoms of allergic disease including AD. Food sensitivities should be considered but careful replacement and not full elimination diets should be encouraged to avoid nutritional deficiency which may contribute to increased symptom severity Kim et al.,2013



• Dairy is often related to allergic illness; however, a Japanese study following over 1000 women found dairy consumption during pregnancy inversely correlated with respiratory symptoms in the offspring

• Dairy and cheese consumption during pregnancy also independently associated with reduced wheeze but only in children whose mothers consumed full fat varieties

• Although dairy and calcium intake did not correlate with eczema risk in the infant, vitamin D intake did, with those mothers consuming more than 4µg or more of vitamin D per day having children significantly less likely to develop eczema

• Correlations remained even after controlling for other nutritional factors including omega-6, vegetables, citrus fruit and beta-carotene

Miyake et al., 2010



Fatty acid intervention studiesAcne



• 13 healthy males aged 18-40 with mild to severe acne not currently using any treatment

• 12 week intervention of 930mg EPA,720mg DHA and 174g DPA in 3 capsules

• Total lesions, acne severity and redness were determined at regular intervals

• 8 participants saw improvement, 4 worsening and 1 no change in symptoms

• Despite lack of significance overall, those with the most severe symptoms showed the best improvements

• Those whose symptoms worsened were the least severe at baseline

Khayef et al., 2012



Other nutrition intervention studiesAcne



Milk:

• Total milk consumption has been linked to increased self-reported acne in a number of large cohort studies

• Low fat and total milk intake showed greater links to whole milk in case controlled studies

• Lactoferrin-enriched fermented milk may, however, benefit acne

Dietary fat:

• Frequent omega-3 consumption may be protective

• High fat and fried foods may contribute to acne development

Burris et al., 2013



Glycaemic load:

• A series of studies by Smith and colleagues (2007-08) link glycaemic load to acne

• Low glycaemic load diet improved symptoms of acne, as well as insulin sensitivity and reducing IGF activity

• Limitations due to participant heterogeneity, higher fibre and lower fat in the low GL diet

• After controlling for weight loss, changes in lesions and insulin sensitivity were not significant

• Numerous subsequent studies further support low GL diet for improved acne

• Ketogenic diets have been found to reduce inflammatory markers and IGF-1 and subsequently acne severity Paoli et al., 2012



Summary and conclusion



Studies are generally inconclusive due to:

• Low participant number

• Differing dose

• Formulation given: EPA/DHA alone, together or with omega-6

• Method of delivery – oral, intravenous, topical

• Self-reported dietary intake and symptom severity

• Lack of controls

• Non validated reference tools



• Skin disorders have a strong inflammatory aetiology

• PUFAs play a vital role in skin health and inflammatory regulation

• Low levels of PUFA intake or poor conversion correlates with symptom severity

• Dietary intervention with PUFAs shows promising results and is very well tolerated

• Dose, delivery and length of treatment is important

• AA:EPA levels correlate with symptom severity

• Restoring EPA levels and replacing poorly metabolised omega-6, specifically GLA, seems the most effective course of action



• Oxidative stress also contributes to skin disorders

• Dietary antioxidants may help attenuate skin conditions

• Severe elimination diets may not be helpful or necessary

• Consuming a healthy varied diet that controls body mass, GL and associated issues may contribute to reduced symptoms and prevalence

References

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Ala S, Shokrzadeh M, Golpour M, Salehifar E, Alami M, Ahmadi A. Zinc and copper levels in Iranian patients with psoriasis: a case control study. Biol Trace Elem Res. 2013 Jun;153(1-3):22-7. doi: 10.1007/s12011-013-9643-6. Epub 2013 Mar 14. PubMed PMID: 23483426. Kaczmarski M, Cudowska B, Sawicka-Żukowska M, Bobrus-Chociej A. Supplementation with long chain polyunsaturated fatty acids in treatment of atopic dermatitis in children. Postepy Dermatol Alergol. 2013 Apr;30(2):103-7. doi: 10.5114/pdia.2013.34160. Epub 2013 Apr 12. Review. PubMed PMID: 24278056; PubMed Central PMCID: PMC3834680. Burris J, Rietkerk W, Woolf K. Acne: the role of medical nutrition therapy. J Acad Nutr Diet. 2013 Mar;113(3):416-30. doi: 10.1016/j.jand.2012.11.016. Review. PubMed PMID: 23438493. Nicolaou A. Eicosanoids in skin inflammation. Prostaglandins Leukot Essent Fatty Acids. 2013 Jan;88(1):131-8. doi: 10.1016/j.plefa.2012.03.009. Epub 2012 Apr 21. Review. PubMed PMID: 22521864. Khayef G, Young J, Burns-Whitmore B, Spalding T. Effects of fish oil supplementation on inflammatory acne. Lipids Health Dis. 2012 Dec 3;11:165. doi: 10.1186/1476-511X-11-165. PubMed PMID: 23206895; PubMed Central PMCID: PMC3543297. De Benedetto A, Kubo A, Beck LA. Skin barrier disruption: a requirement for allergen sensitization? J Invest Dermatol. 2012 Mar;132(3 Pt 2):949-63. doi: 10.1038/jid.2011.435. Epub 2012 Jan 5. Review. PubMed PMID: 22217737; PubMed Central PMCID: PMC3279586.

http://www.ncbi.nlm.nih.gov/pubmed/24353835








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A nutritional approach to managing skin conditions