A nutritional approach to managing skin conditions

Common inflammatory ailments:
A nutritional approach to managing skin
conditions
Sophie Tully
BSc (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

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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)

UK:
• 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

UK:

UK:
Inflammatory skin conditions:
• Over 40 listed online
• Most common: atopic dermatitis (eczema)
psoriasis
acne
rosacea
• Sunburn and skin cancer

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Inflammation in specific skin conditions

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Psoriasis:
• Common, chronic
• Inflammatory and proliferative
• Genetic and environmental aetiology
• Abnormal skin lipids and increased inflammatory products
• Increased: phospholipase activity
eicosanoids
LOX reactions
oxidative stress

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Atopic dermatitis (eczema)
• Common, chronic, allergic (IgE), inflammatory
• Genetic and environmental aetiology
• Abnormal skin barrier function
• Increased: phospholipase activity
COX derived inflammatory eicosanoids

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Acne vulgaris
• Common, complex, inflammatory
• Increased: activated leukocytes release inflammatory mediators
excess sebum production by sebaceous glands
proliferation of propionobacterium acnes
• Potential role for increased IGF-1 and androgen hormones
• Sex hormones and insulin also a factor

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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

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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

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Anti-inflammatory
eicosanoids
Anti-inflammatory
eicosanoids
Anti-inflammatory
docosanoids
Inflammatory
eicosanoids
Series-3 prostaglandins
Series-3 thromboxanes
Series-5 leukotrienes
Hydroxy fatty acids
Series-4 leukotrienes
Hydroxy fatty acids
Resolvins
Protectins
DGLA
EPA
DHA
AA
Omega-6
Omega-3

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Fatty acid intervention studies
Psoriasis

UK:
• 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

UK:
• 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

UK:
• 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

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Other nutritional considerations
Psoriasis

UK:
• 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

UK:
• 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

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Atopic Dermatitis (AD)

UK:
• 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

UK:
• 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

UK:
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

UK:
• 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

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Other nutritional considerations
Atopic Dermatitis

UK:
• 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

UK:
• 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

UK:
Acne

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• 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

UK:
Other nutrition intervention studies
Acne

UK:
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

UK:
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

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Summary and conclusion

UK:
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

UK:
• 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

UK:
• 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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