(fatty acids, omega 3 [mesh] | omega-3 [all] | eicosapentaen* [all] | docosahexaen* [all]) & (skin diseases [mesh] | dermatos* [all] | dermatit* [all] | psoria* [all]) (only with abstract)

373 articles - 10.09.10

1: Clin Dermatol. 2010 Jul-Aug;28(4):440-51.

Healing fats of the skin: the structural and immunologic roles of the omega-6 and omega-3 fatty acids.

McCusker MM, Grant-Kels JM.

Department of Dermatology University of Connecticut Health Center, 263 Farmington Avenue, MC 6230, Farmington, CT 06030, USA.

Linoleic acid (18:2omega6) and alpha-linolenic acid (18:3omega3) represent the parent fats of the two main classes of polyunsaturated fatty acids: the omega-6 (n-6) and the omega-3 (n-3) fatty acids, respectively. Linoleic acid and alpha-linolenic acid both give rise to other long-chain fatty acid derivatives, including gamma-linolenic acid and arachidonic acid (omega-6 fatty acids) and docosahexaenoic acid and eicosapentaenoic acid (omega-3 fatty acids). These fatty acids are showing promise as safe adjunctive treatments for many skin disorders, including atopic dermatitis, psoriasis, acne vulgaris, systemic lupus erythematosus, nonmelanoma skin cancer, and melanoma. Their roles are diverse and include maintenance of the stratum corneum permeability barrier, maturation and differentiation of the stratum corneum, formation and secretion of lamellar bodies, inhibition of proinflammatory eicosanoids, elevation of the sunburn threshold, inhibition of proinflammatory cytokines (tumor necrosis factor-alpha, interferon-gamma, and interleukin-12), inhibition of lipoxygenase, promotion of wound healing, and promotion of apoptosis in malignant cells, including melanoma. They fulfill these functions independently and through the modulation of peroxisome proliferator-activated receptors and Toll-like receptors. Copyright 2010 Elsevier Inc. All rights reserved.

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20620762&dopt=ExternalLink

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2: Exp Biol Med (Maywood). 2010 Jul;235(7):785-95.

Genetic variants in the metabolism of omega-6 and omega-3 fatty acids: their role in the determination of nutritional requirements and chronic disease risk.

Simopoulos AP.

The Center for Genetics, Nutrition and Health, 2001 S Street NW, Washington, DC 20009, USA. cgnh@bellatlantic.net

The tissue composition of polyunsaturated fatty acids is important to health and depends on both dietary intake and metabolism controlled by genetic polymorphisms that should be taken into consideration in the determination of nutritional requirements. Therefore at the same dietary intake of linoleic acid (LA) and alpha-linolenic acid (ALA), their respective health effects may differ due to genetic differences in metabolism. Delta-5 and delta-6 desaturases, FADS1 and FADS2, respectively, influence the serum, plasma and membrane phospholipid levels of LA, ALA and long-chain polyunsaturated fatty acids during pregnancy, lactation, and may influence an infant's IQ, atopy and coronary heart disease (CHD) risk. At low intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), polymorphisms at the 5-lipoxygenase (5-LO) level increase the risk for CHD whereas polymorphisms at cyclooxgenase-2 increase the risk for prostate cancer. At high intakes of LA the risk for breast cancer increases. EPA and DHA influence gene expression. In future, intervention studies on the biological effects of LA, ALA and LC-PUFAs, and the effects of genetic variants in FADS1 and FADS2, 5-LO and cyclooxygenase-2 should be taken into consideration both in the determination of nutritional requirements and chronic disease risk. Furthermore, genome-wide association studies need to include environmental exposures and include diet in the interaction between genetic variation and disease association.

Publication Types: Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20558833&dopt=ExternalLink

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3: J Korean Med Sci. 2010 Jun;25(6):930-7. Epub 2010 May 24.

Prevention of UV-induced skin damages by 11,14,17-eicosatrienoic acid in hairless mice in vivo.

Jin XJ, Kim EJ, Oh IK, Kim YK, Park CH, Chung JH.

Department of Dermatology, Seoul Nationa University College of Medicine, Seoul, Korea.

Polyunsaturated fatty acids (PUFAs) are known to play important roles in various physiological and pathological processes. Recent studies have shown that some omega-3 (omega-3) PUFAs, such as eicosapentaenoic acid (EPA) and dodecahexaenoic acid (DHA), have protective effects on acute and chronic UV-induced changes. However, the effects of other omega-3 PUFAs including 11,14,17-eicosatrienoic acid (20:3) (ETA) on UV-induced skin damages are poorly understood. In this study, we investigated the cutaneous photoprotective effects of ETA in hairless mice in vivo. Female HR-1 hairless mice were topically treated with vehicle (ethanol:polyethylene glycol=30:70) only, 0.1% ETA, or 1% ETA once a day for 3 successive days after one time UV irradiation (200 mJ/cm(2)) on dorsal skins. Skin biopsy was carried out on the fourth day (72 hr after UV irradiation). We found that topical treatment with ETA attenuated UV-induced epidermal and dermal thickness and infiltration of inflammatory cells, and impairment of skin barrier function. In addition, ETA suppressed the expression of IL-1beta, COX-2, and MMP-13 induced by UV irradiation. Our results show that the topical application of ETA protects against UV-induced skin damage in hairless mice and suggest that ETA can be a potential agent for preventing and/or treating UV-induced inflammation and photoaging.

Publication Types: Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20514317&dopt=ExternalLink

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4: J Nutr. 2010 Jul;140(7):1302-10. Epub 2010 May 19.

Biomarkers of dietary exposure are associated with lower risk of breast fibroadenomas in Chinese women.

Dijkstra SC, Lampe JW, Ray RM, Brown R, Wu C, Li W, Chen C, King IB, Gao D, Hu Y, Shannon J, Wahala K, Thomas DB.

Public Health Sciences Division, Fred Hutchinson Research Center, Seattle, WA 98109, USA.

Fibroadenomas are the most common benign breast condition among women and account for up to 50% of all breast biopsies being performed. Although considered a benign condition, fibroadenomas utilize substantial resources for management and treatment to rule out potential malignancies. Dietary factors may influence benign fibrocystic breast conditions, but little is known of their association with fibroadenomas. We examined possible associations between a broad spectrum of circulating biomarkers of dietary intake and risk of fibroadenomas. Participants were women in a breast self-examination trial in Shanghai, China who were diagnosed with fibroadenomas (n = 258) and 1035 controls. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% CI. Isoflavone concentrations were inversely associated with risk of fibroadenomas. Adjusted OR (95% CI) for the highest versus the lowest quartile of plasma concentration were 0.36 (0.16-0.79; P-trend < 0.001) for daidzein and 0.39 (0.19-0.84; P-trend = 0.010) for genistein. We also observed inverse associations between higher percentages of the RBC (n-3) fatty acids, eicosapentaenoic acid (EPA) ([0.38 (0.19-0.77); P-trend = 0.007] and docosapentaenoic acid (DPA) [0.32 (0.15-0.70); P-trend = 0.024], and fibroadenoma risk. Circulating concentrations of carotenoids, vitamin C, retinol, and ferritin were not associated with fibroadenoma risk. The inverse associations between plasma isoflavone concentrations and RBC EPA and DPA and fibroadenoma risk suggest that higher intakes of soy foods and fatty fish may lower the risk of fibroadenomas.

Publication Types: Randomized Controlled Trial Research Support, N.I.H., Extramural Validation Studies

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20484550&dopt=ExternalLink

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5: BMC Dermatol. 2010 Apr 22;10:3.

Factors accounting for the association between anxiety and depression, and eczema: the Hordaland health study (HUSK).

Klokk M, Gotestam KG, Mykletun A.

Department of Adult Psychiatry, Aalesund Hospital, Helse Sunnmore HF, N-6026 Aalesund, Norway. ma-klokk@online.no

BACKGROUND: The association between anxiety and depression, and eczema is well known in the literature, but factors underlying this association remain unclear. Low levels of omega-3 fatty acids and female gender have been found to be associated with both depression and eczema. Somatization and health anxiety are known to be associated with anxiety and depression, further, somatization symptoms and health anxiety have also been found in several dermatological conditions. Accordingly, omega-3 fatty acid supplement, female gender, somatization and health anxiety are possible contributing factors in the association between anxiety and depression, and eczema. The aim of the study is to examine the relevance of proposed contributing factors for the association between anxiety and depression, and eczema, including, omega-3 fatty acid supplement, female gender, health anxiety and somatization. METHODS: Anxiety and depression was measured in the general population (n = 15715) employing the Hospital Anxiety and Depression Scale (HADS). Information on eczema, female gender, omega-3 fatty acid supplement, health anxiety and somatization was obtained by self-report. RESULTS: Somatization and health anxiety accounted for more than half of the association between anxiety/depression, and eczema, while the other factors examined were of minor relevance for the association of interest. CONCLUSIONS: We found no support for female gender and omega-3 fatty acid supplement as contributing factors in the association between anxiety/depression, and eczema. Somatization and health anxiety accounted for about half of the association between anxiety/depression, and eczema, somatization contributed most. The association between anxiety/depression, and eczema was insignificant after adjustment for somatization and health anxiety. Biological mechanisms underlying the mediating effect of somatization are yet to be revealed.

Publication Types: Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20412596&dopt=ExternalLink

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6: Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):237-41. Epub 2010 Apr 2.

Fatty acids and breast cancer: the role of stem cells.

Erickson KL, Hubbard NE.

Department of Cell Biology and Human Anatomy, University of California, School of Medicine, Davis, CA 95616-8643, USA. klerickson@ucdavis.edu

Studies with animal models in vivo as well as with animal and human tumor cells in vitro suggest that specific fatty acids could reduce breast tumorigenesis. The most striking dietary fatty acid studies in animal models that show promise for reduction of breast cancer risk in humans are with conjugated linoleic acids (CLA) and n-3 fatty acids. Although a number of mechanisms have been proposed, the specific target of those fatty acids is not yet known. We sought to determine whether the effects of those fatty acids on terminally differentiated tumor cell seen could be due to alteration of breast cancer stem cells. The isomers, cis9, trans11-CLA and trans10, cis12-CLA, and the n-3 fatty acids, docosahexaenoic and eicosapentaenoic, reduced the proliferation of, and had increased toxicity towards, mammary tumor initiating cells. One mechanism involved in the effect of n-3 fatty acids may be due to alteration of the profile of prostaglandins. These results indicate that select fatty acids may be useful for preventing or reducing the risk of breast cancer as they may target the tumor initiating cell. Copyright 2010 Elsevier Ltd. All rights reserved.

Publication Types: Research Support, U.S. Gov't, Non-P.H.S.

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20363115&dopt=ExternalLink

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7: Nutr Cancer. 2010 Apr;62(3):284-96.

Enhancing cytotoxic therapies for breast and prostate cancers with polyunsaturated fatty acids.

Shaikh IA, Brown I, Wahle KW, Heys SD.

Cancer Medicine Group, Division of Applied Medicine, Medical School, University of Aberdeen, Aberdeen, UK.

The role of omega-3 and omega-6 fatty acids has been extensively studied in most of the human malignancies including breast, colon, prostate, pancreas, and stomach cancers. In particular, the role of omega-3 and omega-6 fatty acids in carcinogenesis has been extensively investigated in epidemiological, laboratory cell culture studies and studies in vivo in animal. Findings from these studies suggest that omega-3 and omega-6 fatty acids are cytotoxic in different cancers and act synergistically with cytotoxic drugs. Although experimental evidence for the potential beneficial role of polyunsaturated fatty acids (PUFAs) in enhancing the effectiveness of various chemotherapeutic agents in animal models and in cell culture studies is increasing, there are only a few reports that have shown supportive evidence for linking these natural compounds with augmentation of anticancer chemotherapeutics in human trials. This review presents evidence for a commonality in the proposed molecular mechanisms of action elicited by various PUFAs believed to be responsible for their enhancement of the effectiveness of anticancer chemotherapy, specifically in breast and prostate cancers, and reviews laboratory and animal studies and few reported human clinical trials. It concludes that sufficient evidence is available to suggest that major clinical trials with these natural compounds as adjuncts to standard therapies should be undertaken as a priority.

Publication Types: Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20358465&dopt=ExternalLink

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8: Prostaglandins Leukot Essent Fatty Acids. 2010 Jul;83(1):23-9. Epub 2010 Mar 26.

Uptake of dihomo-gamma-linolenic acid by murine macrophages increases series-1 prostaglandin release following lipopolysaccharide treatment.

Kakutani S, Kawashima H, Tanaka T, Shiraishi-Tateishi A, Kiso Y.

Institute for Health Care Science, Suntory Wellness Ltd., Shimamoto, Osaka 618-8503, Japan. Saki_Kakutani@suntory.co.jp

Administration of dihomo-gamma-linolenic acid is useful for atopic dermatitis and atherosclerosis in mice; however, the metabolites of dihomo-gamma-linolenic acid have been little studied. We employed a method which enabled simultaneous analysis of nine prostaglandins using liquid chromatography-tandem mass spectrometry, and determined the concentrations of prostaglandins in the supernatants of cultures of mouse peritoneal macrophages stimulated with lipopolysaccharide after pre-incubation with dihomo-gamma-linolenic acid, arachidonic acid, or eicosapentaenoic acid. Accumulated prostaglandin concentrations from mouse macrophages with dihomo-gamma-linolenic acid uptake increased in a dihomo-gamma-linolenic acid concentration-dependent fashion. These increases were mainly due to prostaglandin D(1) and prostaglandin E(1). The order of accumulated prostaglandin concentrations was dihomo-gamma-linolenic acid>arachidonic acid>eicosapentaenoic acid in supernatants with the same concentration of polyunsaturated fatty acid. Since mouse macrophages can clearly produce series-1 prostaglandins, they must be formed in vivo. These findings suggest that the effects of dihomo-gamma-linolenic acid on diseases may be due to series-1 prostaglandins. Copyright 2010 Elsevier Ltd. All rights reserved.

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20347284&dopt=ExternalLink

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9: Rev Med Liege. 2010 Feb;65(2):98-102.

[Evaluation of the role of dietary intake in the occurrence of alopecia]

[Article in French]

El Fekih N, Kamoun H, Fazaa B, El Ati J, Zouari B, Kamoun MR, Gaigi S.

Service de Dermatologie, Hopital Charles Nicolle, Tunis, Tunisie. fekih.nadia@planet.tn

Transversal case-control study was conducted among 42 patients aged between 20 and 35 years who had diffuse alopecia. Alimentary inquiry according to the 3-day method was achieved in each case. The following nutriments were evaluated: total proteins, calcium, copper, iron, iodine, magnesium, manganese, phosphorus, potassium, selenium, zinc, omega 3 and omega 6. A control group (composed of 230 individuals), matched for age, gender and metabolic profile was established. These persons did not suffer from hair and nail disorder. The nutriments were codified according to the data of the software Food processor 8.3 version. The data were analyzed using "SPSS" 11.5 version. Comparisons of the means were performed using the Student's t test. ROC graphics allowed to determine the statistically significative limits for the comparison of both groups. On multivariate analysis, only a protein intake was directly associated to alopecia, odds ratio of 1,5 (1,06 - 2,3) p=0,02.

Publication Types: English Abstract

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20344921&dopt=ExternalLink

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10: J Am Acad Dermatol. 2010 Jul;63(1):124-41. Epub 2010 Mar 24.

Diet and acne.

Bowe WP, Joshi SS, Shalita AR.

Department of Dermatology, State University of New York Downstate Medical Center, Brooklyn, New York, USA. wpbowe@gmail.com

Historically, the relationship between diet and acne has been highly controversial. Before the 1960s, certain foods were thought to exacerbate acne. However, subsequent studies dispelled these alleged associations as myth for almost half a century. Several studies during the last decade have prompted dermatologists to revisit the potential link between diet and acne. This article critically reviews the literature and discusses how dermatologists might address diet when counseling patients with acne. Dermatologists can no longer dismiss the association between diet and acne. Compelling evidence exists that high glycemic load diets may exacerbate acne. Dairy ingestion appears to be weakly associated with acne, and the roles of omega-3 fatty acids, antioxidants, zinc, vitamin A, and dietary fiber remain to be elucidated. This study was limited by the lack of randomized controlled trials in the literature. We hope that this review will encourage others to explore the effects of diet on acne. Copyright (c) 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Publication Types: Research Support, Non-U.S. Gov't Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20338665&dopt=ExternalLink

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11: Am J Clin Nutr. 2010 May;91(5):1185-94. Epub 2010 Mar 24.

Omega-3 fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition.

Yee LD, Lester JL, Cole RM, Richardson JR, Hsu JC, Li Y, Lehman A, Belury MA, Clinton SK.

Department of Surgery, The Ohio State University, Columbus, OH, USA. lisa.yee@osumc.edu

BACKGROUND: Preclinical evidence of the preventive benefits of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) in breast cancer continues to fuel interest in the potential role of dietary fat content in reducing breast cancer risk. The dose of fish-oil/omega-3 PUFAs needed to achieve maximal target tissue effects for breast cancer prevention remains undefined. OBJECTIVE: To determine the dose effects of omega-3 fatty acids on breast adipose tissue fatty acid profiles, we conducted a study of 4 doses of omega-3 PUFAs in women at high risk of breast cancer. DESIGN: In this 6-mo randomized open-label study, 48 women with increased breast cancer risk received 1, 3, 6, or 9 capsules/d of an omega-3 PUFA supplement that provided 0.84, 2.52, 5.04, and 7.56 g docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) daily, respectively. Subjects made monthly visits, at which time pill counts were made and fasting blood samples were collected to determine fatty acid profiles; anthropometric measurements were made, breast adipose tissue samples were collected, and laboratory tests of toxicity (alanine aminotransferase, LDL cholesterol, and platelet function) were made at baseline and at 3 and 6 mo. RESULTS: All doses led to increased serum and breast adipose tissue EPA and DHA concentrations, but the response to 0.84 g DHA+EPA/d was less than the maximum possible response with > or = 2.52 g/d. Body mass index attenuated the dose response for serum tissue DHA and EPA (P = 0.015 and 0.027, respectively) and breast adipose tissue DHA (P = 0.0022) in all of the treatment groups. The incremental increase in DHA and EPA correlated inversely with baseline fat and serum values. Compliance over 6 mo was 92.9 +/- 9.2% and was unaffected by treatment arm. No severe or serious toxicities were reported. CONCLUSIONS: Daily doses up to 7.56 g DHA+EPA were well tolerated with excellent compliance in this cohort at high risk of breast cancer. Body mass index and baseline fatty acid concentrations modulated the dose-response effects of omega-3 PUFA supplements on serum EPA and DHA and breast adipose tissue DHA.

Publication Types: Randomized Controlled Trial Research Support, N.I.H., Extramural

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20335550&dopt=ExternalLink

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12: Cancer Prev Res (Phila Pa). 2010 Apr;3(4):466-77. Epub 2010 Mar 16.

Weight Loss via exercise with controlled dietary intake may affect phospholipid profile for cancer prevention in murine skin tissues.

Ouyang P, Jiang Y, Doan HM, Xie L, Vasquez D, Welti R, Su X, Lu N, Herndon B, Yang SS, Jeannotte R, Wang W.

Department of Human Nutrition, Kansas State University, Manhattan, KS 66506, USA.

Exercise has been linked to a reduced cancer risk in animal models. However, the underlying mechanisms are unclear. This study assessed the effect of exercise with dietary consideration on the phospholipid profile in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin tissues. CD-1 mice were randomly assigned to one of the three groups: ad libitum-fed sedentary control; ad libitum-fed treadmill exercise at 13.4 m/min for 60 min/d, 5 d/wk (Ex+AL); and treadmill-exercised but pair-fed with the same amount as the control (Ex+PF). After 14 weeks, Ex+PF but not Ex+AL mice showed approximately 25% decrease in both body weight and body fat when compared with the controls. Of the total 338 phospholipids determined by electrospray ionization-tandem mass spectrometry, 57 were significantly changed, and 25 species could distinguish effects of exercise and diet treatments in a stepwise discriminant analysis. A 36% to 75% decrease of phosphatidylinositol (PI) levels in Ex+PF mice occurred along with a significant reduction of PI 3-kinase in TPA-induced skin epidermis, as measured by both Western blotting and immunohistochemistry. In addition, approximately 2-fold increase of the long-chain polyunsaturated fatty acids, docosahexaenoic and docosapentaenoic acids, in phosphatidylcholines, phosphatidylethanolamines, and lysophosphatidylethanolamines was observed in the Ex+PF group. Microarray analysis indicated that the expression of fatty acid elongase-1 increased. Taken together, these data indicate that exercise with controlled dietary intake, but not exercise alone, significantly reduced body weight and body fat as well as modified the phospholipid profile, which may contribute to cancer prevention by reducing TPA-induced PI 3-kinase and by enhancing omega-3 fatty acid elongation. (c) 2010 AACR.

Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20233900&dopt=ExternalLink

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13: J Pediatr. 2010 Jun;156(6):902-6, 906.e1. Epub 2010 Mar 15.

The impact of early nutrition on incidence of allergic manifestations and common respiratory illnesses in children.

Birch EE, Khoury JC, Berseth CL, Castaneda YS, Couch JM, Bean J, Tamer R, Harris CL, Mitmesser SH, Scalabrin DM.

Retina Foundation of the Southwest, Dallas, TX, USA.

OBJECTIVE: To investigate the incidence of allergic and respiratory diseases through age 3 years in children fed docosahexaenoic acid (DHA)- and arachidonic acid (ARA)-supplemented formula during infancy. STUDY DESIGN: Children who completed randomized, double-blind studies of DHA/ARA-supplemented (0.32%-0.36%/0.64%-0.72% of total fatty acids, respectively) versus nonsupplemented (control) formulas, fed during the first year of life, were eligible. Blinded study nurses reviewed medical charts for upper respiratory infection (URI), wheezing, asthma, bronchiolitis, bronchitis, allergic rhinitis, allergic conjunctivitis, otitis media, sinusitis, atopic dermatitis (AD), and urticaria. RESULTS: From the 2 original cohorts, 89/179 children participated; 38/89 were fed DHA/ARA formula. The DHA/ARA group had significantly lower odds for developing URI (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.08-0.58), wheezing/asthma (OR, 0.32; 95% CI, 0.11-0.97), wheezing/asthma/AD (OR, 0.25; 95% CI, 0.09-0.67), or any allergy (OR, 0.28; 95% CI, 0.10-0.72). The control group had significantly shorter time to first diagnosis of URI (P = .006), wheezing/asthma (P = .03), or any allergy (P = .006). CONCLUSIONS: DHA/ARA supplementation was associated with delayed onset and reduced incidence of URIs and common allergic diseases up to 3 years of age. Copyright 2010 Mosby, Inc. All rights reserved.

Publication Types: Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20227721&dopt=ExternalLink

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14: Vet Dermatol. 2010 Feb;21(1):112-7.

Effects of polyunsaturated fatty acids on isolated canine peripheral blood mononuclear cells and cytokine expression (IL-4, IFN-gamma, TGF-beta) in healthy and atopic dogs.

Stehle ME, Hanczaruk M, Schwarz SC, Gobel TW, Mueller RS.

Clinic of Small Animal Medicine, Ludwig Maximilian University, Munich, Veterinaerstr. 13, 80539 Munich, Germany.

Polyunsaturated fatty acids (PUFA) have been used to treat dogs with atopic dermatitis but the mechanism of action has not been well understood. The aim of this study was to evaluate the in vitro influence of PUFA on canine peripheral blood mononuclear cells (PBMC). PBMC isolated from eleven dogs with atopic dermatitis and eleven healthy control dogs were stimulated with concanavalin A and Dermatophagoides farinae extract in the presence of linoleic acid (LA), gamma-linolenic acid (GLA), alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) and GLA/EPA/DHA. Subsequently, quantitative polymerase chain reaction (qPCR) for interferon (IFN)-gamma, interleukin (IL)-4 and transforming growth factor (TGF)-beta m-RNA was performed. In the presence of concanavalin A, only PBMC of healthy dogs showed a gradual reduction in proliferation index from incubation without PUFA to incubation with ALA, EPA/DHA and GLA/EPA/DHA, respectively. A similar reduction was seen in normal and in atopic dogs in the presence of D. farinae allergen after incubation with ALA, EPA/DHA and GLA/EPA/DHA. In both groups IL-4 and IFN-gamma but not TGF-beta gene transcription was upregulated, when cells were incubated with D. farinae. Allergen-induced upregulation was not influenced by incubation with PUFA. These findings suggest that PUFA are able to influence proliferation of peripheral blood mononuclear cells in healthy and atopic dogs but do not seem to influence gene transcription of IL-4, IFN-gamma and TGF-beta.

Publication Types: Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20187917&dopt=ExternalLink

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15: Bioorg Med Chem. 2010 Mar 1;18(5):1866-74. Epub 2010 Jan 25.

Characterization of anticancer properties of 2,6-diisopropylphenol-docosahexaenoate and analogues in breast cancer cells.

Harvey KA, Xu Z, Whitley P, Davisson VJ, Siddiqui RA.

Cellular Biochemistry Laboratory, Methodist Research Institute, Clarian Health Partners, Inc., 1800 N. Capital Ave., Indianapolis, IN 46202, USA.

The present study describes the characterization and evaluation of novel anticancer conjugates, 2,6-diisopropylphenol-docosahexaenoate (PP-DHA), and its analogues including 2,4-diisopropylphenol-docosahexaenoate (DIPP-DHA), 2-isopropylphenol-docosahexaenoate (IPP-DHA), 2-cyclohexanephenol-docosahexaenoate (CHP-DHA) and phenol-docosahexaenoate (P-DHA) on breast cancer cell lines. Representative breast cancer cell lines, based on estrogen alpha receptor (ER) and oncogene Her-2 expression, were used and include MDA-MB-231 (ER-negative, Her-2-negative), MCF-7 (ER-positive, Her-2-negative) AU565 (ER-negative, Her-2-positive) and MDA-MB-361 (ER-positive, Her-2-positive). The PP-DHA conjugate significantly inhibited cell growth and induced cell loss in the breast cancer cell lines similarly; however, this conjugate was not effective against normal mammary epithelial cells. The effect of various conjugates were in PP-DHA>IPP-DHA>DIPP-DHA>CHP-DHA>>P-DHA order. PP-DHA and IPP-DHA conjugates were stable in human and mouse serum. Furthermore, the non-hydrolyzable amide-linked conjugate analogues affected breast cancer cells in a manner similar to that of the ester-linked conjugates. This suggests that ester-linked PP-DHA and IPP-DHA conjugates were stable during treatment to breast cancer cells due to structural hindrance. PP-DHA did not affect PPARalpha or PPARgamma activities but its anticancer effects appear to be mediated in part though the inhibition of histone deacetylase (HDAC) activity. Further experiments are needed to confirm their molecular target and to test the effectiveness of these compounds in an in vivo model for their anticancer properties. In conclusion, these results suggest that the novel PP-DHA and IPP-DHA conjugates and their amide derivatives may be useful for the treatment of breast cancer. Copyright 2010 Elsevier Ltd. All rights reserved.

Publication Types: Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20153203&dopt=ExternalLink

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16: Clin Dermatol. 2010 Jan-Feb;28(1):57-61.

Complementary therapy for atopic dermatitis and other allergic skin diseases: facts and controversies.

Boneberger S, Rupec RA, Ruzicka T.

Department of Dermatology and Allergology, Ludwig-Maximilian-University, Frauenlobstr 9-11, 80337 Munich, Germany.

The term complementary or alternative medicine encompasses numerous diverse therapeutic concepts, ranging from as herbal medicine, diet with essential fatty acids, and probiotics, to acupuncture. The main focus of these treatment methods is inflammatory skin disease, in particular atopic dermatitis. Although integrative medicine enjoys increasing popularity, particularly in industrialized countries, clinical studies that meet the double-blind, placebo-controlled standard are rare or nonexistent. The aim of this contribution is to provide the various concepts of integrative medicine. Copyright 2010 Elsevier Inc. All rights reserved.

Publication Types: Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20082952&dopt=ExternalLink

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17: Int J Pharm. 2010 Mar 15;387(1-2):161-6. Epub 2009 Dec 16.

In vitro delivery of anti-breast cancer agents directly via the mammary papilla (nipple).

Lee LM, Davison Z, Heard CM.

Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, Wales, UK.

The objective of this study was to investigate, in vitro, the plausibility of a novel method for delivering a combination of anti-breast cancer agents to the breast via the mammary papilla (nipple). Mammary papillae were prepared from freshly excised strips of porcine sow breasts by blunt dissection. Permeation studies were performed using all glass Franz diffusion cells in both upright and lateral position, with drugs examined individually and in combination. Donor phase was comprised of equimolar PD98059, LY294002 and tamoxifen; 2.54x10(-4) mol dissolved in 950 microL fish oil (containing approximately 23% (w/v) eicosapentaenoic acid, EPA), 25 microL DMSO and 25 microL 1,8-cineole. Also, 4 or 10% Cabosil M5P (w/v) was added to thicken the formulation. After 6 h, the papillae were recovered, cleaned, centrifuged and extracted thrice with methanol. Pooled extracts were analysed by reversed-phase HPLC. The significance of the papilla orientation was also investigated. When applied singly and laterally, the amount extracted from the porcine breast tissue for PD98059, LY294002 and tamoxifen were 1.83+/-0.30, 10.67+/-1.78 and 0.74+/-0.19x10(-2) micromol g(-1) respectively; applied simultaneously and laterally, 2.03+/-0.14, 4.86+/-0.47 and 0.22+/-0.04x10(-2) micromol g(-1) respectively. With 4% Cabosil formulation, amount extracted for PD98059 and LY294002 were 5.71+/-0.95 and 9.91+/-0.92x10(-2) micromol g(-1) respectively; with 10% formulation, 2.64+/-0.5 and 3.90+/-0.78x10(-2) micromol g(-1) respectively. Tamoxifen was below its limit of detection in both Cabosil M5P formulations. To conclude, localized passive delivery via the mammary papilla is a plausible non-invasive means of delivering anti-breast cancer drugs directly to the breast, in levels that have previously been shown to markedly inhibit the growth of breast cancer cell lines, in vitro. The amounts deliverable may be influenced by differential interactions with the thickening agent and patient orientation. 2009 Elsevier B.V. All rights reserved.

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20025946&dopt=ExternalLink

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18: Clin Rev Allergy Immunol. 2009 Dec 9; [Epub ahead of print]

Atopy Risk in Infants and Children in Relation to Early Exposure to Fish, Oily Fish, or Long-Chain Omega-3 Fatty Acids: A Systematic Review.

Kremmyda LS, Vlachava M, Noakes PS, Diaper ND, Miles EA, Calder PC.

Institute of Human Nutrition and Institute of Developmental Sciences, School of Medicine, University of Southampton, IDS Building, MP887 Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK.

There are two main families of polyunsaturated fatty acids (PUFAs), the n-6 and the n-3 families. It has been suggested that there is a causal relationship between n-6 PUFA intake and allergic disease, and there are biologically plausible mechanisms, involving eicosanoid mediators of the n-6 PUFA arachidonic acid, that could explain this. Fish and fish oils are sources of long-chain n-3 PUFAs and these fatty acids act to oppose the actions of n-6 PUFAs. Thus, it is considered that n-3 PUFAs will protect against atopic sensitization and against the clinical manifestations of atopy. Evidence to examine this has been acquired from epidemiologic studies investigating associations between fish intake in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children and from intervention studies with fish oil supplements in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children. All five epidemiological studies investigating the effect of maternal fish intake during pregnancy on atopic or allergic outcomes in infants/children of those pregnancies concluded protective associations. One study investigating the effects of maternal fish intake during lactation did not observe any significant associations. The evidence from epidemiological studies investigating the effects of fish intake during infancy and childhood on atopic outcomes in those infants or children is inconsistent, although the majority of the studies (nine of 14) showed a protective effect of fish intake during infancy or childhood on atopic outcomes in those infants/children. Fish oil supplementation during pregnancy and lactation or during infancy or childhood results in a higher n-3 PUFA status in the infants or children. Fish oil provision to pregnant women is associated with immunologic changes in cord blood and such changes may persist. Studies performed to date indicate that provision of fish oil during pregnancy may reduce sensitization to common food allergens and reduce prevalence and severity of atopic dermatitis in the first year of life, with a possible persistence until adolescence with a reduction in eczema, hay fever, and asthma. Fish oil provision to infants or children may be associated with immunologic changes in the blood but it is not clear if these are of clinical significance and whether they persist. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, but this benefit may not persist as other factors come into play. It is not clear whether fish oil can be used to treat children with asthma as the two studies conducted to date give divergent results. Further studies of increased long-chain n-3 PUFA provision in during pregnancy, lactation, and infancy are needed to more clearly identify the immunologic and clinical effects in infants and children and to identify protective and therapeutic effects and their persistence.

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19997989&dopt=ExternalLink

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19: Carcinogenesis. 2010 Mar;31(3):489-95. Epub 2009 Dec 7.

Dietary omega-3 polyunsaturated fatty acids suppress expression of EZH2 in breast cancer cells.

Dimri M, Bommi PV, Sahasrabuddhe AA, Khandekar JD, Dimri GP.

Department of Medicine, NorthShore University HealthSystem Research Institute, 1001 University Place, Evanston, IL 60201, USA.

The polycomb group (PcG) protein, enhancer of zeste homologue 2 (EZH2), is overexpressed in several human malignancies including breast cancer. Aberrant expression of EZH2 has been associated with metastasis and poor prognosis in cancer patients. Despite the clear role of EZH2 in oncogenesis and therapy failure, not much is known about chemotherapeutics and chemopreventive agents that can suppress its expression and activity. Here, we show that dietary omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) can regulate the expression of EZH2 in breast cancer cells. The treatment of breast cancer cells with omega-3 PUFAs, but not omega-6 PUFAs, led to downregulation of EZH2. Studies using proteosome inhibitor MG132 suggested that omega-3 PUFAs induce degradation of the PcG protein EZH2 through posttranslational mechanisms. Furthermore, downregulation of EZH2 by omega-3 PUFAs was accompanied by a decrease in histone 3 lysine 27 trimethylation (H3K27me3) activity of EZH2 and upregulation of E-cadherin and insulin-like growth factor binding protein 3, which are known targets of EZH2. Treatment with omega-3 PUFAs also led to decrease in invasion of breast cancer cells, an oncogenic phenotype that is known to be associated with EZH2. Thus, our studies suggest that the PcG protein EZH2 is an important target of omega-3 PUFAs and that downregulation of EZH2 may be involved in the mediation of anti-oncogenic and chemopreventive effects of omega-3 PUFAs.

Publication Types: Research Support, N.I.H., Extramural

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19969553&dopt=ExternalLink

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20: Br J Cancer. 2009 Dec 15;101(12):1978-85. Epub 2009 Nov 17.

Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial.

Bougnoux P, Hajjaji N, Ferrasson MN, Giraudeau B, Couet C, Le Floch O.

INSERM U921 Nutrition, Croissance et Cancer, Tours, France. bougnoux@med.univ-tours.fr

BACKGROUND: Breast cancer becomes lethal when visceral metastases develop. At this stage, anti-cancer treatments aim at relieving symptoms and delaying death without resulting in additional toxicity. On the basis of their differential anti-oxidant defence level, tumour cells can be made more sensitive to chemotherapy than non-tumour cells when membrane lipids are enriched with docosahexaenoic acid (DHA), a peroxidisable and oxidative-stress-inducing lipid of marine origin. METHODS: This open-label single-arm phase II study evaluated the safety and efficacy (response rate), as primary end points, of the addition of 1.8 g DHA daily to an anthracycline-based chemotherapy (FEC) regimen in breast cancer patients (n = 25) with rapidly progressing visceral metastases. The secondary end points were time to progression (TTP) and overall survival (OS). RESULTS: The objective response rate was 44%. With a mean follow-up time of 31 months (range 2-96 months), the median TTP was 6 months. Median OS was 22 months and reached 34 months in the sub-population of patients (n = 12) with the highest plasma DHA incorporation. The most common grade 3 or 4 toxicity was neutropaenia (80%). CONCLUSION: DHA during chemotherapy was devoid of adverse side effects and can improve the outcome of chemotherapy when highly incorporated. DHA has a potential to specifically chemosensitise tumours.

Publication Types: Clinical Trial, Phase II Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19920822&dopt=ExternalLink

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