Recently, the prevalence of atopic dermatitis has increased drastically, especially in urban populations. This multifactorial skin disease is caused by complex interactions between various factors including genetics, environment, lifestyle, and diet. In eczema, apart from using an elimination diet, the adequate content of fatty acids from foods (saturated, monounsaturated, and polyunsaturated fatty acids) plays an important role as an immunomodulatory agent. Different aspects regarding atopic dermatitis include connections between lipid metabolism in atopic dermatitis, with the importance of the MUFA levels, as well as of the omega-6/omega-3 balance that affects the formation of long-chain (C20 eicosanoic and C22 docosaenoic) fatty acids and bioactive lipids from them (such as prostaglandins). Impair/repair of the functioning of epidermal barrier is influenced by these fatty acid levels. The purpose of this review is to drive attention to membrane fatty acid composition and its involvement as the target of fatty acid supplementation. The membrane-targeted strategy indicates the future direction for dermatological research regarding the use of nutritional synergies, in particular using red blood cell fatty acid profiles as a tool for checking the effects of supplementations to reach the target and influence the inflammatory/anti-inflammatory balance of lipid mediators. This knowledge gives the opportunity to develop personalized strategies to create a healthy balance by nutrition with an anti-inflammatory outcome in skin disorders.

Antioxidant activity and the oxidative stability were investigated in flax, sesame, silybum oils and oils with different omega-6/omega-3 fatty acid ratio. The content of antioxidants (AO) in crude oils and their reactivity towards peroxyl radicals were studied using kinetic method for addition of oil in a model reaction of cumol oxidation. There were correlations between PUFA/omega-9 and thermal stability (50 degrees C); between gamma-tocopherol content and resistantance to oxidative changes after storage at (10 +/- 2) degrees C for 6 months.

Twenty-nine dogs were included in a double-blinded, placebo-controlled, randomised trial and were orally supplemented for 10 weeks with either flax oil (200 mg/kg/day), eicosapentaenoic acid (50 mg/kg/day) and docosahexaenoic acid (35 mg/kg/day) in a commercial preparation, or mineral oil as a placebo. For each dog, clinical scores were determined based on a scoring system developed prior to the trial. Total omega-6 and omega-3 intake and the ratio of omega-6:omega-3 (omega-6:3) were calculated before and after the trial. The dogs' clinical scores improved in those supplemented with flax oil and the commercial preparation, but not in the placebo group. No correlation was identified between total fatty acid intake or omega-6:3 ratio and clinical scores. Based on the results of this study, the total intake of fatty acids or the omega-6:3 ratio do not seem to be the main factors in determining the clinical response.

The Workshop document is welcome and important in its content and objectives. My comments deal with three topics, and are intended to set the historical perspective and take the discussion further as regards attitudes to infant nutrition. 1. ADVERSE ARACHIDONIC EFFECTS. I have some difficulty with the statement on the need to reduce LA (linoleic acid) content of the diet because 'This is necessary to reduce adverse effects of excesses of arachidonic acid and its eicosanoid products.'I have no problem with suggesting a reduction in the present level of LA in the USA but consider the expression 'adverse effects of arachidonic acid ...' to be misleading. Linking LA and AA in this way also implies a direct conversion of LA to AA, which is not the case. In fact, a very high dietary LA will reduce membrane AA. 2. EFA RATIOS. I suspect that their choice of omega 3/omega 6 ratio of 5.7 for early life may be high. Their recommendation for adults gives the much lower ratio of about 1.4. In view of the high requirement for DHA during neural development, I would have thought the ratios would have been the other way round or the same for infants as adults but with AA included in the omega 6. Also, I have some difficulty with the concept of a unitary ratio when there is clear disunity in the biological activities of the different parent and LCP EFAs. Hence the concept of omega 6/omega 3 ratio based on activity equality does not reflect the biological reality. 3. FDA RECOMMENDATIONS ON INFANT FORMULA. The Workshop essentially disagrees with the recent FDA recommendations on inclusion of LCPs in infant formula. There is, in addition, a need to re-think the requirements of the preterm infant beyond their recommendation.

To evaluate the influence of omega-6/omega-3 poly unsaturated fatty acid (PUFA) containing oils on lipid profile and endogenous antioxidant enzymes in normal and stressed (immobilization) rats, 28 day old male Wistar rats were fed for 45 days with fat enriched special diet (10% fat) prepared with sunflower oil (SO)--omega-6 rich, mustard oil (MO)--omega-3 rich and groundnut oil--control respectively. SO treated normal rats have significantly reduced total cholesterol, high density lipoprotein-cholesterol (HDL-C) and catalase thereby significantly increased the atherogenic index (AI) and lipid peroxidation (LPO). However, treatment with MO increased superoxide dismutase; decreased LPO significantly. Under stress conditions AI and LPO were significantly high with SO and significantly less with MO. In addition, SO decreased HDL-C whereas MO decreased non-HDL-C significantly. Results suggest a protective role against AI and LPO in normal and stress conditions in MO. The quantity of omega-3 fatty acids in dietary oil may play a crucial role in the body against atherogenicity. The findings signify that not just PUFA, but type of PUFA present in dietary oil used is important.

The typical Western dietary pattern has an elevated ω-6:ω-3 fatty acid ratio (FAR), which may exacerbate the risk of chronic disease. Conversely, the consumption of diets containing green leafy vegetables (GLVs) have been demonstrated to attenuate disease risk. This study investigated the effects of collard greens (CG), purslane (PL) and orange flesh sweetpotato greens (SPG) on measures of disease risk in rats fed diets with a 25:1 ω-6:ω-3 FAR. Male spontaneously hypertensive rats (SHRs) were randomly assigned to four dietary groups ( = 10/group) with a 25:1 ω-6:ω-3 FAR. Experimental diets contained 4% (dried weight) CG, PL or SPG. Dietary intake, body weight, blood pressure, plasma adiponectin, high sensitivity C-reactive protein (hsCRP), oxygen radical absorbance capacity and lipid profile were determined using standardized procedures. Following a 6-week consumption period, systolic blood pressure, plasma adiponectin, total and low-density lipoprotein (LDL) cholesterol decreased following the consumption of diets containing GLVs. While hsCRP increased in SHRs fed diets containing CG and PL, plasma antioxidant capacity was significantly reduced ( < 0.05) with the consumption of diets containing the GLVs. These findings suggest that CG, PL and SPG have the potential to decrease risks for cardiovascular disease (CVD) associated with the consumption of diets with an elevated ω-6:ω-3 FAR.

Anthropological and epidemiological studies and studies at the molecular level indicate that human beings evolved on a diet with a ratio of omega-6 to omega-3 essential fatty acids (EFA) of approximately 1 whereas in Western diets the ratio is 15/1 to 16.7/1. A high omega-6/omega-3 ratio, as is found in today's Western diets, promotes the pathogenesis of many diseases, including cardiovascular disease, cancer, osteoporosis, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 polyunsaturated fatty acids (PUFA) (a lower omega-6/omega-3 ratio), exert suppressive effects. Increased dietary intake of linoleic acid (LA) leads to oxidation of low-density lipoprotein (LDL), platelet aggregation, and interferes with the incorporation of EFA in cell membrane phospholipids. Both omega-6 and omega-3 fatty acids influence gene expression. Omega-3 fatty acids have anti-inflammatory effects, suppress interleukin 1beta (IL-1beta), tumor necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6), whereas omega-6 fatty acids do not. Because inflammation is at the base of many chronic diseases, dietary intake of omega-3 fatty acids plays an important role in the manifestation of disease, particularly in persons with genetic variation, as for example in individuals with genetic variants at the 5-lipoxygenase (5-LO). Carotid intima media thickness (IMT) taken as a marker of the atherosclerotic burden is significantly increased, by 80%, in the variant group compared to carriers with the common allele, suggesting increased 5-LO promoter activity associated with the (variant) allele. Dietary arachidonic acid (AA) and LA increase the risk for cardiovascular disease in those with the variants, whereas dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decrease the risk. A lower ratio of omega-6/omega-3 fatty acids is needed for the prevention and management of chronic diseases. Because of genetic variation, the optimal omega-6/omega-3 fatty acid ratio would vary with the disease under consideration.

Several sources of information suggest that human beings evolved on a diet with a ratio of omega-6 to omega-3 essential fatty acids (EFA) of approximately 1 whereas in Western diets the ratio is 15/1-16.7/1. Western diets are deficient in omega-3 fatty acids, and have excessive amounts of omega-6 fatty acids compared with the diet on which human beings evolved and their genetic patterns were established. Excessive amounts of omega-6 polyunsaturated fatty acids (PUFA) and a very high omega-6/omega-3 ratio, as is found in today's Western diets, promote the pathogenesis of many diseases, including cardiovascular disease, cancer, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 PUFA (a lower omega-6/omega-3 ratio), exert suppressive effects. In the secondary prevention of cardiovascular disease, a ratio of 4/1 was associated with a 70% decrease in total mortality. A ratio of 2.5/1 reduced rectal cell proliferation in patients with colorectal cancer, whereas a ratio of 4/1 with the same amount of omega-3 PUFA had no effect. The lower omega-6/omega-3 ratio in women with breast cancer was associated with decreased risk. A ratio of 2-3/1 suppressed inflammation in patients with rheumatoid arthritis, and a ratio of 5/1 had a beneficial effect on patients with asthma, whereas a ratio of 10/1 had adverse consequences. These studies indicate that the optimal ratio may vary with the disease under consideration. This is consistent with the fact that chronic diseases are multigenic and multifactorial. Therefore, it is quite possible that the therapeutic dose of omega-3 fatty acids will depend on the degree of severity of disease resulting from the genetic predisposition. A lower ratio of omega-6/omega-3 fatty acids is more desirable in reducing the risk of many of the chronic diseases of high prevalence in Western societies, as well as in the developing countries.

Up until about 100 years ago, the omega-6/3 ratio has been around 4:1 or less. However, the typical Western diet now provides an omega-6/3 ratio of approximately 20:1 in favor of omega-6. This predisposes to supraphysiologic inflammatory responses and perpetuates chronic low-grade inflammation. The overconsumption of linoleic acid, mainly from industrial omega-6 seed oils, and the lack of long-chain omega-3s in the diet creates a pro-inflammatory, pro-allergic, pro-thrombotic state. Reducing the omega-6/3 ratio, particularly through reductions in the intake of refined omega-6 seed oil, and increasing the intake of marine omega-3s, either through dietary means or supplementation, may be an effective strategy for reducing inflammation, allergies, and autoimmune reactions.