Chronic Immune Disorders

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  • Impact of fish oil on TNF influenced by genetic polymorphisms

Grimble RF, Howell WM, et al. The ability of fish oil to suppress tumor necrosis factor production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumor necrosis factor production.

Background:
Tumor necrosis factor (TNF-) mediates inflammation. High TNF- production has adverse effects during disease. Polymorphisms in the TNF- and lymphotoxin genes influence TNF- production. Fish oil suppresses TNF- production and has variable antiinflammatory effects on disease.

Objective:
We examined the relation between TNF- and lymphotoxin genotypes and the ability of dietary fish oil to suppress TNF- production by peripheral blood mononuclear cells (PBMCs) in healthy men.

Design:
Polymorphisms in the TNF- (TNF*1 and TNF*2) and lymphotoxin (TNFB*1 and TNFB*2) genes were determined in 111 healthy young men. TNF- production by endotoxin-stimulated PBMCs was measured before and 12 wk after dietary supplementation with fish oil (6 g/d).
Results:
Homozygosity for TNFB*2 was 2.5 times more frequent in the highest than in the lowest tertile of inherent TNF- production. The percentage of subjects in whom fish oil suppressed TNF- production was lowest (22%) in the lowest tertile and doubled with each ascending tertile.
In the highest and lowest tertiles, mean TNF- production decreased by 43% (P < 0.05) and increased by 160% (P < 0.05), respectively. In the lowest tertile of TNF- production, only TNFB*1/TNFB*2 heterozygous subjects were responsive to the suppressive effect of fish oil.
In the middle tertile, this genotype was 6 times more frequent than the other lymphotoxin genotypes among responsive individuals. In the highest tertile, responsiveness to fish oil appeared unrelated to lymphotoxin genotype.

Conclusion:
The ability of fish oil to decrease TNF- production is influenced by inherent TNF- production and by polymorphisms in the TNF- and lymphotoxin genes.

  • EPA has greater effects on innate immune function in older men

Rees D, Miles EA, Banerjee T, et al. Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men. Am J Clin Nutr, 2006;83(2):331-342.

Background:
Increasing intakes of long-chain n?3 polyunsaturated fatty acids (PUFAs) can decrease markers of immunity. However, dose- and age-related responses have not been identified.

Objective:
The objective was to determine the effects of different amounts of eicosapentaenoic acid (EPA) on innate immune outcomes in young and older males.

Design:
In a controlled, double-blind study, healthy young and older men consumed 1 of 4 supplements provided as capsules: placebo (corn oil) or different amounts of an oil providing 1.35, 2.7, or 4.05 g EPA/d for 12 wk. Blood samples were collected at baseline and after 12 wk.

Results:
EPA was incorporated in a linear dose-response fashion into plasma and mononuclear cell (MNC) phospholipids; incorporation was greater in the older men.
EPA treatment did not alter neutrophil or monocyte phagocytosis, monocyte respiratory burst, or the production of inflammatory cytokines by MNCs in the young or older men. EPA treatment caused a dose-dependent decrease in neutrophil respiratory burst only in the older men.
Increased incorporation of EPA into plasma or MNC phospholipids was associated with decreased production of prostaglandin E2 by MNCs from both young and older men.

Conclusions:
Older subjects incorporate EPA into plasma and MNC phospholipids more readily than do younger subjects. Other than prostaglandin E2 production, innate immune responses in young subjects are not affected by an EPA intake of 4.05 g/d.

Older subjects are more sensitive to the immunologic effects of EPA, and the neutrophil respiratory burst is lower at higher EPA intakes.

  • Fish oil plus antioxidants shown to favorably modulate inflammatory markers in individuals with crohn's

Trebble TM, Arden NK, Wootton SA et al. Fish oil and antioxidants alter the composition and function of circulating mononuclear cells in Crohn disease. Am J Clinical Nutrition, 2004; 80 (5):1137-1144.

Background:
Crohn disease (CD) is associated with osteoporosis and other extraintestinal manifestations that might be mediated by cytokines from circulating (peripheral blood) mononuclear cells (PBMCs).
Fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduces disease activity in patients with CD with raised laboratory markers of inflammation and in healthy subjects alters PBMC function.

Objective:
We investigated the effect of fish oil plus antioxidants on cytokine production by PBMCs from patients with CD with raised C-reactive protein concentrations (6.9 mg/L) or erythrocyte sedimentation rates (18 mm/h).

Design:
A randomized placebo-controlled trial of fish oil (2.7 g EPA and DHA/d; n = 31) or placebo (olive oil; n = 31) for 24 wk was conducted in patients with CD. The fish-oil group additionally received an antioxidant preparation (vitamins A, C, and E and selenium).
Exclusion criteria included corticosteroid use. Fatty acid composition was measured by gas chromatography.
Production of tumor necrosis factor , interferon (IFN-gamma), and prostaglandin E2 (PGE2) was measured by enzyme-linked immunosorbent assays after stimulation with mitogen and endotoxin (lipopolysaccharide).

Results:
Fish-oil plus antioxidant dietary supplementation was associated with higher EPA and DHA incorporation into PBMCs (P < 0.001) and lower arachidonic acid (P = 0.006) and lower production of IFN-gamma by mitogen-stimulated PBMCs (P = 0.012) and of PGE2 by lipopolysaccharide-stimulated PBMCs (P = 0.047).

Conclusion:
Dietary supplementation with fish oil plus antioxidants is associated with modified PBMC composition and lower production of PGE2 and IFN-gamma by circulating monocytes or macrophages. The response of extraintestinal manifestations of CD should be investigated in a randomized controlled trial.

  • Fish oil supplementation helps reduce inflammation, helps immune response

Trebble T, Wootton S, et al. Prostaglandin E2 production and T cell function after fish-oil supplementation: response to antioxidant co-supplementation. Am J Clin Nutr 2003;78(3):376-382

Background: Prostaglandin E2 (PGE2) inhibits lymphocyte proliferation and the production of interferon-gamma (IFN-gamma) by peripheral blood mononuclear cells, but the effect of PGE2 on interleukin 4 (IL-4) production is unclear.

Fish oil, which contains eicosapentaenoic and docosahexaenoic acids, inhibits production of PGE2. The effects of fish oil on lymphocyte proliferation and production of IFN-gamma and IL-4 are unclear and may be influenced by the availability of antioxidants.

Objective: We investigated the effect of dietary fish oil with and without antioxidant cosupplementation on lymphocyte proliferation and the production of PGE2, IFN-gamma, and IL-4 by peripheral blood mononuclear cells.

Design: Sixteen healthy men received dietary fish-oil supplements providing 0.3, 1, and 2 g eicosapentaenoic acid plus docosahexaenoic acid/d for 4 consecutive weeks each (total of 12 wk). All subjects were randomly assigned to daily cosupplementation with either antioxidants (200 µg Se, 3 mg Mn, 30 mg RRR-alph-tocopheryl succinate, 90 mg ascorbic acid, 450 µg vitamin A) or placebo.

Results: Fish-oil supplementation decreased PGE2 production and increased IFN-gamma production and lymphocyte proliferation from baseline values. Cosupplementation with antioxidants did not affect cytokine production or lymphocyte proliferation.

Conclusion: Dietary fish oil modulates production of IFN-gamma and lymphocyte proliferation in a manner consistent with decreased production of PGE2, but this effect is not modified by antioxidant cosupplementation.

  • Multifaceted and beneficial role of EPA and DHA in inflammation

Calder P. n-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clinical Nutr, 2006;83(6):S1505-1519S.

Inflammation is part of the normal host response to infection and injury. However, excessive or inappropriate inflammation contributes to a range of acute and chronic human diseases and is characterized by the production of inflammatory cytokines, arachidonic acid-derived eicosanoids (prostaglandins, thromboxanes, leukotrienes, and other oxidized derivatives), other inflammatory agents (eg, reactive oxygen species), and adhesion molecules.

At sufficiently high intakes, long-chain n-3 polyunsaturated fatty acids (PUFAs), as found in oily fish and fish oils, decrease the production of inflammatory eicosanoids, cytokines, and reactive oxygen species and the expression of adhesion molecules.
Long-chain n-3 PUFAs act both directly (eg, by replacing arachidonic acid as an eicosanoid substrate and inhibiting arachidonic acid metabolism) and indirectly (eg, by altering the expression of inflammatory genes through effects on transcription factor activation).
Long-chain n-3 PUFAs also give rise to a family of antiinflammatory mediators termed resolvins.

Thus, n-3 PUFAs are potentially potent antiinflammatory agents.

As such, they may be of therapeutic use in a variety of acute and chronic inflammatory settings. Evidence of their clinical efficacy is reasonably strong in some settings (eg, in rheumatoid arthritis) but is weak in others (eg, in inflammatory bowel diseases and asthma). More, better designed, and larger trials are required to assess the therapeutic potential of long-chain n-3 PUFAs in inflammatory diseases.

The precursor n-3 PUFA -linolenic acid does not appear to exert antiinflammatory effects at achievable intakes.

  • Polyunsaturated fatty acids and anti-infammation in monocyte THP-1 cells

Zhao G, Etherton TD, Martin KR, et al. Anti-inflammatory effects of polyunsaturated fatty acids in THP-1 cells. Biochem Biophys Res Commun, 2005; 336(3): 909-917.

Medline Abstract

The effects of linoleic acid (LA), alpha-linolenic acid (ALA), and docosahexaenoic acid (DHA) were compared to that of palmitic acid (PA), on inflammatory responses in human monocytic THP-1 cells.

When cells were pre-incubated with fatty acids for 2-h and then stimulated with lipopolysaccharide for 24-h in the presence of fatty acids, secretion of interleukin (IL)-6, IL-1beta, and tumor necrosis factor-alpha (TNFalpha) was significantly decreased after treatment with LA, ALA, and DHA versus PA (P < 0.01 for all); ALA and DHA elicited more favorable effects. These effects were comparable to those for 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2) and were dose-dependent.

In addition, LA, ALA, and DHA decreased IL-6, IL-1beta, and TNFalpha gene expression (P < 0.05 for all) and nuclear factor (NF)-kappaB DNA-binding activity, whereas peroxisome proliferator-activated receptor-gamma (PPARgamma) DNA-binding activity was increased.

The results indicate that the anti-inflammatory effects of polyunsaturated fatty acids may be, in part, due to the inhibition of NF-kappaB activation via activation of PPARgamma.

  • Psoriasis and inflammation - omega-3s from fish oil are beneficial

Wolters M. Diet and psoriasis: experimental data and clinical evidence. British Journal of Dermatology, 2005.

Psoriasis is considered as a T-cell-mediated inflammatory skin disease which is characterized by hyperproliferation and poor differentiation of epidermal keratinocytes.

While susceptibility to psoriasis is inherited, the disease is influenced by environmental factors such as infections and stress.

Diet has been suggested to play a role in the aetiology and pathogenesis of psoriasis. Fasting periods, low-energy diets and vegetarian diets improved psoriasis symptoms in some studies, and diets rich in n-3 polyunsaturated fatty acids from fish oil also showed beneficial effects.

All these diets modify the polyunsaturated fatty acid metabolism and influence the eicosanoid profile, so that inflammatory processes are suppressed.

Some patients with psoriasis show an elevated sensitivity to gluten. In patients with IgA and/or IgG antigliadin antibodies the symptoms have been shown to improve on a gluten-free diet.

The active form of vitamin D, 1,25-dihydroxyvitamin D3, exhibits antiproliferative and immunoregulatory effects via the vitamin D receptor, and thus is successfully used in the topical treatment of psoriasis.

In this review, dietary factors which play a role in psoriasis are assessed and their potential benefit is evaluated. Furthermore, the risk of drug-nutrient interactions in psoriasis therapy is discussed.

  • Benefits of omega-3, reducing risk in breast oncology, found in animal study

Hilakivi-Clarke L, Cho E, Cabanes A, et al. Dietary Modulation of Pregnancy Estrogen Levels and Breast Cancer Risk among Female Rat Offspring. Clinical Cancer Research, 2002; 8; 3601-3610.

Purpose:
Against the hypothesis that high estrogen levels in utero increase the risk of developing breast cancer in later life are data showing that pregnancy estrogen levels are significantly higher in Asian women who have low breast cancer risk than in Caucasian women.

We investigated whether maternal dietary intake of genistein or n-3 polyunsaturated fatty acids (PUFAs), which are typical to Asian but not Caucasian diet, affect pregnancy estrogen levels and susceptibility to mammary tumorigenesis among offspring.

Experimental Design:
For that purpose, pregnant female Sprague Dawley rats were fed isocaloric AIN-93-based diets containing either at 15 mg (low), 150 mg (medium), or 300 mg (high)/kg genistein/diet or low- or high-fat (16 versus 39% energy from fat) diet composed either of n-3 PUFA menhaden fish oil or n-6 PUFA corn oil. All diets were switched to regular AIN-93 diet when pups were born.

Results:
Maternal intake of n-3 PUFA diets significantly increased pregnancy 17?estradiol (E2) levels (48% increase when compared with high n-6 PUFA diet; P < 0.0045).
High genistein exposure also increased pregnancy estrogen levels, but the increase did not reach statistical significance (P < 0.14).

The offspring of high-fat n-3 PUFA-consuming dams were significantly less likely to develop 7,12-dimethylbenz-[a]anthracene-induced mammary tumors (38% of these rats developed tumors during week 17 versus 64% of high n-6 PUFA offspring; P < 0.003).

Maternal genistein intake did not affect offspring?s tumor incidence. The mammary glands of high fat n-3 PUFA offspring contained more lobules (P < 0.07) and were thus more differentiated, whereas the glands of high genistein offspring contained more terminal end buds (P < 0.0015), which are the sites of malignant transformation.

Conclusions:
Our findings indicate that the elevated estrogen levels in the n-3 PUFA mothers were linked to reduced rather than increased breast cancer risk among their offspring, suggesting that other effects of n-3 PUFA may counteract the effects of high fetal estrogenicity on the mammary gland.

High maternal genistein intake did not reduce offspring?s breast cancer risk, and therefore high maternal soy intake in Asian women may not be associated with daughters? low breast cancer risk.

  • Fish oil supplements help reduce exercise-induced bronchoconstriction in people with asthma

Mickleborough TD, Lindley MR, Ionescu AA, Fly AD. Protective Effect of Fish Oil Supplementation on Exercise-Induced Bronchoconstriction in Asthma. Chest, 2006;129:39-49.

Background:
Previous research has demonstrated that fish oil supplementation has a protective effect on exercise-induced bronchoconstriction (EIB) in elite athletes, which may be attributed to its antiinflammatory properties.

Since EIB in asthma involves proinflammatory mediator release, it is feasible that fish oil supplementation may reduce the severity of EIB in asthmatic subjects.

Study objectives:
To determine the efficacy of fish oil supplementation on severity of EIB in subjects with asthma.

Design:
Randomized, double-blind, crossover study.

Setting:
Lung function and exercise testing in a university research laboratory.

Patients and measurements:
Sixteen asthmatic patients with documented EIB entered the study on their normal diet and then received either fish oil capsules containing 3.2 g of eicosapentaenoic acid and 2.0 g of docohexaenoic acid (fish oil diet, n = 8) or placebo capsules (placebo diet, n = 8) daily for 3 weeks.

At the beginning of the study (normal diet) and at the end of each treatment phase, the following pre-exercise and postexercise measures were assessed: (1) pulmonary function; (2) induced sputum differential cell count percentage and proinflammatory eicosanoid metabolite (leukotriene C4 [LTC4]-leukotriene E4 [LTE4] and prostaglandin D2 [PGD2]) and cytokine (interleukin [IL]-1?and tumor necrosis factor [TNF]-) concentrations; and (3) eicosanoid metabolites leukotriene B4 (LTB4) and leukotriene B5 (LTB5) generation from activated polymorphonuclear leukocytes (PMNLs).

Results:
On the normal and placebo diet, subjects exhibited EIB. However, the fish oil diet improved pulmonary function to below the diagnostic EIB threshold, with a concurrent reduction in bronchodilator use.
Induced sputum differential cell count percentage and concentrations of LTC4-LTE4, PGD2, IL-1? and TNF- were significantly reduced before and following exercise on the fish oil diet compared to the normal and placebo diets.
There was a significant reduction in LTB4 and a significant increase in LTB5 generation from activated PMNLs on the fish oil diet compared to the normal and placebo diets.

Conclusion:
Our data suggest that fish oil supplementation may represent a potentially beneficial nonpharmacologic intervention for asthmatic subjects with EIB.

  • Omega-3s and modulation of inflammation

Mori T, Beilin L. Omega-3 fatty acids and inflammation. Curr Atheroscler Rep 2004; 6(6):461-467

Dietary omega-3 (n-3) fatty acids have a variety of anti-inflammatory and immune-modulating effects that may be of relevance to atherosclerosis and its clinical manifestations of myocardial infarction, sudden death, and stroke.

The n-3 fatty acids that appear to be most potent in this respect are the long-chain polyunsaturates derived from marine oils, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and this review is restricted to these substances.

A variety of biologic effects of EPA and DHA have been demonstrated from feeding studies with fish or fish oil supplements in humans and animals. These include effects on triglycerides, high-density lipoprotein cholesterol, platelet function, endothelial and vascular function, blood pressure, cardiac excitability, measures of oxidative stress, pro- and anti-inflammatory cytokines, and immune function.

Epidemiologic studies provide evidence for a beneficial effect of n-3 fatty acids on manifestations of coronary heart disease and ischemic stroke, whereas randomized, controlled, clinical feeding trials support this, particularly with respect to sudden cardiac death in patients with established disease.

Clinically important anti-inflammatory effects in man are further suggested by trials demonstrating benefits of n-3 fatty acids in rheumatoid arthritis, psoriasis, asthma, and inflammatory bowel disorders.

Given the evidence relating progression of atherosclerosis to chronic inflammation, the n-3 fatty acids may play an important role via modulation of the inflammatory processes.

  • Benefits of fish oil in asthma and exercise-induced bronchoconstriction.

Mickleborough TD, Rundell KW. Dietary polyunsaturated fatty acids in asthma- and exercise-induced bronchoconstriction. Euro J Clinical Nutrition, 2005;59:1335?1346. doi:10.1038/sj.ejcn.1602250; published online.

Despite progress that has been made in the treatment of asthma, the prevalence and burden of this disease has continued to increase.

While pharmacological treatment of asthma is usually highly effective, medications may have significant side effects or exhibit tachyphylaxis.

Alternative therapies for treatment that reduce the dose requirements of pharmacological interventions would be beneficial, and could potentially reduce the public health burden of this disease.

Ecological and temporal data suggest that dietary factors may have a role in recent increases in the prevalence of asthma.

A possible contributing factor to the increased incidence of asthma in Western societies may be the consumption of a proinflammatory diet.

In the typical Western diet, 20- to 25-fold more omega (n)-6 polyunsaturated fatty acids (PUFA) than n-3 PUFA are consumed, which promotes the release of proinflammatory arachidonic acid metabolites (leukotrienes and prostanoids).

This review will analyze the evidence for the health effects of n-3 PUFA in asthma- and exercise-induced bronchoconstriction (EIB).

While clinical data evaluating the effect of omega-3 fatty acid supplementation in asthma has been equivocal, it has recently been shown that fish oil supplementation, rich in n-3 PUFA, reduces airway narrowing, medication use, and proinflammatory mediator generation in nonatopic elite athletes with EIB.

These findings are provocative and suggest that dietary fish oil supplementation may be a viable treatment modality and/or adjunct therapy in asthma and EIB.

  • Fish oil given to children with bronchial asthma reduced symptoms

Nagakura T, Matsuda S, Shichijyo K, et al. Dietary supplementation with fish oil rich in omega-3 polyunsaturated fatty acids in children with bronchial asthma. Eur Respir J, 2000;16:861-865.

Omega-3 polyunsaturated fatty acids have anti-inflammatory effects in vitro, and high dietary levels are associated with a lower incidence of inflammatory diseases. However, only limited effects have been demonstrated in asthma.

The effects of dietary supplementation with fish oil for 10 months in 29 children with bronchial asthma was investigated in a randomized controlled fashion. In order to minimize the effects of environmental inhaled allergens and diet, this study was performed in a long-term treatment hospital.

Subjects received fish oil capsules containing 84 mg eicosapentaenoic acid (EPA) and 36 mg docosahexaenoic acid (DHA) or control capsules containing 300 mg olive oil. The daily dosages of EPA and DHA were 17.0-26.8 and 7.3-11.5 mg x kg body weight(-1), respectively.

Asthma symptom scores decreased and responsiveness to acetylcholine decreased in the fish oil group but not in the control group. In addition, plasma EPA levels increased significantly only in the fish oil group (p<0.0088). No significant side-effects were observed.

The present results suggest that dietary supplementation with fish oil rich in the omega-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid is beneficial for children with bronchial asthma in a strictly controlled environment in terms of inhalant allergens and diet.

  • Beneficial effect of omega-3s on immune and inflammatory processes

Simopoulos A. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 2002;21(6):495-505

Abstract: Among the fatty acids, it is the omega-3 polyunsaturated fatty acids (PUFA) which possess the most potent immunomodulatory activities, and among the omega-3 PUFA, those from fish oileicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)are more biologically potent than alpha-linolenic acid (ALA).

Some of the effects of omega-3 PUFA are brought about by modulation of the amount and types of eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways, transcription factor activity and gene expression.

Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohns disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB4 produced by omega-6 fatty acids.

There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohns disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches.

Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.

  • Investigators learn more about role of fish oil in immume health, preliminary report

Zhang P, Smith R, et al. Dietary (n-3) Polyunsaturated Fatty Acids Modulate Murine Th1/Th2 Balance toward the Th2 Pole by Suppression of Th1 Development. J Nutr, 2005; 135:1745-1751

We showed that dietary long-chain (n-3) PUFAs present in fish oil (FO) affect CD4+ T cell proliferation and cytokine production in C57BL/6 mice.

To test the hypothesis that the anti-inflammatory effect of dietary (n-3) PUFAs could be due to the indirect suppression of T helper (Th)1 cells by cross-regulation of enhanced Th2 activation, mice were fed a wash-out control diet [5% corn oil (CO), (n-6) PUFA] for 1 wk, followed by the control diet or a fish oil diet [1% CO + 4% FO, (n-3) PUFA] for 2 wk.

Splenic CD4+ T cells were cultured under both neutral and Th2 polarizing conditions for 2 d. Cells were reactivated and analyzed for interleukin-4 and interferon- by intracellular cytokine staining.

Dietary fish oil significantly increased the percentage of Th2 polarized cells and suppressed Th1 cell frequency under neutral conditions. However, under Th2 polarizing conditions, although the suppression of Th1 cells was maintained in FO-fed mice, no effect was observed in Th2 cells.

Dietary fish oil increased the Th2/Th1 ratio in the presence of homologous mouse serum under both neutral (P = 0.0009) and Th2 polarizing conditions (P = 0.0185). The FO diet did not significantly affect proliferation under Th2 polarizing conditions.

Thus, the anti-inflammatory effects of FO may be explained in part by a shift in the Th1/Th2 balance, due to the direct suppression of Th1 development, and not by enhancement of the propensity of CD4+ T cells to be polarized toward a Th2 phenotype, at least in vitro.

  • News - Fish oil helping folks with MS

Fish oil can help depression in MS patients
By Jean Enersen / KING 5 News. Seattle, WA.


Patients with multiple sclerosis can suffer from serious depression. But Oregon researchers now think the best drug for these patients may not be a drug at all.

Simply putting on makeup can be difficult for Kendall Minter. She has multiple sclerosis -- a disease that causes double vision, numbness in her hand -- and also depression.

"I just get stuck in this cycle of doubt and just sadness, and I don't want to do anything about it," she said.

Minter's antidepressant doesn't work as well as she'd like, so everyday, as part of a clinical trial, she also takes six grams of fish oil.

Lynne Shinto, naturopathic researcher at Oregon Health & Science University in Portland, says the fish oils, just with MS, look promising.

People with MS have high levels of inflammation in their blood, which could cause depression.

In a pilot study, Shinto gave fish oil to ms patients to see if it could decrease those levels.

"We gave them fish oils for three months, and we looked at the same marker three months later, and we see that the levels decrease," she said.

Their inflammation levels dropped by about 50 percent.

"Then, what we did is we took them off fish oil for three months, and we looked at the same marker," Shinto said. "We see that the levels go back up, which is what we expect if they're not taking the fish oil."

Now, Shinto and colleagues are conducting another study to find out if the fish oil reduces depression and other symptoms of MS.

Minter is excited about the new study.

"I thought it couldn't hurt, so you know, if it helps, then it's a bonus," she said, and she hopes it will also be a bonus for the up to 60 percent of MS patients who suffer depression.

If you take a fish oil supplement, you should look on the label to make sure it contains no mercury or other heavy metals. Shinto says there is some evidence that fish oil can help patients with depression who don't have MS, but more research needs to be done to confirm that.

  • News - Fish oil helps reduce symptoms of Lupus



Fish oil has been found to greatly reduce the symptoms of lupus disease, offering hope to millions of sufferers with little alternative to steroid treatment.
br> At present there is no cure for lupus. Steroids are used to reduce side effects but cannot be administered long-term. Now researchers from the University of Ulster in Belfast report that a key way of managing lupus may be through diet.

Systemic Lupus Erythematosus (SLE) or lupus is a disorder of the immune system, where the body harms its own healthy cells and tissues. The body tissues become damaged causing painful or swollen joints, unexplained fever, skin rashes, kidney problems, complications to the cardiovascular system and extreme fatigue.

Fish oils contain long-chained polyunsaturated fatty acids which are essential for normal growth and development but also have anti-inflammatory and anti-autoimmune properties, noted researchers Dr Emeir Duffy, from the School of Biomedical Sciences, and Dr Gary Meenagh, from Musgrave Park Hospital, Belfast.

Dr Duffy said: "We have been investigating how fish oil can improve the quality of life for lupus sufferers. In lupus, the body?s immune system does not work as it should. Antibodies, which help fight viruses, bacteria and other foreign substances, are not produced effectively. The immune system actually produces antibodies against the body?s own healthy cells and tissues. These auto-antibodies contribute to inflammation and other symptoms of the disease."

Participants in a recent study who were taking fish oil supplements three times daily for 24 weeks, saw a reduction in disease activity, an improvement in quality of life and reported an overall feeling of improved health by the end of the study compared to those taking a placebo, reported Dr Duffy.

Participants taking the fish oil also showed a reduction in fatigue severity, the most debilitating symptom for lupus sufferers, she added.
"From our study and from other work, there is evidence that increasing dietary intake of the polyunsaturated fats found in fatty fish can have beneficial effects for lupus sufferers," concluded Dr Duffy.

Good examples of fatty fish include mackerel, lake trout, herring, sardines, tuna and salmon.

There are approximately 500 diagnosed cases of SLE in Northern Ireland and it is most common in women of child-bearing age.

Previous research has suggested that a developing foetus uses up large quantities of the mother's omega-3 and makes women more susceptible to degenerative diseases including lupus.

Source: http://www.nutraingredients.com/news/news.asp?id=6602

  • News: Doctors say fish oil supplements could help ME patients



News: Chronic fatigue syndrome or ME may be caused by a chemical imbalance in the brain, find doctors, who also suggest that taking daily fish oil supplements may help to alleviate some of the symptoms associated with the condition, reports BBC Health.
br> Chronic fatigue syndrome symptoms include muscle pain, memory loss, and severe exhaustion which can last many years and leave victims bedridden.

Dr Basant Puri and colleagues at Hammersmith Hospital in London used state-of-the-art scanning technology to assess chemical activity in the brain. Their study is published in the journal Acta Psychiatrica Scandinavica.

The doctors studied one group of eight people who had been diagnosed with the syndrome and another group of eight healthy people. The team found that the ME patients had higher levels of two key chemicals - choline and creatine - in their brains. Choline is important for controlling fat levels in brain cells while creatine provides energy.

The doctors said the findings suggested CFS patients had abnormal phospholipid metabolisms. As phospholipids are protected by certain types of fatty acids, the doctors said that fatty acid supplements could help to restore the chemical imbalance in the brain and alleviate the symptoms of CFS. EPA found in fish oil supplements, may be particularly useful, they suggested.

DR Puri said: "This study suggests that if patients with CFS take a high-EPA fatty acid supplement, then this should have a beneficial action on the chemical imbalances in the brain which we have identified."

According to the BBC, the disease affects an estimated 243,000 people of all ages in the UK.

  • Fish oil may help you live longer

Muthukumar A, Avula CP, et al. Life span is prolonged in food-restricted autoimmune-prone (NZB x NZW)F(1) mice fed a diet enriched with (n-3) fatty acids. Nutr., 2001;131(10):2753-2760.

Moderate food and/or energy (calorie) restriction delays age-related immune dysfunction and prolongs life span in multiple animal models. The amount and type of dietary fatty acids can also profoundly affect life span.
br> Marine-derived fish oils contain (n-3) fatty acids, which have potent anti-inflammatory properties. We therefore examined the influence of food restriction (40% overall reduction in intake of all dietary components) combined with substitution of fish oil for corn oil in a factorial design. Autoimmune-prone (NZB x NZW)F(1) (B/W) mice, which develop fatal autoimmune renal disease, were used.

The food-restricted/fish oil diet maximally extended median life span to 645 d (vs. 494 d for the food-restricted corn oil diet).

Similarly, fish oil prolonged life span in the ad libitum-fed mice to 345 d (vs. 242 for the ad libitum/corn oil diet). Increased life span was partially associated with decreased body weight, blunting renal proinflammatory cytokine (interferon-gamma, interleukins-10 and -12 and tumor necrosis factor-alpha) levels and lower nuclear factor-kappaB (NF-kappaB). Reductions in NF-kappaB were preceded by enhanced superoxide dismutase, catalase and glutathione peroxidase activities.

These findings demonstrate the profound additive effects of food restriction and (n-3) fatty acids in prolonging life span in B/W mice. These observations may have additional implications in the management of obesity, diabetes, cancer and/or the aging process.

  • Consuming fish oil reduces inflammation

Calder PC. Dietary modification of inflammation with lipids. Proc Nutr Soc,2002;61(3):345-358.

The n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in high proportions in oily fish and fish oils.
br> The n-3 PUFA are structurally and functionally distinct from the n-6 PUFA.

Typically, human inflammatory cells contain high proportions of the n-6 PUFA arachidonic acid and low proportions of n-3 PUFA. The significance of this difference is that arachidonic acid is the precursor of 2-series prostaglandins and 4-series leukotrienes, which are highly-active mediators of inflammation.

Feeding fish oil results in partial replacement of arachidonic acid in inflammatory cell membranes by EPA. This change leads to decreased production of arachidonic acid-derived mediators.

This response alone is a potentially beneficial anti-inflammatory effect of n-3 PUFA.

However, n-3 PUFA have a number of other effects which might occur downstream of altered eicosanoid production or might be independent of this activity.
For example, animal and human studies have shown that dietary fish oil results in suppressed production of pro-inflammatory cytokines and can decrease adhesion molecule expression. These effects occur at the level of altered gene expression. This action might come about through antagonism of the effects of arachidonic acid-derived mediators or through more direct actions on the intracellular signalling pathways which lead to activation of transcription factors such as nuclear factor kappa B (NFB).

Recent studies have shown that n-3 PUFA can down regulate the activity of the nuclear transcription factor NFB. Fish oil feeding has been shown to ameliorate the symptoms in some animal models of chronic inflammatory disease and to protect against the effects of endotoxin and similar inflammatory challenges.

Clinical studies have reported that oral fish oil supplementation has beneficial effects in rheumatoid arthritis and among some patients with asthma, supporting the idea that the n-3 PUFA in fish oil are anti-inflammatory.

There are indications that inclusion of n-3 PUFA in enteral and parenteral formulas might be beneficial to patients in intensive care or post-surgery.