114 articles - 10.09.10
1: JPEN J Parenter Enteral Nutr. 2010 Mar-Apr;34(2):151-5.
Bahadori B, Uitz E, Thonhofer R, Trummer M, Pestemer-Lach I, McCarty M, Krejs GJ.
Internal Medicine, State Hospital Muerzzuschlag, Muerzzuschlag, Austria.
BACKGROUND: The present study investigated the efficacy and safety of parenteral omega-3 fatty acids (omega-3 FA) in patients with active rheumatoid arthritis (RA). METHODS: We performed a double-blind, randomized, placebo-controlled study in 23 patients with moderate to severe RA. Patients received either 0.2 g of fish oil emulsion/kg (active) or 0.9% saline (placebo) infusion intravenously for 14 consecutive days, followed by 20 weeks of 0.05 g of fish oil/kg (active) or paraffin wax (placebo) ingested orally as capsules. A decrease in swollen and tender joint counts was the primary efficacy measure. RESULTS: At baseline, both swollen and tender joint counts were not significantly different between patients in the treatment and placebo groups. Twenty patients completed the infusion portion of the study, and 13 completed the oral portion. Swollen joint count was significantly lower in the omega-3 FA group compared with the placebo group after 1 week of infusion (P = .002) as well as after 2 weeks of infusion (P = .046). Tender joint count also tended to be lower in the omega-3 FA group, although this did not reach statistical significance. Both swollen and tender joint counts were significantly lower in the omega-3 FA group compared with the placebo group during and at the end of oral treatment. CONCLUSION: Our pilot study indicates that parenteral omega-3 FAs are well tolerated and improve clinical symptoms of RA. Subsequent oral administration of omega-3 FAs may prolong the beneficial effects of the infusion therapy. These results warrant validation in larger multicenter studies.
Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20375422&dopt=ExternalLink
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PMID: 20375422 [PubMed - indexed for MEDLINE]2: J Immunol. 2010 May 1;184(9):5280-6. Epub 2010 Apr 5.
Halade GV, Rahman MM, Bhattacharya A, Barnes JL, Chandrasekar B, Fernandes G.
Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
The therapeutic efficacy of individual components of fish oils (FOs) in various human inflammatory diseases still remains unresolved, possibly due to low levels of n-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or lower ratio of DHA to EPA. Because FO enriched with DHA (FO-DHA) or EPA (FO-EPA) has become available recently, we investigated their efficacy on survival and inflammatory kidney disease in a well-established animal model of human systemic lupus erythematosus. Results show for the first time that FO-DHA dramatically extends both the median (658 d) and maximal (848 d) life span of (NZB x NZW)F1 (B x W) mice. In contrast, FO-EPA fed mice had a median and maximal life span of approximately 384 and 500 d, respectively. Investigations into possible survival mechanisms revealed that FO-DHA (versus FO-EPA) lowers serum anti-dsDNA Abs, IgG deposition in kidneys, and proteinuria. Further, FO-DHA lowered LPS-mediated increases in serum IL-18 levels and caspase-1-dependent cleavage of pro-IL-18 to mature IL-18 in kidneys. Moreover, FO-DHA suppressed LPS-mediated PI3K, Akt, and NF-kappaB activations in kidney. These data indicate that DHA, but not EPA, is the most potent n-3 fatty acid that suppresses glomerulonephritis and extends life span of systemic lupus erythematosus-prone short-lived B x W mice, possibly via inhibition of IL-18 induction and IL-18-dependent signaling.
Publication Types: Comparative Study 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=20368275&dopt=ExternalLink
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PMID: 20368275 [PubMed - indexed for MEDLINE]3: Bangladesh Med Res Counc Bull. 2009 Aug;35(2):63-8.
Das Gupta AB, Hossain AK, Islam MH, Dey SR, Khan AL.
Department of Pharmacology, Sylhet M. A. G. Osmani Medical College, Sylhet 3100, Bangladesh.
A study was conducted to see the disease activity suppression role of omega-3 fatty acids with indomethacin in patients with rheumatoid arthritis. One group received indomethacin (75 mg) only daily while another group received indomethacin (75 mg) along with omega-3 fatty acids (3 g) daily for 12 weeks. The main outcome measures were DAS 2-28 joints score, number of swollen joints, number of tender joints, duration of morning stiffness, grip strength, pain VAS, patients global VAS, erythrocyte sedimentation rate and C-reactive protein. In terms of outcome both the groups experienced a modest improvement in disease activity after 12 weeks of treatment. However, compared to indomethacin-treated group, omega-3 plus indomethacin-treated group achieved a better improvement in terms of reducing disease activity. Physical functioning, physical role, bodily pain, general health, vitality, social functioning, grip strength, duration of morning stiffness improved significantly better in the combination group compared to indomethacin only group. The safety measures included liver and kidney function tests done didn't differ between the study groups. This study suggests that omega-3 fatty acid supplementation with indomethacin might ameliorate disease activity and be non-steroidal anti-inflammatory drugs (NSAIDs) sparing in rheumatoid arthritis.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20120782&dopt=ExternalLink
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PMID: 20120782 [PubMed - indexed for MEDLINE]4: Curr Pharm Des. 2009;15(36):4135-48.
Ruggiero C, Lattanzio F, Lauretani F, Gasperini B, Andres-Lacueva C, Cherubini A.
Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. ruggieroc07@hotmail.it
Inflammation is part of the normal host response to infection and injury. However, inappropriate inflammation contributes to several diseases, including inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Both conditions are characterized by the excessive production of inflammatory cytokines, arachidonic acid (AA)-derived eicosanoids, and other inflammatory agents (e.g., reactive oxygen species, adhesion molecules). By virtue of their anti-inflammatory action, omega-3 polyunsaturated fatty acids (PUFA) may be beneficial in inflammatory diseases. A large body of evidence supports a protective effect of omega-3 PUFA in experimental animal and ex-vivo models of Crohn's disease (CD), Ulcerative colitis (UC) and Rheumatoid arthritis (RA). Although fish oil supplementation in patients with IBD results in omega-3 PUFA incorporation into gut mucosal tissue and modification of inflammatory mediator profiles, the evidence of clinical benefits of omega-3 PUFA is weak. On the other hand, more convincing data support the efficacy of omega-3 PUFA in reducing pain, number of tender joints, duration of morning stiffness, use of non-steroidal anti-inflammatory drugs and improving physical performance in RA patients. In both IBD and RA further clinical trials with large sample size are needed to clarify the efficacy of omega-3 PUFA as a treatment.
Publication Types: Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20041815&dopt=ExternalLink
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PMID: 20041815 [PubMed - indexed for MEDLINE]5: Br J Nutr. 2009 May;101(10):1517-26. Epub 2009 Feb 27.
Dawczynski C, Schubert R, Hein G, Muller A, Eidner T, Vogelsang H, Basu S, Jahreis G.
Department of Nutritional Physiology, Institute of Nutrition, Friedrich Schiller University of Jena, Jena, Germany.
n-3 long-chain PUFA (n-3 LC-PUFA) may improve cardiovascular and inflammatory diseases. The effects of n-3 LC-PUFA-supplemented dairy products on inflammation and immunological parameters, biomarkers of oxidative stress, serum lipids, and on disease activity were determined in patients with rheumatoid arthritis (RA). Forty-five subjects (forty-three females and two males) were randomly divided into two groups in a double-blind, placebo-controlled cross-over study. Both groups received placebo or verum products consecutively for 3 months with a 2-month washout phase between the two periods. Blood samples were taken at the beginning and at the end of each period. The dairy products generally improved serum lipids by increasing HDL and lowering lipoprotein a. The n-3 LC-PUFA supplements act to lower TAG. Additionally, a decreased lipopolysaccharide-stimulated cylo-oxygenase-2 expression was found in patients who had consumed the enriched dairy products. The majority of the CD analysed were not influenced, although n-3 LC-PUFA did suppress the immune response as lymphocytes and monocytes were found to be significantly decreased. The n-3 LC-PUFA did not increase the biomarkers of oxidative stress such as 8-iso-PGF(2alpha) and 15-keto-dihydro PGF(2alpha), and DNA damage like 7,8-dihydro-8-oxo-2'-deoxyguanosine. The long-term consumption of dairy products (2 x 12 weeks) diminished the excretion of hydroxypyridinium crosslinks, and favoured the diastolic blood pressure. The consumption of moderate doses of n-3 LC-PUFA in combination with dairy products did not improve the disease activity. However, there is evidence of cardioprotective effects. Furthermore, the long-term consumption of dairy products acts against the cartilage and bone destruction in RA.
Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19245735&dopt=ExternalLink
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PMID: 19245735 [PubMed - indexed for MEDLINE]6: Prostaglandins Leukot Essent Fatty Acids. 2009 Feb-Mar;80(2-3):131-6. Epub 2009 Jan 25.
Shinto L, Marracci G, Baldauf-Wagner S, Strehlow A, Yadav V, Stuber L, Bourdette D.
Department of Neurology, Oregon Health & Science University (OHSU), 3181 SW Sam Jackson Park Road, CR120 Portland, OR 97239, USA. shintol@ohsu.edu
OBJECTIVES: The primary objective was to evaluate the effect of omega-3 fatty acids (omega-3 FA) on matrix metalloproteinase-9 (MMP-9) production by immune cells in multiple sclerosis (MS). Quality of life, fatty acid levels, and safety were also evaluated. MATERIALS AND METHODS: Ten participants with relapsing-remitting MS (RRMS) received omega-3 FA supplementation (9.6g/day fish oil) in an open-label study. Participants were evaluated at four time points, baseline, after 1 month of omega-3 FA supplementation, after 3 months of omega-3 FA supplementation, and after a 3-month wash out. RESULTS: Immune cell secretion of MMP-9 decreased by 58% after 3 months of omega-3 FA supplementation when compared with baseline levels (p<0.01). This effect was coupled with a significant increase in omega-3 FA levels in red blood cell membranes. CONCLUSIONS: Omega-3 FA significantly decreased MMP-9 levels in RRMS and may act as an immune-modulator that has potential therapeutic benefit in MS patients.
Publication Types: Clinical Trial 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=19171471&dopt=ExternalLink
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PMID: 19171471 [PubMed - indexed for MEDLINE]7: G Ital Nefrol. 2008 Nov-Dec;25 Suppl 44:83-7.
[Article in Italian]
Pozzi C.
Direttore U.O. Nefrologia e Dialisi, Ospedale E. Bassini, Cinisello Balsamo, Milano, Italy.
INTRODUCTION: About 25-50% of patients with IgA nephropathy (IgAN) progress toward end-stage renal disease (ESRD) within 25 years. Negative prognostic factors are hypertension, proteinuria >1 g/day, high values of plasma creatinine, and the extension of chronic histological lesions. METHODS AND RESULTS: Only a few studies have evaluated the effectiveness of treatment in IgAN patients with chronic renal failure (CRF) and most of these had methodological flaws. However, some studies produced interesting results. Alexopoulos and Donadio found that the progression of IgAN slowed down with the use of omega-3 fatty acids; Woo and Nakao used angiotensin inhibitors to obtain the same result, while Ballardie used immunosuppressors. Evidence of treatment efficacy in chronic histological lesions is almost completely lacking. Yoshikawa found that a two-year course of corticosteroids and azathioprine could arrest the progression of glomerular sclerosis, and Shoji obtained similar results using corticosteroids alone for one year. In 2007 we presented the results of a study that compared corticosteroids alone vs corticosteroids and azathioprine in 253 IgAN patients. In all patients, including 46 with serum creatinine >2 mg/dL, both therapy schemes appeared effective in slowing the progression towards ESRD, even if patients in the azathioprine group experienced more side effects. CONCLUSIONS: At the moment, Italian nephrologists preferably use ACE inhibitors alone or associated with corticosteroids in patients with IgAN and CRF. Recently, the Renal Immunopathology Group of the Italian Society of Nephrology (SIN) proposed a therapeutic study that would compare steroids and ACE inhibitors in patients with IgAN and CRF in order to provide more certain therapeutic indications.
Publication Types: English Abstract
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19048591&dopt=ExternalLink
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PMID: 19048591 [PubMed - indexed for MEDLINE]8: Proc Nutr Soc. 2008 Nov;67(4):409-18.
Calder PC.
Institute of Human Nutrition, School of Medicine, University of Southampton, IDS Building, MP887, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. pcc@soton.ac.uk
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease manifested by swollen and painful joints, bone erosion and functional impairment. The joint lesions are characterised by infiltration of T lymphocytes, macrophages and B lymphocytes into the synovium and by synovial inflammation involving eicosanoids, cytokines and matrix metalloproteinases. In relation to inflammatory processes, the main fatty acids of interest are the n-6 PUFA arachidonic acid, which is the precursor of inflammatory eicosanoids such as PGE2 and leukotriene B4, and the n-3 PUFA EPA and DHA, which are found in oily fish and fish oils. Eicosanoids derived from the n-6 PUFA arachidonic acid play a role in RA, and the efficacy of non-steroidal anti-inflammatory drugs in RA indicates the importance of pro-inflammatory cyclooxygenase pathway products of arachidonic acid in the pathophysiology of the disease. EPA and DHA inhibit arachidonic acid metabolism to inflammatory eicosanoids. EPA also gives rise to eicosanoid mediators that are less inflammatory than those produced from arachidonic acid and both EPA and DHA give rise to resolvins that are anti-inflammatory and inflammation resolving. In addition to modifying the lipid mediator profile, n-3 PUFA exert effects on other aspects of immunity relevant to RA such as antigen presentation, T-cell reactivity and inflammatory cytokine production. Fish oil has been shown to slow the development of arthritis in an animal model and to reduce disease severity. Randomised clinical trials have demonstrated a range of clinical benefits in patients with RA that include reducing pain, duration of morning stiffness and use of non-steroidal anti-inflammatory drugs.
Publication Types: Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=18847518&dopt=ExternalLink
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PMID: 18847518 [PubMed - indexed for MEDLINE]9: Rheum Dis Clin North Am. 2008 May;34(2):469-79.
Proudman SM, Cleland LG, James MJ.
Rheumatology Unit, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia.
There is high level evidence (meta-analysis of randomized, controlled trials) for symptomatic benefits from fish oil use in rheumatoid arthritis, and there is biologic plausibility for its clinical effects. Fish oil also has safety advantages in reducing cardiovascular risk via direct cardiovascular effects and via nonsteroidal anti-inflammatory drug-sparing. This is an important aspect of fish oil use, given the increased cardiovascular risk in rheumatoid arthritis. Perceived barriers to clinical use are readily addressed.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=18638687&dopt=ExternalLink
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PMID: 18638687 [PubMed - indexed for MEDLINE]10: Lipids. 2008 Jun;43(6):485-97. Epub 2008 Apr 8.
Merzouk SA, Saker M, Reguig KB, Soulimane N, Merzouk H, Guermouche B, Berrouiguet AY, Hichami A, Narce M, Khan NA.
Departement de Physique, Faculte des Sciences, Universite de Tlemcen, Tlemcen, Algeria.
In this work, we assessed the in-vitro effects of eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3) (final concentration, 15 microM) on T cell blastogenesis, interleukin-2 and -4 (IL-2, IL-4) secretion, fatty acid composition and intracellular oxidative status in type I diabetic patients with or without complications. Con A stimulated lymphocyte proliferation, glucose uptake, intracellular reduced glutathione levels and catalase activity were lower in diabetics as compared to controls, regardless to the presence of complications. EPA and DHA diminished T-lymphocyte proliferation and IL-2 production but enhanced IL-4 secretion in both diabetic and control groups. No changes in the levels of reduced glutathione and in the activities of catalase and SOD were observed in control T cells cultured in the presence of EPA and DHA. However, in diabetic patients, addition of n-3 PUFA to culture induced an increase in T cell levels of reduced glutathione and hydroperoxide, and in activities of catalase and SOD. Low levels of arachidonic acid (C20:4n-6) were found in plasma membrane phospholipids of lymphocytes from diabetic patients compared to controls. Incubation of lymphocytes with EPA and DHA was associated with an incorporation of these fatty acids in membrane phospholipids. In conclusion, the beneficial effects of n-3 PUFA on T cell functions in type I diabetes could be attributed to their suppressive action and modulation of cytokine secretion, and to the improvement of intracellular oxidative status.
Publication Types: In Vitro Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=18392872&dopt=ExternalLink
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PMID: 18392872 [PubMed - indexed for MEDLINE]11: Pediatr Diabetes. 2008 Feb;9(1):40-5.
Stene LC, Thorsby PM, Berg JP, Ronningen KS, Joner G; Norwegian Childhood Diabetes Study Group.
Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo,Norway. lars.christian.stene@fhi.no
OBJECTIVE: We have previously described an association between use of cod liver oil (a dietary n-3 fatty acid supplement) and reduced risk of type 1 diabetes. n-3 fatty acids are ligands for the peroxisome proliferator-activated receptor-gamma (PPARG), which has recently been implicated in the control of inflammation and possibly autoimmunity. We aimed to estimate the association between the common Pro12Ala polymorphism of PPARG2 and risk of type 1 diabetes, and to test whether there is gene-environment interaction with use of cod liver oil in the first year of life or gene-gene interaction with the established insulin gene (INS) and human leukocyte antigen DQ (HLA-DQ) genetic susceptibility loci. METHODS: We designed a population-based case-control study of childhood-onset type 1 diabetes in Norway with information on use of cod liver oil in the first year of life from questionnaires and PPARG2 genotype data for 483 cases and 1520 control subjects. We used logistic regression for analysis. RESULTS: The odds ratio for the PPARG2 Ala/Ala or Pro/Ala vs. Pro/Pro genotype and type 1 diabetes was 0.89 (95% CI: 0.69-1.13, p = 0.33). There was no significant interaction with cod liver oil in the first year of life [P (interaction) = 0.35] or with the INS polymorphism [P(interaction) = 0.42]. CONCLUSIONS: Although the association between PPARG2 and type 1 diabetes was not significant, the observed odds ratio was almost identical to that observed in two previous studies and can contribute to meta-analysis indicating a weak but significant association. Our hypothesized interaction between cod liver oil and PPARG2 in reducing type 1 diabetes risk was not supported.
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=18211635&dopt=ExternalLink
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PMID: 18211635 [PubMed - indexed for MEDLINE]12: J Behav Med. 2008 Apr;31(2):127-35.
Aupperle RL, Denney DR, Lynch SG, Carlson SE, Sullivan DK.
Department of Psychology, University of Kansas, 1415 Jayhawk Blvd, Lawrence, KS 66045-7556, USA.
Depression is a common problem among patients with multiple sclerosis (MS). Previous research has shown differences between MS patients and controls in the levels of certain fatty acids, and differences in many of these same fatty acids have also been reported in psychiatric patients with major depression. The current study sought to determine whether fatty acid levels in MS patients might be associated with depression. Fatty acids were measured in red blood cells (RBCs) for 38 patients with relapsing-remitting MS and 33 healthy controls who also completed 3-day dietary records and depression questionnaires. Levels of certain omega-3 and omega-6 fatty acids were lower and levels of certain monounsaturated and saturated fatty acids were higher in the MS patients. These differences were generally of medium effect size and occurred despite the fact that no differences were found between the two groups in dietary intake of any fatty acids. However, neither RBC nor dietary fatty acid levels were related to depression in the MS sample.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=18157629&dopt=ExternalLink
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PMID: 18157629 [PubMed - indexed for MEDLINE]13: JAMA. 2007 Sep 26;298(12):1420-8.
Norris JM, Yin X, Lamb MM, Barriga K, Seifert J, Hoffman M, Orton HD, Baron AE, Clare-Salzler M, Chase HP, Szabo NJ, Erlich H, Eisenbarth GS, Rewers M.
Department of Preventive Medicine and Biostatistics, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262, USA. jill.norris@uchsc.edu
CONTEXT: Cod liver oil supplements in infancy have been associated with a decreased risk of type 1 diabetes mellitus in a retrospective study. OBJECTIVE: To examine whether intakes of omega-3 and omega-6 fatty acids are associated with the development of islet autoimmunity (IA) in children. DESIGN, SETTING, AND PARTICIPANTS: A longitudinal, observational study, the Diabetes Autoimmunity Study in the Young (DAISY), conducted in Denver, Colorado, between January 1994 and November 2006, of 1770 children at increased risk for type 1 diabetes, defined as either possession of a high diabetes risk HLA genotype or having a sibling or parent with type 1 diabetes. The mean age at follow-up was 6.2 years. Islet autoimmunity was assessed in association with reported dietary intake of polyunsaturated fatty acids starting at age 1 year. A case-cohort study (N = 244) was also conducted in which risk of IA by polyunsaturated fatty acid content of erythrocyte membranes (as a percentage of total lipids) was examined. MAIN OUTCOME MEASURE: Risk of IA, defined as being positive for insulin, glutamic acid decarboxylase, or insulinoma-associated antigen-2 autoantibodies on 2 consecutive visits and still autoantibody positive or having diabetes at last follow-up visit. RESULTS: Fifty-eight children developed IA. Adjusting for HLA genotype, family history of type 1 diabetes, caloric intake, and omega-6 fatty acid intake, omega-3 fatty acid intake was inversely associated with risk of IA (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.21-0.96; P = .04). The association was strengthened when the definition of the outcome was limited to those positive for 2 or more autoantibodies (HR, 0.23; 95% CI, 0.09-0.58; P = .002). In the case-cohort study, omega-3 fatty acid content of erythrocyte membranes was also inversely associated with IA risk (HR, 0.63; 95% CI, 0.41-0.96; P = .03). CONCLUSION: Dietary intake of omega-3 fatty acids is associated with reduced risk of IA in children at increased genetic risk for type 1 diabetes.
Publication Types: Research Support, N.I.H., Extramural
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=17895458&dopt=ExternalLink
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PMID: 17895458 [PubMed - indexed for MEDLINE]14: Ann Rheum Dis. 2008 Jun;67(6):841-8. Epub 2007 Sep 17.
Wright SA, O'Prey FM, McHenry MT, Leahey WJ, Devine AB, Duffy EM, Johnston DG, Finch MB, Bell AL, McVeigh GE.
Department of Therapeutics and Pharmacology, Queens University Belfast, Belfast, Northern Ireland, UK. drsawright@yahoo.co.uk
OBJECTIVE: To determine the clinical effect of dietary supplementation with low-dose omega-3-polyunsaturated fatty acids on disease activity and endothelial function in patients with systemic lupus erythematosus. METHODS: A 24-week randomised double-blind placebo-controlled parallel trial of the effect of 3 g of omega-3-polyunsaturated fatty acids on 60 patients with systemic lupus erythematosus was performed. Serial measurements of disease activity using the revised Systemic Lupus Activity Measure (SLAM-R) and British Isles Lupus Assessment Group index of disease activity for systemic lupus erythematosus (BILAG), endothelial function using flow-mediated dilation (FMD) of the brachial artery, oxidative stress using platelet 8-isoprostanes and analysis of platelet membrane fatty acids were taken at baseline, 12 and 24 weeks. RESULTS: In the fish oil group there was a significant improvement at 24 weeks in SLAM-R (from 9.4 (SD 3.0) to 6.3 (2.5), p<0.001); in BILAG (from 13.6 (6.0) to 6.7 (3.8), p<0.001); in FMD (from 3.0% (-0.5 to 8.2) to 8.9% (1.3 to 16.9), p<0.001) and in platelet 8-isoprostanes (from 177 pg/mg protein (23-387) to 90 pg/mg protein (32-182), p = 0.007). CONCLUSIONS: Low-dose dietary supplementation with omega-3 fish oils in systemic lupus erythematosus not only has a therapeutic effect on disease activity but also improves endothelial function and reduces oxidative stress and may therefore confer cardiovascular benefits.
Publication Types: Randomized Controlled Trial Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=17875549&dopt=ExternalLink
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PMID: 17875549 [PubMed - indexed for MEDLINE]15: Clin J Am Soc Nephrol. 2006 Nov;1(6):1167-72. Epub 2006 Sep 27.
Hogg RJ, Fitzgibbons L, Atkins C, Nardelli N, Bay RC; North American IgA Nephropathy Study Group.
St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA. spnsg@chw.edu
Previous studies that have evaluated fish oil preparations in patients with IgA nephropathy (IgAN) have produced a wide range of conclusions. Proposed explanations for these discordant results have not provided a unifying hypothesis. Results from two clinical trials were analyzed to examine whether there is a dosage-dependent effect of Omacor, a purified preparation of omega-3 fatty acids, in patients with IgAN. Whether changes in the level of proteinuria and plasma phospholipid fatty acid profiles were dependent on the dose of Omacor factored by body size was determined. In a post hoc analysis of the first trial results, correlations were found between (1) phospholipid eicosapentaenoic acid (EPA)/arachidonic acid (AA) and docosahexaenoic acid (DHA)/AA ratios and the dosage of Omacor, expressed as milligrams per kilogram of body weight (r = 0.78, P < 0.001 for EPA/AA; r = 0.86, P < 0.001 for DHA/AA), (2) phospholipid EPA/AA and DHA/AA levels and percentage change in urine protein/creatinine ratio after 21 to 24 mo of therapy (r = -0.50, P = 0.02 for EPA/AA; r = -0.52, P = 0.01 for DHA/AA), and (3) dosage of Omacor per kilogram of body weight and change in proteinuria after 21 to 24 mo (r = -0.50, P = 0.02). A similar relationship was observed between urine protein/creatinine ratio and dosage of Omacor per kilogram of body weight in trial 2 (r = -0.38, P < 0.001). It is concluded from these data that the effect of Omacor on proteinuria in patients with IgAN is dosage dependent and is associated with a dosage-dependent effect of Omacor on plasma phospholipid EPA and DHA levels.
Publication Types: Controlled Clinical Trial Multicenter Study 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=17699343&dopt=ExternalLink
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PMID: 17699343 [PubMed - indexed for MEDLINE]16: Clin J Am Soc Nephrol. 2006 May;1(3):467-74. Epub 2006 Apr 12.
Hogg RJ, Lee J, Nardelli N, Julian BA, Cattran D, Waldo B, Wyatt R, Jennette JC, Sibley R, Hyland K, Fitzgibbons L, Hirschman G, Donadio JV Jr, Holub BJ; Southwest Pediatric Nephrology Study Group.
St. Joseph's Hospital and Medical Center, 222 W. Thomas Road, Suite 410, Phoenix, AZ, USA. spnsg@chw.edu
This randomized, placebo-controlled, double-blind trial evaluated the role of prednisone and omega 3 fatty acids (O3FA) in patients with IgA nephropathy. Entry criteria were (1) biopsy-proven IgA nephropathy, (2) estimated GFR > or = 50 ml/min per 1.73 m2, and (3) moderate to severe proteinuria. Thirty-three patients were randomly assigned to receive prednisone 60 mg/m2 every other day for 3 mo, then 40 mg/m2 every other day for 9 mo, then 30 mg/m2 every other day for 12 mo (prednisone group); 32 were randomly assigned to receive O3FA 4 g/d for 2 yr (1.88 g eicosapentaenoic acid, 1.48 g docosahexaenoic acid; O3FA group); and 31 were randomly assigned to receive placebo (placebo group). Most (73%) patients completed 2 yr of treatment. Randomly assigned patients who were hypertensive were given enalapril 2.5 to 40 mg/d. The primary end point was time to failure, defined as estimated GFR <60% of baseline. An overall significance level of 0.10 was used. The three groups were comparable at baseline except that the O3FA group had higher urine protein to creatinine (UP/C) ratios than the placebo group (P = 0.003). Neither treatment group showed benefit over the placebo group with respect to time to failure, with 14 patient failures overall (two in the prednisone group, eight in the O3FA group, and four in the placebo group). The primary factor associated with time to failure was higher baseline UP/C ratios (P = 0.009). Superiority of prednisone or O3FA over placebo in slowing progression of renal disease was not demonstrated in this study. However, the relatively short follow-up period, inequality of baseline UP/C ratios, and small numbers of patients precludes definitive conclusions.
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=17699247&dopt=ExternalLink
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PMID: 17699247 [PubMed - indexed for MEDLINE]17: Clin J Am Soc Nephrol. 2006 Sep;1(5):933-9. Epub 2006 Aug 2.
Donadio JV, Bergstralh EJ, Bibus DM, Grande JP.
Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. donadio.james@mayo.edu
Re-analysis of the North American IgA Nephropathy Study suggested that efficacy of omega-3 polyunsaturated fatty acids (omega-3 PUFA) was dosage-dependent on the basis of body size and plasma omega-3/omega-6 and eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratios. The objective of this study was to confirm these assertions. Data from a previously reported randomized 2-yr clinical trial in which two dosages of an ethyl ester omega-3 PUFA (Omacor) were given to 73 high-risk patients with IgA nephropathy were reviewed. Omacor also was used in the North American IgA Nephropathy Study. Parameters included body weight; body mass index (BMI); plasma phospholipid AA, EPA, and docosahexanoic acid (DHA) levels and serum creatinine and 24-h urine protein (UP) levels during the 2-yr trial; and time to ESRD after 6.4 yr. Plasma phospholipid levels of EPA, DHA, and EPA/AA ratios were significantly inversely correlated with increasing body weight and BMI in the Omacor 4-g dosage group but not in the Omacor 8-g dosage group. Conversely, increasing levels of lipid parameters were observed with increasing dosages of Omacor (EPA+DHA) in grams per kilogram of body weight at 6 wk of treatment. None of the plasma omega-3 PUFA levels, EPA/AA ratios, or Omacor dosage per kilogram was significantly associated with reciprocal serum creatinine or UP slopes during the 2-yr trial or with ESRD. This post hoc analysis of body weight and BMI, plasma omega-3 PUFA status, and renal outcome did not find that treatment efficacy of omega-3 PUFA was dosage dependent on the basis of body size.
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=17699310&dopt=ExternalLink
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PMID: 17699310 [PubMed - indexed for MEDLINE]18: Rev Med Brux. 2006 Sep;27(4):S355-60.
[Article in French]
Herbaut C.
Service de Medecine Interne/Endocrino-Diabetologie, C.H.U. Brugmann, Bruxelles.
N-3 PUFA (omega-3), and the n-6 PUFA (omega-6) are essential fatty acids. They must be absorbed by alimentation and play a very important role in the coagulation (inhibition of platelets aggregation) and in the inflammatory reaction (anti-inflammatory effects). Their effects have been studied in different sicknesses. In cardiovascular diseases, particularly in coronary diseases, studies demonstrated a decreased mortality in populations who eat an omega-3 rich diet or who take an omega-3 supplement. Among others, sudden death after myocardial infarction is decreased. In inflammatory diseases an effect seem to be found in some studies. In rheumatoid arthritis a decrease of different biological markers of inflammation and in some case a clinical improvement has been noticed. It may be the same in COPD. On the other hand, they seem not to give any protection against cancer in general. At this moment the recommendations for healthy people are to eat twice a week fat fish and to take omega-3 rich oils. For pathological cases, recommendations exist only for coronary disease: 1 g of fish oils : mixture of eicosapentaenoic and docosahexaenoic acids (EPA/DHA) should be given after a myocardial infarction.
Publication Types: English Abstract
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=17091903&dopt=ExternalLink
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PMID: 17091903 [PubMed - indexed for MEDLINE]19: Nutr Clin Pract. 2006 Aug;21(4):323-41.
Lee S, Gura KM, Kim S, Arsenault DA, Bistrian BR, Puder M.
Children's Hospital Boston, 300 Longwood Ave., MA 02115, USA.
BACKGROUND: Recent years have brought a resurgence of research interest in fatty acids, with studied fields running the gamut of human disease. This movement has run in parallel with an increased interest in using nutrition modalities as therapeutic measures, as opposed to their conventional role as energy sources. The aim of this manuscript is to provide a basic review of current clinical applications of omega-6 and omega-3 fatty acids, with a particular focus on the latter. METHODS: A selective review of the voluminous literature, including randomized controlled trials, meta-analyses, population studies, and case reports, was used to compile data and identify trends in pertinent clinical applications of fatty acid therapy. CONCLUSIONS: There are a myriad of disorders and maladies that seem to benefit from fatty acid supplementation, specifically omega-3 fatty acids. It has clearly been shown that omega-3 fatty acid supplementation provides a protective benefit in heart disease, and in particular sudden cardiac death. Rheumatoid arthritis (RA) is another disease entity that has been proven to benefit from this nutrition intervention, with improvement in symptoms and diminished nonsteroidal antiinflammatory drug (NSAID) usage. In addition, many psychiatric disorders, particularly schizophrenia and major depressive disorder (MDD), have shown positive results when supplementation has been used as an adjunct to standard pharmacotherapy. The remainder of clinical applications for omega-3 fatty acids requires further investigation. Specifically, according to preliminary clinical evidence, parenteral administration of fatty acids warrants further study.
Publication Types: Meta-Analysis Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=16870801&dopt=ExternalLink
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PMID: 16870801 [PubMed - indexed for MEDLINE]20: J Autoimmun. 2006 Jun;26(4):268-77. Epub 2006 May 18.
Khan NA, Yessoufou A, Kim M, Hichami A.
Department of Physiology, UPRES Lipides & Nutrition, Universite de Bourgogne, Faculte des Sciences de la vie, Dijon, France. naim.khan@u-bourgogne.fr
We assessed the implication of Th (helper)-cells and the modulation of the Th1/Th2 dichotomy by n-3 polyunsaturated fatty acids (PUFA) in type I diabetic pregnancy (DP) and macrosomia. Female gestant rats fed a standard diet or n-3 PUFA regimen were rendered diabetic by administration of five low doses of streptozotocin. The macrosomic (MAC) offspring were sacrificed at the age of 90 days. The mRNAs of IL-2 and IFN-gamma (Th1 cytokines) and IL-4 (Th2 cytokine) were downregulated in the pancreas and spleen of diabetic pregnant rats. The levels of IL-10 mRNA, another Th2 cytokine, were unchanged in the spleen or upregulated in the pancreas of these animals. Feeding an n-3 PUFA diet to rats with DP upregulated IL-10 mRNA in the pancreas and IL-4 and IL-10 mRNA in the spleen. In MAC offspring, high expression of IL-2 and IFN-gamma mRNA, but not of Th2 cytokines, was observed. The n-3 PUFA diet diminished Th1 mRNA quantities and increased the levels of IL-4, but not of IL-10, mRNA in MAC offspring. Our study shows that DP is associated with a decreased Th1 phenotype and IL-4 mRNA expression in the pancreas and spleen, and an n-3 PUFA diet upregulates Th2 profile. In MAC offspring, the Th1 phenotype is upregulated and an n-3 PUFA diet downregulates this phenomenon.
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=16713180&dopt=ExternalLink
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PMID: 16713180 [PubMed - indexed for MEDLINE]