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The Health Benefits of Omega-3 Fish Oils

Updated on 7th May 2009 by Dr Charles Tweed and Alistair Tweed.

Introduction
This is a huge subject with an enormous amount of data to pore over and complex assessments of statistical relevance to assess. Numerous reputable organisations argue about this and cannot come to an agreement – so where does this leave the lay person with no training in deciphering likelihood ratios, confidence intervals and P values?

Lost, actually.

We would like to provide our view on this difficult topic.

Background
Approximately 40 years ago, it was noticed that a number of fatty acids were essential to normal growth and development, and cannot be manufactured by the body. These were further divided onto various categories based on their chemical structure into omega–3, -6 and –9 fatty acids. They are all unsaturated fatty acids.

Over time it was found that the omega-6 fatty acids were found to include precursors of eicosanoids that promoted inflammation such as arachidonic acid, and it’s metabolites: leukotrienes and thromboxanes. Conversely, omega-3s were found to have anti-inflammatory effects. The quantities of inflammatory eicosanoids is raised in numerous disease states; primarily auto-immune disorders, but also as a hallmark of the development of cardiovascular disease.

The most common omega-3 oils are alpha linoleic acid (ALA), Eicosapentaenoic acid (EPA), and Docosahexaenoic acid (DHA). The latter two are found primarily in fish that consume algae that produce omega-3 oils, or the larger fish that eat those fish. ALA is usually found in botanical sources, most commonly flaxseed oil.

ALA vs EPA vs DHA
DHA is the long chain omega-3 that is incorporated into cells and membranes. It also is the most biologically active in terms of switching off the pro-inflammatory pathways and instead turns on the anti-inflammatory pathways through compounds termed “resolvins”. Pathways exist for the conversion of ALA into EPA and then into DHA. Theoretically, at least, it should be possible to consume any of these and still end up with DHA. In practice it seems that this does not happen to any significant effect, so our advice is to consume DHA and EPA over ALA. This unfortunately means that flaxseed oil, although a rich source of the omega-3 ALA, may not have the end effects that we are all after. [29]

Anchovies - Omega 3 Fish Oils for Health

Cardiovascular Health. [1, 2]
- Total CVS outcomes.
- Sudden death.
- Lipid profiles.
- Blood pressure.
Depression and bipolar disorders. [4, 5, 6, 7]
Cognitive decline. [8, 9, 10, 11]
Eye Health. [11, 12, 13]
Cancer. [14, 15, 16]
Rheumatoid Arthritis and Joint Pain. [17, 18, 19]
Pregnancy and childhood nutrition. [20 21, 22, 23, 24]
Asthma. [25, 26 27, 28]

Please see the Google Scholar links below for dynamic, constantly updating data of recent studies so that you can research Fish Oil's benefits for yourself.

Cardiovascular Health.

Depression and bipolar disorders.

Cognitive decline.

Eye Health.

Cancer.

Rheumatoid Arthritis.

Pregnancy.

Asthma.

The science

Cardiovascular Health
The main body of work has been performed on fish oils and cardiovascular outcomes. Rather than re-invent the wheel, it is probably best to state that every major cardiological society in the western world recommends the regular consumption of oily fish, or taking fish oil supplements [2]. Statisticians still argue over the confidence intervals for certain indications, but there is little doubt that as a general agent to improve the health of your heart and blood vessels, fish oils are a very sensible idea. It has been likened to the benefits of taking a “polypill” which is estimated to reduce cardiovascular events by 80% [1]. The greatest improvement is probably seen in people who have metabolic syndrome. This is most common in people with a bit too much around the middle. In these people fish oils can markedly improve their lipid profile. Please take the time to read "Omega-3 fatty acids - Their beneficial role in cardiovascular health" for a comprehensive review of all the published data on omega-3 oil consumption and cardiovascular health outcomes. It covers everything you need to know about omega-3s and the cardiovascular system.

Depression and bipolar disorder (BPD)
The jury is out, so far, on depression and bipolar disorder. There have been conflicting results, as detailed by most reviews on this subject, including the Cochrane Database [4, 5, 7]. Having said that, there are an increasing number of small studies reporting positive findings when used as an adjunct to normal therapy [6]. Hopefully, there will be some clarity soon but fish oils certainly seem harmless, and quite possibly helpful for these indications.

Cognitive decline
There are good epidemiological studies available to suggest that omega-3 consumption is a good idea for age related cognitive decline (ARCD) and Alzheimer’s disease (AD). Both the Framingham heart study [11] and the Italian Longitudinal Study on aging (ILSA) [10] show a clear correlation between increased consumption of omega-3 oils and a decreased risk of developing AD and ARCD. This can be condensed into the statement “1 fish oil pill per day decreases your risk of dementia by 50%” [11]. To confidently state this, though, you need to go out and prove it by doing an intervention study – which is where life gets complicated, because who is going to do that? Animal models are also very suggestive that DHA consumption will decrease the production of, and damage caused by, the amyloid sheets, diagnostic of AD [8, 9]. There is even one study suggesting that fish oil supplementation reduces the progression of mild AD. On balance we would strongly recommend fish oils for this indication.

Eye health
The mechanisms behind omega-3’s benefits in neurodegeneration are almost identical to those in the eye [11]. In addition, the eye is exposed to constant bombardment by UV, with the associated damage it can cause. It appears that many of the damaging processes that occur to the cells and blood vessels in the eye are to some extent prevented by DHA [12]. Epidemiological data would tend to support this theory [11, 13] with a 38% reduction in macular degeneration reported in those that consume more fish. As usual, decent prospective randomised controlled trials (RCTs) are lacking!

Cancer
Whilst trawling through the hundreds of citations for omega-3 consumption and cancer risk, it is possible to find numerous examples that are encouraging [14, 15], but it is difficult to get away from the overall conclusion of this excellent review in JAMA in 2006 [16]: A large body of literature spanning numerous cohorts from many countries and with different demographic characteristics does not provide evidence to suggest a significant association between omega-3 fatty acids and cancer incidence. Dietary supplementation with omega-3 fatty acids is unlikely to prevent cancer. This should be interpreted with a very big caveat, though. Omega-3 s may be profoundly beneficial for the prevention of certain cancers, or conversely, possibly even increase the risk of certain cancers, although this has not been suggested in any studies. It is, however, unlikely that they alter the risk of cancers as a whole. We would not currently recommend Omega-3s for this indication. Treat any source that does recommend omega-3 for reducing cancer risk with suspicion!

Rheumatoid arthritis and joint pain
This is the second area that has really robust trials supporting the use of fish oils. The biochemical anti-inflammatory effects are well described with omega-3s having both direct and indirect effects on inflammation [18]. Gratifyingly, the prototype inflammatory condition – rheumatoid arthritis – seems to prove the lab boffins right [17]. Multiple studies show that giving fish oils to people with RA reduces their pain, number of painful joints, morning stiffness, amount of painkillers they need to use and improves their quality of life [19]. All pretty impressive for a fish – fishician heal thyself?

Pregnancy and childhood development
There are excellent observational correlations between quantity of fish and omega-3 consumption and positive outcomes of pregnancy and lactation: higher birthweight, less maternal depression, better neurological development, less hyperactivity and possibly even higher IQ [20 21, 22, 24]. Good interventional studies are lacking for normal children but it seems that DHA supplementation in preterm infants is of marginal benefit at best [23] and most authorities caution against the possibility of inadvertently exposing the developing brain to methyl-mercury which is well recognised to have bad effects on development [22]. On balance, it is likely that deficiency is to be avoided and that if you don’t eat 2-3 three portions of fish per week as a pregnant or breast-feeding mum, you should supplement. For kids, it is less clear what the best option is. At aging management we reckon the same advice still holds, but be extremely careful to avoid fish with a high mercury content (see below).

Asthma
Asthma is considered a chronic inflammatory disease affecting the large airways and as such might be amenable to modulation with omega-3 oils. Indeed, lab research would tend to support this with decreased inflammatory interleukin and leukotriene production in the mouse model [25]. Numerous small-scale studies are hopeful [26, 27] but most reviews of the evidence to date would say that there is insufficient evidence to claim any significant response [28]. As with most other reviews, they also conclude that there are no reported side effects.

Safety
It should be noted that people taking coumadin (warfarin) and digoxin should consult their doctor before taking fish oil supplements, particularly in high dose, as it can alter the effects of their medications. Fish oils do thin the blood slightly (which is part of the reason they are good) but at high dose this may become significant, particularly in those taking aspirin, or aspirin-like drugs [3]. Having said that, cases of major bleeding or increases in haemorrhagic stroke have not been reported.

The second major point to be considered is the contamination of fish oils – primarily with mercury. For more information, please read "Quantitative Approach for Incorporating Methylmercury Risks and Omega-3 Fatty Acid Benefits in Developing Species-Specific Fish Consumption Advice". Long chain omega-3 oils come initially from the algae that marine creatures feed on. Unfortunately, mercury is everywhere now, and these organisms are not spared. As you go further up the foodchain, the mercury becomes more and more concentrated; a bit like the DDT disaster in the 50s and 60s. Consequently, eating swordfish, shark and tuna should now be regarded as an occasional activity. Clearly, if you are aiming to consume omega-3 oils on a daily basis, which we wholeheartedly recommend that you should, you want to make damn sure there is no contamination with mercury, or you may be doing more harm than good. Basically, the smaller the fish, the lower the mercury. So, anchovies, sardines, herring and pollack are pretty safe. Similarly, if you are consuming a supplement, make sure that it is extracted from these species and not larger ones. The other factor to consider is the degree of oxidation of the omega-3 oils that may occur. In the same way that butter goes rancid, so too do fish oils exposed to the air for prolonged periods. It is unlikely that these oxidised oils are good for your health. A reputable supplier will provide a supplement that is extracted from small fish, with minimal delays between extraction, processing and encapsulation. For those wanting further information on how to grade the risk:benefit ratio of various fish, please read the "Consumer Report: Omega-3 fish oil supplements".

aging-management.com Buyer's Guide and Recommendation
There are many fish oil products being offered in the market place today. How does one choose the best? The priorities are finding a provider that will source the best raw materials, not compromise on safety and will ensure delivery of a high quality product in excellent condition. The most important aspects of safety are avoiding mercury, dioxins and PCBs. This is done by firstly ensuring that the source of the fish oil is the best possible and then ensuring that the processing is faultless. Finally, the product must be delivered in a way that ensures that the high quality achieved is not compromised by oxidation en route to the customer.

Looking at the market place for fish oil, there are many cheap offerings to be found in the bargain buckets of health food shops. These will be of variable quality. What are the problems and concerns with the cheaper, lower quality end of the market?

Although they are a highly economic source of fish oil, larger and longer lived fish and marine mammals that are higher up the food chain tend to accumulate concentrations of mercury, dioxins and PCBs. These are not the best sources of fish oil.
Many preparations of ordinary fish oil do not undergo purification.
Fish oils obtained from the pressing of fish livers can contain high amounts of Vitamin A, which needs to be managed carefully if one`s intake of vitamin A is already high due to dietary reasons or poorly designed supplements that are already being taken. Also, the liver being an excretory organ, contains higher amounts of impurities – this, clearly, is not the ideal source from which to derive omega-3.
Some fish oil capsules are left exposed to air, light and heat for long periods of time resulting in a rancid product by the time it is consumed.

We have researched the market, and while there may be other products that satisfy all these criteria, we have found one provider that has met all our requirements and has particularly impressed us. Igennus` fish oil contains ultra-pure eicosapentaenoic acid (EPA) derived from small, short-lived marine anchovies from the clean waters of the South Pacific Ocean. Sourcing EPA from the flesh of anchovies ensures that the source of omega-3 oil is as pure as possible, even before it undergoes purification. This minimises pollutant bioaccumulation from mercury, dioxins and PCBs. The molecular distillation process then removes any remaining impurities.

Vegepa is a patented formulation which combines the benefits of ultra-pure EPA from marine fish oil and GLA from organic virgin evening primrose oil, providing a highly concentrated source of omega-3 & -6 long chain fatty acids and botanical triterpenes. Vegepa is produced under pharmaceutical control in MHRA approved facilities that are licenced to produce medicines, is GMP approved and endorsed by medical professionals for a variety of conditions. Igennus` products are then packaged in blister packs so that each capsule is fresh from the packet the moment before you take it and there is no chance of oxidation or rancidity.

Additionally, they have formulated Echiomega, an innovative, plant derived product that offers the extremely well documented benefits of omega-3 fatty acids to vegans, vegetarians and those with an intolerance to fish products.

The Igennus products we stock can be found on the aging-management.com Igennus Product page.

For further information on options for omega-3 supplementation, please read Current choices in omega 3 supplementation.

References:

(Back) Lipids Health Dis. 2008 Oct 15;7:37. Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules. Das UN. Lowering plasma low density lipoprotein-cholesterol (LDL-C), blood pressure, homocysteine, and preventing platelet aggregation using a combination of a statin, three blood pressure lowering drugs such as a thiazide, a beta blocker, and an angiotensin converting enzyme (ACE) inhibitor each at half standard dose; folic acid; and aspirin-called as polypill- was estimated to reduce cardiovascular events by approximately 80%. Essential fatty acids (EFAs) and their long-chain metabolites: gamma-linolenic acid (GLA), dihomo-GLA (DGLA), arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and other products such as prostaglandins E1 (PGE1), prostacyclin (PGI2), PGI3, lipoxins (LXs), resolvins, protectins including neuroprotectin D1 (NPD1) prevent platelet aggregation, lower blood pressure, have anti-arrhythmic action, reduce LDL-C, ameliorate the adverse actions of homocysteine, show anti-inflammatory actions, activate telomerase, and have cytoprotective properties. Thus, EFAs and their metabolites show all the classic actions expected of the "polypill". Unlike the proposed "polypill", EFAs are endogenous molecules present in almost all tissues, have no significant or few side effects, can be taken orally for long periods of time even by pregnant women, lactating mothers, and infants, children, and adults; and have been known to reduce the incidence cardiovascular diseases including stroke. In addition, various EFAs and their long-chain metabolites not only enhance nitric oxide generation but also react with nitric oxide to yield their respective nitroalkene derivatives that produce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, and possess PPAR-gamma ligand activity and release NO, thus prevent platelet aggregation, thrombus formation, atherosclerosis, and cardiovascular diseases. Based on these evidences, I propose that a rational combination of omega-3 and omega-6 fatty acids and the co-factors that are necessary for their appropriate action/metabolism is as beneficial as that of the combined use of a statin, thiazide, a beta blocker, and an angiotensin converting enzyme (ACE) inhibitor, folic acid, and aspirin. Furthermore, appropriate combination of omega-3 and omega-6 fatty acids may even show additional benefits in the form of protection from depression, schizophrenia, Alzheimer`s disease, and enhances cognitive function; and serve as endogenous anti-inflammatory molecules; and could be administered from childhood for life long. PMID: 18922179 [PubMed - indexed for MEDLINE]
(Back) Cardiovasc Res. 2007 Jan 15;73(2):310-5. Epub 2006 Sep 1. Cardiovascular benefits of omega-3 fatty acids. von Schacky C, Harris WS. Cardiac societies recommend the intake of 1 g/day of the two omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for cardiovascular disease prevention, treatment after a myocardial infarction, prevention of sudden death, and secondary prevention of cardiovascular disease. These recommendations are based on a body of scientific evidence that encompasses literally thousands of publications. Of four large scale intervention studies three also support the recommendations of these cardiac societies. One methodologically questionable study with a negative result led a Cochrane meta-analysis to a null conclusion. This null conclusion, however, has not swayed the recommendations of the cardiac societies mentioned, and has been refuted with good reason by scientific societies. Based on the scientific evidence just mentioned, we propose a new risk factor to be considered for sudden cardiac death, the omega-3 index. It is measured in red blood cells, and is expressed as a percentage of EPA + DHA of total fatty acids. An omega-3 index of >8% is associated with 90% less risk for sudden cardiac death, as compared to an omega-3 index of <4%. The omega-3 index as a risk factor for sudden cardiac death has striking similarities to LDL as a risk factor for coronary artery disease. Moreover, the omega-3 index reflects the omega-3 fatty acid status of a given individual (analogous to HbA1c reflecting glucose homeostasis). The omega-3 index can therefore be used as a goal for treatment with EPA and DHA. As is the case now for LDL, in the future, the cardiac societies might very well recommend treatment with EPA and DHA to become goal oriented (e.g. an omega-3 index>8%). PMID: 16979604 [PubMed - indexed for MEDLINE]
(Back) J Cardiopulm Rehabil Prev. 2008 Mar-Apr;28(2):92-8. The role of fish oil in arrhythmia prevention. Anand RG, Alkadri M, Lavie CJ, Milani RV. Department of Cardiology, Ochsner Medical Center, New Orleans, LA 70121, USA. Numerous epidemiological studies, case-control series, and randomized trials have demonstrated the ability of fish oil to reduce major cardiovascular events, particularly sudden cardiac death and all-cause mortality. We discuss the potential benefits of fish oil therapy to improve overall autonomic tone and potentially reduce the risk of major ventricular and atrial arrhythmias. Specifically, this review focuses on how fish oil therapy has performed in 3 primary prevention trials in patients with implantable cardioverter defibrillators, reviews the effects that fish oil has on the autonomic nervous system, focuses on the use of fish oil as a novel therapy for atrial fibrillation, and revisits other beneficial properties of fish oil (ie, ability to lower serum triglycerides, anti-inflammatory effects, and possible improvements in arterial pressure/diastolic function). We also discuss the safety profile of fish oil, including effects on bleeding time and bleeding complications as well as provide commentary regarding fish oil supplementation in light of increasing contaminants contained in fish. In summary, any patient with documented coronary heart disease and those with risk factors for sudden cardiac death, such as left ventricular dysfunction, left ventricular hypertrophy, prior myocardial infarction, or high-grade ventricular dysrhythmias, should consider fish oil supplementation. The American Heart Association recommends four 3-ounce servings of oily fish weekly. For those who cannot eat fish or do not have access to fish, as well as those who would prefer not to eat fish regularly, capsules of fish oil are readily available in various concentrations. At the present time, we recommend doses of eicosapentanoic acid and docosahexanoic acid in the combined range of 800 to 1000 mg/day for primary and secondary prevention of cardiovascular disease. PMID: 18360184 [PubMed - indexed for MEDLINE
(Back) Curr Opin Investig Drugs. 2008 Jan;9(1):57-64. The role of omega-3 fatty acids in mood disorders. Stahl LA, Begg DP, Weisinger RS, Sinclair AJ. La Trobe University, School of Psychological Science, Bundoora, VIC, Australia. Research has established that docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid (PUFA), plays a fundamental role in brain structure and function. Epidemiological and cross-sectional studies have also identified a role for long-chain omega-3 PUFA, which includes DHA, eicosapentaenoic acid, and docosapentaenoic acid, in the etiology of depression. In the past ten years, there have been 12 intervention studies conducted using various preparations of longchain omega-3 PUFA in unipolar and bipolar depression. The majority of these studies administered long-chain omega-3 PUFA as an adjunct therapy. The studies have been conducted over 4 to 16 weeks of intervention and have often included small cohorts. In four out of the seven studies conducted in depressed individuals and in two out of the five studies in bipolar patients, individuals have reported a positive outcome following supplementation with ethyl-eicosapentaenoic acid or fish oil containing long-chain omega-3 PUFA. In the three trials that researched the influence of DHA-rich preparations, no significant effects were reported. The mechanisms that have been invoked to account for the benefits of long-chain omega-3 PUFA in depression include reductions in prostaglandins derived from arachidonic acid, which lead to decreased brain-derived neurotrophic factor levels and/or alterations in blood flow to the brain. PMID: 18183532 [PubMed - indexed for MEDLINE
(Back) J Affect Disord. 2008 Sep;110(1-2):16-26. Epub 2008 May 5. Complementary and alternative medicine in the treatment of bipolar disorder--a review of the evidence. Andreescu C, Mulsant BH, Emanuel JE. The Advanced Center for Interventions and Services Research for Late-life Mood Disorders, Department of Psychiatry, University of Pittsburgh School of Medicine, USA. A growing number of patients with mood disorders are using complementary and alternative medicine (CAM) interventions. In this paper, we review the published scientific evidence on the benefits and risks of CAM for the treatment of patients with bipolar disorder. Since very few studies of CAM have involved patients with bipolar disorder, most available evidence is derived from trials conducted in patients with major depressive disorder. The use of omega-3 fatty acids has been studied in two controlled studies in bipolar disorder while St. John`s wort (Hypericum perforatum), S-adenosyl-l-methionine (SAMe), and acupuncture have been studied in a series of randomized controlled trials in patients with major depression. Overall, the best evidence supports the use of St. John`s wort for the treatment of mild to moderate depression. SAMe may also be effective for depression. However, both of these products have the potential to induce mania; the extent of this risk needs to be quantified. St. John`s wort can also interact with a variety of medications. Evidence regarding the benefits of omega-3 fatty acids or acupuncture is inconsistent. Data regarding other CAM interventions (e.g., aromatherapy massage, massage therapy, yoga) are almost entirely lacking. In conclusion, better studies are needed before CAM interventions can be recommended to patients with bipolar disorder. In the meantime, patients need to be informed about the possible risks associated with the use of these interventions. PMID: 18456339 [PubMed - indexed for MEDLINE]
(Back) Eur J Clin Nutr. 2009 Jan 21. [ Reduced mania and depression in juvenile bipolar disorder associated with long-chain omega-3 polyunsaturated fatty acid supplementation. Clayton EH, Hanstock TL, Hirneth SJ, Kable CJ, Garg ML, Hazell PL. [1] 1NSW Department of Primary Industries, Wagga Wagga Agricultural Institute, Wagga Wagga, New South Wales, Australia [2] 2Nutraceuticals Research Group, University of Newcastle, Callaghan, New South Wales, Australia. Long-chain omega-3 polyunsaturated fatty acid (LCn-3PUFA) supplementation may improve symptoms of depression in children and bipolar disorder (BD) in adults. No studies have examined the effectiveness of LCn-3PUFA supplementation in the treatment of mania and depression in juvenile BD (JBD) when given as an adjunct to standard pharmacological treatment. Eighteen children and adolescents with JBD received supplements containing 360 mg per day eicosapentaenoic acid (EPA) and 1560 mg per day docosahexaenoic acid (DHA) for 6 weeks in an open-label study. Intake and fasting red blood cell (RBC) LCn-3PUFA, mania, depression and global function were assessed before and after supplementation. RBC EPA and DHA were significantly higher following supplementation. Clinician ratings of mania and depression were significantly lower and global functioning significantly higher after supplementation. Parent ratings of internalizing and externalizing behaviours were also significantly lower following supplementation. A larger randomized controlled trial appears warranted in this participant population.European Journal of Clinical Nutrition advance online publication, 21 January 2009; doi:10.1038/ejcn.2008.81. PMID: 19156158 [PubMed - as supplied by publisher
(Back) 1: Cochrane Database Syst Rev. 2008 Apr 16;(2):CD005169. Omega-3 fatty acids for bipolar disorder. Montgomery P, Richardson AJ. University of Oxford, Centre for Evidence-Based Intervention, Barnett House, 32 Wellington Square, Oxford, UK, OX1 2ER. paul.montgomery@socres.ox.ac.uk BACKGROUND: Bipolar disorder is a complex psychiatric disorder and is amongst the top thirty causes of worldwide disability. Mood stabilisers are the primary pharmacological intervention, both in the treatment of acute episodes and in prophylaxis. There is, however, mounting evidence that dietary supplementation with omega-3 fatty acids may be beneficial in psychiatric conditions, particularly those involving disturbances of mood. OBJECTIVES: To review the efficacy of omega-3 fatty acids as either a monotherapy or an adjunctive treatment for bipolar disorder. SEARCH STRATEGY: Electronic searches of the following databases were performed: CCDANCTR-Studies and CCDANCTR-References were searched on 12/2/2008, Supplementary searches were carried out on Biological Abstracts, CINAHL, The Cochrane Library, CCDAN Register, EMBASE, MEDLINE, and PsycINFO. The search strategy also included cited reference searching, personal contact with all authors of studies initially included and contact with the omega-3 producing pharmaceutical companies. SELECTION CRITERIA: All relevant randomised controlled trials were included in the review. Studies involving males and females of all ages with a diagnosis of bipolar disorder qualified for inclusion. Studies using any type or dose of omega-3 fatty acid treatment as monotherapy or in addition to standard pharmacotherapy were eligible. The primary outcome was symptom severity; and secondary outcomes were adverse effects, dropout and satisfaction with treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently inspected the citations identified from the search. Potentially relevant abstracts were identified and full papers ordered and reassessed for inclusion and methodological quality. All relevant data were extracted. The weighted mean difference (WMD) was used for continuous outcome data, with 95% confidence intervals (CI). MAIN RESULTS: Five studies met inclusion criteria for the review, however, methodological quality was highly variable. Only one study, involving 75 participants, provided data for analysis, and showed a benefit of active treatment over control for depression symptom levels (WMD -3.93, 95% CI -7.00 to -0.86)and Clinical Global Impression scores (WMD -0.75, 95% CI -1.33 to -0.17) but not for mania (WMD -2.81, 95% CI -7.68 to 1.90). No serious adverse effects were reported in the five studies. The pattern of dropout was highly variable between studies. AUTHOR`S CONCLUSIONS: Results from one study showed positive effects of omega-3 as an adjunctive treatment for depressive but not manic symptoms in bipolar disorder. These findings must be regarded with caution owing to the limited data available. There is an acute need for well-designed and executed randomised controlled trials in this field. PMID: 18425912 [PubMed - indexed for MEDLINE]
(Back) Prostaglandins Leukot Essent Fatty Acids. 2007 Nov-Dec;77(5-6):287-93. Epub 2007 Nov 26. Neuroprotective action of omega-3 polyunsaturated fatty acids against neurodegenerative diseases: evidence from animal studies. Calon F, Cole G. Studies in animals clearly show that oral intake of docosahexaenoic acid (DHA) can alter brain DHA concentrations and thereby modify brain functions. This provides us with an opportunity to use DHA as a nutraceutical or pharmaceutical tool in brain disorders such as Alzheimer disease (AD) and Parkinson disease (PD). Most of the published epidemiological studies are consistent with a positive association between high reported DHA consumption or high DHA blood levels and a lower risk of developing AD later in life. Such observations have prompted the investigation of DHA in three different transgenic models of AD. These analyses show that animal models of AD are more vulnerable to DHA depletion than controls and that DHA exerts a beneficial effect against pathological signs of AD, including A beta accumulation, cognitive impairment, synaptic marker loss, and hyperphosphorylation of tau. Multiple mechanisms of action can be associated with the neuroprotective effects of DHA and include antioxidant properties and activation of distinct cell signaling pathways. Although the first randomized clinical assays have yet failed to demonstrate convincing beneficial effects of DHA for AD patients, the knowledge gathered in recent years holds out a hope for prevention and suggests that the elderly and people bearing a genetic risk for AD should at least avoid DHA deficiency. PMID: 18037281 [PubMed - indexed for MEDLINE
(Back) J Nutr. 2008 Dec;138(12):2510-4. Docosahexaenoic acid and the aging brain. Lukiw WJ, Bazan NG. Department of Ophthalmology, LSU Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. wlukiw@lsuhsc.edu The dietary essential PUFA docosahexaenoic acid [DHA; 22:6(n-3)] is a critical contributor to cell structure and function in the nervous system, and deficits in DHA abundance are associated with cognitive decline during aging and in neurodegenerative disease. Recent studies underscore the importance of DHA-derived neuroprotectin D1 (NPD1) in the homeostatic regulation of brain cell survival and repair involving neurotrophic, antiapoptotic and antiinflammatory signaling. Emerging evidence suggests that NPD1 synthesis is activated by growth factors and neurotrophins. Evolving research indicates that NPD1 has important determinant and regulatory interactions with the molecular-genetic mechanisms affecting beta-amyloid precursor protein (betaAPP) and amyloid beta (Abeta) peptide neurobiology. Deficits in DHA or its peroxidation appear to contribute to inflammatory signaling, apoptosis, and neuronal dysfunction in Alzheimer disease (AD), a common and progressive age-related neurological disorder unique to structures and processes of the human brain. This article briefly reviews our current understanding of the interactions of DHA and NPD1 on betaAPP processing and Abeta peptide signaling and how this contributes to oxidative and pathogenic processes characteristic of aging and AD pathology. PMID: 19022980 [PubMed - indexed for MEDLINE]
(Back) J Nutr Health Aging. 2008 Jun-Jul;12(6):382-6. Dietary fatty acids, age-related cognitive decline, and mild cognitive impairment. Solfrizzi V, Capurso C, D`Introno A, Colacicco AM, Frisardi V, Santamato A, Ranieri M, Fiore P, Vendemiale G, Seripa D, Pilotto A, Capurso A, Panza F. Department of Geriatrics, Center for Aging Brain, Memory Unit University of Bari, Bari, Italy. v.solfrizzi@geriatria.uniba.it Currently available epidemiological evidence suggested that an increase of saturated fatty acids (SFA) could have negative effects on cognitive functions, while increased polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA) may be protective against cognitive decline. In a Southern Italian elderly population from the Italian Longitudinal Study on Aging (ILSA), a clear reduction of risk of age-related cognitive decline (ARCD) has been found with elevated intake of PUFA and MUFA. Furthermore, in the ILSA, while dietary fatty acids intakes were not associated with incident mild cognitive impairment (MCI), high PUFA intake appeared to have borderline non-significant trend for a protective effect against the development of MCI. These epidemiological findings on predementia syndromes, i.e. MCI or ARCD, together with a recent randomised controlled trial on a possible effect on cognitive and depressive symptoms of omega-3 PUFA supplementation in patients with very mild AD, suggested a possible role of fatty acids intake in maintaining adequate cognitive functioning and possibly in preventing or delaying the onset of dementia. PMID: 18548175 [PubMed - indexed for MEDLINE] Am J Clin Nutr. 2006 Jun;83(6 Suppl):1494S-1498S.Click here to read Links Erratum in: Am J Clin Nutr. 2006 Dec;84(6):1555.
(Back) Potential role of dietary n-3 fatty acids in the prevention of dementia and macular degeneration. Johnson EJ, Schaefer EJ. Carotenoid & Health and Lipid Metabolism Laboratories, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA. elizabeth.johnson@tufts.edu Dementia and age-related macular degeneration (AMD) are major causes of disability in the elderly. n-3 Fatty acids, particularly docosahexaenoic acid (DHA), are highly concentrated in brain and retinal tissue and may prevent or delay the progression of dementia and AMD. Low dietary intakes and plasma concentrations have been reported to be associated with dementia, cognitive decline, and AMD risk. The major dietary sources of DHA are fish and fish oils, although dietary supplements are available. At this point, it is not possible to make firm recommendations regarding n-3 fatty acids and the prevention of dementia and AMD. Our own unpublished observations from the Framingham Heart Study suggest that > or =180 mg/d of dietary DHA (approximately 2.7 fish servings/wk) is associated with an approximately 50% reduction in dementia risk. At least this amount of DHA is generally found in one commercially available 1-g fish oil capsule given daily. PMID: 16841859 [PubMed - indexed for MEDLINE
(Back) Prog Retin Eye Res. 2005 Jan;24(1):87-138. The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. SanGiovanni JP, Chew EY. Division of Epidemiology and Clinical Research, National Eye Insitute, National Institutes of Health, 31 Center Drive, Building 31, Room 6A52, MSC 2510, Bethesda, MD 20892-2510, USA. jpsangio@nei.nih.gov In this work we advance the hypothesis that omega-3 (omega-3) long-chain polyunsaturated fatty acids (LCPUFAs) exhibit cytoprotective and cytotherapeutic actions contributing to a number of anti-angiogenic and neuroprotective mechanisms within the retina. omega-3 LCPUFAs may modulate metabolic processes and attenuate effects of environmental exposures that activate molecules implicated in pathogenesis of vasoproliferative and neurodegenerative retinal diseases. These processes and exposures include ischemia, chronic light exposure, oxidative stress, inflammation, cellular signaling mechanisms, and aging. A number of bioactive molecules within the retina affect, and are effected by such conditions. These molecules operate within complex systems and include compounds classified as eicosanoids, angiogenic factors, matrix metalloproteinases, reactive oxygen species, cyclic nucleotides, neurotransmitters and neuromodulators, pro-inflammatory and immunoregulatory cytokines, and inflammatory phospholipids. We discuss the relationship of LCPUFAs with these bioactivators and bioactive compounds in the context of three blinding retinal diseases of public health significance that exhibit both vascular and neural pathology. How is omega-3 LCPUFA status related to retinal structure and function? Docosahexaenoic acid (DHA), a major dietary omega-3 LCPUFA, is also a major structural lipid of retinal photoreceptor outer segment membranes. Biophysical and biochemical properties of DHA may affect photoreceptor membrane function by altering permeability, fluidity, thickness, and lipid phase properties. Tissue DHA status affects retinal cell signaling mechanisms involved in phototransduction. DHA may operate in signaling cascades to enhance activation of membrane-bound retinal proteins and may also be involved in rhodopsin regeneration. Tissue DHA insufficiency is associated with alterations in retinal function. Visual processing deficits have been ameliorated with DHA supplementation in some cases. What evidence exists to suggest that LCPUFAs modulate factors and processes implicated in diseases of the vascular and neural retina? Tissue status of LCPUFAs is modifiable by and dependent upon dietary intake. Certain LCPUFAs are selectively accreted and efficiently conserved within the neural retina. On the most basic level, omega-3 LCPUFAs influence retinal cell gene expression, cellular differentiation, and cellular survival. DHA activates a number of nuclear hormone receptors that operate as transcription factors for molecules that modulate reduction-oxidation-sensitive and proinflammatory genes; these include the peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and the retinoid X receptor. In the case of PPAR-alpha, this action is thought to prevent endothelial cell dysfunction and vascular remodeling through inhibition of: vascular smooth muscle cell proliferation, inducible nitric oxide synthase production, interleukin-1 induced cyclooxygenase (COX)-2 production, and thrombin-induced endothelin 1 production. Research on model systems demonstrates that omega-3 LCPUFAs also have the capacity to affect production and activation of angiogenic growth factors, arachidonic acid (AA)-based vasoregulatory eicosanoids, and MMPs. Eicosapentaenoic acid (EPA), a substrate for DHA, is the parent fatty acid for a family of eicosanoids that have the potential to affect AA-derived eicosanoids implicated in abnormal retinal neovascularization, vascular permeability, and inflammation. EPA depresses vascular endothelial growth factor (VEGF)-specific tyrosine kinase receptor activation and expression. VEGF plays an essential role in induction of: endothelial cell migration and proliferation, microvascular permeability, endothelial cell release of metalloproteinases and interstitial collagenases, and endothelial cell tube formation. The mechanism of VEGF receptor down-regulation is believed to occur at the tyrosine kinase nuclear factor-kappa B (NFkappaB). NFkappaB is a nuclear transcription factor that up-regulates COX-2 expression, intracellular adhesion molecule, thrombin, and nitric oxide synthase. All four factors are associated with vascular instability. COX-2 drives conversion of AA to a number angiogenic and proinflammatory eicosanoids. Our general conclusion is that there is consistent evidence to suggest that omega-3 LCPUFAs may act in a protective role against ischemia-, light-, oxygen-, inflammatory-, and age-associated pathology of the vascular and neural retina. PMID: 15555528 [PubMed - indexed for MEDLINE]
(Back) Arch Ophthalmol. 2008 Jun;126(6):826-33. Dietary omega-3 fatty acid and fish intake in the primary prevention of age-related macular degeneration: a systematic review and meta-analysis. Chong EW, Kreis AJ, Wong TY, Simpson JA, Guymer RH. Centre for Eye Research Australia, University of Melbourne, Victoria, Australia. OBJECTIVE: To systematically review the evidence on dietary omega-3 fatty acid and fish intake in the primary prevention of age-related macular degeneration (AMD). METHODS: Seven databases were systematically searched with no limits on publication year or language using standardized criteria. Randomized controlled trials and prospective cohort, case-control, and cross-sectional studies were included. Of 2754 abstracts identified, 3 prospective cohort, 3 case-control, and 3 cross-sectional studies met the criteria. Measures of associations were pooled quantitatively using meta-analytic methods. RESULTS: Nine studies provided data on a total sample of 88 974 people, including 3203 AMD cases. A high dietary intake of omega-3 fatty acids was associated with a 38% reduction in the risk of late AMD (pooled odds ratio [OR], 0.62; 95% confidence interval [CI], 0.48-0.82). Fish intake at least twice a week was associated with a reduced risk of both early AMD (pooled OR, 0.76; 95% CI, 0.64-0.90) and late AMD (pooled OR, 0.67; 95% CI, 0.53-0.85). CONCLUSIONS: Although this meta-analysis suggests that consumption of fish and foods rich in omega-3 fatty acids may be associated with a lower risk of AMD, there is insufficient evidence from the current literature, with few prospective studies and no randomized clinical trials, to support their routine consumption for AMD prevention.
(Back) Clin Cancer Res. 2009 Mar 24. [Epub ahead of print]Click here to read Links Dietary Omega-3 Fatty Acids, Cyclooxygenase-2 Genetic Variation, and Aggressive Prostate Cancer Risk. Fradet V, Cheng I, Casey G, Witte JS. Authors` Affiliations: Departments of Urology and Epidemiology and Biostatistics and Institute for Human Genetics, University of California at San Francisco, San Francisco, California and Department of Preventive Medicine, University of Southern California, Los Angeles, California. PURPOSE: Dietary intake of long-chain omega-3 (LC n-3) polyunsaturated fatty acids may reduce inflammation and in turn decrease risk of prostate cancer development and progression. This potential effect may be modified by genetic variation in cyclooxygenase-2 (COX-2), a key enzyme in fatty acid metabolism and inflammation.EXPERIMENTAL DESIGN: We used a case-control study of 466 men diagnosed with aggressive prostate cancer and 478 age- and ethnicity-matched controls. Diet was assessed with a semiquantitative food frequency questionnaire, and nine COX-2 tag single nucleotide polymorphisms (SNP) were genotyped. We used logistic regression models to estimate odds ratios (OR) for association and interaction.RESULTS: Increasing intake of LC n-3 was strongly associated with a decreased risk of aggressive prostate cancer (Ptrend PMID: 19318492 [PubMed - as supplied by publisher]
(Back) Cancer Detect Prev. 2006;30(3):224-32. Epub 2006 Jul 26. The potential of omega-3 fatty acids in the prevention of non-melanoma skin cancer. Black HS, Rhodes LE. Department of Dermatology, Baylor College of Medicine, Houston, TX 77030, USA. hblack@bcm.tmc.edu In toto, there is strong circumstantial evidence from both experimental and clinical studies to support a role for omega-3 FA in the prevention of non-melanoma skin cancer (NMSC). In experimental animal studies there is direct evidence that dietary omega-3 FA inhibits ultraviolet radiation (UVR) carcinogenic expression, with regard to both increased tumor latent period and reduced tumor multiplicity. Equivalent levels of omega-6 FA increase UVR carcinogenic expression. Dietary omega-3 FA dramatically reduces the plasma and cutaneous pro-inflammatory and immunosuppressive PGE(2) levels in mice. Dietary omega-6 FA increases prostaglandin E synthase type 2 (PGE(2)) level. Dietary omega-3 FA significantly reduces the inflammatory response and sustains, or enhances, the delayed type hypersensitivity immune response in mice when compared to an equivalent dietary level of omega-6 FA. Supplementary omega-3 FA significantly increases the UVR-mediated erythema threshold in humans. Supplementary omega-3 FA significantly reduces the level of pro-inflammatory and immunosuppressive PGE(2) levels in Ultraviolet B-irradiated human skin.
(Back) JAMA. 2006 Jan 25;295(4):403-15. Effects of omega-3 fatty acids on cancer risk: a systematic review. MacLean CH, Newberry SJ, Mojica WA, Khanna P, Issa AM, Suttorp MJ, Lim YW, Traina SB, Hilton L, Garland R, Morton SC. Southern California Evidence-Based Practice Center, RAND Health, Santa Monica 90407-2138, USA. maclean@rand.org CONTEXT: Omega-3 fatty acids are purported to reduce the risk of cancer. Studies have reported mixed results. OBJECTIVE: To synthesize published and unpublished evidence to determine estimates of the effect of omega-3 fatty acids on cancer risk in prospective cohort studies. DATA SOURCES: Articles published from 1966 to October 2005 identified through MEDLINE, PREMEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CAB Health; unpublished literature sought through letters to experts in the neutraceutical industry. STUDY SELECTION: A total of 38 articles with a description of effects of consumption of omega-3 fatty acids on tumor incidence, prospective cohort study design, human study population; and description of effect of omega-3 among groups with different levels of exposure in the cohort were included. Two reviewers independently reviewed articles using structured abstraction forms; disagreements were resolved by consensus. DATA EXTRACTION: Two reviewers independently abstracted detailed data about the incidence of cancer, the type of cancer, the number and characteristics of the patients, details on the exposure to omega-3 fatty acids, and the elapsed time between the intervention and outcome measurements. Data about the methodological quality of the study were also abstracted. DATA SYNTHESIS: Across 20 cohorts from 7 countries for 11 different types of cancer and using up to 6 different ways to categorize omega-3 fatty acid consumption, 65 estimates of the association between omega-3 fatty acid consumption were reported. Among these, only 8 were statistically significant. The high degree of heterogeneity across these studies precluded pooling of data. For breast cancer 1 significant estimate was for increased risk (incidence risk ratio [IRR], 1.47; 95% confidence interval [CI], 1.10-1.98) and 3 were for decreased risk (RR, 0.68-0.72); 7 other estimates did not show a significant association. For colorectal cancer, there was 1 estimate of decreased risk (RR, 0.49; 95% CI, 0.27-0.89) and 17 estimates without association. For lung cancer one of the significant associations was for increased cancer risk (IRR, 3.0; 95% CI, 1.2-7.3), the other was for decreased risk (RR, 0.32; 95% CI, 0.13-0.76), and 4 other estimates were not significant. For prostate cancer, there was 1 estimate of decreased risk (RR, 0.43; 95% CI, 0.22-0.83) and 1 of increased risk (RR, 1.98; 95% CI, 1.34-2.93) for advanced prostate cancer; 15 other estimates did not show a significant association. The study that assessed skin cancer found an increased risk (RR, 1.13; 95% CI, 1.01-1.27). No significant associations between omega-3 fatty acid consumption and cancer incidence were found for aerodigestive cancer, bladder cancer, lymphoma, ovarian cancer, pancreatic cancer, or stomach cancer. CONCLUSIONS: A large body of literature spanning numerous cohorts from many countries and with different demographic characteristics does not provide evidence to suggest a significant association between omega-3 fatty acids and cancer incidence. Dietary supplementation with omega-3 fatty acids is unlikely to prevent cancer. PMID: 17047219 [PubMed - indexed for MEDLINE]
(Back) Semin Arthritis Rheum. 2005 Oct;35(2):77-94. Diet and rheumatoid arthritis: a review of the literature. Stamp LK, James MJ, Cleland LG. Department of Medicine, Christchurch School of Medicine and Health Sciences, University of Otago, New Zealand. lisa.stamp@cdhb.govt.nz INTRODUCTION: Rheumatoid arthritis is a common inflammatory condition. A large number of patients seek alternative or complementary therapies of which diet is an important component. This article reviews the evidence for diet in rheumatoid arthritis along with the associated concept of oral tolerization. METHODS: References were taken from Medline from 1966 to September 2004. The keywords, rheumatoid arthritis, diet, n-3 fatty acids, vitamins, and oral tolerization, were used. RESULTS: Randomized controlled trials (RCTs) indicate that dietary supplementation with n-3 fatty acids provides modest symptomatic benefit in groups of patients with rheumatoid arthritis. Epidemiological studies and RCTs show cardiovascular benefits in the broader population and patients with ischemic heart disease. A number of mechanisms through which n-3 fats may reduce inflammation have been identified. In a small number of patients with rheumatoid arthritis, other dietary manipulation such as fasting, vegan, and elimination diets may have some benefit. However, many of these diets are impractical or difficult to sustain long term. CONCLUSIONS: Dietary manipulation provides a means by which patients can a regain a sense of control over their disease. Dietary n-3 supplementation is practical and can be easily achieved with encapsulated or, less expensively, bottled fish oil. PMID: 16194694 [PubMed - indexed for MEDLINE
(Back) Am J Clin Nutr. 2006 Jun;83(6 Suppl):1505S-1519S. n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Calder PC. Institute of Human Nutrition, School of Medicine, University of Southampton, Southampton, United Kingdom. pcc@soton.ac.uk 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 (e.g., 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 (e.g., by replacing arachidonic acid as an eicosanoid substrate and inhibiting arachidonic acid metabolism) and indirectly (e.g., 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 (e.g., in rheumatoid arthritis) but is weak in others (e.g., 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 alpha-linolenic acid does not appear to exert antiinflammatory effects at achievable intakes. PMID: 16841861 [PubMed - indexed for MEDLINE]
(Back) Curr Opin Clin Nutr Metab Care. 2008 Nov;11(6):752-7. Vitamin D in the prevention and treatment of coronary heart disease. Zittermann A, Koerfer R. Department of Thoracic and Cardiovascular Surgery, Heart and Diabetes Center North-Rhine Westfalia, Ruhr University Bochum, Bad Oeynhausen, Germany. azittermann@hdz-nrw.de PURPOSE OF REVIEW: The pathogenesis of coronary heart disease is of multifactorial origin. Probably, not all risk factors are satisfactorily understood. This article outlines beneficial vitamin D effects on cardiac function and the vasculature. In addition, human data associating serum vitamin D metabolite levels or oral vitamin D dosages or both with coronary heart disease outcome parameters are reviewed. RECENT FINDINGS: There is accumulating evidence that the vitamin D hormone calcitriol exerts important physiological effects in cardiomyocytes, vascular smooth muscle cells, and the vascular endothelium. Low levels of the calcitriol precursor 25-hydoxyvitamin D are associated with myocardial infarction, congestive heart failure, and calcific aortic stenosis. Deficient calcitriol concentrations probably contribute to the massive vascular calcification seen in chronic kidney disease. In patients with end-stage renal disease and end-stage heart failure, very low-circulating calcitriol levels or nonuse of active vitamin D or both are independently associated with high mortality rates. SUMMARY: Despite these exciting data, it is still too early to recommend exact dosages for the prevention or therapy of coronary heart disease. Prospective, randomized controlled trials with different amounts of vitamin D and probably with its active form calcitriol are needed to determine whether vitamin D can prevent coronary heart disease events and mortality. PMID: 18827580 [PubMed - in process]
(Back) Pain. 2007 May;129(1-2):210-23. Epub 2007 Mar 1. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Goldberg RJ, Katz J. Department of Psychology, York University, Toronto, ON, Canada. Between 40% and 60% of Americans use complementary and alternative medicine to manage medical conditions, prevent disease, and promote health and well-being. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been used to treat joint pain associated with several inflammatory conditions. We conducted a meta-analysis of 17 randomized, controlled trials assessing the pain relieving effects of omega-3 PUFAs in patients with rheumatoid arthritis or joint pain secondary to inflammatory bowel disease and dysmenorrhea. Meta-analysis was conducted with Cochrane Review Manager 4.2.8. for six separate outcomes using standardized mean differences (SMDs) as a measure of effect size: (1) patient assessed pain, (2) physician assessed pain, (3) duration of morning stiffness, (4) number of painful and/or tender joints, (5) Ritchie articular index, and (6) nonselective nonsteroidal anti-inflammatory drug consumption. Supplementation with omega-3 PUFAs for 3-4 months reduces patient reported joint pain intensity (SMD: -0.26; 95% CI: -0.49 to -0.03, p=0.03), minutes of morning stiffness (SMD: -0.43; 95% CI: -0.72 to -0.15, p=0.003), number of painful and/or tender joints (SMD: -0.29; 95% CI: -0.48 to -0.10, p=0.003), and NSAID consumption (SMD: -0.40; 95% CI: -0.72 to -0.08, p=0.01). Significant effects were not detected for physician assessed pain (SMD: -0.14; 95% CI: -0.49 to 0.22, p=0.45) or Ritchie articular index (SMD: 0.15; 95% CI: -0.19 to 0.49, p=0.40) at 3-4 months. The results suggest that omega-3 PUFAs are an attractive adjunctive treatment for joint pain associated with rheumatoid arthritis, inflammatory bowel disease, and dysmenorrhea.
(Back) Am J Clin Nutr. 2009 Feb;89(2):678S-84S. Epub 2008 Dec 30. Docosahexaenoic acid supplementation in pregnancy and lactation. Carlson SE. Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, KS 66160, USA. scarlson@kumc.edu The goal of the Experimental Biology symposium on maternal supplementation was to review all available lines of evidence, delineate unanswered questions, and develop, if it seemed reasonable, a research agenda to determine whether maternal supplementation with specific nutrients might be beneficial. In the case of maternal docosahexaenoic acid (DHA) status, the topic addressed in this article, few clinical studies show benefits of maternal DHA supplementation during pregnancy or lactation for the infant or child. However, quite a large number of observational studies link higher intrauterine DHA exposure to a number of positive developmental outcomes. This article reviews the factors known to contribute to DHA status of women and their offspring during the reproductive cycle, relates maternal DHA status to that of the developing fetus and newborn, and reviews the evidence for functional differences in behavior related to DHA status, including the available evidence related to DHA supplementation of women pregnant and lactating and their offspring. Other outcomes for infants and children and for women themselves appear plausible and are also addressed as part of a research agenda for future work. PMID: 19116324 [PubMed - indexed for MEDLINE]
(Back) Curr Opin Pediatr. 2008 Apr;20(2):178-83. Fish consumption, methylmercury and child neurodevelopment. Oken E, Bellinger DC. Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Healthcare, Boston, Massachusetts 02215, USA. emily_oken@hphc.org PURPOSE OF REVIEW: To summarize recent evidence regarding associations of early life exposure to mercury from maternal fish consumption during pregnancy, thimerosal in vaccines and dental amalgam with child neurodevelopment. RECENT FINDINGS: Recent publications have built upon previous evidence demonstrating mild detrimental neurocognitive effects from prenatal methylmercury exposure from maternal fish consumption during pregnancy. New studies examining the effects of prenatal fish consumption as well as methylmercury suggest there are benefits from prenatal fish consumption, but also that consumption of fish high in mercury should be avoided. Future studies incorporating information on both the methylmercury and the docosahexaenoic acid contained within fish will help to refine recommendations to optimize outcomes for mothers and children. Additional recent studies have supported the safety of vaccines containing thimerosal and of dental amalgam for repair of dental caries in children. SUMMARY: Exposure to mercury may harm child development. Interventions intended to reduce exposure to low levels of mercury in early life must, however, be carefully evaluated in consideration of the potential attendant harm from resultant behavior changes, such as reduced docosahexaenoic acid exposure from lower seafood intake, reduced uptake of childhood vaccinations and suboptimal dental care. PMID: 18332715
(Back) JAMA. 2009 Jan 14;301(2):175-82. Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: a randomized controlled trial. Makrides M, Gibson RA, McPhee AJ, Collins CT, Davis PG, Doyle LW, Simmer K, Colditz PB, Morris S, Smithers LG, Willson K, Ryan P. Child Nutrition Research Centre, Women`s and Children`s Health Research Institute, Women`s and Children`s Hospital, 72 King William Rd, North Adelaide SA 5006, Australia. maria.makrides@cywhs.sa.gov.au CONTEXT: Uncertainty exists about the benefit of dietary docosahexaenoic acid (DHA) on the neurodevelopment of preterm infants. OBJECTIVE: To determine the effect of meeting the estimated DHA requirement of preterm infants on neurodevelopment at 18 months corrected age. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind controlled trial enrolling infants born at less than 33 weeks gestation from April 2001 to October 2005 at 5 Australian tertiary hospitals, with follow-up to 18 months. INTERVENTION: High-DHA (approximately 1% total fatty acids) enteral feeds compared with standard DHA (approximately 0.3% total fatty acids) from day 2 to 4 of life until term corrected age. MAIN OUTCOME MEASURES: Bayley Mental Development Index (MDI) at 18 months corrected age. A priori subgroup analyses were conducted based on randomization strata (sex and birth weight < 1250 g vs > or = 1250 g). RESULTS: Of the 657 infants enrolled, 93.5% completed the 18-month follow-up. Bayley MDI scores did not differ between the high- and standard-DHA groups (mean difference, 1.9; 95% confidence interval [CI], -1.0 to 4.7). The MDI among girls fed the high-DHA diet was higher than girls fed standard DHA in unadjusted and adjusted analyses (unadjusted mean difference, 4.7; 95% CI, 0.5-8.8; adjusted mean difference, 4.5; 95% CI, 0.5-8.5). The MDI among boys did not differ between groups. For infants born weighing less than 1250 g, the MDI in the high-DHA group was higher than with standard DHA in the unadjusted comparison (mean difference, 4.7; 95% CI, 0.2-9.2) but did not reach statistical significance following adjustment for gestational age, sex, maternal education, and birth order (mean difference, 3.8; 95% CI, -0.5 to 8.0). The MDI among infants born weighing at least 1250 g did not differ between groups. CONCLUSION: A DHA dose of approximately 1% total fatty acids in early life did not increase MDI scores of preterm infants overall born earlier than 33 weeks but did improve the MDI scores of girls. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12606000327583.
(Back) J Child Psychol Psychiatry. 2008 Oct;49(10):1061-8. Epub 2008 Apr 15. Oily fish intake during pregnancy--association with lower hyperactivity but not with higher full-scale IQ in offspring. Gale CR, Robinson SM, Godfrey KM, Law CM, Schlotz W, O`Callaghan FJ. MRC Epidemiology Resource Centre (University of Southampton), Southampton General Hospital, UK. crg@mrc.soton.ac.uk BACKGROUND: Long-chain omega-3 polyunsaturated fatty acids are thought to be important for fetal neurodevelopment. Animal studies suggest that a deficiency of omega-3 fatty acids may lead to behavioural or cognitive deficits. As oily fish is a major dietary source of omega-3 fatty acids, it is possible that low intake of fish during pregnancy may have adverse effects on the developing fetal brain. METHODS: We used the Strengths and Difficulties Questionnaire and the Wechsler Abbreviated Scale of Intelligence to assess behavioural problems and intelligence in 217 nine-year-old children. The mothers of these children had participated in a study of nutrition during pregnancy during which fish intake was assessed in early and late gestation. RESULTS: Children whose mothers had eaten oily fish in early pregnancy had a reduced risk of hyperactivity compared to those whose mothers did not eat oily fish: OR .34, 95% CI .15 to .78, after adjustment for potential confounding factors. Children whose mothers had eaten fish (whether oily or non-oily) in late pregnancy had a verbal IQ that was 7.55 points higher (95% CI .75 to 14.4) than those whose mothers did not eat fish. There were, however, no significant associations between fish intake in pregnancy and other behavioural problems or full-scale and performance intelligence, after adjustment for potential confounding factors. CONCLUSIONS: Although maternal fish intake in pregnancy was associated with hyperactivity scores and verbal IQ in children, in general, how much fish women ate during pregnancy appeared to have little long-term relation with neurodevelopmental outcomes in their child. PMID: 18422546
(Back) Nat Immunol. 2008 Aug;9(8):873-9. Epub 2008 Jun 22. Resolvin E1 regulates interleukin 23, interferon-gamma and lipoxin A4 to promote the resolution of allergic airway inflammation. Haworth O, Cernadas M, Yang R, Serhan CN, Levy BD. Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women`s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. Interleukin 23 (IL-23) is integral to the pathogenesis of chronic inflammation. The resolution of acute inflammation is an active process mediated by specific signals and mediators such as resolvin E1 (RvE1). Here we provide evidence that RvE1, in nanogram quantities, promoted the resolution of inflammatory airway responses in part by directly suppressing the production of IL-23 and IL-6 in the lung. Also contributing to the pro-resolution effects of RvE1 treatment were higher concentrations of interferon-gamma in the lungs of RvE1-treated mice. Our findings indicate a pivotal function for IL-23 and IL-6, which promote the survival and differentiation of IL-17-producing T helper cells, in maintaining inflammation and also identify an RvE1-initiated resolution program for allergic airway responses. PMID: 18568027
(Back) Acta Paediatr. 2009 Apr;98(4):737-42. Epub 2008 Jan 11. Omega-3 fatty acids, vitamin C and Zn supplementation in asthmatic children: a randomized self-controlled study. Biltagi MA, Baset AA, Bassiouny M, Kasrawi MA, Attia M. Department of Paediatric, Faculty of Medicine, Tanta University, Tanta, Egypt. mbelrem@hotmail.com OBJECTIVES: Bronchial asthma is a chronic inflammatory airways disease. Nutritional intervention is an important tool to decrease the severity of many chronic inflammatory diseases including asthma. The aim of this study is to evaluate the role of omega-3 fatty acids, vitamin C and Zn in children with moderately persistent asthma. PATIENTS AND METHODS: Randomly assigned, placebo-self-controlled 60 children with moderate persistent asthma completed the study, were subjected to alternating phases of supplementation with omega-3 fatty acids, vitamin C and Zn either singly or in combination separated with washout phases. Childhood asthma control test (C-ACT), pulmonary function tests and sputum inflammatory markers were evaluated at the beginning of the study and at the end of each therapeutic phase. RESULTS: There was a significant improvement of C-ACT, pulmonary function tests and sputum inflammatory markers with diet supplementation with omega-3 fatty acids, vitamin C and Zn (p < 0.001*). There was also significant improvement with the combined use of the three supplementations than single use of any one of them (p < 0.001*). CONCLUSION: Diet supplementation with omega-3 fatty acids, Zn and vitamin C significantly improved asthma control test, pulmonary function tests and pulmonary inflammatory markers in children with moderately persistent bronchial asthma either singly or in combination. PMID: 19154523
(Back) Curr Med Res Opin. 2008 Feb;24(2):559-67. The impact of a medical food containing gammalinolenic and eicosapentaenoic acids on asthma management and the quality of life of adult asthma patients. Surette ME, Stull D, Lindemann J. BACKGROUND: Leukotriene synthesis inhibitors and receptor antagonists are efficacious for the treatment of asthma. Diets containing the fatty acids gammalinolenic acid (GLA) and eicosapentaenoic acid (EPA) decrease leukotriene synthesis; however, their impact on asthma management and quality of life (QOL) has not been evaluated in asthmatic subjects. OBJECTIVE: To evaluate asthma management and the QOL of asthmatic adult subjects consuming a medical food emulsion containing GLA and EPA. RESEARCH DESIGN AND METHODS: Trial 1 was a randomized, prospective, double-blind, placebo-controlled, parallel group trial in atopic subjects with mild-to-moderate asthma (n = 35 evaluable) consuming a low dose (0.75 g GLA + 0.5 g EPA), high dose (1.13 g GLA + 0.75 g EPA) or placebo emulsion daily. Subjects were questioned about their asthma management using a non-validated questionnaire after 2 and 4 weeks. Blood leukotrienes were measured at baseline and after 4 weeks. Trial 2 was an open-label study (n = 65 evaluable) where subjects consumed the low-dose medical food emulsion, EFF1009, daily. QOL and asthma management were measured using the validated Mini Asthma Quality of Life (MiniAQLQ) and the Asthma Control (ACQ) questionnaires, respectively, administered at baseline and after 4 weeks. RESULTS: In Trial 1, leukotriene biosynthesis decreased (p < 0.05). Self-reported asthma status and bronchodilator use improved in subjects consuming low- and high-dose emulsion between week 2 and week 4 (p < 0.01), but not compared to placebo (p > 0.1). In Trial 2, mean +/- standard error total MiniAQLQ and ACQ scores improved by 1.5 +/- 0.2 and 1.0 +/- 0.1, respectively (p < 0.001). Subdomain scores from MiniAQLQ improved and rescue bronchodilator use decreased (p < 0.001). CONCLUSION: The inclusion of the medical food EFF1009 in asthma management regimens can improve patient quality of life and decrease reliance on rescue medication. PMID: 18194593
(Back) BMC Complement Altern Med. 2006 Jul 19;6:26. Treating asthma with omega-3 fatty acids: where is the evidence? A systematic review. Reisman J, Schachter HM, Dales RE, Tran K, Kourad K, Barnes D, Sampson M, Morrison A, Gaboury I, Blackman J. Department of Pediatrics, Children`s Hospital of Eastern Ontario, Ottawa, ON, Canada. jreisman@cheo.on.ca BACKGROUND: Considerable interest exists in the potential therapeutic value of dietary supplementation with the omega-3 fatty acids. Given the interplay between pro-inflammatory omega-6 fatty acids, and the less pro-inflammatory omega-3 fatty acids, it has been thought that the latter could play a key role in treating or preventing asthma. The purpose was to systematically review the scientific-medical literature in order to identify, appraise, and synthesize the evidence for possible treatment effects of omega-3 fatty acids in asthma. METHODS: Medline, Premedline, Embase, Cochrane Central Register of Controlled Trials, CAB Health, and, Dissertation Abstracts were searched to April 2003. We included randomized controlled trials (RCTs) of subjects of any age that used any foods or extracts containing omega-3 fatty acids as treatment or prevention for asthma. Data included all asthma related outcomes, potential covariates, characteristics of the study, design, population, intervention/exposure, comparators, and co interventions. RESULTS: Ten RCTs were found pertinent to the present report. CONCLUSION: Given the largely inconsistent picture within and across respiratory outcomes, it is impossible to determine whether or not omega-3 fatty acids are an efficacious adjuvant or monotherapy for children or adults. Based on this systematic review we recommend a large randomized controlled study of the effects of high-dose encapsulated omega-3 fatty acids on ventilatory and inflammatory measures of asthma controlling diet and other asthma risk factors. This review was limited because Meta-analysis was considered inappropriate due to missing data; poorly or heterogeneously defined populations, interventions, intervention-comparator combinations, and outcomes. In addition, small sample sizes made it impossible to meaningfully assess the impact on clinical outcomes of co-variables. Last, few significant effects were found. PMID: 16854238
(Back) Prostaglandins Leukot Essent Fatty Acids. 2009 February - March;80(2-3):85-91. Epub 2009 Mar 9. alpha-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Brenna JT, Salem N Jr, Sinclair AJ, Cunnane SC; for the International Society for the Study of Fatty Acids and Lipids, ISSFAL. Division of Nutritional Sciences, Cornell University, Savage Hall, Ithaca, NY 14853, USA. Blood levels of polyunsaturated fatty acids (PUFA) are considered biomarkers of status. Alpha-linolenic acid, ALA, the plant omega-3, is the dietary precursor for the long-chain omega-3 PUFA eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Studies in normal healthy adults consuming western diets, which are rich in linoleic acid (LA), show that supplemental ALA raises EPA and DPA status in the blood and in breast milk. However, ALA or EPA dietary supplements have little effect on blood or breast milk DHA levels, whereas consumption of preformed DHA is effective in raising blood DHA levels. Addition of ALA to the diets of formula-fed infants does raise DHA, but no level of ALA tested raises DHA to levels achievable with preformed DHA at intakes similar to typical human milk DHA supply. The DHA status of infants and adults consuming preformed DHA in their diets is, on average, greater than that of people who do not consume DHA. With no other changes in diet, improvement of blood DHA status can be achieved with dietary supplements of preformed DHA, but not with supplementation of ALA, EPA, or other precursors. PMID: 19269799