The Role of n-3 PUFAs in Preventing the Arrhythmic Risk in Patients with Idiopathic Dilated Cardiomyopathy

Section of Cardiovascular Diseases, Department of Experimental and Applied Medicine, University of Brescia, c/o Spedali Civili, P.zza Spedali Civili, 25100, Brescia, Italy.
Cardiovascular Drugs and Therapy (Impact Factor: 3.19). 11/2008; 23(1):5-15. DOI: 10.1007/s10557-008-6142-7
Source: PubMed


N-3 polyunsaturated fatty acids (n-3 PUFAs) intake is associated with a reduction in sudden cardiac death in patients with ischemic heart disease. Their effects in patients with heart failure caused by idiopathic dilated cardiomyopathy (IDC) are unknown.
We compared with placebo the effects of n-3 PUFAs administration in 44 patients with IDC and with frequent or repetitive ventricular arrhythmias at Holter monitoring using a randomized, double-blind design. Arrhythmic risk was assessed by microvolt T-wave analysis (MTWA), signal averaged ECG (SAECG), Holter monitoring, power spectral analysis of heart rate (HR) variability, catecholamine and cytokine plasma levels, at baseline and after 6 months.
At MTWA, 7/12 patients (58%) initially positive became negative after n-3 PUFAs while one patient became positive after placebo (p = 0.019). N-3 PUFAs administration was also associated to normalization of SAECG (11/15 patients, p < 0.0015), decrease in non-sustained ventricular tachycardia (NSVT) episodes (p = 0.0002) and NSVT HR (p = 0.0003), improvement in HR variability and decrease in catecholamine and cytokine plasma levels. The ratio of plasma n-6 PUFAs to n-3 PUFAs decreased from 12.01 to 3.48 after n-3 PUFAs.
N-3 PUFAs administration is associated with favorable effects on parameters related to arrhythmic risk in patients with idiopathic dilated cardiomyopathy. These results are consistent with antiarrhythmic activity independent from their antiischemic effects.

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    • "oil Olive oil CRP 8 wk P 1 . 84 1 . 52 3 . 51 35 55 . 6 0 . 57 27 . 1 Chronic renal impairment Munro et al . 2012 [ 75 ] Fish oil Sunola oil CRP , IL - 6 , TNF - a 14 wk P 0 . 42 1 . 62 2 . 04 29 41 . 3 UN 32 . 8 Obesity Murphy et al . 2007 [ 76 ] Food enriched in fish oil Non - fortified food CRP 6 mon P UN UN 1 74 50 . 3 0 . 48 31 . 9 Overweight Nodari et al . 2009 [ 77 ] Fish oil Olive oil IL - 6 , TNF - a 6 mon P 0 . 54 0 . 9 1 . 44 44 63 0 . 91 UN Idiopathic dilated cardiomyopa - thy Nodari et al . 2011 [ 78 ] Fish oil Olive oil IL - 6 , TNF - a 12 mon P UN UN 1 . 95 133 62 . 5 0 . 9 25 . 8 Chronic heart failure Pooya et al . 2010 [ 80 ] Fish oil High linoleic sunflower oil CRP 2 mon P 1 . 548 "
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    ABSTRACT: Previous studies did not draw a consistent conclusion about the effects of marine-derived n-3 polyunsaturated fatty acids (PUFAs) on fasting blood level of C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). A comprehensive search of Web of Science, PubMed, Embase and Medline (from 1950 to 2013) and bibliographies of relevant articles was undertaken. Sixty-eight RCTs with a total of 4601 subjects were included in the meta-analysis. Marine-derived n-3 PUFAs supplementation showed a lowering effect on Marine-derived n-3 PUFAs supplementation had a significant lowering effect on TNF-α, IL-6 and CRP in three groups of subjects (subjects with chronic non-autoimmune disease, subjects with chronic autoimmune disease and healthy subjects). A significant negative linear relationship between duration and effect size of marine-derived n-3 PUFAs supplementation on fasting blood levels of TNF-α and IL-6 in subjects with chronic non-autoimmune disease was observed, indicating that longer duration of supplementation could lead to a greater lowering effect. A similar linear relationship was also observed for IL-6 levels in healthy subjects. Restricted cubic spline analysis and subgroup analysis showed that the lowering effect of marine-derived n-3 PUFAs on CRP, IL-6 and TNF-α in subjects with chronic non-autoimmune disease became weakened when body mass index was greater than 30 kg/m(2). The effect of marine-derived n-3 PUFAs from dietary intake was only assessed in subjects with chronic non-autoimmune disease, and a significant lowering effect was observed on IL-6, but not on CRP and TNF-α. Marine-derived n-3 PUFAs supplementation had a significant lowering effect on CRP, IL-6 and TNF-α level. The lowering effect was most effective in non-obese subjects and consecutive long-term supplementation was recommended.
    Full-text · Article · Feb 2014 · PLoS ONE
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    • "The ω-3 PUFAs provide a wide range of benefits (Table 3) from general improvements in health to protection against inflammation and disease. DHA and EPA have been used in a number of small clinical trials to understand their efficacy Lowers insulin resistance ALA Human (Vuksan et al., 2007) Reduces atherosclerosis DHA, EPA Human (Dyerberg et al., 2004) Aids neural and brain development ALA, DHA Human, rodents, other primates (Lauritzen et al., 2000; McCann and Ames, 2005) Anti-tumor DHA Human, rat (Conklin, 2002; Holian and Nelson, 1992) Prevents apoptosis DHA, EPA Rat (Calviello et al., 1999; German et al., 2006) Prevents inflammation ALA Mouse, rat (Ren et al., 2007) Improves bone density DHA Human (Hogstrom et al., 2007) Alleviates inflammation in cystic fibrosis DHA, EPA Human (De Vizia et al., 2003) Combats oxidative stress DHA Cat, dog, human (Brown, 2008; Yavin et al., 2002) Anti-thrombosis EPA Human (Tamura et al., 1992) Anti-arrhythmia DHA, EPA Human (Lombardi and Terranova, 2007; Nodari et al., 2009) Immuno-modulation DHA, EPA Human (Yaqoob and Calder, 2007) Augments neural, vision, and brain functions DHA, EPA Human (Chen et al., 2008; German et al., 2006; Lauritzen et al., 2000; Valentine and Valentine, 2004) Mitigates fatality from cardiovascular disease DHA, EPA Human (GISSI, 1999) Note: ALA, alpha-linolenic acid, EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid. "
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    ABSTRACT: A $600 million nutritional supplements market growing at 30% every year attests to consumer awareness of, and interests in, health benefits attributed to these supplements. For over 80 years the importance of polyunsaturated fatty acid (PUFA) consumption for human health has been established. The FDA recently approved the use of ω-3 PUFAs in supplements. Additionally, the market for ω-3 PUFA ingredients grew by 24.3% last year, which affirms their popularity and public awareness of their benefits. PUFAs are essential for normal human growth; however, only minor quantities of the beneficial ω-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are synthesized by human metabolism. Rather PUFAs are obtained via dietary or nutritional supplementation and modified into other beneficial metabolites. A vast literature base is available on the health benefits and biological roles of ω-3 PUFAs and their metabolism; however, information on their dietary sources and palatability of foods incorporated with ω-3 PUFAs is limited. DHA and EPA are added to many foods that are commercially available, such as infant and pet formulae, and they are also supplemented in animal feed to incorporate them in consumer dairy, meat, and poultry products. The chief sources of EPA and DHA are fish oils or purified preparations from microalgae, which when added to foods, impart a fishy flavor that is considered unacceptable. This fishy flavor is completely eliminated by extensively purifying preparations of n-3 PUFA sources. While n-3 PUFA lipid autoxidation is considered the main cause of fishy flavor, the individual oxidation products identified thus far, such as unsaturated carbonyls, do not appear to contribute to fishy flavor or odor. Alternatively, various compound classes such as free fatty acids and volatile sulfur compounds are known to impart fishy flavor to foods. Identification of the causative compounds to reduce and eventually eliminate fishy flavor is important for consumer acceptance of PUFA-fortified foods. [Supplementary materials are available for this article. Go to the publisher's online edition of Critical Reviews in Food Science and Nutrition for the following free supplemental files: Additional text, tables, and figures.].
    Full-text · Article · Jan 2014 · Critical reviews in food science and nutrition
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    • "In addition to these direct effects on the generation and duration of the action potential, other less direct mechanisms of actions have been proposed. There is also evidence for antiarrhythmic effects mediated through a reduced production of proarrhythmic eicosanoids, reduced levels of circulating catecholamines [38], and a reduced agonist affinity of beta-receptors [17]. The latter observation might be one of the mechanisms responsible for an improvement in the cardiac sympathetic-vagal balance, revealed clinically as a reduction in the mean heart rate (HR) [39] as well as an increase in HR variability [40]. "
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    ABSTRACT: This paper reviews the current evidence regarding long-chained marine omega-3 polyunsaturated fatty acids (PUFAs) and cardiovascular disease (CVD), their possible mechanisms of action, and results of clinical trials. Also, primary and secondary prevention trials as studies on antiarrhythmic effects and meta-analyses are summarized. However, the individual bioavailability of n-3 PUFAs along with the highly different study designs and estimations of FAs intake or supplementation dosages in patient populations with different background intake of n-3 PUFAs might be some of the reasons for the inconsistent findings of the studies evaluating the impact of n-3 PUFAs on CVD. The question of an optimum dose of n-3 PUFAs or whether there exists a dose-response relation for n-3 PUFA supplementation is widely discussed. Moreover, the difficulties in interpreting meta-analyses are clearly demonstrated by two recently published meta-analyses (Rizos et al. and Delgado Lista et al.), evaluating the efficacy of n-3 PUFAs on CVD, including 12 common studies, but drawing opposite conclusions. We definitely need more large-scale, randomized clinical trials of long duration, also reporting harmful effects of n-3 PUFAs.
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