Eicosapentaenoic Docosahexaenoic Acid Research Articles

Omega-3 fatty acid supplements and risk of atrial fibrillation and ‘micro-atrial fibrillation’: A secondary analysis from the OMEMI trial

Recent randomized clinical trials have raised concerns regarding potential off target adverse effects from supplementation of n-3 polyunsaturated fatty acids (PUFA) on atrial fibrillation (AF) risk. We aimed to assess risk and potential mediators of AF and 'micro-AF' from n-3 PUFA in post-myocardial infarction (MI) patients. In the OMEMI trial, 70-82 y. o. patients with a recent MI were randomized to 1.8g/day of eicosapentaenoic-/docosahexaenoic acid (EPA/DHA) or placebo (corn oil) for two years. New-onset AF and 'micro-AF' was recorded by clinical detection and by screening with Zenicor thumb-ECG (adjudicated by blinded investigators). Serum EPA and DHA were measured at baseline and study end. At baseline, 759 of 1014 (75%) patients had no AF history. These patients were aged 75±4 years and 71% were male. During follow-up, 43 patients developed new-onset AF (39 clinically-detected and 4 by thumb-ECG screening). In addition, 27 patients had episodes of micro-AF, yielding a total of 70 patients with new-onset AF or 'micro-AF'. In the n-3 PUFA group 46 (11.9%) had AF/'micro-AF' (28 AF, 18 'micro-AF') and in the placebo group 24 (6.5%) had AF/micro-AF (15 AF, 9 micro-AF); HR 1.90 (95%CI 1.16-3.11), P=0.011. Changes in serum EPA (but not DHA) mediated the effect from n-3 PUFA on AF risk, explaining 65% of the association. Supplementation of n-3 PUFA post MI increases the risk of 'micro-AF' and AF, and increases in EPA seems to be an important mediator of the treatment effect from n-3 PUFA on the risk of AF. OMEMI Study; ClinicalTrails.gov identifier: NCT0184194.

Effects of omega-3 fatty acid supplementation on the risk of atrial fibrillation (AF) and micro-AF in the OMEMI trial

Abstract Background Findings from recent clinical outcome trials have raised concerns regarding potential off target adverse effects from supplementation with n-3 polyunsaturated fatty acids (PUFA) on atrial fibrillation (AF) risk. Purpose We aimed to assess AF and “micro-AF” in elderly patients with myocardial infarction (MI), randomized to n-3 PUFA or placebo. Methods In the OMEMI trial, 70–82 years old patients with a recent MI were randomized to 1.8g/day of eicosapentaenoic/docosahexaenoic acid (EPA/DHA) or placebo (corn oil) for two years. New-onset AF was recorded by clinical detection and by screening, also for “micro-AF” (episodes of ≥3 consecutive irregular supraventricular ectopic beats), by two weeks Zenicor thumb ECG (adjudicated by investigators blinded to treatment allocation). Serum phospholipid content of EPA and DHA was determined by gas chromatography at baseline and study end. Results Of 1014 patients in the OMEMI trial, 759 (75%) had no history of AF at baseline. These patients were aged 75±4 years and 542 (71%) were male. During the two year follow-up 43 patients developed new-onset AF (39 clinically-detected and 4 by thumb-ECG screening). In addition, 27 patients had episodes of micro-AF, yielding a total of 70 patients with new-onset AF or micro-AF. In the n-3 PUFA group 46 (11.9%) had AF/micro-AF (28 AF and 18 micro-AF) while in the placebo group 24 (6.5%) had AF/micro-AF (15 AF and 9 micro-AF); HR 1.90 (95% CI 1.16–3.11, P=0.011; Figure 1, panel A). In both treatment arms combined, EPA increased with a mean of 60% in no-AF, 80% in micro-AF and 110% in AF (P=0.003 for linear trend; Figure 1, panel B). In patients randomized to n-3 PUFA, EPA increased with a mean of 120% in no-AF, 130% in micro-AF and 180% in clinical-AF (P=0.04 for linear trend). There were no significant associations between changes in DHA and new-onset AF. Conclusion Supplementation with 1.8 g of n-3 PUFA to post MI patients increased the risk of micro-AF and AF, and there seemed to be a graded association between increases in serum EPA and the risk of micro-AF and AF. Changes in serum DHA was not related to the risk of AF/micro-AF. Funding Acknowledgement Type of funding sources: None.

EPA/DHA Concentrate by Urea Complexation Decreases Hyperinsulinemia and Increases Plin5 in the Liver of Mice Fed a High-Fat Diet.

Dietary intake of eicosapentaenoic/docosahexaenoic acid (EPA/DHA) reduces insulin resistance and hepatic manifestations through the regulation of metabolism in the liver. Obese mice present insulin resistance and lipid accumulation in intracellular lipid droplets (LDs). LD-associated proteins perilipin (Plin) have an essential role in both adipogenesis and lipolysis; Plin5 regulates lipolysis and thus contributes to fat oxidation. The purpose of this study was to compare the effects of deodorized refined salmon oil (DSO) and its polyunsaturated fatty acids concentrate (CPUFA) containing EPA and DHA, obtained by complexing with urea, on obesity-induced metabolic alteration. CPUFA maximum content was determined using the Box–Behnken experimental design based on Surface Response Methodology. The optimized CPUFA was administered to high-fat diet (HFD)-fed mice (200 mg/kg/day of EPA + DHA) for 8 weeks. No significant differences (p > 0.05) in cholesterol, glycemia, LDs or transaminase content were found. Fasting insulin and hepatic Plin5 protein level increased in the group supplemented with the EPA + DHA optimized product (38.35 g/100 g total fatty acids) compared to obese mice without fish oil supplementation. The results suggest that processing salmon oil by urea concentration can generate an EPA+DHA dose useful to prevent the increase of fasting insulin and the decrease of Plin5 in the liver of insulin-resistant mice.

The association between dietary omega-3 fatty acids and cardiovascular death: the Singapore Chinese Health Study

Although studies suggest that omega-3 fatty acids intake may reduce cardiovascular disease (CVD) mortality risk, few studies have differentiated dietary eicosapentaenoic/docosahexaenoic acid (EPA/DHA) from alpha-linolenic acid (ALA), and epidemiological research in Asian populations is limited. The Singapore Chinese Health Study is a population-based cohort that recruited 63,257 Chinese adults aged 45-74 years from 1993 to 1998. Usual diet was measured at recruitment using a validated semiquantitative food-frequency questionnaire, and mortality information was identified via registry linkage up to 31 December 2011. Cox proportional hazard models were used to calculate hazard ratios (HRs) with adjustment for potential confounders. We documented 4780 cardiovascular deaths (including 2697 coronary heart disease (CHD) deaths and 1298 stroke deaths) during 890,473 person-years of follow up. Omega-3 fatty acids intake was monotonically associated with reduced risk of cardiovascular mortality. Compared to the lowest quartile, the HR was 0.88 (95% confidence interval, CI, 0.81-0.96), 0.88 (95% CI 0.80-0.97), and 0.83 (95% CI 0.74-0.92) for the second, third, and highest quartile, respectively (p-trend = 0.003). Both EPA/DHA and ALA were independently associated with reduced risk of cardiovascular mortality: HR comparing extreme quartiles was 0.86 (95% CI 0.77-0.96, p-trend = 0.002) and 0.81 (95% CI 0.73-0.90, p-trend < 0.001), respectively. The associations were similar for deaths from CHD and stroke and persisted in participants who were free of CVD at baseline. Higher intakes of marine (EPA/DHA) and plant (ALA) omega-3 fatty acids are both associated with reduced risk of cardiovascular mortality in a Chinese population.

Reducing the Genetic Risk of Age-Related Macular Degeneration With Dietary Antioxidants, Zinc, and ω-3 Fatty Acids

To investigate whether dietary nutrients can reduce the genetic risk of early age-related macular degeneration (AMD) conferred by the genetic variants CFH Y402H and LOC387715 A69S in a nested case-control study. For 2167 individuals (≥55 years) from the population-based Rotterdam Study at risk of AMD, dietary intake was assessed at baseline using a semiquantitative food frequency questionnaire and genetic variants were determined using TaqMan assay. Incident early AMD was determined on fundus photographs at 3 follow-up visits (median follow-up, 8.6 years). The synergy index was used to evaluate biological interaction between risk factors; hazard ratios were calculated to estimate risk of early AMD in strata of nutrient intake and genotypes. Five hundred seventeen participants developed early AMD. Significant synergy indices supported the possibility of biological interaction between CFH Y402H and zinc, β-carotene, lutein/zeaxanthin, and eicosapentaenoic/docosahexaenoic acid (EPA/DHA) and between LOC387715 A69S and zinc and EPA/DHA (all P<.05). Homozygotes of CFH Y402H with dietary intake of zinc in the highest tertile reduced their hazard ratio of early AMD from 2.25 to 1.27. For intakes of β-carotene, lutein/zeaxanthin, and EPA/DHA, these risk reductions were from 2.54 to 1.47, 2.63 to 1.72, and 1.97 to 1.30, respectively. Carriers of LOC387715 A69S with the highest intake of zinc and EPA/DHA reduced their risk from 1.70 to 1.17 and 1.59 to 0.95, respectively (all P trends <.05). High dietary intake of nutrients with antioxidant properties reduces the risk of early AMD in those at high genetic risk. Therefore, clinicians should provide dietary advice to young susceptible individuals to postpone or prevent the vision-disabling consequences of AMD.

Effect of plant and marine sources of n‐3 fatty acids on markers of bone turnover in healthy adults

Scientific evidence suggests that n‐3 polyunsaturated fatty acids (n‐3 PUFA) may exert protective effects on bone. We investigated the effects of n‐3 PUFA from plant and marine sources on markers of bone turnover. This was a controlled, single blind, randomized crossover feeding trial. Twenty‐five (12 females and 13 males) healthy participants completed the study which included three isoenergetic diets for four weeks each: [1] Control, [2] á‐linolenic acid (ALA) rich diet (1.5 oz of walnuts/d, 6 times/wk per 2400 kcal), and [3] eicosapentaenoic/docosahexaenoic acid (EPA/DHA) rich diet (8 oz of salmon/wk per 2400 kcal). Serum markers of bone turnover [c‐telopeptide (CTX), procollagen Type I N‐terminal propeptide (P1NP) and osteocalcin (OC)] and phospholipid (PL) fatty acid composition were analyzed at the end of each diet period. Plasma phospholipid EPA/DHA and ALA were significantly higher in subjects on the EPA/DHA rich and ALA rich diets (p &lt; 0.0001), respectively. There were no significant changes in serum CTX, P1NP and OC between the diets, but there was a significant negative association between P1NP levels and age (p = 0.005). In conclusion, we did not observe changes in any of the markers of bone turnover in healthy adults with either plant or marine n‐3 PUFA at amounts used in this study.