Omega-3 Long-Chain Polyunsaturated Fatty Acids, EPA and DHA: Bridging the Gap between Supply and Demand

The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina.

The aim of this study was to evaluate the dietary supplementation with omega-3 and omega-6 long-chain polyunsaturated fatty acids on the fatty acid composition of plasma and red blood cell membranes in rats with thioacetamide-induced liver cirrhosis. Thirty-eight female Wistar rats were given 300 mg thioacetamide/L in drinking water for 4 months to induce the experimental liver cirrhosis. Sixteen rats were used as controls. After treatment with thioacetamide, nine rats of each group were killed. Then, thioacetamide-treated rats were divided into three new groups, each receiving a different diet for 2 weeks: a semipurified diet (n = 9), the same diet supplemented with omega-3 long-chain polyunsaturated fatty acids (n = 10), or the same semipurified diet supplemented with omega-3 and omega-6 long-chain polyunsaturated fatty acids simultaneously (n = 10). The remaining control rats were fed the semipurified diet. Liver histology and plasma and erythrocyte fatty acid composition were assessed. An apparent improvement of the histological damage took place in the rats fed the omega-3+ omega-6-supplemented diet. The diet supplemented with polyunsaturated fatty acids of the omega-3 series induced increases in the omega-3 long-chain polyunsaturated fatty acid levels in total plasma lipids, plasma lipid fractions and in erythrocyte phospholipids, and decreases in omega-6 long-chain polyunsaturated fatty acids in erythrocyte phospholipids during the recovery of rats with thioacetamide-induced liver cirrhosis. The administration of the diet supplemented with both omega-3 and omega-6 long-chain polyunsaturated fatty acids contributed to increase the levels of total plasma saturated, monounsaturated, and omega-6 long-chain polyunsaturated fatty acids from cirrhotic rats. We conclude that the simultaneous supply of long-chain fatty acids of the omega-3 and the omega-6 series can be beneficial to improve the fatty acid status of this experimental model of liver cirrhosis.

BackgroundOmega-3 long chain-polyunsaturated fatty acids (LC-PUFAs)–docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and eicosapentaenoic acid (EPA)– and omega-6 LC-PUFA arachidonic acid (ARA), are essential for optimum physical and mental development in children. Prior to this study, the blood omega-3 LC-PUFA levels were unknown in Zimbabwean children, particularly in those aged 7–9 years, despite the documented benefits of LC-PUFAs. Documentation of the LC-PUFA levels in this age group would help determine whether interventions, such as fortification, are necessary. This study aimed to determine dried whole blood spot omega-3 and omega-6 LC-PUFA levels and LC-PUFA reference intervals among a selected group of Zimbabwean children aged 7–9 years old.MethodsWe conducted a cross sectional study from September 2011 to August 2012 on a cohort of peri-urban, Zimbabwean children aged 7–9 years. The children were born to mothers enrolled at late pregnancy into an HIV prevention program between 2002 and 2004. Dried whole blood spots were sampled on butylated hydroxytoluene antioxidant impregnated filter papers and dried. LC-PUFAs were quantified using gas liquid chromatography. Differences in LC-PUFAs between groups were compared using the Kruskal Wallis test and reference intervals determined using non-parametric statistical methods.ResultsLC-PUFAs levels were determined in 297 Zimbabwean children of whom 170 (57.2 %) were girls. The study determined that LC-PUFAs (wt/wt) ranges were EPA 0.06–0.55 %, DPA 0.38–1.98 %, DHA 1.13–3.52 %, ARA 5.58–14.64 % and ARA: EPA ratio 15.47–1633.33. Sixteen participants had omega-3 LC-PUFAs levels below the determined reference intervals, while 18 had higher omega-6 LC-PUFAs. The study did not show gender differences in omega-3 and omega-6 LC-PUFAs levels (all p > 0.05). EPA was significantly higher in the 8 year age group compared to those aged 7 and 9 years (median; 0.20 vs 0.17 vs 0.18, respectively, p = 0.049). ARA: EPA ratio was significantly higher in the 7 year age group compared to those aged 8 and 9 years (median; 64.38 vs 56.43 vs 55.87 respectively, p = 0.014).ConclusionsIn this cohort of children, lower EPA levels and higher ARA: EPA ratios were observed compared to those reported in apparently healthy children elsewhere. The high ARA: EPA ratios might increase the vulnerability of these children to inflammatory pathologies. Identification and incorporation into diet of locally produced foodstuffs rich in omega-3 LC-PUFAs is recommended as well as advocating for dietary supplementation with omega-3 fish oils and algae based oils.

We hypothesized that reduction/loss of very long chain PUFAs (VLC-PUFAs) due to mutations in the ELOngase of very long chain fatty acid-4 (ELOVL4) protein contributes to retinal degeneration in autosomal dominant Stargardt-like macular dystrophy (STGD3) and age-related macular degeneration; hence, increasing VLC-PUFA in the retina of these patients could provide some therapeutic benefits. Thus, we tested the efficiency of elongation of C20-C22 PUFA by the ELOVL4 protein to determine which substrates are the best precursors for biosynthesis of VLC-PUFA. The ELOVL4 protein was expressed in pheochromocytoma cells, while green fluorescent protein-expressing and nontransduced cells served as controls. The cells were treated with 20:5n3, 22:6n3, and 20:4n6, either individually or in equal combinations. Both transduced and control cells internalized and elongated the supplemented FAs to C22-C26 precursors. Only ELOVL4-expressing cells synthesized C28-C38 VLC-PUFA from these precursors. In general, 20:5n3 was more efficiently elongated to VLC-PUFA in the ELOVL4-expressing cells, regardless of whether it was in combination with 22:6n3 or with 20:4n6. In each FA treatment group, C34 and C36 VLC-PUFAs were the predominant VLC-PUFAs in the ELOVL4-expressing cells. In summary, 20:5n3, followed by 20:4n6, seems to be the best precursor for boosting the synthesis of VLC-PUFA by ELOVL4 protein.

BackgroundPolycystic ovary syndrome (PCOS) is strongly associated with abdominal obesity and insulin resistance and effective approaches to nutrition (e.g., omega-3 fatty acids intake) might improve the cardiometabolic risk profile. This study aimed to examine the associations of dietary and serum omega-3 fatty acids with insulin resistance (IR) and body composition among PCOS patients.MethodsA total of 185 patients with PCOS were included in our analysis. Dietary information was collected through face-to-face interviews using a 102-item food frequency questionnaire (FFQ). Serum omega-3 fatty acid levels were measured with the gas chromatography method. Body composition was measured by both dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance (BIA) methods. The multivariable linear regression model was applied to analyze the associations of dietary and serum omega-3 fatty acids with the levels of Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and body composition parameters among PCOS patients.ResultsOur results indicated that the dietary long-chain omega-3 polyunsaturated fatty acids (PUFA) intakes were negatively associated with HOMA-IR (β = –0.089, P = 0.040), fat mass (β = –0.022, P = 0.047), and body fat percentage (β = –0.026, P = 0.032). For serum biomarkers, higher total omega-3 PUFAs levels (β = –0.158, P = 0.021) and long-chain omega-3 PUFAs levels (β = –0.187, P < 0.001), particularly eicosapentaenoic acid (EPA) (β = –164, P = 0.011) and docosahexaenoic acid (DHA) (β = –0.158, P = 0.001) were also associated with decreased HOMA-IR. In addition, generally, dietary and serum long-chain omega-3 PUFA levels, DPA, and DHA levels were both positively associated with muscle mass measured by DXA; whereas serum total, long-chain and individual omega-3 PUFA levels (e.g., DPA, EPA, and DHA) were all negatively associated with fat mass and body fat percentage. These findings were further confirmed by the findings for body composition measured by the BIA method.ConclusionHigher levels of dietary and serum omega-3 PUFAs, particularly long-chain omega PUFAs (DPA and DHA), might have beneficial effects on metabolic parameters and body composition among PCOS patients.

Requirement for omega-3 long-chain polyunsaturated fatty acids by Atlantic salmon is relative to the dietary lipid level

Physical Activity, Omega-3 Supplements No Cognitive Panacea

Introduction. The concept of a balanced diet provides for the need for adequate intake of not only energy, macro- and micronutrients, but also a number of minor components with proven physiological significance (biological activity) with the diet. These compounds include long-chain omega-3 fatty acids. Materials and methods. Actual nutrition was studied by reproduction methods: three times 24-hour recall. Based on the results of the studies, the content of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids was calculated, and their main sources were determined. The study involved three hundred fourteen students of the First Moscow State Medical University named after I.M. Sechenov. The comparison groups were divided by gender and by course of study. Results. An adequate level of consumption of DHA and EPA was registered in 50.6% and 35.7% of students, respectively. Extremely low intake (less than 25% of the recommended level) with the diet of EPA and DHA was observed in 30.9% and 15% of respondents, respectively. Deficiency in EPA and DHA intake (less than 50% of the recommended level) was found in 44.6% and 34.1% of students. The study did not find a gender difference in the content of EPA and DHA in the diet. The level of medical education significantly affected the quality of the diet in terms of the content of EPA and DHA: an almost direct relationship was established between the course of study and the amount of EPA and DHA received. In the diet of senior students, the amount of EPA and DHA exceeded the similar average values in first-year students by 81.9% and 67.4%, respectively. Limitations. The study has age and regional restrictions: young people aged of 18-29 years living in the Moscow region, and restrictions on the analyzed indicators: long-chain omega-3 polyunsaturated fatty acids supplied with the diet. Conclusions. A significant deficit in the intake of long-chain omega-3 polyunsaturated fatty acids (EPA and DHA) with the diet was established in more than half of the respondents. To achieve an adequate intake of EPA and DHA, several servings of fish and crustaceans should be included in the weekly diet.

PurposeTo evaluate bioavailability of omega-3 long-chain polyunsaturated fatty acids (LCPUFA) from foods enriched with novel vegetable-based encapsulated algal oil across Australian and Singaporean populations.Methods27 men (n = 12 Australian European; n = 15 Singaporean Chinese), 21–50 yr; 18–27.5 kg/m2, with low habitual intake of omega-3 LCPUFA completed a multicentre randomised controlled acute 3-way cross-over single-blind trial. They consumed, in random order 1-week apart after an overnight fast, standard breakfast meals including 400 mg docosahexanoic acid (DHA) from either extruded rice snacks or soup both containing cauliflower-encapsulated HiDHA® algal oil or gel capsules containing HiDHA® algal oil. Blood samples for analysis of plasma DHA and eicosapentaenoic acid (EPA) were taken pre-meal and after 2, 4, 6, 8 and 24 h. Primary analyses comparing 24-h incremental area under the plasma DHA, EPA and DHA + EPA concentration (µg/ml) curves (iAUC0-24 h) between test foods were performed using linear mixed models by including ethnicity as an interaction term.ResultsPlasma iAUC0-24 h did not differ significantly between test foods (adjusted mean [95% CI] plasma DHA + EPA: extruded rice snack, 8391 [5550, 11233] µg/mL*hour; soup, 8862 [6021, 11704] µg/mL*hour; capsules, 11,068 [8226, 13910] µg/mL*hour, P = 0.31) and did not differ significantly between Australian European and Singaporean Chinese (treatment*ethnicity interaction, P = 0.43).ConclusionThe vegetable-based omega-3 LCPUFA delivery system did not affect bioavailability of omega-3 LCPUFA in healthy young Australian and Singaporean men as assessed after a single meal over 24 h, nor was bioavailability affected by ethnicity. This novel delivery system may be an effective way to fortify foods/beverages with omega-3 LCPUFA.Trial registrationThe trial was registered with clinicaltrials.gov (NCT04610983), date of registration, 22 November 2020.

In the overall analysis, preterm birth < 37 weeks and early preterm birth < 34 weeks were reduced in women receiving omega-3 LCPUFA compared with no omega-3. There was a possibly reduced risk of perinatal death and of neonatal care admission, a reduced risk of LBW babies; and possibly a small increased risk of LGA babies with omega-3 LCPUFA.For our GRADE quality assessments, we assessed most of the important perinatal outcomes as high-quality (e.g. preterm birth) or moderate-quality evidence (e.g. perinatal death). For the other outcome domains (maternal, child/adult and health service outcomes) GRADE ratings ranged from moderate to very low, with over half rated as low. Reasons for downgrading across the domain were mostly due to design limitations and imprecision.Omega-3 LCPUFA supplementation during pregnancy is an effective strategy for reducing the incidence of preterm birth, although it probably increases the incidence of post-term pregnancies. More studies comparing omega-3 LCPUFA and placebo (to establish causality in relation to preterm birth) are not needed at this stage. A further 23 ongoing trials are still to report on over 5000 women, so no more RCTs are needed that compare omega-3 LCPUFA against placebo or no intervention. However, further follow-up of completed trials is needed to assess longer-term outcomes for mother and child, to improve understanding of metabolic, growth and neurodevelopment pathways in particular, and to establish if, and how, outcomes vary by different types of omega-3 LCPUFA, timing and doses; or by characteristics of women.

Although there are many recognized health benefits for the consumption of omega-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFA), intake in the United States remains below recommended amounts. This analysis was designed to provide an updated assessment of fish and n-3 LCPUFA intake (eicosapentaenoic (EPA), docosahexaenoic acid (DHA), and EPA+DHA) in the United States adult population, based on education, income, and race/ethnicity, using data from the 2003–2014 National Health and Nutrition Examination Survey (NHANES) (n = 44,585). Over this survey period, participants with less education and lower income had significantly lower n-3 LCPUFA intakes and fish intakes (p < 0.001 for all between group comparisons). N-3 LCPUFA intake differed significantly according to ethnicity (p < 0.001), with the highest intake of n-3 LCPUFA and fish in individuals in the “Other” category (including Asian Americans). Supplement use increased EPA + DHA intake, but only 7.4% of individuals consistently took supplements. Overall, n-3 LCPUFA intake in this study population was low, but our findings indicate that individuals with lower educational attainment and income are at even higher risk of lower n-3 LCPUFA and fish intake.

Fish oil contains a complex mixture of omega-3 fatty acids, which are predominantly eicosapentaenoic acid (EPA), docosapentaenoic acid, and docosahexaenoic acid (DHA). Each of these omega-3 fatty acids has distinct biological effects that may have variable clinical effects. In addition, plasma levels of omega-3 fatty acids are affected not only by dietary intake, but also by the polymorphisms of coding genes fatty acid desaturase 1-3 for the desaturase enzymes that convert short-chain polyunsaturated fatty acids to long-chain polyunsaturated fatty acids. The clinical significance of this new understanding regarding the complexity of omega-3 fatty acid biology is the purpose of this review. FADS polymorphisms that result in either lower levels of long-chain omega-3 fatty acids or higher levels of long-chain omega-6 polyunsaturated fatty acids, such as arachidonic acid, are associated with dyslipidemia and other cardiovascular risk factors. EPA and DHA have differences in their effects on lipoprotein metabolism, in which EPA, with a more potent peroxisome proliferator-activated receptor-alpha effect, decreases hepatic lipogenesis, whereas DHA not only enhances VLDL lipolysis, resulting in greater conversion to LDL, but also increases HDL cholesterol and larger, more buoyant LDL particles. Overall, these results emphasize that blood concentrations of individual long-chain polyunsaturated fatty acids, which reflect both dietary intake and metabolic influences, may have independent, but also complementary- biological effects and reinforce the need to potentially provide a complex mixture of omega-3 fatty acids to maximize cardiovascular risk reduction.

Compared with other mammalian tissues, retina is highly enriched in PUFA. Long-chain PUFA (LC-PUFA; C18-C24) are essential FAs that are enriched in the retina and are necessary for maintenance of normal retinal development and function. The retina, brain, and sperm also contain very LC-PUFA (VLC-PUFA; >C24). Although VLC-PUFA were discovered more than two decades ago, very little is known about their biosynthesis and functional roles in the retina. This is due mainly to intrinsic difficulties associated with working on these unusually long polyunsaturated hydrocarbon chains and their existence in small amounts. Recent studies on the FA elongase elongation of very long chain fatty acids-4 (ELOVL4) protein, however, suggest that VLC-PUFA probably play some uniquely important roles in the retina as well as the other tissues. Mutations in the ELOVL4 gene are found in patients with autosomal dominant Stargardt disease. Here, we review the recent literature on VLC-PUFA with special emphasis on the elongases responsible for their synthesis. We focus on a novel elongase, ELOVL4, involved in the synthesis of VLC-PUFA, and the importance of these FAs in maintaining the structural and functional integrity of retinal photoreceptors.

Long-chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFAs) are important components in healthy diets. Adequate intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) maintains proper neurodevelopment and reduces the risk of heart disease. Long-chain omega-3 polyunsaturated fatty acids are found primarily in fish, seafood, eggs, supplements, and fortified foods. The cost of food is a major influence on food choices. This study sought to determine the cost of 500 mg of EPA + DHA (the recommended intake) in seafood, food and supplements in order to identify the most economical sources. Stores from five retail grocery chains in Honolulu, Hawaii were visited in June and July 2010 to collect data on the price of foods and supplements containing significant amounts of EPA or DHA. The analysis used information from a nutrient database comprising fourteen food composition databases detailing the omega-3 content of a wide variety of fish and seafood products. While fish oil supplements provided 500 mg of EPA + DHA at the lowest cost, relatively low-cost sources of EPA and DHA were available in fish with a variety of consumption characteristics, such as salmon and pelagic marine fishes. The most expensive sources of 500 mg of EPA +DHA were demersal marine fishes, milk and soy milk, and seaweeds. Strategies to increase intake of EPA and DHA include educating consumers on health benefits and sources, encouraging the consumption of seafood, improving the fatty acid profile of farmed seafood, and increasing the number of foods with EPA and DHA fortification.

Long-chain polyunsaturated fatty acids (LC-PUFA) are critical for the health of aquatic and terrestrial organisms; therefore, understanding the production, distribution, and abundance of these compounds is imperative. Although the dynamics of LC-PUFA production and distribution in aquatic environments has been well documented, a systematic and comprehensive comparison to LC-PUFA in terrestrial environments has not been rigorously investigated. Here we use a data synthesis approach to compare and contrast fatty acid profiles of 369 aquatic and terrestrial organisms. Habitat and trophic level were interacting factors that determined the proportion of individual omega-3 (n-3) or omega-6 (n-6) PUFA in aquatic and terrestrial organisms. Higher total n-3 content compared with n-6 PUFA and a strong prevalence of the n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) characterized aquatic versus terrestrial organisms. Conversely, terrestrial organisms had higher linoleic acid (LNA) and alpha-linolenic acid (ALA) contents than aquatic organisms; however, the ratio of ALA:LNA was higher in aquatic organisms. The EPA + DHA content was higher in aquatic animals than terrestrial organisms, and increased from algae to invertebrates to vertebrates in the aquatic environment. An analysis of covariance (ANCOVA) revealed that fatty acid composition was highly dependent on the interaction between habitat and trophic level. We conclude that freshwater ecosystems provide an essential service through the production of n-3 LC-PUFA that are required to maintain the health of terrestrial organisms including humans.