Dietary intake of different ratios of ARA/DHA in early stages and its impact on infant development.

Long-chain polyunsaturated fatty acids (LC-PUFAs), arachidonic acid (ARA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3) are essential in the development of infants. ARA and DHA from breast milk or infant formula are the main sources of access for infants to meet their physiological and metabolic needs. The ratio of ARA to DHA in breast milk varies among regions and different lactation stages. Different ratios of ARA and DHA mainly from algal oil, animal fat, fish oil, and microbial oil, are added to infant formula in different regions and infant age ranges. Supplementing with appropriate ratios of ARA and DHA during infancy promotes brain, neural, visual, and other development aspects. In this review, we first introduced the current intake status of ARA and DHA in different locations, lactation stages, and age ranges in breast milk and infant formula. Finally, we discussed the effect of different ratios of ARA and DHA on infant development. This review provided a comprehensive research basis for the nutritional research of infants who consume different ratios of ARA and DHA.

n-3 polyunsaturated fatty acids in phospholipid or triacylglycerol form attenuate nonalcoholic fatty liver disease via mediating cannabinoid receptor 1/adiponectin/ceramide pathway.

n-3 polyunsaturated fatty acids (PUFA) have shown to exert beneficial effects in the treatment of nonalcoholic fatty liver disease (NAFLD). Supplements of n-3 PUFA occur in either phospholipid or triacylglycerol form. The present study aimed to compare whether the different n-3 PUFA of marine-origin, namely krill oil, DHA/EPA-phospholipid (PL), and EPA/DHA-triacylglycerol (TAG) forms had differential abilities to ameliorate NAFLD. The NAFLD model was established in mice fed a high-fat and high-cholesterol diet (HFD). The mice showed evidence of weight gain, dyslipidemia, insulin resistance and hepatic steatosis after 9 weeks of HFD, while the three forms of the n-3 PUFA reduced hepatic TAG accumulation, fatty liver and improved insulin instance, and hepatic biomarkers after 9 weeks of intervention. Of these, krill oil intervention significantly reduced adipocyte hypertrophy and hepatic steatosis in comparison with DHA/EPA-PL and EPA/DHA-TAG groups. Importantly, only krill oil intervention significantly reduced serum alanine transaminase, aspartate transaminase concentrations and low-density lipoprotein-cholesterol, compared with the HFD group. Supplemental n-3 PUFA lowered circulating anandamide (AEA) and 2-arachidonoylglycerol (2-AG) concentrations, compared with the HFD group, which was associated with down-regulating CB1 and upregulating adiponectin expressions in adipose tissue. Besides, targeted lipidomic analyses indicated that the increased adiponectin levels were accompanied by reductions in hepatic ceramide levels. The reduced ceramide levels were associated with inhibiting lipid synthesis and increasing fatty acid ß-oxidation, finally inhibiting TAG accumulation in the liver. Through mediating CB1/adiponectin/ceramide pathway, the present study suggested that administration of krill oil had superior health effects in the therapy of NAFLD in comparison with DHA/EPA-PL and EPA/DHA-TAG.

Targeted quantitation of furan fatty acids in edible oils by gas chromatography/triple quadrupole tandem mass spectrometry (GC-TQ/MS).

Furan fatty acids (FuFAs) have been recognized as beneficial food ingredients to human health. Herein, a targeted quantitation approach by gas chromatography coupled to triple quadrupole tandem mass spectrometry (GC-TQ/MS) was developed for the identification of FuFAs in common marine and other edible oils in multiple reaction monitoring (MRM) mode without any isolation and enrichment. The limit-of-quantitation (LOQ, 0.6 pg) was determined under the optimized parameters in MRM mode. Identification of FuFAs in common edible oils demonstrated that marine fish oils were concentrated sources of 9-(3-methyl-5-pentylfuran-2-yl)nonanoic acid (9M5), 11-(3,4-dimethyl-5-propylfuran-2-yl)undecanoic acid (11D3) and 11-(3,4-dimethyl-5-pentylfuran-2-yl)undecanoic acid (11D5). However, FuFAs were not identified in common plant oils. Additionally, 11D5 was identified in the lipids of Schizochytrium limacinum at a comparable level with that in marine fish oil. We believe that this protocol could facilitate the qualitative and quantitative analysis of FuFAs in food and biological samples.

The effects of fish oil plus vitamin D3 intervention on non-alcoholic fatty liver disease: a randomized controlled trial.

PURPOSE: The present study aimed to investigate fish oil plus vitamin D3 (FO + D) supplementation on biomarkers of non-alcoholic fatty liver disease (NAFLD). METHODS: In a 3-month randomized controlled trial, 111 subjects with NAFLD, aged 56.0 ± 15.9 y, were randomized into FO + D group (n = 37), fish oil group (FO, n = 37) or corn oil group (CO, n = 37). The subjects consumed the following capsules (3 g/day), which provided 2.34 g/day of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) + 1680 IU vitamin D3 (FO + D group), or 2.34 g/day of EPA + DHA (FO group), or 1.70 g/d linoleic acid (CO group). RESULTS: Using multivariable-adjusted general linear model, there were significant net reductions in serum alanine aminotransferase (ALT), and triacylglycerol (TAG) and TNF-α levels in the FO + D and FO groups, compared with the control group (P < 0.05). The supplemental FO + D also showed significant reductions in insulin (- 1.58 ± 2.00 mU/L vs. - 0.63 ± 1.55 mU/L, P = 0.050) and IL-1ß (- 6.92 ± 7.29 ng/L vs. 1.06 ± 5.83 ng/L, P < 0.001) in comparison with control group. Although there were no significant differences between FO + D and FO groups regarding biochemical parameters, supplemental FO + D showed decreases in ALT (from 26.2 ± 13.5 U/L to 21.4 ± 9.6 U/L, P = 0.007), aspartate aminotransferase (AST, from 22.5 ± 7.0 U/L to 20.2 ± 4.0 U/L, P = 0.029), HOMA-IR (from 3.69 ± 1.22 to 3.38 ± 1.10, P = 0.047), and TNF-α (from 0.43 ± 0.38 ng/L to 0.25 ± 0.42 ng/L, P < 0.001) levels following the intervention. CONCLUSION: The present study demonstrated that groups supplemented with FO + D and FO had similar beneficial effects on biomarkers of hepatocellular damage and plasma TAG levels in subjects with NAFLD, while in the FO + D group, there were some suggestive additional benefits compared with FO group on insulin levels and inflammation. TRIAL REGISTRATION: ChiCTR1900024866.

Enrichment of n-3 containing ether phospholipids in plasma after 30 days of krill oil compared with fish oil supplementation.

There are conflicting findings over the bioavailability of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) from krill oil (KO) compared with fish oil (FO) in short- and long-term studies. The aim of this study was to compare the effects of KO versus FO on the enrichment of molecular species of plasma phospholipids in young women following a 30-day consumption of the n-3 oils. Eleven healthy women aged 18-45 years consumed seven capsules of KO per day (containing a total of 1.27 g n-3 PUFA) or five capsules of FO per day (total of 1.44 g n-3 PUFA) for 30 days in a randomized crossover study, separated by at least a 30-day washout period. Fasting blood samples were collected at day zero (baseline), day 15 and day 30 and analyzed by HPLC-MS/MS for molecular species of phospholipids. Supplementation increased n-3 PUFA in main phospholipids classes in both groups. After 30 days of supplementation, 35 out of 70 molecular species containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPAn-3) had a significantly greater concentration in KO group compared with the FO treated group. The majority (89%) of the differentiated molecular species were choline and ethanolamine ether-phospholipids. These data reveal that analysis of plasma phospholipids following 30 days of consumption of KO (a marine oil rich in phospholipids, including ether phospholipids) resulted in an enrichment of n-3 PUFA in molecular species of ether-phospholipids compared with FO (a triacylglycerol-rich marine oil).

What Is the Evidence for Dietary-Induced DHA Deficiency in Human Brains?

Docosahexaenoic acid (DHA) is a major constituent of neural and visual membranes and is required for optimal neural and visual function. DHA is derived from food or by endogenous synthesis from α-linolenic acid (ALA), an essential fatty acid. Low blood levels of DHA in some westernised populations have led to speculations that child development disorders and various neurological conditions are associated with sub-optimal neural DHA levels, a proposition which has been supported by the supplement industry. This review searched for evidence of deficiency of DHA in human populations, based on elevated levels of the biochemical marker of n-3 deficiency, docosapentaenoic acid (22:5n-6). Three scenarios/situations were identified for the insufficient supply of DHA, namely in the brain of new-born infants fed with high-linoleic acid (LA), low-ALA formulas, in cord blood of women at birth who were vegetarians and in the milk of women from North Sudan. Twenty post-mortem brain studies from the developed world from adults with various neurological disorders revealed no evidence of raised levels of 22:5n-6, even in the samples with reduced DHA levels compared with control subjects. Human populations most likely at risk of n-3 deficiency are new-born and weanling infants, children and adolescents in areas of dryland agriculture, in famines, or are refugees, however, these populations have rarely been studied. This is an important topic for future research.

Effects of dietary eicosapentaenoic acid and docosahexaenoic acid supplementation on metabolic syndrome: A systematic review and meta-analysis of data from 33 randomized controlled trials.

BACKGROUND & AIMS: Previous randomized controlled trials (RCTs) have compared the effects of pure preparations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in reducing metabolic syndrome (MetS) risk factors, but the results were inconsistent. The present study aimed to clarify whether EPA and DHA have differential effects on MetS features in humans. METHODS: A systematic literature search was conducted in CNKI, PubMed, Embase and Scopus updated to February 2021. The mean changes in the characteristics of MetS were calculated as weighted mean differences by using a random-effects model. Thirty-three RCTs were included. RESULTS: The results showed that both EPA and DHA were effective at lowering serum triglycerides (TG) levels. EPA supplementation decreased the serum levels of total cholesterol (TC) (WMD = -0.24 mmol/L; 95% CI, -0.43, -0.05 mmol/L), TG (WMD = -0.77 mmol/L; 95% CI, -1.54, -0.00 mmol/L) and low density lipoprotein-cholesterol (LDL-C) (WMD = -0.13 mmol/L; 95% CI, -0.25, -0.01 mmol/L), while DHA increased the serum levels of TC (WMD = 0.14 mmol/L; 95% CI, 0.03, 0.25 mmol/L), LDL-C (WMD = 0.26 mmol/L; 95% CI, 0.15, 0.38 mmol/L) and high density lipoprotein-cholesterol (HDL-C) (WMD = 0.07 mmol/L; 95% CI, 0.04, 0.09 mmol/L). Moreover, DHA increased the serum levels of insulin compared with EPA, especially in subgroups whose mean age was <60 years (0.43 mU/L; 95% CI: 0.04, 0.81 mU/L) and duration of DHA supplementation < 3 months (0.39 mU/L; 95% CI: 0.01, 0.77 mU/L). CONCLUSIONS: The present meta-analysis provides evidence that EPA and DHA have different effects on risk factors of MetS.

Fingertip Whole Blood as an Indicator of Omega-3 Long-Chain Polyunsaturated Fatty Acid Changes during Dose-Response Supplementation in Women: Comparison with Plasma and Erythrocyte Fatty Acids.

The sensitivity of fingertip whole blood to reflect habitual dietary and dose-dependent supplemental omega-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) intake in premenopausal women was compared to that of venous erythrocytes and plasma fatty acids. Samples were obtained from women in a randomised, double-blind, placebo-controlled trial in which premenopausal women (n = 53) were supplemented with DHA-rich tuna oil capsules and/or placebo (Sunola oil) capsules (6 capsules per day) for 8 weeks to achieve doses of either 0, 0.35, 0.7 or 1.05 g/day n-3 LCPUFA. All blood biomarkers were very similar in their ability to reflect dietary n-3 LCPUFA intake (r = 0.38-0.46 for EPA and DHA intake), and in their dose-dependent increases in n-3 LCPUFA levels after supplementation (R2 = 0.41-0.51 for dose effect on biomarker EPA and DHA levels (mol %)). Fingertip whole blood is an effective alternative to erythrocytes and plasma as a biomarker n-3 LCPUFA intake in premenopausal women.

Multiple micronutrient supplementation improves micronutrient status in primary school children in Hai Phong City, Vietnam: a randomised controlled trial.

We aimed to determine the efficacy of multiple micronutrient supplementation on the biomarkers of iron, zinc, and vitamin A status across anthropometric status categories in Vietnamese school children. In this 22-week randomised controlled trial, 347 undernourished, normal weight, or overweight/obese children aged 6-9 years were allocated to receive every school day a multiple micronutrient supplement (10 mg iron, 10 mg zinc, 400 µg vitamin A) or a placebo. Haematological indices; circulating ferritin, zinc, and retinol (corrected for inflammation); and C-reactive protein were measured at baseline and 22 weeks. At week 22, linear mixed models showed that mean corpuscular volume increased by 0.3 fL, serum ferritin by 9.1 µg/L, plasma zinc by 0.9 µmol/L, and plasma retinol by 15%, and the prevalence of zinc deficiency decreased by 17.3% points in the intervention group compared to placebo. No intervention effects were found for other haematological indices, or the prevalence of anaemia. Multiple micronutrient supplementation for 22 weeks improved the biomarkers of zinc and vitamin A status and some biomarkers of iron status, and reduced the prevalence of zinc deficiency in Vietnamese school children.Trial registration: This trial was registered on 06/09/2016 at www.anzctr.org.au as ACTRN12616001245482.

n - 3 Docosapentaenoic acid: the iceberg n - 3 fatty acid.

PURPOSE OF REVIEW: Docosapentaenoic acid (DPA) is a minor omega-3 fatty acid (FA) which has been frequently overlooked in lipid research. This review examines the biochemical and physiological outcomes of human trials which have used pure preparations of DPA (n - 3 DPA) and also recent developments in specialized proresolving lipid mediators (SPMs) derived from n - 3 DPA. RECENT FINDINGS: There have been only been two human studies and eleven animal studies with pure n - 3 DPA. The doses of n - 3 DPA used in the human trials have been 1-2 g/day. n - 3 DPA abundance is increased in blood lipid fractions within 3-4 days of supplementation. n - 3 DPA has the potential for unique properties, with a greater similarity in biological functioning with docosahexaenoic acid (DHA), than eicosapentaenoic acid (EPA). Despite the typically low levels of n - 3 DPA in most tissue lipids relative to EPA and DHA, unique SPMs, such as resolvins, maresins and protectins of the n - 3 DPA type, are involved in resolution of inflammation and regulating immune function. SUMMARY: We suggest that measurement of blood levels of n - 3 DPA gives no indication of its broad biological roles, but that the true functionality of this enigmatic n - 3 polyunsaturated fatty acid (PUFA) remains obscure until more is known about the properties of the unique DPA-derived SPMs.

Krill Oil Has Different Effects on the Plasma Lipidome Compared with Fish Oil Following 30 Days of Supplementation in Healthy Women: A Randomized Controlled and Crossover Study.

This is a follow-up of our previous postprandial study and it focused on the plasma lipidomic responses to 30 days of krill oil (KO) versus fish oil (FO) supplementations in healthy women. Eleven women (aged 18-50 years) consumed KO or FO for 30 days in a randomized, cross-over study, with at least a four-week washout period between supplementations. The daily supplements provided 1.27 g/day of long-chain (LC) omega-3 polyunsaturated fatty acids (PUFA) from KO (containing 0.76 g eicosapentaenoic acid (EPA), 0.42 g docosahexaenoic acid (DHA)) and 1.44 g/day from FO (containing 0.79 g EPA, 0.47 g DHA). Fasting plasma samples at days 0, 15, and 30 were analyzed using gas chromatography and liquid chromatography electrospray ionisation-tandem mass spectrometry. KO resulted in a significantly greater relative area under the curve (relAUC) for plasma EPA after 30 days. Lipidomic analysis showed that 26 of 43 lipid molecular species had a significantly greater relAUC in the KO group, while 17/43 showed a significantly lower relAUC compared with the FO group. More than 38% of the lipids species which increased more following KO contained omega-3 PUFA, while where FO was greater than KO, only 12% contained omega-3 PUFA. These data show that KO and FO do not have equivalent effects on the plasma lipidome.

High Variability in Erythrocyte, Plasma and Whole Blood EPA and DHA Levels in Response to Supplementation.

(1) Aim: the aim of this secondary analysis was to report the variability in response to n-3 long chain polyunsaturated fatty acids (LCPUFA) supplementation in erythrocytes, plasma and whole blood of a previously published dose response study. (2) Methods: a randomized, double-blind, placebo-controlled trial of parallel design was conducted, whereby pre-menopausal women were randomly assigned to consume 0, 0.35, 0.7 or 1 g/day of supplemental eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). Fasted blood samples were taken at baseline and after eight weeks intervention. Erythrocyte, plasma and whole blood fatty acids were extracted using the method of Lepage and Roy and analysed using gas chromatography. (3) Results: There were significant increases in EPA plus DHA levels in the 0.7 g and 1 g dose groups, with the highest increase with the 1 g dose notably: in erythrocytes (from 5.69% to 7.59%), plasma (from 2.94% to 5.48%) and in whole blood (from 3.81% to 6.03%). There was high variability in response to the supplement in erythrocytes, plasma and whole blood across the different doses. (4) Conclusion: there is high individual variability in n-3 LCPUFA levels in response to n-3 LCPUFA supplementation, which should be taken into account in clinical trials using n-3 LCPUFA supplements.

Pure omega 3 polyunsaturated fatty acids (EPA, DPA or DHA) are associated with increased plasma levels of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) in a short-term study in women.

3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is a metabolite of furan fatty acids found in plasma and urine of humans after consumption of foods containing these fatty acids. Recently, CMPF has been identified as a prominent metabolite following the consumption of either fish oil, fish oil fatty acid-ethyl esters or diets rich in fish. As furan fatty acids are known to occur in fish and fish oils (at a low level), it is possible that in these studies the CMPF in plasma originated from furan fatty acids. We report the plasma CMPF levels in 10 healthy women who consumed 1 gram of pure eicosapentaenoic acid (EPA), or docosapentaenoic acid (DPA) or docosahexaenoic acid (DHA), or olive oil daily for 6 days, in a cross-over study. The supplemented omega 3 fatty acids contained no detectable levels of furan fatty acids. The plasma CMPF and omega 3 fatty acid levels were measured by LC-MS/MS. Consumption of pure omega 3 fatty acids led to a significant increase in the plasma CMPF levels, but not with olive oil (from 1.6 to 2.5-fold compared with baseline). The plasma free fatty acid levels of EPA, DPA and DHA also increased significantly when they were supplemented (p < 0.05). Significant positive correlations existed between the plasma free fatty acid DPA and DHA levels (p < 0.05 and r = +0.49 to +0.81), but not between the EPA and CMPF levels. These data suggest that purified long chain omega 3 fatty acids may be precursors of CMPF; however the metabolic pathway(s) from omega 3 fatty acids to CMPF remain to be elucidated.

Microencapsulated Tuna Oil Results in Higher Absorption of DHA in Toddlers.

: Docosahexaenoic acid (DHA) is an essential component for brain and visual acuity development during foetal and early postnatal life. A newly released directive under the European Commission stipulates DHA as a mandatory ingredient in infant formula. This poses challenges to manufacturers in preserving the stability and bioavailability of DHA at levels akin to human breast milk. The aims of this study were (a) to investigate the bioavailability of microencapsulated omega-3 DHA formulations in healthy toddlers compared with high DHA fish oil for a one-month period and (b) to assess the effect of DHA supplementation on children's sleep and cry patterns. Sixty toddlers were randomly allocated to four groups: 1. unfortified formula, 2. unfortified formula plus high DHA tuna oil, 3. fortified formula with dairy-based microencapsulated high DHA tuna oil powder, and 4. fortified formula with allergenic-free microencapsulated high DHA tuna oil powder. Bioavailability was assessed from both blood and faecal fatty acid levels. The results showed an enhanced bioavailability with significantly greater concentrations of blood DHA levels in formulas with microencapsulated powders. There were no significant effects of treatment on sleep and cry patterns. Application and delivery of microencapsulated DHA tuna oil powder in toddlers' formula provided better bioavailability of the active DHA.

Different metabolism of EPA, DPA and DHA in humans: A double-blind cross-over study.

This study aimed to compare eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) incorporated into red blood cells (RBC) phospholipids (PL), plasma PL, plasma triglyceride (TAG), and plasma cholesteryl ester (CE) fractions, and the metabolomics profiles in a double-blind cross-over study. Twelve female healthy subjects randomly consumed 1 g per day for 6 days of pure EPA, DPA, or DHA. The placebo treatment was olive oil. The fasting venous blood was taken at days 0, 3 and 6, and the RBC PL and plasma lipid fractions were separated for fatty acid determination using thin layer chromatography followed by gas chromatography. Plasma metabolites were analyzed by UHPLC-Q-Exactive Orbitrap/MS. Supplemental EPA significantly increased the concentrations of EPA in RBC PL (days 3 and 6). For subjects consuming the DPA supplement, the concentrations of both DPA and EPA were significantly increased in RBC PL over a 6-day period, respectively. For plasma PL fraction, EPA and DPA supplementation significantly increased the concentrations of EPA and DPA at both days 3 and 6, respectively. Supplemental DHA significantly increased the concentrations of DHA in plasma PL at day 6. For plasma TAG fraction, supplementation with EPA and DPA significantly increased the concentrations of EPA and DPA at both days 3 and 6, respectively. After DHA supplementation, significant increases in the concentrations of DHA were found relative to baseline at both days 3 and 6. For plasma CE fraction, EPA supplementation significantly increased the concentrations of EPA (days 3 and 6) and DPA (days 6), respectively. Supplemental DPA significantly increased the concentrations of EPA at day 6. Meanwhile, the concentrations of DHA were significantly increased over a 6-day period of intervention after subjects consuming the DHA supplements. There were a total of 922 plasma metabolites identified using metabolomics analyses. Supplementation with DPA and DHA significantly increased the levels of sphingosine 1-phosphate (P for DPA = 0.025, P for DHA = 0.029) and 15-deoxy-Δ12,14-prostaglandin A1 (P for DPA = 0.034; P for DHA = 0.021) in comparison with olive oil group. Additionally, supplementation with EPA (P = 0.007) and DHA (P = 0.005) significantly reduced the levels of linoleyl carnitine, compared with olive oil group. This study shows that DPA might act as a reservoir of n-3 LCP incorporated into blood lipid fractions, metabolized into DHA, and retro-converted back to EPA. Metabolomics analyses indicate that supplemental EPA, DPA and DHA have shared and differentiated metabolites. The differences of these metabolic biomarkers should be investigated in additional studies.

Differential plasma postprandial lipidomic responses to krill oil and fish oil supplementations in women: A randomized crossover study.

OBJECTIVES: There is no convincing evidence that krill oil (KO) consumption results in a higher incorporation of long chain ω-3 polyunsaturated fatty acids into blood lipid fractions than fish oil (FO). This study examined the postprandial plasma lipidomic responses to KO supplementation compared with FO supplementation in healthy women. METHODS: Ten women (aged 18-45 y) consumed a high-fat (15 g of olive oil) breakfast, supplemented with 5 g of KO or FO in a randomized crossover study with a minimum 7-d washout period between the supplementations. Plasma samples collected at the fasting state and at 3 and 5 h postprandially were analyzed using liquid chromatography electrospray ionization-tandem mass spectrometry. RESULTS: After the supplementations, 5 out of 34 lipid classes or subclasses had significantly greater concentrations from KO compared with FO. There were 27 molecular species including 5 ether-phospholipid species, out of a total of 701, which had significant differences between supplementations in the postprandial period. Eicosapentaenoic acid and docosahexaenoic acid from KO were preferentially partitioned toward phospholipid molecular species, whereas eicosapentaenoic acid and docosahexaenoic acid from FO were preferentially partitioned toward neutral lipids.

Advances in n-3 polyunsaturated fatty acid nutrition.

There is conclusive evidence to demonstrate the role of omega-3 polyunsaturated fatty acids (n-3 PUFA) in human development and growth, vision, and cell membrane fluidity (membrane order). N-3 PUFA also contribute to human health maintenance through correction of arrhythmias, inhibition of platelet aggregation and prolongation of clotting time, lowering blood pressure, lowering serum triglycerides and plasma homocysteine, being antiinflammatory and immunomodulatory, being cardio-protective, increasing insulin sensitivity in Asians, and decreasing the risk of breast and colorectal cancers. This understanding of a wide spectrum of biological effects attributable to n-3 PUFA has been unsettled by a systematic review of randomized clinical intervention trials (RCTs) which has reported that n-3 PUFA have negligible or no effect on all-cause or cardiovascular mortality. Here, possible reasons for the inconsistencies in regard to n-3 PUFA and cardiovascular diseases, along with the implications for their broader biology, are considered.

How does high DHA fish oil affect health? A systematic review of evidence.

The health benefits of fish oil, and its omega-3 long chain polyunsaturated fatty acid content, have attracted much scientific attention in the last four decades. Fish oils that contain higher amounts of eicosapentaenoic acid (EPA; 20:5n-3) than docosahexaenoic acid (DHA; 22:6n-3), in a distinctive ratio of 18/12, are typically the most abundantly available and are commonly studied. Although the two fatty acids have traditionally been considered together, as though they were one entity, different physiological effects of EPA and DHA have recently been reported. New oils containing a higher quantity of DHA compared with EPA, such as fractionated and concentrated fish oil, tuna oil, calamari oil and microalgae oil, are increasingly becoming available on the market, and other oils, including those extracted from genetically modified oilseed crops, soon to come. This systematic review focuses on the effects of high DHA fish oils on various human health conditions, such as the heart and cardiovascular system, the brain and visual function, inflammation and immune function and growth/Body Mass Index. Although inconclusive results were reported in several instances, and inconsistent outcomes observed in others, current data provides substantiated evidence in support of DHA being a beneficial bioactive compound for heart, cardiovascular and brain function, with different, and at times complementary, effects compared with EPA. DHA has also been reported to be effective in slowing the rate of cognitive decline, while its possible effects on depression disorders are still unclear. Interestingly, gender- and age- specific divergent roles for DHA have also been reported. This review provides a comprehensive collection of evidence and a critical summary of the documented physiological effects of high DHA fish oils for human health.

Effect of Low Dose Docosahexaenoic Acid-Rich Fish Oil on Plasma Lipids and Lipoproteins in Pre-Menopausal Women: A Dose⁻Response Randomized Placebo-Controlled Trial.

Omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation has been shown to improve plasma lipid profiles in men and post-menopausal women, however, data for pre-menopausal women are lacking. The benefits of intakes less than 1 g/day have not been well studied, and dose⁻response data is limited. The aim of this study was to determine the effect of low doses of docosahexaenoic acid (DHA)-rich tuna oil on plasma triglyceride (TG) lowering in pre-menopausal women, and investigate if low dose DHA-rich tuna oil supplementation would increase the low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle sizes. A randomized, double-blind, placebo-controlled trial was conducted, in which 53 healthy pre-menopausal women with mildly elevated plasma TG levels consumed 0, 0.35, 0.7, or 1 g/day n-3 LCPUFA as HiDHA™ tuna oil or placebo (Sunola oil) capsules for 8 weeks. Supplementation with 1 g/day n-3 LCPUFA, but not lower doses, reduced plasma TG by 23% in pre-menopausal women. This was reflected in a dose-dependent reduction in very-low-density lipoprotein (VLDL)-TG (R² = 0.20, p = 0.003). A weak dose-dependent shift in HDL (but not LDL) particle size was identified (R² = 0.05, p = 0.04). The results of this study indicate that DHA-rich n-3 LCPUFA supplementation at a dose of 1 g/day is an effective TG-lowering agent and increases HDL particle size in pre-menopausal women.

Protective Effects of a Lipid Extract from Hard-Shelled Mussel (Mytilus coruscus) on Intestinal Integrity after Lipopolysaccharide Challenge in Mice.

This study investigated the protective effects of a lipid extract from hard-shelled mussel (HMLE) on intestinal integrity and the underlying mechanisms after a lipopolysaccharide (LPS) challenge in mice by using a 3 × 2 factorial design. Mice received olive oil, fish oil, and HMLE (n = 12 per group) by using gastric gavage for six weeks, respectively. Then half the mice in each group was injected intraperitoneally with LPS and the other half with phosphate buffered saline. Four hours after injection, mice were sacrificed and samples were collected. n-3 PUFAs were significantly enriched in erythrocytes following fish oil and HMLE supplementation. Both fish oil and HMLE improved intestinal morphology by restoring the ileac villus height and barrier function, which is indicated by decreased colonic myeloperoxidase activity and increased diamine oxidase activity as well as enhanced mRNA expression of intestinal tight junction proteins known as occludin and claudin-1 when compared with olive oil. In addition, both fish oil and HMLE increased colon production and the expression of anti-inflammatory cytokine, IL-10, while they inhibited the abnormal production and expression of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6 relative to the olive oil. Lastly, in comparison with olive oil, both fish oil and HMLE downregulated the TLR-4 signaling pathway by reducing the expression of two key molecules in this pathway, which are called TLR-4 and MyD88. These results suggest that HMLE had a protective effect on intestinal integrity after the LPS challenge, which was equivalent to that of fish oil. This effect might be associated with the regulation of inflammatory mediators and the inhibition of the TLR-4 signaling pathway.