Higher Docosahexaenoic Acid Concentrations Research Articles

Integrated Process for Schizochytrium Oil Extraction, Enzymatic Modification of Lipids and Concentration of DHA Fatty Acid Esters Using Alternative Methodologies.

Marine microalgae Schizochytrium sp. have a high content of docosahexaenoic acid (DHA), an omega-3 fatty acid that is attracting interest since it prevents certain neurodegenerative diseases. The obtention of a bioactive and purified DHA fatty acid ester using a whole-integrated process in which renewable sources and alternative methodologies are employed is the aim of this study. For this reason, lyophilized Schizochytrium biomass was used as an alternative to fish oil, and advanced extraction techniques as well as enzymatic modification were studied. Microalgal oil extraction was optimized via a surface-response method using pressurized liquid extraction (PLE) obtaining high oil yields (29.06 ± 0.12%) with a high concentration of DHA (51.15 ± 0.72%). Then, the enzymatic modification of Schizochytrium oil was developed by ethanolysis using immobilized Candida antarctica B lipase (Novozym® 435) at two reaction temperatures and different enzymatic loads. The best condition (40 °C and 200 mg of lipase) produced the highest yield of fatty acid ethyl ester (FAEE) (100%) after 8 h of a reaction attaining a cost-effective and alternative process. Finally, an enriched and purified fraction containing DHA-FAEE was obtained using open-column chromatography with a remarkably high concentration of 93.2 ± 1.3% DHA. The purified and bioactive molecules obtained in this study can be used as nutraceutical and active pharmaceutical intermediates of marine origin.

Association of Red Blood Cell Omega-3 Fatty Acids With MRI Markers and Cognitive Function in Midlife: The Framingham Heart Study.

Diet may be a key contributor to brain health in midlife. In particular, omega-3 fatty acids have been related to better neurologic outcomes in older adults. However, studies focusing on midlife are lacking. We investigated the cross-sectional association of red blood cell (RBC) omega-3 fatty acid concentrations with MRI and cognitive markers of brain aging in a community-based sample of predominantly middle-aged adults and further explore effect modification by APOE genotype. We included participants from the Third-Generation and Omni 2 cohorts of the Framingham Heart Study attending their second examination. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations were measured from RBC using gas chromatography, and the Omega-3 index was calculated as EPA + DHA. We used linear regression models to relate omega-3 fatty acid concentrations to brain MRI measures (i.e., total brain, total gray matter, hippocampal, and white matter hyperintensity volumes) and cognitive function (i.e., episodic memory, processing speed, executive function, and abstract reasoning) adjusting for potential confounders. We further tested for interactions between omega-3 fatty acid levels and APOE genotype (e4 carrier vs noncarrier) on MRI and cognitive outcomes. We included 2,183 dementia-free and stroke-free participants (mean age of 46 years, 53% women, 22% APOE-e4 carriers). In multivariable models, higher Omega-3 index was associated with larger hippocampal volumes (standard deviation unit beta ±standard error; 0.003 ± 0.001, p = 0.013) and better abstract reasoning (0.17 ± 0.07, p = 0.013). Similar results were obtained for DHA or EPA concentrations individually. Stratification by APOE-e4 status showed associations between higher DHA concentrations or Omega-3 index and larger hippocampal volumes in APOE-e4 noncarriers, whereas higher EPA concentrations were related to better abstract reasoning in APOE-e4 carriers. Finally, higher levels of all omega-3 predictors were related to lower white matter hyperintensity burden but only in APOE-e4 carriers. Our results, albeit exploratory, suggest that higher omega-3 fatty acid concentrations are related to better brain structure and cognitive function in a predominantly middle-aged cohort free of clinical dementia. These associations differed by APOE genotype, suggesting potentially different metabolic patterns by APOE status. Additional studies in middle-aged populations are warranted to confirm these findings.

Predicting dynamic response to neoadjuvant chemotherapy in breast cancer: a novel metabolomics approach.

Neoadjuvant chemotherapy (NACT) outcomes vary according to breast cancer (BC) subtype. Since pathologic complete response is one of the most important target endpoints of NACT, further investigation of NACT outcomes in BC is crucial. Thus, identifying sensitive and specific predictors of treatment response for each phenotype would enable early detection of chemoresistance and residual disease, decreasing exposures to ineffective therapies and enhancing overall survival rates. We used liquid chromatography−high‐resolution mass spectrometry (LC‐HRMS)‐based untargeted metabolomics to detect molecular changes in plasma of three different BC subtypes following the same NACT regimen, with the aim of searching for potential predictors of response. The metabolomics data set was analyzed by combining univariate and multivariate statistical strategies. By using ANOVA–simultaneous component analysis (ASCA), we were able to determine the prognostic value of potential biomarker candidates of response to NACT in the triple‐negative (TN) subtype. Higher concentrations of docosahexaenoic acid and secondary bile acids were found at basal and presurgery samples, respectively, in the responders group. In addition, the glycohyocholic and glycodeoxycholic acids were able to classify TN patients according to response to treatment and overall survival with an area under the curve model > 0.77. In relation to luminal B (LB) and HER2+ subjects, it should be noted that significant differences were related to time and individual factors. Specifically, tryptophan was identified to be decreased over time in HER2+ patients, whereas LysoPE (22:6) appeared to be increased, but could not be associated with response to NACT. Therefore, the combination of untargeted‐based metabolomics along with longitudinal statistical approaches may represent a very useful tool for the improvement of treatment and in administering a more personalized BC follow‐up in the clinical practice.

Docosahexaenoic acid and arachidonic acid levels are correlated in human milk: Implications for new European infant formula regulations.

From February 2022, all infant formula sold in the European Union must contain docosahexaenoic acid (DHA) at ~0.33%-1.14% of total fat with no minimum requirement for arachidonic acid (ARA). This work examines the association between DHA and ARA levels in human milk, the gold standard for infant feeding. Human milk (n = 470) was collected over 12-weeks postpartum from lactating mothers (n = 100) of infants born weighing <1250 g (NCT02137473). Fatty acids were analyzed by gas chromatography. ARA and DHA concentrations were associated in human milk (β = 0.47 [95% confidence interval 0.38-0.56] mol%), including transitional and mature milk, but not colostrum. This remained significant upon adjustment for percentages of other saturated, monounsaturated, n-3, or n-6 fatty acids, day of sample collection, or maternal characteristics (body mass index, ethnicity, education, and income). Infant formulas containing relatively high concentrations of DHA without ARA, as permitted by the new regulations, would not reflect the balance of these fatty acids in human milk.

Analysis of Phytosterol, Fatty Acid, and Carotenoid Composition of 19 Microalgae and 6 Bivalve Species

ABSTRACTIn this study, the functional components of 19 microalgae and 6 bivalve species were investigated in the context of the application in bivalve feeding and human health food. Principal component analysis was performed to detect any association between the functional components and individual microalgal species or taxonomic group. The proportions of the functional components differed depending on the taxonomic group or species of microalga. The genera Cheatoceros, Thalassiosira, and Isochrysis contained high concentrations of fucosterol and fucoxanthin, which are present in large amounts in brown algae. Diatoms, haptophytes, and eustigmatophytes, which are used as feed for bivalves, were rich in fucosterol and eicosapentenoic acid (EPA); further, haptophytes were rich in docosahexaenoic acid (DHA). In addition, the microalgae associated with red tide, i.e., the raphidophytes, were found to be rich in fucoxanthin, β-sitosterol, and EPA, whereas dinoflagellates were rich in DHA. Seven bivalve species also contained high concentrations of fucosterol, EPA, and DHA, as did microalgae, which were used to feed by bivalves. These results are useful in selecting microalgae effectively as feed of the bivalves.

Disrupted Blood-Retina Lysophosphatidylcholine Transport Impairs Photoreceptor Health But Not Visual Signal Transduction.

Retinal photoreceptor cells contain the highest concentration of docosahexaenoic acid (DHA) in our bodies, and it has been long assumed that this is critical for supporting normal vision. Indeed, early studies using DHA dietary restriction documented reduced light sensitivity by DHA-deprived retinas. Recently, it has been demonstrated that a major route of DHA entry in the retina is the delivery across the blood-retina barrier by the sodium-dependent lipid transporter, Mfsd2a. This discovery opened a unique opportunity to analyze photoreceptor health and function in DHA-deprived retinas using the Mfsd2a knock-out mouse as animal model. Our lipidome analyses of Mfsd2a-/- retinas and outer segment membranes corroborated the previously reported decrease in the fraction of DHA-containing phospholipids and a compensatory increase in phospholipids containing arachidonic acid. We also revealed an increase in the retinal content of monounsaturated fatty acids and a reduction in very long chain fatty acids. These changes could be explained by a combination of reduced DHA supply to the retina and a concomitant upregulation of several fatty acid desaturases controlled by sterol regulatory element-binding transcription factors, which are upregulated in Mfsd2a-/- retinas. Mfsd2a-/- retinas undergo slow progressive degeneration, with ∼30% of photoreceptor cells lost by the age of 6 months. Despite this pathology, the ultrastructure Mfsd2a-/- photoreceptors and their ability to produce light responses were essentially normal. These data demonstrate that, whereas maintaining the lysophosphatidylcholine route of DHA supply to the retina is essential for long-term photoreceptor survival, it is not important for supporting normal phototransduction.SIGNIFICANCE STATEMENT Phospholipids containing docosahexaenoic acid (DHA) are greatly enriched in the nervous system, with the highest concentration found in the light-sensitive membranes of photoreceptor cells. In this study, we analyzed the consequences of impaired DHA transport across the blood-retina barrier. We have found that, in addition to a predictable reduction in the DHA level, the affected retinas undergo a complex, transcriptionally-driven rebuilding of their membrane lipidome in a pattern preserving the overall saturation/desaturation balance of retinal phospholipids. Remarkably, these changes do not affect the ability of photoreceptors to produce responses to light but are detrimental for the long-term survival of these cells.

Polyunsaturated fatty acid production by Yarrowia lipolytica employing designed myxobacterial PUFA synthases

Long-chain polyunsaturated fatty acids (LC-PUFAs), particularly the omega-3 LC-PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), have been associated with beneficial health effects. Consequently, sustainable sources have to be developed to meet the increasing demand for these PUFAs. Here, we demonstrate the design and construction of artificial PUFA biosynthetic gene clusters (BGCs) encoding polyketide synthase-like PUFA synthases from myxobacteria adapted for the oleaginous yeast Yarrowia lipolytica. Genomic integration and heterologous expression of unmodified or hybrid PUFA BGCs yielded different yeast strains with specific LC-PUFA production profiles at promising yield and thus valuable for the biotechnological production of distinct PUFAs. Nutrient screening revealed a strong enhancement of PUFA production, when cells were phosphate limited. This represents, to the best of our knowledge, highest concentration of DHA (16.8 %) in total fatty acids among all published PUFA-producing Y. lipolytica strains.

Quercetin Potentiates Docosahexaenoic Acid to Suppress Lipopolysaccharide-induced Oxidative/Inflammatory Responses, Alter Lipid Peroxidation Products, and Enhance the Adaptive Stress Pathways in BV-2 Microglial Cells

High levels of docosahexaenoic acid (DHA) in the phospholipids of mammalian brain have generated increasing interest in the search for its role in regulating brain functions. Recent studies have provided evidence for enhanced protective effects when DHA is administered in combination with phytochemicals, such as quercetin. DHA and quercetin can individually suppress lipopolysaccharide (LPS)–induced oxidative/inflammatory responses and enhance the antioxidative stress pathway involving nuclear factor erythroid-2 related factor 2 (Nrf2). However, studies with BV-2 microglial cells indicated rather high concentrations of DHA (IC50 in the range of 60–80 µM) were needed to produce protective effects. To determine whether quercetin combined with DHA can lower the levels of DHA needed to produce protective effects in these cells is the goal for this study. Results showed that low concentrations of quercetin (2.5 µM), in combination with DHA (10 µM), could more effectively enhance the expression of Nrf2 and heme oxygenase 1 (HO-1), and suppress LPS–induced nitric oxide, tumor necrosis factor-α, phospho-cytosolic phospholipase A2, reactive oxygen species, and 4-hydroxynonenal, as compared to the same levels of DHA or quercetin alone. These results provide evidence for the beneficial effects of quercetin in combination with DHA, and further suggest their potential as nutraceuticals for improving health.

Omega-3 gantz azidoak eta osasuna

Kate luzeko omega-3 gantz-azido poliasegabeak, azido eikosapentaenoikoa (EPA) eta azido dokosahexaenoikoa (DHA) kasurako, kantitate handitan aurkitzen dira arrain koipetsuetan eta haietatik eratorritako arrain-olioan, zeina elikadura-osagarri gisa erabiltzen den (nutrazeutiko gisa, alegia). EPA zein DHA mintz zelularren fosfolipidoei gehitzen zaizkio, non lipooxigenasa eta ziklooxigenasa entzimen bidez jaria dai- tezkeen, eta zelula babesten duten hanturen kontrako produktuak eratu. Hainbat ikerketaren arabera, EPA eta DHA kontsumitzea baliagarria da zenbait gaixotasun ekiditeko edota haien tratamendurako, hantura-prozesuak eragindako gaixotasunetan bereziki. Hain zuzen ere, EPA eta DHAk hanturaren kontrako propietateak dituzte, bai erresolbina gisako hanturaren kontrako eragileak ekoiztuz, edota hantura eragileak blokeatuz. Ebidentzia zientifiko honen arabera, kate luzeko omega-3 gantz-azidoek zenbait aplikazio izan patologia kliniko edo nutrizional ezberdinen tratamenduan nahiz edota prebentzioan. Alabaina, gaur egun gantz-azido aseen kontsumoa zeharo hazi da, eta lipido onuragarrien kontsumoa, berriz, jaitsi egin da; era honetan, populazioaren atal handi batek omega-3 gantz-azidoen gabezia aurkezten du. Frogatu da egoera honek eragin handia duela endekapenezko gaixotasunen garapenean esaterako, gaixotasun kardiobaskularrak, minbizia, hantura-prozesuak eta bereziki ikusmenaren eta nerbio sistema zentralaren osasunean eta garapenean, non DHA kontzentrazio handiak dauden.

Effect of n-3 long-chain polyunsaturated fatty acids supplementation in healthy mothers on DHA and EPA profiles in maternal and umbilical blood: a randomized controlled trial.

Background The objective of the study was to compare the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) dietary supplementation on their concentration in total lipids (TL) and lipid fractions of maternal and umbilical vein (UV) blood. The specific objective was to analyze the impact of EPA and DHA supplementation on pregnancy outcome and neonatal birth weight. Methods Women were randomly single-blinded (randomized controlled trial; ISRCTN36705743) allocated to the group receiving EPA and DHA supplementation (supplemented group) or the group receiving placebo-corn oil (control group) in the time period from January 1st, 2016 until March 1st, 2017. Women in the supplemented group (n=45) took 360 mg EPA and 240 mg DHA daily while controls (n=42) were given a placebo. Maternal and UV bloods were obtained at delivery. After lipid extraction, phospholipids (PL), cholesterol esters (CE), triacylglycerols (TG) and non-esterified fatty acids were separated by thin layer chromatography and analyzed by gas chromatography. Results Higher DHA concentrations in TL (37.24±21.87 mg/L), PL (13.14±8.07 mg/L) and triacylglycerols (2.24±2.21 mg/L) were recorded in mothers from the supplemented group when compared to the study group (TL 21.89±14.53 mg/L; P<0.001; PL 9.33±5.70 mg/L; P=0.013; TG 0.56±0.43 mg/L; P<0.001). Higher DHA concentrations in UV samples were found in TL (11.51±7.34 mg/L), PL (5.29±3.31 mg/L) and triacylglycerols (0.62±0.46 mg/L) from the supplemented groups compared with controls (TL 7.37±3.60 mg/L; P=0.002; PL 3.52±2.19 mg/L; P=0.005; TG 0.40±0.46 mg/L; P=0.035). The ratio of AA:DHA was lower in maternal (2.43) and UV serum (4.0) of the supplemented group than in the control group (maternal 3.85 P<0.001; UV 4.91 P<0.001). Conclusion The study demonstrated the higher ratio of AA/DHA in the control group indicating that pregnant women on the traditional Herzegovina diet need supplementation with DHA and EPA.

Dietary supplementation with DHA-rich microalgae improves performance, serum composition, carcass trait, antioxidant status, and fatty acid profile of broilers

This experiment was conducted with 126 as-hatched male Arbor Acres chicks (1-d-old, weighing 45.3 ± 0.72g) to determine the effects of microalgae [MA, containing 29% docosahexaenoic acid (DHA)] on performance, serum composition, carcass trait, antioxidant status, and fatty acid deposition of birds. The birds were allocated randomly to 1 of 3 treatments with 7 replicate pens per treatment (6 birds per pen). The dietary treatments included a control diet [corn-soybean basal diet supplemented with 3% soybean oil (SO), CON], 1% MA diet (basal diet supplemented with 1% MA and 2% SO, 1MA), and 2% MA diet (basal diet supplemented with 2% MA and 1% SO, 2MA). All birds were raised in wire-floored cages. The trial consists of a starter phase from d 1 to 21 and a grower phase from d 22 to 42. Compared with CON, birds supplemented with MA (1MA or 2MA) had greater (P < 0.05) average daily gain, liver percentage (liver weight/body weight), and serum glucose, as well as lower (P < 0.05) feed conversation ratio, abdominal fat percentage (abdominal fat weight/body weight), and total serum cholesterol. Moreover, due to the high concentration of DHA in MA, birds fed MA showed increased (P < 0.05) concentration of eicosapentaenoic acid, DHA, superoxide dismutase, and total antioxidant capacity, as well as decreased (P < 0.05) n-6/n-3 polyunsaturated fatty acid ratio, polyunsaturated fatty acid/saturated fatty acid ratio, and malondialdehyde in the breast and thigh muscle compared with CON. In conclusion, dietary supplementation with 1% or 2% DHA-rich microalgae had positive effects on performance, serum composition, carcass trait, antioxidant status, and fatty acid deposition in birds.

Gas chromatographic analysis of fatty acid composition in the fresh water fishes in North Sulawesi

Fresh water fish is one of the nutritious food sources for the people in Indonesia including in North Sulawesi. Other than its protein, the fish oil has an important source of energy as well as nutraceutical of the people. Some fatty acids, especially omega three fatty acids have been known for their function in prevention of some artery diseases. There is not so much information available about the fatty acid composition in the fresh water fishes. Therefore, the purposes of this research are to determine the present of fatty acids and their composition in the fresh water fishes. The fish samples including, tilapia (mujair), carp (ikan mas), catfish (lele), snakehead (gabus) have been collected from various parts in North Sulawesi. Fatty acids were identified using standard fatty acid mix and measured for their concentration using gas chromatographic technique. The main fatty acids are following to their abundancy: oleic acid varies from 27.24 % for snakehead to 42.22 % for catfish; palmitic acid varies from 22.32 % for carp to 26.91 % for snakehead fish; and linolenic acid varies from 11.89 % for snakehead to 22.46 % for carp. Among the fresh water fishes, the snakehead fish has a unique fatty acid composition, it has high concentration of docosahexaenoic acid (C22:6, DHA).

Mechanisms of BK Channel Activation by Docosahexaenoic Acid in Rat Coronary Arterial Smooth Muscle Cells.

Aim: Docosahexaenoic acid (DHA) is known to activate the vascular large-conductance calcium-activated potassium (BK) channels and has protective effects on the cardiovascular system. However, the underlying mechanisms through which DHA activates BK channels remain unclear. In this study, we determined such mechanisms by examining the effects of different concentrations of DHA on BK channels in freshly isolated rat coronary arterial smooth muscle cells (CASMCs) using patch clamp techniques.Methods and Results: We found that BK channels are the major potassium currents activated by DHA in rat CASMCs and the effects of DHA on BK channels are concentration dependent with a bimodal distribution. At concentrations of <1 μM, DHA activated whole-cell BK currents with an EC50 of 0.24 ± 0.05 μM and the activation effects were abolished by pre-incubation with SKF525A (10 μM), a cytochrome P450 (CYP) epoxygenase inhibitor, suggesting the role of DHA-epoxide. High concentrations of DHA (1–10 μM) activated whole-cell BK currents with an EC50 of 2.38 ± 0.22 μM and the activation effects were unaltered by pre-incubation with SKF525A. Single channel studies showed that the open probabilities of BK channels were unchanged in the presence of low concentrations of DHA, while significantly increased with high concentrations of DHA. In addition, DHA induced a dose-dependent increase in cytosolic calcium concentrations with an EC50 of 0.037 ± 0.01 μM via phospholipase C (PLC)–inositol triphosphate (IP3)–Ca2+ signal pathway, and inhibition of this pathway reduced DHA-induced BK activation.Conclusion: These results suggest that DHA can activate BK channels by multiple mechanisms. Low concentration DHA-induced BK channel activation is mediated through CYP epoxygenase metabolites, while high concentration DHA can directly activate BK channels. In addition, DHA at low and high concentrations can both activate BK channels by elevated cytosolic calcium through the PLC–IP3–Ca2+ signal pathway.

Supplementation of Maternal Diets with Docosahexaenoic Acid and Methylating Vitamins Impacts Growth and Development of Fetuses from Malnourished Gilts

BackgroundLike many species, pregnant swine mobilize and repartition body nutrient stores during extreme malnutrition to support fetal development. ObjectiveThe objective of this study was to model chronic human maternal malnutrition and measure effects of methylating-vitamins (MVs, containing choline, folate, B-6, B-12, and riboflavin) and docosahexaenoic acid (DHA) supplementation on fetal growth and development. MethodsPregnant gilts (n = 24) were either fully nourished (2.0 kg/d) with a corn-plus-isolated-soy-protein basal diet (control) supplemented with MVs and DHA or nourishment was restricted throughout gestation. Basal diet fed to malnourished gilts was reduced progressively from 50% to 70% restriction (1.0 to 0.6 kg/d) and was supplemented following a 2 (±MVs) x 2 (±DHA) factorial design. Full-term c-sections were performed to assess impacts on low and normal birth weight (LBW/NBW) fetuses (n = 238). ResultsBody weight gain of malnourished gilts was 10% of full-fed control dams (P < 0.05), but offspring birth weight, length, girth, and percentage of LBW fetuses were not different between treatments. The number of pigs per litter was reduced by 30% in malnourished control dams. Fetal brain weights were reduced by 7% compared to positive controls (P < 0.05). Micronutrient supplementation to malnourished dams increased fetal brain weights back to full-fed control levels. Dams with DHA produced offspring with higher DHA concentrations in brain and liver (P < 0.05). Plasma choline concentration was 4-fold higher in fetuses from unsupplemented malnourished dams (P < 0.0001). Global DNA methylation status of fetuses from restricted dams was higher than in control fetuses, including brain, liver, heart, muscle, and placenta tissues (P < 0.05). Addition of DHA increased methylation in LBW fetal brains (P < 0.05). ConclusionsDespite the mobilization of maternal stores, malnourished litters displayed reduced brain development that was fully mitigated by micronutrient supplementation. Severe maternal malnutrition increased global DNA methylation in several fetal tissues that was unaltered by choline and B-vitamin supplementation.

A Mini-Review on the Effect of Docosahexaenoic Acid (DHA) on Cerulein-Induced and Hypertriglyceridemic Acute Pancreatitis.

Acute pancreatitis refers to the sudden inflammation of the pancreas. It is associated with premature activation and release of digestive enzymes into the pancreatic interstitium and systemic circulation, resulting in pancreatic tissue autodigestion and multiple organ dysfunction, as well as with increased cytokine production, ultimately leading to deleterious local and systemic effects. Although mechanisms involved in pathogenesis of acute pancreatitis have not been completely elucidated, oxidative stress is regarded as a major risk factor. In human acute pancreatitis, lipid peroxide levels in pancreatic tissues increase. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (C22:6n-3), exerts anti-inflammatory and antioxidant effects on various cells. Previous studies have shown that DHA activates peroxisome proliferator-activated receptor-γ and induces catalase, which inhibits oxidative stress-mediated inflammatory signaling required for cytokine expression in experimental acute pancreatitis using cerulein. Cerulein, a cholecystokinin analog, induces intra-acinar activation of trypsinogen in the pancreas, which results in human acute pancreatitis-like symptoms. Therefore, DHA supplementation may be beneficial for preventing or inhibiting acute pancreatitis development. Since DHA reduces serum triglyceride levels, addition of DHA to lipid-lowering drugs like statins has been investigated to reduce hypertriglyceridemic acute pancreatitis. However, high DHA concentrations increase cytosolic Ca2+, which activates protein kinase C and may induce hyperlipidemic acute pancreatitis. In this review, effect of DHA on cerulein-induced and hypertriglyceridemic acute pancreatitis has been discussed. The relation of high concentration of DHA to hyperlipidemic acute pancreatitis has been included.

Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Fetal Pulmonary Circulation: An Experimental Study in Fetal Lambs

Background: Persistent pulmonary hypertension of the newborn (PPHN) causes significant morbidity and mortality in neonates. n-3 Poly-unsaturated fatty acids have vasodilatory properties in the perinatal lung. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep and in fetal pulmonary arterial rings. Methods: At 128 days of gestation, catheters were placed surgically in fetal systemic and pulmonary circulation, and a Doppler probe around the left pulmonary artery (LPA). Pulmonary arterial pressure and LPA flow were measured while infusing EPA or DHA for 120 min to the fetus, to compute pulmonary vascular resistance (PVR). The dose effects of EPA or DHA were studied in vascular rings pre-constricted with serotonin. Rings treated with EPA were separated into three groups: E+ (intact endothelium), E− (endothelium stripped) and LNA E+ (pretreatment of E+ rings with l-nitro-arginine). Results: EPA, but not DHA, induced a significant and prolonged 25% drop in PVR (n = 8, p < 0.001). Incubation of vascular rings with EPA (100 µM) caused a maximum relaxation of 60% in the E+ (n = 6), whereas vessel tone did not change in the E− (n = 6, p < 0.001). The vascular effects of EPA were significantly decreased in LNA E+ (n = 6). Incubation with DHA resulted in only a mild relaxation at the highest concentration of DHA (300 µM) compared to E+. Conclusions: EPA induces a sustained pulmonary vasodilatation in fetal lambs. This effect is endothelium- and dose-dependent and involves nitric oxide (NO) production. We speculate that EPA supplementation may improve pulmonary circulation in clinical conditions with PPHN.

Methylmercury Concentration in Fish and Risk-Benefit Assessment of Fish Intake among Pregnant versus Infertile Women in Taiwan.

This study examined methylmercury (MeHg) concentrations in fish, the daily MeHg exposure dose, and the risk–benefit of MeHg, ω-3 polyunsaturated fatty acid (ω-3 PUFA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) related to fish intake among pregnant and infertile women in Taiwan. The measured MeHg concentrations in fish did not exceed the Codex guideline level of 1 mg/kg. Swordfish (0.28 ± 0.23 mg/kg) and tuna (0.14 ± 0.13 mg/kg) had the highest MeHg concentrations. The MeHg concentration in the hair of infertile women (1.82 ± 0.14 mg/kg) was significantly greater than that of pregnant women (1.24 ± 0.18 mg/kg). In addition, 80% of infertile women and 68% of pregnant women had MeHg concentrations in hair that exceeded the USEPA reference dose (1 mg/kg). The MeHg concentrations in hair were significantly and positively correlated with the estimated daily MeHg exposure dose. Based on the risk–benefit evaluation results, this paper recommends consumption of fish species with a low MeHg concentration and high concentrations of DHA + EPA and ω-3 PUFA (e.g., salmon, mackerel, and greater amberjack).

Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment.

A randomized trial (VITACOG) in people with mild cognitive impairment (MCI) found that B vitamin treatment to lower homocysteine slowed the rate of cognitive and clinical decline. We have used data from this trial to see whether baseline omega-3 fatty acid status interacts with the effects of B vitamin treatment. 266 participants with MCI aged ≥70 years were randomized to B vitamins (folic acid, vitamins B6 and B12) or placebo for 2 years. Baseline cognitive test performance, clinical dementia rating (CDR) scale, and plasma concentrations of total homocysteine, total docosahexaenoic and eicosapentaenoic acids (omega-3 fatty acids) were measured. Final scores for verbal delayed recall, global cognition, and CDR sum-of-boxes were better in the B vitamin-treated group according to increasing baseline concentrations of omega-3 fatty acids, whereas scores in the placebo group were similar across these concentrations. Among those with good omega-3 status, 33% of those on B vitamin treatment had global CDR scores >0 compared with 59% among those on placebo. For all three outcome measures, higher concentrations of docosahexaenoic acid alone significantly enhanced the cognitive effects of B vitamins, while eicosapentaenoic acid appeared less effective. When omega-3 fatty acid concentrations are low, B vitamin treatment has no effect on cognitive decline in MCI, but when omega-3 levels are in the upper normal range, B vitamins interact to slow cognitive decline. A clinical trial of B vitamins combined with omega-3 fatty acids is needed to see whether it is possible to slow the conversion from MCI to AD.

Intravitreal docosahexaenoic acid in a rabbit model: preclinical safety assessment.

PurposeThe purpose of the present study was to evaluate the retinal toxicity of a single dose of intravitreal docosahexaenoic acid (DHA) in rabbit eyes over a short-term period.MethodsSixteen New Zealand albino rabbits were selected for this pre-clinical study. Six concentrations of DHA (Brudy Laboratories, Barcelona, Spain) were prepared: 10 mg/50 µl, 5 mg/50 µl, 2’5 mg/50 µl, 50 µg/50 µl, 25 µg/50 µl, and 5 µg/50 µl. Each concentration was injected intravitreally in the right eye of two rabbits. As a control, the vehicle solution was injected in one eye of four animals. Retinal safety was studied by slit-lamp examination, and electroretinography. All the rabbits were euthanized one week after the intravitreal injection of DHA and the eyeballs were processed to morphologic and morphometric histological examination by light microscopy. At the same time aqueous and vitreous humor samples were taken to quantify the concentration of omega-3 acids by gas chromatography. Statistical analysis was performed by SPSS 21.0.ResultsSlit-lamp examination revealed an important inflammatory reaction on the anterior chamber of the rabbits injected with the higher concentrations of DHA (10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µ) Lower concentrations showed no inflammation. Electroretinography and histological studies showed no significant difference between control and DHA-injected groups except for the group injected with 50 µg/50 µl.ConclusionsOur results indicate that administration of intravitreal DHA is safe in the albino rabbit model up to the maximum tolerated dose of 25 µg/50 µl. Further studies should be performed in order to evaluate the effect of intravitreal injection of DHA as a treatment, alone or in combination, of different retinal diseases.

Role of Omega-3 Polyunsaturated fatty acids in Inflammation and rheumatoid arthritis disorders

Reviewing the relationships between polyunsaturated FAs (PUFAs) with inflammation and rheumatoid arthritis disorders, the PUFAs containing ω-3, ω-6 and ω-9, these ω-3FAs levels were correlated with ω-6: ω-3 ratios including arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Based on previously-reports, the levels of ω-3 FAs considered being as a 'lower risk' category for inflammation and rheumatoid arthritis. Certain PUFAs ratios may aid in inflammation and rheumatoid arthritis-related risk assessment. PUFA are the most effective for the production of oil with high concentration of DHA and EPA content significantly.DOI: http://dx.doi.org/10.3126/ijasbt.v2i1.9783Int J Appl Sci Biotechnol, Vol. 2(1): 3-17