Mg Of EPA Research Articles

ω-3 PUFA for Secondary Prevention of White Matter Lesions and Neuronal Integrity Breakdown in Older Adults

Older adults with lower intake and tissue levels of long-chain ω-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6) have more brain white matter lesions (WMLs), an association suggesting that small-vessel ischemic disease, a major contributor to the development of dementia, including Alzheimer disease, may be preventable through ω-3 treatment. To determine whether ω-3 treatment reduces WML accumulation in older adults without dementia harboring WMLs and with suboptimal ω-3 status. This quadruple-blinded, placebo-controlled, randomized clinical trial with treatment stratification by apolipoprotein E ε4 allele (APOE*E4) carrier status used linear mixed-effects models to estimate mean annual change between groups. The study was conducted at Oregon Health & Science University, a major academic medical center in the Pacific Northwest, from May 2014 to final participant visit in September 2019. Data analysis concluded in July 2022. Participants were adults without dementia aged 75 years and older with WMLs greater than or equal to 5 cm3 and plasma ω-3 PUFA less than 5.5 weight percentage of total. Three-year treatment with 1.65 g of ω-3 PUFA (975 mg of EPA and 650 mg of DHA) vs a soybean oil placebo matched for taste, smell, and appearance. The primary outcome was annual WML progression measured using magnetic resonance imaging. Secondary outcomes included diffusion tensor imaging of fractional anisotropy (DTI-FA), representing neuronal integrity breakdown. A total of 102 participants (62 women [60.8%]; mean age, 81 years [range, 75-96 years]) were equally randomized, 51 per treatment group. Although the ω-3 group had less annual WML accumulation than the placebo group, the difference was not statistically significant (1.19 cm3 [95% CI, 0.64-1.74 cm3] vs 1.34 cm3 [95% CI, 0.80-1.88 cm3]; P = .30). Similarly, the ω-3 group had less annual DTI-FA decline than the placebo group, but the difference was not statistically significant (-0.0014 mm2/s [95% CI, -0.0027 to 0.0002 mm2/s] vs -0.0027 mm2/s [95% CI, -0.0041 to -0.0014 mm2/s]; P = .07). Among APOE*E4 carriers, the annual DTI-FA decline was significantly lower in the group treated with ω-3 than the placebo group (-0.0016 mm2/s [95% CI, -0.0032 to 0.0020 mm2/s] vs -0.0047 mm2/s [95% CI, -0.0067 to -0.0025 mm2/s]; P = .04). Adverse events were similar between treatment groups. In this 3-year randomized clinical trial, ω-3 treatment was safe and well-tolerated but failed to reach significant reductions in WML accumulation or neuronal integrity breakdown among all participants, which may be attributable to sample size limitations. However, neuronal integrity breakdown was reduced by ω-3 treatment in APOE*E4 carriers, suggesting that this treatment may be beneficial for this specific group. ClinicalTrials.gov Identifier: NCT01953705.

Replacement of fish oil by alternative n-3 LC-PUFA rich lipid sources in diets for European sea bass (Dicentrarchus labrax)

IntroductionIn order to ensure lipid quality of cultured fish and an environmentally sustainable production, new alternative sources of EPA and DHA are needed to replace traditional lipid sources, such as fish oil.MethodsDifferent combinations of alternative marine lipid sources rich in n-3 LC-PUFA available in the market were herein evaluated to replace traditional fish oil (sardine oil) in diets for European sea bass (Dicentrarchus labrax). A commercial-type diet (CTRL), containing 1.6% of EPA + DHA, 5% sardine oil and 8% rapeseed oil was used as a negative control. Another diet (SARDINE) formulated with 8.5% sardine oil, 4.5% rapeseed oil and 2.5% EPA + DHA was used as the positive control. Three experimental diets were formulated to completely replace sardine oil with alternative sources, targeting approximately the same EPA + DHA level as the positive control: the SALMON diet contained 9.9% salmon by-product oil mixed with 3.1% of an algal oil rich in EPA and DHA, while the ALGARAPE and the ALGASOY diets included 4.4% of the algal oil and 8.6% of either rapeseed or soybean oil, respectively. A sixth diet (ALGABLEND) was formulated to partially replace sardine oil with salmon by-product oil and rapeseed oil, balanced with 2% of algae biomass. The experimental diets were hand-fed to 118 g fish for 54 days. ResultsAll diets were well-accepted by fish and no significant differences were found in feed efficiency, growth performance, somatic indexes or whole body composition among treatments. At the end of the trial, regardless the dietary EPA + DHA level, all fillets contained more than 250 mg of EPA + DHA per 100 g fresh weight, meeting EFSA recommendations for cardiovascular risk prevention for European adults (> 250 mg day -1). DiscussionOverall, this study demonstrated that combining expensive sources of n-3 LC PUFA (Veramaris® or Algaessence Feed™ with low-priced sustainable oils (salmon by-products oil or vegetable oils) allows fortifying European sea bass flesh with EPA and DHA, without major textural changes. This approach is a successful strategy for mitigating the negative effects associated with the high inclusion of vegetable oils. However, the retention of n-3 LC-PUFA in muscle was not significantly increased, suggesting that there is a maximum dietary threshold beyond which β-oxidation might be promoted, and hence there is no advantage in increasing the dietary level of these fatty acids in European sea bass diets.

The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: a randomized, double-blind, placebo-controlled trial

Objective Imbalances in immune regulation are important features of migraine pathophysiology. In line with this, the current study investigated the efficacy of omega-3 fatty acids supplementation on inflammatory and anti-inflammatory markers in patients with migraines. Materials and Methods This randomized, double-blind, placebo-controlled trial consisted of 40 patients that were prone to experiencing episodic migraines. For two months, participants were randomized into one group that received omega-3 supplementation (n= 20), 600 mg of EPA and 300 mg of DHA, twice daily) or another group that received a placebo (n= 20). Transforming growth factor β (TGF-β), interleukin (IL)-4, interferon-gamma (IFN-γ), and interleukin (IL)-17 serum levels were assessed using enzyme-linked immunosorbent assay methods at baseline and following the intervention. The current study was registered on ClinicalTrials.gov with the registration number NCT02532023. Results After two months of intervention, the administration of omega-3 fatty acids resulted in a significant rise in the concentrations of anti-inflammatory cytokine IL-4 (p=0.010) as well as a significant reduction in concentrations of pro-inflammatory cytokine IFN-γ (p=0.001) compared with the placebo. However, no significant changes were observed in serum TGF-β and IL-17 levels. Discussion Our findings indicated consumption of omega-3 fatty acids may have a potentially beneficial response on the inflammatory immune response in patients with migraines. Larger trials are needed to corroborate these findings.

Effect Of Omega-3 Fatty Acids On Cardiovascular Protection- A Randomised Controlled Clinical Interventional Study

There is a great deal of public belief in the cardiovascular benefits of omega-3 fats. Recent trials of omega-3 fatty acids in cardiovascular issues are unclear or failed to show the significant benefit for reducing cardiovascular events. To perform a human trial of omega 3 fatty acids supplementation to test its effectiveness on cardiovascular diseases. A randomized interventional study was carried out in 145 patients in the age group of 18 or older at any risk of cardiovascular disease. Treatment period of 6 months with supplementation of daily dose of 360 mg of EPA and 480 mg of DHA for one group and to the other group, atorvastatin 10 mg was given. Biochemical and clinical evaluation was performed for the baseline, 3rd and the 6th months to assess the effectiveness of omega 3 fatty acids on cardiovascular diseases. The changes in the biochemical parameters total cholesterol, HDL, LDL and triglycerides among the omega 3 fatty acid group and statin group were as 218.17 vs 204.45, 55.24 vs 60.3, 142.9 vs 132.41and 168.95 vs 152.5 respectively with a p value of 0.0001. Omega 3 supplements have little or no effect on the risk of cardiovascular diseases according to the research. The better evidence identified in this research does not demonstrate any cardiovascular protection with the supplementation of omega 3 fats.

Increased Plasma L-Arginine Levels and L-Arginine/ADMA Ratios after Twelve Weeks of Omega-3 Fatty Acid Supplementation in Amateur Male Endurance Runners.

It is not fully understood how supplementation with omega-3 fatty acids affects the metabolism of amino acids required for the bioavailability/synthesis of NO, i.e., L-arginine (L-arg), asymmetric dimethylarginine (ADMA), their metabolites, and the L-arg/ADMA ratio and their impact on running economy (RE) in runners. Thus, 26 male amateur endurance runners completed a twelve-week study in which they were divided into two supplemented groups: the OMEGA group (n = 14; 2234 mg and 916 mg of eicosapentaenoic and docosahexaenoic acid daily) or the MCT group (n = 12; 4000 mg of medium-chain triglycerides daily). At the same time, all participants followed an endurance training program. Before and after the 12-week intervention, blood was collected from participants at two time points (at rest and immediately post-exercise) to determine EPA and DHA in red blood cells (RBCs) and plasma levels of L-arg, ADMA, and their metabolites. RBC EPA and DHA significantly increased in the OMEGA group (p < 0.001), which was related to the resting increase in L-arg (p = 0.001) and in the L-arg/ADMA ratio (p = 0.005) with no changes in the MCT group. No differences were found in post-exercise amino acid levels. A total of 12 weeks of omega-3 fatty acid supplementation at a dose of 2234 mg of EPA and 916 mg of DHA daily increased levels of L-arg and the L-arg/ADMA ratio, which indirectly indicates increased bioavailability/NO synthesis. However, these changes were not associated with improved RE in male amateur endurance runners.

Abstract P2-11-17: Feasibility of microbiome analysis from random periareolar fine needle aspiration in premenopausal women at increased risk for breast cancer

Abstract Background: Nearly 10% of breast cancers (BC) are diagnosed in premenopausal woman under age 45 and of childbearing potential. Women considering future childbearing are typically excluded from BC prevention trials and are ineligible for standard of care chemoprevention. More biomarkers are needed to support BC prevention trials in this young cohort. Women of childbearing potential are encouraged to supplement diet with minimum of 300mg of EPA + DHA omega-3 fatty acids (FA) per day. EPA and DHA are thought to have a favorable effect on the gut microbiome implicated in cancer development. Few studies have characterized the breast microbiome by core biopsy or surgical sample but to our knowledge no studies have explored the feasibility of breast microbiome collection using the less invasive technique Random Periareolar Fine Needle Aspiration (RPFNA). In a pilot study, we demonstrated feasibility of recruiting premenopausal women considering future pregnancy to a BC prevention trial with a 6-month intervention of omega-3 FA supplementation (19-A-1921-SABCS). RPFNA was used to collect breast tissue for biomarker analysis, which is a mildly invasive technique used for repeated sample collection in BC prevention trials. Objectives: 1) To determine the feasibility of characterizing breast microbiome from specimens collected by RPFNA in premenopausal woman at high risk for BC, 2) To identify changes in the breast and stool microbiome with omega-3 FA supplementation in this population. Methods: Ten women between the ages of 21 and 40 who were considering future pregnancy and at high risk for BC were enrolled to a pilot study and took Omega-3-Acid Ethyl Ester (total of 750mg DHA and 930mg EPA) daily for 6 months. Tissue collection with RPFNA of breast as well as blood, urine and stool were completed at baseline and off-study visit. RPFNA samples from the first 2 passes at each site of breast (4 sites total) were collected for microbiome and placed in a 2mL tube with 0.5 – 1cc of PBS and flash frozen and stored at -80C. DNA was isolated from RPFNA samples using QIAamp DNA Mini Kit (51304). Microbiome profiling analysis was performed by Veracet using 16S V4 rRNA gene sequencing on the Illumina MiSeq platform. Wilcoxon signed rank test was used to compare paired samples. Results: Of the 10 women enrolled, median age was 33 years (range 22-37). 90% (9 of 10) returned for off-study visit. Of the 9 women who completed the off-study visit, 2 elected to not undergo off-study RPFNA. There were 16 total stool samples and 17 total RPFNA samples for microbiome evaluation. There were 6 paired (baseline and off-study) stool and 7 paired RPFNA samples. Mean DNA concentration from RPFNA samples was 10.36ng/µl (range 0.62 – 74.10). From all samples, 52.1% of operational taxonomic units (OTUs) were classified at the genus level. Breast samples were sequenced to a depth of mean 27,767 reads (range 5,745 – 125,445) and stool to a depth of mean 119,296 reads (range 72,979 – 188,867). The alpha diversity metric of OTU richness was 1069 (breast) and 438 (stool). Shannon diversity was 4.51 (breast) and 3.89 (stool). Mean OTU richness for baseline and off-study RPFNA samples were 1098 and 1028 respectively (V = 25, p value = 0.076). Mean OTU richness for baseline and off-study stool samples were 440 and 437 respectively (V = 15, p value = 0.40). Conclusion: We demonstrated feasibility of analyzing breast microbiome from an RPFNA specimen. Additional investigation with modifications to technique and/or sample population is. needed to achieve adequate sequencing depth for characterization of breast microbiome. Lower depth of sequencing in breast samples is thought to reflect differences in microbial DNA quantity. We were unable to assess change in microbiome composition in breast or stool samples with omega-3 fatty acid supplementation due to small sample size. Citation Format: Lauren E Nye, Jennifer R Klemp, Kandy R Powers, Anne P O'Dea, Amy L Kreutzjans, Trina Metheny, Teresa A Phillips, Susan E Carlson, Bruce F Kimler, Carol J Fabian. Feasibility of microbiome analysis from random periareolar fine needle aspiration in premenopausal women at increased risk for breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-17.

Maternal supplementation of high-value PUFA-Rich Isochrysis sp. biomass prevents monosodium glutamate-induced neurotoxicity in first-generation Wistar rats

Prenatal supplementation of high-value PUFA (HVPUFA) is essential for adequate brain development in infants. As marine microalgal derived omega-3 fatty acids are considered an alternative source of fish oil, their neuroprotective role on monosodium glutamate (MSG)-induced neurotoxicity, bioavailability, and disease prevention in first-generation (F1) animals need to be explored at molecular level. This study tested the long term supplementation of microalgal derived ω-3 PUFAs from parent rats to its offspring rats and studied the neuroprotective role in monosodium glutamate (MSG)-induced neurotoxicity in F1 rats. The parent animals were divided into three groups: control, microalgal-administered group (5.7 mg of EPA and 1.4 mg of DHA/kg BW from Isochrysis sp.), and fish oil-administered group (4.2 mg of EPA and 2.9 mg of DHA/kg BW derived from fish oil) (FG) and continued up to F1 generation. The F1 male rats from respective parents were separated for disease induction: group I animals (control) were administered with 500 μl of Milli-q water alone and group II (disease control), III (Microalga), and IV (fish oil) animals were administered with 2 g/kg bodyweight of MSG for 10 alternative days. Microalga-treated F1 rats showed significant HDL (43 mg/dl) levels when compared to their experimental groups. Brain tissues of microalga-treated F1 rats (MG) showed higher concentration of DHA (10.1 mg/100 mg tissue) and ARA (18.7 mg/100 mg tissue) levels and significant reduction of MDA (30 nM mg protein) levels. Furthermore, MSG induced neurotoxicity was ameliorated through the activation of CREB and BDNF genes The mRNA expressions of CREB and BDNF were 1.5-fold higher and NMDA levels were 2.0-fold higher in treated groups compared to disease control group. However, the expressions of antioxidant genes (SOD, catalase, and GPX) and apoptotic genes (Bcl-2 and Caspase-3) were significantly reduced in MG treated F1 rats when compared to disease control rats. Histopathological results also showed minimal focal damage in the tissues of MG F1 rats. Prenatal and continuous supply of microalgal biomass improves brain DHA and greatly reduced the consequences of MSG neurotoxicity in F1 rats.

Marine n‐3 fatty acids and cognitive change among older adults in the VITAL randomized trial

AbstractBackgroundHigh intake of marine omega‐3 (n‐3) fatty acids has been associated with lower risk of cognitive decline; however, few large‐scale, long‐term randomized trials have been conducted. We evaluated n‐3 supplementation (1 gram/day, including 840 mg of EPA + DHA) and change in cognitive function over 2‐3 years.MethodCommunity‐dwelling participants aged 60+ years (mean[SD]=70.9[5.8]y) in the Vitamin D and Omega‐3 Trial (VITAL) were included: 3424 had cognitive function assessment by phone (VITAL‐Cog; 8 neuropsychological tests; mean follow‐up=2.8 years) and 794 were evaluated in‐person at the Harvard Clinical and Translational Science Center (CTSC‐Cog; 9 neuropsychological tests; mean follow‐up=2.0 years). The primary, pre‐specified outcome was a global composite score (average z‐scores across all tests) of change over two assessments. We used multivariable‐adjusted linear mixed models and meta‐analyzed the results for the two settings.ResultWe observed no significant effect of n‐3 supplementation on the global composite score: the mean difference in annual rate of change for the n‐3 versus placebo group was ‐0.01 standard units (95% CI:‐0.02,0.003) in VITAL‐Cog and ‐0.002 (95% CI:‐0.04,0.03) in CTSC‐Cog; the pooled mean difference was ‐0.01 (95%CI:‐0.02,0.003; p=0.15). For secondary outcomes of change in verbal memory, executive function/attention and general cognition, we observed null results to trends of adverse associations with n‐3 treatment versus placebo that were not statistically significant after multiple‐testing correction. In pre‐specified secondary analyses, we observed no significant interaction of the intervention with baseline plasma omega‐3 fatty acid levels for the global composite score (pooled p‐interaction=0.37).ConclusionMarine n‐3 supplementation (1 gram/day) did not confer cognitive benefits over 2‐3 years in community‐dwelling older adults.

Effects of dietary high dose DHA omega-3 supplement in dry eye with meibomian gland dysfunction.

To evaluate the clinical efficacy of dietary supplement of high dose DHA omega-3 in dry eye with meibomian gland dysfunction (MGD). Prospective randomized double-masked, placebo-controlled clinical trial was conducted in mild to moderate dry eye patients with MGD. Patients have no history of taking any dietary omega-3 supplements before 3mo. Patients were divided into two groups: 24 patients in the omega-3 group and 26 patients in the placebo group. The omega-3 group received two capsules of Easyeye Dry®, total containing 600 mg of EPA and 1640 mg of DHA, while the placebo group received two capsules containing 3000 mg of olive oil. All patients take two pills once a day. The examination of MGD scores, tear break-up time (TBUT), corneal staining test (NEI), strip meniscometry (SM tube), and ocular surface disease index (OSDI) scores were performed at baseline, after 4 and 8wk. A total of 50 patients were included. There were no differences in baseline characteristics between the two groups, such as age, sex, and other ocular examination findings. The TBUT, NEI, and OSDI scores significantly improved after 4 and 8wk in both groups. While after 8wk TBUT (6.00±1.62s vs 5.08±1.28s, P=0.034) and MGD score (7.2±1.8 vs 8.1±2.6, P=0.033) in the omega-3 group was more significantly improved than that of the placebo group. Dry eye with the MGD patient, a high dose of DHA omega-3 dietary supplement can improve TBUT and MGD score after 8wk, effective in stabilizing the tear film.

Evaluating the Lipid Quality of Yellowfin Tuna (Thunnus albacares) Harvested from Different Oceans by Their Fatty Acid Signatures.

The aim of this study was to evaluate the influence of the fishing location on yellowfin tuna’s (YFT; Thunnus albacares) white muscle total lipid (TL) content and fatty acid profile. The comparison included 45 YFT loins, equally divided between the Atlantic, Indian and Pacific Oceans. The ocean had no significant influence on YFT TL content, total PUFA and total n-3 PUFA (p > 0.05), averaging 1.09 g/100 g of muscle, 229.2 and 192.8 mg/100 g of muscle, respectively. On the other hand, the YFT harvested on the Indian Ocean displayed significantly higher contents of both SFA and MUFA totals than the Atlantic Ocean counterparts (p < 0.05), while the YFT harvested in the Pacific Ocean presented intermediate values, not differing significantly from the other two origins. The YFT from the Indian and Pacific oceans held twice the n-6 PUFA content recorded in the Atlantic YFT (44.1 versus 21.1 mg/100 g of muscle). Considering the recommended daily intake of EPA plus DHA is 250 mg, the consumption of 100 g of YFT from the Atlantic, Indian and Pacific Oceans would provide 149.2 mg, 191.8 mg or 229.6 mg of EPA plus DHA, representing 59.7%, 76.7% or 91.8% of the recommended daily intake, respectively.

Cultivated and Wild Juvenile Thick-Lipped Grey Mullet, Chelon labrosus: A Comparison from a Nutritional Point of View.

Simple SummaryThe thick-lipped grey mullet (Chelon labrosus) has good potential for aquaculture diversification in Europe. However, research studies about this species are scarce, particularly focusing on the nutritional attributes of wild and cultivated thick-lipped grey mullets that might help to optimize its feeding regime. In order to determine the nutritional composition of thick-lipped grey mullet juveniles, wild and cultivated specimens were collected and compared. To do so, the liver fatty acids, muscle proximate composition, fatty acids and amino acids were analyzed. The wild specimens had higher levels of polyunsaturated fatty acids and a higher content of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids than the farmed specimens. Furthermore, all the amino acid scores were above 100% compared to the Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO) standard. This study provides new knowledge and contributes to understanding the nutritional attributes of wild and cultured C. labrosus and helps to design diets according to their nutritional demands.The thick-lipped grey mullet (Chelon labrosus) is a nominee fish species for aquaculture diversification in Spain because it is an omnivore and euryhaline species, but limited knowledge about the nutritional attributes of this species is available. This study aimed to characterize the chemical composition of wild and cultured fish. The muscle proximate composition, and fatty acid and amino acid profiles were assessed. The cultivated specimens showed a higher lipid content and lower protein and ash contents compared with the wild specimens. The predominant tissue fatty acids in both the wild and cultivated fish were palmitic acid (16:0), oleic acid (18:1n-9) and docosahexaenoic acid (DHA, 22:6n-3). A higher content of arachidonic acid (ARA, 20:4n-6), eicosapentaenoic acid (20:5n-3) and DHA were detected in the muscle of wild mullets, while the fish supplied with commercial pellets showed higher quantities of monounsaturated fatty acids, and lower quantities of saturated fatty acids and polyunsaturated fatty acids (PUFAs). Regarding PUFAs, n-3 fatty acids were predominant in wild mullets, while n-6 and n-9 were more abundant in farmed fish. In terms of amino acid composition, except for histidine in wild specimens, the amino acid amounts were higher than the FAO/WHO standard. In conclusion, C. labrosus may contribute to improving the dietary intake of highly polyunsaturated n-3 fatty acids, with a benefit to human health, owing to that fact that a 100-g fillet portion of cultivated and wild C. labrosus can provide 770 mg and 1160 mg of EPA and DHA, respectively, which exceeds the 250 mg dietary daily intake recommended by the FAO/WHO.

Effective Nutraceuticals on Age-Associated Cognitive Decline: A Systematic Review

Abstract Objectives The prevalence of neurodegenerative disorders such as dementia is positively correlated to aging. As there is insufficient evidence for the medicinal remedies of dementia, focusing on prevention strategies to use nutraceuticals could provide positive results. Therefore, this systematic review aimed to evaluate the effect of various nutraceuticals on age-associated cognitive decline. Methods Literature was searched using PubMed, EMBASE, Cochrane, and PsycINFO databases with the search terms being nutraceuticals in cognitive dysfunction. The literature was limited to human studies, randomized controlled trials, and a single material. Selection of literature, evaluation of the risk of bias, and assessment of the quality of evidence was conducted independently by two reviewers. Results We finally included 17 studies of literature after excluding the risk of bias ‘high.’ The evidence was rated ‘high’ quality for both omega-3 fatty acids and vitamin Bs. Other materials, including vitamins D &amp; E, anserine/carnosine, and chromium were identified as ‘moderate’ quality. Omega-3 fatty acids (0.48–2.2 g of DHA and 203–720 mg of EPA) relieved cognitive decline and amyloid β related proteins in participants with mild cognitive impairment. However, the cognitive decline did not have an effect on dementia patients. Vitamin B (25–500 µg of B12 and 20 mg of B6) group exhibited decreased homocysteine levels, followed by enhanced cognitive function. However, vitamin D &amp; E, anserine/carnosine, and chromium showed a shred of limited evidence owing to limited studies. Conclusions This study suggests that omega-3 fatty acids and vitamin B have protective effects against age-associated cognitive decline. Funding Sources This research was funded by Ottogi, grant number HY-201900000670003.

Synthesis of lipase/silica biocatalysts through the immobilization of CALB on porous SBA-15 and their application on the resolution of pharmaceutical derivatives and on nutraceutical enrichment of natural oil

• A recombinant lipase was produced in a low-cost medium. • The immobilization process was studied. • The use of ammonium fluoride, APTES and GA allowed a most active biocatalyst. • Resolution of racemic myo -inositol derivatives was done with eep>99 %. • It was possible to obtain lipids containing 181.6 mg of EPA and DHA in coconut oil. A recombinant lipase from Candida antarctica , LIPB, was obtained through fermentation using an alternative low-cost medium and immobilized on the distinct mesoporous silica particles. The performance and versatility of the new biocatalysts was evaluated, for the first time, on two biotechnological interest reactions: resolution of racemic myo-inositol derivative and acidolysis reaction of coconut oil. For the racemate, the covalent biocatalyst SBA-15-F-APTES-GA-LIPB exhibited the highest conversions and enantiomeric excess of up to 99 %. It was the first time that covalent biocatalyst was used for resolution of racemic myo-inositol derivative. The most active biocatalyst (SBA-15-F-APTES-GA-LIPB) was used on ten different reaction cycles maintaining its activity, highlighting the operational stability of the developed biocatalyst. Moreover, it was possible to produce food oils enriched with polyunsaturated fatty acids (PUFA), obtaining lipids containing 181.6 mg of EPA and DHA in coconut oil. The preliminary economic analyses also indicate that the enzymatic production of such nutraceuticals and pharmaceutics compounds may be economically feasible, principally exploring low-cost strategies for enzyme production.

The Effect of Omega-3 Fatty Acid Supplementation on Serum Adipocytokines, Lipid Profile and Biochemical Markers of Inflammation in Recreational Runners.

Background: The study aimed to evaluate the effects of a 3-week ω-3 PUFA supplementation on serum adipocytokines (i.e., adiponectin, leptin), neuregulin-4 (NRG4) and erythrocyte omega-3 (ω-3) fatty acid content, as well as the blood antioxidant defense capacity in non-elite endurance runners. Methods: Twenty-four runners were randomized into two groups: the supplemented group, who received omega free fatty acids extract containing 142 mg of EPA, 267 mg of DHA, 12 mg of vitamin E and 5 µg of vitamin D, each administrated at a dose of six capsules twice a day for three weeks, or the placebo group. Venous blood samples were withdrawn at the start and at the end of the study protocols to estimate serum biochemical variables. Results: A significantly higher ω-3 index and lower AA/EPA ratio was observed after ω-3 PUFA compared to pre-supplementation levels (p < 0.001 and p < 0.001, respectively). An increase in baseline adiponectin and NRG4 levels, as well as a decrease of leptin concentration and lipid profile improvement, were observed in subjects after a ω-3 PUFA diet. The increased ω-3 index had a significant effect on TNFα levels and a serum marker of antioxidant defense. Conclusions: The ω-3 PUFA extract with added vitamin E and D supplementation may have a positive effect on the function of the adipocyte tissue, as well as the ability to prevent cardiovascular complications in athletes.

Evaluation of the Effect of Fish Oil Alone and in Combination with a Proprietary Chromium Complex on Endothelial Dysfunction, Systemic Inflammation and Lipid Profile in Type 2 Diabetes Mellitus - A Randomized, Double-Blind, Placebo-Controlled Clinical Study.

PurposeThis study was conducted to evaluate the effectiveness of fish oil alone and with an adjunct, a proprietary chromium complex (PCC), on cardiovascular parameters – endothelial dysfunction, lipid profile, systemic inflammation and glycosylated hemoglobin – in a 12-week randomized, double-blind, placebo-controlled clinical study in type 2 diabetes mellitus subjects.Patients and MethodsIn this randomized, double-blind, parallel group study, 59 subjects in three groups completed the study: Group A, fish oil 2000 mg; Group B, fish oil 2000 mg + PCC 10 mg (200 µg of Cr3+); and Group C, fish oil 2000 mg + PCC 20 mg (400 µg of Cr3+) daily for 12 weeks (2000 mg of fish oil contained 600 mg of eicosapentaenoic acid [EPA] and 400 mg of docosahexaenoic acid [DHA], the omega-3 fatty acids). Endothelial function, by estimating reflection index (RI), biomarkers of oxidative stress (nitric oxide [NO], malondialdehyde [MDA], glutathione [GSH]) and inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP], intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], endothelin-1) were evaluated at baseline, and 4 and 12 weeks. Lipid profile, platelet aggregation and glycosylated hemoglobin [HbA1c) were tested at baseline and 12 weeks. Any reported adverse drug reactions were recorded. Statistical analysis was performed using GraphPad Prism 8.ResultsThe present study shows that fish oil by itself, at a dose of 2000 mg (600 mg of EPA + 400 mg of DHA) per day, led to significant, but only modest, improvement in cardiovascular parameters (RI from −2.38±0.75 to −3.92±0.60, MDA from 3.77±0.16 to 3.74±0.16 nM/mL, NO from 30.60±3.18 to 32.12±3.40 µM/L, GSH from 568.93±5.91 to 583.95±6.53 µM/L; p≤0.0001), including triglyceride levels. However, when PCC was added to fish oil, especially at the 20 mg dose, there were highly significant improvements in all the parameters tested (RI from −2.04±0.79 to −8.73±1.36, MDA from 3.67±0.39 to 2.89±0.34 nM/mL, NO from 28.98±2.93 to 40.01±2.53 µM/L, GSH from 553.82±8.18 to 677.99±10.19 µM/L; p≤0.0001), including the lipid profile. It is noteworthy that the triglycerides were decreased significantly by addition of 20 mg of PCC although the dose of fish oil was only 2 g/day and the baseline triglyceride levels were only about 200 mg/dL. Fish oil alone did not significantly decrease the HbA1c, whereas the addition of 20 mg of PCC did.ConclusionAddition of PCC, especially at 20 mg dose, significantly improves the efficacy of fish oil in addressing cardiovascular risk factors compared to fish oil given alone.

A4142 Omega-3 fatty acid has effect on improvement of peripheral artery disease in correlation with degree of lowering remnant-like lipoprotein cholesterol in hemodialysis patients with dyslipidemia

Objectives: Recently, we showed the therapeutic effect of high dose omega-3 fatty acid (EPA/DHA) on peripheral artery disease (PAD) by lowering remnant-like lipoprotein cholesterol (RLP-C) in hemodialysis patients with dyslipidemia. In the present study, we aimed to investigate whether improving effect on PAD by lowering RLP-C can be observed even in low dose of EPA/DHA. Methods: We randomly assigned 38 hemodialysis patients with dyslipidemia to receive either add-on of high dose EPA/DHA (1860 mg of EPA and 1500 mg of DHA) with conventional therapy (H group: n = 19) or conventional therapy alone (C group) for 3 months. Sixteen out of 19 patients enrolled in the C group continued the study for another 3 months add-on of low dose EPA/DHA (930 mg of EPA and 750 mg of DHA: L group). RLP-C as an atherogenic lipid parameter, and ankle-brachial index (ABI) as an index of PAD were measured before and after the intervention. Results: After 3 months intervention of EPA/DHA, RLP-C and ABI changed by − 3.25 ± 3.15 mg/dL and 0.07 ± 0.11 in H group, by − 0.37 ± 3.50 mg/dL and − 0.01 ± 0.14 in L group (between group difference, p = 0.015 and p = 0.049, respectively). There was a significant negative correlation between the change in RLP-C and the change in ABI in H group (r = − 0.475, p = 0.040) and it was also significant when L group was analysed together (r = −0.546, p = 0.001). The change in RLP-C was an independent determinant of the change in ABI after adjustment for confounding factors in H and L group analyzed together (p < 0.001). Conclusion: Low dose EPA/DHA did not show decrease in RLP-C or improvement of PAD, supporting the fact that the degree of lowering RLP-C is a key factor for improving effect of PAD in hemodialysis patients with dyslipidemia undergoing conventional therapy such as use of statin.

MTHFR 677C → T genotype modulates the effect of a 5-year supplementation with B-vitamins on homocysteine concentration: The SU.FOL.OM3 randomized controlled trial.

AimsTo study how MTHFR 677C→T genotype modulates the effect of supplementation with B-vitamins on total homocysteine (tHcy) and B-vitamin concentrations.Methods2381 patients with a personal history of cardiovascular disease were randomly assigned to one of four groups: 1) B-vitamins alone (560 μg of 5-methyl-THF, 3 mg of vitamin B6 and 20 μg of vitamin B12), 2) n-3 fatty acids alone (600 mg of EPA and DHA in a 2:1 ratio), 3) B-vitamins and n-3 fatty acids, and 4) placebo. Participants were followed up for 4.7 years. At baseline and annually thereafter, biological parameters were assessed. Multivariate and linear mixed models were fit to study the interaction between B-vitamins and MTHFR genotype.ResultsAmong supplemented participants, concentrations of all three B-vitamins increased during the first year (all p<0.0001) across MTHFR genotype categories. tHcy decreased by 26.3% during the first year (p<0.0001), then steadily increased throughout the 5 years (ptrend<0.001). However, at the end of follow-up, that increase was smaller among TT than among CT or CC subjects (pinteraction<0.02). At baseline, the difference in tHcy concentrations between TT homozygous and CC homozygous subjects was 2.33 μmol/l (p<0.001). After 5 years, that difference was reduced to 1.06 μmol/l and remained statistically significant (p<0.001).ConclusionParticipants with the TT genotype exhibited a lower 5-year decrease in tHcy concentrations following a B-vitamin supplementation than did participants with the CC or CT genotype.Clinical trial registrationCurrent Controlled Trials # ISRCTN41926726.

Fatty acids, polychlorinated dibenzo-p-dioxins and dibenzofurans, and dioxin-like polychlorinated biphenyls in paired muscle and skin from fish from the Bohai coast, China: Benefits and risks associated with fish consumption

Fish consumption benefits early cognitive development and cardiovascular health because of the n-3 long-chain polyunsaturated fatty acids in the fish, but toxic pollutants in fish, like dioxin-like polychlorinated biphenyls (dl-PCBs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), may decrease or counteract these benefits. In this study, the fatty acids, dl-PCBs, and PCDD/Fs were analyzed in paired muscle and skin from 13 fish and one squid species from the Bohai coast, which have been influenced by serious dioxin pollution from the Bohai Rim Region. The total fatty acid concentrations in the muscle and skin were 2.6–87 and 3.6–156 mg/g wet weight (ww), respectively. The total polyunsaturated fatty acid concentrations were higher in skin than muscle for almost half of the species. The total PCDD/F and dl-PCB toxic equivalents in the muscle and skin were 0.055–0.68 and 0.0099–0.43 pg/g ww, respectively, and were up to five times higher in the muscle than in the skin for eight species. Few benefit–risk studies for fish consumption with and without skin have been performed, so benefit–risk quotients (BRQs) for eating only muscle, only skin, and eating both were calculated. To achieve the recommended 250 mg of EPA + DHA intake, eating only muscle, only skin, and eating both from seven species with BRQs < 1 would cause no significant risk. Removing skin before eating is not necessary for these species. Three fish species had BRQs < 1 for muscle only but BRQs > 1 for skin only. Removing skin before eating would be better for these species. The other four fish species had BRQs > 1 for eating only muscle, only skin, and eating both, indicating the potential risk caused by PCDD/F and dl-PCB. Amounts of the four fish species consumed should be decreased, and other sources of EPA and DHA should be selected.

Supplementation of n-3 Polyunsaturated Fatty Acids for Major Depressive Disorder: A Randomized, Double-Blind, 12-Week, Placebo-Controlled Trial in Korea

Background: Controversy over the efficacy of n-3 polyunsaturated fatty acids (PUFAs) in depression continues to this day. The present study investigated the hypothesis that n-3 PUFA supplementation reduces depressive symptoms in Korean patients with major depressive disorder. Methods: In a randomized, double-blind, placebo-controlled, 12-week, parallel-group trial, 35 patients with Center for Epidemiological Studies Depression Scale Korean version (CES-D-K) scores ≥25 and depression confirmed by a psychiatrist were assigned to take either 3 capsules of n-3 PUFAs (1,140 mg of EPA + 600 mg of DHA; n = 18) or placebo (olive oil + safflower oil; n = 17). Results: Supplementation with n-3 PUFAs significantly reduced Clinical Global Impression Improvement (CGI-I) scores as compared with intake of placebo using intention-to-treat analysis with last-observation-carried-forward after adjusting for energy, fat, and fish intake. However, the CES-D-K, Hamilton Depression Rating Scale-17, and Clinical Global Impression Scale scores did not significantly differ between the n-3 PUFA and placebo groups. After supplementation with n-3 PUFAs, the erythrocyte levels of n-3 PUFAs were significantly increased, but n-6 PUFA levels were decreased. Conclusions: n-3 PUFAs demonstrated an advantage over placebo that did not reach clinical significance, although CGI-I score was significantly decreased in the n-3 PUFA group as compared with the placebo group.

Long-term ω-3 fatty acid supplementation induces anti-stress effects and improves learning in rats.

Chronic stress leads to secretion of the adrenal steroid hormone corticosterone, inducing hippocampal atrophy and dendritic hypertrophy in the rat amygdala. Both alterations have been correlated with memory impairment and increased anxiety. Supplementation with ω-3 fatty acids improves memory and learning in rats. The aim of this study was to evaluate the effects of ω-3 supplementation on learning and major biological and behavioral stress markers. Male Sprague–Dawley rats were randomly assigned to three experimental groups: 1) Control, 2) Vehicle, animals supplemented with water, and 3) ω-3, rats supplemented with ω-3 (100 mg of DHA+25 mg of EPA). Each experimental group was divided into two subgroups: one of which was not subjected to stress while the other was subjected to a restraint stress paradigm. Afterwards, learning was analyzed by avoidance conditioning. As well, plasma corticosterone levels and anxiety were evaluated as stress markers, respectively by ELISA and the plus-maze test. Restraint stress impaired learning and increased both corticosterone levels and the number of entries into the open-arm (elevated plus-maze). These alterations were prevented by ω-3 supplementation. Thus, our results demonstrate that ω-3 supplementation had two beneficial effects on the stressed rats, a strong anti-stress effect and improved learning.