Fishy Business: Effect of Omega-3 Fatty Acids on Zinc Transporters and Free Zinc Availability in Human Neuronal Cells

Omega-3 (ω-3) fatty acids are one of the two main families of long chain polyunsaturated fatty acids (PUFA). The main omega-3 fatty acids in the mammalian body are α-linolenic acid (ALA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Central nervous tissues of vertebrates are characterized by a high concentration of omega-3 fatty acids. Moreover, in the human brain, DHA is considered as the main structural omega-3 fatty acid, which comprises about 40% of the PUFAs in total. DHA deficiency may be the cause of many disorders such as depression, inability to concentrate, excessive mood swings, anxiety, cardiovascular disease, type 2 diabetes, dry skin and so on. On the other hand, zinc is the most abundant trace metal in the human brain. There are many scientific studies linking zinc, especially excess amounts of free zinc, to cellular death. Neurodegenerative diseases, such as Alzheimer’s disease, are characterized by altered zinc metabolism. Both animal model studies and human cell culture studies have shown a possible link between omega-3 fatty acids, zinc transporter levels and free zinc availability at cellular levels. Many other studies have also suggested a possible omega-3 and zinc effect on neurodegeneration and cellular death. Therefore, in this review, we will examine the effect of omega-3 fatty acids on zinc transporters and the importance of free zinc for human neuronal cells. Moreover, we will evaluate the collective understanding of mechanism(s) for the interaction of these elements in neuronal research and their significance for the diagnosis and treatment of neurodegeneration.     

A Consistency Model for Identifying the Effects of n-3 and n-6 Fatty Acids on Lipoproteins in Dialysis Patients

Numerous randomized controlled trials (RCTs) and meta-analyses have assessed the effects of supplemental dietary polyunsaturated fatty acids (PUFAs) on levels of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) and the LDL/HDL ratio in patients receiving renal replacement therapy (RRT). However, results are ambiguous due to mixed reports of various nutrients used in the intervention group. We performed a network meta-analysis of RCTs to assess the effects of PUFAs on lipid profiles in patients undergoing RRT. RCTs performed before November 2021 were gathered from three databases. The means, standard deviations and the number of cases for each arm were independently extracted by two authors to form a network meta-analysis of LDL and HDL levels and the LDL/HDL ratio in a random effects model. Twenty-eight RCTs (n = 2017 subjects) were included in this study. The pooled results revealed that the combination of omega-3 fatty acids (n-3) and omega-6 fatty acids (n-6) produced significantly lower LDL (standardized mean difference (SMD) = −1.43, 95% confidence interval: −2.28 to −0.57) than the placebo. Both n-3 fatty acids (SMD = 0.78) and the combination of n-3 + n-6 (SMD = 1.09) benefited HDL significantly compared with placebo. Moreover, n-3 alone also exhibited a significantly lower LDL/HDL ratio than placebo. Collectively, PUFAs seem to be adequate nutrients for controlling lipoproteins in patients undergoing RRT. Specifically, n-3 + n-6 supplementation improved LDL levels, while n-3 improved HDL levels and the LDL/HDL ratio. However, our data provide limited information on specific dosages of PUFAs to form a concrete recommendation.     

Interactions between prebiotics,probiotics, polyunsaturated fatty acids and polyphenols: diet or supplementation for metabolic syndrome prevention?

The metabolic syndrome can be prevented by the Mediterranean diet, characterized by fiber, omega-3 polyunsaturated fatty acids and polyphenols. However, the composition of the Mediterranean diet, which can be viewed as a natural multiple supplement, is poorly controlled, and its beneficial effects poorly predictable. The metabolic syndrome is associated with intestinal dysbiosis and the gut microbioma seems to be the main target and player in the interactions occurring between probiotics, prebiotics, omega 3 polyunsaturated fatty acids, and polyphenols. From the reviewed evidence, it is reasonable to manage growth and metabolism of gut microflora with specific prebiotics and polyphenols. Even though the healthy properties of functional foods and nutraceuticals still need to be fully elucidated, available data suggest that well-designed supplements, containing the better ratio of omega-3 polyunsaturated fatty acids and antioxidants, specific probiotic strains, and selected polyphenols and prebiotics, could be useful in metabolic syndrome prevention and treatment.     

Omega-3 polyunsaturated fatty acids and ionizing radiation: combined cytotoxicity on human colorectal adenocarcinoma cells

OBJECTIVE: This study evaluated whether omega-3 polyunsaturated fatty acids (PUFAs) could enhance the radiosensitivity of three different human colorectal adenocarcinoma cell lines. To understand the underlying mechanisms, the effects of omega-3 PUFAs on the cell growth, survival, and apoptosis were evaluated alone or in combination with an antioxidant (vitamin E) and compared with the effects of omega-6 PUFAs. METHODS: LS174T, CO112, and Caco-2 cell survival was assessed by clonogenic assay after a 3-d pretreatment with omega-3/omega-6 PUFAs and/or vitamin E before a single X-ray exposure to 4 Gy. Cell growth and viability were measured by double fluorescence-activated cell sorter analyses using propidium iodide and fluorescein isothiocyanate-conjugated annexin V. Student's t test or multivariable linear regression analyses were used for comparison. RESULTS: Preincubation with 30 to 100 mumol/L of omega-3 PUFAs induced a dose-dependent additive decrease in cell survival after irradiation (P < 0.05). Evaluation of the underlying mechanisms indicated that omega-3 PUFAs mainly decreased the cell number via apoptosis induction. Moreover, formation of lipid peroxidation products and modulation of cyclooxygenase II activity seemed to be involved, because coincubation with 10 mumol/L vitamin E abolished the effect of 50 mumol/L of omega-3 PUFAs (P < 0.05), whereas omega-6 PUFAs could partly mimic omega-3 PUFA effects. CONCLUSION: These observations suggest that omega-3 PUFAs may be potential candidates as nutritional adjuvants to enhance the efficacy of human colorectal cancer radiotherapy.     

Serum Omega-6 Polyunsaturated Fatty Acids and the Metabolic Syndrome: A Longitudinal Population-based Cohort Study

The serum fatty acid composition reflects the dietary fatty acid composition from the past few days to several weeks. However, the role of serum omega-3 (from fish and fish oils) and omega-6 (from vegetable oils) polyunsaturated fatty acids (PUFAs) in the course of metabolic syndrome is poorly understood. At the Primary Health Care Unit in Pieks?m?ki, Finland, all subjects born in 1942, 1947, 1952, 1957, and 1962 (n = 1,294) were invited for health checkups in 1997-1998 and 2003-2004. Metabolic syndrome was defined by using the new, harmonized criteria. The serum omega-3 PUFAs, omega-6 PUFAs, and total fatty acids were analyzed by proton nuclear magnetic resonance spectroscopy. Altogether, data from both checkups were available for 665 subjects. After adjustment for age, sex, and baseline body mass index, the incidence of metabolic syndrome between the 2 checkups with a 6.4-year follow-up was inversely associated (P < 0.001) with the increased relative proportion of omega-6 PUFAs in serum lipids. Further adjustment for body mass index change, lipid medication, smoking, alcohol intake, and physical activity conveyed similar results. The authors did not find any significant associations between omega-3 PUFAs and the incidence of metabolic syndrome. Therefore, their results suggest that the change in the relative proportion of omega-6 PUFAs in serum lipids is inversely related to the incidence of metabolic syndrome.     

Dietary Intake of Polyphenols or Polyunsaturated Fatty Acids and Its Relationship with Metabolic and Inflammatory State in Patients with Type 2 Diabetes Mellitus

Background: The aim of the study was to evaluate the relationship between polyphenol or polyunsaturated fatty acids (PUFAs) consumption and the selected metabolic and inflammatory markers in type 2 diabetes (T2DM) patients. Methods: The study enrolled 129 diabetics (49 men, mean age 64.1 ± 9.8 years) with different amounts of polyphenol and PUFAs consumption. Results: A significant effect of polyphenol or PUFAs omega-3 consumption on fasting glucose concentration (FG) or glycated haemoglobin fraction (HbA1c) was reported. A negative association was observed between FG and total polyphenol, flavonoid, flavan-3-ol and stilbene intake. In the group with high flavonoid intake, the FG was significantly lower compared to the group characterised by low flavonoid intake. Polyphenols, except stilbenes, did not modulate HbA1c. Additionally, higher consumption of PUFAs omega-3 significantly decreased HbA1c, and the intake of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids negatively and significantly correlated with FG and HbA1c. Further analysis confirmed a significant association between EPA + DHA intake and HbA1c, with significant interactions with age and gender or with body mass index and waist-to-hip ratio. The dietary intake of polyphenols or PUFAs was independent of familial diabetes or diabetic diet application. Conclusions: Our study indicates a positive effect of high consumption of flavonoids, omega-3 PUFAs and stilbenes on the markers of carbohydrate metabolism balance and the absence of such an effect on other cardiometabolic markers and inflammatory conditions.     

Monounsaturated and omega-3 but not omega-6 polyunsaturated fatty acids improve hepatic fibrosis in hypercholesterolemic rabbits

OBJECTIVE: Although the influence of saturated fatty acids, monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), lipids, cholesterol levels, and other blood lipids has been established, few studies have examined the influence of these dietary lipids on the composition and histologic damage of organs in situations of hypercholesterolemia. Biliary lipids come from the liver, and this organ is essential in cholesterol homeostasis; thus, it may be helpful to evaluate the inter-relations among biliary, hepatic lipids, and hepatotoxic effects in situations of hypercholesterolemia with different dietary lipids. This study investigated whether administration of diets differing in fatty acid profiles (omega-3 PUFA, omega-6 PUFA, or MUFA) influence the content of biliary lipids, the lithogenic index of gallbladder bile, and the development of hepatic fibrosis in hypercholesterolemic rabbits. METHODS: Thirty rabbits were randomized to one of five groups. A control group received rabbit chow for 80 d. The remaining four groups received a 50-d diet that contained 3% lard and 13% cholesterol to provoke hypercholesterolemia. After this period, three groups were fed for another 30 d on a diet enriched with omega-6 PUFAs, MUFAs, and omega-3 PUFAs, respectively. Liver, bile, and plasma lipid compositions, lipid peroxidation in hepatic mitochondria, and histologic hepatic lesions were analyzed. RESULTS AND CONCLUSIONS: There was a beneficial effect of MUFA and omega-3 PUFA on hepatic fibrosis in hypercholesterolemic rabbits because both dietary fats led to recovery from hepatic lesions. However, because intake of omega-3 PUFA provoked lithogenic bile in rabbits, MUFA intake would be more advisable.     

Omega-3 Polyunsaturated Fatty Acids Inhibited Tumor Growth via Preventing the Decrease of Genomic DNA Methylation in Colorectal Cancer Rats

Omge-3 polyunsaturated fatty acids (PUFAs) exhibited significant effect in inhibiting various tumors. However, the mechanisms of its anticancer role have not been fully demonstrated. The declination of 5-methylcytosine (5 mC) was closely associated with poor prognosis of tumors. To explore whether omega-3 PUFAs influences on DNA methylation level in tumors, colorectal cancer (CRC) rat model were constructed using N-methyl phosphite nitrourea and omega-3 PUFAs were fed to part of the rats during tumor induction. The PUFAs contents in the rats of 3 experimental groups were measured using gas chromatography and 5 mC level were detected by liquid chromatography tandem mass spectrometry. The results showed that tumor incidence in omega-3 treated rats was much lower than in CRC model rats, which confirmed significant antitumor role of omega-3 PUFAs. Six PUFA members categorized to omega-3 and omega-6 families were quantified and the ratio of omega-6/omega-3 PUFAs was remarkably lower in omega-3 PUFAs treatment group than in CRC model group. 5 mC content in omega-3 PUFAs treated rats was higher than in CRC model rats, suggesting omega-3 PUFAs promoted 5 mC synthesis. Therefore, omega-3 PUFAs probably inhibited tumor growth via regulating DNA methylation process, which provided a novel anticancer mechanism of omega-3 PUFAs from epigenetic view.     

Composition of Dietary Fatty Acids and Health Risks in Japanese Youths

In the overall composition of dietary fatty acids (FAs), the quantity of each FA is interrelated with that of others. We examined the associations between dietary FA composition and cardiometabolic risk in Japanese youths. Risk factors (anthropometric characteristics, serum lipid and liver enzyme levels, and blood pressure) were measured in 5485 junior-high-school students. Dietary intake was assessed using a food frequency questionnaire. The mean saturated FA (SFA), monounsaturated FA (MUFA), omega-6 polyunsaturated FAs (PUFAs), and omega-3 PUFAs intake were 9.6%E, 10.3%E, 6.3%E, and 1.1%E, respectively. In compositional regression analysis controlled for confounders, a high intake of omega-6 PUFAs relative to others was associated with low low-density-lipoprotein cholesterol levels (LDL-C; p = 0.003), and relative SFA intake was associated with high levels of gamma-glutamyl transpeptidase (p = 0.019). Relative omega-3 PUFAs intake was associated with low blood pressure (p = 0.005–0.034) but had unfavorable effects on adiposity and alanine transaminase. Substitutional models showed similar results for omega-6 PUFAs on LDL-C, but MUFA had inconsistent effects on risk factors. The results from the compositional data analysis were consistent with previous studies and clinical practice/knowledge. Focusing on increasing omega-6 PUFAs in Japanese youths could have favorable consequences in the long term.     

Enhancing Cytotoxic Therapies for Breast and Prostate Cancers With Polyunsaturated Fatty Acids

The role of omega-3 and omega-6 fatty acids has been extensively studied in most of the human malignancies including breast, colon, prostate, pancreas, and stomach cancers. In particular, the role of omega-3 and omega-6 fatty acids in carcinogenesis has been extensively investigated in epidemiological, laboratory cell culture studies and studies in vivo in animal. Findings from these studies suggest that omega-3 and omega-6 fatty acids are cytotoxic in different cancers and act synergistically with cytotoxic drugs. Although experimental evidence for the potential beneficial role of polyunsaturated fatty acids (PUFAs) in enhancing the effectiveness of various chemotherapeutic agents in animal models and in cell culture studies is increasing, there are only a few reports that have shown supportive evidence for linking these natural compounds with augmentation of anticancer chemotherapeutics in human trials. This review presents evidence for a commonality in the proposed molecular mechanisms of action elicited by various PUFAs believed to be responsible for their enhancement of the effectiveness of anticancer chemotherapy, specifically in breast and prostate cancers, and reviews laboratory and animal studies and few reported human clinical trials. It concludes that sufficient evidence is available to suggest that major clinical trials with these natural compounds as adjuncts to standard therapies should be undertaken as a priority.     

The alpha-linolenic acid content of green vegetables commonly available in Australia

Green vegetable consumption has long been considered to have health benefits mainly due to the vitamins, minerals and phytonutrients (such as vitamin C, folate, antioxidants etc) contained in a vegetable-rich diet. Additionally, green vegetables are known to contain a relatively high proportion of omega-3 polyunsaturated fatty acids (PUFAs), primarily in the form of alpha-linolenic acid (18:3n-3). However, there are no data available on the fatty acid composition and concentration of green vegetables commonly consumed in Australia. The present study determined the fatty acid content of 11 green vegetables that are commonly available in Australia. The total fatty acid concentrations of the vegetables under study ranged from 44 mg/100 g wet weight in Chinese cabbage to 372 mg/100 g in watercress. There were three PUFAs in all vegetables analyzed; these were 16:3n-3, 18:2n-6, and 18:3n-3 fatty acids. Sample vegetables contained significant quantities of 16:3n-3 and 18:3n-3, ranging from 23 to 225 mg/100 g. Watercress and mint contained the highest amounts of 16:3n-3 and 18:3n-3, and parsley had the highest amount of 18:2n-6 in both percentage composition and concentration. Mint had the highest concentration of 18:3n-3 with a value of 195 mg/100 g, while watercress contained the highest concentration of 16:3n-3 at 45 mg/100 g. All 11 green vegetables contained a high proportion of PUFAs, ranging from 59 to 72% of total fatty acids. The omega-3 PUFA composition ranged from 40 to 62% of total fatty acids. Monounsaturated fatty acid composition was less than 6% of total fatty acids. The proportion of saturated fatty acids ranged from 21% in watercress and mint to 32% of total fatty acids in Brussels sprouts. No eicosapentaenoic and docosahexaenoic acids were detected in any of the samples. Consumption of green vegetables could contribute to 18:3n-3 PUFA intake, especially for vegetarian populations.     

Fish oil alters T-lymphocyte proliferation and macrophage responses in Walker 256 tumor-bearing rats

OBJECTIVE: We investigated the effect of the dietary ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) from postweaning until adulthood on T-lymphocyte proliferation, T-lymphocyte subpopulations (helper and cytotoxic), and production of cytotoxic mediators by macrophages in tumor-bearing rodents. METHODS: Weanling male Wistar rats received a normal low-fat (40 g/kg of diet) chow diet or a high-fat (300 g /kg) diet that included fish or sunflower oil or blends of fish and sunflower oils to yield omega-6:omega-3 PUFA ratios of approximately 6:1, 30:1, and 60:1 ad libitum. After 8 wk, 50% of rats in each group were inoculated with 1 mL of 2 x 10(7) Walker 256 cells. Fourteen days after tumor inoculation, animals were killed and lymphocytes and macrophages were obtained for study. RESULTS: The diets richest in omega-6 PUFA resulted in higher proliferation of thymus, spleen, and gut-associated lymphocytes compared with the chow diet irrespective of tumor burden. In contrast, the fish oil diet resulted in lower proliferation of thymus and spleen lymphocytes compared with the chow diet. Diets rich in omega-6 PUFA decreased the proportion of CD8+ lymphocytes. In non-tumor-bearing and tumor-bearing rats, hydrogen peroxide production by macrophages was highest in rats that consumed diets high in omega-3 PUFAs. Superoxide and nitric oxide production were little affected by the dietary ratio of omega-6 to omega-3 PUFAs. CONCLUSION: Dietary omega-6 and omega-3 PUFA contents alter immune function in non-tumor-bearing and tumor-bearing rats. The omega-3 PUFAs decreased T-cell proliferation but increased hydrogen peroxide production compared with omega-6 PUFAs. Decreased tumor growth and cachexia and increased survival previously reported for fish oil in Walker 256 tumor-bearing rats may be related to improved macrophage function rather than to improved T-cell function.     

Efficacy and Safety of Nutrient Supplements for Glycaemic Control and Insulin Resistance in Type 2 Diabetes: An Umbrella Review and Hierarchical Evidence Synthesis

Background: Nutrient supplements are widely used for type 2 diabetes (T2D), yet evidence-based guidance for clinicians is lacking. Methods: We searched the four electronic databases from November 2015–December 2021. The most recent, most comprehensive, high-ranked systematic reviews, meta-analyses, and/or umbrella reviews of randomised controlled trials in adults with T2D were included. Data were extracted on study characteristics, aggregate outcome measures per group (glycaemic control, measures of insulin sensitivity and secretion), adverse events, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessments. Quality was assessed using A Measurement Tool to Assess Systematic Reviews Version 2.0 (AMSTAR 2). Results: Twelve meta-analyses and one umbrella review were included. There was very low certainty evidence that chromium, Vitamin C, and omega-3 polyunsaturated fatty acids (Ω-3 PUFAs) were superior to placebo for the primary outcome of glycated hemoglobin (HbA1c) (Mean Difference/MD −0.54, −0.54 and ES −0.27, respectively). Probiotics were superior to placebo for HbA1c (Weighted Mean Difference/WMD −0.43%). There was very low certainty evidence that Vitamin D was superior to placebo for lowering HbA1c in trials of <6 months (MD −0.17%). Magnesium, zinc, Vitamin C, probiotics, and polyphenols were superior to placebo for FBG. Vitamin D was superior to placebo for insulin resistance. Data on safety was limited. Conclusions: Future research should identify who may benefit from nutrient supplementation, safety, and optimal regimens and formulations.     

Comparison between omega-3 and omega-6 polyunsaturated fatty acid intakes as assessed by a food frequency questionnaire and erythrocyte membrane fatty acid composition in young children

OBJECTIVE: We conducted a dietary validation study in youth aged 1-11 years by comparing dietary intake of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) as assessed by a parent-completed semiquantitative food frequency questionnaire (FFQ) over time to erythrocyte membrane composition of the same fatty acids. DESIGN: The study population included youth aged 1-11 years who were participants in the Diabetes Autoimmunity Study in the Young (DAISY), a longitudinal study in Denver, Colorado that is following a cohort of youth at risk for developing type I diabetes. Four hundred and four children who had erythrocyte membrane fatty acid data matched to an FFQ corresponding to the same time frame for a total of 917 visits (matches) were included. PUFA intake was expressed both as g/day (adjusted for total energy) and as percent of total fat intake. We used mixed models to test the association and calculate the correlation between the erythrocyte membrane estimates and PUFA intake using all records of data for each youth. RESULTS: Intakes of total omega-3 fatty acids (beta=0.52, P<0.0001, rho=0.23) and marine PUFAs (beta=1.62, P<0.0001, rho=0.42), as a percent of total fat in the diet, were associated with percent of omega-3 and marine PUFAs in the erythrocyte membrane. Intakes of omega-6 PUFAs (beta=0.04, P=0.418, rho=0.05) and arachidonic acid (beta=0.31, P=0.774, rho=0.01) were not associated. CONCLUSIONS: In these young children, an FFQ using parental report provided estimates of average long-term intakes of marine PUFAs that correlated well with their erythrocyte cell membrane fatty acid status.     

Omega 3 fatty acids: biological activity and effects on human health

Polyunsaturated fatty acids (PUFAs) have an important role in human diet, both for the prevention and the therapy of different pathologies. In this review, a critical evaluation of PUFAs dietary sources and biological functions in human organism has been done. In particular, the efficacy of omega-3 fatty acids in the improvement of the lipidic pattern and in the excitability of myocardium has been analyzed, and, therefore, their usefulness in the prevention of cardiovascular diseases and postinfarction arrhythmias. As PUFAs are precursors of prostaglandins and leucotriens, which are involved in phlogosis and immune response, a diet rich in fish oil reduces the production of PGE2 involved in many phlogosis events. Moreover, an increase in the eicosapentaenoic acid (EPA) intake leads to a reduction in the production of inflammatory cytokines (interleukin 1, 2, 6 and tumor necrosis factor); so, it is important to use omega-3 in chronic inflammatory diseases, as the rheumatoid arthritis. It seems that omega-3 could prevent the onset of hormone-dependent tumours (i.e. breast and prostatic cancer); in vitro observations, in fact, have shown that the PG of the series 2, derived from omega-6, have a carcinogenic action; instead, the anticancer effect of omega-3 could derive from their effect in antagonizing the formation of such PG; it can be useful, therefore, to increase the dietary omega-3/omega-6 ratio. Moreover, the effects of omega-3 on the anatomic and functional central nervous system development and of their possible therapeutical use in some psychiatric pathologies were evaluated.     

Folic acid says NO to vascular diseases

OBJECTIVES: The possible link between folic acid or folate and tetrahydrobiopterin (H(4)B), vitamin C, polyunsaturated fatty acids (PUFAs), and nitric oxide (NO), which may explain the beneficial actions of these nutrients in various vascular conditions, was investigated. METHODS: The literature pertaining to the actions of folic acid/folate, H(4)B, vitamin C, PUFAs, and NO was reviewed. RESULTS: Impaired endothelial NO (eNO) activity is an early marker for cardiovascular disease. Most risk factors for atherosclerosis are associated with impaired endothelium-dependent vasodilatation due to reduced NO production. Folate not only reduces plasma homocysteine levels but also enhances eNO synthesis and shows anti-inflammatory actions. It stimulates endogenous H(4)B regeneration, a cofactor necessary for eNO synthesis, inhibits intracellular superoxide generation, and thus enhances the half-life of NO. H(4)B in turn enhances NO generation and augments arginine transport into the cells. Folic acid increases the concentration of omega-3 PUFAs, which also enhance eNO synthesis. Vitamin C augments eNO synthesis by increasing intracellular H(4)B and stabilization of H(4)B. Insulin stimulates H(4)B synthesis and PUFA metabolism, suppresses the production of proinflammatory cytokine tumor necrosis factor-alpha and superoxide anion, and enhances NO generation. The ability of folate to augment eNO generation is independent of its capacity to lower plasma homocysteine levels. CONCLUSIONS: The common mechanism by which folic acid, H(4)B, vitamin C, omega-3 fatty acids, and L-arginine bring about their beneficial actions in various vascular diseases is by enhancing eNO production. Hence, it remains to be determined whether a judicious combination of folic acid, vitamins B12, B6, and C, H(4)B, L-arginine, and omega-3 fatty acids in appropriate amounts may form a novel approach in the prevention and management of various conditions such as hyperlipidemias, coronary heart disease, atherosclerosis, peripheral vascular disease, and some neurodegenerative conditions.     

Lack of influence of omega-3 fatty acid-enriched lipids on apoptosis and secondary necrosis of cultured human lymphocytes

OBJECTIVE: The anti-inflammatory properties of parenteral nutrition might be improved by enrichment with omega-3 polyunsaturated fatty acids (PUFAs), which are responsible for the enhanced release of metabolites derived from eicosapentaenoic acid. Under physiologic conditions, lymphocyte populations are regulated by cellular mechanisms such as apoptosis. In contrast to cell death by necrosis, apoptosis does not induce an inflammatory response that might injure the host. METHODS: Apoptosis and necrosis of cultured human blood lymphocytes were investigated in vitro after incubation for 48 and 72 h with three lipid emulsions containing 50% medium-chain triacylglycerols. The lipid emulsions differed in the percentage of long-chain triacylglycerols, which were replaced in part by different amounts of omega-3 PUFA (8%, 20%, or 40%). Rates of apoptosis and necrosis of lymphocyte subpopulations were analyzed with a sensitive annexin V flow cytometric assay. RESULTS: After 48 and 72 h of incubation, time- and dose-dependent increases of apoptosis and necrosis, respectively, were found in all lymphocyte subsets regardless of the percentage of omega-3 PUFAs. CONCLUSIONS: Our results suggested that enrichment with omega-3 PUFAs in the tested lipid emulsions does not alter apoptosis and secondary necrosis of lymphocyte populations. Thus PUFAs may exert their functional effects through other mechanisms.     

Higher Serum DHA and Slower Cognitive Decline in Patients with Alzheimer’s Disease: Two-Year Follow-Up

Omega-3 polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been associated with slower rates of cognitive decline. We investigated the association between omega-3 PUFAs and cognitive function in patients with Alzheimer’s disease (AD) receiving acetylcholinesterase inhibitors (AChEIs). This was a prospective cohort study using registered data. Patients with AD receiving AChEIs were recruited from 1 May 2016 to 30 April 2019 and were followed up for two years. Their daily diet record and blood concentration of omega-3 PUFAs were analyzed. Multiple linear and binary logistic regression was used to determine the factors associated with cognitive decline (continuous and dichotomized cognitive change). In the research, 129 patients with AD were identified with a mean age of 76.5 ± 6.6. Patients with AD with lower baseline omega-3 PUFAs levels were associated with a higher risk of cognitive decline than those with higher levels (odds ratio [OR] = 1.067, 95% confidence interval [CI]: 1.012, 1.125; p = 0.016) after adjustment. Patients with AD with a lower baseline DHA (OR = 1.131, 95% CI: 1.020, 1.254; p = 0.020), but not EPA, were associated with a higher risk of cognitive decline. We found that higher Mini-Nutritional Assessment scores (beta = −0.383, 95% CI = −0.182–−0.048, p = 0.001) and total fat (beta = −0.248, 95% CI = −0.067–−0.003, p = 0.031) were independently associated with slow cognitive decline in patients with AD receiving AChEIs. The baseline blood levels of omega-3 PUFAs were associated with cognitive decline in patients with AD receiving AChEIs. Future randomized controlled trials are needed to clarify whether this association is causal.     

Omega-3 polyunsaturated fatty acids and depression: a review of the evidence and a methodological critique

Several lines of evidence indicate an association between omega-3 polyunsaturated fatty acids (PUFAs) and depression. The purpose of this review was to evaluate the evidence to date within the context of the study design and methodology used. In case-control and cohort studies, concentrations of omega-3 PUFAs were lower in participants with unipolar and postpartum depression. Fish are the major dietary source of omega-3 PUFAs, and infrequent fish consumption is associated with depression in epidemiological studies. While these findings do not appear to be the result of confounding, in some studies failure to detect confounding may be due to a lack of power or incomplete control. In four of seven double-blind randomized controlled trials, depression was significantly improved upon treatment with at least 1 g/day of eicosapentaenoic acid, an omega-3 PUFA. While clinical significance was demonstrated, preservation of blinding may be a limitation in this area of research. It remains unclear whether omega-3 supplementation is effective independently of antidepressant treatment, for depressed patients in general or only those with abnormally low concentrations of these PUFAs. The relationship between omega-3 PUFAs and depression is biologically plausible and is consistent across study designs, study groups, and diverse populations, which increases the likelihood of a causal relationship.