Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects

n-3 fatty acids reduce the risk of cardiovascular disease via a number of possible mechanisms. Despite this, there has been concern that these fatty acids may increase lipid peroxidation. The data in vivo are inconclusive, due in part to limitations in the methodologies. In this regard, the measurement of F2-isoprostanes provides a reliable assessment of in vivo lipid peroxidation and oxidant stress. This study aimed to assess the effects of supplementation with purified eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), the two major n-3 fatty acids, on urinary F2-isoprostanes and markers of inflammation, in type 2 diabetic patients. In a double-blind, placebo controlled trial of parallel design, 59 nonsmoking, treated-hypertensive, type 2 diabetic subjects, were randomized to 4 g daily of purified EPA, DHA, or olive oil for 6 weeks, while maintaining their usual diet. F2-isoprostanes, measured using gas chromatography-mass spectrometry in 24 h urines and C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), were measured before and after intervention. Thirty-nine men and 12 women aged 61.2 +/- 1.2 years, with body mass index (BMI), 29.5 +/- 0.5 kg/m2; 24 h blood pressure, 138/73 mmHg; HbA1c, 7.3 +/- 0.1% and fasting glucose, 7.9 +/- 0.2 mmol/l completed the intervention. Baseline urinary F2-isoprostanes were positively associated with HbA1c (p=.011) and fasting glucose (p=.032). Relative to the olive oil group, postintervention urinary F2-isoprostanes were decreased 19% by EPA (p=.017) and 20% by DHA (p=.014). There were no significant changes in CRP, IL-6, and TNF-alpha following EPA or DHA supplementation. In regression analysis, Delta F2-isoprostanes were positively associated with Delta HbA1c (p=.007) independent of treatment group; and with Delta TNF-alpha (p=.034) independent of age, gender, BMI, and treatment group. There were no associations with Delta CRP or Delta IL-6. This study is the first report demonstrating that either EPA or DHA reduce in vivo oxidant stress without changing markers of inflammation, in treated hypertensive, type 2 diabetic subjects.     

Differential Effect of w3 PUFA Supplementations on Na,K-ATPase and Mg-ATPase Activities: Possible Role of the Membrane w6/w3 Ratio

Several functional properties of Na,K-ATPase are strongly dependent on membrane fatty acid composition, but the underlying mechanism is still not well defined. We have studied the effects of two types of supplementations enriched in the w3 polyunsaturated fatty acids on the Na,K-ATPase and Mg-ATPase activities in sciatic nerve (SN) and red blood cells (RBC). Eight groups of rats, controls and diabetics, received a standard diet, supplemented or not with 30 or 60 mg/kg/day of docosahexaenoic acid (DHA) or with soybean for eight weeks. Diabetes induced significant decrease of Na,K-ATPase activity in SN (-23%) and RBC (-25%), without affecting Mg-ATPase activity. In RBC, soybean and DHA supplementations caused significant increases in Na,K-ATPase activity (in various range, +13% to +145%) in all groups, and in Mg-ATPase activity in control soybean (+65%), control and diabetic DHA high dose (+39%, +53%) and diabetic DHA low dose (+131%) groups. In SN, the soybean caused a significant decrease in Na,K-ATPase activity (-26%) and still more in the diabetic group (-53%). The DHA diet induced a slight decrease in activity in control groups, whilst during diabetes, at high dose, we noted an aggravation of this decrease (-36%). Mg-ATPase activity was not modified by supplementations except for the low dose of DHA where the activity was slightly decreased in the control group (-16%). The supplementations induced multiple tissue-specific modifications in the membrane fatty acid composition of RBC and of SN homogenates. Several specific correlations have been found between variations in fatty acids amounts and Na,K-ATPase activity in these tissues but only in RBC for Mg-ATPase activity. Indeed, we observed that the variations in Na,K-ATPase activity are positively and significantly correlated with changes in the omega6/omega3 ratio in SN as well as in RBC. These data clearly show, for the first time, that the diet could modulate the Na,K-ATPase activity via the omega6/omega3 ratio in the membranes. A similar correlation was observed with Mg-ATPase activity in RBC, suggesting also a dietary regulation of the enzyme; but for the SN, this activity might be regulated by a different omega6/omega3 ratio or by another pathway.     

Protection by DHA of Early Hippocampal Changes in Diabetes: Possible Role of CREB and NF-κB

The mechanisms underlying diabetic encephalopathy, are only partially understood. In this study, we try to address the mechanisms of diabetes induced damage and whether docosahexaenoic acid (DHA) could attenuate the degenerative changes in diabetic hippocampus in a rodent model of diabetes. Diabetes was induced in rats by an intraperitoneal injection of streptozotocin. Animals were divided into the following experimental groups: control rats; control animals treated with DHA; untreated diabetic rats; diabetic rats treated with insulin; diabetic rats treated with DHA; diabetic rats treated with insulin and DHA. At the end of week 12, rats were killed and one of the hemispheres was cryosectioned and the other was dissected and hippocampi homogenized. The number of bromodeoxyuridine positive cells in the hippocampus of diabetic rats was decreased, and the latency time to find the platform in the Morris Water maze was significantly increased in the diabetic rats when compared to controls. No changes where observed in the expression of p21 in the hippocampus of control and diabetic rats. Biochemical markers of oxidative stress were altered in hippocampus of diabetic rats, and NFκB-positive cells were increased in the hippocampus of diabetic rats when compared to controls. Treatment with DHA, or the combination of DHA with insulin, significantly restored to control levels all the values mentioned above. Our findings confirm a pivotal role for oxidative stress as well as NF-κB, but not p21, in diabetes-induced hippocampal impairments. Administration of DHA as well as insulin prevented the changes induced by diabetes in hippocampus.     

α-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans

Blood levels of polyunsaturated fatty acids (PUFA) are considered biomarkers of status. Alpha-linolenic acid, ALA, the plant omega-3, is the dietary precursor for the long-chain omega-3 PUFA eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Studies in normal healthy adults consuming western diets, which are rich in linoleic acid (LA), show that supplemental ALA raises EPA and DPA status in the blood and in breast milk. However, ALA or EPA dietary supplements have little effect on blood or breast milk DHA levels, whereas consumption of preformed DHA is effective in raising blood DHA levels. Addition of ALA to the diets of formula-fed infants does raise DHA, but no level of ALA tested raises DHA to levels achievable with preformed DHA at intakes similar to typical human milk DHA supply. The DHA status of infants and adults consuming preformed DHA in their diets is, on average, greater than that of people who do not consume DHA. With no other changes in diet, improvement of blood DHA status can be achieved with dietary supplements of preformed DHA, but not with supplementation of ALA, EPA, or other precursors.     

Docosahexaenoic acid (DHA) and cardiovascular disease risk factors

Numerous epidemiological and controlled interventional trials have supported the health benefits of long-chain omega-3 fatty acids in the form of docosahexaenoic acid (DHA, 22:6n-3) plus eicosapentaenoic acid (EPA, 20:5n-3) from fish and fish oils as well as from algal sources. The beneficial effects on cardiovascular disease and related mortality including various risk factors for cardiovascular disease (particularly lowering circulating triglyceride levels and the triglyceride:HDL-cholesterol ratio) have been observed in the absence of any concomitant blood cholesterol lowering. With appropriate dosages, consistent reductions in both fasting and postprandial triglyceride levels and moderate increases in fasting HDL-cholesterol levels have been observed with algal DHA in the majority of trials. These results are similar to findings for fish oils containing DHA and EPA. Related to greater fish intake, higher levels of DHA in circulating blood biomarkers (such as serum phospholipid) have been associated with reduced risks for the progression of coronary atherosclerosis and lowered risk from sudden cardiac death. Controlled clinical trials have also indicated the potential for algal DHA supplementation to have moderate beneficial effects on other cardiovascular disease risk factors including blood pressures and resting heart rates. Recommended intakes of DHA+EPA from numerous international groups for the prevention and management of cardiovascular disease have been forthcoming, although most have not offered specific recommendations for the optimal individual intake of DHA and EPA.     

Docosahexaenoic acid-enriched egg phospholipids supplementation induces accretion of arachidonic acid in rat blood lipids.

Animal and humans studies have shown that supplementation with triacylglycerides containing omega3 fatty acids, mainly docosahexaenoic acid (DHA) and eicosapentaenoic acid, can induce a decrease in arachidonic acid (AA) in blood lipids. Interestingly, we observed in a previous work that a supplementation with DHA enriched eggs in a healthy elderly population induced an accretion of AA in their blood lipids. The present study investigates whether purified DHA enriched egg phospholipids could be responsible for this effect. Four groups of rats were supplemented daily, for eight weeks, with DHA phospholipids (10, 30 or 60 mg/kg) or with soybean phospholipids. Red blood cell membranes and plasma fatty acid levels were compared with that of rats without supplementation. Soybean phospholipids supplementation increased the level of AA in blood lipids but decreased that of DHA. The doses of DHA phospholipids, 30 and 60 mg/kg, induced greater amounts of AA without affecting significantly DHA levels. In contrast, DHA phospholipids supplementation, 10 mg/kg, in which there was the greatest amount of AA, induced only a slight increase in AA levels. Moreover, DHA levels were decreased by this supplementation. These results demonstrate that specific increases in AA levels are preferentially associated with DHA phospholipids levels in supplementation.     

Omega-3 fatty acids from fish oils and cardiovascular disease

Fish and fish oils contain the omega-3 fatty acids known as eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). Epidemiological studies have shown an inverse relation between the dietary consumption of fish containing EPA/DHA and mortality from coronary heart disease. These relationships have been substantiated from blood measures of omega-3 fatty acids including DHA as a physiological biomarker for omega-3 fatty acid status. Controlled intervention trials with fish oil supplements enriched in EPA/DHA have shown their potential to reduce mortality in post-myocardial infarction patients with a substantial reduction in the risk of sudden cardiac death. The cardioprotective effects of EPA/DHA are widespread, appear to act independently of blood cholesterol reduction, and are mediated by diverse mechanisms. Their overall effects include anti-arrhythmic, blood triglyceride-lowering, anti-thrombotic, anti-inflammatory, endothelial relaxation, plus others. Current dietary intakes of EPA/DHA in North America and elsewhere are well below those recommended by the American Heart Association for the management of patients with coronary heart disease. (Mol Cell Biochem 263: 217–225, 2004)     

Effect of docosahexaenoic acid intake on lipid peroxidation in diabetic rat retina under oxidative stress

Docosahexaenoic acid (DHA) plays an important role in visual function but has a highly oxidation-prone chemical structure. Therefore, we investigated how dietary DHA affects the generation of lipid peroxides in rat retina under oxidative stress in diabetes with/without vitamin E (VE) deficiency. Streptozotocin-induced (50 mg i.p./kg B.W.) diabetic Sprague-Dawley (SD) rats were assigned to four groups: (i) control/VE(+), (ii) DHA/VE(+), (iii) control/VE( - ) and (iv) DHA/VE( - ), and raised for 28 days. We then measured lipid peroxide levels in the retina, serum and liver. With a normal intake of VE, dietary DHA increased only the retinal level of thiobarbituric acid-reactive substances (TBARS) slightly. In contrast, in rats with VE deficiency, dietary DHA increased serum and liver lipid peroxide levels but not in the retina. These results suggest that dietary DHA does not necessarily promote lipid peroxidation in the retina even under high oxidative stress.     

Dose dependent accretion of docosahexaenoic acid (DHA) in cardiac membranes of rats fed egg yolk powder enriched in DHA.

We tested the hypothesis that enrichment of the diet with docosahexaenoic acid (DHA) enriched egg yolk powder could modify specifically the (n-3) fatty acids content of rat plasma, red blood cells and heart membranes. Dose-dependent effect of DHA was studied in rats supplemented during 4 weeks. Three groups of adult male rats, DHA10, DHA35 and DHA60 (n = 5 each), had their diet supplemented with 10 mg, 35 mg or 60 mg DHA/kg body weight/day, respectively. Fatty acid composition of membranes and plasma lipids were determined. A significant dose-dependent increase in DHA was observed in all three types of samples. Arachidonic acid (AA) levels did not change in heart and red blood cell membranes whereas it increased significantly in plasma with the DHA35 diet. These results contrast with that previously reported for fish oil supplementation where a decrease in AA levels was reported. Hence, DHA enriched egg yolk supplementation leads to a specific accretion of DHA without competition on AA status.     

Metabolism and functional effects of plant-derived omega-3 fatty acids in humans

Alpha-linolenic acid (ALA) is an essential fatty acid and the substrate for the synthesis of longer-chain, more unsaturated ω-3 fatty acids, eicosapentaenoic acid (EPA), docosapentaenoic acid and docosahexaenoic acid (DHA). EPA and DHA are associated with human health benefits. The primary source of EPA and DHA is seafood. There is a need for sustainable sources of biologically active ω-3 fatty acids. Certain plants contain high concentrations of ALA and stearidonic acid (SDA). Here we review the literature on the metabolism of ALA and SDA in humans, the impact of increased ALA and SDA consumption on concentrations of EPA and DHA in blood and cell lipid pools, and the extent to which ALA and SDA might have health benefits. Although it is generally considered that humans have limited capacity for conversion of ALA to EPA and DHA, sex differences in conversion to DHA have been identified. If conversion of ALA to EPA and DHA is limited, then ALA may have a smaller health benefit than EPA and DHA. SDA is more readily converted to EPA and appears to offer better potential for health improvement than ALA. However, conversion of both ALA and SDA to DHA is limited in most humans.     

Circulating Docosahexaenoic Acid Levels Are Associated with Fetal Insulin Sensitivity

Background

Arachidonic acid (AA; C20∶4 n-6) and docosahexaenoic acid (DHA; C22∶6 n-3) are important long-chain polyunsaturated fatty acids (LC-PUFA) in maintaining pancreatic beta-cell structure and function. Newborns of gestational diabetic mothers are more susceptible to the development of type 2 diabetes in adulthood. It is not known whether low circulating AA or DHA is involved in perinatally “programming” this susceptibility. This study aimed to assess whether circulating concentrations of AA, DHA and other fatty acids are associated with fetal insulin sensitivity or beta-cell function, and whether low circulating concentrations of AA or DHA are involved in compromised fetal insulin sensitivity in gestational diabetic pregnancies.

Methods and Principal Findings

In a prospective singleton pregnancy cohort, maternal (32-35 weeks gestation) and cord plasma fatty acids were assessed in relation to surrogate indicators of fetal insulin sensitivity (cord plasma glucose-to-insulin ratio, proinsulin concentration) and beta-cell function (proinsulin-to-insulin ratio) in 108 mother-newborn pairs. Cord plasma DHA levels (in percentage of total fatty acids) were lower comparing newborns of gestational diabetic (n = 24) vs. non-diabetic pregnancies (2.9% vs. 3.5%, P = 0.01). Adjusting for gestational age at blood sampling, lower cord plasma DHA levels were associated with lower fetal insulin sensitivity (lower glucose-to-insulin ratio, r = 0.20, P = 0.036; higher proinsulin concentration, r = −0.37, P <0.0001). The associations remained after adjustment for maternal and newborn characteristics. Cord plasma saturated fatty acids C18∶0 and C20∶0 were negatively correlated with fetal insulin sensitivity, but their levels were not different between gestational diabetic and non-diabetic pregnancies. Cord plasma AA levels were not correlated with fetal insulin sensitivity.

Conclusion

Low circulating DHA levels are associated with compromised fetal insulin sensitivity, and may be involved in perinatally “programming” the susceptibility to type 2 diabetes in the offspring of gestational diabetic mothers.     

Are diabetic neuropathy,retinopathy and nephropathy caused by hyperglycemic exclusion of dehydroascorbate uptake by glucose transporters?

Vitamin C exists in two major forms. The charged form, ascorbic acid (AA), is taken up into cells via sodium-dependent facilitated transport. The uncharged form, dehydroascorbate (DHA), enters cells via glucose transporters (GLUT) and is then converted back to AA within these cells. Cell types such as certain endothelial and epithelial cells as well as neurons that are particularly prone to damage during diabetes tend to be those that appear to be dependent on GLUT transport of DHA rather than sodium-dependent AA uptake. We hypothesize that diabetic neuropathies, nephropathies and retinopathies develop in part by exclusion of DHA uptake by GLUT transporters when blood glucose levels rise above normal. AA plays a central role in the antioxidant defense system. Exclusion of DHA from cells by hyperglycemia would deprive the cells of the central antioxidant, worsening the hyperglycemia-induced oxidative stress level. Moreover, AA participates in many cellular oxidation-reduction reactions including hydroxylation of polypeptide lysine and proline residues and dopamine that are required for collagen production and metabolism and storage of catecholamines in neurons. Increase in the oxidative stress level and metabolic perturbations can be expected in any tissue or cell type that relies exclusively or mainly on GLUT for co-transport of glucose and DHA including neurons, epithelial cells, and vascular tissues. On the other hand, since DHA represents a significant proportion of total serum ascorbate, by increasing total plasma ascorbate concentrations during hyperglycemia, it should be possible to correct the increase in the oxidative stress level and metabolic perturbations, thereby sparing diabetic patients many of their complications.     

Toward optimizing vision and cognition in term infants by dietary docosahexaenoic and arachidonic acid supplementation: A review of randomized controlled trials

The question of whether a dietary supply of docosahexaenoic acid (DHA) and arachidonic acid (ARA) imparts advantages to visual or cognitive development in term infants has been debated for many years. DHA and ARA are present in human milk, and nursing infants consume these fatty acids needed for rapid synthesis of cell membranes, particularly neural cells. The reported mean DHA and ARA levels of human milk worldwide are 0.32% and 0.47% of total fatty acids, respectively. Prior to 2002 in the US, formula-fed infants did not receive these fatty acids and relied solely on endogenous conversion of the dietary essential omega-3 (n-3) and omega-6 (n-6) fatty acids, α-linolenic and linoleic acids, to DHA and ARA, respectively. Formula-fed infants were found to have significantly less accretion of DHA in brain cortex after death than breastfed infants. Numerous studies have found positive correlations between blood DHA levels and improvements in cognitive or visual function outcomes of breastfed and formula-fed infants. Results of randomized controlled clinical trials of term formula-fed infants evaluating functional benefits of dietary DHA and ARA have been mixed, likely due to study design heterogeneity. A comparison of visual and cognitive outcomes in these trials suggests that dietary DHA level is particularly relevant. Trials with formulas providing close to the worldwide human milk mean of 0.32% DHA were more likely to yield functional benefits attributable to DHA. We agree with several expert groups in recommending that infants receive at least 0.3% DHA, with at least 0.3% ARA, in infant feedings; in addition, some clinical evidence suggests that an ARA:DHA ratio greater than 1:1 is associated with improved cognitive outcomes.     

A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA

Specific fatty acid alterations have been described in the blood and tissues of cystic fibrosis (CF) patients. The principal alterations include decreased levels of linoleic acid (LA) and docosahexaenoic acid (DHA). We investigated the potential mechanisms of these alterations by studying the cellular uptake of LA and DHA, their distribution among lipid classes, and the metabolism of LA in a human bronchial epithelial cell model of CF. CF (antisense) cells demonstrated decreased levels of LA and DHA compared with wild type (WT, sense) cells expressing normal CFTR. Cellular uptake of LA and DHA was higher in CF cells compared with WT cells at 1 h and 4 h. Subsequent incorporation of LA and DHA into most lipid classes and individual phospholipids was also increased in CF cells. The metabolic conversion of LA to n-6 metabolites, including 18:3n-6 and arachidonic acid, was upregulated in CF cells, indicating increased flux through the n-6 pathway. Supplementing CF cells with DHA inhibited the production of LA metabolites and corrected the n-6 fatty acid defect. In conclusion, the evidence suggests that low LA level in cultured CF cells is due to its increased metabolism, and this increased LA metabolism is corrected by DHA supplementation.     

Docosahexaenoic acid in red blood cells of women of reproductive age is positively associated with oral contraceptive use and physical activity

Optimal intake of the long-chain n-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and proper balance between intake of n-6 PUFA and n-3 PUFA are important for human health. Considerable evidence exists to show that DHA has a marked benefit during pregnancy. Lifestyle factors can affect the biosynthesis of DHA from dietary precursors, incorporation into membranes and degradation. The purpose of this study was to investigate the PUFA composition of red blood cells (RBCs) from women (n=40) in reproductive age, and how it is affected by diet and other lifestyle factors. Of all the lifestyle factors tested oral contraceptive use and physical activity were the ones correlated with DHA in RBCs, after adjustment for DHA intake. The findings indicate that oral contraceptive use and physical activity have a positive impact on the DHA status, as assessed by RBC level, of women in reproductive age.     

The mechanism of docosahexaenoic acid-induced phospholipase D activation in human lymphocytes involves exclusion of the enzyme from lipid rafts

Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid that inhibits T lymphocyte activation, has been shown to stimulate phospholipase D (PLD) activity in stimulated human peripheral blood mononuclear cells (PBMC). To elucidate the mechanisms underlying the DHA-induced PLD activation, we first characterized the PLD expression pattern of PBMC. We show that these cells express PLD1 and PLD2 at the protein and mRNA level and are devoid of oleate-dependent PLD activity. DHA enrichment of PBMC increased the DHA content of cell phospholipids, which was directly correlated with the extent of PLD activation. The DHA-induced PLD activation was independent of conventional protein kinase C but inhibited by brefeldin A, which suggests ADP-ribosylation factor (ARF)-dependent mechanism. Furthermore, DHA enrichment dose-dependently stimulated ARF translocation to cell membranes. Whereas 50% of the guanosine 5'-3-O-(thio)triphosphate plus ARF-dependent PLD activity and a substantial part of PLD1 protein were located to the detergent-insoluble membranes, so-called rafts, of non-enriched PBMC, DHA treatment strongly displaced them toward detergent-soluble membranes where ARF is present. Collectively, these results suggest that the exclusion of PLD1 from lipid rafts, due to their partial disorganization by DHA, and its relocalization in the vicinity of ARF, is responsible for its activation. This PLD activation might be responsible for the immunosuppressive effect of DHA because it is known to transmit antiproliferative signals in lymphoid cells.     

The influence of dietary docosahexaenoic acid and arachidonic acid on central nervous system polyunsaturated fatty acid composition

Numerous studies on perinatal long-chain polyunsaturated fatty acid nutrition have clarified the influence of dietary docosahexaenoic acid (DHA) and arachidonic acid (ARA) on central nervous system PUFA concentrations. In humans, omnivorous primates, and piglets, DHA and ARA plasma and red blood cells concentrations rise with dietary preformed DHA and ARA. Brain and retina DHA are responsive to diet while ARA is not. DHA is at highest concentration in cells and tissues associated with high energy consumption, consistent with high DHA levels in mitochondria and synaptosomes. DHA is a substrate for docosanoids, signaling compounds of intense current interest. The high concentration in tissues with high rates of oxidative metabolism may be explained by a critical role related to oxidative metabolism.     

The effects of a diet rich in docosahexaenoic acid on organ and vascular fatty acid composition in spontaneously hypertensive rats

Previous research has shown that dietary docosahexaenoic acid (DHA) attenuates the development of high blood pressure in young spontaneously hypertensive rats (SHR). The purpose of this study was to investigate the effects of dietary DHA on organ and vascular fatty acid composition in SHR. Given the important structural and functional role of fatty acids in cell membranes, alterations in fatty acid composition may contribute to the antihypertensive effect of DHA. SHR were fed a purified diet containing either a corn/soybean oil mixture (CSO, control) or a DHA-enriched oil for 6 weeks. The DHA diet markedly increased the levels of DHA in the aorta, renal artery, plasma, liver, heart, kidney, and lung by 5-, 15-, 7-, 6-, 3.8-, 3.5-, and 8.8-fold (P<0.001), respectively. The levels of eicosapentaenoic acid were also increased while there was a concomitant reduction in arachidonic and adrenic acids. Therefore, dietary DHA increases the incorporation of omega-3 polyunsaturated fatty acids in specific organs and vascular tissue in SHR at the expense of omega-6 polyunsaturated fatty acids.     

The pleiotropic effects of omega-3 docosahexaenoic acid on the hallmarks of Alzheimer's disease

Among omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA, 22:6n-3) is important for adequate brain development and cognition. DHA is highly concentrated in the brain and plays an essential role in brain functioning. DHA, one of the major constituents in fish fats, readily crosses the blood–brain barrier from blood to the brain. Its critical role was further supported by its reduced levels in the brain of Alzheimer's disease (AD) patients. This agrees with a potential role of DHA in memory, learning and cognitive processes. Since there is yet no cure for dementia such as AD, there is growing interest in the role of DHA-supplemented diet in the prevention of AD pathogenesis. Accordingly, animal, epidemiological, preclinical and clinical studies indicated that DHA has neuroprotective effects in a number of neurodegenerative conditions including AD. The beneficial effects of this key omega-3 fatty acid supplementation may depend on the stage of disease progression, other dietary mediators and the apolipoprotein ApoE genotype. Herein, our review investigates, from animal and cell culture studies, the molecular mechanisms involved in the neuroprotective potential of DHA with emphasis on AD.     

Essential role of docosahexaenoic acid towards development of a smarter brain

Evolution of the high order brain function in humans can be attributed to intake of poly unsaturated fatty acids (PUFAs) of which the ω-3 fatty acid, docosahexaenoic acid (DHA) has special significance. DHA is abundantly present in the human brain and is an essential requirement in every step of brain development like neural cell proliferation, migration, differentiation, synaptogenesis etc. The multiple double bonds and unique structure allow DHA to impart special membrane characteristics for effective cell signaling. Evidences indicate that DHA accumulate in areas of the brain associated with learning and memory. Many development disorders like dyslexia, autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia etc. are causally related to decreased level of DHA. The review discusses the various reports of DHA in these areas for a better understanding of the role of DHA in overall brain development. Studies involving laboratory animals and clinical findings in cases as well as during trials have been taken into consideration. Additionally the currently available dietary source of DHA for supplementation as nutraceutics with general caution for overuse has been examined.