DHA Group Research Articles

Proteomic analysis of aorta of LDLR−/− mice given omega‐3 fatty acids reveals modulation of energy metabolism and oxidative stress pathway

AbstractLong chain omega 3 polyunsaturated fatty acids (LC‐n‐3PUFAs) exert potent anti‐atherosclerotic action but the mechanisms of action at the vascular level remain unclear. The present study used a non‐targeted nutrigenomic approach to investigate the modulations of the aortic proteome in atherosclerotic prone mice following DHA supplementation. LDLR−/− male mice received an atherogenic diet (20 weeks) in parallel with daily oral gavages with either oleic acid‐rich oil (Control) or a mixture of oils providing 2% of energy as DHA. The overall protein expression was determined by a proteomic approach followed by bioinformatics analysis. In addition, protein oxidative modifications, namely 4‐hydroxynonenal (4‐HNE) protein adducts, were detected with a specific antibody followed by MS analysis of the identified spots. Nineteen differentially expressed proteins have been identified in the aorta of the DHA group. The top 5 canonical pathways analysis associated all proteins to metabolic pathways and showed that most of them were related to glucose or lipid metabolism. Up‐regulation of superoxide dismutase also suggests an impact of DHA supplementation on vascular antioxidant defenses. The analysis of 4‐HNE‐protein adducts indicated that DHA supplementation did not enhance oxidative modification of proteins with 4‐HNE. This study also identified some new proteins with 4‐HNE adducts at the aortic level. In summary, DHA supplementation induces significant modifications of aorta proteome which point out the importance of metabolic changes occurring in the vascular tissue in the presence of LC‐n‐3PUFAs.

Telomere shortening in elderly individuals with mild cognitive impairment may be attenuated with ω-3 fatty acid supplementation: A randomized controlled pilot study

ObjectivesExcessive shortening of the telomeric ends of chromosomes is a marker of accelerated aging. Oxidative stress and nutritional deficiency may influence this process. The aim of this study was to investigate the effect of ω-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation on telomeric shortening in elderly individuals with mild cognitive impairment (MCI). MethodsThirty-three adults ages > 65 y with MCI were randomized to receive a supplement rich in the long-chain ω-3 PUFAs eicosapentaenoic acid (EPA; 1.67 g EPA + 0.16 g docosahexaenoic acid DHA/d; n = 12) or DHA (1.55 g DHA + 0.40 g EPA/d; n = 12), versus ω-6 PUFA linoleic acid (LA; 2.2 g/d; n = 9) for 6 mo. ResultsThe intervention did not show an increase in telomere length with treatment and there was a trend toward telomere shortening during the intervention period. Linear mixed modeling produced a robust model although statistically underpowered. Telomere shortening was greatest in the LA group (d = 0.21) than in the DHA (d = 0.12) and EPA groups (d = 0.06). Increased erythrocyte DHA levels were associated with reduced telomere shortening (r = −0.67; P = 0.02) in the DHA group. ConclusionTelomeric shortening may be attenuated by ω-3 PUFA supplementation, requiring further investigation in larger samples.

Does early n.3 fatty acid exposure alter DNA methylation in the developing human immune system?

Evaluation of: Lee HS, Barraza‑Villarreal A, Hernandez‑Vargas H et al. Modulation of DNA methylation states and infant immune system by dietary supplementation with n‑3 PUFA during pregnancy in an intervention study. Am. J. Clin. Nutr. 98(2), 480–487 (2013). Long-lasting effects of n-3 fatty acids on the immune cells involved in allergic disease may be due to epigenetic alterations. Pregnant women consumed the n-3 fatty acid docosahexaenoic acid (DHA; 400 mg/day) or placebo from mid-gestation until delivery, and the methylation status of CpG loci within the promoter regions of several genes involved in immune function was measured in umbilical cord blood mononuclear cells (CBMCs) using pyrosequencing. There was no significant effect of DHA supplementation in pregnancy on methylation within the promoter regions of any of the cytokine or transcription factor genes measured in CBMCs. Methylation of the promoter region of the genome stabilizer LINE-1 was higher in CBMCs from infants of mothers who smoked in the DHA group compared with those in the placebo group, although this effect was lost following statistical correction for confounders, but did not differ between nonsmoking women in the two groups. Several factors limit interpretation of the findings. It remains unknown whether there is a role for epigenetic alterations as a mechanism for long-lasting immune and clinical effects of very early n-3 fatty acid exposure.

A possible role for lutein and zeaxanthin in cognitive function in the elderly

Epidemiologic studies suggest that dietary lutein and zeaxanthin may be of benefit in maintaining cognitive health. Among the carotenoids, lutein and zeaxanthin are the only two that cross the blood-retina barrier to form macular pigment (MP) in the eye. They also preferentially accumulate in the human brain. Lutein and zeaxanthin in macula from nonhuman primates were found to be significantly correlated with their concentrations in matched brain tissue. Therefore, MP can be used as a biomarker of lutein and zeaxanthin in primate brain tissue. This is of interest given that a significant correlation was found between MP density and global cognitive function in healthy older adults. An examination of a relation between cognition and lutein and zeaxanthin concentrations in the brain tissue of decedents from a population-based study in centenarians found that zeaxanthin concentrations in brain tissue were significantly related to antemortem measures of global cognitive function, memory retention, verbal fluency, and dementia severity after adjustment for age, sex, education, hypertension, and diabetes. In univariate analyses, lutein was related to recall and verbal fluency, but the strength of the associations was attenuated with adjustment for covariates. However, lutein concentrations in the brain were significantly lower in individuals with mild cognitive impairment than in those with normal cognitive function. Last, in a 4-mo, double-blinded, placebo-controlled trial in older women that involved lutein supplementation (12 mg/d), alone or in combination with DHA (800 mg/d), verbal fluency scores improved significantly in the DHA, lutein, and combined-treatment groups. Memory scores and rate of learning improved significantly in the combined-treatment group, who also showed a trend toward more efficient learning. When all of these observations are taken into consideration, the idea that lutein and zeaxanthin can influence cognitive function in older adults warrants further study.

Margarines Fortified with α-Linolenic Acid, Eicosapentaenoic Acid, or Docosahexaenoic Acid Alter the Fatty Acid Composition of Erythrocytes but Do Not Affect the Antioxidant Status of Healthy Adults1–3

We aimed to investigate the effects of increased intake of α-linolenic acid (ALA), EPA, or DHA incorporated into a food matrix on the fatty acid composition of erythrocytes and on biomarkers of oxidant/antioxidant status. To this end, a controlled dietary study was conducted in 74 healthy men and women. The participants were randomly assigned to 1 of 3 interventions in which margarines fortified with either 10 weight percent ALA, EPA, or DHA ethyl esters replaced their normal spread for 6 wk. The total intakes of ALA, EPA, and DHA were 4.4, 2.2, and 2.3 g/d, respectively. Consuming EPA increased the erythrocyte proportion of EPA (394%) and the omega-3 index (sum of EPA and DHA, 38%). Consumption of DHA increased erythrocyte DHA (91%), the omega-3 index (98%), and EPA (137%). The omega-3 index increased to a significantly greater extent in the DHA group than in the EPA group. ALA did not increase erythrocyte EPA or the omega-3 index. We found no change in plasma uric acid or antioxidant capacity in any of the groups. Plasma malondialdehyde (MDA) increased with the EPA and DHA interventions. All 3 interventions decreased erythrocyte linoleic acid hydroperoxides but did not affect their MDA concentrations. In conclusion, the intake of both isolated EPA and DHA incorporated into margarine resulted in an enhanced incorporation of EPA and DHA into erythrocytes. Our findings indicate that DHA is quantitatively superior to EPA in view of the EPA+DHA tissue incorporation and also that 4 g/d ALA is not sufficient to increase the omega-3 index over a 6-wk period.

Auditory- and Visual-Evoked Potentials in Mexican Infants Are Not Affected by Maternal Supplementation with 400 mg/d Docosahexaenoic Acid in the Second Half of Pregnancy1–4

The evidence relating prenatal supplementation with DHA to offspring neurological development is limited. We investigated the effect of prenatal DHA supplementation on infant brainstem auditory-evoked responses and visual- evoked potentials in a double-blind, randomized controlled trial in Cuernavaca, Mexico. Pregnant women were supplemented daily with 400 mg DHA or placebo from gestation wk 18–22 through delivery. DHA and placebo groups did not differ in maternal characteristics at randomization or infant characteristics at birth. Brainstem auditory-evoked responses were measured at 1 and 3 mo in 749 and 664 infants, respectively, and visual-evoked potentials were measured at 3 and 6 mo in 679 and 817 infants, respectively. Left-right brainstem auditory-evoked potentials were moderately correlated (range, 0.26–0.43; all P < 0.001) and left-right visual-evoked potentials were strongly correlated (range, 0.79–0.94; all P < 0.001) within any assessment. Correlations across visits were modest to moderate (range, 0.09–0.38; all P < 0.01). The offspring of DHA-supplemented women did not differ from those of control women with respect to any outcome measure (all comparisons P > 0.10). We conclude that DHA supplementation during pregnancy did not influence brainstem auditory-evoked responses at 1 and 3 mo or visual-evoked potentials at 3 and 6 mo.

Fish-oil supplementation in pregnancy does not reduce the risk of gestational diabetes or preeclampsia

There is uncertainty regarding the efficacy of increasing n-3 long-chain PUFA (LCPUFA) intake during pregnancy in reducing the risk of gestational diabetes mellitus (GDM) and preeclampsia. The objective was to determine whether n-3 LCPUFA supplementation in pregnancy reduces the incidence of GDM or preeclampsia. A secondary objective was to assess the effect of n-3 LCPUFA supplementation on perinatal complications. This was a double-blind, multicenter randomized control trial-the DHA to Optimize Mother Infant Outcome (DOMInO) trial. Pregnant women (n = 2399) of <21 wk gestation were randomly assigned to receive DHA-enriched fish oil (800 mg/d) or vegetable oil capsules without DHA from trial entry to birth. The presence of GDM or preeclampsia was assessed through a blinded audit of medical records. Birth outcomes and prenatal complications were also assessed. The overall incidences of GDM and preeclampsia were 8% and 5%, respectively, based on clinical diagnosis. The RR of GDM was 0.97 (95% CI: 0.74, 1.27) and of preeclampsia was 0.87 (95% CI: 0.60, 1.25), and they did not differ significantly between the groups. Birth weight, length, and head circumference z scores also did not differ between the groups. There were 12 perinatal deaths and 5 neonatal convulsions in the control group compared with 3 perinatal deaths and no neonatal convulsions in the DHA group (P = 0.03 in both cases). DHA supplementation of 800 mg/d in the second half of pregnancy does not reduce the risk of GDM or preeclampsia. Whether supplementation reduces the risk of perinatal death and neonatal convulsions requires further investigation. The DOMInO trial was registered with the Australian New Zealand Clinical Trials Registry as TRN12605000569606.

Orally administered [14C]DPA and [14C]DHA are metabolised differently to [14C]EPA in rats

Previous studies have revealed that C20 PUFA are significantly less oxidised to CO₂ in whole-body studies compared with SFA, MUFA and C18 PUFA. The present study determined the extent to which three long-chain PUFA, namely 20:5n-3 EPA, 22:5n-3 docosapentaenoic acid (DPA) and 22:6n-3 DHA, were catabolised to CO₂ or, conversely, incorporated into tissue lipids. Rats were administered a single oral dose of 2·5 μCi [1-¹⁴C]DPA, [1-¹⁴C]EPA, [1-¹⁴C]DHA or [1-¹⁴C]oleic acid (18:1n-9; OA), and were placed in a metabolism chamber for 6 h where exhaled ¹⁴CO₂ was trapped and counted for radioactivity. Rats were euthanised after 24 h and tissues were removed for analysis of radioactivity in tissue lipids. The results showed that DPA and DHA were catabolised to CO₂ significantly less compared with EPA and OA (P<0·05). The phospholipid (PL) fraction was the most labelled for all three n-3 PUFA compared with OA in all tissues, and there was no difference between C20 and C22 n-3 PUFA in the proportion of label in the PL fraction. The DHA and DPA groups showed significantly more label than the EPA group in both skeletal muscle and heart. In the brain and heart tissue, there was significantly less label in the cholesterol fraction from the C22 n-3 PUFA group compared with the C20 n-3 PUFA group. The higher incorporation of DHA and DPA into the heart and skeletal muscle, compared with EPA, suggests that these C22 n-3 PUFA might play an important role in these tissues.

Improved Mitochondrial Function with Diet-Induced Increase in Either Docosahexaenoic Acid or Arachidonic Acid in Membrane Phospholipids

Mitochondria can depolarize and trigger cell death through the opening of the mitochondrial permeability transition pore (MPTP). We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA; 22:6n3) and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6) in mitochondrial membranes is associated with a greater Ca2+ load required to induce MPTP opening. Here we manipulated mitochondrial phospholipid composition by supplementing the diet with DHA, ARA or combined DHA+ARA in rats for 10 weeks. There were no effects on cardiac function, or respiration of isolated mitochondria. Analysis of mitochondrial phospholipids showed DHA supplementation increased DHA and displaced ARA in mitochondrial membranes, while supplementation with ARA or DHA+ARA increased ARA and depleted linoleic acid (18:2n6). Phospholipid analysis revealed a similar pattern, particularly in cardiolipin. Tetralinoleoyl cardiolipin was depleted by 80% with ARA or DHA+ARA supplementation, with linoleic acid side chains replaced by ARA. Both the DHA and ARA groups had delayed Ca2+-induced MPTP opening, but the DHA+ARA group was similar to the control diet. In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca2+ load required to induced MPTP opening. Further, high levels of tetralinoleoyl cardiolipin were not essential for normal mitochondrial function if replaced with very-long chain n3 or n6 PUFAs.

Docosahexaenoic Acid PreventsTrans-10,Cis-12–Conjugated Linoleic Acid-Induced Nonalcoholic Fatty Liver Disease in Mice by Altering Expression of Hepatic Genes Regulating Fatty Acid Synthesis and Oxidation

Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented trans-10, cis-12-conjugated linoleic acid (CLA)-induced nonalcoholic fatty liver disease (NAFLD) and insulin resistance. The effective dose of DHA and mechanisms involved are poorly understood. We examined the ability of DHA (0.5% and 1.5%) to prevent increases in NAFLD and homeostatic model assessment of insulin resistance (HOMA-IR) induced by CLA (0.5%) when fed concomitantly for 4 weeks to C57BL/6N female mice. We also examined changes in expression of hepatic genes involved in fatty acid synthesis and oxidation. CLA supplementation increased liver triglycerides (TG) and HOMA-IR by 221% and 547%, respectively, and decreased mass of different adipose depots by 65%-90% when compared to those in the control group. When fed concomitantly, DHA prevented CLA-induced increases in liver TG and circulating insulin with varying efficiency, but it did not prevent loss in adipose tissue mass. In the CLA+0.5% DHA group, the liver TG did not differ from those in the control group, but circulating insulin and HOMA-IR were 285% and 264%, respectively. In the CLA+1.5% DHA group, liver TG were 54% lower than those in the control group, but circulating insulin concentration and HOMA-IR did not differ between these two groups. CLA increased the expression of hepatic genes involved in fatty acid synthesis and decreased the expression of genes involved in fatty acid oxidation, and 1.5% DHA prevented changes in the expression of hepatic genes caused by CLA. Response of different tissues to CLA and DHA varied; CLA was more potent than DHA in altering depot fat and insulin concentrations.

Effects ofn-3 fatty acids, EPAv. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial

Depressive symptoms may increase the risk of progressing from mild cognitive impairment (MCI) to dementia. Consumption of n-3 PUFA may alleviate both cognitive decline and depression. The aim of the present study was to investigate the benefits of supplementing a diet with n-3 PUFA, DHA and EPA, for depressive symptoms, quality of life (QOL) and cognition in elderly people with MCI. We conducted a 6-month double-blind, randomised controlled trial. A total of fifty people aged >65 years with MCI were allocated to receive a supplement rich in EPA (1·67 g EPA + 0·16 g DHA/d; n 17), DHA (1·55 g DHA + 0·40 g EPA/d; n 18) or the n-6 PUFA linoleic acid (LA; 2·2 g/d; n 15). Treatment allocation was by minimisation based on age, sex and depressive symptoms (Geriatric Depression Scale, GDS). Physiological and cognitive assessments, questionnaires and fatty acid composition of erythrocytes were obtained at baseline and 6 months (completers: n 40; EPA n 13, DHA n 16, LA n 11). Compared with the LA group, GDS scores improved in the EPA (P=0·04) and DHA (P=0·01) groups and verbal fluency (Initial Letter Fluency) in the DHA group (P=0·04). Improved GDS scores were correlated with increased DHA plus EPA (r 0·39, P=0·02). Improved self-reported physical health was associated with increased DHA. There were no treatment effects on other cognitive or QOL parameters. Increased intakes of DHA and EPA benefited mental health in older people with MCI. Increasing n-3 PUFA intakes may reduce depressive symptoms and the risk of progressing to dementia. This needs to be investigated in larger, depressed samples with MCI.

Dietary Supplementation with Docosahexanoic Acid or Arachidonic Acid Delay Ca2+ ‐Induced Permeability Transition Pore Opening in Cardiac Mitochondria

Supplementation with docosahexanoic acid (DHA, commonly found in fish oil) in clinically relevant amounts causes a 2-fold increase in DHA in cardiac phospholipids, and delays Ca2+-induced mitochondrial permeability transition pore (MPTP) opening. The mechanism for this effect is not clear, however the increase in DHA is accompanied by a decrease in the ù-6 PUFA arachidonic acid (ARA), which could be responsible for the effects on the MPTP. We determined the role of ARA on MPTP opening by feeding rats DHA, ARA or DHA+ARA. Male Wistar rats were fed either a los DHA+AHA diet(CTRL), a diet containing DHA or ARA at 2.5% of energy intake, or both DHA and ARA at 2.5% each, for 10 wks. Cardiac mitochondria were isolated. All three diets profoundly altered the phospholipid composition of mitochondria compared to CTRL. Both the DHA and ARA groups delayed Ca2+-induced MPTP opening vs. CTRL (p<0.05) while DHA+ARA increased sensitivity to MPTP opening (p<0.05 vs CTRL, DHA or ARA). Furthermore, both diets containing ARA significantly increased the pro-inflammatory marker TBX B2 by 2- to 3-fold compared to CTRL and DHA diets (p<0.05). DHA+ARA also increased lipid peroxidation compared to ARA alone (p=0.008) and to CTRL (p=0.034). This suggests that the effect of DHA on MPTP is not due to depletion of ARA. DHA+ARA showed no added benefit, but rather sensitized MPTP to opening, suggesting that a very large dose of PUFA might be detrimental.

Docosahexaenoic Acid Supplementation from Mid-Pregnancy to Parturition Influenced Breast Milk Fatty Acid Concentrations at 1 Month Postpartum in Mexican Women1–4

(n-3) PUFA, including DHA, are essential for neural development and accumulate extensively in the fetal and infant brain. (n-3) PUFA concentrations in breast milk, which are largely dependent on maternal diet and tissue stores, are correlated with infant PUFA status. We investigated the effect of prenatal DHA supplementation on PUFA concentrations in breast milk at 1 mo postpartum. In a double-blind, randomized, controlled trial conducted in Mexico, pregnant women were supplemented daily with 400 mg DHA or placebo from 18–22 wk gestation to parturition. Fatty acid concentrations in breast milk obtained from 174 women at 1 mo postpartum were determined using GLC and were expressed as % by weight of total detected fatty acids. Breast milk DHA concentrations in the DHA and placebo groups were (mean ± SD) 0.20 ± 0.06 and 0.17 ± 0.07 (P < 0.01), respectively, and those of a-linolenic acid (ALA) were 1.38 ± 0.47 and 1.24 ± 0.46 (P = 0.01), respectively. Concentrations of EPA and arachidonic acid did not differ between groups (P > 0.05). Maternal plasma DHA concentrations at 1 mo postpartum correlated positively with breast milk DHA at 1 mo postpartum in both the placebo and DHA groups (r = 0.4; P < 0.01 for both treatment groups). Prenatal DHA supplementation from 18–22 wk gestation to parturition increased concentrations of DHA and ALA in breast milk at 1 mo postpartum, providing a mechanism through which breast-fed infants could benefit.

Early Docosahexaenoic Acid Supplementation of Mothers during Lactation Leads to High Plasma Concentrations in Very Preterm Infants1–23

Very preterm infants are vulnerable to deficiency in DHA. In a longitudinal study, 10 mothers who delivered ≤29 wk gestation and planned to breast-feed received DHA (1200 mg/d) until 36 wk after conception. The plasma DHA status was assessed in their 12 infants (including 2 pairs of twins) from birth to d 49. Fatty acid profiles were measured weekly in breast milk, and in plasma of mothers and infants at baseline and at d15 and 49. Plasma and breast milk fatty acid concentrations in the DHA-supplemented group at d 49 were compared with a reference group of very preterm infants (n = 24, including triplets) whose mothers (n = 22) did not receive DHA during lactation. The infants’ plasma DHA concentration tended to be greater in the DHA group than in the reference group (P = 0.10) and was greater when expressed as a percentage of total fatty acids (P = 0.009). At d 49, maternal milk DHA in the DHA group (1.92 ± 1.10 mmol/L) was ~12 times higher than in the reference group (0.15 ± 0.27 mmol/L) (P < 0.001). The amount of DHA provided to the infants increased from wk 1 through wk 7 in the DHA group (P < 0.001). Although enteral intake at wk 7 did not differ between the DHA group [119 ± 51 mL/(kg.·d)] and the reference group [113 ± 66 mL/(kg·d)], DHA group infants received 55 ± 38 mg/(kg.·d) of DHA, and the reference group infants received 7 ± 11 mg/(kg·d) (P < 0.001). Early supplementation with DHA to lactating mothers with low dietary DHA intake successfully increased the plasma DHA status in very preterm infants.

Docosapentaenoic acid (omega-3): is it a reservoir of EPA in mammals?

Long chain omega 3 polyunsaturated fats play an important role in brain and cardiovascular function, and in reducing pain and inflammation in conditions such as rheumatoid arthritis. EPA is regarded as important for inflammation and cardiovascular function, while DHA is regarded as crucial for brain function. The role of docosapentaenoic acid (DPA) is unknown. Many studies have shown cardiovascular, arthritis relief or neural benefits of consuming fish or fish oils which typically contain all three of these omega 3 fatty acids. In addition, EPA and DHA have been studied as individual compounds and shown to contribute to the benefits described above. DPA has not been studied in human subjects, however, there are a small number of studies on DPA in cell culture and animals (1) . A major reason DPA has not been studied is because it has not been available pure in sufficient quantity to conduct long-term studies on human subjects or animals. We have data from cell culture and rodent studies which show that DPA is converted to EPA. FAO liver cells were incubated with 50 mM DPA for up to 24 h after which the phospholipid fraction was analysed for fatty acid composition. There was evidence of the appearance of EPA in the cells incubated with DPA by 8 h (3.1% of cell phospholipid fatty acids) and by 24 h the proportion reached 15.9%. Incubation of the cells with EPA led to the appearance of DPA (10.2% of fatty acids). There was no appearance of DHA in this time in the case of either the EPA or DPA treated cells. In young rats (n 8/group), fed 50 mg of DPA/day orally for 7 d, there was a significant increase in EPA in liver, heart, adipose and skeletal muscle, but not in brain (2) . There was also a small but significant increase in the DHA concentration in liver (P < 0.05) (2) . Rats fed with 50 mg/d of EPA in the same study, also showed a similar increase in the concentration of DHA in the liver (P < 0.05). The conversion of DPA to EPA is described as retroconversion and is thought to involve peroxisomal acyl-CoA oxidase and one cycle of beta-oxidation in peroxisomes (3) . In a second rat study, rats were given an oral dose of either 1- 14 C labelled EPA, DPA or DHA (n 5/group) and then placed in a metabolic chamber to collect the expired radiolabelled carbon dioxide over the next 6 h. It was found that significantly more CO2 was collected from rats fed the EPA (19.31.1% of the dose) compared with those fed DPA (5.11.1 %) and DHA (7.00.4 %, P < 0.05). In this study, there was significantly more radioactivity recovered in lipids of liver, brain and kidney for the DHA group compared with the EPA and DPA groups (P < 0.05). In heart and skeletal muscle, the incorporation of the radioactivity into lipids was significantly lower in the EPA group compared with DPA and DHA groups (P < 0.05). These novel data indicate that further studies of the role of DPA in mammals should be conducted.

Effect of a Novel Eicosapentaenoic Acid‐Rich Oil on Serum Cholesterol in Man: Comparison to Docosahexaenoic Acid

BackgroundFish oil and DHA raise LDL cholesterol (LDL‐C); the effects of EPA are less defined.Study Design121 healthy volunteers were recruited into a randomized, double‐blinded, placebo‐controlled, parallel‐arm, 6 week study. The placebo group received olive oil; the low dose EPA group (EPA600) received 600 mg/day of a yeast derived EPA; the high dose EPA group (EPA1800) received 1800 mg/day, and the DHA group (DHA600) received 600 mg/day of an algal derived DHA. Notably, the EPA oil did not contain any DHA and the DHA oil did not contain any EPA.Results110 subjects completed the study. The study population was 21–70 yrs of age, 67% male, 33% female, with an average BMI of 27.4. Subjects were not allowed lipid‐lowering medications or omega‐3 dietary supplements during the study and were counseled to maintain their normal diet and exercise programs. The number of subjects who remained free of fishy aftertaste or eructation was 92% for placebo, 85% for EPA600, 72% for EPA1800, and 61% for DHA600. The placebo group exhibited a 6% decrease in LDL‐C (n=26, P&lt;0.01); the EPA600 group a 3% decrease in LDL‐C (n=27, NS), the EPA1800 group a 2% decrease in LDL‐C (n=29, NS); in contrast, the DHA group exhibited a 14% increase in LDL‐C (n=28, P&lt;0.02). HDL and TG levels were relatively unaffected.ConclusionDHA, but not EPA, raised LDL‐C in normal lipidemic subjects at a dietary intake of 600 mg/day for 6 weeks. Funded by DuPont.

Docosahexaenoic acid supplementation increases prefrontal cortex activation during sustained attention in healthy boys: a placebo-controlled, dose-ranging, functional magnetic resonance imaging study

Emerging evidence suggests that docosahexaenoic acid (DHA, 22:6n-3), the principal omega-3 (n-3) fatty acid in brain gray matter, positively regulates cortical metabolic function and cognitive development. However, the effects of DHA supplementation on functional cortical activity in human subjects are unknown. The objective was to determine the effects of DHA supplementation on functional cortical activity during sustained attention in human subjects. Healthy boys aged 8-10 y (n = 33) were randomly assigned to receive placebo or 1 of 2 doses of DHA (400 or 1200 mg/d) for 8 wk. Relative changes in cortical activation patterns during sustained attention at baseline and endpoint were determined by functional magnetic resonance imaging. At 8 wk, erythrocyte membrane DHA composition increased significantly from baseline in subjects who received low-dose (by 47%) or high-dose (by 70%) DHA but not in those who received placebo (-11%). During sustained attention, both DHA dose groups had significantly greater changes from baseline in activation of the dorsolateral prefrontal cortex than did the placebo group, and the low-dose and high-dose DHA groups had greater decreases in the occipital cortex and cerebellar cortex, respectively. Relative to low-dose DHA, high-dose DHA resulted in greater decreases in activation of bilateral cerebellum. The erythrocyte DHA composition was positively correlated with dorsolateral prefrontal cortex activation and was inversely correlated with reaction time, at baseline and endpoint. Dietary DHA intake and associated elevations in erythrocyte DHA composition are associated with alterations in functional activity in cortical attention networks during sustained attention in healthy boys. This trial was registered at clinicaltrials.gov as NCT00662142.

Supplementation of DHA but not DHA with arachidonic acid during pregnancy and lactation influences general movement quality in 12-week-old term infants

DHA and arachidonic acid (AA) are important for neurodevelopment. A traditional neonatal neurological examination and the evaluation of general movement quality are sensitive techniques for assessing neurodevelopment in young infants. Mildly abnormal general movements at 3 months have been associated with a non-optimal current brain condition. We investigated whether supplementation of DHA during pregnancy and lactation influences the infant's brain development and whether additional AA modulates this effect. Healthy women were randomly assigned to DHA (220 mg/d, n 42), DHA+AA (220 mg each/d, n 41) or control (n 36), from about week 17 (range 14-20 weeks) of pregnancy until 12 weeks postpartum. The control and the DHA+AA groups had approximately comparable dietary DHA/AA ratios. The standardised neonatal neurological examination was carried out at 2 weeks. General movement quality was assessed at 2 and 12 weeks. Neither DHA alone nor DHA+AA influenced outcomes in the traditional examination. General movement quality of infants in the DHA group was lower than that of infants in the other two groups, especially at 12 weeks: 61 % of the infants in the DHA group showed mildly abnormal general movements compared with 31 % in the control group (P = 0.008) and 34 % in the DHA+AA group (P = 0.015). We conclude that general movement quality at 12 weeks is sensitive to the maternal dietary DHA/AA balance.

N-3계 지방산 적절 함량 식이의 docosahexaenoic acid 첨가가 기억력 관련 뇌 기능에 미치는 영향

SD계 흰쥐를 사용하여 motor activity 실험에서 동물들의 자발적인 운동성을 측정한 결과, 주어진 시간 내 움직인 시간과 움직인 거리에는 n-3 지방산이 적절히 함유된 식이군 (Adq group)과 DHA가 첨가된 식이군(Adq+DHA group)간에 유의적 차이를 관찰할 수가 없었다. 학습효과 실험에서 n-3 지방산이 적절히 함유된 식이군 (Adq group)의 경우 목적 플랫트폼까지 걸리는 시간이 DHA 첨가 식이군(Adq+DHA group)에 비하여 다소 길었으나 유의적 차이는 관찰할 수가 없었다. 수영 속도(swimming speed)에서 DHA 첨가 식이군(Adq+DHA group)의 경우, n-3 지방산이 적절히 함유된 식이군 (Adq group)에 비해 유의적으로 빨랐으나 수영 풀에서 움직인 거리 (swimming distance)에는 두 식이군 간의 유의적 차이가 없었다. 두 식이군의 흰쥐들이 수영한 시간(swimming time)과 쉬고 있는 시간(resting time)의 경우, 쉬는 시간에는 유의적 차이가 없었으나 수영 시간 또한 n-3 지방산이 적절이 함유된 식이(Adq group)로 사육된 쥐가 DHA가 첨가된 식이로 사육된 쥐(Adq+DHA group)보다 수영한 시간이 길었으나 여기서도 유의적 차이는 없었다. 기억력 테스트에서 n-3 지방산이 적절히 함유된 식이군(Adq group) 및 DHA가 첨가된 식이군(Adq+DHA group) 모두는 목적 플랫트폼이 있었던 A 지역에 대한 기억이 우수하여 다른 지역들인 B, C, D를 지나가는 횟수보다 유의적으로 많았음을 관찰하였다(p<0.05). 이상의 결과로부터 임신에서부터 성인이 될 때까지 n-3 지방산이 적절히 함유된 식이로 사육된 쥐와 비교할 때 DHA가 첨가된 식이로 사육된 흰쥐가 Morris water maze를 이용한 공간기억력 실험에서 다소 우수한 기억 학습효과를 나타내었으나 유의적 차이는 없었음을 관찰 할 수가 있었다. The effect of adding docosahexaenoic acid into an n-3 fatty acid adequate diet on the improvement of learning related brain function was investigated. On the second day after conception, Sprague Dawley strain dams were subjected to a diet containing either n-3 fatty acid adequate (Adq, 3.4% linolenic acid) or n-3 fatty acid adequate+docosahexaenoic acid (Adq+DHA, 3.31%linolenic acid plus 9.65% DHA). After weaning, male pups were fed on the same diet of their respective dams until adulthood. Motor activity and Morris water maze tests were measured at 10 weeks. In the motor activity test, there were no statistically significant differences in moving time and moving distance between the Adq and Adq+DHA diet groups. The n-3 fatty acid adequate with DHA (Adq+DHA) group tended to show a shorter escape latency, swimming time and swimming distance compared to the n-3 fatty acid adequate group (Adq), but the differences were not statistically significant. There was no difference in resting time, but the Adq+DHA group showed a higher swimming speed compared to the Adq group. In memory retention trials, the numbers of crossing of the platform position (region A), in which the hidden platform was placed, were significantly greater than those of other regions for both Adq and Adq+DHA groups. Based on these results, adding DHA into the n-3 fatty acid adequate diet from gestation to adulthood tended to induce better spatial learning performance in Sprague Dawley rats as assessed by the Morris water maze test, although the difference was not significant.

High Protein Diet and DHA Supplementation may be Effective to Recover the Impaired Immune Function in Irradiated Rats

Most cancer patients with radiation treatment have a tendency to avoid animal foods and prefer vegetables which may cause accelerated malnutrition with impairment of immune function. These overall conditions could contribute eventual poor prognosis and poor quality of life. The major goal of this study was to determine the effects of high protein diet (HP) and DHA supplementation in minimizing the adverse effects of radiation for cancer treatment. Rats were divided into four groups: normal protein diet (NP) and HP groups and NP + DHA and HP + DHA groups. Each diet group was further divided into treatment groups that received radiation (RT group) and one that did not (non‐RT group). The diet administration supplied from 12th day prior to radiation treatment with irradiation dose of 17.5 Gy. The diets were continued until 10th day after radiation treatment and animals were sacrificed. Radiation treatment significantly decrease the proportion of lymphocyte and increase the proportion of neutrophil and eosinophil. Radiation treatment also caused the significant increase in WBC and decrease in platelets. HP and DHA supplementation resulted the change of lymphocyte and neutrophil proportions into similar to non‐radiated group levels, thereby effective to recover the impaired immune function in irradiated rats.