Plasma Phospholipid DHA Research Articles

Determinants of maternal and infant omega-3 status at 3 months postpartum: findings from the APrON longitudinal cohort study.

Omega-3 long-chain-polyunsaturated fatty acids (LCPUFAs) are important dietary components for maternal and infant health during pregnancy and lactation. This study investigated determinants of maternal and infant LCPUFAs status at 3 mo postpartum and the relationship between maternal serum, maternal milk, and infant LCPUFAs. This cross-sectional study included mothers (n = 1481) and their offspring (n = 526) at 3 mo postpartum from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort. Maternal dietary intake (24-h recall), blood samples from mothers and infants, and maternal milk were collected. Fatty acid composition (relative % of total fatty acids) was determined by gas-liquid chromatography. Linear regression analyses explored associations between diet, sociodemographic factors, and fatty acid status. In a multivariable-adjusted analysis, maternal total dietary intake (supplement + food) was positively associated with the percentage of DHA (standardized ß [Sβ] = 0.394; ß = 0.394; 95% [confidence interval] CI: 0.192, 0.558; P < 0.001) in maternal serum phospholipids. Similar associations were found for DHA and eicosapentaenoic acid in maternal milk and plasma phospholipids of infants. Prepregnancy body mass index (BMI) was negatively associated with DHA (Sß = -0.073; ß = -0.003; 95% CI: -0.006, -0.001; P = 0.008) and positively associated with total saturated fatty acids (Sß = 0.086; ß = 0.111; 95% CI: 0.042, 0.180; P = 0.002) in maternal milk. Infants receiving formula combination with maternal milk had lower percentage of DHA (Sß = -0.177; ß = -0.390; 95% CI: -0.604, -0.175; P < 0.001) and arachidonic acid (Sß = -0.106; ß = -0.595; 95% CI: -1.122, -0.067; P = 0.027) in their plasma phospholipids compared with those who fed exclusively maternal milk. Maternal total dietary intake and prepregnancy BMI are independently associated with their serum fatty acid status during lactation, whereas maternal diet, milk fatty acid composition, and lactation status are important determinants of infant n-3 LCPUFAs fatty acid status. Future research should investigate the impact of these differences in fatty acid status on infant health outcomes.

Sex differences in lipid mediators derived from omega-3 fatty acids in older individuals with low-grade chronic inflammation

The rate of cardiovascular disease (CVD) death is higher in men than women before age 50 y, but the gap between sexes significantly narrows after menopause. Lipid mediators derived from EPA, DHA and AA play a role in inflammation and CVD. The aim of our study was to assess whether plasma concentrations of these lipid mediators differ between postmenopausal women and men. Twelve postmenopausal women and 9 men with low-grade chronic inflammation completed a randomized, double-blind, crossover study consisting of a 4-week lead-in placebo phase (3 g/d high-oleic acid sunflower oil) followed by randomization to either 3 g/d DHA or 3 g/d EPA for 10 weeks and crossover for additional 10 weeks, separated by a washout phase. Plasma phospholipid content of EPA, DHA and AA and plasma concentrations of their derived lipid mediators were measured at the end of the placebo lead-in phase (baseline) and the DHA and EPA supplementation phases. There were no sex differences in plasma phospholipid EPA, DHA and AA at baseline and after DHA and EPA supplementation. However, plasma concentrations of lipid mediators derived from EPA, DHA and AA via 15-lipoxygenase were lower in postmenopausal women than men, especially after supplementation. Sex differences in EPA- and DHA-derived lipid mediators with anti-inflammatory and pro-resolving actions may partly explain the faster rise in CVD in postmenopausal women than age-matched men.

A 16-week randomized controlled trial of a fish oil and whey protein-derived supplement to improve physical performance in older adults losing autonomy-A pilot study.

Low functional capacity may lead to the loss of independence and institutionalization of older adults. A nutritional intervention within a rehabilitation program may attenuate loss of muscle function in this understudied population. This pilot study assessed the feasibility for a larger RCT of a nutritional supplementation in older adults referred to an outpatient assessment and rehabilitation program. Participants were randomized to receive a supplement (EXP: 2g fish oil with 1500 IU vitamin D3 1x/d + 20-30g whey protein powder with 3g leucine 2x/d) or isocaloric placebo (CTR: corn oil + maltodextrin powder) for 16 weeks. Handgrip and knee extension strength (using dynamometry), physical performance tests and plasma phospholipid n-3 fatty acids (using GCMS) were evaluated at weeks 0, 8 and 16; and lean soft tissue mass (using DXA), at weeks 0 and 16. Over 2 years, 244 patients were screened, 46 were eligible (18.9%), 20 were randomized, 10 completed the study (6 CTR, 4 EXP). Median age was 87 y (77-94 y; 75% women) and gait speed was 0.69 m/s; 55% had low strength, and all performed under 420m on the 6-minute walk test, at baseline. Overall self-reported compliance to powder and oil was high (96% and 85%) but declined at 16 weeks for fish oil (55%). The EXP median protein intake surpassed the target 1.2-1.5 g/kg/d, without altering usual diet. Proportions of plasma phospholipid EPA and DHA increased significantly 3- and 1.5-fold respectively, at week 8 in EXP, with no change in CTR. Participants were able to complete most assessments with sustained guidance. Because of low eligibility, the pilot study was interrupted and deemed non-feasible; adherence to rigorous study assessments and to supplements was adequate except for long-term fish oil. The non-amended protocol may be applied to populations with greater functional capacity. ClinicalTrials.gov NCT04454359.

Feeding a Bioactive Oil Enriched in Stearidonic Acid during Early Life Influences Immune System Maturation in Neonatal Sprague-Dawley Rats

Long-chain n-3 PUFAs (LCPUFAs) improve immune development and reduce atopic disease risk in infants. Stearidonic acid (SDA) can be a substrate for biosynthesis of n-3 LCPUFAs. We aimed to determine the effect of feeding an SDA-enriched diet during suckling and weaning on offspring immunity and ability to develop oral tolerance (OT). Pregnant Sprague-Dawley rats were randomly assigned to consume either SDA (3g SDA/100g fat) or a control (no SDA) diet, 5 d before parturition and through lactation (21 d). For the OT treatment, 10-d-old pups were fed ovalbumin (Ova; 200 μL of 8mg/mL) or placebo daily for 5 d. At 21 d, pups (both sexes) were weaned to their respective maternal diet until 6 wk of age or killed. Systemic immunization was induced using Ova (in 3-wk-old pups) or Ova+adjuvant (in 6-wk-old pups). The effect of suckling diet (in 3-wk-old pups) or weaning diet (in 6-wk-old pups) and OT treatment on immune function (main outcome) in spleen and blood was compared using 2-factor ANOVA. An SDA-enriched maternal diet, compared with the control diet, resulted in higher plasma phospholipid (PL) EPA (15 times higher), docosapentaenoic acid (DPA; 3 times higher), and DHA (1.3 times higher) content in 3-wk-old pups, accompanied by higher B-cell function [plasma ovalbumin-specific IgG1 (Ova-IgG1), 2 times higher] ( P<0.05). Compared with pups fed a control diet, the splenocytes from these pups had more (23%) helper T (Th) cells (CD3+CD4+) and activated (12%) Th cells (CD4+CD28+) (P<0.02) than controls. At 6 wk, the SDA group had 30% more CD4+CD25+splenocytes, and when stimulated ex vivo with LPS, produced less inflammatory IL-6 (50%) and TNF-α (30%) and more immunoregulatory IL-10 (45%) cytokines (P<0.05) than the control group. The Ova-exposed group had less (30%) plasma Ova-IgG1 than the placebo group. Splenocytes and plasma PLs from the 6-wk-old SDA group had more EPA (2x) and DPA (3.5x) (P<0.05), but not DHA, than the control group. Feeding SDA during lactation and weaning altered immune responses in directions believed to be beneficial.

Four-oil intravenous lipid emulsion effect on plasma fatty acid composition, inflammatory markers and clinical outcomes in acutely ill patients: A randomised control trial (Foil fact)

Data in critically ill patients on the effect of intravenous lipid emulsions (LEs), containing omega-3 polyunsaturated fatty acids (PUFAs), in parenteral nutrition (PN) are scarce and conflicting. This study compared the effects of a four-oil LE (30% soybean oil, 30% medium-chain triglycerides, 25% olive oil and 15% fish oil (FO)) (SMOFlipid®) to those of a 100% soybean oil-based LE in critically ill adult intensive care unit (ICU) patients. In this double-blind, randomised study, patients (n=75) predicted to need PN for more than 5 days were randomised to receive either a four-oil LE (Study Group (SG)) or a 100% soybean oil LE (Control Group (CG)). Isocaloric, isonitrogenous PN was administered continuously for 5 days. FO was provided at a dose of 0.09-0.22g/kg body weight. Measurements included biochemical parameters and sequential organ failure assessment (SOFA) score daily and plasma total phospholipid fatty acids (FAs) and cytokine levels on days 1, 3, 6. Days on mechanical ventilation, length of stay and mortality were also recorded. ANOVA was used to compare response variables between the two groups over the time and Pearson correlation was used to measure relationships between continuous variables. 68 patients completed the study (n=35 SG, n=33 CG), with male predominance (66% SG, 56% CG). Average age was 60.8±13.9 years (SG) versus 55.7±14.8 (CG) (p=0.143). The majority were surgical admissions (85% SG versus 91% CG) followed by medical. Plasma phospholipid oleic acid (p=0.022) and alpha-linolenic acid (p<0.0005) increased in both groups. In the SG, plasma phospholipid EPA and DHA increased (both p<0.001), whereas the omega-6:omega-3 PUFA (n-6:n-3 PUFA) ratio decreased (p<0.001). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin decreased in both treatment groups. Considering only the change from day 1 to day 6 there was a bigger decrease in AST, ALT and bilirubin levels in the SG. Concentrations of TNF-α decreased from day 1 to day 6 in the SG, whereas they increased in the CG, but the change was not statistically significant (p=0.112). A significant negative correlation was found between EPA provision on day 3 and the SOFA score (r=-0.4047, p=0.018). Days on mechanical ventilation (1.24±0.83 days in SG versus 0.88±1.63 days in CG, p=0.385) and ICU LOS (9.5±7.09 days in SG versus 10.7±7.6 days in CG, p=0.490) were not different between groups. PN containing a four-oil LE increased plasma EPA and DHA, decreased n-6:n-3 PUFA ratio, and was safe and well tolerated. The negative relationship between day 3 EPA and SOFA score seems promising, but EPA intake and effects may have been diluted by enteral nutrition which was started in more than half of patients on day 4. There was no significant difference in terms of other biochemical measurements, SOFA score, length of ICU stay and mortality. More research is needed in this patient population, particularly regarding dose, duration and timing of FO and the effects on clinical outcomes.

Effect of fish oil on monoepoxides derived from fatty acids during cardiac surgery

Our objective was to assess the dynamics of monoepoxides derived from polyunsaturated fatty acids (MEFAs), and their response to n-3 PUFA supplementation, in the setting of acute tissue injury and inflammation (cardiac surgery) in humans. Patients (479) undergoing cardiac surgery in three countries were randomized to perioperative fish oil (EPA + DHA; 8-10 g over 2-5 days preoperatively, then 2 g/day postoperatively) or placebo (olive oil). Plasma MEFAs derived from n-3 and n-6 PUFAs were measured 2 days postoperatively. Based on serial measures in a subset of the placebo group, levels of all MEFAs declined substantially following surgery (at postoperative day 2), with declines ranging from 37% to 63% (P < 0.05 each). Compared with placebo at postoperative day 2, levels of EPA- and DHA-derived MEFAs were 40% and 18% higher, respectively (P ≤ 0.004). The n-3 PUFA supplementation did not significantly alter the decline in n-6 PUFA-derived MEFAs. Both enrollment level and changes in plasma phospholipid EPA and DHA were associated with their respective MEFAs at postoperative day 2 (P < 0.001). Under the acute stress of cardiac surgery, n-3 PUFA supplementation significantly ameliorated the reduction in postoperative n-3 MEFAs, but not n-6 MEFAs, and the degree of increase in n-3 MEFAs related positively to the circulating level of their n-3 PUFA precursors.

Biomarkers of dairy fat

Dear Editor: There were 2 interesting articles in a recent issue of the Journal in which odd-chain fatty acids (15:0 and 17:0) were used as circulating biomarkers of dairy fat (1, 2). In one of the studies (1), serum pentadecanoic acid (15:0) was shown to be inversely associated with incident type 2 diabetes, and in the other study (2) the association of pentadecanoic acid and heptadecanoic acid (17:0) with the risk of incident stroke was studied and no significant association was found. These odd-chain fatty acids are considered to be validated biomarkers for dairy fat and they correlated with dairy consumption in many studies (1–4). However, the association between the intake of dairy fat and the relative serum content of heptadecanoic acid has not been clear in all studies (5, 6). In a large cohort study [EPIC (European Prospective Investigation into Cancer and Nutrition)], there was a strong positive ecologic correlation (r = 0.8, P ≤ 0.01) between the total intake of fish and plasma concentration of heptadecanoic acid, whereas there was no correlation between heptadecanoic acid or pentadecanoic acid and dairy products (6). Accordingly, we have seen in our studies (MA Lankinen et al., 2015) a positive correlation between pentadecanoic and heptadecanoinc acids with DHA in plasma phospholipids. The fatty acid heptadecanoic acid is present in the fat of fish (0.31–2.0% depending on fish species) (7, 8). Salmon contains ∼40 mg heptadecanoic acid and 20 mg pentadecanoic acid per 100 g (9). Therefore, we are a bit concerned if these odd-chain fatty acids are considered to be a valid biomarker for dairy fat intake in populations who consume considerable amounts of fish. In populations with a high consumption of dairy fat and a low consumption of fish, odd-chain fatty acids are probably valid biomarkers for dairy fat intake. In populations who consume fish, the presence of odd-chain fatty acids in fish should be taken into account to avoid misleading conclusions.

The omega smart baby project: effect of maternal DHA on infant development (269.1)

A randomized placebo controlled trial was conducted to examine the effect of DHA on gestational length and cognitive development. 115 pregnant women were supplemented with 300 mg DHA/d or placebo during pregnancy and thru the first 3 mo of breastfeeding (BF). Bayley Scales of Infant Development (BSID) were administered at 4 mo and 1y. Dietary DHA intake during pregnancy, was 81.9 +/‐ 5.8 mg/day (95% CI 72.3,91.5) and increased only slightly during BF. Some took prenatal vitamins with 0– 300 mg DHA per day resulting in total DHA intakes of 80 to 1100 mg/day. RBC and plasma phospholipid DHA at entry (expressed as % total fatty acids) were5.94 +/‐ 1.52 and 5.04 +/‐ 1.44 (mean +/‐ SD), respectively. Breastmilk (BM) % total DHA was .53 +/‐ .037 (mean +/‐ sem) at 2 mo and decreased to .35 +/‐ /039 at 4 mo. BM DHA was significantly greater in the DHA treatment ( p&lt;.02) and with the highest DHA intake compared to the lowest. BM DHA was lowest in carriers of the minor allele of the delta‐5 desaturase gene. Data were analyzed by treatment and by DHA intake. DHA supplementation resulted in a 1 wk increase in gestation with a significant (p&lt;.03) 8 d increase in gestational length comparing the highest intake of DHA( &gt; 600 mg/d) to the lowest (&lt; 300 mg/d). BSID cognitive and language scores were 10 points higher with high intake of DHA compared to the lowest (p&lt;.02). Maternal DHA impacts both pregnancy outcome and subsequent development.

Lipid Metabolic Dose Response to Dietary Alpha‐Linolenic Acid in Monk Parrot (Myiopsitta monachus)

Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a progressive disease characterized by the formation of plaques in the arteries accompanied by underlying chronic inflammation. The family of n-3 fatty acids, especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have consistently been shown to reduce atherosclerotic risk factors in humans and other mammals. Some avian species have been observed to convert α-linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk 71:258-266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore, the metabolic effects of including flaxseed oil, as a source of ALA, in the diet at three different levels (low, medium, and high) on the lipid metabolism of Monk parrots was evaluated through measuring plasma total cholesterol (TC), free cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed intake, body weight, and body condition score were also assessed. Thus the dose and possible saturation response of increasing dietary ALA at constant linoleic acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M. monachus) was evaluated. Calculated esterified cholesterol in addition to plasma TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn-3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid 20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the present data were combined with data from a previous study (Petzinger et al. in J Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6Δ7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA.

The Dutch Healthy Diet index as assessed by 24h recalls and FFQ: associations with biomarkers from a cross-sectional study.

The Dutch Healthy Diet index (DHD-index) was developed using data from two 24h recalls (24hR) and appeared useful to evaluate diet quality in Dutch adults. As many epidemiologic studies use FFQ, we now estimated the DHD-index score using FFQ data. We compared whether this score showed similar associations with participants' characteristics, micronutrient intakes, and biomarkers of intake and metabolism compared with the DHD-index using 24hR data. Data of 121 Dutch participants of the European Food Consumption Validation study were used. Dietary intake was assessed by two 24hR and a 180-item FFQ. Biomarkers measured were serum total cholesterol and carotenoids, EPA+DHA in plasma phospholipids and 24h urinary Na. A correlation of 0·48 (95 % CI 0·33, 0·61) was observed between the DHD-index score based on 24hR data and on FFQ data. Classification of participants into the same tertiles of the DHD-index was achieved for 57 %. Women showed higher DHD-index scores. Energy intake was inversely associated with both DHD-index scores. Furthermore, age and intakes of folate, Fe, Mg, K, vitamin B6 and vitamin C were positively associated with both DHD-index scores. DHD-index scores showed acceptable correlations with the four combined biomarkers taking energy intake into account (r 24hR 0.55; r FFQ 0.51). In conclusion, the DHD-index score based on FFQ data shows similar associations with participants' characteristics, energy intake, micronutrient intake and biomarkers compared with the score based on 24hR data. Furthermore, ranking of participants was acceptable for both methods. FFQ data may therefore be used to assess diet quality using the DHD-index in Dutch populations.

Plasma phospholipid EPA and DHA are divergently associated with overall mortality in newly diagnosed diabetic patients: results from a follow-up of the Nord-Trøndelag Health (HUNT) Study, Norway.

Data concerning the long-term effects of n-3 and n-6 PUFA on disease control and development of complications in diabetic patients are inconsistent. The relationship between plasma phospholipid PUFA and total mortality in type 2 diabetes is unknown. The present study aims to investigate the association between plasma phospholipid fatty acid relative concentrations expressed as weight percentage and total mortality in patients with type 2 diabetes. Mortality rates were evaluated at 5, 10, 15 and 20 years in patients with newly diagnosed diabetes (n 323) and matched non-diabetic controls (n 200) recruited from the Nord-Trøndelag Health (HUNT) Study, Norway. Kaplan-Meier survival curves were constructed and Cox regression analysis was used to calculate hazard ratios (HR) adjusted for biochemical and clinical covariates. After 10 years of follow-up, EPA in the diabetic population was negatively associated with total mortality, with an HR at the fifth quintile of 0·47 (95 % CI 0·25, 0·90) compared with the first quintile. In contrast, DHA was positively associated with total mortality, with an HR at the fifth quintile of 2·87 (95 % CI 1·45, 5·66). Neither EPA nor DHA was associated with total mortality in matched non-diabetic controls. In conclusion, plasma phospholipid relative concentrations of EPA were negatively associated, while those of DHA were positively associated with total mortality in diabetics. This difference in associations suggests a differential effect of EPA and DHA in patients with type 2 diabetes.

Dietary methods and biomarkers of omega 3 fatty acids: a systematic review

The aims of the present study were to review the validity of dietary methods used to measure the usual long chain (LC) omega-3 polyunsaturated fatty acid (n-3 PUFA) intake of a population and to assess the usefulness of different biomarkers of n-3 PUFA in healthy humans. Two systematic literature searches were conducted until May 2011 to update previous systematic reviews. The first literature search aimed to find studies validating the methodology used for measuring the dietary intake of n-3 PUFA. The second search aimed to find human intervention studies in which n-3 PUFA status changed after 2 weeks of n-3 PUFA supplementation. Sixteen studies were identified for inclusion in the first review. Correlation coefficients between fatty acids in subcutaneous fat or blood lipids and dietary intake of n-3 PUFA from different questionnaires were similar. Subcutaneous fat has been reported as the best reference method for some authors, and these studies showed moderate correlation coefficients with no dietary intake method being superior to any other. As for the evaluation of biomarkers of docosahexaenoic acid (DHA, 22 : 6 n-3) and eicosapentaenoic acid (EPA, 20 : 5n-3) status in response to supplementation, the new search reaffirmed and reinforced the evidence supporting that plasma phospholipid DHA, erythrocyte DHA, and platelet DHA were all effective and robust biomarkers of DHA status. Our findings only confirmed earlier studies and did not provide evidence for reaching new conclusions.

Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids

The conversion of the plant-derived omega-3 (n-3) α-linolenic acid (ALA, 18:3n-3) to the long-chain eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) can be increased by ALA sufficient diets compared to ALA deficient diets. Diets containing ALA above an optimal level result in no further increase in DHA levels in animals and humans. The present study evaluates means of maximizing plasma DHA accumulation by systematically varying both linoleic acid (LA, 18:2n-6) and ALA dietary level. Weanling rats were fed one of 54 diets for three weeks. The diets varied in the percentage of energy (en%) of LA (0.07–17.1 en%) and ALA (0.02–12.1 en%) by manipulating both the fat content and the balance of vegetable oils. The peak of plasma phospholipid DHA (>8% total fatty acids) was attained as a result of feeding a narrow dietary range of 1–3 en% ALA and 1–2 en% LA but was suppressed to basal levels (∼2% total fatty acids) at dietary intakes of total polyunsaturated fatty acids (PUFA) above 3 en%. We conclude it is possible to enhance the DHA status of rats fed diets containing ALA as the only source of n-3 fatty acids but only when the level of dietary PUFA is low (<3 en%).

Effects of high-dose fish oil supplementation during early infancy on neurodevelopment and language: a randomised controlled trial

n-3 Long-chain PUFA (LC-PUFA) intake during infancy is important for neurodevelopment; however, previous studies of n-3 LC-PUFA supplementation have been inconclusive possibly due to an insufficient dose and limited methods of assessment. The present study aimed to evaluate the effects of direct supplementation with high-dose fish oil (FO) on infant neurodevelopmental outcomes and language. In the present randomised, double-blind, placebo-controlled trial, 420 healthy term infants were assigned to receive a DHA-enriched FO supplement (containing at least 250 mg DHA/d and 60 mg EPA/d) or a placebo (olive oil) from birth to 6 months. Assessment occurred at 18 months via the Bayley Scales of Infant and Toddler Development (3rd edition; BSID-III) and the Child Behavior Checklist. Language assessment occurred at 12 and 18 months via the Macarthur-Bates Communicative Development Inventory. The FO group had significantly higher erythrocyte DHA (P = 0·03) and plasma phospholipid DHA (P = 0·01) levels at 6 months of age relative to placebo. In a small subset analysis (about 40% of the total population), children in the FO group had significantly higher percentile ranks of both later developing gestures at 12 and 18 months (P = 0·007; P = 0·002, respectively) and the total number of gestures (P = 0·023; P = 0·006, respectively). There was no significant difference between the groups in the standard or composite scores of the BSID-III. The results suggest that improved postnatal n-3 LC-PUFA intake in the first 6 months of life using high-dose infant FO supplementation was not beneficial to global infant neurodevelopment. However, some indication of benefits to early communicative development was observed.

Total dietary fat and fatty acid content modifies plasma phospholipid fatty acids, desaturase activity indices, and urinary prostaglandin E in women

Compared with diets high in fat, low-fat diets are associated with reduced risk of cardiovascular disease. We hypothesized that a low-fat (LF) (20% fat) and an LF high-omega-3 (n-3) fatty acid diet (LFn3) (23% fat with 3% as α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid [DHA]) would enhance n-3 composition of plasma phospholipid fatty acid and reduce urinary prostaglandin E(2) (PGE(2)) relative to a high-fat diet (HF) (40% fat) and that these changes would be associated with alterations in δ5 desaturase (D5D) and δ6 desaturase (D6D) activity. Phospholipid fatty acids and urinary PGE(2) were measured, and D5D and D6D activity indices calculated in a crossover trial in 17 postmenopausal women fed each of 3 test diets (HF, LF, and LFn3) for 8-week feeding periods. Desaturase activity indices were calculated as D5D, 20:4n-6/20:3n-6, and D6D, 20:3n-6/18:2n-6. Plasma phospholipid fatty acid, α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid (DPA), DHA, and total n-3 fatty acids increased, whereas linoleic acid and arachidonic acid decreased with consumption of LFn3. The LF resulted in enhanced arachidonic acid and DHA. High fat reduced D6D, whereas both HF and LF increased D5D. Urinary PGE(2) was reduced in response to both the LF and LFn3 diets. Low-fat diets, with or without long-chain n-3 fatty acids, promote positive health effects due in part to favorable alteration of plasma phospholipid fatty acid profiles and modification in desaturase activity indices, suggesting that the type and amount of fat consumed are modifiable risk factors for the prevention of cardiovascular disease.

Results of the MIDAS trial: Effects of docosahexaenoic acid on physiological and safety parameters in age-related cognitive decline

Docosahexaenoic acid, (DHA), the principle omega-3 fatty acid in brain, plays an important role in neural function. Decreases in plasma DHA are associated with cognitive decline in healthy elderly and Alzheimer's patients. Higher DHA intake and plasma levels are inversely correlated with relative risk of Alzheimer's disease (AD). Diet supplementation with Martek algal DHA oil reduces Aβ and tau levels in transgenic AD mouse models. Based on this collective data, we examined the effects of DHA clinically as a nutritional neuroprotective supplement for age-related cognitive decline (ARCD). Memory Improvement with DHA Study (MIDAS) was a randomized, double-blind, placebo-controlled, multi-center, six month study to determine the effects of 900 mg/d DHA on improving cognitive functions (assessed by CANTAB® cognitive battery) in healthy elderly with ARCD. Safety and tolerability were also assessed. Four hundred eighty-five subjects with a Logical Memory (WMS III) baseline score ≥1 SD below the younger adult mean were enrolled across 19 US sites. Additional study details were presented at ICAD’07. Primary outcome was a change from baseline in CANTAB Paired Associate Learning (PAL), a visuospatial episodic memory test. Demographics: 59% female, mean age 70 ± 9, mean education 14.6 ± 2.6 years. Primary efficacy showed significantly fewer errors made on the PAL with DHA versus placebo at six months compared to baseline (diff. score -1.63 ± 0.76, p < 0.03). A significant decrease in heart rate (DHA change from baseline of -3.2 vs. -1BPM, p < 0.03) occurred and highly correlated with week 24 plasma levels (p < 0.01). Blood pressure and body weight remained unchanged between groups. Abeta1-40,1-42 and hs-CRP plasma levels were not significantly different. Plasma phospholipid DHA levels doubled (3.2 to 6.4 weight%, p < 0.001) and correlated with the PAL response (p < 0.04). Compliance was >82%, no treatment-related SAEs were reported and the number of subjects with SAEs were equivalent across the 2 arms. Six month supplementation with DHA (900 mg/d) improves memory function and decreases heart rate in healthy older adults with ARCD. This improvement on the PAL is associated with a shift in the normative distribution to a younger age. DHA exhibits an excellent safety profile in this older population.

Methods of assessment of n–3 long-chain polyunsaturated fatty acid status in humans: a systematic review

Background: The availability of reliable biomarkers of n–3 (omega-3) long-chain polyunsaturated fatty acid (LCPUFA) status is a prerequisite for linking dietary n–3 LCPUFA status to clinical outcomes.Objective: The objective of this meta-analysis was to assess the usefulness of different biomarkers of n–3 LCPUFA status in healthy humans.Design: We searched Ovid MEDLINE, EMBASE (Ovid), and Cochrane databases from inception to September 2007 for human intervention studies in which n–3 LCPUFA status changed after ≥2 wk of n–3 LCPUFA supplementation. We used formal inclusion/exclusion criteria and applied standard procedures for data extraction, validity assessment, and meta-analysis.Results: We included 41 studies (34 randomized controlled trials and 7 before-after studies) reporting on 18 different biomarkers. The data allowed specific evaluation of biomarkers of docosahexaenoic acid (DHA, 22:6n–3) and eicosapentaenoic acid (EPA, 20:5n–3) status in response to supplementation. There were sufficient data to determine that plasma DHA, plasma phospholipid DHA, plasma triacylglycerol DHA, plasma cholesteryl ester DHA, plasma nonesterified DHA, erythrocyte DHA, erythrocyte phospholipid DHA, and platelet DHA were all effective biomarkers of DHA status and that plasma phospholipid EPA was an effective marker of EPA status. Plasma phospholipid DHA appears to be a good marker of DHA status in adult men and women irrespective of DHA baseline status or supplementation dose, but its usefulness in other population subgroups is unclear.Conclusion: There appears to be a range of useful biomarkers of DHA status in humans, but further research is needed to characterize which work best in particular population subgroups.

EPA and DHA status and indicators of atrophy on MRI scans of older adults

Omega‐3 fatty acids may reduce the risk of Alzheimer's disease. Brain atrophy, particularly of the cortex and medial temporal lobe, indicates tissue pathology and is commonly seen on MRI scans of dementia patients. Our aim was to examine the cross‐sectional association between these fatty acids and MRI indicators of atrophy in 331 elderly home care clients in Boston, MA. Dietary intake was estimated from a validated, interviewer‐administered FFQ. Plasma phospholipid fatty acid profiles were assessed on a subset of subjects. Outcomes were based on clinical MRI measurements. After adjustment for major dementia risk factors, positive associations with total brain volume were seen for dietary EPA+DHA (β=0.84, P=0.02) and plasma phospholipid DHA (β=2.25, P=0.03). Higher sulcal grades, indicating more cortical atrophy, were negatively associated with dietary EPA+DHA (β=‐0.22, P=0.03) and plasma phospholipid DHA (β=‐0.56 (P=0.06). Hippocampal volume was positively associated with dietary EPA+DHA (β=0.007, P=0.01), but not with plasma fatty acids. EPA and DHA may play a role in preserving neuronal tissue, particularly the cortex, from damage and atrophy commonly seen in Alzheimer's disease. Longitudinal studies are needed to establish causality and confirm these associations.This study was supported by NIA AG21790‐01, GCRC‐NIH MO1‐RR00054, and USDA‐ARS agreement 58‐1950‐7‐707.

Relationships Among Omega‐3 fatty acids, Anthropometrics, and Biochemical Markers in College Students

Students participated in a college life survey, an n‐3 FFQ, and a fasting blood draw. Participants were classified as normal weight (BMI &lt; 25 kg/m2, n=27.), overweight (25–29.9 kg/m2, n=16), or obese (≥30 kg/m2, n=12.). IL‐6 negatively correlated with plasma phospholipid EPA (−0.387) and DHA (−0.396) and positively with saturated fat (0.469) (P&lt;0.05) only in the normal weight. While IL‐6 correlated with lipids in the normal weight, a positive correlation was found with IL‐6 and body weight (BW) in the obese (0.627) and overweight (0.506). Ghrelin had a negative correlation with BW (−0.504), EPA (−0.415) and total n3 (−0.397) and a positive correlation with the n6:n3 ratio (0.496) in the normal weight (P&lt;0.01) while not correlating with any of these variables in the overweight and obese.Blood n‐3 PUFAs were similar in overweight and obese women, but were 25% higher in overweight than normal weight women. The difference in women total n‐3 PUFA levels was induced by cumulative differences in EPA, DHA, and DPA and the combined influence on total n‐3 PUFA as there was no difference within the sex for the specific n‐3 PUFA. There was no difference in total n‐3 PUFA in men; however, the overweight had significantly lower DHA than the normal and obese men at a mean of 3.0 mol% vs. 4.9 and 4.6 mol%, respectively. While there were differences between individuals with different BMI's the health implication need to be evaluated.

Relationship between long-chain polyunsaturated fatty acids at birth and motor function at 7 years of age

Long-chain polyunsaturated fatty acids (LCPUFA) rapidly accumulate in the central nervous system (CNS) during the perinatal CNS growth spurt. This particularly concerns arachidonic acid (AA: 20:4n-6) and docosahexaenoic acid (DHA: 22:6n-3), which are thought to play important roles in CNS development and function. The aim of this study was to investigate the relation between motor function at 7 years of age and the levels of AA and DHA in umbilical venous plasma phospholipids, representing the prenatal availability of these fatty acids, and in plasma phospholipids sampled at age 7 years. Motor function was assessed both quantitatively (the ability to perform a movement) and qualitatively (how the movement is performed) with the Maastricht Motor Test (MMT) in 306 children, born at term, at 7 years of age as part of a follow-up study. Backward stepwise multiple regression analyses revealed a significant, positive relation between umbilical plasma DHA concentrations (but not plasma DHA levels at 7 years) and the MMT total and quality score, corrected for the covariables gender, cognitive performance, gestational age and age at measurement (partial beta=0.13, P=0.01 and 0.14, P=0.01, respectively). The contributions of DHA and AA (both at birth and at 7 years of age) to quantitative movement scores were not significant. Our results suggest that prenatal DHA availability, which can be influenced by maternal dietary DHA intake during pregnancy, can have an effect on quality of movement in later life.