An abundance of seafood consumption studies presents new opportunities to evaluate effects on neurocognitive development.

The relationship between seafood eaten during pregnancy and neurocognition in offspring has been the subject of considerable scientific study for over 25 years. Evaluation of this question led two scientific advisory committees to the Dietary Guidelines for Americans (DGAC), the Food and Agriculture Organization of the United Nations with the World Health Organization (FAO/WHO), Health Canada, the European Food Safety Authority (EFSA), and the U.S. Food and Drug Administration (FDA) to conclude through 2014 that seafood consumed by pregnant women is likely to benefit the neurocognitive development of their children. The evidence they reviewed included between four and ten studies of seafood consumption during pregnancy that reported beneficial associations. In contrast there are now 29 seafood consumption studies available describing over 100,000 mothers-child pairs and 15 studies describing over 25,000 children who ate seafood. A systematic review of these studies using Nutrition Evaluation Systematic Review methodology is warranted to determine whether recent research corroborates, builds on, or significantly alters the previous conclusions. Studies that evaluate the integrated effects of seafood as a complete food more directly and completely evaluate impacts on neurocognition as compared to studies that evaluate individual nutritients or toxicological constituents in isolation. Here we address how the findings could add to our understanding of whether seafood consumed during pregnancy and early childhood affects neurocognition, including whether such effects are clinically meaningful, lasting, related to amounts consumed, and affected by any neurotoxicants that may be present, particularly mercury, which is present at varying levels in essentially all seafood. We provide the history, context and rationale for reexamining these questions in light of currently available data.

Relationships between seafood consumption during pregnancy and childhood and neurocognitive development: Two systematic reviews.

Abundant data are now available to evaluate relationships between seafood consumption in pregnancy and childhood and neurocognitive development. We conducted two systematic reviews utilizing methodologies detailed by the Dietary Guidelines for Americans Scientific Advisory Committee 2020-2025. After reviewing 44 publications on 106,237 mother-offspring pairs and 25,960 children, our technical expert committee developed two conclusion statements that included the following: "Moderate and consistent evidence indicates that consumption of a wide range of amounts and types of commercially available seafood during pregnancy is associated with improved neurocognitive development of offspring as compared to eating no seafood. Overall, benefits to neurocognitive development began at the lowest amounts of seafood consumed (∼4 oz/wk) and continued through the highest amounts, above 12 oz/wk, some range up to >100 oz/wk.", "This evidence does not meet the criteria for "strong evidence" only due to a paucity of randomized controlled trials that may not be ethical or feasible to conduct for pregnancy" and "Moderate and consistent evidence indicates that consumption of >4 oz/wk and likely >12 oz/wk of seafood during childhood has beneficial associations with neurocognitive outcomes." No net adverse neurocognitive outcomes were reported among offspring at the highest ranges of seafood intakes despite associated increases in mercury exposures. Data are insufficient for conclusive statements regarding lactation, optimal amounts, categories or specific species characterized by mercury content and neurocognitive development; although there is some evidence that dark/oily seafood may be more beneficial. Research was conducted in healthy women and children and is generalizable to US populations. Assessment of seafood as a whole food integrates inherently integrates any adverse effects from neurotoxicants, if any, and benefits to neurocognition from omega-3 fats, as well as other nutrients critical to optimal neurological development. Understanding of the effects of seafood consumption on neurocognition can have significant public health implications.

Mercury, Polychlorinated Biphenyls, Selenium, and Fatty Acids in Tribal Fish Harvests of the Upper Great Lakes.

The Chippewa Ottawa Resource Authority monitors fish contaminants in Anishinaabe (Great Lake Native American) tribal fisheries. This article updates previously reported trends in two persistent bioaccumulative toxic (PBT) substances that are the primary contributors to consumption advisory limits for these fish: methylmercury (MeHg) and polychlorinated biphenyls (PCBs). Also, we report, for the first time, an analysis of nutritional benefit bioindicators and metrics in these same Upper Great Lakes fish harvests: selenium (Se) and omega-3 fatty acids (PUFA-3s). A novel risk/benefit quantification originally presented by Ginsberg et al. is reported here to characterize the tradeoffs between fatty acid benefits and toxic MeHg health outcomes. We also report a Se benefit metric to characterize the possible protective value against MeHg neurotoxicity based on Ralston et al. Congruent with Anishinaabe cultural motivations to consume fish from their ancestral fisheries, nutritional content was high in locally caught fish and, in some respects, superior to farmed/store-bought fish. These Great Lakes fish still contained levels of PBTs that require careful education and guidance for consumers. However, the contaminant trends suggest that these fish need not be abandoned as important (both culturally and nutritionally) food sources for the Anishinaabe who harvested them.

Directly quantified dietary n-3 fatty acid intakes of Canadian toddlers are lower than current dietary recommendations.

To date, few studies have evaluated the intake of dietary n-3 polyunsaturated fatty acids (PUFA) in young North American children and current estimates are based on indirect approaches which have concerning limitations. Furthermore, there is a lack of available knowledge regarding the proportion of children meeting current dietary recommendations for the consumption of long-chain n-3 PUFA as α-linolenic acid (ALA) and eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA). The objective of the present study was to directly quantify the intake of n-3 PUFA in toddlers aged 2 to 3 years and determine if intakes met international recommendations. Given the low intakes of fish in North America, we predicted that n-3 PUFA intakes in toddlers would fall short of recommended intakes. Duplicated diets were collected from 20 Canadian children over a 3-day period. Diets were then directly analyzed by gas chromatography. Daily intakes (means ± SEM) of ALA, EPA, and DHA were as follows: 710.1 ± 69.7, 9.6 ± 2.9, and 19.2 ± 6.8 mg/d, respectively. Compared with North American dietary reference intakes, 45% of our children met the minimal recommended intake of ALA, whereas only 5% consumed the target intake of EPA plus DHA. These results indicate that Canadian children aged 2 to 3 years struggle to consume adequate intakes of the n-3 PUFA ALA and particularly EPA/DHA; efforts to narrow this gap should focus on increasing EPA and DHA intakes by appropriate fish/seafood consumption along with enriched foods or supplements if necessary.

N-3 polyunsaturated fatty acid supplementation does not reduce vulnerability to atrial fibrillation in remodeling atria.

BACKGROUND: Prophylactic supplementation with omega-3 polyunsaturated fatty acids (PUFAs) reduce vulnerability to atrial fibrillation (AF). The effect of PUFAs given after cardiac injury has occurred is unknown. OBJECTIVE: To investigate using a model of pacing-induced cardiac injury, the time course of development of injury and whether it was altered by postinjury PUFAs. METHODS: Sixty-five dogs were randomized to undergo simultaneous atrial and ventricular pacing (SAVP, 220 beats/min) for 0, 2, 7, or 14 days. Twenty-two dogs received PUFAs (850 mg/d) either prophylactically or after some pacing had occurred (postinjury). Electrophysiologic and echocardiographic measurements were taken at baseline and sacrifice. Atrial tissue samples were collected at sacrifice for histologic and molecular analyses. RESULTS: With no PUFAs, the inducibility of AF increased with pacing duration (P < .001). Postinjury PUFAs (started after 7 days of pacing) did not reduce the inducibility of AF after 14 days of pacing (9.3% ± 8.8% no PUFAs vs 9.7% ± 9.9% postinjury PUFAs; P = .91). Atrial myocyte size and fibrosis increased with pacing duration (P < .05). Postinjury PUFAs did not significantly attenuate the cell size increase after 14 days of pacing (no PUFAs 38% ± 30% vs postinjury PUFAs 19% ± 28%; P = .11). Similarly, postinjury PUFAs did not attenuate the increase in fibrosis after 14 days of pacing (no PUFAs 66% ± 51% vs postinjury PUFAs 63% ± 76%; P = .90). CONCLUSION: PUFA supplementation begun after cardiac injury has already occurred does not reduce atrial structural remodeling or vulnerability to AF.

Effects of a supplementation of n-3 polyunsaturated fatty acids with or without fish gelatin on gene expression in peripheral blood mononuclear cells in obese, insulin-resistant subjects.

AIM: To investigate gene expression changes in peripheral blood mononuclear cells (PBMCs) following an n-3 polyunsaturated fatty acid (PUFA) and n-3 PUFA plus fish gelatin (+FG) supplementation. METHODS: A transcriptome comparison of 8-week supplementation with n-3 PUFA and n-3 PUFA+FG was carried out in PBMCs of 16 obese insulin-resistant subjects. RESULTS: Erythrocyte n-3 PUFA concentration increased and plasma triglycerides decreased significantly without altering inflammatory parameters after both supplementations. n-3 PUFA supplementation changed the expression of 805 genes, whereas n-3 PUFA+FG supplementation altered the expression of 184 genes. Three genes were commonly changed: fatty acid desaturase 1, free fatty acid receptor 3, and ectodysplasin. Pathway analyses indicate changes in gene expression via the nuclear receptor peroxisome proliferator-activated receptor α pathway after both supplementations. Further, the extent of modifications in the expression of genes implicated in the inflammatory pathways - the oxidative stress response mediated by nuclear factor (erythroid-derived 2)-like 2, nuclear transcription factor κB, oxidative stress, and hypoxia-inducible factor signaling - was different after each supplementation. CONCLUSION: Although n-3 PUFA and n-3 PUFA+FG supplementations have a distinct impact on gene expression levels, the consequences on biochemical parameters and metabolic pathways were comparable after both supplementations.

Oral docosapentaenoic acid (22:5n-3) is differentially incorporated into phospholipid pools and differentially metabolized to eicosapentaenoic acid in tissues from young rats.

The present study assessed the effect of oral supplementation with docosapentaenoic acid (DPA, 22:5n-3) on the levels of serum and tissue lipid classes and their fatty acid compositions including individual phospholipid types in rat liver, heart, and kidney. Sprague-Dawley rats received daily oral gavage over 10 days as corn oil without (controls) or with purified DPA in free fatty acid form (21.2 mg/day). The DPA group exhibited significantly lower serum lipid concentrations. The concentrations in µmol/100 g serum or µmol/g tissue of DPA in the total lipid (TL) were higher by 2.3-, 2.4-, 10.9-, and 5.1-fold in the DPA group of serum, liver, heart, and kidney, respectively, with the phospholipids (PL) being the major DPA reservoir (45.2-52.1% of the DPA in the TL). No significant differences in DHA (22:6n-3) amounts in TL appeared. The highest relative mol% values as DPA were in heart tissue (means of 11.1% in PL and 16.2% in phosphatidylinositol) and lowest in kidney. The EPA (20:5n-3) concentrations were markedly higher in the DPA group and most pronounced in the kidney (5.1 times higher in the TL as compared to controls) relative to liver and heart yielding an estimated apparent % conversion of DPA to EPA of 67% and EPA:DPA ratios reaching 5.74 in kidney phosphatidylethanolamine. The serum lipid-lowering potential of dietary DPA and its impact in the kidney with the derived EPA warrants investigation.

Validation of the use of peripheral blood mononuclear cells as surrogate model for skeletal muscle tissue in nutrigenomic studies.

Peripheral blood mononuclear cells (PBMCs) offer a significant promise for gene expression analyses as a substitute for tissues that are not easily accessible. The objective of this study was to validate the use of PBMCs for gene expression analysis as a marker of nutritional intervention as an alternative to skeletal muscle tissue (SMT) biopsies. We performed a transcriptome comparison of PBMCs versus SMT after an 8-week supplementation with n-3 polyunsaturated fatty acid (PUFA) in 16 obese and insulin-resistant subjects. Expression levels of 48,803 transcripts were assessed by the Human-6 v3 Expression BeadChips (Illumina, San Diego, CA). In SMT, 36,738 (75%) transcripts were detected, whereas 34,182 (70%) transcripts were detected in PBMCs. Further, 88% (32,341) of these transcripts were coexpressed in both tissues. Importantly, a strong correlation (r = 0.84, p < 0.0001) was observed between transcript expression levels of PBMCs and SMT after n-3 PUFA supplementation. In conclusion, PBMCs express the majority of transcripts expressed in SMT subsequent to n-3 PUFA supplementation and their expression levels are comparable. In the interest of practicalities and cost, these results support the use of PBMCs as a surrogate model for SMT gene expression in nutrigenomic studies. Further research on PBMC and SMT gene expression in response to other nutritional exposures is warranted.

n-3 Polyunsaturated fatty acids alter expression of fibrotic and hypertrophic genes in a dog model of atrial cardiomyopathy.

BACKGROUND: We previously showed that omega-3 polyunsaturated fatty acids (PUFAs) reduce vulnerability to atrial fibrillation (AF). The mechanisms underlying this effect are unknown. OBJECTIVE: The purpose of this study was to use a genome-wide approach to identify gene expression profiles involved in a new model of AF vulnerability and to determine whether they were altered by PUFA therapy. METHODS: Thirty-six dogs were randomized evenly into three groups. Two groups were paced using simultaneous atrioventricular pacing (SAVP) at 220 bpm for 14 days to induce atrial enlargement, fibrosis, and susceptibility to AF. One group was supplemented with oral PUFAs (850 mg/day) for 21 days, commencing 7 days before the start of pacing (SAVP-PUFAs). The second group received no PUFAs (SAVP-No PUFAs). The remaining dogs were unpaced, unsupplemented controls (CTRL). Atrial tissue was sampled at the end of the protocol. Gene expression was analyzed in four dogs randomly selected from each group (n = 12) via microarray. Results were confirmed with quantitative real-time polymerase chain reaction (RT-PCR) and histology on all 36 dogs. RESULTS: Microarray or quantitative RT-PCR results showed that SAVP-No PUFAs dogs had significantly increased mRNA levels of protein kinase B (Akt), epidermal growth factor (EGF), JAM3, myosin heavy chain alpha (MHCalpha), and CD99 and significantly decreased levels of Smad6 compared with CTRL dogs. Quantitative RT-PCR showed that PUFA supplementation was associated with significant down-regulation of Akt, EGF, JAM3, MHCalpha, and CD99 levels compared with SAVP-No PUFAs dogs. CONCLUSION: The effect of PUFAs on these fibrosis, hypertrophy, and inflammation related genes suggests that, in this model, PUFA-mediated prevention of AF may be due to attenuation of adverse remodeling at the genetic level in response to mechanical stress.

Effects of diets high in walnuts and flax oil on hemodynamic responses to stress and vascular endothelial function.

BACKGROUND: Polyunsaturated fatty acids (PUFA) have beneficial effects on cardiovascular risk, although the mechanisms are incompletely understood. In a previous article, we showed significant reductions in low-density lipoprotein cholesterol and several markers of inflammation with increasing intake of alpha-linolenic acid (ALA) from walnuts and flax. OBJECTIVE: To examine effects of ALA on cardiovascular responses to acute stress, flow-mediated dilation (FMD) of the brachial artery, and blood concentrations of endothelin-1 and arginine-vasopressin (AVP). DESIGN: Using a randomized, crossover study design, cardiovascular responses to acute stress were assessed in 20 hypercholesterolemic subjects, a subset of whom also underwent FMD testing (n  =  12). Participants were fed an average American diet (AAD) and 2 experimental diets that varied in the amount of ALA and linoleic acid (LA) that they contained. The AAD provided 8.7% energy from PUFA (7.7% LA, 0.8% ALA). On the LA diet, saturated fat was reduced, and PUFA from walnuts and walnut oil provided 16.4% of energy (12.6% LA, 3.6% ALA). On the ALA diet, walnuts, walnut oil, and flax oil provided 17% energy from PUFA (10.5% LA, 6.5% ALA). RESULTS: The ALA and LA diets significantly reduced diastolic blood pressure (-2 to -3 mm Hg) and total peripheral resistance (-4%), and this effect was evident at rest and during stress (main effect of diet, p < 0.02). FMD increased (+34%) on the diet containing additional ALA. AVP also increased by 20%, and endothelin-1 was unchanged. CONCLUSIONS: These results suggest novel mechanisms for the cardioprotective effects of walnuts and flax, and further work is needed to identify the bioactives responsible for these effects.

Correlation of omega-3 levels in serum phospholipid from 2053 human blood samples with key fatty acid ratios.

BACKGROUND: This research was conducted to explore the relationships between the levels of omega-3 fatty acids in serum phospholipid and key fatty acid ratios including potential cut-offs for risk factor assessment with respect to coronary heart disease and fatal ischemic heart disease. METHODS: Blood samples (n = 2053) were obtained from free-living subjects in North America and processed for determining the levels of total fatty acids in serum phospholipid as omega-3 fatty acids including EPA (eicosapentaenoic acid, 20:5 n-3) and DHA (docosahexaenoic acid, 22:6 n-3) by combined thin-layer and gas-liquid chromatographic analyses. The omega-3 levels were correlated with selected omega-6: omega-3 ratios including AA (arachidonic acid, 20:4n-6): EPA and AA:(EPA+DHA). Based on previously-published levels of omega-3 fatty acids considered to be in a 'lower risk' category for heart disease and related fatality, 'lower risk' categories for selected fatty acid ratios were estimated. RESULTS: Strong inverse correlations between the summed total of omega-3 fatty acids in serum phospholipid and all four ratios (omega-6:omega-3 (n-6:n-3), AA:EPA, AA:DHA, and AA:(EPA+DHA)) were found with the most potent correlation being with the omega-6:omega-3 ratio (R(2) = 0.96). The strongest inverse relation for the EPA+DHA levels in serum phospholipid was found with the omega-6: omega-3 ratio (R(2) = 0.94) followed closely by the AA:(EPA+DHA) ratio at R(2) = 0.88. It was estimated that 95% of the subjects would be in the 'lower risk' category for coronary heart disease (based on total omega-3 >or= 7.2%) with omega-6:omega-3 ratios <4.5 and AA:(EPA+DHA) ratios <1.4. The corresponding ratio cut-offs for a 'lower risk' category for fatal ischemic heart disease (EPA+DHA >or= 4.6%) were estimated at < 5.8 and < 2.1, respectively. CONCLUSIONS: Strong inverse correlations between the levels of omega-3 fatty acids in serum (or plasma) phospholipid and omega-6: omega-3 ratios are apparent based on this large database of 2053 samples. Certain fatty acid ratios may aid in cardiovascular disease-related risk assessment if/when complete profiles are not available.

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.

Acute fish oil and soy isoflavone supplementation increase postprandial serum (n-3) polyunsaturated fatty acids and isoflavones but do not affect triacylglycerols or biomarkers of oxidative stress in overweight and obese hypertriglyceridemic men.

Chronic consumption of fish and fish oil high in (n-3) PUFA reduces triacylglycerols (TG) but may increase oxidative stress, whereas consumption of soy isoflavones may reduce oxidative stress. Elevated serum TG and oxidative stress are considered cardiovascular disease (CVD) risk factors, but the effects of acute (n-3) PUFA and soy isoflavones on these CVD risk factors are unknown. The purpose of the study was to determine the effects of acutely supplementing a high-fat, high-fructose meal with fish oil and isoflavone placebo (FO) and fish oil placebo and soy isoflavones (ISO). In a randomized, double-blind, placebo-controlled, crossover study, 10 overweight or obese men consumed a high-fat, high-fructose meal with 4 dietary supplement combinations: fish oil placebo and isoflavone placebo (placebo); fish oil and isoflavone placebo (FO); fish oil placebo and isoflavones (ISO); and fish oil and isoflavones (FO + ISO). Serum collected at baseline and at 2, 4, and 6 h postprandially was analyzed for fatty acids, isoflavones, TG, and oxidative stress biomarkers (lipid hydroperoxides, oxidized-LDL, total antioxidant status). FO significantly increased serum (n-3) PUFA and ISO increased serum isoflavones. The study meal significantly increased serum total fatty acids and TG without affecting oxidative stress biomarkers. Serum TG and oxidative stress biomarkers did not differ between treatments. The FO and ISO were bioavailable but did not attenuate the postprandial rise in serum TG. Neither the study meal nor the FO or ISO induced significant changes in oxidative stress biomarkers. The current study adds to a limited literature on the acute effects of FO and ISO interventions on postprandial biomarkers of CVD risk.

Plasma omega-3 and psychological distress among Nunavik Inuit (Canada).

Marine omega-3 (n-3) fatty acid eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids have been associated with beneficial effects in mental health. Cultural and social changes have been related to a decline in mental health of the Inuit, but the role of diet has received scant attention. We examined the relationship between psychological distress (PD) and plasma n-3 among 368 Nunavik Inuit aged 18-74 years who took part in a survey in 1992. Participants were categorized as high-level PD if they scored over the 80th percentile of the PD Index Santé-Québec Survey (PDISQS-14), and non-distressed subjects were those who scored less than this cutoff. Compared with the non-distressed group, n-3 concentrations in the PD group were significantly lower in women but not in men. Compared with the lowest tertile of EPA + DHA, the odds ratios for high-level PD among women were 0.32 (95% CI: 0.13-0.82) for the second, and 0.30 (95% CI: 0.10-0.90) for the third tertile, after controlling for confounders. In males, there were no significant associations between EPA+DHA and PDISQS-14 scores. Our findings suggest that marine n-3 may play a role in PD among Inuit women. The gender difference observed in our analysis must be examined more carefully in future studies.

Plasma n-3 fatty acids and psychological distress in aboriginal Cree Indians (Canada).

OBJECTIVE: To examine the relationship between psychological distress (PD) and plasma n-3 long-chain (LC) PUFA, i.e. EPA, docosapentaenoic acid (DPAn-3) and DHA. DESIGN: Population-based, cross-sectional Santé-Québec Health Survey (1991). Participants were categorized as high-level PD if they scored over the 80th percentile of the PD Index in the Santé-Québec Survey; non-distressed subjects were those who scored less than this cut-off. Associations between tertiles of n-3 fatty acids (FA) and the risk of high-level PD were expressed as odds ratios, with the lowest tertile as the reference group. SETTING: Québec, Canada. SUBJECTS: Data were analysed from a representative sample of 852 James Bay Cree Indian adults aged 18 years and over. RESULTS: Proportions of n-3 FA were statistically significantly lower in the PD than in the non-distressed group. After adjustment for confounders, EPA was the only individual n-3 FA significantly associated with the risk of high-level PD. Combinations of EPA + DHA or EPA + DPAn-3 + DHA or the sum of n-3 were also associated with the risk of high-level PD. Compared with the lowest tertile of EPA + DHA, the OR for high-level PD was 0.89 (95 % CI 0.59, 1.36) for the second and 0.56 (95 % CI 0.32, 0.98) for the third tertile, after controlling for confounders. CONCLUSIONS: In the present retrospective, cross-sectional study, we found that proportions of n-3 LC PUFA in plasma phospholipids, markers of n-3 LC PUFA consumption from fish, were inversely associated with PD.

Direct diet quantification indicates low intakes of (n-3) fatty acids in children 4 to 8 years old.

Estimates of essential fatty acid intakes, including (n-3) PUFA, are available in pediatric populations based on limited indirect approaches. Furthermore, recommended intakes for short- and long-chain (LC) (n-3) PUFA have emerged for this population. This study provides direct quantification of fatty acid intakes in children aged 4-8 y. Identical portions of all food and natural health products consumed over 3 d were collected. Duplicate samples were analyzed for energy, macronutrients, and fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) by high performance capillary GLC. The results for 41 children [25 females, 16 males; 5.8 +/- 0.2 y (mean age +/- SEM)] showed daily energy intakes of 5879 +/- 211 kJ (mean +/- SEM) and (n-3) PUFA intakes in mg/d as follows: ALA, 1161 +/- 108; EPA, 38.4 +/- 9.3; DPA, 26.3 +/- 3.9; and DHA, 54.1 +/- 11.4. Based on the Dietary Reference Intakes from the Institute of Medicine, 61% of the children met the adequate intake for ALA and 22% met the suggested adequate intake for DHA+EPA (10% of the adequate intake for ALA). These intakes were also compared with the recent Australia/New Zealand recommendations for children, where only 51% met the recommended intake for EPA+DPA+DHA. These results demonstrate a moderate shortfall in ALA intake in Canadian children and a nutrient gap for the LC (n-3) PUFA, including DHA, when comparing intakes for this population to suggested and recommended intakes.

Dietary cod protein reduces plasma C-reactive protein in insulin-resistant men and women.

Chronic low-grade inflammation has been associated with insulin resistance and type 2 diabetes. Recently, we showed that cod protein (CP) improved insulin sensitivity in insulin-resistant subjects. In this study, we investigated the effects of dietary CP compared with those of other animal proteins on plasma concentrations of inflammatory markers, lipids, and lipoproteins in insulin-resistant subjects. Nineteen Caucasian men and women aged 40-65 y, overweight or obese (BMI > 25 kg/m(2)), and insulin resistant, rotated in a crossover design and consumed a CP diet and a similar diet containing lean beef, pork, veal, eggs, milk, and milk products (BPVEM) for 4 wk each. Diets differed only in protein source and thus provided equivalent amounts of dietary fibers, monounsaturated fat, PUFA [including (n-3) fatty acids], and SFA. Blood samples were collected before and after each experimental diet. Notably, the CP diet decreased high-sensitivity C-reactive protein (hsCRP; P = 0.021), whereas the BPVEM diet tended to increase it (P = 0.063), leading to a significant difference between diets (P = 0.041). Changes in plasma interleukin-6, tumor necrosis factor-alpha, and adiponectin concentrations did not differ between diets. Plasma total cholesterol (P = 0.0007), LDL cholesterol (P = 0.014), and apolipoprotein B (P = 0.005) were reduced only by the BPVEM diet. Thus, changes in total cholesterol differed between diets (P = 0.040), whereas changes in LDL cholesterol (P = 0.052) and apolipoprotein B (P = 0.075) tended to differ. Changes in all other lipids and lipoproteins did not differ between diets. Therefore, these results show that CP can lower hsCRP, a marker of inflammation associated with insulin resistance and type 2 diabetes.

Clinical trial to evaluate omega-3 fatty acids and alternate day prednisone in patients with IgA nephropathy: report from the Southwest Pediatric Nephrology Study Group.

This randomized, placebo-controlled, double-blind trial evaluated the role of prednisone and omega 3 fatty acids (O3FA) in patients with IgA nephropathy. Entry criteria were (1) biopsy-proven IgA nephropathy, (2) estimated GFR > or = 50 ml/min per 1.73 m2, and (3) moderate to severe proteinuria. Thirty-three patients were randomly assigned to receive prednisone 60 mg/m2 every other day for 3 mo, then 40 mg/m2 every other day for 9 mo, then 30 mg/m2 every other day for 12 mo (prednisone group); 32 were randomly assigned to receive O3FA 4 g/d for 2 yr (1.88 g eicosapentaenoic acid, 1.48 g docosahexaenoic acid; O3FA group); and 31 were randomly assigned to receive placebo (placebo group). Most (73%) patients completed 2 yr of treatment. Randomly assigned patients who were hypertensive were given enalapril 2.5 to 40 mg/d. The primary end point was time to failure, defined as estimated GFR <60% of baseline. An overall significance level of 0.10 was used. The three groups were comparable at baseline except that the O3FA group had higher urine protein to creatinine (UP/C) ratios than the placebo group (P = 0.003). Neither treatment group showed benefit over the placebo group with respect to time to failure, with 14 patient failures overall (two in the prednisone group, eight in the O3FA group, and four in the placebo group). The primary factor associated with time to failure was higher baseline UP/C ratios (P = 0.009). Superiority of prednisone or O3FA over placebo in slowing progression of renal disease was not demonstrated in this study. However, the relatively short follow-up period, inequality of baseline UP/C ratios, and small numbers of patients precludes definitive conclusions.

Anthocyanins exist in the circulation primarily as metabolites in adult men.

Anthocyanins are reported to have many "health promoting" properties; however, despite numerous reports of their bioactivities, their absorption and metabolism in humans are poorly understood. The objective of this research was to detail the pharmacokinetic parameters of anthocyanins after the administration of a 721-mg oral dose of cyanidin 3-glycosides from chokeberry extract to human subjects. Solid-phase extraction, preparative-HPLC, preparative-TLC, HPLC-diode array detection, HPLC-MS, and NMR were utilized to isolate, identity, and quantify anthocyanins in 0- to 7-h (0, 1, 2, 3, 4, 5, 6, 7 h) serum and 0- to 24-h urine samples (total individual urine voids over 24 h). The cumulative concentration of total anthocyanins (parent and metabolites) detected in the serum (0-7 h) was 376.65 +/- 16.20 (nmol x h)/L (area under the concentration time curve), reaching a maximum concentration (C(max) = 96.08 +/- 6.04 nmol/L) within 2.8 h. The parent anthocyanins represented only 32.0% [120.63 +/- 2.85 (nmol x h)/L] of the total anthocyanins detected with 68.0% [256.02 +/- 5.23 (nmol x h) identified as conjugated metabolites. Additionally, the total urinary excretion of anthocyanins over 24 h was 1071.54 +/- 375.46 microg, reaching a maximal rate of excretion (R(max) = 202.74 +/- 85.06 microg/h) at 3.72 +/- 0.83 h. Parallel to the serum data, only 32.5% (347.85 +/- 60.61 microg) of the anthocyanins excreted in the urine (total 24 h) were the parent compounds with 67.5% (723.69 +/- 92.59 microg) occurring as conjugated metabolites. The metabolites were identified as glucuronidated and methylated derivatives of the parent cyanidin 3-glycosides. The above results indicate that cyanidin 3-glycosides are rapidly absorbed and metabolized extensively following a moderate-to-high oral dose in humans.