Accretion of Dietary Docosahexaenoic Acid in Mouse Tissues Did Not Differ between Its Purified Phospholipid and Triacylglycerol Forms.

Recent studies suggest that dietary krill oil leads to higher omega-3 polyunsaturated fatty acids (n-3 PUFA) tissue accretion compared to fish oil because the former is rich in n-3 PUFA esterified as phospholipids (PL), while n-3 PUFA in fish oil are primarily esterified as triacylglycerols (TAG). Tissue accretion of the same dietary concentrations of PL- and TAG-docosahexaenoic acid (22:6n-3) (DHA) has not been compared and was the focus of this study. Mice (n = 12/group) were fed either a control diet or one of six DHA (1%, 2%, or 4%) as PL-DHA or TAG-DHA diets for 4 weeks. Compared with the control, DHA concentration in liver, adipose tissue (AT), heart, and eye, but not brain, were significantly higher in mice consuming either PL- or TAG-DHA, but there was no difference in DHA concentration in all tissues between the PL- or TAG-DHA forms. Consumption of PL- and TAG-DHA at all concentrations significantly elevated eicosapentaenoic acid (20:5n-3) (EPA) in all tissues when compared with the control group, while docoshexapentaenoic acid (22:5n-6) (DPA) was significantly higher in all tissues except for the eye and heart. Both DHA forms lowered total omega-6 polyunsaturated fatty acids (n-6 PUFA) in all tissues and total monounsaturated fatty acids (MUFA) in the liver and AT; total saturated fatty acid (SFA) were lowered in the liver but elevated in the AT. An increase in the DHA dose, independent of DHA forms, significantly lowered n-6 PUFA and significantly elevated n-3 PUFA concentration in all tissues. Our results do not support the claim that the PL form of n-3 PUFA leads to higher n-3 PUFA tissue accretion than their TAG form.

A Review of the Health Benefits of Cherries.

Increased oxidative stress contributes to development and progression of several human chronic inflammatory diseases. Cherries are a rich source of polyphenols and vitamin C which have anti-oxidant and anti-inflammatory properties. Our aim is to summarize results from human studies regarding health benefits of both sweet and tart cherries, including products made from them (juice, powder, concentrate, capsules); all referred to as cherries here. We found 29 (tart 20, sweet 7, unspecified 2) published human studies which examined health benefits of consuming cherries. Most of these studies were less than 2 weeks of duration (range 5 h to 3 months) and served the equivalent of 45 to 270 cherries/day (anthocyanins 55-720 mg/day) in single or split doses. Two-thirds of these studies were randomized and placebo controlled. Consumption of cherries decreased markers for oxidative stress in 8/10 studies; inflammation in 11/16; exercise-induced muscle soreness and loss of strength in 8/9; blood pressure in 5/7; arthritis in 5/5, and improved sleep in 4/4. Cherries also decreased hemoglobin A1C (HbA1C), Very-low-density lipoprotein (VLDL) and triglycerides/high-density lipoprotein (TG/HDL) in diabetic women, and VLDL and TG/HDL in obese participants. These results suggest that consumption of sweet or tart cherries can promote health by preventing or decreasing oxidative stress and inflammation.

Emotion-Based Cognition in Mice Is Differentially Influenced by Dose and Chemical Form of Dietary Docosahexaenoic Acid.

Docosahexaenoic acid (DHA) is a major constituent, and primary omega-3 fatty acid, in the brain. Evidence suggests that DHA consumption may promote cognitive functioning and prevent cognitive decline, and these effects may be particularly relevant in the context of fear or stress. However, the potency and efficacy of dietary DHA may depend on the form of DHA (e.g., phospholipid; PL vs. triglyceride; TG). In this study, we compared in mice the effects of consuming PL and TG forms of DHA on associative, avoidance (fear) based learning and memory. Diets consisted of either no DHA or 1%, 2%, and 4% PL- or TG-DHA. After 4 weeks on the test diets (n = 12/group), we used the 3-day passive avoidance (PA) and elevated plus maze (EPM) to examine fear and fear-associated learning and memory. We found a significant (p < 0.05) diet by time interaction in the PA and EPM. Compared to the control and the 1% TG-DHA group, mice consuming the diet supplemented with 1% PL-DHA displayed a significantly greater latency by test day 2 in the 3-day PA. No differences in latency between any of the groups were observed during trials 1 and 3. Mice consuming the 2% PL-DHA diet spent significantly more time frequenting the open arms during the first minute, but not the last 4 min, of the test. Compared to all other groups, mice fed the 4% TG-DHA diet had increased spleen, liver, and visceral fat weight. Consumption of the lower dose PL-DHA may confer enhanced efficacy, particularly on fear-based learning behavior.

Docosahexaenoic Acid and Eicosapentaenoic Acid Did not Alter trans-10,cis-12 Conjugated Linoleic Acid Incorporation into Mice Brain and Eye Lipids.

trans 10,cis 12-CLA has been reported to alter fatty acid composition in several non-neurological tissues, but its effects are less known in neurological tissues. Therefore, the purpose of this study was to determine if CLA supplementation would alter brain and eye fatty acid composition and if those changes could be prevented by concomitant supplementation with docosahexaenoic acid (DHA; 22:6n3) or eicosapentaenoic acid (EPA; 20:5n3). Eight-week-old, pathogen-free C57BL/6N female mice (n = 6/group) were fed either the control diet or diets containing 0.5% (w/w) t10,c12-CLA in the presence or absence of either 1.5% DHA or 1.5% EPA for 8 weeks. CLA concentration was significantly (P < 0.05) greater in the eye but not in the brain lipids of the CLA group when compared with the control group. The sums of saturated, monounsaturated, polyunsaturated fatty acids, and n3:n6 ratio did not differ between these two groups for both tissues. The n3:n6 ratio and concentrations of 20:5n3 and 22:5n3 were significantly greater, and those of 20:4n6, 22:4n6, and 22:5n6 were lesser in the CLA + DHA and CLA + EPA groups than in the control and CLA groups for either tissue. DHA concentration was higher in the CLA + DHA group only but not in the CLA + EPA group when compared with the CLA group for both tissues. The dietary fatty acids generally induced similar changes in brain and eye fatty acid concentration and at the concentrations used both DHA and EPA fed individually with CLA were more potent than CLA alone in altering the tissue fatty acid concentration.

Increased cytokine production by monocytes from human subjects who consumed grape powder was not mediated by differences in dietary intake patterns.

Recently, in a randomized, double-blind crossover study, we reported that consumption of grape powder by obese human subjects increased the production of the proinflammatory cytokines interleukin (IL)-1ß and IL-6 by peripheral blood monocytes after ex vivo stimulation with bacterial lipopolysaccharide compared with the placebo treatment. We hypothesized that dietary grape powder increased the production of these cytokines by stimulated monocytes. To test this hypothesis, we used 24-hour dietary recall data to determine if differences in dietary patterns played a role in increased cytokine production. No differences in total energy, protein, carbohydrates, or fat intake in the diets were observed between the grape powder and placebo intervention periods. There were no differences observed in consumption of meats and poultry, eggs, fish, vegetables, grains, total dairy, or nuts and seeds by the participants between the 2 intervention periods. When participants received the grape powder, the recall data showed decreased intakes of butyric and capric acids (P<.05), and a possible trend toward decreased intake of cheese and total fruit (P<.1). Positive associations between the intakes of margaric acid, butter, total dairy, or whole grain and IL-6 production were observed (P<.05). However, path analysis showed that total energy, protein, carbohydrates, and fats, and individual fatty acids did not influence the production of cytokines by monocytes. The path analysis indicated that the increased cytokine production by lipopolysaccharide-stimulated monocytes from obese human subjects was caused by the grape powder and not mediated by differences in dietary intake.

Dietary supplementation with purified citrus limonin glucoside does not alter ex vivo functions of circulating T lymphocytes or monocytes in overweight/obese human adults.

Overweight/obesity is associated with chronic inflammation and impairs both innate and adaptive immune responses. Limonoids found in citrus fruits decreased cell proliferation and inflammation in animal studies. We hypothesized that limonin glucoside (LG) supplementation in vivo will decrease the ex vivo proliferation of T cells and the production of inflammatory cytokines by monocytes and T cells. In a double-blind, randomized, cross-over study, 10 overweight/obese human subjects were served purified LG or placebo drinks for 56 days each to determine the effects of LG on immune cell functions. The percentage of CD14+CD36+ cells in whole blood was analyzed by flow cytometry. Peripheral blood mononuclear cells were isolated and activated with CD3 plus CD28 antibodies (T-lymphocyte activation) or lipopolysaccharide (monocyte activation). Interferon γ, tumor necrosis factor α, interleukin (IL) 2, IL-4, and IL-10 were measured in supernatants from activated T cells. Supernatants from activated monocytes were analyzed for the production of tumor necrosis factor α, IL-1ß, and IL-6. Peripheral blood mononuclear cells were prestained with PKH dye and activated with CD3 plus CD28 antibodies to determine the proliferative responses of CD4+ and CD8+ T lymphocytes by flow cytometry. No differences were observed for CD14+CD36+ monocyte populations, T-cell proliferation, or the production of T cell and monocyte cytokines between the 2 treatments. Thus, LG supplementation in vivo did not affect ex vivo functions of T cells and monocytes, whereas it decreased several circulating markers of hepatic inflammation as we previously reported.

DHA concentration of red blood cells is inversely associated with markers of lipid peroxidation in men taking DHA supplement.

An increase in the proportion of fatty acids with higher numbers of double bonds is believed to increase lipid peroxidation, which augments the risk for many chronic diseases. (n-3) Polyunsaturated fatty acids provide various health benefits, but there is a concern that they might increase lipid peroxidation. We examined the effects of docosahexaenoic acid [22:6 (n-3)] supplementation on lipid peroxidation markers in plasma and red blood cells (RBC) and their associations with red blood cell and plasma fatty acids. Hypertriglyceridemic men (n = 17 per group) aged 39-66 years participated in a double-blind, randomized, placebo-controlled, parallel study. They received no supplements for the first 8 days and then received 7.5 g/day docosahexaenoic acid oil (3 g/day docosahexaenoic acid) or olive oil (placebo) for 90 days. Fasting blood samples were collected 0, 45, and 91 days after supplementation. Docosahexaenoic acid supplementation did not change plasma or RBC concentrations of lipid peroxidation markers (total hydroxyoctadecadienoic acid, total hydroxyeicosatetraenoic acid, total 8-isoprostaglandin F2α, 7α-hydroxycholesterol, 7ß-hydroxycholesterol) when pre- and post-supplement values were compared. However, the post-supplement docosahexaenoic acid (DHA) concentration was inversely associated with RBC concentrations of ZE-HODE, EE-HODE, t-HODE, and total 8-isoprostaglandin F2α, (p<0.05). RBC concentration of hydroxycholesterol was also inversely associated with DHA but it did not attain significance (p = 0.07). Our results suggest that increased concentration of DHA in RBC lipids reduced lipid peroxidation. This may be another health benefit of DHA in addition to its many other health promoting effects.

Dietary long-chain omega-3 fatty acids do not diminish eosinophilic pulmonary inflammation in mice.

Although the effects of fish oil supplements on airway inflammation in asthma have been studied with varying results, the independent effects of the fish oil components, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), administered separately, are untested. Here, we investigated airway inflammation and hyperresponsiveness using a mouse ovalbumin exposure model of asthma assessing the effects of consuming EPA (1.5% wt/wt), DHA (1.5% wt/wt), EPA plus DHA (0.75% each), or a control diet with no added omega-3 polyunsaturated fatty acids. Consuming these diets for 6 weeks resulted in erythrocyte membrane EPA contents (molar %) of 9.0 (± 0.6), 3.2 (± 0.2), 6.8 (± 0.5), and 0.01 (± 0.0)%; DHA contents were 6.8 (± 0.1), 15.6 (± 0.5), 12.3 (± 0.3), and 3.8 (± 0.2)%, respectively. The DHA group had the highest bronchoalveolar lavage (BAL) fluid eosinophil and IL-6 levels (P < 0.05). Similar trends were seen for macrophages, IL-4, and IL-13, whereas TNF-α was lower in omega-3 polyunsaturated fatty acid groups than the control (P < 0.05). The DHA group also had the highest airway resistance, which differed significantly from the EPA plus DHA group (P < 0.05), which had the lowest. Oxylipins were measured in plasma and BAL fluid, with DHA and EPA suppressing arachidonic acid-derived oxylipin production. DHA-derived oxylipins from the cytochrome P450 and 15-lipoxygenase pathways correlated significantly with BAL eosinophil levels. The proinflammatory effects of DHA suggest that the adverse effects of individual fatty acid formulations should be thoroughly considered before any use as therapeutic agents in asthma.

Sweet bing cherries lower circulating concentrations of markers for chronic inflammatory diseases in healthy humans.

A limited number of studies have demonstrated that some modulators of inflammation can be altered by the consumption of sweet cherries. We have taken a proteomics approach to determine the effects of dietary cherries on targeted gene expression. The purpose was then to determine changes caused by cherry consumption in the plasma concentrations of multiple biomarkers for several chronic inflammatory diseases in healthy humans with modestly elevated C-reactive protein (CRP; range, 1-14 mg/L; mean, 3.5 mg/L; normal, <1.0 mg/L). Eighteen men and women (45-61 y) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. Fasting blood samples were taken before the start of consuming the cherries (study d 7), 28 d after the initiation of cherry supplementation (d 35), and 28 d after the discontinuation (d 63). Of the 89 biomarkers assessed, cherry consumption for 28 d altered concentrations of 9, did not change those of 67, and the other 13 were below the detection limits. Cherry consumption decreased (P < 0.05) plasma concentrations of extracellular newly identified ligand for the receptor for advanced glycation end products (29.0%), CRP (20.1%), ferritin (20.3%), plasminogen activator inhibitor-1 (19.9%), endothelin-1 (13.7%), epidermal growth factor (13.2%), and IL-18 (8.1%) and increased that of IL-1 receptor antagonist (27.9%) compared with corresponding values on study d 7. The ferritin concentration continued to decrease between d 35 and 63 and it was significantly lower on d 63 than on d 7. Because the participants in this study were healthy, no clinical pathology end points were measured. However, results from the present study demonstrate that cherry consumption selectively reduced several biomarkers associated with inflammatory diseases.

The effect of docosahexaenoic acid on t10, c12-conjugated linoleic acid-induced changes in fatty acid composition of mouse liver, adipose, and muscle.

BACKGROUND: Concomitant supplementation of 1.5% docosahexaenoic acid (22:6 n-3; DHA) with 0.5% t10, c12-conjugated linoleic acid (18:2 n-6; CLA) prevented the CLA-induced increase in expression of hepatic genes involved in fatty acid synthesis and the decrease in expression of genes involved in fatty acid oxidation. The effect of CLA on fatty acid compositions of adipose tissue and muscle and whether DHA can prevent those CLA-induced changes in fatty acid composition is not known. METHODS: We investigated if DHA fed concomitantly with CLA for 4 weeks will prevent the CLA-induced changes in fatty acid compositions of liver, adipose, and muscle lipids in C57BL/6N female mice. We also examined changes in expression of adipose tissue genes involved in fatty acid synthesis, oxidation, uptake, and lipolysis. RESULTS: CLA supplementation increased liver fat and decreased total n-3 polyunsaturated fat (PUFA) concentration. DHA not only prevented the CLA-induced changes in liver fat, but also increased n-3 PUFA by >350% as compared with the control group. CLA decreased adipose weight and the expression of genes involved in fatty acid synthesis, oxidation, and uptake and increased that of uncoupling protein 2 (UCP2). Supplementing DHA along with CLA increased adipose n-3 PUFA by >1000% compared with control group, but did not prevent the CLA-induced changes in mass or gene expression. Both CLA and DHA were incorporated into muscle lipids, but had minor effects on fatty acid composition. CONCLUSIONS: Liver, adipose tissue, and muscle responded differently to CLA and DHA supplementation. DHA prevented CLA-induced increase in liver fat but not loss of adipose mass.

Arachidonate 5-lipoxygenase gene variants affect response to fish oil supplementation by healthy African Americans.

Arachidonate 5-lipoxygenase (ALOX5) gene variants that are common in people of African ancestry are associated with a differential cardiovascular disease (CVD) risk that may be ameliorated by intake of (n-3) PUFA, such as EPA or DHA. We conducted a double-masked, placebo (PL)-controlled trial of fish oil (FO) supplements to determine if changes in erythrocyte (n-3) PUFA composition, heart rate, blood pressure, and plasma lipid and lipoprotein concentrations are modified by genotype. Participants received 5 g/d FO (2 g EPA, 1 g DHA) or 5 g/d corn/soy oil (PL). A total of 116 healthy adults of African ancestry with selected genotypes (genotypes = "dd," "d5," and "55" with "d" representing the deletion of 1 or 2 Sp1 binding sites in the ALOX5 promoter and "5" indicating the common allele with 5 sites) were enrolled and 98 completed the study. FO caused significant increases (relative to PL) in erythrocyte EPA, DHA, and total (n-3) PUFA and a decrease in the (n-6) PUFA:(n-3) PUFA ratio in the low-CVD risk "d5" and "55" genotypes but not in the high-risk "dd" genotype. Similarly, HDL particle concentration decreased with FO relative to PL in the "d5" and "55" but not "dd" genotypes. The plasma TG concentration decreased significantly with FO relative to PL in the "d5" but not "dd" and "55" genotypes. No changes were seen in LDL particle or cholesterol concentrations, heart rate, or blood pressure. These findings indicate that the efficacy of FO supplements vary by ALOX5 genotype.

Docosahexaenoic acid prevents trans-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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Response of different tissues to CLA and DHA varied; CLA was more potent than DHA in altering depot fat and insulin concentrations.

Modulation of blood cell gene expression by DHA supplementation in hypertriglyceridemic men.

Our previous study with docosahexaenoic acid (DHA) supplementation to hypertriglyceridemic men showed that DHA reduced several risk factors for cardiovascular disease, including the plasma concentration of inflammatory markers. To determine the effect of DHA supplementation on the global gene expression pattern, we performed Affymetrix GeneChip microarray analysis of blood cells [treated with lipopolysaccharide (LPS) or vehicle] drawn before and after the supplementation of DHA from the hypertriglyceridemic men who participated in that study. Genes that were significantly differentially regulated by the LPS treatment and DHA supplementation were identified. Differential regulation of 18 genes was then verified by quantitative real-time polymerase chain reaction (qRT-PCR). Both microarray and qRT-PCR data showed that DHA supplementation significantly suppressed the expression of low-density lipoprotein (LDL) receptor and cathepsin L1, both of which were also up-regulated by LPS. DHA supplementation also suppressed oxidized LDL (lectin-like) receptor 1 (OLR1). However, LPS did not induce OLR1 mRNA expression. Enrichment with Gene Ontology categories demonstrated that the genes related to transcription factor activity, immunity, host defense and inflammatory responses were inversely regulated by LPS and DHA. These results provide supporting evidence for the anti-inflammatory effects of DHA supplementation, and reveal previously unrecognized genes that are regulated by DHA and are associated with risk factors of cardiovascular diseases.

Docosahexaenoic acid supplementation improved lipocentric but not glucocentric markers of insulin sensitivity in hypertriglyceridemic men.

BACKGROUND: Increase in obesity and metabolic syndrome are associated with increases in insulin resistance (IR) and type 2 diabetes mellitus. Results from animal intervention studies and human epidemiological studies suggest that n-3 polyunsaturated fatty acids can prevent and reverse IR, but results from human intervention studies have varied. Results from some human and animal studies suggest that docosahexaenoic acid (22:6n-3; DHA) may be more effective than eicosapentaenoic acid (20:5n-3; EPA) in the prevention of IR. METHODS: By using a placebo-controlled, parallel study design, we examined the effects of DHA supplementation (3 grams/day, 90 days) in the absence of EPA on glucocentric and lipocentric markers of IR in hypertriglyceridemic men (n=14-17/group). RESULTS: DHA supplementation increased fasting plasma glucose concentration by 4.7% (P<0.05), but did not alter other indices of IR based on fasting (insulin and homeostasis model assessment of insulin resistance [HOMA-IR]) or postprandial insulin and glucose concentrations (areas under curves for insulin and glucose, Matsuda index). Glucose increased by 2.7% in the placebo group and was not significant; increases in glucose in the two groups did not differ from each other. DHA decreased circulating concentrations of several lipocentric markers of IR, including plasma concentrations of nonesterified fatty acids (13.0%), small, dense low-density lipoprotein (LDL) particles (21.7%), and ratio of tryglycerides to high-density lipoprotein cholesterol (TG/HDL-C) (34.0%) (P<0.05). None of the variables changed in the placebo group. CONCLUSIONS: Our results suggest that lipocentric markers of IR are more responsive to DHA supplementation than the glucocentric markers. Future studies with DHA in prediabetic subjects and direct measures of insulin sensitivity are needed.

Mechanisms underlying the cardioprotective effects of omega-3 polyunsaturated fatty acids.

Typical omega 3 polyunsaturated fatty acids (n-3 PUFAs) are docosahexaenoic acid and eicosapentaenoic acid in the form of fish oils and alpha linolenic acid from flaxseed oil. Epidemiological studies suggested the benefits of n-3 PUFA on cardiovascular health. Intervention studies confirmed that the consumption of n-3 PUFA provided benefits for primary and secondary prevention of cardiovascular disease. Evidence from cellular and molecular research studies indicates that the cardioprotective effects of n-3 PUFA result from a synergism between multiple, intricate mechanisms that involve antiinflammation, proresolving lipid mediators, modulation of cardiac ion channels, reduction of triglycerides, influence on membrane microdomains and downstream cell signaling pathways and antithrombotic and antiarrhythmic effects. n-3 PUFAs inhibit inflammatory signaling pathways (nuclear factor-kappa B activity) and down-regulate fatty acid (FA) synthesis gene expression (sterol regulatory element binding protein-1c) and up-regulate gene expression involved in FA oxidation (peroxisome proliferator-activated receptor alpha). This review examines the various mechanisms by which n-3 PUFA exert beneficial effects against CVD.

Prevention of insulin resistance by n-3 polyunsaturated fatty acids.

PURPOSE OF REVIEW: Review results from recent human and animal studies regarding the effects of n-3 polyunsaturated fatty acid (PUFA) in the prevention of insulin resistance. RECENT FINDINGS: Overall, results from animal studies indicate that fish oil and individual n-3 PUFA [alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)] prevented insulin resistance in animal models; results from two studies in mice showed that EPA increased insulin secretion. ALA, EPA, and DHA may act at different sites and involve different mechanisms. Fish oil or purified EPA reduced insulin resistance in some but not other human studies in normal weight and obese individuals. Discrepancies may be due to differences in health status of participants, macronutrient, fatty acid, and antioxidant nutrient composition of basal diet; amount, duration, and fatty acid composition of n-3 PUFA, and methods used to assess insulin resistance. Moderate amounts of n-3 PUFA did not improve or deteriorate glucose control in type 2 diabetics. SUMMARY: n-3 PUFA supplementation has clinical significance in the prevention and reversal of insulin resistance. However, increased intake of n-3 PUFA should be part of an overall healthy lifestyle that includes weight control, exercise, and reduction in the intake of refined sugars, n-6, saturated, and trans fatty acids.

DHA supplementation decreases serum C-reactive protein and other markers of inflammation in hypertriglyceridemic men.

Dietary (n-3) PUFA reduce inflammation, an independent risk factor for cardiovascular disease. The antiinflammatory effects of docosahexaenoic acid (DHA) in hypertriglyceridemic men have not been previously reported, to our knowledge, and were the focus of this study. Hypertriglyceridemic men (n = 17 per group) aged 39-66 y, participated in a double-blind, randomized, placebo-controlled parallel study. They received no supplements for the first 8 d and then received either 7.5 g/d DHA oil (3 g DHA/d) or olive oil (placebo) for the last 90 d. Blood samples were collected from fasting men on study days -7, 0, 45, 84, and 91. DHA supplementation for 45 and 91 d decreased the number of circulating neutrophils by 11.7 and 10.5%, respectively (P < 0.05). It did not alter the circulating concentrations of other inflammatory markers tested within 45 d, but at 91 d it reduced (P < 0.05) concentrations of C-reactive protein (CRP) by 15%, interleukin-6 by 23%, and granulocyte monocyte-colony stimulating factor by 21% and DHA increased the concentration of antiinflammatory matrix metalloproteinase-2 by 7%. The number of circulating neutrophils was positively associated with the weight percent (wt %) of 20:4(n-6) in RBC lipids, and negatively to the wt % of 20:5(n-3) and 22:6(n-3). Concentrations of CRP and serum amyloid A were positively associated with the sum of SFA and negatively with the wt % of 18:1(n-9) and 17:0 in RBC lipids; CRP was also positively associated with the wt % of 20:2(n-6). The mean size of VLDL particles was positively associated with plasma concentrations of neutrophils and CRP. In conclusion, DHA may lessen the inflammatory response by altering blood lipids and their fatty acid composition.

Flaxseed oil prevents trans-10, cis-12-conjugated linoleic acid-induced insulin resistance in mice.

Insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) are found in 35 and 30 % of US adults, respectively. Trans-10, cis-12-conjugated linoleic acid (CLA) has been found to cause both these disorders in several animal models. We hypothesised that IR and NAFLD caused by CLA result from n-3 fatty acid deficiency. Pathogen-free C57BL/6N female mice (aged 8 weeks; n 10) were fed either a control diet or diets containing trans-10, cis-12-CLA (0.5 %) or CLA+flaxseed oil (FSO) (0.5 %+0.5 %) for 8 weeks. Weights of livers, concentration of circulating insulin, values of homeostatic model 1 (HOMA1) for IR and HOMA1 for beta cell function were higher by 160, 636, 985 and 968 % in the CLA group compared with those in the control group. FSO decreased fasting glucose by 20 % and liver weights by 37 % compared with those in the CLA group; it maintained circulating insulin, HOMA1-IR and HOMA1 for beta cell function at levels found in the control group. CLA supplementation decreased n-6 and n-3 wt% concentrations of liver lipids by 57 and 73 % and increased the n-6:n-3 ratio by 58 % compared with corresponding values in the control group. FSO increased n-6 and n-3 PUFA in liver lipids by 33 and 342 % and decreased the n-6:n-3 ratio by 70 % compared with corresponding values in the CLA group. The present results suggest that some adverse effects of CLA may be due to n-3 PUFA deficiency and that these can be corrected by a concomitant increase in the intake of alpha-linolenic acid, 18 : 3n-3.

Docosahexaenoic acid supplementation decreases remnant-like particle-cholesterol and increases the (n-3) index in hypertriglyceridemic men.

Plasma remnant-like particle-cholesterol (RLP-C) and the RBC (n-3) index are novel risk factors for cardiovascular disease. Effects of docosahexaenoic acid (DHA) supplementation on these risk factors in hypertriglyceridemic men have not been studied. We determined effects of DHA supplementation on concentrations of plasma RLP-C, the RBC (n-3) index, and associations between concentrations of plasma RLP-C with those of plasma lipids and fatty acids. Hypertriglyceridemic men aged 39-66 y, participated in a randomized, placebo-controlled, parallel study. They received no supplements for 8 d and then received either 7.5 g/d DHA oil (3 g DHA/d) or olive oil (placebo) for the last 90 d. Fasting blood samples were collected on study d -7, 0 (baseline), 45 (mid-intervention), 84, and 91 (end-intervention). DHA supplementation for 45 d decreased (P < 0.05) fasting RLP-C (36%) and increased plasma eicosapentaenoic acid (EPA):arachidonic acid (AA) (100%) and the RBC (n-3) index (109%). Continued supplementation with DHA between d 45 and 91 further increased the RBC (n-3) index (162%) and plasma EPA:AA (137%) compared with baseline values. RLP-C concentration was positively associated (P < 0.01) with the plasma concentrations of triacylglycerols (Kendall's correlation coefficient or r = 0.46), triacylglycerol:HDL cholesterol (HDL-C) (r = 0.44), total cholesterol:HDL-C (r = 0.26), Apo B (r = 0.22), C III (r = 0.41), and E (r = 0.17), and 18:1(n-9) (r = 0.32); it was negatively associated (P < 0.05) with plasma concentrations of DHA (r = -0.32), EPA (r = -0.25), HDL-C (r = -0.21), LDL cholesterol:Apo B (r = -0.30), and HDL-C:Apo A (r = -0.25). Supplementation with placebo oil did not alter any of the response variables tested. Decreased atherogenic RLP-C and increased cardio-protective (n-3) index may improve cardio-vascular health.

Docosahexaenoic acid supplementation improves fasting and postprandial lipid profiles in hypertriglyceridemic men.

BACKGROUND: The effects of docosahexaenoic acid (DHA) on the mean size and concentrations of VLDL, LDL, and HDL subclasses have not been previously studied. OBJECTIVE: We determined the effects of DHA supplementation on the concentrations of apoproteins; large, medium, and small VLDL, LDL, and HDL particles; and the mean diameters of these particles in fasting and postprandial plasma. DESIGN: Hypertriglyceridemic men aged 39-66 y (n = 34) participated in a double-blind, randomized, placebo-controlled parallel study. They received no supplements for the first 8 d and received either 7.5 g DHA oil/d (3 g DHA/d) or olive oil (placebo) for the last 90 d. Lipoprotein particle diameters and concentrations were measured by nuclear magnetic resonance spectroscopy. RESULTS: DHA supplementation for 45 d significantly (P < 0.05) decreased concentrations of fasting triacylglycerol (24%), large VLDL (92%), and intermediate-density lipoproteins (53%) and the mean diameter of VLDL particles (11.1 nm). It elevated concentrations of LDL cholesterol (12.6%), small VLDL particles (133%), and large LDL particles (120%) and the mean diameter of LDL particles (0.6 nm) in fasting plasma. Similar changes were observed for area under the curve for postprandial samples (0-6 h); however, the number of small dense LDL particles decreased significantly (21%), and the change in LDL cholesterol was not significant. Continued supplementation with DHA beyond 45 d caused no further changes; placebo treatment altered none of the responses tested. CONCLUSION: DHA supplementation may improve cardiovascular health by lowering concentrations of triacylglycerols and small, dense LDL particles.