Effects of omega-3 supplementation on psychological symptoms in men with prostate cancer: Secondary analysis of a double-blind placebo-controlled randomized trial.

BACKGROUND: In the general population, a higher omega-3 polyunsaturated fatty acids intake is associated with lower levels of several psychological symptoms, especially depression. However, the existing evidence in cancer is equivocal. METHODS: This phase IIB double-blind, placebo-controlled trial was aimed at comparing the effects of eicosapentaenoic acid monoacylglyceride (MAG-EPA) supplementation and high oleic acid sunflower oil (HOSO; placebo) on depression levels (primary outcome) and other symptoms (anxiety, fear of cancer recurrence, fatigue, insomnia, perceived cognitive impairments; secondary outcomes). Participants, recruited in a prostate cancer clinic, were randomized to MAG-EPA (3.75 g daily; n = 65) or HOSO (3.75 g daily; n = 65) for 1 year post-radical prostatectomy (RP), starting 4-10 weeks before surgery. Patients completed self-report scales at baseline (before RP) and 3, 6, 9, and 12 months after: Hospital Anxiety and Depression Scale (HADS), Fear of Cancer Recurrence Inventory (FCRI), Insomnia Severity Index (ISI), Fatigue Symptom Inventory (FSI), and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). RESULTS: Analyses showed significant reductions in HADS-depression, HADS-anxiety, FCRI, ISI, FSI-number of days, and FACT-Cog-impact scores over time. A significant group-by-time interaction was obtained on FACT-Cog-Impact scores only; yet, the temporal change was significant in HOSO patients only. CONCLUSIONS: Several symptoms significantly decreased over time, mainly within the first months of the study. However, MAG-EPA did not produce greater reductions than HOSO. Omega-3 supplementation does not seem to improve psychological symptoms of men treated with RP.

Eicosapentaenoic Acid Influences the Lipid Profile of an In Vitro Psoriatic Skin Model Produced with T Cells.

Psoriasis is a skin disease characterized by epidermal hyperplasia and an inappropriate activation of the adaptive immunity. A dysregulation of the skin's lipid mediators is reported in the disease with a predominance of the inflammatory cascade derived from n-6 polyunsaturated fatty acids (n-6 PUFAs). Bioactive lipid mediators derived from arachidonic acid (AA) are involved in the inflammatory functions of T cells in psoriasis, whereas n-3 PUFAs' derivatives are anti-inflammatory metabolites. Here, we sought to evaluate the influence of a supplementation of the culture media with eicosapentaenoic acid (EPA) on the lipid profile of a psoriatic skin model produced with polarized T cells. Healthy and psoriatic skin substitutes were produced following the auto-assembly technique. Psoriatic skin substitutes produced with or without T cells presented increased epidermal and dermal linolenic acid (LA) and AA levels. N-6 PUFA lipid mediators were strongly measured in psoriatic substitutes, namely, 13-hydroxyoctadecadienoic acid (13-HODE), prostaglandin E2 (PGE2) and 12-hydroxyeicosatetraenoic acid (12-HETE). The added EPA elevated the amounts of EPA, n-3 docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) in the epidermal and dermal phospholipids. The EPA supplementation balanced the production of epidermal lipid mediators, with an increase in prostaglandin E3 (PGE3), 12-hydroxyeicosapentaenoic acid (12-HEPE) and N-eicosapentaenoyl-ethanolamine (EPEA) levels. These findings show that EPA modulates the lipid composition of psoriatic skin substitutes by encouraging the return to a cutaneous homeostatic state.

Effects of Concentrated Long-Chain Omega-3 Polyunsaturated Fatty Acid Supplementation on Quality of Life after Radical Prostatectomy: A Phase II Randomized Placebo-Controlled Trial (RCT-EPA).

Prostate cancer (PCa) and associated treatments incur symptoms that may impact patients' quality of life. Studies have shown beneficial relationships between diet, especially omega-3 fatty acids, and these symptoms. Unfortunately, only few data describing the relationship between long-chain omega-3 fatty acids (LCn3) and PCa-related symptoms in patients are available. The purpose of this study was to evaluate the effects of LCn3 supplementation on PCa-specific quality of life in 130 men treated by radical prostatectomy. Men were randomized to receive a daily dose of either 3.75 g of fish oil or a placebo starting 7 weeks before surgery and for up to one-year post-surgery. Quality of life was assessed using the validated EPIC-26 and IPSS questionnaires at randomization, at surgery, and every 3 months following surgery. Between-group differences were assessed using linear mixed models. Intention-to-treat analyses showed no significant difference between the two groups. However, at 12-month follow-up, per-protocol analyses showed a significantly greater increase in the urinary irritation function score (better urinary function) (MD = 5.5, p = 0.03) for the LCn3 group compared to placebo. These results suggest that LCn3 supplementation may improve the urinary irritation function in men with PCa treated by radical prostatectomy and support to conduct of larger-scale studies.

Alpha-Linolenic Acid Modulates T Cell Incorporation in a 3D Tissue-Engineered Psoriatic Skin Model.

Psoriasis is an autoimmune skin disease with an increased number of leukocytes infiltrating the dermal and epidermal compartments compared with normal skin. N-3 polyunsaturated fatty acids (n-3 PUFAs) are frequently used in the clinic in order to attenuate the symptoms of psoriasis. For psoriatic patients, a supplementation of the diet with alpha-linolenic acid (ALA) reduces the activation of T cell signaling pathways, leading to a significant reduction in inflammatory cytokine secretion. However, the precise mechanism of action of n-3 PUFAs in psoriasis is still not understood. In the present study, we elucidated the bioaction of ALA on the adaptive immune component of psoriasis by using a psoriatic skin model produced with the addition of activated T cells. Healthy and psoriatic skin substitutes were produced according to the self-assembly method, using culture media supplemented with 10 µM of ALA. T cells were isolated from blood samples using a negative selection isolation method. ALA supplementation regulated the hyperproliferation and abnormal cell differentiation of psoriatic keratinocytes stimulated by T cells. Additionally, the exogenous ALA was correctly incorporated into the phospholipids of keratinocytes, which resulted in increased levels of ALA, eicosapentaenoic acid (EPA) and n-3 docosapentaenoic acid (n-3 DPA). The infiltration of T cells into the epidermis was reduced when ALA was added to the culture medium, and significant decreases in the levels of inflammatory cytokines and chemokines such as CXCL1, interleukin-6 (IL-6) and interleukin-8 (IL-8) were consequently measured in psoriatic substitutes supplemented with this n-3 PUFA. Altogether, our results showed that in this psoriatic skin model enriched with T cells, ALA exerted its beneficial effect by decreasing the quantities of inflammatory mediators released by T cells.

α-Linolenic acid and linoleic acid modulate the lipidome and the skin barrier of a tissue-engineered skin model.

Polyunsaturated fatty acids (PUFAs) play an important role in the establishment and the maintenance of the skin barrier function. However, the impact of their derived lipid mediators remains unclear. Skin substitutes were engineered according to the self-assembly method with a culture medium supplemented with 10 µM of both α-linolenic acid (ALA) and linoleic acid (LA). The supplementation with ALA and LA decreased testosterone absorption through a tissue-engineered reconstructed skin model, thus indicating an improved skin barrier function following supplementation. The exogenously provided fatty acids were incorporated into the phospholipid and triglyceride fractions of the skin substitutes. Indeed, the dual supplementation increased the levels of eicosapentaenoic acid (EPA) (15-fold), docosapentaenoic acid (DPA) (3-fold), and LA (1.5-fold) in the epidermal phospholipids while it increased the levels of ALA (>20-fold), DPA (3-fold) and LA (1.5-fold) in the epidermal triglycerides. The bioactive lipid mediator profile of the skin substitutes, including prostaglandins, hydroxy-fatty acids, N-acylethanolamines and monoacylglycerols, was next analyzed using liquid chromatography-tandem mass spectrometry. The lipid supplementation further modulated bioactive lipid mediator levels of the reconstructed skin substitutes, leading to a lipid mediator profile more representative of the one found in normal human skin. These findings show that an optimized supply of PUFAs via culture media is essential for the establishment of improved barrier function in vitro. STATEMENT OF SIGNIFICANCE: Supplementation of the culture medium with 10 µM of both α-linolenic acid (ALA) and linoleic acid (LA) improved the skin barrier function of a tissue-engineered skin model. The exogenously provided fatty acids were incorporated into the phospholipid and triglyceride fractions of the skin substitutes and further modulated bioactive lipid mediator levels, including prostaglandins, hydroxy-fatty acids, N-acylethanolamines and monoacylglycerols. These findings highlight the important role of ALA and LA in skin homeostasis and show that an optimized supply of polyunsaturated fatty acids via culture media is essential for the establishment of improved barrier function in vitro.

Docosahexaenoic acid-rich algae oil supplementation on breast milk fatty acid profile of mothers who delivered prematurely: a randomized clinical trial.

Preterm infants are deficient in long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), a fatty acid (FA) associated with an increase in bronchopulmonary dysplasia (BPD). In two previous randomized control trials, DHA supplementation did not reduce the risk of BPD. We examined the breast milk FA profile, collected 14 days after birth, of mothers who delivered before 29 weeks of gestation and who were supplemented with DHA-rich algae oil or a placebo within 72 h after birth as part of the MOBYDIck trial. Milk FA were analyzed by gas chromatography. The total amount of FA (mg/mL) was similar in both groups but the supplementation increased DHA (expressed as % of total FA, mean ± SD, treatment vs placebo, 0.95 ± 0.44% vs 0.34 ± 0.20%; P < 0.0001), n-6 docosapentaenoic acid (DPA) (0.275 ± 0.14% vs 0.04 ± 0.04%; P < 0.0001) and eicosapentaenoic acid (0.08 ± 0.08% vs 0.07 ± 0.07%; P < 0.0001) while decreasing n-3 DPA (0.16 ± 0.05% vs 0.17 ± 0.06%; P < 0.05). Supplementation changed the ratio of DHA to arachidonic acid (1.76 ± 1.55% vs 0.60 ± 0.31%; P < 0.0001) and n-6 to n-3 FA (0.21 ± 0.06% vs 0.17 ± 0.04%; P < 0.0001). DHA-rich algae supplementation successfully increased the DHA content of breast milk but also included secondary changes that are closely involved with inflammation and may contribute to changing clinical outcomes.

The plasma antioxidant vitamin status of the INTAPP cohort examined: The unsuspected importance of ß-carotene and γ-tocopherol in preeclampsia.

OBJECTIVE: Examine the levels of plasma antioxidant vitamins before and during a treatment with placebo or vitamin E + C supplement to prevent preeclampsia (PE). STUDY DESIGN: Per-protocol analysis of a subset group of pregnant women (n = 295) from the International Trial of Antioxidants for the Prevention of PE (INTAPP) randomized case-control study. Normotensive receiving placebo or vitamins (n = 115 and 87 respectively) were compared to gestational hypertension (GH) without proteinuria (n = 30 and 27) and PE (n = 21 and 15). Vitamin quantification was performed at 12-18, 24-26 and 32-34 weeks of gestation. MAIN OUTCOME MEASURES: Coenzyme (Co) Q10, ß-carotene and vitamins E (α and γ forms) plasma levels. RESULTS: Vitamin E + C supplementation was found to increase the α-tocopherol levels by 40% but was associated with a 57% decrease in the γ-tocopherol isoform for all study groups (p < 0.001). The ß -carotene was lower in the PE than in the normotensive and GH groups (p < 0.001) while the level of CoQ10 remained unaffected. CONCLUSIONS: A more personalized approach that target the suboptimal levels of specific antioxidants without disturbing the α/γ-tocopherol ratio could be a more successful approach to counteract oxidative stress in PE.

Investigation of Omega-3 Polyunsaturated Fatty Acid Biological Activity in a Tissue-Engineered Skin Model Involving Psoriatic Cells.

Clinical studies have shown that diets enriched with omega-3 (also know as n-3) polyunsaturated fatty acids could relieve the symptoms of patients with psoriasis. However, the mechanisms involved remain poorly understood. The aim of this study was to investigate the effects of α-linolenic acid (ALA) on the proliferation and differentiation of psoriatic keratinocytes in a three-dimensional skin model. Skin models featuring healthy (healthy substitute) or psoriatic (psoriatic substitute) cells were engineered by the self-assembly method of tissue engineering using a culture medium supplemented with 10 µM ALA in comparison with the regular unsupplemented medium. ALA decreased keratinocyte proliferation and improved psoriatic substitute epidermal differentiation, as measured by decreased Ki67 staining and increased protein expression of FLG and loricrin. The added ALA was notably incorporated into the epidermal phospholipids and metabolized into long-chain n-3 polyunsaturated fatty acids, mainly eicosapentaenoic acid and n-3 docosapentaenoic acid. ALA supplementation led to increased levels of eicosapentaenoic acid derivatives (15-hydroxyeicosapentaenoic acid and 18-hydroxyeicosapentaenoic acid) as well as a decrease in levels of omega-6 (also know as n-6) polyunsaturated fatty acid lipid mediators (9-hydroxyoctadecadienoic acid, 12-hydroxyeicosatetraenoic acid, and leukotriene B4). Furthermore, the signal transduction mediators extracellular signal‒regulated kinases 1 and 2 were the kinases most activated after ALA supplementation. Taken together, these results show that ALA decreases the pathologic phenotype of psoriatic substitutes by normalizing keratinocyte proliferation and differentiation in vitro.

Omega-3 Eicosapentaenoic Acid Reduces Prostate Tumor Vascularity.

The impact of omega (ω)-3 fatty acids on prostate cancer is controversial in epidemiological studies but experimental studies suggest a protective effect. However, little is known about the mechanism of action. Here, we studied the effects of purified fatty acid molecules on prostate tumor progression using the TRAMP-C2 syngeneic immunocompetent mouse model. Compared with ω-6 or ω-9-supplemented animals, we observed that late-stage prostate tumor growth was reduced with a monoacylglyceride (MAG)-conjugated form of eicosapentaenoic acid (EPA) supplementation, whereas docosahexanenoic acid (DHA) caused an early reduction. MAG-EPA significantly decreased tumor blood vessel diameter (P < 0.001). RNA sequencing analysis revealed that MAG-EPA downregulated angiogenesis- and vascular-related pathways in tumors. We also observed this tissue vascular phenotype in a clinical trial testing MAG-EPA versus a high oleic sunflower oil placebo. Using anti-CD31 IHC, we observed that MAG-EPA reduced blood vessel diameter in prostate tumor tissue (P = 0.03) but not in normal adjacent tissue. Finally, testing autocrine and paracrine effects in an avascular tumor spheroid growth assay, both exogenous MAG-EPA and endogenous ω3 reduced VEGF secretion and in vitro endothelial cell tube formation and blocked tumor spheroid growth, suggesting that ω3 molecules can directly hinder prostate cancer cell growth. Altogether, our results suggest that fatty acids regulate prostate cancer growth and that a tumor-specific microenvironment is required for the anti-vascular effect of MAG-EPA in patients with prostate cancer. IMPLICATIONS: Increasing the amount of ingested EPA omega-3 subtype for patients with prostate cancer might help to reduce prostate tumor progression by reducing tumor vascularization.

Long chain omega-3 fatty acids and their oxidized metabolites are associated with reduced prostate tumor growth.

INTRODUCTION: Cancer has been associated with increased oxidative stress and deregulation of bioactive oxylipins derived from long-chain polyunsaturated fatty acids (LC-PUFA) like arachidonic acid (AA). There is a debate whether ω-3 LC-PUFA could promote or prevent prostate tumor growth through immune modulation and reduction of oxidative stress. Our aim was to study the association between enzymatically or non-enzymatically produced oxidized-LC-PUFA metabolites and tumor growth in an immune-competent eugonadal and castrated C57BL/6 male mice injected with TRAMP-C2 prostate tumor cells, fed with ω-3 or ω-6 LC-PUFA-rich diets. MATERIALS AND METHODS: Tumor fatty acids were profiled by gas chromatography and 26 metabolites derived from either AA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were assessed by liquid chromatography-mass spectrometry. RESULTS: The enriched ω-3 diet did not reduce oxidative stress overall in tumors but favored the formation of ω-3 rather than ω-6 derived isoprostanoids. We discovered that EPA and its oxidized-derivatives like F3-isoprostanes and prostaglandin (PG)F3α, were inversely correlated with tumor volume (spearman correlations and T-test, p<0.05). In contrast, F2-isoprostanes, adrenic acid, docosapentaenoic acid (DPAω-6) and PGE2 were positively correlated with tumor volume. Interestingly, F4-neuroprostanes, PGD2, PGF2α, and thromboxane were specifically increased in TRAMP-C2 tumors of castrated mice compared to those of eugonadal mice. DISCUSSION: Decreasing tumor growth under ω-3 diet could be attributed in part to increased levels of EPA and its oxidized-derivatives, a reduced level of pro-angiogenic PGE2 and increased levels of F4-neuroprostanes and resolvins content in tumors, suspected of having anti-proliferative and anti-inflammatory effects.

Effect of Maternal Docosahexaenoic Acid Supplementation on Bronchopulmonary Dysplasia-Free Survival in Breastfed Preterm Infants: A Randomized Clinical Trial.

Importance: Maternal docosahexaenoic acid (DHA) supplementation may prevent bronchopulmonary dysplasia, but evidence remains inconclusive. Objective: To determine whether maternal DHA supplementation during the neonatal period improves bronchopulmonary dysplasia-free survival in breastfed infants born before 29 weeks of gestation. Design, Setting, and Participants: Superiority, placebo-controlled randomized clinical trial at 16 Canadian neonatal intensive care units (June 2015-April 2018 with last infant follow-up in July 2018). Lactating women who delivered before 29 weeks of gestation were enrolled within 72 hours of delivery. The trial intended to enroll 800 mothers, but was stopped earlier. Interventions: There were 232 mothers (273 infants) assigned to oral capsules providing 1.2 g/d of DHA from randomization to 36 weeks' postmenstrual age and 229 mothers (255 infants) assigned to placebo capsules. Main Outcomes and Measures: The primary outcome was bronchopulmonary dysplasia-free survival in infants at 36 weeks' postmenstrual age. There were 22 secondary outcomes, including mortality and bronchopulmonary dysplasia. Results: Enrollment was stopped early due to concern for harm based on interim data from this trial and from another trial that was published during the course of this study. Among 461 mothers and their 528 infants (mean gestational age, 26.6 weeks [SD, 1.6 weeks]; 253 [47.9%] females), 375 mothers (81.3%) and 523 infants (99.1%) completed the trial. Overall, 147 of 268 infants (54.9%) in the DHA group vs 157 of 255 infants (61.6%) in the placebo group survived without bronchopulmonary dysplasia (absolute difference, -5.0% [95% CI, -11.6% to 2.6%]; relative risk, 0.91 [95% CI, 0.80 to 1.04], P = .18). Mortality occurred in 6.0% of infants in the DHA group vs 10.2% of infants in the placebo group (absolute difference, -3.9% [95% CI, -6.8% to 1.4%]; relative risk, 0.61 [95% CI, 0.33 to 1.13], P = .12). Bronchopulmonary dysplasia occurred in 41.7% of surviving infants in the DHA group vs 31.4% in the placebo group (absolute difference, 11.5% [95% CI, 2.3% to 23.2%]; relative risk, 1.36 [95% CI, 1.07 to 1.73], P = .01). Of 22 prespecified secondary outcomes, 19 were not significantly different. Conclusions and Relevance: Among breastfed preterm infants born before 29 weeks of gestation, maternal docosahexaenoic acid supplementation during the neonatal period did not significantly improve bronchopulmonary dysplasia-free survival at 36 weeks' postmenstrual age compared with placebo. Study interpretation is limited by early trial termination. Trial Registration: ClinicalTrials.gov Identifier: NCT02371460.

Drinkable lecithin nanovesicles to study the biological effects of individual hydrophobic macronutrients and food preferences.

Fundamental nutritional studies on bioactive molecules require minimizing exposure to confounding foreign elements, like solvents. Herein, aqueous formulations of lecithin nanovesicles are proposed to study three individual trans fatty acids relevant to human nutrition: elaidic acid, trans-vaccenic acid and trans-palmitoleic acid. This proof-of-concept study describes the encapsulation of fatty acids, in vivo bioavailability, and the use of nanovesicles in behavioral experiments. The oral bioavailability of the encapsulated molecules and the selective exposure of animals to each trans-fatty acid of interest were confirmed in healthy rats. Behavioral studies also evidenced that nanovesicles can be used to evaluate the palatability of the lipids and investigate food preferences in mice. Altogether this study shows that lecithin nanovesicles offer an elegant tool to efficiently deliver hydrophobic molecules to animal models. This approach paves the way for future studies deconvoluting the nutritional effects of trans-fatty acids.

Modulation of the Lipid Profile of Reconstructed Skin Substitutes after Essential Fatty Acid Supplementation Affects Testosterone Permeability.

Skin models with efficient skin barrier function are required for percutaneous absorption studies. The contribution of media supplementation with n-3 and n-6 polyunsaturated fatty acids (PUFAs) to the development of the skin barrier function of in vitro skin models remains incompletely understood. To investigate whether PUFAs, alpha-linolenic acid (ALA, n-3 PUFA) and linoleic acid (LA, n-6 PUFA), could enhance the impermeability of a three-dimensional reconstructed human skin model, skin substitutes were produced according to the self-assembly method using culture media supplemented with either 10 µM ALA or 10 µM LA. The impact of PUFAs on skin permeability was studied by using a Franz cell diffusion system to assess the percutaneous absorption of testosterone and benzoic acid. Our findings showed that ALA supplementation induced a decrease in the absorption of testosterone, while LA supplementation did not significantly influence the penetration of testosterone and benzoic acid under present experimental conditions. Both ALA and LA were incorporated into phospholipids of the skin substitutes, resulting in an increase in n-3 total PUFAs or n-6 total PUFAs. Collectively, these results revealed the under-estimated impact of n-3 PUFA supplementation as well as the importance of the n-6 to n-3 ratio on the formation of the skin barrier of in vitro reconstructed human skin models.

Omega-3 Fatty Acids Survey in Men under Active Surveillance for Prostate Cancer: from Intake to Prostate Tissue Level.

Dietary omega-3 fatty acids (ω3), particularly long-chain ω3 (LCω3), have protective effects against prostate cancer (PCa) in experimental studies. Observational studies are conflicting, possibly because of the biomarker used. This study aimed at evaluating associations between grade reclassification and ω3 levels assessed in prostatic tissue, red blood cells (RBC), and diet. We conducted a validation cross-sectional study nested within a phase II clinical trial. We identified 157 men diagnosed with low-risk PCa who underwent a first active surveillance repeat prostate biopsy session. Fatty acid (FA) intake was assessed using a food frequency questionnaire and their levels measured in prostate tissue and RBC. Associations were evaluated using logistic regression. At first repeat biopsy session, 39 (25%) men had high-grade PCa (grade group ≥2). We found that high LCω3-eicosapentaenoic acid (EPA) level in prostate tissue (odds ratio (OR) 0.25; 95% (confidence interval (CI) 0.08-0.79; p-trend = 0.03) was associated with lower odds of high-grade PCa. Similar results were observed for LCω3 dietary intake (OR 0.30; 95% CI 0.11-0.83; p-trend = 0.02) but no association for RBC. LCω3-EPA levels in the target prostate tissue are inversely associated with high-grade PCa in men with low-risk PCa, supporting that prostate tissue FA, but not RBC FA, is a reliable biomarker of PCa risk.

Omega-3 fatty acids decrease prostate cancer progression associated with an anti-tumor immune response in eugonadal and castrated mice.

BACKGROUND: Several lines of evidence suggest effects of dietary fat on prostate cancer (PCa) development and progression. Targeting omega (ω)-3:ω6 fatty acids (FA) ratio could be beneficial against PCa by favorably modulating inflammation. Here, we studied the effects of ω3- and ω6-enriched diets on prostate tumor growth and inflammatory response in androgen-deprived and non-deprived conditions. METHODS: Immune-competent eugonadal and castrated C57BL/6 mice were injected with TRAMP-C2 prostate tumor cells and daily fed with ω3- or ω6-enriched diet. FA and cytokine profiles were measured in blood and tumors using gas chromatography and multiplex immunoassay, respectively. Immune cell infiltration in tumors was profiled by multicolor flow cytometry. RESULTS: ω3-enriched diet decreased prostate TRAMP-C2 tumor growth in immune-competent eugonadal and castrated mice. Cytokines associated with Th1 immune response (IL-12 [p70], IFN-γ, GM-CSF) and eosinophil recruitment (eotaxin-1, IL-5, and IL-13) were significantly elevated in tumors of ω3-fed mice. Using in vitro experiments, we confirmed ω3 FA-induced eotaxin-1 secretion by tumor cells and that eotaxin-1 secretion was regulated by androgens. Analysis of immune cell infiltrating tumors showed no major difference of immune cells' abundance between ω3- and ω6-enriched diets. CONCLUSIONS: ω3-enriched diet reduces prostate tumor growth independently of androgen levels. ω3 FA can inhibit tumor cell growth and induce a local anti-tumor inflammatory response. These findings warrant further examination of dietary ω3's potential to slow down the progression of androgen-sensitive and castrate-resistant PCa by modulating immune cell function in tumors.

F2-isoprostanes and fatty acids profile in early pregnancy complicated by pre-existing diabetes.

BACKGROUND: Diabetes and pregnancy are both associated with oxidative stress, characterized by an increase of F2-isoprostanes from the non-enzymatic oxidation of arachidonic acid, a n - 6 polyunsaturated fatty acid (PUFA). We hypothesized that pregnant women with pre-existing diabetes will be characterized by elevated levels of specific F2-isoPs isomers and altered PUFA composition in plasma early pregnancy when compared to normoglycemic controls. METHODS: Plasma samples from 23 women with uncomplicated pregnancies and 11 women with pre-existing diabetes in pregnancy were collected between 12 and 18 weeks of pregnancy (MIROS cohort). Six F2-isoprostanes isomers were measured by high-performance liquid chromatography coupled to tandem mass spectrometry. Fatty acids concentrations in plasmatic phospholipids were measured by gas chromatography coupled to a flame ionization detector. RESULTS: F2-isoprostanes, specifically the 8-iso-15(R)-PGF2α levels, were 67% higher in diabetic than normoglycemic pregnancies (p = 0.026). The total n - 6 PUFA and arachidonic acid level did not differ between study groups. In contrast, total n - 3 level was 32% lower in diabetic pregnancies than in controls (p = 0.002); EPA(20:5) and DHA(22:6) being specifically reduced (p = 0.035 and p = 0.003 respectively). Delta-6-desaturase (D6D) activity index, calculated using fatty acid ratios, was 9% lower in pre-existing diabetes than in controls (p = 0.042). CONCLUSIONS: Pre-existing diabetes in early pregnancy displays a distinctive F2-isoprostanes profile when compared to other pathologies of pregnancy, such as preeclampsia, as previously assessed in the same cohort.

Association of pre-eclampsia with SOD2 Ala16Val polymorphism among mother-father-infant triads.

OBJECTIVE: To determine whether pre-eclampsia is associated with polymorphisms in superoxide dismutase (SOD) genes among mother-father-infant triads. METHODS: We did this follow-up cohort study at 17 urban hospitals in Canada between October 1, 2008, and September 30, 2010. We recruited Canadian participants who had participated in the International Trial of Antioxidant Supplementation for the Prevention of Pre-eclampsia. Saliva specimens were collected for DNA extraction. The SOD1 +35A/C (rs2234694) and SOD2 Ala16Val C/T (rs4880) single-nucleotide polymorphisms (SNPs) were genotyped. RESULTS: Dual presence of the SOD2 Ala16Val TT variant among mother-father pairs (n=657) was associated with an increased risk of pre-eclampsia when compared with the absence of the TT variant among the mother-father pairs (7/48 [14.6%] vs 11/339 [3.2%]; adjusted odds ratio 6.80, 95% confidence interval 2.32-19.95; P<0.001). By contrast, presence of a single T variant in mother-father pairs (16/270 [5.9%]) or mother-infant pairs (8/179 [4.5%]) was not associated with pre-eclampsia. The SOD1 +35A/CSNP was not associated with pre-eclampsia. CONCLUSION: The SOD2 Ala16Val SNP might be involved in paternal influence on the maternal predisposition to pre-eclampsia. Genotyping of mother-father pairs could be a promising strategy to identify pre-eclampsia genes.

Effects of concentrated long-chain omega-3 polyunsaturated fatty acid supplementation before radical prostatectomy on prostate cancer proliferation, inflammation, and quality of life: study protocol for a phase IIb, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Prostate cancer is the most commonly diagnosed cancer in north-American men. Few dietary or lifestyle interventions have been tested to prevent prostate cancer progression. Omega-3 fatty acid supplementation represents a promising intervention for prostate cancer patients. The aim of the study is to evaluate the effects of long-chain omega-3 polyunsaturated fatty acids (LCn3), more precisely eicosapentaenoic acid monoacylglyceride (MAG-EPA) supplementation, on prostate cancer proliferation, inflammation mediators and quality of life among men who will undergo radical prostatectomy. METHODS/DESIGN: We propose a phase IIb, randomized, double-blind placebo-controlled trial of MAG-EPA supplementation for 130 men who will undergo radical prostatectomy as treatment for a prostate cancer of Gleason score ≥ 7 in an academic cancer center in Quebec City. Participants will be randomized to 6 capsules of 625 mg of fish oil (MAG-EPA) per capsule containing 500 mg of EPA daily or to identically looking capsules of high oleic acid sunflower oil (HOSO) as placebo. The intervention begins 4 to 10 weeks prior to radical prostatectomy (baseline) and continues for one year after surgery. The primary endpoint is the proliferative index (Ki-67) measured in prostate cancer cells at radical prostatectomy. A secondary endpoint includes prostate tissue levels of inflammatory mediators (cytokines and proteins) at time of radical prostatectomy. Changes in blood levels of inflammatory mediators, relative to baseline levels, at time of radical prostatectomy and 12 months after radical prostatectomy will also be evaluated. Secondary endpoints also include important aspects of psychosocial functioning and quality of life such as depression, anxiety, sleep disturbances, fatigue, cognitive complaints and prostate cancer-specific quality of life domains. The changes in these outcomes, relative to baseline levels, will be evaluated at 3, 6, 9 and 12 months after radical prostatectomy. DISCUSSION: The results from this trial will provide crucial information to clarify the role of omega-3 supplementation on prostate cancer proliferation, inflammation and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02333435. Registered on December 17, 2014. Last updated September 6, 2016.

Alterations of fatty acid profiles in gestational diabetes and influence of the diet.

Gestational diabetes mellitus (GDM) is a pregnancy-induced complication with increased prevalence, especially in overweight women. Fatty acid (FA) composition in tissues can reflect dietary fat intake, especially essential FA intake. Moreover, it has been shown that FA profiles in blood lipid fractions are altered in diabetic patients. Consequently, women with GDM may also have a distinctive FA profile. The objective of this review is compare FA profiles in different blood lipid fractions and the influence of dietary fat intake in women with GDM or normoglycemic pregnancies. Results show that women with GDM have more saturated and less polyunsaturated FA (PUFA) in their red blood cell (RBC) membranes than normoglycemic pregnant women. Moreover, some studies reported that women with GDM have a greater energy intake from total fat and saturated FA, along with a lower energy intake from PUFA, when compared to normoglycemic pregnancies. Clinical trials showed that omega-3 PUFA levels in RBC membranes of GDM women can be restored by a dietary intervention. Further research is required to determine whether FA profiles are altered prior to the diagnosis of GDM and can be prevented by diet.