Serum omega-3 fatty acids and treatment outcomes among women undergoing assisted reproduction.
ABSTRACT: STUDY QUESTION:Are serum polyunsaturated fatty acids (PUFA) concentrations, including omega-3 (?3-PUFA) and omega-6 (?6-PUFA), related to ART outcomes? SUMMARY ANSWER:Serum levels of long-chain ?3-PUFA were positively associated with probability of live birth among women undergoing ART. WHAT IS KNOWN ALREADY:Intake of ?3-PUFA improves oocyte and embryo quality in animal and human studies. However, a recent cohort study found no relation between circulating ?3-PUFA levels and pregnancy rates after ART. STUDY DESIGN SIZE, AND DURATION:This analysis included a random sample of 100 women from a prospective cohort study (EARTH) at the Massachusetts General Hospital Fertility Center who underwent 136 ART cycles within one year of blood collection. PARTICIPANTS/MATERIALS, SETTING, METHODS:Serum fatty acids (expressed as percentage of total fatty acids) were measured by gas chromatography in samples taken between Days 3 and 9 of a stimulated cycle. Primary outcomes included the probability of implantation, clinical pregnancy and live birth per initiated cycle. Cluster-weighted generalized estimating equation (GEE) models were used to analyze the association of total and specific PUFAs with ART outcomes adjusting for age, body mass index, smoking status, physical activity, use of multivitamins and history of live birth. MAIN RESULTS AND ROLE OF CHANCE:The median [25th, 75th percentile] serum level of ?3-PUFA was 4.7% [3.8%, 5.8%] of total fatty acids. Higher levels of serum long-chain ?3-PUFA were associated with higher probability of clinical pregnancy and live birth. Specifically, after multivariable adjustment, the probability of clinical pregnancy and live birth increased by 8% (4%, 11%) and 8% (95% CI: 1%, 16%), respectively, for every 1% increase in serum long-chain ?3-PUFA levels. Intake of long-chain ?3-PUFA was also associated with a higher probability of life birth in these women, with RR of 2.37 (95% CI: 1.02, 5.51) when replacing 1% energy of long-chain ?3-PUFA for 1% energy of saturated fatty acids. Serum ?6-PUFA, ratios of ?6 and ?3-PUFA, and total PUFA were not associated with ART outcomes. LIMITATIONS REASONS FOR CAUTION:The generalizability of the findings to populations not undergoing infertility treatment may be limited. The use of a single measurement of serum fatty acids to characterize exposure may lead to potential misclassification during follow up. WIDER IMPLICATIONS OF THE FINDINGS:Serum ?3-PUFA are considered biomarkers of dietary intake. The association of higher serum long chain ?3-PUFA levels with improved ART outcomes suggests that increased intake of these fats be may be beneficial for women undergoing infertility treatment with ART. STUDY FUNDING/COMPETING INTERESTS:NIH grants R01-ES009718 from the National Institute of Environmental Health Sciences, P30-DK046200 and T32-DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases, and L50-HD085359 from the National Institute of Child Health and Human Development, and the Early Life Nutrition Fund from Danone Nutricia US. Dr Rueda is involved in a patent 9,295,662, methods for enhancing, improving, or increasing fertility or reproductive function (http://patents.com/us-9295662.html). This patent, however, does not lead to financial gain for Dr Rueda, or for Massachusetts General Hospital. Dr Rueda does not own any part of the company nor does he have any equity in any fertility related company. As Dr Rueda is not a physician, he does not evaluate patients or prescribe medications. All other coauthors have no conflicts of interest to declare.
Project description:Background: HIV infection and antiretroviral therapy (ART) have both been linked to dyslipidemia and increased cardiovascular disease (CVD) risk. Alterations in the composition of saturated (SaFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids are related to inflammation and CVD progression in HIV-uninfected (HIV-) populations. The relationships among the lipidome and markers of monocyte and immune activation in HIV-infected (HIV+) individuals are not well understood. Methods: Concentrations of serum lipids and their fatty acid composition were measured by direct infusion-tandem mass spectrometry in samples from 20 ART-treated HIV+ individuals and 20 HIV- individuals. Results: HIV+ individuals had increased levels of free fatty acids (FFAs) with enrichment of SaFAs, including palmitic acid (16:0) and stearic acid (18:0), and these levels were directly associated with markers of monocyte (CD40, HLA-DR, TLR4, CD36) and serum inflammation (LBP, CRP). PUFA levels were reduced significantly in HIV+ individuals, and many individual PUFA species levels were inversely related to markers of monocyte activation, such as tissue factor, TLR4, CD69, and SR-A. Also in HIV+ individuals, the composition of lysophosphatidylcholine (LPC) was enriched for SaFAs; LPC species containing SaFAs were directly associated with IL-6 levels and monocyte activation. We similarly observed direct relationships between levels of SaFAs and inflammation in HIV uninfected individuals. Further, SaFA exposure altered monocyte subset phenotypes and inflammatory cytokine production in vitro. Conclusions: The lipidome is altered in ART-treated HIV infection, and may contribute to inflammation and CVD progression. Detailed lipidomic analyses may better assess CVD risk in both HIV+ and HIV- individuals than does traditional lipid profiling.
Project description:Preconceptional folate and vitamin B-12 have been linked to beneficial reproductive outcomes in both natural pregnancies and those after assisted reproductive technology (ART) treatment.The objective of the study was to evaluate the associations of serum folate and vitamin B-12 with ART outcomes.This analysis included a random sample of 100 women (154 ART cycles) participating in a prospective cohort study [Environment and Reproductive Health (EARTH)] at the Massachusetts General Hospital Fertility Center (2007-2013). Serum folate and vitamin B-12 were measured in blood samples collected between days 3 and 9 of treatment. Generalized estimating equations with adjustment for age, BMI, and race were used to evaluate the association of serum folate and vitamin B-12 with ART outcomes.Women in the highest quartile of serum folate (>26.3 ng/mL) had 1.62 (95% CI: 0.99, 2.65) times the probability of live birth compared with women in the lowest quartile (<16.6 ng/mL). Women in the highest quartile of serum vitamin B-12 (>701 pg/mL) had 2.04 (95% CI: 1.14, 3.62) times the probability of live birth compared with women in the lowest quartile (<439 pg/mL). Suggestive evidence of an interaction was observed; women with serum folate and vitamin B-12 concentrations greater than the median had 1.92 (95% CI: 1.12, 3.29) times the probability of live birth compared with women with folate and vitamin B-12 concentrations less than or equal to the median. This translated into an adjusted difference in live birth rates of 26% (95% CI: 10%, 48%; P = 0.02).Higher serum concentrations of folate and vitamin B-12 before ART treatment were associated with higher live birth rates among a population exposed to folic acid fortification. This trial was registered at clinicaltrials.gov as NCT00011713.
Project description:To address limited food frequency questionnaire (FFQ) capacity in public health monitoring in Malaysia, we aimed to develop a semi-quantitative FFQ for an adult multiethnic population for comprehensive fatty acid (FA) profiling inclusive of saturated (SFA), monounsaturated (MUFA), polyunsaturated fatty acids (PUFA), PUFA:SFA ratio, trans fatty acids, omega-3 and omega-6 FAs. A 240-food itemed FFQ used diet records (DR) of Malaysia Lipid Study (MLS) participants and fatty acid composition database from laboratory analyzed foods. The developed MLS-FFQ underwent face and content validation before relative validation in a free-living population (<i>n</i> = 114). Validation was facilitated for macronutrient data comparisons between DR and FFQ via Spearman's correlation coefficient analyses; and for fatty acid composition data by independent pairing of DR, FFQ and plasma triglyceride using the triads method. Moderate correlation between dietary methods was obtained for macronutrients and FAs (<i>r</i> = 0.225-0.457, <i>p</i> < 0.05) except for ?-3 FAs, presenting good agreement with grossly misclassified nutrients <10%. For fatty acid composition data, the magnitude of validity coefficients (<i>z</i>) for SFA, PUFA, PUFA:SFA ratios and ?-6 FAs by all 3 methods were not significantly different (<i>p</i> > 0.05). In conclusion, the MLS-FFQ was shown to be a valid tool to assess population dietary intakes.
Project description:Crohn's disease (CD) has been associated with an increased consumption of n-6 polyunsaturated fatty acid (PUFA), while greater intake of n-3 PUFA has been associated with a reduced risk. We sought to investigate serum fatty acid composition in CD, and associations of fatty acids with disease activity, cytokines, and adipokines. Serum was prospectively collected from 116 CD subjects and 27 non-IBD controls. Clinical disease activity was assessed by the Harvey Bradshaw Index (HBI). Serum fatty acids were measured by gas chromatography. Serum cytokines and adipokines were measured by Luminex assay. Dietary histories were obtained from a subset of patients. Nine serum cytokines and adipokines were increased in CD versus controls. CD subjects had increased percentage serum monounsaturated fatty acids (MUFA), dihomo-gamma linolenic acid (DGLA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and oleic acid, but decreased arachidonic acid (AA) versus controls. The % total n-3 fatty acids and % EPA directly correlated with pro-inflammatory cytokine levels and HBI, whereas the % total n-6 fatty acids were inversely correlated with pro-inflammatory cytokine levels and HBI. CD subjects had increased caloric intake versus controls, but no alterations in total fat or PUFA intake. We found differences in serum fatty acids, most notably PUFA, in CD that correlated both with clinical disease activity and inflammatory cytokines. Our findings indicate that altered fatty acid metabolism or utilization is present in CD and is related to disease activity.
Project description:BACKGROUND: It has been suggested that n-6 and n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) in blood are associated with risk of allergic diseases, although results are inconclusive. Low levels of n-6 LC-PUFA and high levels of n-3 LC-PUFA are anticipated to have beneficial effects. Pregnancy is considered a critical time period for imprinting the developing immune system. We examined whether n-6 LC-PUFA, n-3 LC-PUFA concentrations or the n-6/n-3 ratio in cord blood (CB) serum are associated with allergic diseases up to the age of 10 yr. METHODS: This analysis included 436 children from the Munich LISAplus birth cohort study. Information on doctor-diagnosed asthma, hay fever/allergic rhinitis, and eczema was collected using questionnaires completed at the ages 6 and 10 yr, and for eczema additionally at 2 yr. Specific immunoglobulin E (IgE) against inhalant allergens was measured at 6 and 10 yr. Fatty acid composition was measured by gas chromatography in serum from CB and from blood collected at 2, 6, and 10 yr. Associations between n-3, n-6 LC-PUFA concentrations, and the n-6/n-3 ratio in CB serum and allergic diseases or atopy were assessed using generalized estimating equations (GEE) considering the longitudinal structure. Models were adjusted for LC-PUFA concentrations at follow-up and potential confounding factors. RESULTS: There was no significant association between n-3 LC-PUFA, n-6 LC-PUFA, or the n-6/n-3 ratio in CB serum with eczema, asthma, hay fever/allergic rhinitis, or aeroallergen sensitization. CONCLUSIONS: There is no indication of a beneficial effect of increased n-3 LC-PUFA in CB serum on the development of any of the disease entities.
Project description:High-fat diets (HFD) are commonly used in rodents to induce obesity, increase serum fatty acids and induce lipotoxicity in various organs. In vitro studies commonly utilize individual free fatty acids (FFA) to study lipid exposure in an effort to model what is occurring in vivo; however, these approaches are not physiological as tissues are exposed to multiple fatty acids in vivo. Here we characterize circulating lipids in obesity-prone rats fed an HFD in both fasted and fed states with the goal of developing physiologically relevant fatty acid mixtures for subsequent in vitro studies. Rats were fed an HFD (60% kcal fat) or a control diet (10% kcal fat) for 3 weeks; liver tissue and both portal and systemic blood were collected. Fatty acid profiles and absolute concentrations of triglycerides (TAG) and FFA in the serum and TAG, diacylglycerol (DAG) and phospholipids in the liver were measured. Surprisingly, both systemic and portal serum TAG were ~40% lower in HFD-fed compared to controls. Overall, compared to the control diet, HFD feeding consistently induced an increase in the proportion of circulating polyunsaturated fatty acids (PUFA) with a concomitant decline in monounsaturated fatty acids (MUFA) and saturated fatty acids (SFA) in both serum TAG and FFA. The elevations of PUFA were mostly attributed to increases in n-6 PUFA, linoleic acid and arachidonic acid. In conclusion, fatty acid mixtures enriched with linoleic and arachidonic acid in addition to SFA and MUFA should be utilized for in vitro studies attempting to model lipid exposures that occur during in vivo HFD conditions.
Project description:Ulcerative colitis (UC) is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA). Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines.Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography.UC subjects had increased total fat and oleic acid (OA) intake, but decreased arachidonic acid (AA) intake vs controls. In serum, there was less percent saturated fatty acid (SFA) and AA, with higher monounsaturated fatty acids (MUFA), linoleic acid, OA, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations.In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC.
Project description:BACKGROUND:Randomized trials of supplementation with antioxidant mixtures during infertility treatment show no benefit on pregnancy or live birth rate. However, the roles of individual antioxidants are poorly understood. We examined the association of baseline intake of vitamins A, C, E, and carotenoids with outcomes of assisted reproductive technologies (ARTs). METHODS:We followed 349 women undergoing a total of 588 ART cycles for infertility treatment at the Massachusetts General Hospital. We assessed antioxidant intakes from food and supplements before treatment using a validated food frequency questionnaire. We used generalized linear mixed models to account for multiple ART cycles per woman while adjusting for confounding. RESULTS:Mean (SD) age and body mass index were 35.1 years (4.0 years) and 24.1?kg/m (4.3?kg/m), respectively. Total intake of vitamins A, C, and E was not associated with the probability of live birth. Women in the highest intake category of ?-carotene from foods had a lower probability of live birth than women in the lowest intake quartile (50% vs. 22%; P trend = 0.03); for lutein and zeaxanthin, the probability for the highest intake group was 44% vs. 28% for the lowest. Intake of ?-carotene from supplements and intakes of retinol and all other carotenoids were unrelated to live birth rates. CONCLUSIONS:We found unexpected inverse associations of ?-carotene intake from foods and of lutein and zeaxanthin intake with live birth rates. Within the observed intake ranges, total consumption of vitamins A, C, and E before starting infertility treatment with ART was not associated with live birth rates.
Project description:The relevance of dietary fatty acids (FA) for blood lipids should be assessed in the context of substituting nutrients. Such evidence is lacking for adolescents. This study describes prospective associations of dietary FA with changes in serum lipids during adolescence, and considers the theoretical isocaloric replacements of saturated FA (SFA) with other FA or carbohydrates (CHO). Children from the GINIplus and LISAplus birth cohorts, with data on FA intakes (at age 10 years) and serum lipids (at age 10 and 15 years), were included (n = 1398). Associations of SFA, monounsaturated FA (MUFA), n-3 polyunsaturated FA (n-3 PUFA) and n-6 PUFA, with changes in low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TAG), and total cholesterol to HDL ratio (TOTAL:HDL), were assessed by linear regression. Substitution models assessed isocaloric replacements of SFA with MUFA, n-3 PUFA, n-6 PUFA or CHO. Higher SFA intakes were associated with decreasing TAG. No associations were observed for fatty acid intakes with LDL, HDL or TOTAL:HDL. In females, replacing SFA with CHO was associated with increasing LDL, TAG and TOTAL:HDL. Our findings confirm observations in adults, although sex-specific determinants seem relevant in our adolescent population. Overlooking the nutrient context when limiting SFA intakes might have detrimental consequences appreciable as early as adolescence.
Project description:To study the relation of dietary phytoestrogens intake and clinical outcomes of women undergoing infertility treatment with the use of assisted reproductive technology (ART).Prospective cohort study.Fertility center.A total of 315 women who collectively underwent 520 ART cycles from 2007 to 2013.None.Implantation, clinical pregnancy, and live birth rates per initiated cycle.Soy isoflavones intake was positively related to live birth rates in ART. Compared with women who did not consume soy isoflavones, the multivariable-adjusted odds ratios of live birth (95% confidence interval) for women in increasing categories of soy isoflavones intake were 1.32 (0.76-2.27) for women consuming 0.54-2.63 mg/d, 1.87 (1.12-3.14) for women consuming 2.64-7.55 mg/d, and 1.77 (1.03-3.03) for women consuming 7.56-27.89 mg/d.Dietary soy intake was positively related to the probability of having a live birth during infertility treatment with ART.