Long-chain Polyunsaturated Fatty Acid Status Research Articles

The role of polyunsaturated fatty acids in the neurobiology of major depressive disorder and suicide risk.

Long-chain polyunsaturated fatty acids (LC-PUFAs) are obtained from diet or derived from essential shorter-chain fatty acids, and are crucial for brain development and functioning. Fundamentally, LC-PUFAs' neurobiological effects derive from their physicochemical characteristics, including length and double bond configuration, which differentiate LC-PUFA species and give rise to functional differences between n(omega)-3 and n-6 LC-PUFAs. LC-PUFA imbalances are implicated in psychiatric disorders, including major depression and suicide risk. Dietary intake and genetic variants in enzymes involved in biosynthesis of LC-PUFAs from shorter chain fatty acids influence LC-PUFA status. Domains impacted by LC-PUFAs include 1) cell signaling, 2) inflammation, and 3) bioenergetics. 1) As major constituents of lipid bilayers, LC-PUFAs are determinants of cell membrane properties of viscosity and order, affecting lipid rafts, which play a role in regulation of membrane-bound proteins involved in cell-cell signaling, including monoaminergic receptors and transporters. 2) The n-3:n-6 LC-PUFA balance profoundly influences inflammation. Generally, metabolic products of n-6 LC-PUFAs (eicosanoids) are pro-inflammatory, while those of n-3 LC-PUFAs (docosanoids) participate in the resolution of inflammation. Additionally, n-3 LC-PUFAs suppress microglial activation and the ensuing proinflammatory cascade. 3) N-3 LC-PUFAs in the inner mitochondrial membrane affect oxidative stress, suppressing production of and scavenging reactive oxygen species (ROS), with neuroprotective benefits. Until now, this wealth of knowledge about LC-PUFA biomechanisms has not been adequately tapped to develop translational studies of LC-PUFA clinical effects in humans. Future studies integrating neurobiological mechanisms with clinical outcomes may suggest ways to identify depressed individuals most likely to respond to n-3 LC-PUFA supplementation, and mechanistic research may generate new treatment strategies.

Maternal omega-3 LC-PUFA supplementation programs an improved bone mass in the offspring with a more pronounced effect in females than males at adulthood

Early balanced nutrition is vital in achieving optimal skeletal mass and its maintenance. Although a lower omega-6 (n-6): omega-3 (n-3) long-chain polyunsaturated fatty acid (LC-PUFA) ratio is strongly linked with bone health, its maternal effect in the programming of the offspring's skeleton remains to be elucidated. Plugged C57BL/6 mice were fed either n-3 LC-PUFA Enriched Diet (LED) or a control diet (C) throughout their gestation and lactation. Offspring born to both the groups were weaned onto C till 6, 12, and 24 weeks of their age. Offspring's skeleton metabolism and serum fatty acid composition was studied. In humans, seventy-five mother-female newborns pairs from term gestation were tested for their maternal LC-PUFA status relationships to venous cord blood bone biomarkers. Offspring of maternal LED supplemented mice exhibited a superior bone phenotype over C, more prominent in females than males. A lower serum n-6/n-3 LC-PUFA in the LED group offspring was strongly associated with blood biomarkers of bone metabolism. Sexual dimorphism evidenced had a strong correlation between offspring's LC-PUFA levels and bone turnover markers in serum. A higher potential for osteoblastic differentiation in both LED offspring genders and reduced osteoclastogenesis in females was cell-autonomous effect. The human cross-sectional study also showed a positive correlation between maternal n-3 PUFA and cord blood markers of bone formation in female newborns at birth. Maternal dietary n-6/ n-3 fat quality determines offspring's bone growth and development. Our data suggest that the skeleton of female offspring is likely to be more sensitive to this early exposure.

Maternal Plasma Glycerophospholipids LC-PUFA Levels Have a Sex-Specific Association with the Offspring's Cord Plasma Glycerophospholipids-Fatty Acid Desaturation Indices at Birth.

Fatty acid desaturases, the enzymes responsible for the production of unsaturated fatty acids (FA) in fetal tissues, are known to be influenced by maternal-placental supply of nutrients and hormones for their function. We hypothesize that there could be a gender-specific regulation of unsaturated FA metabolism at birth, dependent on the maternal fatty acid levels. In this study, 153 mother-newborn pairs of uncomplicated and 'full-term' pregnancies were selected and the FA composition of plasma glycerophospholipids (GP) was quantified by gas chromatography. The FA composition of mother blood plasma (MB) was compared with the respective cord blood plasma (CB) of male newborns or female newborns. Product to substrate ratios were estimated to calculate delta 5 desaturase (D5D), delta 6 desaturase (D6D) and delta 9 stearoyl-CoA-desaturase (D9D/SCD) indices. Pearson correlations and linear regression analyses were employed to determine the associations between MB and CB pairs. In the results, the male infant's MB-CB association was positively correlated with the SCD index of carbon-16 FA, while no correlation was seen for the SCD index of carbon-18 FA. Unlike for males, the CB-D5D index of female neonates presented a strong positive association with the maternal n-6 long chain-polyunsaturated FA (LC-PUFA), arachidonic acid. In addition, the lipogenic desaturation index of SCD18 in the CB of female new-borns was negatively correlated with their MB n-3 DHA. In conclusion, sex-related differences in new-borns' CB desaturation indices are associated with maternal LC-PUFA status at the time of the birth. This examined relationship appears to predict the origin of sex-specific unsaturated FA metabolism seen in later life.

Long-Chain Polyunsaturated Fatty Acid Status at Birth and Development of Childhood Allergy: A Systematic Review.

The associations of fetal fatty acids status to immune-related health parameters later in life are unclear. Our aim is to collect all available information on the relationship between fatty acid status at birth and allergy in childhood. Systematic literature search was performed on Ovid MEDLINE, Cochrane Library, and Embase. The search retrieved 897 articles without duplicates; 14 articles remained after excluding those that did not fit into our inclusion criteria. When the dichotomous parameter of suffering or not from allergic condition in childhood was analyzed, cord blood eicosapentaenoic acid (EPA) values proved to be significantly lower in allergic than non-allergic children in four comparisons from three studies. When the linear parameters of odds ratios and relative risks for allergy were taken into consideration, high cord blood EPA, but also high docosahexaenoic acid (DHA) and high total n-3 long-chain polyunsaturated fatty acid values were associated to clinically relevant reduction (at least 38%) in eight comparisons from five studies. Within the cord blood samples, higher EPA, docosapentaenoic acid, and DHA values were significantly and negatively associated in eight correlation analyses from three studies with laboratory parameters considered to reflect allergic trait. The data reported here may provide information for defining optimal fatty acid intakes for pregnant women.

Maternal and Neonatal Polyunsaturated Fatty Acid Intake and Risk of Neurodevelopmental Impairment in Premature Infants.

The N3 and N6 long chain polyunsaturated fatty acids (LCPUFA) docosahexaenoic acid (DHA) and arachidonic acid (AA) are essential for proper neurodevelopment in early life. These fatty acids are passed from mother to infant via the placenta, accreting into fetal tissues such as brain and adipose tissue. Placental transfer of LCPUFA is highest in the final trimester, but this transfer is abruptly severed with premature birth. As such, efforts have been made to supplement the post-natal feed of premature infants with LCPUFA to improve neurodevelopmental outcomes. This narrative review analyzes the current body of evidence pertinent to neurodevelopmental outcomes after LCPUFA supplementation in prematurely born infants, which was identified via the reference lists of systematic and narrative reviews and PubMed search engine results. This review finds that, while the evidence is weakened by heterogeneity, it may be seen that feed comprising 0.3% DHA and 0.6% AA is associated with more positive neurodevelopmental outcomes than LCPUFA-deplete feed. While no new RCTs have been performed since the most recent Cochrane meta-analysis in 2016, this narrative review provides a wider commentary; the wider effects of LCPUFA supplementation in prematurely born infants, the physiology of LCPUFA accretion into preterm tissues, and the physiological effects of LCPUFA that affect neurodevelopment. We also discuss the roles of maternal LCPUFA status as a modifiable factor affecting the risk of preterm birth and infant neurodevelopmental outcomes. To better understand the role of LCPUFAs in infant neurodevelopment, future study designs must consider absolute and relative availabilities of all LCPUFA species and incorporate the LCPUFA status of both mother and infant in pre- and postnatal periods.

Long-chain polyunsaturated fatty acid (LC-PUFA) status in severe preeclampsia and preterm birth: a cross sectional study

Long-Chain Polyunsaturated Fatty Acid (LCPUFA) is essential throughout pregnancy, since deficiency of LPUFA may linked to obstetrical complications. This study aimed to investigate LCPUFA status in severe preeclampsia and preterm birth. A cross sectional study was conducted in 104 pregnant women, which divided into normal pregnancy, severe preeclampsia and preterm birth groups. Serum percentage and concentration of total LCPUFA, omega-3, alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), omega-6, linoleic acid (LA), and arachidonic acid (AA) were measured using gas chromatography/mass spectrometry. Receiver operating characteristic (ROC), bivariate and multivariate analysis were performed. Severe preeclampsia showed the highest concentration of total PUFA and the lowest DHA percentage, with significantly higher Omega-6/Omega-3 ratio (p = 0.004) and lower omega-3 index (p < 0.002) compared to control. Preterm birth showed the least omega-3 concentrations, with significantly low omega-6 derivates (LA (p = 0.014) and AA (p = 0.025)) compared to control. LCPUFA parameters have shown to increase the risk in both conditions, particularly ALA ≤ 53 µmol/L in preeclampsia with OR 5.44, 95%CI 1.16–25.42 and preterm birth with OR 4.68, 95%CI 1.52–14.38. These findings suggest that severe preeclampsia and preterm birth have an imbalance in LCPUFA status.

Maternal long-chain polyunsaturated fatty acid status during early pregnancy: Association with child behavioral problems and the role of autonomic nervous system activity

The prenatal environment, including availability of critical nutrients, has a profound impact on offspring development. The present study examined the association between maternal long-chain polyunsaturated fatty acid (LC-PUFA) status during pregnancy and later child behavioral problems at the age of 5-6 years. In light of evidence of autonomic nervous system (ANS) dysregulation in some behavioral problems, study further tested if the above association is statistically mediated by cardiac ANS activity. Data was collected as part of the Amsterdam Born Children and their Development-study and complete data were available for 1717 mothers and their offspring. Maternal LC-PUFA status was assessed during early pregnancy (mean gestation=12.7, SD=2.5 weeks) and quantified as levels of docosahexenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (EPA), as well as the ratio of n-6:n-3 fatty acids. Child emotional problems and peer problems (internalizing problems), as well as conduct problems and inattention/hyperactivity (externalizing problems), were assessed using the Strengths and Difficulties Questionnaire as rated by the mother and teacher at 5-6 years. Child cardiac respiratory sinus arrhythmia (RSA), pre-ejection period (PEP), and heart rate (HR) were utilized as measures of ANS activity at 5-6 years. The results confirmed an association between maternal LC-PUFA status and internalizing behavioral problems as rated by the mother, as shown for DHA (β=-0.11;p<0.01), EPA (β=-0.22;p<0.05), and n-6:n-3 LC-PUFA (β=0.17;p<0.01). Statistical mediation was only demonstrated for HR. No associations were observed between LC-PUFA status and externalizing behavioral problems. The present results are consistent with a role of maternal LC-PUFA status in internalizing behavioral problems as rated by the mother. These results were not observed when problem behavior was rated by the teacher. Analyses did not yield strong evidence supporting ANS activity as a possible mediator in this relationship.

Levels of n-3 and n-6 Fatty Acids in Maternal Erythrocytes during Pregnancy and in Human Milk and Its Association with Perinatal Mental Health

Omega-3 long-chain polyunsaturated fatty acid (n-3 FA) status may be associated with mood disorders. Here, we evaluated the potential association between antenatal depression/anxiety and n-3/n-6 FA in (a) maternal erythrocytes and (b) human milk. In addition, we explored associations between n-3/n-6 FA in erythrocytes and in human milk and postpartum depression, while controlling for antenatal depression. Twenty-seven pregnant women diagnosed with a current major depressive disorder (MDD; n = 9), anxiety disorder (AD; n = 10) or a mixed anxiety-depression disorder (MADD; n = 8), and 40 healthy controls were included. n-3/n-6 FA were determined in maternal erythrocytes in gestational week 32 and in human milk in postpartum week 1. In the first week postpartum, the Edinburgh-Postnatal-Depression-Questionnaire was used to assess postpartum depression. Results show that women with M(A)DD had significantly lower erythrocyte levels of total n-3 FA, EPA, DHA and DGLA, and significantly higher n-6 DPA, and n-6:n-3, AA:EPA and n-6 DPA:DHA ratios compared to healthy controls. No significant associations between antenatal depression or anxiety and n-3/n-6 FA in human milk were found. After controlling for antenatal mental health, n-3/n-6 FA in maternal erythrocytes or in human milk were not significantly associated with postpartum depression. In conclusion, antenatal depression, alone or with an anxiety disorder, was associated with lower n-3 FA levels and higher n-6:n-3 FA ratios in maternal erythrocytes during gestation. This study provides some insights into the associations between n-3/n-6 FA levels during pregnancy and lactation and perinatal mental health.

Does polymorphisms in PPAR and APOE genes modify associations between fatty acid desaturase (FADS), n-3 long-chain PUFA and cardiometabolic markers in 8-11-year-old Danish children?

n-3 Long-chain PUFA (LCPUFA) can improve cardiometabolic blood markers, but studies in children are limited. SNP in the FADS genes, which encode fatty acid desaturases, influence endogenous LCPUFA production. Moreover, SNP in genes that encode PPAR and apoE may modulate the effects of n-3 LCPUFA. We explored whether FADS polymorphisms were associated with blood cholesterol and TAG, insulin and glucose and whether polymorphisms in PPAR and APOE modified associations between FADS or n-3 LCPUFA status and the cardiometabolic blood markers. We measured fasting cholesterol and TAG, insulin, glucose and n-3 LCPUFA in 757 Danish 8-11-year-old children and genotyped SNP in FADS (rs1535 and rs174448), PPARG2 (rs1801282), PPARA (rs1800206) and APOE (rs7412+rs429358). Carriage of two FADS rs174448 major alleles was associated with lower TAG (P = 0·027) and higher HDL-cholesterol (P = 0·047). Blood n-3 LCPUFA was inversely associated with TAG and insulin in PPARG2 minor allele carriers and positively with LDL-cholesterol in major allele homozygotes (Pn-3 LCPUFA × rs180182 < 0·01). Associations between n-3 LCPUFA and cardiometabolic markers were not modified by APOE genotype (Pn-3 LCPUFA × APOE > 0·11), but interaction between FADS rs1535 and APOE showed that rs1535 major allele homozygotes who also carried APOE2 had higher HDL-cholesterol than all other genotype combinations (Prs1535 × APOE = 0·019, pairwise-P < 0·05). This indicates that FADS genotypes, which increase endogenous LCPUFA production, may beneficially affect children's cardiometabolic profile in a partly APOE-dependent manner. Also, the degree to which children benefit from higher n-3 LCPUFA intake may depend on their PPARG2 genotype.

Increased adiposity in children with obesity is associated with low red blood cell omega-3 fatty acid status and inadequate polyunsaturated fatty acid dietary intake.

The association between total dietary fat intake and measures of body fatness in children with obesity remains inconsistent. This study aimed to determine whether dietary long-chain polyunsaturated fatty acids (LCPUFA) and LCPUFA status relate to body composition in children with obesity. Children (n = 63, 9.0 ± 0.2 year, BMI Z-score 3.1 ± 0.2) were divided into tertiles of percentage body fat assessed by dual-energy X-ray absorptiometry. Diet was assessed 3-days food diaries. Fatty acid proportions in red blood cells (RBC) were measured by gas chromatography. Data stratified by sex and Tanner stages were compared with a MIXED model ANOVA. Associations between RBC fatty acid status and dietary intakes were examined with Spearman correlation. Moderate correlations were observed between RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) proportions, dietary EPA and DHA (r = 0.39, P < .05) as well as fish servings (r = 0.33, P < .05). Dietary LCPUFA did not differ among tertiles. Children in tertile 3 had lower RBC α-linolenic acid (-40%) and EPA + DHA (-15%) proportions adjusted for age, Tanner stages and race compared with tertile 1. The lower omega-3 LCPUFA status in children with greater adiposity is consistent with suboptimal intakes of omega-3 LCPUFA and fish in the diet.

Maternal Long-Chain Polyunsaturated Fatty Acid Status, Methylmercury Exposure, and Birth Outcomes in a High-Fish-Eating Mother–Child Cohort

Maternal status of long-chain PUFAs (LC-PUFAs) may be related to fetal growth. Maternal fish consumption exposes the mother to the neurotoxicant methylmercury (MeHg), which, in contrast, may restrict fetal growth. Our aim was to examine relations between maternal LC-PUFA status at 28 wk and birth outcomes (birth weight, length, and head circumference), controlling for MeHg exposure throughout pregnancy, in the Seychelles Child Development Study Nutrition Cohort 2. Our secondary aim was to examine the influence of maternal variation in genes regulating the desaturation of LC-PUFAs [fatty acid desaturase (FADS)] on birth outcomes. From nonfasting blood samples collected at 28 wk of gestation, we measured serum total LC-PUFA concentrations and FADS1 (rs174537, rs174561), FADS1-FADS2rs3834458, and FADS2rs174575 genotypes, with hair total mercury concentrations assessed at delivery. Data were available for n=1236 mother-child pairs. Associations of maternal LC-PUFAs, MeHg, and FADS genotype with birth outcomes were assessed by multiple linear regression models, adjusting for child sex, gestational age, maternal age, BMI, alcohol use, socioeconomic status, and parity. In our cohort of healthy mothers, neither maternal LC-PUFA status nor MeHg exposure were significant determinants of birth outcomes. However, when compared with major allele homozygotes, mothers who were heterozygous for the minor allele of FADS1 (rs174537 and rs174561, GT compared with TT, β = 0.205, P=0.03; TC compared with CC, β = 0.203, P=0.04) and FADS1-FADS2 (rs3834458, Tdel compared with DelDel, β = 0.197, P=0.04) had infants with a greater head circumference (all P<0.05). Homozygosity for the minor allele of FADS2 (rs174575) was associated with a greater birth weight (GG compared with CC, β = 0.109, P=0.04). In our mother-child cohort, neither maternal LC-PUFA status nor MeHg exposure was associated with birth outcomes. The observed associations of variation in maternal FADS genotype with birth outcomes should be confirmed in other populations.

Methylmercury and long chain polyunsaturated fatty acids are associated with immune dysregulation in young adults from the Seychelles child development study.

BackgroundExposure to the environmental toxicant mercury (Hg) has been associated with immune dysregulation, including autoimmune disease, but few human studies have examined methylmercury (MeHg) exposure from fish consumption. ObjectivesWe examined associations between MeHg exposure and biological markers of autoimmunity and inflammation while adjusting for long chain polyunsaturated fatty acids (LCPUFA). MethodAt age 19 years, hair total Hg (Y19Hg), LCPUFA status, a panel of 13 antinuclear antibodies (ANA), total serum immunoglobulins (Ig) IgG, IgA, and IgM and serum markers of inflammation (IL-1, IL-2, IL-6, IL-10, C-reactive protein (CRP), IFN-γ, TNF-α) were measured in the Seychelles Child Development Study (SCDS) Main Cohort (n = 497). Multivariable regression models investigated the association between Y19Hg and biomarkers, adjusting for prenatal total hair Hg (MatHg) and other relevant covariates, and with and without adjustment for LCPUFA. ResultsWith each 1 ppm increase in Y19Hg (mean 10.23 (SD 6.02) ppm) we observed a 4% increased odds in a positive Combined ANA following adjustment for the n6:n3 LCPUFA ratio (β = 0.036, 95%; CI: 0.001, 0.073). IgM was negatively associated with Y19Hg (β = −0.016, 95%CI: 0.016, −0.002) in models adjusted for n-3, n-6 LCPUFA and when separately adjusted for the n-6:n-3 LCPUFA ratio. No associations were observed with MatHg. Total n-3 LCPUFA status was associated with reduced odds of a positive anti-ribonuclear protein (RNP) A. The n-3 LCPUFA were negatively associated with IL-6, IL-10, CRP, IFN-γ, TNF-α and positively with TNF-α:IL-10. There were positive associations between the n-6:n-3 ratio and IL-6, IL-10, CRP, IFN-γ, TNF-α and a negative association with TNF-α:IL-10. DiscussionThe Y19Hg exposure was associated with higher ANA and lower IgM albeit only following adjustment for the n-3 LCPUFA or the n-6:n-3 LCPUFA ratio. The clinical significance of these findings is unclear, but warrant follow up at an older age to determine any relationship to the onset of autoimmune disease.

Associations between methylmercury, n-3 polyunsaturated fatty acids and antinuclear antibodies in young adults from the Seychelles Child Development Study (SCDS).

AbstractThe association of MeHg exposure through fish consumption on human autoimmunity remains unclear. Fish also contain n-3 long chain polyunsaturated fatty acids (LCPUFA) that are known to regulate inflammation and mitigate autoimmune disease symptoms. We studied the association of low-level exposure to methylmercury (MeHg) through fish consumption in the SCDS. We examined this association at age 19 years in the SCDS Main Cohort (n = 497). We measured MeHg exposure at 3 time points [prenatal, weighted average (6 months to 19 years) and concurrent (19 years) and LCPUFA status and a panel of 13 autoimmune markers at age 19 years. The autoimmune markers included antinuclear antibodies (ANA), anti-dsDNA and anti-RNP, and total (non-specific) immunoglobulins (Ig) IgG, IgA, and IgM. A combined ANA variable was also calculated based on being within or above reference range for any of the ANA markers; 56% of the subjects met this criterion. Multivariable regression models adjusted for prenatal MeHg, sex and waist circumference, with and without adjustment for LCPUFA, were fit for the three MeHg exposure metrics and each immune marker. Mean (SD) prenatal, weighted average and concurrent MeHg was 6.84 (4.55), 7.46 (2.82), and 10.23 (6.02) ppm, respectively. Combined ANA was positively associated with concurrent MeHg following adjustment for the n6:n3 LCPUFA ratio (β = 0.036, 95%; CI: 0.001, 0.073). Prenatal and average MeHg exposures were not significantly associated with any individual ANA. IgM was negatively associated with concurrent (β = -0.016, 95%CI: -0.016, -0.002), and average (β = -0.042, 95%CI: -0.042, -0.009) MeHg exposure in the models adjusted for n-3, n-6 LCPUFA and when separately adjusted for the n6:n3 LCPUFA ratio. Total (19-year) n-3 PUFA status was negatively associated with anti-RNP (β = -20.355, 95%CI: -36.89, -4.34) and IgG (β = -1.384, 95%CI: -2.682, -0.087). Total n-3 LCPUFA was associated with lower markers of autoimmunity. MeHg exposure at 19 years was associated with higher ANA and lower IgM but only following adjustment for LCPUFA. The clinical significance of these findings is unclear and further research is warranted to determine if these associations precede autoimmune disease development.

Maternal and neonatal red blood cell n-3 polyunsaturated fatty acids inversely associate with infant whole-body fat mass assessed by dual-energy X-ray absorptiometry.

Research regarding polyunsaturated fatty acid (PUFA) status and body composition in neonates is limited. This study tested the relationship between newborn docosahexaenoic acid (DHA) status and body composition. Healthy mothers and their term-born infants (n = 100) were studied within 1 month postpartum for anthropometry and whole-body composition using dual-energy X-ray absorptiometry. Maternal and infant red blood cell (RBC) membrane PUFA profiles were measured using gas chromatography (expressed as percentage of total fatty acids). Data were grouped according to infant RBC DHA quartiles and tested for differences in n-3 status and infant body composition using mixed-model ANOVA, Spearman correlations, and regression analyses (P < 0.05). Mothers were 32.2 ± 4.6 years (mean ± SD) of age, infants (54% males) were 0.68 ± 0.23 month of age, and 80% exclusively breastfed. Infant RBC DHA (ranged 3.96% to 7.75% of total fatty acids) inversely associated with infant fat mass (r = -0.22, P = 0.03). Infant and maternal RBC n-6/n-3 PUFA ratio (r2 = 0.28, P = 0.043; r2 = 0.28, P = 0.041 respectively) were positively associated with fat mass. These results demonstrate that both maternal and infant long-chain PUFA status are associated with neonatal body composition. Novelty Our findings support an early window to further explore the relationship between infant n-3 PUFA status and body composition. Maternal and infant n-3 PUFA status is inversely related to neonatal whole-body fat mass. DHA appears to be the best candidate to test in the development of a lean body phenotype.

Efficacy of novel small-quantity lipid-based nutrient supplements in improving long-chain polyunsaturated fatty acid status of South African infants: a randomised controlled trial.

The objective of this study was to investigate the efficacy of small-quantity lipid-based nutrient supplements (SQ-LNS) containing essential fatty acids (EFAs) with or without long-chain polyunsaturated fatty acids (LCPUFAs) in improving LCPUFA status in South African infants fed complementary food. Six-month-old infants (n = 750) were randomised to receive SQ-LNS, SQ-LNS-plus, or no supplement. Both SQ-LNSs contained micronutrients and EFAs. SQ-LNS-plus additionally contained the LCPUFAs arachidonic acid (AA) and docosahexaenoic acid (DHA), lysine, phytase and other nutrients. Plasma total phospholipid FA composition (% of total FAs) was measured at baseline (n = 353) and at 12 months (n = 293). At baseline, geometric mean (95% CI) plasma DHA and AA were 4.1 (4.0-4.3) and 11.5 (11.2-11.8)% respectively, with significantly higher plasma DHA and AA in breastfed than non-breastfed infants. Infants receiving the SQ-LNS-plus had significantly higher plasma DHA (4.52 (4.3-4.9)) at 12 months than the controls (3.8 (3.6-4.0)), with a higher effect size in infants who no longer received breast milk (β = 1.148 (95% CI = 0.597, 1.699)) than in infants who were still breastfeeding (β = 0.544 (95% CI = 0.179, 0.909)). There was no effect of either of the two SQ-LNSs on plasma AA. Consequently, infants receiving the SQ-LNS-plus had a significantly lower plasma n-6 to n-3 PUFA ratio at 12 months than control infants did. Our study suggests that the provision of SQ-LNS-plus is efficacious in improving plasma DHA status. Particularly, infants who are no longer breastfed may benefit most from LCPUFA-enriched SQ-LNS.

Omega-3 Uzun Zincirli Çoklu Doymamış Yağ Asitleri ve Fenilketonüri

Beyin, retina ve diğer sinir dokuları uzun zincirli çoklu doymamış yağ asitlerinden (UZÇDYA) zengindir. Birçok klinik ve epidemiyolojik çalışma ile omega-3 UZÇDYA’ların çocukluk çağındaki nöral gelişim üzerine olumlu etkileri olduğu kanıtlanmıştır. Uzun zincirli ÇDYA’lar, diyetle alımları yeterli olduğu sürece temel elzem yağ asitlerinden endojen olarak sentezlenebilirler. Aynı zamanda, et, balık, yumurta, karaciğer ve süt ürünleri gibi proteinden zengin besinler eikosapentaenoik asit (EPA) ve dokosaheksaenoik asit (DHA) gibi UZÇDYA’ların en belirgin diyetsel kaynaklarıdır. Bununla birlikte, klasik fenilketonürili (FKÜ) hastalar yüksek plazma fenilalanin konsantrasyonları ve nörolojik hasarı önlemek için diyet protein alımında sıkı ve ömür boyu süren bir sınırlamaya ihtiyaç duyarlar. Bu katı metabolik kontrol sadece düşük miktarda vitamin ve mineral sağlamakla kalmaz, genellikle doymuş yağ asitleri ve ÇDYA’ların da düşük miktarda alınmasına neden olur. Bu nedenle, FKÜ’lü hastalar sağlıklı kontrollerle karşılaştırıldığında UZÇDYA alımları daha az olmakta ve daha düşük plazma ve eritrosit UZÇDYA konsantrasyonlarına sahip olmaktadırlar. Bebeklik ve çocukluk döneminde, UZÇDYA’lar normal nörogelişim için önemlidir. Yetersizliği, okul öncesi ve okul çağındaki FKÜ’lü çocuklarda erken dönemde saptanabilen merkezi sinir sistemi işlev bozukluklarına katkıda bulunabilir. Ayrıca, UZÇDYA yetersizliğinin kronik nörolojik, inflamatuvar ve metabolik bozukluklara neden olabileceği de ileri sürülmektedir. Diğer taraftan, randomize kontrollü çalışmalardan elde edilen veriler, FKÜ’lü hastalardaki UZÇDYA durumunun diyet takviyesi ile iyileştirilebileceğini önermektedir. Bu derleme yazıda, fenilalaninden kısıtlı diyetler ile UZÇDYA arasındaki ilişki incelenmiş ve FKÜ’lü hastalar için UZÇDYA’ların önemi ele alınmıştır.

Long-chain polyunsaturated fatty acid status in first-trimester pregnant women

Background: The beneficial effects of long-chain polyunsaturated fatty acid (LCPUFA) on maternal health have been widely investigated in pregnant women. First-trimester supplementation of LCPUFA has been reported to play a role in the inflammatory response, thus reducing a preterm birth and preeclampsia. However, there is a lack of studies investigating the blood concentration of LCPUFA in pregnant women in Indonesia. This study was conducted to evaluate the status of LCPUFA in first-trimester pregnant women in Jakarta, Indonesia.Methods: A descriptive study was conducted using the secondary data of 197 pregnant women in their first trimester who received antenatal care in Budi Kemuliaan Hospital during February 2012 to April 2015. Nutrient intake data were collected through interviews conducted using a semi-quantitative frequency food questionnaire (SQ-FFQ). Total concentrations of linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were measured using gas-chromatography/mass spectrometry (GC-MS). Statistical analysis of the data was conducted using SPSS 20.0.Results: Most subjects had deficient blood concentrations of LA (74.1%), AA (85.3%), ALA (76.6%), and DHA (73.1%). The median total concentrations of LA, AA, ALA, EPA, and DHA were as follows: 76.08%, 14.97%, 2.64%, 6.36%, and 1.18%, respectively. The median EPA+DHA level was 7.98%. A total of 38 women (19.3%) were classified as high-risk subjects based on the omega-3 index. No correlation was observed between total DHA+EPA concentration and birth weight (r=0.027, p=0.709). However, a significant difference was detected between the concentrations of LA, AA, and ALA and the maternal body mass index (p&lt;0.05).Conclusion: Most subjects had low intake and blood concentrations of LA, AA, ALA, EPA, and DHA in the first trimester of pregnancy.

Prenatal n-3 long-chain fatty acid status and offspring metabolic health in early and mid-childhood: results from Project Viva

Higher maternal and biomarker levels of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) have been associated with improved perinatal outcomes and may also influence offspring metabolic health. Past studies were not powered to examine metabolic outcomes and few have specifically targeted metabolically vulnerable populations. We examined the associations of prenatal n-3 LCPUFA status with markers of metabolic health in early and mid-childhood in the full population as well as stratified by maternal glucose tolerance. Our data consisted of 1418 mother–child dyads from Project Viva, a longitudinal, prospective pre-birth cohort enrolled in eastern Massachusetts. We assessed maternal dietary intake of fish and n-3 LCPUFA in mid-pregnancy using a validated food frequency questionnaire. N-3 LCPUFA levels were quantified in maternal second trimester and umbilical cord plasma using liquid-gas chromatography. We assessed offspring anthropometry, adiposity, and blood pressure at early (median age: 3.2 years) and mid-childhood (median age: 7.7 years); and assayed blood samples collected at these visits for metabolic biomarkers. We report here multivariable effect estimates and 95% CI. Early childhood BMI z-score was on average 0.46 (1.03) units and waist circumference 51.3 (3.7) cm. At mid-childhood these measures were 0.39 (1.00) units and 60.0 (8.3) cm, respectively. Higher cord plasma DHA levels were associated with lower BMI z-score ((Q)uartile 4 vs. Q1: −0.21, 95% CI: −0.38, −0.03), waist circumference (Q4 vs. Q1: −0.63, 95% CI: −1.27, 0.00 cm), and leptin levels (Q4 vs. Q1: −0.36, 95% CI: −0.77, 0.05 ng/mL) in early childhood. These associations were strongest and reached significance in offspring of women with isolated hyperglycemia vs. better or worse glycemic status. Higher maternal DHA + EPA (Q4 vs. Q1: −1.59, 95% CI: −2.80, −0.38 μg/mL) and fish (≥3 vs. 0 portions/week: −2.18, 95% CI: −3.90, −0.47 μg/mL) intake was related to lower adiponectin in early childhood. None of these associations persisted with mid-childhood outcomes. We did not find associations with any of the other outcomes. This study supports early and possibly transient effects of prenatal n-3 LCPUFA status on anthropometric measures and adipokine levels. It also raises the possibility that offspring of women with isolated hyperglycemia derive the most benefits from higher n-3 LCPUFA status.

Incorporation of Dairy Lipids in the Diet Increased Long-Chain Omega-3 Fatty Acids Status in Post-weaning Rats.

In human nutrition, optimized the status of n-3 long-chain polyunsaturated fatty acids (LCPUFA) and especially docosahexaenoic acid (DHA) during growth appears to be one of the most important goal. We investigated the potential impact of a partial incorporation of dairy lipids (DL) in the diet to increase the n-3 LCPUFA content in tissues, compared to a mixture of vegetable oils. Rats were fed with vegetable oil diet or DL diet, supplemented or not supplemented with DHA, from weaning for 6 weeks. All diets provided the same quantity of 2.3% of total fatty acids of precursor α-linolenic acid. LCPUFA levels in brain, retina, liver, heart, red blood cells and epididymal adipose tissue, Δ-6 desaturase activity and mRNA expression in liver, and plasma cholesterol were measured. Rats fed a DL diet increased their DHA content in brain and retina compared with rats fed a vegetable oil diet and reached the same level than rats directly supplemented with DHA. The status of n-3 docosapentaenoic acid increased with DL diet in heart, red blood cells and liver. The n-3 docosapentaenoic acid specifically discriminated DL diets in the heart. DL diet increased α-linolenic acid content in liver and epididymal adipose tissue, provided specific fatty acids as short- and medium-chain fatty acids and myristic acid, and increased plasma cholesterol. We hypothesized that dairy lipids may increase the n-3 LCPUFA enrichment in tissues by preserving precursor α-linolenic acid from β-mitochondrial oxidation, associated with the presence of short- and medium-chain fatty acids in DL diets. In conclusion, a partial incorporation of dairy lipids in the diet with an adequate α-linolenic acid content improved the n-3 LCPUFA status, especially DHA in brain and retina.

Effect of a daily snack containing green leafy vegetables on women's fatty acid status: a randomized controlled trial in Mumbai, India.

There are few data on the fatty acid status of non-pregnant Indian women. Our objective was to investigate the effect of a snack containing green leafy vegetables (GLVs) on women's erythrocyte long chain polyunsaturated fatty acid status (LCPUFA). Non-pregnant women (n=222) aged 14-35 years from Mumbai slums were randomized to consume a snack containing GLVs, fruit and milk (treatment) or a control snack containing foods of low micronutrient content such as potato and onion, daily under observation. One treatment snack contained a mean (SD) of 54.1 (33.7) mg alpha-linolenic acid (ALA) and one control snack contained 4.1 (3.4) mg ALA. Blood was collected at baseline (0 weeks) and after 12 weeks of supplementation. Erythrocyte fatty acids were analyzed using gas chromatography and expressed as g/100g fatty acids. Plasma malondialdehyde, homocysteine, and erythrocyte superoxide dismutase and glutathione peroxidase were measured. The effect of the treatment on 12 week LCPUFA was assessed using ANCOVA models. Median (IQR) erythrocyte DHA in the treatment group increased from 1.50 (1.11, 2.03) at baseline to 1.86 (1.50, 2.43) (p<0.001) at 12 weeks, and fell in controls from 1.78 (1.37, 2.32) to 1.60 (1.32, 2.04) (p<0.001). The total n-3 fatty acids increased in the treatment group. There was no effect on malondialdehyde and antioxidant enzyme levels. Plasma homocysteine at 0 and 12 weeks was inversely associated with erythrocyte DHA at 12 weeks. Daily consumption of a snack containing GLV improved women's erythrocyte DHA levels without increasing oxidative stress.