An abundance of seafood consumption studies presents new opportunities to evaluate effects on neurocognitive development Publication date: December 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 151 Author(s): Philip Spiller, Joseph R. Hibbeln, Gary Myers, Gretchen Vannice, Jean Golding, Michael A Crawford, J.J. Strain, Sonja L. Connor, J. Thomas Brenna, Penny Kris-Etherton, Bruce J. Holub, William S. Harris, Bill Lands, Robert K. McNamara, Michael F. Tlusty, Norman Salem, Susan E. Carlson Abstract The relationship between seafood eaten during pregnancy and neurocognition in offspring has been the subject of considerable scientific study for over 25 years. Evaluation of this question led two scientific advisory committees to the Dietary Guidelines for Americans (DGAC), the Food and Agriculture Organization of the United Nations with the World Health Organization (FAO/WHO), Health Canada, the European Food Safety Authority (EFSA), and the U.S. Food and Drug Administration (FDA) to conclude through 2014 that seafood consumed by pregnant women is likely to benefit the neurocognitive development of their children. The evidence they reviewed included between four and ten studies of seafood consumption during pregnancy that reported beneficial associations. In contrast there are now 29 seafood consumption studies available describing over 100,000 mothers-child pairs and 15 studies describing over 25,000 children who ate seafood. A systematic review of these studies using Nutrition Evaluation Systematic Review methodology is warranted to determine whether recent research corroborates, builds on, or significantly alters the previous conclusions. Studies that evaluate the integrated effects of seafood as a complete food more directly and completely evaluate impacts on neurocognition as compared to studies that evaluate individual nutritients or toxicological constituents in isolation. Here we address how the findings could add to our understanding of whether seafood consumed during pregnancy and early childhood affects neurocognition, including whether such effects are clinically meaningful, lasting, related to amounts consumed, and affected by any neurotoxicants that may be present, particularly mercury, which is present at varying levels in essentially all seafood. We provide the history, context and rationale for reexamining these questions in light of currently available data.

Effects of prostaglandin E2 and D2 on cell proliferation and osteogenic capacity of human mesenchymal stem cells Publication date: December 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 151 Author(s): C. Ern, I. Frasheri, T. Berger, H.G. Kirchner, R. Heym, R. Hickel, M. Folwaczny Abstract The manifestation of periodontitis-related inflammatory reaction is inevitably bound to the production of prostaglandins E2 and D2 which have been suggested to mediate osteoclastic and osteogenic effects within the affected tissue. We demonstrated the presence of PGE2 and PGD2 receptors on hMSCs on RNA level and with immunofluorescence. For each Prostaglandin, three concentrations were studied: 0.1; 0.5 or 1.0 µg/ml. A lower expression of EP1 and EP4 (PGE2 receptors 1 and 4) after stimulation with PGE2 was shown, thus a tendency to compromise osteogenic differentiation and metabolism. PGE2 induced a higher growth-rate during the first week, while a continuous inflammatory challenge determined a decrease of the proliferation of hMSCs. PGD2 inhibited cell growth irrespective of the duration of the stimulation. PGE2 and PGD2 have also negative effects on calcium deposition osteogenic, thus on differentiation of hMSCs. PGE2 and PGD2 seem to induce bone resorption also having indirectly a negative impact on the osteogenic differentiation of hMSCs. Thus, inhibitors of PGE2 and PGD2 can be used as adjunct to mechanical periodontal treatment.

Different Metabolism of EPA, DPA and DHA in humans: a double-blind cross-over study Publication date: Available online 12 November 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): Xiao-fei Guo, Wen-feng Tong, Yue Ruan, Andrew J. Sinclair, Duo Li Abstract This study aimed to compare eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) incorporated into red blood cells (RBC) phospholipids (PL), plasma PL, plasma triglyceride (TAG), and plasma cholesteryl ester (CE) fractions, and the metabolomics profiles in a double-blind cross-over study. Twelve female healthy subjects randomly consumed 1 gram per day for 6 days of pure EPA, DPA, or DHA. The placebo treatment was olive oil. The fasting venous blood was taken at days 0, 3 and 6, and the RBC PL and plasma lipid fractions were separated for fatty acid determination using thin layer chromatography followed by gas chromatography. Plasma metabolites were analyzed by UHPLC-Q-Exactive Orbitrap/MS. Supplemental EPA significantly increased the concentrations of EPA in RBC PL (days 3 and 6). For subjects consuming the DPA supplement, the concentrations of both DPA and EPA were significantly increased in RBC PL over a 6-day period, respectively. For plasma PL fraction, EPA and DPA supplementation significantly increased the concentrations of EPA and DPA at both days 3 and 6, respectively. Supplemental DHA significantly increased the concentrations of DHA in plasma PL at day 6. For plasma TAG fraction, supplementation with EPA and DPA significantly increased the concentrations of EPA and DPA at both days 3 and 6, respectively. After DHA supplementation, significant increases in the concentrations of DHA were found relative to baseline at both days 3 and 6. For plasma CE fraction, EPA supplementation significantly increased the concentrations of EPA (days 3 and 6) and DPA (days 6), respectively. Supplemental DPA significantly increased the concentrations of EPA at day 6. Meanwhile, the concentrations of DHA were significantly increased over a 6-day period of intervention after subjects consuming the DHA supplements. There were a total of 922 plasma metabolites identified using metabolomics analyses. Supplementation with DPA and DHA significantly increased the levels of sphingosine 1-phosphate (P for DPA = 0.025, P for DHA = 0.029) and 15-deoxy-Δ12,14-prostaglandin A1 (P for DPA = 0.034; P for DHA = 0.021) in comparison with olive oil group. Additionally, supplementation with EPA (P = 0.007) and DHA (P = 0.005) significantly reduced the levels of linoleyl carnitine, compared with olive oil group. This study shows that DPA might act as a reservoir of n-3 LCP incorporated into blood lipid fractions, metabolized into DHA, and retro-converted back to EPA. Metabolomics analyses indicate that supplemental EPA, DPA and DHA have shared and differentiated metabolites. The differences of these metabolic biomarkers should be investigated in additional studies.

Breast milk and erythrocyte fatty acid composition of lactating women residing in a peri-urban South African township Publication date: Available online 6 November 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): Linda P. Siziba, Tsitsi Chimhashu, Sicelosethu S. Siro, Jennifer Osei Ngounda, Adriaan Jacobs, Linda Malan, Cornelius M. Smuts, Jeannine Baumgartner Abstract Data on breast milk fatty acid (FA) composition in South African lactating women in relation to their FA status, as well as on potential compositional changes within feed, are limited. The aim of this study was to assess the FA composition of breast milk sampled at three time points within feed, and to determine associations with red blood cell (RBC) total phospholipid FA levels in lactating South African mothers of 2-4-month-old breastfed infants. FA composition (% total FAs) was analyzed in RBC total phospholipids, and in fore-, mid-feed and hind-milk samples of lactating mothers (n=100) of Black African descent living in a peri-urban township. The mean age of the lactating women was 27.8 ± 6.8 years. Geometric mean (95% CI) breast milk saturated FA, MUFA and PUFA contents were 37.7 (37.3,38.1), 28.5 (27.9, 28.8), and 23.5 (23.2, 24.5)%, respectively. Breast milk DHA and AA contents were 0.25 (0.24, 3.71) and 0.81 (0.79, 0.83)%, respectively, in fore-, mid- and hind-milk combined. Maternal RBC EPA, DHA and AA levels were 0.37 (0.34, 0.40), 3.8 (3.6, 4.0) and 15.4 (14.8, 16.1)%, respectively. Women who reported to consume fish often (n=3) had significantly higher RBC EPA levels than women who consumed fish sometimes (n = 56), never (n=14) or rarely (n=19). Breast milk DHA positively correlated with maternal RBC DHA, while no correlations were found between breast milk AA and maternal RBC AA. Breast milk ALA and DHA contents were significantly higher in mid-feed [ALA= 0.8 (0.2, 0.2), DHA=0.3 (0.2, 0.3)] and hind-milk [ALA=0.8 (0.8, 0.9), DHA=0.3 (0.3, 0.3)] than foremilk [ALA=0.8 (0.7, 0.9), DHA=0.2 (0.2, 0.3)]. In contrast, LA and AA contents remained constant within feed. In this sample of peri-urban South African lactating mothers, breast milk was low in DHA and high in AA compared to global means. Breast milk DHA was associated with maternal RBC status, while breast milk AA was not. We further showed that breast milk ALA and DHA increased, while LA and AA remained unchanged within feed. This suggests that n-3 PUFA maybe preferentially transferred to breast milk within feed through biomagnification.

Association of Vitamin D with Fatty Acids in Pregnancy Publication date: Available online 6 November 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): A. Nandi, N. Wadhwani, K. Randhir, G. Wagh, S.R. Joshi Abstract Preeclampsia is a pregnancy complication, associated with an increased risk of maternal and neonatal morbidity and mortality. The etiology of preeclampsia is not yet fully understood, although the current literature indicates an up regulation of inflammatory mediators. Vitamin D is known to have anti-inflammatory properties and influence vascular function. Fatty acids are also known to regulate inflammation in pregnancy. This study was carried out to explore the association of maternal vitamin D and fatty acids in pregnancy. The present study includes 69 normotensive control (NC) and 50 women with preeclampsia (PE). Maternal and cord serum 25-hydroxyvitamin D [25(OH)D] levels were lower (p<0.01for both) in women with PE compared to NC women. Maternal plasma total polyunsaturated fatty acids (PUFA) levels were lower (p<0.05) while levels of total saturated fatty acids (SFA) and total monounsaturated fatty acids (MUFA) were higher (p<0.05 for both) in women with PE. Cord erythrocyte PUFA levels were higher (p<0.01) in PE women. Maternal 25(OH)D levels were negatively associated with maternal systolic and diastolic BP (p<0.01 for both). Maternal 25(OH)D levels were positively associated with maternal total PUFA (p<0.01) and negatively associated with maternal total SFA (p<0.05), total MUFA (p<0.01). This study for the first time demonstrates an association of maternal vitamin D with fatty acid levels in pregnancy. Our results suggest that vitamin D and fatty acids may work in concert to regulate fetal growth. Graphical Abtract

Umbilical Cord Blood Stearoyl-CoA Desaturase index and Lipoprotein Lipase Mass Level in Small-for-Gestational Age Newborns Publication date: Available online 6 November 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): Kazumasa Fuwa, Nobuhiko Nagano, Yohei Kitamura, Fujihiko Iwata, Tomoo Okada, Ichiro Morioka Abstract We previously reported that triglyceride (TG) levels in small-for-gestational age (SGA) newborns were significantly higher than those in appropriate-for-gestational age (AGA) newborns. Stearoyl-CoA desaturase (SCD) activity is required for TG synthesis, while lipoprotein lipase mass (LPLm) facilitates TG clearance. The purpose of this study is to reveal whether SCD activity or LPLm is the cause of high TG levels in SGA newborns. Fifty-five newborns were classified as AGA (n=42) and SGA (n=13). Serum LPLm, TG and fatty acids in umbilical cord blood were analyzed. Then, [16:1 (n-7)]/ [16:0] and [18:1 (n-9)]/ [18:0] were calculated as SCD16 and SCD18 activities, respectively. The SGA group showed significantly higher TG levels and significantly lower LPLm levels than the AGA group. However, SCD16 and 18 activities were lower in SGA newborns than in AGA newborns. In conclusion, LPLm, rather than SCD activity may be involved in the increased TG levels in SGA newborns.

Associations of erythrocyte fatty acid compositions with FADS1 gene polymorphism in Japanese mothers and infants Publication date: Available online 6 November 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): Reiko Nita, Terue Kawabata, Yasuo Kagawa, Kazuhiro Nakayama, Yoshiko Yanagisawa, Sadahiko Iwamoto, Fumiko Kimura, Teruo Miyazawa, Nozomi Tatsuta, Takahiro Arima, Nobuo Yaegashi, Kunihiko Nakai Abstract Long-chain polyunsaturated fatty acids (LC-PUFAs) are involved in the fetal growth in utero, and are essential for the development of visual and cognitive functions during infancy. The purpose of this study was to examine the associations of erythrocyte fatty acid compositions with FADS1 gene polymorphism in Japanese mothers and infants. The subjects were 383 mothers who participated in an adjunct birth cohort study of the Japan Environment and Children's Study (JECS). In maternal FADS1 SNP genotypes, the precursor fatty acids composition of the Δ5 desaturase in the maternal blood showed significant differences in levels among the groups, and showed increasing values in the order of TT < TC < CC genotype groups. On the other hand, many product fatty acids levels were significantly reduced in the order of TT > TC > CC genotype groups, and DHA levels were significantly lower in the CC genotype group relative to the other groups. Likewise, the relationship between fetal genotype group and fatty acid composition in cord blood was very similar to the maternal relationship. These results indicate the maternal and fetal blood fatty acid compositions are strongly influenced by the FADS1 genotypes. With respect to the cord blood DHA composition, the levels in the fetal CC genotype group showed a trend toward lower values in the maternal CC genotype group pair (p = 0.066) compared to the maternal TC genotype group pair. However, in the fetal TT and TC genotype groups (p = 0.131, p =0.729, respectively), the maternal genotype did not have a significant effect. The DHA composition was more influenced by the maternal genotype in the fetal CC genotype group than in the fetal TT and TC genotype groups. It was shown that DHA transport via the placenta from the mother might be promoted in the fetal CC genotype compared to the other fetal genotype groups. In conclusion, differences in the FADS1 SNP genotypes of pregnant women and their children may greatly affect the supply of LC-PUFAs. Further studies on the involvement of the FADS1 polymorphisms and the fetal LC-PUFA levels in the fetal growth and development are warranted.

Development and evaluation of a simultaneous and efficient quantification strategy for final prostanoid metabolites in urine Publication date: Available online 6 November 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): Tian-qi Zhang, Hirotaka Kuroda, Kazuya Nagano, Soshi Terada, Jian-Qing Gao, Kazuo Harada, Kazumasa Hirata, Hirofumi Tsujino, Kazuma Higashisaka, Hiroshi Matsumoto, Yasuo Tsutsumi Abstract Prostanoids (PNs) play critical roles in various physiological and pathological processes. Therefore, it is important to understand the alternation of PN expression profiles. However, a simultaneous and efficient quantification system for final PN metabolites in urine has not yet been established. Here, we developed and evaluated a novel method to quantify all final PN metabolites. By purification using a reverse phase solid phase extraction (SPE) column, the matrix effects against the final PGD2, PGE2, and PGF2α metabolites were low, and their accuracies were nearly 100%. The matrix effects against the final PGI2 and TXA2 metabolites were high using reverse phase SPE column purification alone. By applying a tandem SPE method that combined reverse phase and ion exchange SPE columns, the matrix effects decreased so that the accuracy was nearly 100%. To validate the reliability of the method, each final metabolite was quantified from mouse urine to which the PNs (PGD2, PGE2, and PGI2) were intravenously administered. As a result, the amounts of PN metabolites were correlated with those of the PNs administered to the blood in a dose-dependent manner. To validate the method using human samples, the urinary metabolites of Crohn's disease (CD, a PN-related disease) patients and healthy individuals were quantified. All five metabolites were successfully quantified. Only final PGE2 metabolite levels were significantly higher in CD patients than those in healthy individuals, so that the urinary metabolite profiles of CD patients is determined. In conclusion, we developed a novel method to quantify all final PN metabolites simultaneously and efficiently and demonstrated the practicality of the method using human CD patient samples.

ISSFAL Official Statement Number 6 The importance of measuring blood omega-3 long chain polyunsaturated fatty acid levels in research Publication date: Available online 6 November 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): Renate H.M. de Groot, Barbara J. Meyer Abstract A statement on measuring blood omega-3 long chain polyunsaturated fatty acid levels developed and edited based on input from ISSFAL members and accepted by vote of the ISSFAL Board of Directors. Summary of Statement: Omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) levels at baseline and post-intervention should be assessed and reported in future research to evaluate the efficacy of n-3 LCPUFA supplementation Because: 1. There are numerous factors that affect n-3 LCPUFA levels in humans as described in the systematic literature review [1]. 2. Assessing intake of n-3 LCPUFA from the diet and/or supplements is not sufficient to accurately determine n-3 LCPUFA levels in humans. 3. Some studies do not provide sufficient doses of n-3 LCPUFA to produce a significant impact on bloodstream/organ content and there is substantial variability in the uptake of n-3 LPCUFA into tissues between individuals. In secondary analyses, clinical trials should consider the influence of fatty acid status (baseline, endpoint and change from baseline to endpoint) on the outcome variables.

Intravenous fat induces changes in PUFA and their bioactive metabolites: Comparison between Japanese and Australian preterm infants. Publication date: Available online 6 November 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): Hiroki Suganuma, Andrew J McPhee, Carmel T Collins, Ge Liu, Shalem Leemaqz, Chad C Andersen, Naho Ikeda, Natsuki Ohkawa, Ameer Y Taha, Robert A Gibson Abstract Objective Oxylipins are biologically active signaling molecules that initiate and resolve inflammation; they are synthesized by oxidation of polyunsaturated fatty acids (PUFAs) and reflect PUFA intake and status. The PUFA intake in preterm infants differs between countries because of the type of lipid emulsions used and the PUFA content of breast milk. We compared total blood PUFA, free PUFA and their oxylipin levels in dried whole blood samples from preterm infants born in Australia and Japan. Methods We enrolled 30 and 14 preterm infants born less than 31 weeks’ gestation, from Adelaide and Japan respectively. Blood samples were obtained from cord blood, and on postnatal days 4, 7, 14 and 28. Total PUFAs were measured using gas chromatography, while free fatty acids and oxylipins were screened using ultra high-performance liquid chromatography mass spectroscopy. Results Differences in the levels of blood PUFA between the centres were found which were in line with the timing and type of lipid emulsion administration. Significant differences in longitudinal levels were seen more often in free PUFA and their oxylipins than in total blood PUFA. This was particularly true for AA and DHA. In contrast, differences in the levels could be seen in total blood EPA, as well as in free EPA and its oxylipins. Further, levels of many free PUFA and their oxylipins were higher in Japanese infants than in Australian infants. Conclusion Differences in total and free fatty acids and unesterified oxylipins, were observed during the first weeks of life and between preterm infants born in Australia and Japan, which were likely a reflection of the type of lipid emulsion and timing of administration. The clinical significance of these changes remains to be explored.