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Background: Very-long-chain SFAs (VLSFAs) have recently gained considerable attention as having beneficial effects on health and aging., Objectives: The objective of this study was to assess the associations of plasma phospholipid VLSFAs [arachidic acid (20:0), behenic acid (22:0), tricosanoic acid (23:0), and lignoceric acid (24:0)] with 20-y cognitive decline in the Atherosclerosis Risk in Communities (ARIC) participants. Furthermore, this study compared the associations of plasma phospholipid VLSFAs with 5 common groups of fatty acids [i.e., total SFAs, total MUFAs, total ω-3 (n-3) PUFAs, total marine-derived ω-3 PUFAs, total ω-6 PUFAs]., Methods: This study used a cohort study design of 3229 ARIC participants enrolled at the Minnesota field center. Fatty acids were measured at visit 1 (1987-1989); and cognition was assessed at visits 2 (1990-1992), 4 (1996-1998), and 5 (2011-2013) using 3 tests: the Delayed Word Recall Test (DWRT), the Digit-Symbol Substitution Test (DSST), and the Word Fluency Test (WFT)., Results: Higher proportions of plasma phospholipid total VLSFAs and each individual VLSFA were associated with less decline in WFT, a test of verbal fluency. For example, 1 SD higher in total VLSFAs at baseline was associated with 0.057 SD (95% CI: 0.018, 0.096, P = 0.004) less cognitive decline over 20 y as measured by WFT score. None of the 5 common fatty acid groups were associated with change in WFT, but a higher proportion of plasma phospholipid total MUFAs was associated with greater decline in DWRT; higher total ω-6 PUFAs with less decline in DWRT; and higher total ω-3 and total marine-derived ω-3 PUFAs with less decline in DSST., Conclusions: This study suggests that higher proportions of plasma phospholipid VLSFAs in midlife may be associated with less 20-y cognitive decline., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Subclinical hypothyroidism (SCH) is a common endocrine disorder affecting women of reproductive age. Although SCH and abnormal fatty acid composition are often associated with adverse pregnancy outcomes and metabolic syndrome later in maternal and fetal life, the longitudinal relationship between SCH and serum fatty acids during pregnancy has rarely been studied. Therefore, the aim of this study was to investigate the association between SCH and maternal serum fatty acids throughout gestation. A total of 240 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) study in Chongqing, China were included in our study. Clinical information and maternal serum samples were collected at three time points during pregnancy: 11-14 th , 22-28 th , and 32-34 th weeks of gestation. Twenty serum fatty acids were quantified using gas chromatography-mass spectrometry (GC-MS) analysis. A majority of the 20 serum fatty acids increased as gestation progressed in women with a normal pregnancy and women experiencing SCH. Levels of arachidic acid, docosahexaenoic acid, and eicosenoic acid were significantly higher in the serum of women with SCH when compared to women with a normal pregnancy, in the second trimester. On the other hand, the levels of eicosadienoic acid and octadecanoic acid were significantly higher in SCH in the third trimester. Our findings demonstrate that serum fatty acid composition during the second and third trimesters was significantly associated with SCH in pregnant Chinese women.

Background: Ceramides exhibit multiple biological activities that may influence the pathophysiology of heart failure. These activities may be influenced by the saturated fatty acid carried by the ceramide (Cer). However, the associations of different circulating Cer species, and their sphingomyelin (SM) precursors, with heart failure have received limited attention., Methods and Results: We studied the associations of plasma Cer and SM species with incident heart failure in the Cardiovascular Health Study. We examined 8 species: Cer and SM with palmitic acid (Cer-16 and SM-16), species with arachidic acid (Cer-20 and SM-20), species with behenic acid (Cer-22 and SM-22), and species with lignoceric acid (Cer-24 and SM-24). During a median follow-up of 9.4 years, we identified 1179 cases of incident heart failure among 4249 study participants. In Cox regression analyses adjusted for risk factors, higher levels of Cer-16 and SM-16 were associated with higher risk of incident heart failure (hazard ratio for one SD increase:1.25 [95% CI, 1.16-1.36] and 1.28 [1.18-1.40], respectively). In contrast, higher levels of Cer-22 were associated with lower risk of heart failure in multivariable analyses further adjusted for Cer-16 (hazard ratio, 0.85 [0.78-0.92]); and higher levels of SM-20, SM-22 and SM-24 were associated with lower risk of heart failure in analyses further adjusted for SM-16 (hazard ratios, 0.83 [0.77-0.90], 0.81 [0.75-0.88], and 0.83 [0.77-0.90], respectively). No statistically significant interactions with age, sex, black race, body mass index, or baseline coronary heart disease were detected. Similar associations were observed for heart failure with preserved (n=529) or reduced (n=348) ejection fraction., Conclusions: This study shows associations of higher plasma levels of Cer-16 and SM-16 with increased risk of heart failure and higher levels of Cer-22, SM-20, SM-22, and SM-24 with decreased risk of heart failure., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00005133.

The effect of saturated fatty acids (SFAs) on incident type 2 diabetes (T2D) is controversial and few have systematically appraised the evidence. We conducted a comprehensive search of prospective studies examining these relationships that were published in PubMed, Web of Science, or EMBASE from 21 February 1989 to 21 February 2019. A total of 19 studies were included for systematic review and 10 for meta-analysis. We estimated the summarized relative risk (RR) and 95% confidence interval (95% CI) using a random (if I 2 > 50%) or a fixed effects model (if I 2 ≤ 50%). Although the included studies reported inconclusive results, the majority supported a protective effect of odd-chain and an adverse impact of even-chain SFAs. Meta-analysis showed that the per standard deviation (SD) increase in odd-chain SFAs was associated with a reduced risk of incident T2D (C15:0: 0.86, 0.76-0.98; C17:0: 0.76, 0.59-0.97), while a per SD increase in one even-chain SFA was associated with an increased risk of incident T2D (C14:0: 1.13, 1.09-1.18). No associations were found between other SFAs and incident T2D. In conclusion, our findings suggest an overall protective effect of odd-chain SFAs and the inconclusive impact of even- and very-long-chain SFAs on incident T2D., Competing Interests: The authors declare no conflict of interest.

Background: Saturated fatty acids (SFAs) of different chain lengths have unique metabolic and biological effects, and a small number of recent studies suggest that higher circulating concentrations of the very-long-chain SFAs (VLSFAs) arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) are associated with a lower risk of diabetes. Confirmation of these findings in a large and diverse population is needed., Objective: We investigated the associations of circulating VLSFAs 20:0, 22:0, and 24:0 with incident type 2 diabetes in prospective studies., Methods: Twelve studies that are part of the Fatty Acids and Outcomes Research Consortium participated in the analysis. Using Cox or logistic regression within studies and an inverse-variance-weighted meta-analysis across studies, we examined the associations of VLSFAs 20:0, 22:0, and 24:0 with incident diabetes among 51,431 participants., Results: There were 14,276 cases of incident diabetes across participating studies. Higher circulating concentrations of 20:0, 22:0, and 24:0 were each associated with a lower risk of incident diabetes. Pooling across cohorts, the RR (95% CI) for incident diabetes comparing the 90th percentile to the 10th percentile was 0.78 (0.70, 0.87) for 20:0, 0.84 (0.77, 0.91) for 22:0, and 0.75 (0.69, 0.83) for 24:0 after adjustment for demographic, lifestyle, adiposity, and other health factors. Results were fully attenuated in exploratory models that adjusted for circulating 16:0 and triglycerides., Conclusions: Results from this pooled analysis indicate that higher concentrations of circulating VLSFAs 20:0, 22:0, and 24:0 are each associated with a lower risk of diabetes., (Copyright © American Society for Nutrition 2019.)

Background Circulating very-long-chain saturated fatty acids ( VLSFAs ) are integrated biomarkers of diet and metabolism that may point to new risk pathways and potential targets for heart failure ( HF ) prevention. The associations of VLSFA to HF in humans are not known. Methods and Results Using a cohort study design, we studied the associations of serially measured plasma phospholipid VLSFA with incident HF in the Cardiovascular Health Study. We investigated the associations of time-varying levels of the 3 major circulating VLSFAs , lignoceric acid (24:0), behenic acid (22:0), and arachidic acid (20:0), with the risk of incident HF using Cox regression. During 45030 person-years among 4249 participants, we identified 1304 cases of incident HF , including 489 with preserved and 310 with reduced ejection fraction. Adjusting for major HF risk factors and other circulating fatty acids, higher levels of each VLSFAs were associated with lower risk of incident HF ( P trend≤0.0007 each). The hazard ratio comparing the highest quintile to the lowest quintile was 0.67 (95% confidence interval, 0.55-0.81) for 24:0, 0.72 (95% confidence interval, 0.60-0.87) for 22:0 and 0.72 (95% confidence interval, 0.59-0.88) for 20:0. The associations were similar in subgroups defined by sex, age, body mass index, coronary heart disease, and diabetes mellitus. Among those with ejection fraction data, the associations appeared similar for those with preserved and with reduced ejection fraction. Conclusions Higher levels of circulating VLSFAs are associated with lower risk of incident HF in older adults. These novel associations should prompt further research on the role of VLSFA in HF , including relevant new risk pathways. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 00005133.

The association between circulating saturated fatty acids (SFAs) and incident type 2 diabetes (T2D) is reported in Western populations with inconsistent results, while evidence from Asian populations is scarce. We aimed to examine the associations between erythrocyte SFAs and incident T2D in a Chinese population. Between 2008 and 2013, a total of 2683 participants, aged 40⁻75 years, free of diabetes were included in the present analyses. Incident T2D cases were ascertained during follow-up visits. Gas chromatography was used to measure erythrocyte fatty acids at baseline. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). During 13,508 person years of follow-up, 216 T2D cases were identified. Compared with the first quartile, multivariable-adjusted HRs (95% CIs) of the fourth quartile were 1.20 (0.82⁻1.76; p = 0.242) for myristic acid (14-carbon tail, zero double bonds; 14:0), 0.69 (0.48⁻0.99; p = 0.080) for palmitic acid (16:0), 1.49 (1.02⁻2.19; p = 0.047) for stearic acid (18:0), 1.46 (1.00⁻2.12; p = 0.035) for arachidic acid (20:0), 1.48 (0.99⁻2.22; p = 0.061) for behenic acid (22:0), and 1.08 (0.74⁻1.56; p = 0.913) for lignoceric acid (24:0). Our findings indicate that individual erythrocyte SFAs are associated with T2D in different directions, with 18:0 and 20:0 SFAs positively associated with the risk, whereas no convincing inverse association for 16:0 SFAs., Competing Interests: The authors declare no conflicts of interest.

Background: Not much is known about the relations of circulating saturated fatty acids (SFAs), which are influenced by both metabolic and dietary determinants, with total and cause-specific mortality., Objective: We examined the associations of plasma phospholipid SFAs with total and cause-specific mortality among 3941 older adults from the Cardiovascular Health Study, a population-based prospective study of adults aged ≥65 y who were followed from 1992 through 2011., Methods: The relations of total and cause-specific mortality with plasma phospholipid palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) were assessed using Cox proportional hazards models., Results: During 45,450 person-years of follow-up, 3134 deaths occurred. Higher concentrations of the plasma phospholipid SFAs 18:0, 22:0, and 24:0 were associated with a lower risk of total mortality [multivariable-adjusted HRs (95% CIs)] for the top compared with the bottom quintile: 0.85 (0.75, 0.95) for 18:0; 0.85 (0.75, 0.95) for 22:0; and 0.80 (0.71, 0.90) for 24:0. In contrast, plasma 16:0 concentrations in the highest quintile were associated with a higher risk of total mortality compared with concentrations in the lowest quintile [1.25 (1.11, 1.41)]. We also found no association of plasma phospholipid 20:0 with total mortality., Conclusions: These findings suggest that the associations of plasma phospholipid SFAs with the risk of death differ according to SFA chain length and support future studies to better characterize the determinants of circulating SFAs and to explore the mechanisms underlying these relations., (© 2016 American Society for Nutrition.)

Background: Circulating saturated fatty acids (SFAs) are integrated biomarkers of diet and metabolism that may influence the pathogenesis of diabetes. In epidemiologic studies, circulating levels of palmitic acid (16:0) are associated with diabetes; however, very-long-chain SFAs (VLSFAs), with 20 or more carbons, differ from palmitic acid in their biological activities, and little is known of the association of circulating VLSFA with diabetes., Objective: By using data from the Cardiovascular Health Study, we examined the associations of plasma phospholipid VLSFA levels measured at baseline with subsequent incident diabetes., Design: A total of 3179 older adults, with a mean age of 75 y at study baseline (1992-1993), were followed through 2011. We used multiple proportional hazards regression to examine the associations of arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) with diabetes., Results: Baseline levels of each VLSFA were cross-sectionally associated with lower triglyceride levels and lower circulating palmitic acid. We identified 284 incident diabetes cases during follow-up. Compared with the lowest quartile, levels of arachidic acid in the highest quartile of the fatty acid distribution were associated with a 47% lower risk of diabetes (95% CI: 23%, 63%; P-trend: <0.001), after adjustment for demographics, lifestyle factors, and clinical conditions. In analogous comparisons, levels of behenic and lignoceric acid were similarly associated with 33% (95% CI: 6%, 53%; P-trend: 0.02) and 37% (95% CI: 11%, 55%; P-trend: 0.01) lower diabetes risk, respectively. Adjustment for triglycerides and palmitic acid attenuated the associations toward the null, and only the association of arachidic acid remained statistically significant (32% lower risk for fourth vs. first quartile; P-trend: 0.04)., Conclusions: These results suggest that circulating VLSFAs are associated with a lower risk of diabetes, and these associations may be mediated by lower triglycerides and palmitic acid. The study highlights the need to distinguish the effects of different SFAs and to explore determinants of circulating VLSFAs. This trial was registered at clinicaltrials.gov as NCT00005133., (© 2015 American Society for Nutrition.)

Background: Prior studies suggest that circulating fatty acids may influence the risk of atrial fibrillation (AF), but little is known about the associations of circulating saturated fatty acids with risk of AF., Methods and Results: The study population included 2899 participants from the Cardiovascular Health Study, a community-based longitudinal cohort of adults aged 65 years or older in the United States who were free of prevalent coronary heart disease and AF in 1992. Cox regression was used to assess the association of all the long-chain saturated fatty acids-palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0)-with incident AF. During a median of 11.2 years of follow-up, 707 cases of incident AF occurred. After adjustment for other AF risk factors, higher levels of circulating 16:0 were associated with a higher risk of AF (hazard ratio comparing highest and lowest quartiles: 1.48; 95% CI: 1.18, 1.86). In contrast, higher levels of circulating 18:0, 20:0, 22:0, and 24:0 were each associated with a lower risk of AF. The hazard ratios (95% CI) for AF in the top and bottom quartiles were 0.76 (95% CI: 0.61, 0.95) for 18:0; 0.78 (95% CI: 0.63, 0.97) for 20:0; 0.62 (95% CI: 0.50, 0.78) for 22:0; and 0.68 (95% CI: 0.55, 0.85) for 24:0., Conclusions: Results from this prospective cohort study of older adults demonstrate divergent associations of circulating 16:0 versus longer-chain saturated fatty acids with incident AF, highlighting the need to investigate both determinants of these levels and potential pathways of the observed differential risk., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Cytochrome P450 (CYP)-dependent metabolites of arachidonic acid (AA) contribute to the regulation of cardiovascular function. CYP enzymes also accept EPA and DHA to yield more potent vasodilatory and potentially anti-arrhythmic metabolites, suggesting that the endogenous CYP-eicosanoid profile can be favorably shifted by dietary omega-3 fatty acids. To test this hypothesis, 20 healthy volunteers were treated with an EPA/DHA supplement and analyzed for concomitant changes in the circulatory and urinary levels of AA-, EPA-, and DHA-derived metabolites produced by the cyclooxygenase-, lipoxygenase (LOX)-, and CYP-dependent pathways. Raising the Omega-3 Index from about four to eight primarily resulted in a large increase of EPA-derived CYP-dependent epoxy-metabolites followed by increases of EPA- and DHA-derived LOX-dependent monohydroxy-metabolites including the precursors of the resolvin E and D families; resolvins themselves were not detected. The metabolite/precursor fatty acid ratios indicated that CYP epoxygenases metabolized EPA with an 8.6-fold higher efficiency and DHA with a 2.2-fold higher efficiency than AA. Effects on leukotriene, prostaglandin E, prostacyclin, and thromboxane formation remained rather weak. We propose that CYP-dependent epoxy-metabolites of EPA and DHA may function as mediators of the vasodilatory and cardioprotective effects of omega-3 fatty acids and could serve as biomarkers in clinical studies investigating the cardiovascular effects of EPA/DHA supplementation., (Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.)

Background: Fatty acid (FA)-alterations may mediate the mutual association between Major Depressive Disorder (MDD) and cardiovascular disease (CVD). However, etiology of observed FA-alterations in MDD and CVD remains largely unclear. An interesting candidate may be a mutation in the fatty acid-binding protein 2 (FABP2)-gene, because it regulates dietary FA-uptake. Therefore, we aimed to test the hypotheses that in MDD-patients the FABP2 Ala54Thr-polymorphism would be (I) more prevalent than in sex- and age-matched controls, (II) associated with observed alterations in FA-metabolism, and (III) associated with CVD-risk factor waist circumference., Methods: We measured concentrations of 29 different erythrocyte FAs, FABP2-genotype, and waist circumference in recurrent MDD-patients and matched never-depressed controls., Results: FABP2-genotype distribution did not significantly differ between the 137 MDD-patients and 73 matched controls. However, patients with the Ala54Thr-polymorphism had (I) higher concentrations of especially eicosadienoic acid (C20:2ω6; P=.009) and other 20-carbon FAs, and associated (II) lower waist circumference (P=.019). In addition, FABP2-genotype effects on waist circumference in patients seemed (I) mediated by its effect on C20:2ω6, and (II) different from controls., Conclusions: Although Ala54Thr-polymorphism distribution was not associated with recurrent MDD, our results indicate that FABP2 may play a role in the explanation of observed FA-alterations in MDD. For Ala54Thr-polymorphism patients, potentially adaptive conversion of increased bioavailable dietary precursors into eicosadienoic acid instead of arachidonic acid might be related to a low waist circumference. Because this is the first investigation of these associations, replication is warranted, preferably by nutrigenetic studies applying lipidomics and detailed dietary assessment.

Unlabelled: Cornus wilsoniana Wanger is a woody oil plant distributed in the south region of the Yellow River, China. Its oil has been taken as edible oil for over 100 y, and consumption of such oil is believed to prevent hyperlipidemia in Chinese folk recipe. This study has investigated the hypolipidemic effect of Cornus wilsoniana oil (CWO) in Sprague-Dawley rats. The results demonstrated that CWO could significantly decrease total cholesterol (TC), total triacylglycerol (TG), and low-density lipoprotein cholesterol (HDL-C) in serum, liver weight, hepatic TC, and TG. After analyzing the chemical constituents of CWO, we found that the content of unsaturated fatty acids (UFA) was very high (69.12%). Specially, the n-6 polyunsaturated fatty acids (PUFA), including linoleic acid, γ-linolenic acid, and 11,14-eicosadienoic acid, accounted very great proportion (38.86%). The high hypolipidemic activity of CWO might be attributed to the lipid-lowering functions of these polyunsaturated fatty acids. Molecular docking was further performed to study the binding model of fatty acids (FA) from CWO to a possible hypolipidemic target, peroxisome proliferator-activated receptor δ (PPARδ). The results showed that linoleic acid and γ-linolenic acid could bind PPARδ very well., Practical Application: Cornus wilsoniana oil could be used as equilibrated dietary oil, not only having hypolipidemic function, but also helping to overcome essential fatty acids deficiency., (© 2012 Institute of Food Technologists®)

The aim of this study was to investigate whether fatty acid profile is a suitable marker for diagnostic purposes in mouse melanoma. Twelve C57Bl/6 male mice were implanted with B16 mouse melanoma cells (106 cells/animal) orthotopically (subcutaneously). After the implantation 4-4 animals were bled by cardiac puncture following narcosis, at days 7, 14, and 21. In order to investigate fatty acid profiles a method based on extraction and HPLC-MS was developed. Signal intensities of 14 fatty acids were determined by mass spectrometry in tumor-free animals as well as tumor bearing animals at the three time points. Mathematical analysis showed non-significant profile changes when control (tumor-free) animals were compared to tumor-implanted ones as well as during tumor progression on week 1, 2 and 3. In case of three fatty acids (myristic acid, palmitoleic acid and eicosadienoic acid) a trend was observed during tumor progression but its statistical significance cannot be evaluated without further investigations. The fatty acid profile cannot be used for early diagnoses in mouse melanoma.

Aim: To explore the relationship between essential fatty acids (FA) and weight changes in adolescent girls with eating disorders (ED)., Methods: Blood samples were obtained from 220 girls with ED and 39 healthy controls. The girls with ED were 15.3 ± 1.5 years of age and weighed 49.8 ± 8.7 kg (BMI 18.3 ± 2.8 kg/m(2)) after a weight loss of 6.8 ± 6.4 kg. FA were analysed in plasma phospholipids (PPL) and erythrocyte membranes (ERY)., Results: The proportions of saturated and monounsaturated FA were increased during weight loss, while linoleic acid (18:2ω6) was decreased. The proportions of eicosapentanoic acid (EPA) (20:5ω3) and docosahexanoic acid (DHA) (22:6ω3) in PPL and ERY did not differ from controls. The activity of stearoyl-CoA-desaturase was increased as evidenced by an increased product/precursor ratio and correlated with the rate of weight loss. The activities of delta-6-desaturase and delta-5-desaturase did not differ from controls. The rate of weight loss was inversely correlated with delta-6-desaturase and directly correlated with delta-5-desaturase., Conclusion: The FA profile indicates low-fat intake, fat mobilization from stores and an increased conversion of essential FA at the delta-5-desaturase step during weight loss in adolescent girls with ED. Normal levels of EPA and DHA were maintained., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Peroxisomal disorders are characterized biochemically by elevated levels of very long chain fatty acids (VLCFAs) in serum. Herein, we describe a novel approach for quantification of VLCFAs in serum, namely, eicosanoic acid (C20:0), docosanoic acid (C22:0), tetracosanoic acid (C24:0), and hexacosanoic acid (C26:0). The methodology is based on (i) enrichment of VLCFA derivatives using multiwalled carbon nanotubes (MWCNTs); (ii) quantification using stable isotope-labeled internal standards; and (iii) direct detection using MWCNT-based surface-assisted laser desorption/ionization-time-of-flight mass spectrometry (SALDI-TOFMS). Four kinds of MWCNTs (Aldrich 636843, 636495, 636509, and 636819) of different lengths and diameters were tested using the developed technique. The data show that 636843, the MWCNT with the largest outer diameter (o.d.), the widest wall thickness, and shortest length, had the best limit of detection (0.5-1 microg/mL) We also found that there was no significant difference in enrichment efficiency of VLCFAs between the four MWCNTs, which suggests that the size of the MWCNT may contribute to desorption/ionization efficiency. To our knowledge, this is the first study to test the enrichment of VLCFAs using MWCNTs of different sizes. We have shown that the VLCFAs adsorbed by MWCNTs can be analyzed by SALDI-TOFMS. In addition, this method does not require liquid/gas chromatography separation, thereby allowing for high-throughput screening of VLCFAs in peroxisomal disorders.

High intakes of linoleic acid (LA,18:2n-6) have raised concern due to possible increase in arachidonic acid (ARA, 20:4n-6) synthesis, and inhibition of alpha linolenic acid (ALA, 18:3n-3) desaturation to eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). In healthy men, 10.5% energy compared to 3.8% energy LA with 1% energy ALA increased plasma phospholipid LA and 20:2n-6, the elongation product of LA, and decreased EPA, with no change in ARA. However, LA was inversely related to ARA at both 10.5% energy and 3.8% energy LA, (r=-0.761, r=-0.817, p<0.001, respectively). A two-fold variability in ARA among individuals was not explained by the dietary LA, ARA, ALA, or fish intake. Our results confirm LA requirements for ARA synthesis is low, <3.8% energy, and they suggest current LA intakes saturate Delta-6 desaturation and adversely affect n-3 fatty acid metabolism. Factors other than n-6 fatty acid intake are important modifiers of plasma ARA.

Information on the status of long-chain polyunsaturated fatty acids (LCPUFAs) in pregnancy and breast milk in very high fish-eating populations is limited. The aim of this study was to examine dietary intake and changes in fatty acid status in a population of pregnant women in the Republic of Seychelles. Serum docosahexaenoic acid (DHA) decreased significantly between 28-week gestation and delivery (n=196). DHA status did not correlate significantly with length of gestation and was not associated with self-reported fish intake, which was high at 527 g/week. In breast milk, the ratio of DHA to arachidonic acid (AA) was consistent with those observed in other high fish-eating populations. Overall the data suggest that high exposure to LCPUFAs from habitual fish consumption does not prevent the documented decrease in LCPUFA status in pregnancy that occurs as a result of foetal accretion in the third trimester of pregnancy.

Objective: The aim of the present study was to examine the immune-modulating effect of two different fat blends enriched with a low dose of anti- or proinflammatory polyunsaturated fatty acids on the fatty acid status and subsequently on the immune response of healthy volunteers., Methods: Thirty healthy volunteers were randomly assigned to group A (anti-inflammatory blend rich in polyunsaturated fatty acids: alpha-linolenic acid, 240 mg/d; eicosapentaenoic acid, 120 mg/d; stearidonic acid, 49 mg/d; and gamma-linolenic acid, 73 mg/d) or group B (arachidonic acid, 40 mg/d; containing an inflammatory fat blend) for a 2-wk dietary supplementation period. Concentrations of interleukin-8, interleukin-10, tumor necrosis factor-alpha, prostaglandins E(1) and E(2), and leukotriene B(4) were investigated before, after 2 wk of supplementation, and 2 wk after stopping supplementation using a whole blood ex vivo lipopolysaccharide-stimulation assay., Results: Plasma concentrations of alpha-linolenic acid and eicosapentaenoic acid were significantly increased in group A. In addition, dietary fat blends influenced eicosapentaenoic acid concentration in erythrocyte membranes. Supplementation of the fat blends resulted in contrasting effects on the expression of lipid mediators and cytokines after ex vivo lipopolysaccharide stimulation. Release of prostaglandin E(1) and leukotriene B(4) were significantly decreased in group A, whereas prostaglandin E(2) and interleukin-10 concentrations were significantly increased in group B. No effect on interleukin-8 or tumor necrosis factor-alpha release was found after supplementation with either fat blend., Conclusions: These results show an immune-modulating effect of a low-dose dietary polyunsaturated fatty acid supplementation. However, further studies regarding fat-blend composition and period of supplementation in patients with inflammatory conditions are required.

The identification of risks associated with sudden cardiac death requires further investigations. The question was addressed whether parameters can be established which not only describe an increased risk for an enhanced electrical instability of the heart but also of inflammatory events underlying plaque rupture. Emphasis is placed on dose-dependent effects of the long-chain omega-(omega-)3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Since free acids of EPA and DHA are required for most of their biological effects, it appears essential not only to build up stores in the body for release of these fatty acids, but also to provide a sustained uptake of EPA and DHA in the form of ethyl esters. In contrast to rapidly absorbed triacylglycerols from fish, ethyl esters are taken up more slowly within 24 h. For the administration of 1 g/day highly purified EPA+DHA ethyl esters (Omacor) to healthy volunteers, it is shown that EPA is increased from 0.6% to 1.4% within 10 days, while DHA is increased from 2.9% to 4.3%. After withdrawal, EPA and DHA approach baseline values within 10 days. A gas chromatographic procedure was established which requires only 10 microl of whole blood for the identification of more than 35 fatty acids. Evidence is summarized strengthening the concept that a low "EPA+DHA level" presents a risk for sudden cardiac death and that the administration of 840 mg/day of EPA+DHA ethyl esters raises the "EPA+DHA level" to approximately 6% that is associated with a marked protection from sudden cardiac death. For reducing pro-inflammatory eicosanoids and cytokines, a higher "EPA+DHA level" is required which can be achieved with an intake of 2-4 g/day of 84% EPA+DHA ethyl esters. For assessing influences from pro-inflammatory eicosanoids and cytokines, the EPA/arachidonic acid ratio ("EPA/AA ratio") was identified as diagnostic parameter. To assess the dietary EPA+DHA intake, fatty acids were determined in fish dishes of the cafeteria of the Philipps University Hospital Marburg, Germany. The EPA+DHA content of the popular Alaska Pollock was 125 +/- 70 mg/100 g. A once daily fish dish can thus not provide the 840 mg/day EPA+DHA administered in the GISSI Prevention Study in the form of ethyl ester which markedly reduced the risk of sudden cardiac death in postmyocardial infarction patients. Nonetheless, at least two preferably oily fish meals per week should be consumed as preventive measure by persons without coronary artery disease. With documented coronary heart disease, it was advised to consume approximately 1 g/day of EPA+DHA.

The objective of this study was to investigate the pattern of serum non-esterified fatty acid (NEFA) fraction in association with atherosclerosis development. We have studied possible relationships between eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) in the NEFA fraction and biochemical markers of endothelial activation or dysfunction. The study population consisted of 152 elderly men with high risk for coronary heart disease. The composition of fasting serum NEFA was analysed by gas-liquid chromatography. Endothelial activation was evaluated using biochemical analyses of some markers of endothelial function. A significant inverse linear association was found between serum non-esterified EPA and DHA, and soluble vascular cell adhesion molecule-1 (sVCAM-1) (P=0.02 and 0.001, respectively). An inverse linear association was found between serum non-esterified AA and sVCAM-1 (P=0.001) and von Willebrand Factor (P=0.005). The significant inverse associations for DHA and AA were independent from the serum content of other NEFAs. Taken together, negative associations were found between sVCAM-1 and the serum levels of non-esterified DHA, EPA and AA. The inverse relation between the levels of sVCAM-1 and very long-chain n-3 fatty acids might indicate an anti-inflammatory effect of the latter.

The administration of n-3 polyunsaturated fatty acids (PUFAs) is known to be effective against allergic diseases by suppressing the production of eicosanoids derived from arachidonic acid. To investigate the mechanisms and efficacy of n-3 PUFA treatment in patients with atopic dermatitis (AD), we administered four different formulas of alpha-linolenic acid for 6 weeks in an AD model using NC/Nga mice. According to the doses of alpha-linolenic acid given, the levels of alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid in the red blood cell membranes increased while the levels of linoleic acid and arachidonic acid decreased. However, there was no significant difference among the four dose groups in clinical skin severity score, histopathological findings of skin lesions, or levels of total plasma IgE. Moreover, there was no significant difference in the production of leukotriene B(4) and Leukotriene C(4) from skin lesions after stimulation with A23187 among the groups, although the production of prostaglandin E(2) (PGE(2)) was significantly reduced and skin blood flow in the ear was significantly higher in the group given the highest dose of alpha-linolenic acid. Our results suggest that the administration of alpha-linolenic acid can change the fatty acid composition, PGE(2) production, and skin blood flow but may not prevent the development of dermatitis in NC/Nga mice., (Copyright 2002 Elsevier Science Ltd. All rights reserved.)

Background: To assess the relationship between the mothers' intake of n-3 long chain polyunsaturated fatty acids (LC PUFA) during pregnancy and their levels in plasma and tissue., Methods: 162 mothers were studied during labor. Three groups were differentiated according to the n3 LC PUFA intake assessed by means of a dietetic interview: superior intake (SIG) (> 0.721 g/day), medium intake (MIG) (from 0.382 to 0.721 g/day) and inferior intake (IIG) (< 0.381 g/day). Fatty acids (FA) were studied by capillary chromatography in plasma and in erythrocyte phospholipids., Results: The fatty acids (FA), expressed in absolute values, did not show any significant differences among the aforementioned groups. However, three were some trends which were confirmed when the FA were expressed in percentages. Thus, higher levels of docosahexaenoic acid (DHA) were found in SIG both in plasma and in the erythrocyte membrane, when expressed in percentages. Eicosapentaenoic acid (EPA) was also higher in the SIG in the erythrocyte membrane, whereas in plasma the differences were of marginal significance. On the other hand, arachidonic and linoleic acids had lower values in the SIG in erythrocytes. The theoretical optimal intake of n-3 LC PUFA corresponded to a plasma concentration of 117.9 +/- 45.9 mcg/ml n-3 LC PUFA or 2.54% of the total fatty content (2.29% of DHA). The corresponding cut-offs in erythrocyte membranes were 7.54% of total lipids (5.59% of DHA)., Conclusion: The best markers of n-3 LC PUFA intake were DHA for plasma and DHA and EPA for erythrocyte phospholipids, all of them expressed in proportions of total FA. The arachidonic and linoleic acids (in percentages) in erythrocyte phospholipids were also good markers of n-3 intake. This probably reflects the metabolic competition between both PUFA families.

In this study we investigated the hepatic uptake of liposomes containing a novel synthetic glycolipid, lactose mono-arachidic acid amide (LAA). Liposomes containing LAA were aggregated by Ricinus communis agglutinin from caster bean, while the control liposomes were not, and the results suggested that the galactose residues of LAA were exposed to the outer surface of the liposomes. Next, the blood clearance and hepatic uptake of liposomes containing LAA after intravenous administration were compared with those of the control liposomes in rat. Hepatic uptake of liposomes containing LAA was greater than that of the control liposomes, rising significantly with dose. As a result of separation of the parenchymal and non-parenchymal cells, it was shown that the increase in hepatic uptake was mostly accounted for by a greater uptake by parenchymal cells. The inhibitory activity of asialofetuin on the hepatic uptake of liposomes containing LAA suggested that a galactose-specific recognition is involved in this uptake. These results demonstrate that the lactose mono-fatty acid amides (LFAs) are promising novel compounds for the introduction of carbohydrate residues onto the liposomal surface and that liposomes containing LFAs are potential carriers for the selective delivery of drugs to specific cells.

To determine the incidence of essential fatty acid (EFA) deficiency during short term fat-free parenteral nutrition, the authors investigated prospectively the EFA status of nine low birthweight (1145 +/- 343 g) preterm (28.2 +/- 1.9 weeks) infants, in whom delivery of dietary fat was delayed postnatally for 2-9 days. Serial determinations of plasma fatty acids showed that during fat-free alimentation, the major EFA, linoleic acid (LA), decreased rapidly (-0.75% total fatty acids per day), accompanied by a rise in endogenously produced non-essential fatty acid, eicosatrienoic acid (Mead acid). Essential fatty acid deficiency was confirmed biochemically by an elevation in the triene-tetraene ratio in six of the infants, only one of whom developed clinical symptoms. Abnormal fatty acid profiles were corrected within a few days of fat delivery by either intravenous or enteral routes. Essential fatty acids and their metabolites are involved in a wide range of physiological functions vital to postnatal growth and development. Depletion of these nutrients can be corrected by providing a minimum of 0.25 g LA/kg per day (equivalent to 0.50 g/kg per day of 20% intralipid or 30-50 mL/kg per day of breast milk).

The oxidation of arachidonic acid in a superoxide-generating environment results in the formation of a potent chemoattractant that appears to be identical to a chemotactic material generated by hepatocytes when they metabolize alcohol. The product was extracted, chromatographed and characterized by physical methods including GC/MS. The physical properties are consistant with the parent structure: 19-hydroperoxy, 20-hydroxyarachidic acid. This novel saturated 20 carbon product, derived from arachidonic acid by free radical-generating reactions, may play a role in the neutrophilic infiltration observed during the course of acute alcoholic hepatitis.

A rapid gas chromatographic method to determine phytanic acid in plasma from Refsum's disease is described. After a brief alkaline hydrolysis of lipids, the biological sample is directly injected into a glass pre-column; an acid carrier gas (formic acid in nitrogen) is used to displace the long-chain fatty acids from their sodium salts and from their binding to proteins. Formic acid introduced through the column may also be used as a reagent gas for chemical ionization in combined gas chromatography--mass spectrometry; fatty acids (C14 to C18:2 and phytanic acid) are easily identified by their M + 1 (base peak) and M - 17 peaks. The described procedure is also suitable for studying normal fatty acids from plasma lipids.

It has been suggested by several investigators that eicosapentaenoic acid (C20:5 omega 3, EPA) might have anti-thrombotic effects. In this experiment, the effect of the oral administration of EPA rich fish oil concentrate on platelet aggregation and the release and the metabolism of [1-14C]arachidonic acid and [(U)-14C]eicosapentaenoic acid by human platelets was studied. Eight healthy male subjects ingested 18 capsules of fish oil concentrate (EPA 1.4 g) per day for 4 weeks. Plasma and platelet concentrations of EPA markedly increased, while those of arachidonic acid (C20:4 omega 6, AA) and docosahexaenoic acid (C22:6 omega 3, DHA) did not change. Platelet aggregation induced by collagen and ADP was reduced. Collagen induced [14C]thromboxane B2 (TXB2) formation from [14C]AA prelabeled platelets decreased. There was no detectable formation of [14C]TXB3 from [14C]EPA prelabeled platelets, and the conversion of exogenous [14C]EPA to [14C]TXB3 was lower than that of [14C]AA to [14C]TXB2. The release of [14C]AA from [14C]AA prelabeled platelets by collagen was significantly decreased. These observations raise the possibility that the release of arachidonic acid from platelet lipids might be affected by the alteration of EPA content in platelets.

5,8,11,14,17-[1-14C]Eicosapentaenoic acid was prepared biosynthetically from [1-14C]arachidonic acid using the fungus, Saprolegnia parasitica. Incubation of 5,8,11,14,17-[1-14C]eicosapentaenoic acid with suspensions of human platelets led to the formation of three labeled compounds which were identified as thromboxane B3 (2-5% yield), 12-hydroxy-5,8,10,14-heptadecatetraenoic acid (2-5% yield), and 12-hydroxy-5,8,10,14,17-eicosapentaenoic acid (7-59% yield).

Fifty patients with neurological symptoms and signs resembling those of Refsum's disease were analyzed for phytanic acid in serum. In addition, the phytanic acid oxidase capacity in skin fibroblasts was determined. The patients suffered from retinitis pigmentosa, cerebellar ataxia and/or chronic polyneuropathy of unknown cause. The serum level of phytanic acid was not increased, and the alpha-oxidation of (1-14C) phytanic acid was found to be normal in all patients. The present investigation lends no support to the theory that so-called atypical or mild cases of Refsum's disease exist. This disorder appears to be a disease entity with a specific genetic phenotype.

The link between dietary salt intake and the development of hypertension in the salt-sensitive Dahl strain of rats remains elusive. There is evidence that Dahl salt-sensitive rats (DS) produce less vasodilator and natriuretic prostaglandins in response to salt loading than do control salt-resistant rats (DR), although the reason for this blunted response is unknown. We examined the effects of chronic dietary salt loading on the plasma levels of nonesterified fatty acids in DS and DR. Animals were fed the same chow containing either 0.4% or 4% NaCl (wt/wt). At 12 weeks, 75 microliters of tail capillary blood was obtained from restrained, conscious rats, and principal nonesterified fatty acids were measured by high performance liquid chromatography. Total nonesterified fatty acids rose in the 15 DR on high salt diets compared with values in 11 rats eating low salt (0.57 +/- 0.05 vs 0.35 +/- 0.01 mM; p less than 0.001). The greatest changes occurred in levels of arachidonic acid (+287%) and in the arachidonic precursors, linoleic (+89%) and linolenic (+107%) acids. In marked contrast, there was no change in levels of plasma nonesterified fatty acids in DS fed 4% NaCl compared with DS fed 0.4% NaCl. These observations suggest that defective production of natriuretic and vasodilator prostaglandins by DS may be due in part to an inability to produce or release eicosanoid precursors from phospholipid stores in response to dietary salt.

When rats were fed a diet containing chow or fish oil for six weeks, the platelet phospholipid content and percent distribution were similar. In the fish oil fed animals there was a 54, 40, 41, and 24% reduction, respectively, in the levels of 20:4(n-6) in the choline-, ethanolamine-, inositol- and serine-containing glycerophospholipids. Dietary fish oil increased the total (n-3) polyunsaturated fatty acid content in all lipids. This effect was most pronounced in the ethanolamine glycerophospholipids which now contained 26, 11, and 4 nmols of 20:5(n-3), 22:5(n-3), and 22:6(n-3) in 10(9) cells. Ionophore A23187 stimulation of platelets from the chow fed rats resulted in the synthesis of 7, 64, and 3.5 nmols of 12-hydroxy-5,8,10-heptadecatrienoic acid, 12-hydroxy-5,8,10,14-eicosatetraenoic acid and 12-hydroxy-5,8,10,14,17-eicosapentaenoic acid, respectively, from 1 X 10(9) cells. The values from animals fed fish oil were 4, 18, and 27 nmol/10(9) platelets. It was not possible to detect any lipoxygenase products from 22:5(n-3) or 22:6(n-3), even though both acids are readily metabolized by lipoxygenase when added directly to platelets. These findings suggest that 22-carbon (n-3) fatty acids are not liberated when phospholipases are activated by calcium mobilization.

A typical case of Refsum disease with high phytanic acid plasma levels is described. Two siblings showed some features but not the entire clinical spectrum of the disease. The unusual condition of the patient's father, a presumed heterozygotic carrier with characteristic bone abnormalities and a delayed onset retinopathy, is discussed.

In this reliable assay for determining the non-esterified long-chain fatty acid pattern in plasma, only 100 microliters of sample are needed and a single assay can be done within 40 min. The isolation procedure was performed by adsorption of fatty acids from plasma onto graphitized carbon black (Carbopack B) using a column method. After desorption and removal of the eluting phase, fatty acids are methylated by diazomethane and quantified by packed column gas chromatography. Analytical recoveries ranged between 91% and 103%. Within-run precision gave coefficients of variation of 2.3% and 11% for fatty acid concentrations of 58.2 and 0.6 mumol/l, respectively. Studies of plasma samples under various storage conditions indicated that reliable measurement of the non-esterified fatty acid fraction can be obtained even after 60 days if specimens are conserved at -18 degrees C in the presence of a suitable phospholipase inhibitor.

The pathogenesis of atherosclerosis, a major cause of age-related mortality, remains poorly understood. Although platelets and their products, including thromboxane A2, may be of importance in this process, little is known about eicosenoid biosynthesis and platelet function with increasing age. In order to address the hypothesis that platelet activation increases with age, we measured various indices of platelet function in a group of apparently healthy individuals over the age of 50 years. The circulating platelet aggregate ratio, plasma beta-thromboglobulin and threshold aggregating concentration of arachidonic acid were similar to those in healthy subjects aged less than 40 years. Although the bleeding time (168 +/- 24 vs 300 +/- 24 seconds) was significantly (p less than 0.001) shorter in the older volunteers this may be unrelated to platelet function and merely reflect age related changes in skin and/or vascular function. To further assess platelet and vascular function in vivo, we measured excretion of the major thromboxane and prostacyclin metabolites in urine, 2,3-donor-thromboxane B2 (Tx-M) and 2,3-dinor-6-keto-PGF1 alpha (PGI-M). Both Tx-M (223 +/- 22 vs 152 +/- 19 pg/mg creatinine; p less than 0.005) and PGI-M (198 +/- 21 vs 121 +/- 13 pg/mg creatinine; p less than 0.005) excretion were significantly higher in the older volunteers. These subtle but significant changes in eicosenoid biosynthesis are consistent with the presence of platelet activation in vivo increasing with age in apparently healthy individuals.

The relative proportions of the diphytanyl, monophytanyl and nonphytanyl triglycerides ("triglyceride pattern"), the phytanic acid content of the triglycerides and the phytanic acid levels in the serum of 3 patients with Refsum's disease (heredopathia atactica polyneuritiformis, phytanic acid storage disease) were estimated by thin-layer chromatography, densitometry and gas chromatography, respectively. The individual triglyceride patterns were clearly dependent on the phytanic acid content of the triglycerides: the more phytanic acid in the triglycerides, the higher the percentage of the diphytanyl and the lower the percentage of the nonphytanyl triglycerides. The monophytanyl triglycerides were also related to the phytanic acid content of the triglycerides, although in a complex manner. The triglyceride pattern can be taken as a parameter of the phytanic acid accumulation in Refsum's disease to be at least as sensitive as the serum phytanic acid level in the biochemical evaluation of the efficiency of the dietary treatment.

Cisternal and lumbar cerebrospinal fluid obtained some days following a subarachnoid haemorrhage contains abnormally large quantities of various prostanoids; some may be partly the result of abnormal production by the cerebral arteries. The extra-arterial and intra-arterial production of 6 oxo PGF1 alpha (prostacyclin metabolite), PGE2, PGF2 alpha and TXB2 were measured in perfused rabbit common carotid arteries taken both from normal rabbits and from rabbits in which the arteries had been ensheathed by blood clot in vivo for 7 days using two techniques. Prostaglandin production by control arteries was highest during the first hour of perfusion but declined or increased marginally (PGE2) during the succeeding three hours. Arteries exposed to a periarterial haematoma for 7 days produced prostaglandins at a high rate throughout the 4 hours of study, and there was a progressive and marked increase in PGE2 production. The disproportionate increase in the cerebral vasoconstrictor PGE2 may reflect the inflammatory response which occurred in the adventitia of the vessels. Increased prostanoid production by cerebral arteries probably does contribute to the increased levels in CSF after subarachnoid haemorrhage.

Plasma samples from several Zellweger patients were found to contain elevated phytanic acid levels. It was subsequently found that the level of phytanic acid in plasma from Zellweger patients depends upon the age of the patients at the time of sampling. In patients 17 weeks of age or younger, plasma phytanic acid levels were found to be normal, whereas in patients 40 weeks of age or older plasma phytanic acid levels were found to be elevated. The relationship between the age of the patients at sampling and the level of phytanic acid in the patients' plasma is probably the resultant of dietary intake of phytanic acid combined with a defective catabolism of this compound.

Phytanic acid accumulation has for more than 20 years been used as a diagnostic criterion of Refsum's disease. Recently, however, phytanic acid has also been found in peroxisomal disorders (Zellweger's syndrome, neonatal adrenoleukodystrophy, infantile Refsum's syndrome, rhizomelic chondrodysplasia punctata). The 17 patients with Refsum's disease in the present study had serum phytanic acid values differing from 73 to less than 0.5 mg/dl (normal). alpha-Oxidation of phytanic acid in skin fibroblast cultures showed a defective capacity in all, with only small differences in residual activity. Phytanic acid determinations in serum from 3 of the 7 patients with peroxisomal disorders showed slightly elevated levels in 2. The alpha-oxidation capacity in the fibroblasts was defective in all, with a residual activity similar to that of Refsum's disease. An assay of the alpha-oxidation capacity may be useful in the diagnosis of both Refsum's disease and the peroxisomal disorders. The distinction between Refsum's disease and the peroxisomal disorders can easily be done on a clinical basis.

In the pathogenesis of bovine pneumonic pasteurellosis, immunodepression induced by stress or respiratory viral infection permits superinfection of the lungs with Pasteurella hemolytica, which results in exudative fibrinous pneumonia. Therefore, bovine pneumonic pasteurellosis was induced by sequential inoculations of calves with bovine herpes virus-1 (BHV-1, 3 X 10(7) tissue culture infectious dose 50 (TCID50)/nostril), followed 3 days later by challenge with P. hemolytica (15 X 10(9) colony-forming units (cfu) intratracheally). To study the pathogenic mechanisms of the disease, we examined the alterations in plasma prostaglandins (PG), thromboxane B2 (TxB2), histamine, serotonin and long-chain fatty acids (LCFA) during BHV-1 infection alone and after challenge exposure to P. hemolytica (i.e. during BHV-1-pneumonic pasteurellosis). BHV-1 infection alone markedly increased plasma PGE but modestly elevated PGF2 alpha, TxB2 and arachidonic, oleic and palmitic acids. After challenge with P. hemolytica, the levels of plasma arachidonic, oleic, and palmitic acids, together with PGE and 6-keto-PGF1 alpha, were elevated markedly, in association with clinical signs of bovine pneumonic pasteurellosis. However, PGF2 alpha and stearic acid increased only transiently whereas TxB2 was unchanged from the control. On the other hand, plasma linoleic acid, histamine and serotonin remained unaltered. These results indicate enhanced eicosanoid biosynthesis and disproportionate rises in LCFA during BHV-1 pneumonic pasteurellosis. While LCFA are needed for energy metabolism, eicosanoids may mediate the immunologic, inflammatory and pulmonary vascular reactions leading to the clinico-pathologic features of BHV-1 pneumonic pasteurellosis.

Japanese are unique among the peoples of developed countries in having a high intake of eicosapentaenoic acid (C 20:5) from fresh fish and this may in part contribute to their low incidence of cardiovascular diseases. Mass spectroscopic analyses of eicosapolyenoic acids (C20:3, C20:4 and C20:5) were carried out on the serum of aged persons living on Kohama island in Okinawa and known to have the lowest incidence of cardiovascular diseases in Japan. All but 4 of the 77 persons examined (73.94 +/- 7.81 years old) led active fishing-farming lives. The total amount of eicosapolyenoic acids in the serum of persons on Kohama island (46.77 +/- 7.46 mg/100 ml) was higher (p less than 0.001) than that in people on mainland Japan, owing to the higher intake of fresh fish (147.7 g/day). A positive correlation (p less than 0.01) was found between serum C 20:5 concentration (6.82 +/- 2.54 mg/100 ml) and high density lipoprotein concentration (55.38 +/- 13.83 mg/100 ml). In addition, there were positive correlations (p less than 0.01) between serum C 20:3 concentration (6.58 +/- 1.61 mg/100 ml) and total cholesterol (188.60 +/- 32.30 mg/100 ml), and triglyceride and skinfold thickness. The blood pressure level (p less than 0.01), incidence of abnormal ECG (p less than 0.05), and salt intake (6.2-8.3 g/day) estimated from urinalysis, were all lower than the average figures for Japanese of similar ages. No persons examined showed Q-wave on ECG. The percentage of smokers and drinkers were similar for Kohama island and mainland Japan.

Death from cardiovascular disease is rare among Eskimos. Haemostasis was investigated in twenty-one Greeland Eskimos and twenty-one age and sex matched Danish controls. Platelet lipid analysis demonstrated that a high consumption of omega-3 polyunsaturated fatty acids (such as cis 5, 8, 11, 14, 17-eicosapentaenoic acid [C20:5]) by Eskimos increased the proportion of omega-3 polyunsaturated fatty acids in the platelets. The Eskimos had a significantly longer bleeding-time due to a reduction in platelet aggregation. It is suggested that C20:5 in the platelets is converted by the vascular-wall tissue to an anti-aggregatory prostacyclin. Partial dietary substitution of arachidonic acid by eicosapentaenoic acid may reduce the incidence of thrombotic disorders, including myocardial infarction.