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Polyunsaturated fatty acids (PUFAs) are long chain fatty acids that are characterized by the presence of more than one double bond. These include fatty acids such as ꞷ-3-α-linolenic acid (ALA) and ꞷ-6 -linoleic acid (LA) which can only be obtained from dietary sources and are therefore termed essential fatty acids. They contain the building blocks for dihomo-γ-linolenic acid and arachidonic acid in the ꞷ-6 family as well as eicosapentaenoic acid and docosahexaenoic acid in the ꞷ-3 family. Both ALA and LA are important constituents of animal and plant cell membranes and are important components of anti-inflammatory and pro-inflammatory hormones and therefore, often modulate cellular immunity under chronic inflammatory states. The variation in physiological PUFA levels is under significant genetic influence, the fatty acid desaturase (FADS) genes being key regulators of PUFA metabolism. These genetic variants have been shown to alter fatty acid metabolism and influence the onset and progression of various metabolic conditions. This detailed review discusses the role of PUFAs, diet and genotypes in risk for cardiovascular diseases., (Copyright © 2021. Published by Elsevier Ltd.)

Good sources of the long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) include cold-water fish and seafood; however, vegan diets (VGNs) do not include animal-origin foods. Typically, US omnivores obtain enough dietary EPA and DHA, but unless VGNs consume algal n-3 supplements, they rely on endogenous production of long-chain fatty acids. VGN diets have several possible concerns: (1) VGNs have high intakes of linoleic acid (LA) as compared to omnivore/non-vegetarian diets. (2) High intakes of LA competitively interfere with the endogenous conversion of alpha-linolenic acid (ALA) to EPA and DHA. (3) High somatic levels of LA/low ALA indicate a decreased ALA conversion to EPA and DHA. (4) Some, not all VGNs meet the Dietary Reference Intake Adequate Intake (DRI-AI) for dietary ALA and (5) VGN diets are high in fiber, which possibly interferes with fat absorption. Consequently, health professionals and Registered Dietitians/Registered Dietitian Nutritionists working with VGNs need specific essential fatty acid diet guidelines. The purpose of this review was: (1) to suggest that VGNs have a DRI-AI Special Consideration requirement for ALA and LA based on VGN dietary and biochemical indicators of status and (2) to provide suggestions to ensure that VGNs receive adequate intakes of LA and ALA.

Aims: To evaluate whether participant characteristics and way of expressing circulating fatty acids (FA) influence the strengths of associations between self-reported intake and circulating levels of linoleic acid (LA), alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)., Methods: Cross-sectional analyses were performed in pooled data from the CODAM (n = 469) and Hoorn (n = 702) studies. Circulating FA were measured by gas liquid chromatography and expressed as proportions (% of total FA) and concentrations (µg/mL). Dietary intakes were calculated from a validated food frequency questionnaire. Effects of participant characteristics on associations between dietary and circulating FA were calculated using interaction analyses., Results: Standardized regression coefficients between dietary FA and proportions of circulating FA (% of total FA) were LA β = 0.28, ALA β = 0.13, EPA β = 0.34, and DHA β = 0.45. Body mass index (BMI), waist circumference, and presence of CVD influenced associations for LA; gender influenced LA, EPA, and DHA; alcohol intake influenced LA and DHA; and glucose tolerance status influenced ALA (p values interaction <0.05). Coefficients for circulating FA as concentrations were LA β = 0.19, ALA β = 0.10, EPA β = 0.31, and DHA β = 0.41., Conclusions: This study suggests that characteristics such as BMI, alcohol intake, and expressing circulating FA as proportions or concentrations, influence associations between dietary and circulating FA., (© 2018 S. Karger AG, Basel.)

Purpose: Data on the relation between linoleic acid (LA) and alpha-linolenic acid (ALA) and type 2 diabetes mellitus (T2DM) risk are scarce and inconsistent. The aim of this study was to investigate the association of serum LA and ALA with fasting and 2 h post-load plasma glucose and glycated hemoglobin (HbA1c)., Method: This study included 667 participants from third examination (2000) of the population-based Hoorn study in which individuals with glucose intolerance were overrepresented. Fatty acid profiles in serum total lipids were measured at baseline, in 2000. Diabetes risk markers were measured at baseline and follow-up in 2008. Linear regression models were used in cross-sectional and prospective analyses., Results: In cross-sectional analyses (n = 667), serum LA was inversely associated with plasma glucose, both in fasting conditions (B = -0.024 [-0.045, -0.002]) and 2 h after glucose tolerance test (B = -0.099 [-0.158, -0.039]), but not with HbA1c (B = 0.000 [-0.014, 0.013]), after adjustment for relevant factors. In prospective analyses (n = 257), serum LA was not associated with fasting (B = 0.003 [-0.019, 0.025]) or post-load glucose (B = -0.026 [-0.100, 0.049]). Furthermore, no significant associations were found between serum ALA and glucose metabolism in cross-sectional or prospective analyses., Conclusions: In this study, serum LA was inversely associated with fasting and post-load glucose in cross-sectional, but not in prospective analyses. Further studies are needed to elucidate the exact role of serum LA and ALA levels and dietary polyunsaturated fatty acids in glucose metabolism.

Objective: Docosahexaenoic acid (DHA) is an important nutrient required by pregnant women and fetuses. Several studies suggest that fatty acid composition changes during pregnancy. However, the association of longitudinal changes in erythrocyte fatty acid composition and dietary fatty acid intake during pregnancy is not well understood. We assessed the relationship between fatty acid composition of the erythrocyte membranes and fatty acid intake at each trimester in pregnant Japanese women., Methods: We conducted a prospective hospital-based cohort study. We investigated fatty acid composition of the erythrocyte membranes and intake of fatty acids during the three trimesters in 178 healthy, pregnant Japanese women., Results: The eicosapentaenoic acid and arachidonic acid percentage of the erythrocyte membranes significantly decreased. The percentages of linoleic acid and α-linolenic acid significantly increased during pregnancy. The DHA percentage in the erythrocyte membranes decreased from the second to the third trimester. The DHA percentage in the erythrocyte membranes positively correlated with DHA intake in the third trimester., Conclusion: In pregnant Japanese women, the fatty acid composition of the erythrocyte membranes markedly changed throughout pregnancy. The DHA intake in the third trimester may be insufficient to maintain DHA percentage in the maternal erythrocyte membranes., (© 2017 S. Karger AG, Basel.)

The unclear link between intake of polyunsaturated fatty acids (PUFAs) and risk of cardiovascular disease (CVD) could depend on genetic differences between individuals. Minor alleles of single-nucleotide polymorphisms (SNPs) in the ∆5 fatty acid desaturase (FADS) 1 gene were associated with lower blood concentrations of long-chain ω-3 (n-3) and ω-6 (n-6) PUFAs, indicating an associated loss of function effect. We examined whether the SNP rs174546 in FADS1 modifies the association between PUFA intakes and CVD risk. We included 24,032 participants (62% women, aged 44-74 y) from the Malmö Diet and Cancer cohort without prevalent CVD and diabetes. During a mean follow-up of 14 y, 2648 CVD cases were identified. Diet was assessed by a modified diet history method. A borderline interaction was observed between the α-linolenic acid (ALA) (18:3n-3)-to-linoleic acid (LA) (18:2n-6) intake ratio and FADS1 genotype on CVD incidence (P = 0.06). The ALA-to-LA intake ratio was inversely associated with CVD risk only among participants homozygous for the minor T-allele (HR for quintile 5 vs. quintile 1 = 0.72; 95% CI: 0.50, 1.04; P-trend = 0.049). When excluding participants reporting unstable food habits in the past (35%), the interaction between the ALA-to-LA intake ratio and FADS1 genotype on CVD incidence was strengthened and statistically significant (P = 0.04). Additionally, we observed a significant interaction between ALA and FADS1 genotype on ischemic stroke incidence (P = 0.03). ALA was inversely associated with ischemic stroke only among TT genotype carriers (HR for quintile 5 vs. quintile 1 = 0.50; 95% CI: 0.27, 0.94; P-trend = 0.02). In this large cohort, we found some weak, but not convincing, evidence of effect modification by genetic variation in FADS1 on the associations between PUFA intakes and CVD risk. For the 11% of the population homozygous for the minor T-allele of rs174546 that associates with lower ∆5 FADS activity, high ALA intake and ALA-to-LA intake ratio may be preferable in the prevention of CVD and ischemic stroke., (© 2014 American Society for Nutrition.)

Unlabelled: Streptozotocin (STZ)-induced diabetes in mice progresses with decreased desaturase activities and alterations in the metabolism of essential fatty acids (EFA)., Objectives: Based on our previous studies with soybean oil that ameliorated the STZ damage in mice, we tested here the accountability of its main EFA components, i.e. linoleic acid (LA) and alpha linolenic acid (ALA), in the prevention of pancreas damage and Δ6 desaturase decrease., Materials and Methods: Seven days after injection with STZ and EFA gavage, ICR mice were sacrificed. Plasma glucose and insulin levels, pancreas histology and liver fatty acid desaturases were analysed., Results: EFA reduced pancreas damage, insulin and glucose plasma levels and restored Δ6 desaturase activity and mRNA expression levels., Discussion: By reducing pancreas damage, EFA ameliorated insulin levels, Δ6 desaturase and fatty acid metabolism. LA further enhanced Fads2 promoter activity., Conclusion: EFA ameliorate STZ induced diabetes in mice.

Analysis of oxylipins derived from fatty acids may provide insight into the biological effects of dietary lipids beyond their effects on tissue fatty acid profiles. We have previously observed that diets with higher amounts of α-linolenic acid (ALA; 18:3n3) are associated with reduced obesity-related glomerulopathy (ORG). Therefore, to examine the renal oxylipin profile, the effects of dietary linoleic acid (LA; 18:2n6) and ALA on oxylipins and renal phospholipid fatty acid composition, and the relationship between oxylipins and ORG, diet-induced obese rats displaying ORG were fed 8 different diets for 8 wk as follows (oil/oil = combination of two oils) [shown as ALA/LA (in g) per 100 g oil]: canola/flax (20/18), canola (8/18), soy (9/53), high-oleic canola/canola (5/16), high-oleic canola (2/15), lard/soy (1/8), and safflower (0.2/73). Targeted lipidomic analysis by HPLC-tandem mass spectrometry revealed that LA and ALA oxylipins comprised 60% of the total renal oxylipin profile examined. Of the >60 oxylipins screened, only those derived either directly or indirectly from ALA were associated with less glomerulomegaly, indicative of reduced ORG progression. Both the amount and ratio of dietary LA and ALA influenced renal polyunsaturated fatty acids (PUFAs); in contrast, only fatty acid amount altered oxylipins derived from these fatty acids, but there was no apparent competition by LA or ALA on their formation. Dietary LA incorporation into renal phospholipids was higher than for ALA, but ALA oxylipin:ALA ratios were higher than the analogous LA ratios for select lipoxygenase reactions. This indicates that the effect of dietary ALA on renal oxylipins exceeded what was reflected in renal PUFA composition. In conclusion, dietary LA and ALA have differential effects on renal oxylipins and PUFAs, and ALA-derived oxylipins are associated with renoprotection in this model of ORG.

Few trials have evaluated the metabolic effects and health outcomes of lowering dietary n-6 PUFA. The objectives of the present paper were (1) to report the methods employed to lower dietary n-6 PUFA, while either increasing or maintaining n-3 PUFA intake and (2) to validate our methods with 24 h recalls and erythrocyte fatty acid analyses. A total of sixty-seven subjects were randomised to either (1) an average-n-3 PUFA, low-n-6 PUFA (L6) intervention designed to lower linoleic acid (LA; #2·5% of energy (en%)) and arachidonic acid (#60 mg/d), while maintaining an average US intake of n-3 PUFA or (2) a high-n-3 PUFA, low-n-6 PUFA (H3-L6) intervention designed to lower n-6 LA, while increasing the n-3 PUFA a-linolenic acid (ALA; $1·5 en%) and EPA þ DHA ($1000 mg/d). Pre- and intraintervention nutrient intakes were estimated with six 24 h dietary recalls per subject. Both groups achieved the targeted reductions in dietary LA to #2·5 en% (median LA 2·45 (2·1, 3·1); P,0·001). Intakes of n-3 PUFA did not change for the L6 group. Target increases in n-3 ALA (median 1·6 en%, (1·3, 2·0), P,0·001) and EPA þ DHA (1482 mg, (374, 2558), P,0·001) were achieved in the H3-L6 group. Dietary changes were validated by corresponding changes in erythrocyte n-6 and n-3 fatty acid composition. Dietary LA can be lowered to #2·5 en%, with or without concurrent increases in dietary n-3 PUFA, in an outpatient clinical trial setting using this integrated diet method.

Supplementing dairy cows with n-3 fatty acid-rich feeds does not easily increase quantities in milk fat. Previous results demonstrated very long-chain n-3 fatty acids are primarily transported in the PL fraction of blood, making them largely unavailable to the mammary gland for enrichment of milk fat. Our objective was to compare mammary uptake of fatty acids of increasing chain length and unsaturation delivered intravenously as TAG emulsions. Late lactation dairy cows were assigned to a completely randomized block design. Treatments were intravenous TAG emulsions enriched with oleic acid (OLA), linoleic acid (LNA), alpha-linolenic acid (ALA), or docosahexaenoic acid (DHA) and were delivered continuously at 16 mL/h for 72 h. Each treatment supplied 30 g/day of the target fatty acid. Treatment did not affect feed intake, milk yield, or milk composition, but all treatments reduced intake and yield. The proportion of DHA increased in plasma FFA, TAG, and PL with infusion. Increases of n-3 fatty acids, ALA, EPA, and DHA, were evident in the plasma PL fraction, suggesting re-esterification in the liver. Transfer efficiencies were 37.8 ± 4.1, 27.6 ± 5.4, and 10.9 ± 4.1 %, and day 3 total milk fatty acyl yields were 37.0 ± 3.4, 10.8 ± 0.4, and 3.3 ± 0.3 g for LNA, ALA, and DHA. Variation in oleic acyl yield prevented calculation of OLA transfer efficiency. Mammary uptake of fatty acids was reduced with increased chain length and unsaturation. Both liver and mammary mechanisms may regulate transfer of long-chain polyunsaturates.

Background: Cord serum (CS) phospholipid fatty acid composition is associated with maternal diet during foetal life, and maternal intake of linoleic acid (LA, C18:2ω-6) and α-linolenic acid (LNA, C18:3 ω-3) has been shown to influence the LA and LNA levels in CS. A possible connection between the increased incidence of atopic diseases and increased intake of LA and decreased intake of LNA in the Western world has been proposed., Aim: The aim of this study was to explore phospholipid fatty acid proportions and total IgE levels in CS from Swedish children, collected from 1985 to 2005, a period with increasing frequency of allergic diseases in Sweden, and reveal possible changes over time., Method: Phospholipid fatty acids and total IgE antibodies were analysed with gas chromatography and UniCAP(®) technology, respectively, in 300 CS samples., Results: The proportions of LA and LNA decreased significantly from 1985 to 2005 (p < 0.001 for both). However, the LA/LNA ratio did increase (p < 0.001), revealing a relatively larger decrease in LNA than in LA. No correlations were found between ω-6 and ω-3 fatty acids and total IgE antibodies in CS from newborn children., Conclusions: The LA/LNA ratio increased (p < 0.001) in cord serum samples collected between 1985 and 2005, and no correlations between fatty acids and total IgE were found.

Background/aims: Sex hormones may influence the activity of enzymes which are involved in the synthesis of long-chain polyunsaturated fatty acids. The objective of this review was to assess the role of gender in determining the fatty acid composition of human samples, like plasma and erythrocyte membrane lipids, and adipose tissue., Methods: The method included a structured search strategy on MEDLINE, Scopus and the Cochrane databases, with formal inclusion/exclusion criteria, data extraction procedure and meta-analysis., Results: We evaluated 51 publications, dated from 1975 to 2011. Meta-analysis showed significantly lower values of both arachidonic acid (AA) and docosahexaenoic acid (DHA) in total plasma lipids (32 and 33 studies) and in plasma phospholipids (PL; 21 and 23 studies) in men than in women. Primary analysis of the phospholipid fraction showed the mean difference in AA to be 0.42% weight/weight (95% CI: 0.18-0.65, n = 7,769) and in DHA 0.37% weight/weight (95% CI: 0.24-0.51, n = 8,541), while there was no gender difference in the values of linoleic acid and α-linolenic acid., Conclusions: This systematic review based on 51 publications showed significantly lower contribution of AA and DHA to plasma total lipids and plasma PL in men than in women. Gender distribution should be regarded as a significant potential confounding factor in every study assessing data on fatty acid composition., (Copyright © 2013 S. Karger AG, Basel.)

Background and Objective: Children with cystic fibrosis (CF) and pancreatic insufficiency (PI) are at risk for fatty acid (FA) abnormalities and essential FA deficiency, with low linoleic acid (LA) and docosahexaenoic acid (DHA) concentrations and abnormal triene:tetraene (T:T) and arachidonic acid (AA):DHA ratios. The aim of the article was to determine whether type of dietary fat predicted serum LA, DHA, T:T, and AA:DHA ratios in subjects with CF and PI as compared to an unaffected comparison group., Methods: Serum FA concentrations were assessed by capillary gas-liquid chromatography (mol%) and dietary intake by 7-day weighed food records; the 3-day coefficient of fat absorption was calculated. Total energy intake was expressed in kilocalories., Results: A total of 65 subjects with CF and PI (8.4 ± 1.0 years, 32 girls) and 22 controls (8.5 ± 1.1 years, 13 girls) were included. Despite greater energy, saturated fat, and LA intake, the subjects with CF had lower serum LA and DHA and higher T:T and AA:DHA than those in the comparison group. Dietary total fat, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), LA, total ω 6 polyunsaturated fatty acid (Tω6PUFA), and α-linolenic acid (ALA) intake positively predicted serum LA concentration. MUFA, total ω 3 polyunsaturated fatty acid (Tω3PUFA), and ALA intake positively predicted serum DHA concentration. Total dietary fat, MUFA, PUFA, Tω3PUFA, LA, and ALA intake negatively predicted serum T:T. ALA and Tω3PUFA intake negatively predicted serum AA:DHA., Conclusions: Dietary fat patterns influenced serum LA, DHA, T:T, and AA:DHA in children with CF and PI. These data suggest that changes in dietary practices may result in FA profiles associated with improved clinical outcomes.

Background: Polyunsaturated fatty acids (PUFA) have diverse biological effects, from promoting inflammation to preventing cancer and heart disease. Growing evidence suggests that individual PUFA may have independent effects in health and disease. The individual roles of the two essential PUFA, linoleic acid (LA) and α-linolenic acid (ALA), have been difficult to discern from the actions of their highly unsaturated fatty acid (HUFA) downstream metabolites. This issue has recently been addressed through the development of the Δ-6 desaturase knock out (D6KO) mouse, which lacks the rate limiting Δ-6 desaturase enzyme and therefore cannot metabolize LA or ALA. However, a potential confounder in this model is the production of novel Δ-5 desaturase (D5D) derived fatty acids when D6KO mice are fed diets containing LA and ALA, but void of arachidonic acid., Objective: The aim of the present study was to characterize how the D6KO model differentially responds to diets containing the essential n-6 and n-3 PUFA, and whether the direct provision of downstream HUFA can rescue the phenotype and prevent the production of D5D fatty acids., Methodology: Liver and serum phospholipid (PL) fatty acid composition was examined in D6KO and wild type mice fed i) 10% safflower oil diet (SF, LA rich) ii) 10% soy diet (SO, LA+ALA) or iii) 3% menhaden oil +7% SF diet (MD, HUFA rich) for 28 days (n = 3-7/group)., Results: Novel D5D fatty acids were found in liver PL of D6KO fed SF or SO-fed mice, but differed in the type of D5D fatty acid depending on diet. Conversely, MD-fed D6KO mice had a liver PL fatty acid profile similar to wild-type mice., Conclusions: Through careful consideration of the dietary fatty acid composition, and especially the HUFA content in order to prevent the synthesis of D5D fatty acids, the D6KO model has the potential to elucidate the independent biological and health effects of the parent n-6 and n-3 fatty acids, LA and ALA.

Objectives: Long-chain polyunsaturated fatty acid (LC-PUFA) enrichment of preterm infant formulas is recommended to meet high demands. Dietary LC-PUFA may inhibit endogenous LC-PUFA synthesis, thus limiting their benefit. We investigated effects of different docosahexaenoic acid (DHA) intakes on plasma and erythrocyte fatty acids and endogenous LC-PUFA synthesis in preterm infants., Methods: Forty-two preterm infants (birth weight 1000-2200 g) were randomized double-blind to preterm formulas with γ-linolenic acid (0.4%) and arachidonic acid (AA, 0.1%) but different DHA contents (A: 0.04%, B: 0.33%, C: 0.52%); 24 received human milk (HM: 0.51% AA, 0.38% DHA, nonrandomized). Blood was sampled on study days 0, 14, and 28. Uniformly C-labeled linoleic acid (2 mg/kg) and α-linolenic acid (1 mg/kg) were applied orally on day 26 and blood samples collected 48  hours later., Results: On day 28, group A had the lowest and group C the highest plasma phospholipid concentrations of eicosapentaenoic acid and DHA. Erythrocyte phospholipid DHA was lowest in group A, but comparable in groups B, C, and HM. Plasma and erythrocyte AA were lower in formula groups than in HM. DHA intake had no effect on DHA synthesis. LC-PUFA synthesis was lower in HM infants., Conclusions: DHA supply dose dependently increased plasma DHA. Formula DHA levels of 0.33% matched plasma DHA status of infants fed HM. LC-PUFA synthesis was lower in infants fed HM than formulas with different DHA and low AA contents. With the LC-PUFA supplementation used, DHA in formulas did not inhibit AA or DHA synthesis.

Objective: To study the effect of modified polyunsaturated fatty acid (PUFA) profiles of complementary food on long-chain (LC) PUFA composition in healthy infants., Design: Double blinded, randomised, controlled intervention trial., Setting: Dortmund, Germany., Patients: Free-living sample of healthy term infants., Methods: Participants were randomly assigned within the first 2 months of life. During the intervention period from 4 to 10 months, the control group (n = 53) received commercial complementary meals with corn oil (3.4 g/meal) rich in n-6 linoleic acid (LA), the intervention group (n = 49) received the same meals with rapeseed oil (1.6 g/meal) rich in n-3 alpha-linolenic acid (ALA). Fatty acid intake was assessed from dietary records throughout the intervention period. Fatty acid proportions (% of total fatty acid) in total plasma were analysed before and after the intervention., Results: Plasma fatty acid profiles did not differ between the intervention and control groups before the intervention. During the intervention, the only difference in fatty acid intake between the intervention and control groups was a higher intake of ALA in the intervention group, 21% deriving from study food and a lower ratio of LA/ALA (10.7 vs 14.8). At the end of the intervention, the plasma proportions of total n-3 fatty acids and of n-3 LC-PUFA, but not of ALA, were higher and the ratios of n-6/n-3 fatty acids were lower in the intervention group., Conclusions: Feasible dietary modifications of the precursor fatty acid profile via n-3 PUFA-rich vegetable oil favoured n-3 LC-PUFA synthesis in the complementary feeding period when LC-PUFA intake from breast milk and formula is decreasing.

An experiment was conducted to evaluate the effects of pasture finishing versus feedlot finishing, over time, on fatty acid metabolism in Angus crossbred steers (n = 24). Ruminal fluid, serum, and adipose tissue biopsies were obtained on d 0, 28, 84, and 140. Pasture forages and diet ingredient samples were obtained at 14-d intervals to determine nutritive value and fatty acid composition. The feedlot diet consisted of corn silage, cracked corn grain, soybean meal, and a vitamin and mineral supplement. The pasture-finished steers grazed sequentially on triticale (x Triticosecale rimpaui)/annual ryegrass (Lolium multiflorum), alfalfa (Medicago sativa)/orchardgrass (Dactylis glomerata), and a cool-season grass/legume mixture. The feedlot diet contained an average of 57% of total fatty acids as linoleic acid and 2% as linolenic acid. The pasture forages contained 9% of total fatty acids as linoleic acid and 66% as linolenic acid. Concentrations (% of total fatty acids) of linolenic acid were greater (P < 0.05) in ruminal fluid, serum, and adipose tissue of the pasture-finished steers, compared with the feedlot-finished steers. Concentrations (% of total fatty acids) of cis-9, trans-11 CLA were greater (P < 0.05) in adipose tissue of the pasture-finished steers than feedlot-finished steers. Concentrations of cis-9, trans-11 CLA in adipose tissue declined (P < 0.05) in the feedlot-finished steers from d 0 to 28 to 84. In the pasture-finished steers, concentrations of cis-9, trans-11 CLA in adipose tissue (mg/g of tissue) peaked (P < 0.05) on d 28 and remained elevated (ranged from 9.91 to 12.80 mg/g of tissue) throughout the duration of the study. In the pasture-finished steers, linolenic acid concentrations tended to peak (P = 0.07) on d 28 and remained elevated (ranged from 0.64 to 0.80% of total fatty acids) throughout the study. It appears that only a short time is needed to alter the n-3 and CLA composition of adipose tissue in cattle finished on pasture.

Background: The essential fatty acids and their long-chain polyunsaturated derivatives (LC PUFAs) are important for the growth and maturation of the fetal organism., Objective: The aim of a study was to assess the profile of the essential fatty acids and their LC PUFAs in the blood and adipose tissue of pregnant women and in the cord blood after elective caesarean section., Design: The study group comprised 36 women and 38 their full-term babies born after elective caesarean section. In maternal adipose tissue, maternal blood (separately in plasma and erythrocytes) and cord blood (separately arterial and venous) composition of the fatty acids in total lipids was estimated with gas chromatography., Results: In the maternal plasma and erythrocytes the weight percent content of linoleic acid and alfalinolenic acid was higher and of LC PUFAs was lower than in plasma and erythrocytes from the umbilical vein with the exception of EPA and DPA. In the maternal subcutaneous adipose tissue the content of alfalinolenic acid was higher and of linoleic acid and of LC PUFAs were lower than in maternal plasma and erythrocytes. There was no significant difference in the weight percent content of estimated acids between the venous and arterial umbilical blood. In the maternal plasma the weight percent content of linoleic acid, alfalinolenic acid and LC PUFAs was lower than in the maternal erythrocytes., Conclusion: Differences between maternal and cord blood essential fatty acids and their metabolites indicate that preferential placental transfer of n-6 and n-3 fatty acid metabolites or faster metabolic turnover of linolenic and arachidonic acids in the fetus than in mother is possible.

Objective: To validate a 171-item semi-quantitative food-frequency questionnaire (FFQ) for measurement of nutrient intake in an intervention trial based on walnut supplementation., Design and Setting: Free-living adults from Southern California were randomly assigned to either an intervention (walnut-supplemented) or a control diet. The prescribed 6-month intervention was > or = 28 g of walnuts per day for the walnut-supplemented group and > or = 2 g of walnuts per day for the control group. Participants provided at least six 24-hour dietary recalls and completed a self-administered FFQ., Subjects: Eighty-seven adults aged 30-72 years (48 females, 39 males)., Results: Our findings from validation (by correlation with six diet recall measures) of the measurement of 32 nutrients by the FFQ are as follows. We found significant positive correlations (corrected for measurement error) between the FFQ and diet recalls for total energy (r = 0.34), total carbohydrate (r = 0.42), vegetable protein (r = 0.43), total fat (r = 0.51), polyunsaturated fat (r = 0.77), total fibre (r = 0.60), linoleic acid (r = 0.78) and alpha-linolenic acid (r = 0.79) - the last nutrient being an excellent nutrient biomarker of the intervention (walnut supplementation). Significant positive correlations were also found for vitamin C (r = 0.96) and certain minerals (r = 0.46-0.80 for calcium, phosphorus, magnesium, iron and potassium). Uncorrected correlations were also high (r>0.40) for retinol, beta-carotene, folate and alcohol. Both diet recalls and FFQ showed a similar significant difference in alpha-linolenic acid content between the walnut-supplemented and control diets., Conclusions: The FFQ demonstrated good relative validity in the estimation intake of some of the major nutrients in a dietary intervention trial and was a particularly valid estimate of an important nutrient biomarker of walnut supplementation.

Familial adenomatous polyposis (FAP) provides a model of APC inactivation as an early genetic event for the approximately 85% of colorectal cancers that develop from polyps. Abnormal fatty acid composition of tissues and serum phospholipids has been linked to cancer risk. Our aim was to describe the composition of fatty acids in serum phospholipids in 38 colectomized FAP patients as compared to 160 healthy subjects. Mean fatty acid intakes were similar between the groups. Colectomy was done on average 16 years prior to inclusion, and 18% were diagnosed with colorectal cancer at colectomy. The levels (weight %) of linoleic and alpha-linolenic acid were higher among the reference subjects (difference: 3.96, 95% confidence interval (CI) = 2.87, 5.04, and difference: 0.06, 95% CI = 0.04, 0.08, respectively), and the levels of arachidonic and docosahexaenoic acid were lower (difference: -3.70, 95% CI = -4.35, -3.06, and difference: -5.26, 95% CI = -6.25, -4.28, respectively) as compared to the FAP patients (all p < or = 0.0001). The abnormal fatty acid composition was not related to time since colectomy, intestinal reconstruction or history of colorectal cancer for any of the fatty acids assessed. Compositional differences in the fatty acid profile of serum phospholipids have not been described before in FAP patients. Further studies are needed to confirm these findings and assess clinical significances of a possible distorted fatty acid metabolism, including a potentially different dietary need of essential fatty acids. The relevance of these findings for APC induced cancers remains unclear.

Background: Infants in developing countries require early dietary interventions to prevent nutritional deficiencies, above all protein, energy, iron and zinc. To what extent these interventions may affect the fatty acid (FA) status is still unknown., Objectives: To examine and compare the effects of 2 micronutrient "sprinkles" supplementations (iron 12.5 mg + folic acid 150 microg, iron/folate and iron 12.5 mg + folic acid 150 microg + zinc 5 mg + vitamins A, C and D3, mineral/micronutrient [MMN]) versus placebo on the FA status of Cambodian infants., Methods: A total of 204 infants age 6 mo and living in Kompong Chhnang Province, Cambodia, were randomly assigned to receive daily supplementation of MMN (n = 68) and iron/folate (n = 68) or placebo (n = 68) for a 12-mo period in powder form as sprinkles. At the end of the intervention period, FAs in the range of 16 to 24 C were determined in blood drops absorbed on a strip collected from 182 subjects, and values among the 3 intervention subgroups and those of 21 Italian 18-mo-old, normal-growing infants as the reference group were compared., Results: At the end of the supplementation trial, higher levels of the 2 essential FAs (EFAs) (linoleic acid, 18:2n-6, and alpha-linolenic acid, 18:3n-3) were found in the MMN group. No differences occurred for the major longer chain derivatives of both EFAs arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3). In MMN supplemented Cambodians, blood levels of linoleic acid approached those of Italian infants, and in addition their alpha-linolenic acid levels were improved. Cambodian infants, mostly still breast-fed through the second year of life, showed significantly higher levels of long-chain derivatives of both the n-6 and the n-3 series compared with Italians., Conclusions: Supplementation with iron, folic acid, zinc and vitamins was associated with an increase of linoleic acid and alpha-linolenic acid levels in Cambodian infants versus placebo, without significant changes in the concentrations of their longer chain derivatives, resulting in a FA status closer to Italian counterparts for the essential polyunsaturated FA levels. The iron/folate-treated infants showed no differences compared with the other 2 groups. Studies are needed to differentiate the potential effects of the supplemented micronutrients on the FA status.

Background: Human in vivo data on dietary determinants of alpha-linolenic acid (ALA; 18:3n-3) metabolism are scarce., Objective: We examined whether intakes of ALA or linoleic acid (LA; 18:2n-6) or their ratio influences ALA metabolism., Design: During 4 wk, 29 subjects received a control diet (7% of energy from LA, 0.4% of energy from ALA, ALA-to-LA ratio = 1:19). For the next 6 wk, a control diet, a low-LA diet (3% of energy from LA, 0.4% of energy from ALA, ratio = 1:7), or a high-ALA diet (7% of energy from LA, 1.1% of energy from ALA, ratio = 1:7) was consumed. Ten days before the end of each dietary period, [U-13C]ALA was administered orally for 9 d. ALA oxidation was determined from breath. Conversion was estimated by using compartmental modeling of [13C]- and [12C]n-3 fatty acid concentrations in fasting plasma phospholipids., Results: Compared with the control group, ALA incorporation into phospholipids increased by 3.6% in the low-LA group (P = 0.012) and decreased by 8.0% in the high-ALA group (P < 0.001). In absolute amounts, it increased by 34.3 mg (P = 0.020) in the low-LA group but hardly changed in the high-ALA group. Nearly all ALA from the plasma phospholipid pool was converted into eicosapentaenoic acid. Conversion of eicosapentaenoic acid into docosapentaenoic acid and docosahexaenoic acid hardly changed in the 3 groups and was <0.1% of dietary ALA. In absolute amounts, it was unchanged in the low-LA group, but increased from 0.7 to 1.9 mg (P = 0.001) in the high-ALA group. ALA oxidation was unchanged by the dietary interventions., Conclusion: The amounts of ALA and LA in the diet, but not their ratio, determine ALA conversion.

Evidence from animal studies suggests that conjugated linoleic acid (CLA) modulates plasma and tissue appearance of newly synthesized PUFA. The effects of a 1.2g (0.5 % energy) daily intake of the cis-9,trans-11 (c9,t11) isomer of CLA, trans-10,cis-12 (t10,c12) isomer of CLA or olive oil (placebo) on linoleic acid (LA) and linolenic acid (LNA) metabolism in healthy human volunteers was investigated. Fifteen subjects were fed an experimental diet and supplemented with c9,t11-CLA, t10,c12-CLA or placebo for 7 d before consuming a tracer dose of U-[(13)C]LA (50 mg) and U-[(13)C]LNA (50 mg). Blood samples were taken at 0, 2, 4, 6, 8, 24, 48, 72 and 168 h and analysed using high-precision MS. No differences between the groups in peak plasma [(13)C]LA (10.3-11.6 % of dose), [(13)C]LNA (2.5-2.9 % of dose), [(13)C]arachidonic acid (0.09-0.12 % of dose), [(13)C]EPA (0.04-0.06 % of dose) or [(13)C]DHA (0.06-0.10 % of dose) were detected. Concentration v. time curves (area under the curve) also showed no significant differences between groups. This suggests that, in healthy human subjects consuming a diet with adequate intake of essential fatty acids, CLA does not affect metabolism of LA or LNA.

Objective: To investigate the effects of increased alpha-linolenic acid (ALA)-intake on intima-media thickness (IMT), oxidized low-density lipoprotein (LDL) antibodies, soluble intercellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and interleukins 6 and 10., Design: Randomized double-blind placebo-controlled trial., Subjects: Moderately hypercholesterolaemic men and women (55 +/- 10 y) with two other cardiovascular risk factors (n = 103)., Intervention: Participants were assigned to a margarine enriched with ALA (fatty acid composition 46% LA, 15% ALA) or linoleic acid (LA) (58% LA, 0.3% ALA) for 2 y., Results: Dietary ALA intake was 2.3 en% among ALA users, and 0.4 en% among LA users. The 2-y progression rate of the mean carotid IMT (ALA and LA: +0.05 mm) and femoral IMT (ALA:+0.05 mm; LA:+0.04 mm) was similar, when adjusted for confounding variables. After 1 and 2 y, ALA users had a lower CRP level than LA users (net differences -0.53 and -0.56 mg/l, respectively, P < 0.05). No significant effects were observed in oxidized LDL antibodies, and levels of sICAM-1, interleukins 6 and 10., Conclusions: A six-fold increased ALA intake lowers CRP, when compared to a control diet high in LA. The present study found no effects on markers for atherosclerosis., Sponsorship: The Dutch 'Praeventiefonds'.

Two experiments were run concurrently to determine the effect of fresh forage consumption on the production and proportions of plasma and milk fat vaccenic acid (VA), conjugated linoleic acid (CLA), and linolenic acid in diary cattle. In experiment 1, the cows consumed 50, 65, and 80% of their feed intake as pasture with the remainder of intake as a barley-based concentrate. The proportion of VA in milk fatty acids increased 12% when pasture intake increased from 50 to 65% of total dry matter intake and VA, CLA, and linolenic acid proportions increased 26, 18, and 27%, respectively, as pasture increased from 65 to 80% of dietary intake. In experiment 2, fresh forage was compared to conserved hay (cut from the same pasture the previous summer) to determine the effect on plasma and milk fat VA, CLA, and linolenic acid. Also, the effect of crushed solin seed (a flax cultivar that is high in linoleic acid) supplementation to the fresh forage diet was determined. Fresh forage compared to conserved hay in the diet, increased the proportion of CLA in the plasma very low density lipoproteins (VLDL) fraction by 71% but had no effect on linolenic acid. Supplementation of the fresh forage diet with a linoleic acid source increased VA and CLA in the plasma VLDL fraction 25 and 58% and slightly decreased the proportion of linolenic acid. Fresh forage, compared to conserved hay, increased milk fat VA and CLA proportions by 22 and 15%. Supplementing the fresh forage diet with linoleic acid from crushed solin seed further increased milk fat VA and CLA proportions 41 and 25%. Solin supplementation in a lactation diet is a superior method to increase CLA levels in milk fat than feeding fresh forage alone.

Background: Arachidonic acid (AA) and docosahexaenoic acid (DHA) are important for growth and neural development. trans Fatty acids (TFAs) may inhibit desaturation of linoleic acid (LA) and alpha-linolenic acid (ALA) to AA and DHA, respectively. Conjugated linoleic acids (CLAs) also alter lipid metabolism and body fat., Objective: We determined the associations of birth outcome with maternal and infant plasma concentrations of TFAs, CLAs, AA, and DHA., Design: In healthy women, we sampled maternal blood at 35 wk gestation (n = 58) and umbilical cord blood at birth (n = 70)., Results: Mean (+/- SEM) TFA concentrations (% by wt) in infant plasma were as follows: triacylglycerol, 2.83 +/- 0.19 (range: 0.63-12.79); phospholipid, 0.67 +/- 0.03 (0.11-1.33); and cholesteryl ester, 2.04 +/- 0.01 (0.86-4.24). LA, AA, DHA, TFA, and CLA concentrations in infant phospholipids correlated with the same fatty acid in maternal plasma phospholipids (n = 44; P < 0.05). Infant plasma cholesteryl ester and triacylglycerol TFAs and cholesteryl ester CLAs (r = -0.33, -0.42, and -0.49, respectively) were significantly inversely related to length of gestation. Triacylglycerol and cholesteryl ester AA were positively related to length of gestation (r = 0.41 and 0.37, respectively) and birth weight (r = 0.27 and 0.23, respectively). Inverse correlations occurred between infant plasma TFA and DHA concentrations in triacylglycerols (r = -0.33) and between TFA and AA concentrations in cholesteryl esters (r = -0.23)., Conclusion: The results suggest possible important effects of TFAs and of AA on fetal growth and length of gestation.

Background: Prevention of coronary heart disease (CHD) in high-risk subjects., Objective: To investigate the associations of dietary intake of alpha-linolenic acid (ALA) and linoleic acid (LA) as assessed by food frequency questionnaire and in the plasma cholesteryl ester (CE), with CHD risk factors., Design: Baseline data of a double-blind, randomized placebo-controlled trial. Subjects have hypercholesterolemia (6.0-8.0 mmol/l) and at least two other CHD risk factors (n=266)., Results: The reported dietary ALA and LA intakes and the LA/ALA ratio were associated with the contents in the CE (r=0.37, r=0.21, and r=0.42, respectively; P<0.01). In multivariate analysis, CE ALA was inversely associated with diastolic blood pressure (r=-0.13; P<0.05) and positively with serum triacylglycerol (r=0.13; P<0.05), and CE LA was inversely associated with serum triacylglycerol (r=-0.32; P<0.01). The CE LA/ALA ratio was strongly inversely associated with CE ALA (r=-0.95; P<0.01). In the lowest quintile of CE ALA, mean dietary intake was 0.4 energy % ALA (1.2 g/day), 8.4 energy % LA and an LA/ALA ratio of 21, and in the highest quintile 0.6 energy % ALA (1.7 g/day), 6.8 energy % LA and 12 (ratio). In the lowest quintile of CE ALA the diastolic blood pressure was 4 mm Hg lower (P trend<0.05), and the serum triacylglycerol 0.3 mmol/l higher (P trend NS) when compared with the top quintile., Conclusions: In a CHD high-risk population with LA-rich background diet, these cross-sectional data suggest that replacing LA in the diet by ALA may decrease diastolic blood pressure, and may increase serum triacylglycerol concentration.