Dietary Linoleic Acid Research Articles

Reply to Dr. C. K. Chow

Dear Editor, In our article entitled “Dietary β-tocopherol and linoleic acid, serum insulin, and waist circumference predict circulating sex hormone-binding globulin in premenopausal women” (1), we reported an association between β-tocopherol and/or linoleic acid consumption and circulating concentrations of sex hormone-binding globulin (SHBG). Using various statistical approaches, we showed that the β-tocopherol and/or linoleic acid consumption was an independent predictor of circulating SHBG in premenopausal women. We agree with the points Dr. Chow raised, and we adequately discussed all of them in our article, including the measurement of serum concentrations of β-tocopherol and the accuracy of estimated fat intake by the tools used; we limited making causal inferences from our findings due to the cross-sectional design of the study. We also agree with Dr. Chow that a functional relationship between β-tocopherol and SHBG was not clear, and we commented on this in the last paragraph of the Discussion. Dr. Chow's final remark that multiple correlations might be observed for any biomarker studied is also valid. However, to minimize the multiple correlation problem, we examined the data using principal component analysis (PCA), a data reduction procedure that clusters a large number of correlated variables into a smaller number of uncorrelated components or factors. Fifty-four nutrients resulted in 12 components after PCA analysis. Not only did β-tocopherol and linoleic acid cluster in the same component, as would be expected, but this component was also an independent predictor of SHBG by multiple regression analyses, validating the regression analysis results using individual nutrients. The last paragraph of the Introduction summarizes the advantages of PCA compared with analysis of individual nutrients in nutritional epidemiology studies. We do not agree that our findings are “questionable,” but rather, that they suggest a need for further research on the relationships among these nutrients, SHBG, and metabolic differences in humans.

Effect of dietary linolenic acid/linoleic acid ratio on growth performance, hepatic fatty acid profiles and intermediary metabolism of juvenile yellow catfish Pelteobagrus fulvidraco

The present study aimed to evaluate the effect of dietary linolenic acid (LNA)/linoleic acid (LA) ratio on growth performance, hepatic fatty acid profile and intermediary metabolism of juvenile yellow catfish Pelteobagrus fulvidraco. Six isonitrogenous and isolipidic diets were formulated to contain incremental levels of LNA from 0 to 5% at the expense of corn oil (rich in LA), resulting in six dietary treatments with LNA to LA ratios ranging from 0.35 to 14.64. The experiment continued for 7 weeks. Best growth and feed intake were obtained in the fish fed the diets containing the LNA/LA ratios of 1.17 and 2.12 ( P < 0.05). In contrast, feed conversion ratio was the lowest for fish fed the diets containing the LNA/LA ratios of 1.17 and 2.12 ( P < 0.05). Dietary LNA to LA ratios significantly influenced viscerosomatic index and hepatosomatic index ( P < 0.05), but not condition factor ( P > 0.05). Body composition was also significantly influenced by dietary LNA to LA ratios ( P < 0.05). Generally, liver FA compositions reflected dietary FA profiles. Declining LA and increasing LNA contents in liver were observed with the increasing dietary LNA/LA ratios ( P < 0.05). Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increased with the increasing LNA to LA ratios, suggesting that yellow catfish could elongate and desaturate C18 polyunsaturated fatty acids into highly unsaturated fatty acids . As a consequence, the n−6 fatty acids (FA) declined, and total n−3 FA and n−3/ n−6 ratios increased with the dietary ratios of LNA/LA ( P < 0.05). Dietary LNA to LA ratios significantly influenced several enzymatic activities involved in liver intermediary metabolism ( P < 0.05), such as lipoprotein lipase, hepatic lipase, pyruvate kinase, succinate dehydrogenase, malic dehydrogenase and lactate dehydrogenase, suggesting that dietary LNA/LA ratios had significant effects on nutrient metabolism in the liver. To our knowledge this is the first demonstration of the effects of dietary LNA to LA ratios on the enzymatic activities of liver in fish, which provides information on diet quality and utilization, and can also be used as an indicator of the nutritional status of this fish.

Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and the aetiology of ulcerative colitis: a nested case–control study within a European prospective cohort study

Objective:Dietary linoleic acid, an n-6 polyunsaturated fatty acid, is metabolised to arachidonic acid, a component of colonocyte membranes. Metabolites of arachidonic acid have pro-inflammatory properties and are increased in the...

Prostate Tumor Growth Can Be Modulated by Dietarily Targeting the 15-Lipoxygenase-1 and Cyclooxygenase-2 Enzymes

The main objectives of our study were to determine the bioavailability of omega-3 (ω-3) to the tumor, to understand its mechanisms, and to determine the feasibility of targeting the ω-6 polyunsaturated fatty acids (PUFAs) metabolizing 15-lipoxygenase-1 (15-LO-1) and cyclooxygenase-2 (COX-2) pathways. Nude mice injected subcutaneously with LAPC-4 prostate cancer cells were randomly divided into three different isocaloric (and same percent [%] of total fat) diet groups: high ω-6 linoleic acid (LA), high ω-3 stearidonic acid (SDA) PUFAs, and normal (control) diets. Tumor growth and apoptosis were examined as end points after administration of short-term (5 weeks) ω-3 and ω-6 fatty acid diets. Tumor tissue membranes were examined for growth, lipids, enzyme activities, apoptosis, and proliferation. Tumors from the LA diet-fed mice exhibited the most rapid growth compared with tumors from the control and SDA diet-fed mice. Moreover, a diet switch from LA to SDA caused a dramatic decrease in the growth of tumors in 5 weeks, whereas tumors grew more aggressively when mice were switched from an SDA to an LA diet. Evaluating tumor proliferation (Ki-67) and apoptosis (caspase-3) in mice fed the LA and SDA diets suggested increased percentage proliferation index from the ω-6 diet-fed mice compared with the tumors from the ω-3 SDA-fed mice. Further, increased apoptosis was observed in tumors from ω-3 SDA diet-fed mice versus tumors from ω-6 diet-fed mice. Levels of membrane phospholipids of red blood cells reflected dietary changes and correlated with the levels observed in tumors. Linoleic or arachidonic acid and metabolites (eicosanoid/prostaglandins) were analyzed for 15-LO-1 and COX-2 activities by high-performance liquid chromatography. We also examined the percent unsaturated or saturated fatty acids in the total phospholipids, PUFA ω-6/ω-3 ratios, and other major enzymes (elongase, Delta [Δ]-5-desaturase, and Δ-6-desaturase) of ω-6 catabolic pathways from the tumors. We observed a 2.7-fold increase in the ω-6/ω-3 ratio in tumors from LA diet-fed mice and a 4.2-fold decrease in the ratio in tumors from the SDA diet-fed mice. There was an increased Δ-6-desaturase and Δ-9 desaturase enzyme activities and reduced estimated Δ-5-desaturase activity in tumors from mice fed the SDA diet. Opposite effects were observed in tumors from mice fed the LA diet. Together, these observations provide mechanistic roles of ω-3 fatty acids in slowing prostate cancer growth by altering ω-6/ω-3 ratios through diet and by promoting apoptosis and inhibiting proliferation in tumors by directly competing with ω-6 fatty acids for 15-LO-1 and COX-2 activities.

Fatty acid patterns early after premature birth, simultaneously analysed in mothers' food, breast milk and serum phospholipids of mothers and infants

BackgroundThe supply of long-chain polyunsaturated fatty acids via the placenta is interrupted in premature infants, making them exclusively dependent on breast milk, which varies in fatty acid (FA) concentrations depending on the mother's diet.ObjectiveTo in a longitudinal study explore the relation between FA status in mothers and infants from an unselected cohort of prematures, not requiring intensive care.DesignBreast milk and mothers' and infants' plasma phospholipid FA concentrations from birth to 44 weeks of gestational age were analysed and compared with mothers' food intake, assessed using a 3-day diary. Fatty acids were analysed by capillary gas-liquid chromatography.ResultsThe energy intake was low in 75% of mothers, and 90% had low intake of essential FAs (EFAs). Dietary linoleic acid (LA, 18:2w6), but not w3 FAs, correlated to concentrations in breast milk. Infants' plasma and breast milk correlated for arachidonic (AA, 20:4w6), eicosapentaenoic (EPA, 20:5w3) and docosahexaenoic (DHA, 22:6w3) acids. A high concentration of mead acid (20:3w9) in the infants at birth correlated negatively to the concentrations of LA, AA and w3 FAs. Infants of mothers who stopped breastfeeding during the study period showed decreased DHA concentrations and increased w6/w3 ratios, with the opposite FA pattern seen in the mothers' plasma.ConclusionAlthough dietary w3 FAs were insufficient in an unselected cohort of mothers of premature infants, breastfeeding resulted in increased levels of DHA in the premature infants at the expense of the mothers, suggesting a general need to increase dietary w3 FAs during pregnancy and lactation.

Dietary β-Tocopherol and Linoleic Acid, Serum Insulin, and Waist Circumference Predict Circulating Sex Hormone-Binding Globulin in Premenopausal Women1–4

Reduced levels of circulating sex hormone-binding globulin (SHBG) are implicated in the etiology of sex steroid-related pathologies and the metabolic syndrome. Dietary correlates of serum SHBG remain unclear and were studied in a convenient cross-sectional sample of healthy 30- to 40-y-old women (n = 255). By univariate analyses, serum SHBG correlated negatively with several indices of the metabolic syndrome, such as BMI, waist circumference, hip circumference (r = -0.36 to -0.44; P < 0.0001), fasting serum insulin (r = -0.41; P < 0.0001), serum triglycerides (r = -0.27; P < 0.0001), serum glucose (r = -0.23; P < 0.001), and plasma testosterone (r = -0.19; P = 0.002). Serum SHBG correlated positively with serum HDL-cholesterol (r = 0.33; P < 0.0001), plasma progesterone (r = 0.17; P = 0.007), and dietary intake of beta-tocopherol (r = 0.17; P = 0.006), and negatively with that of fructose (r = -0.13; P = 0.04). Principal component analysis (PCA) extracted 12 nutrient factors with eigenvalues > 1.0 from 54 nutrients and vitamins in food records. Multivariate regression analyses showed that the PCA-extracted nutrient factor most heavily loaded with beta-tocopherol and linoleic acid (P = 0.03) was an independent positive predictor of serum SHBG. When individual nutrients were the predictor variables, beta-tocopherol (P = 0.002), but not other tocopherols or fatty acids (including linoleic acid), was an independent positive predictor of serum SHBG. Circulating insulin (P = 0.02) and waist circumference (P = 0.002), but not serum lipids, were negative independent predictors of SHBG in all regression models. Additional studies are needed in women of other age groups and men to determine whether consumption of foods rich in beta-tocopherol and/or linoleic acid may increase serum SHBG concentrations and may thereby decrease the risk for metabolic syndrome and reproductive organ cancer.

Physiological effects of dietary linoleic acid.

Physiological effects of dietary linoleic acid.

Dietary linoleic acid has no effect on arachidonic acid, but increases n-6 eicosadienoic acid, and lowers dihomo-γ-linolenic and eicosapentaenoic acid in plasma of adult men

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 Δ-6 desaturation and adversely affect n-3 fatty acid metabolism. Factors other than n-6 fatty acid intake are important modifiers of plasma ARA.

Differential effects of steroids on the synthesis of polyunsaturated fatty acids by human neuroblastoma cells

Polyunsaturated fatty acids (PUFA) are crucial for proper functioning of cell membranes, particularly in brain. Biologically important PUFA include docosahexaenoic acid (n-3 series) and arachidonic acid (n-6 series) which can be formed from their respective dietary essential precursors, α-linolenic acid (ALA) and linoleic acid (LA). Steroid hormones are thought to modulate PUFA synthesis in humans but whether they regulate PUFA status in brain and/or in neural membranes is unknown. In human neuroblastoma SH-SY5Y cells, we compared the effect of estradiol, testosterone, and progesterone on PUFA synthesis. Cells were incubated with ALA and/or LA 7μM in combination with estradiol, testosterone, or progesterone at 10nM without serum. The fatty acid composition was determined by gas chromatography and the mRNA expression of genes involved in PUFA metabolism by real-time RT-PCR. Estradiol affected both the n-3 and the n-6 PUFA conversion, the n-3 PUFA pathway being more sensitive to the estradiol treatment. In ALA-supplemented cells, estradiol increased while testosterone decreased the long-chain n-3 PUFA content (+17% and −15%, respectively) and the mRNA expression of the Δ5-desaturase (+11% and −9%), these two events being strongly correlated. Progesterone did not affect the PUFA composition. The positive effect of estradiol was blocked by the estrogen receptor antagonist ICI-182,780. We conclude that steroids have differential effects on PUFA synthesis and that their mode of action could involve the modulation of the Δ5-desaturase mRNA expression in neuroblastoma cells. These results help our understanding of the regulation of brain PUFA metabolism by steroid hormones.

Effect of a linseed diet or a sunflower diet on performances, fatty acid composition, lipogenic enzyme activities and stearoyl-CoA-desaturase activity in the pig

The aim of this study was to compare the influence of a high α-linolenic acid (ALA) diet (linseed diet) and a high linoleic acid (LA) diet (sunflower diet) on performances of pigs, on the dietetical quality of their tissues (adipose tissues and muscles), and on the lipogenic potential of these tissues. Growth and carcass performances, and the lipid content of the tissues were not affected by the diet. Feeding the linseed diet increased the content of n-3 PUFA and decreased the LA/ALA ratios in all the tissues, while the sunflower diet led to an increase in the n-6 PUFA contents. Neither the stearoyl-CoA-desaturase and glucose-6-phosphate-dehydrogenase activities nor the β-hydroxyacyl-CoA-dehydrogenase activity were affected by the diet. Acetyl-CoA-carboxylase and fatty acid synthase activities were enhanced with the linseed diet in respectively subcutaneous adipose tissue and intermuscular adipose tissue, while malic enzyme activity was decreased in liver and subcutaneous adipose tissue of pigs fed the linseed diet.

Dietary fatty acids and inflammation

AbstractIntroduction: It is commonly believed that inflammation can be reduced by lowering the dietary ratio of n‐6 (linoleic acid) to n‐3 polyunsaturated fatty acids as a means of lowering arachidonic acid levels in cell membranes. This review will examine this proposition.Results: Although many pro‐inflammatory molecules can be produced from arachidonic acid and this long‐chain n‐6 fatty acid can be produced from linoleic acid, changing dietary linoleic acid intake over a wide range does not have any significant effect on arachidonic acid levels in cell membranes, inflammation or immune functions. There are no data that show lowering dietary n‐6 polyunsaturated fats reduces inflammation. In contrast, arachidonic acid levels in cell membranes and inflammatory parameters are lowered by increasing intakes of long‐chain n‐3 polyunsaturated fatty acids. Resolvins and protectins, both derivatives of long‐chain n‐3 fats, also have potential anti‐inflammatory activity. In high doses, long‐chain n‐3 fats may have modest, beneficial effects on inflammation in rheumatoid arthritis. However, many studies have shown no effects of fish oil on inflammation parameters.Conclusions: The dietary n‐6/n‐3 ratio is not a useful measure of the inflammatory nature of a diet, though the absolute amount of dietary long‐chain n‐3 polyunsaturated fatty acids may be a guide.

Regulation of hepatic fatty acid elongase 5 by LXRα–SREBP-1c

Dietary essential fatty acids linoleic acid and α-linolenic acid are converted to arachidonic-, eicosapentaenoic-, and docosahexaenoic acid under tight regulation by nutritional status and hormones. Hepatic fatty acid elongase 5 (Elovl5) elongates C18-20 polyunsaturated fatty acids (PUFAs) and is important for biosynthesis of C20–22 PUFAs. We demonstrate that Liver X Receptor α (LXRα) and sterol regulatory binding protein-1c (SREBP-1c) regulate hepatic Elovl5 expression. LXRα and LXRβ play different roles in maintenance of basal expression of Elovl5. LXRα is necessary for basal as well as LXR agonist induced Elovl5 transcription. Promoter studies revealed that the mouse Elovl5 gene is a direct SREBP-1c target. The up-regulation of Elovl5 expression by LXR agonist is likely secondary to the induction of SREBP-1c. PUFAs repress expression of SREBP-1c and Elovl5, but when combined with LXR ligand stimulation, which increases SREBP-1c mRNA and nuclear SREBP-1c, Elovl5 mRNA levels are restored to normal. Our studies suggest that an LXRα–SREBP-1c pathway plays a regulatory role in hepatic biosynthesis of PUFAs through transcriptional activation of Elovl5 as well as other desaturases. The stimulatory role of LXRα–SREBP-1c in the production of PUFAs enables the possibility for a feedback regulation of hepatic lipogenesis through PUFA mediated repression of SREBP-1c expression.

5-Lipoxygenase and 5-Lipoxygenase-Activating Protein Gene Polymorphisms, Dietary Linoleic Acid, and Risk for Breast Cancer

The n-6 polyunsaturated fatty acid 5-lipoxygenase pathway has been shown to play a role in the carcinogenesis of breast cancer. We conducted a population-based case-control study among Latina, African-American, and White women from the San Francisco Bay area to examine the association of the 5-lipoxygenase gene (ALOX5) and 5-lipoxygenase-activating protein gene (ALOX5AP) with breast cancer risk. Three ALOX5AP polymorphisms [poly(A) microsatellite, -4900 A>G (rs4076128), and -3472 A>G (rs4073259)] and three ALOX5 polymorphisms [Sp1-binding site (-GGGCGG-) variable number of tandem repeat polymorphism, -1279 G>T (rs6593482), and 760 G>A (rs2228065)] were genotyped in 802 cases and 888 controls. We did not find significant main effects of ALOX5 and ALOX5AP genotypes on breast cancer risk that were consistent across race or ethnicity; however, there was a significant interaction between the ALOX5AP -4900 A>G polymorphism and dietary linoleic acid intake (P=0.03). Among women consuming a diet high in linoleic acid (top quartile of intake, >17.4 g/d), carrying the AA genotype was associated with higher breast cancer risk (age- and race-adjusted odds ratio, 1.8; 95% confidence interval, 1.2-2.9) compared with carrying genotypes AG or GG. Among women consuming <or=17.4 g/d of linoleic acid, ALOX5AP -4900 genotype was not associated with breast cancer risk (age- and race-adjusted odds ratio, 0.9; 95% confidence interval, 0.7-1.2). These results support a role for n-6 polyunsaturated fatty acids in breast carcinogenesis and suggest that epidemiologic studies on dietary fat and breast cancer should take into account genetic predisposition related to n-6 polyunsaturated fatty acid metabolism.

The health implications of changing linoleic acid intakes

Linoleic acid is the most prominent polyunsaturated fatty acid (PUFA) in the Western diet. It is virtually found in every food we eat and is the predominant PUFA in land-based meats, dairy, vegetables, vegetable oils, cereals, fruits, nuts, legumes, seeds and breads. Because linoleic acid is the metabolic precursor of arachidonic acid and bioactive eicosanoids derived from arachidonic acid, there is concern that dietary linoleic acid could augment tissue arachidonic acid content, eicosanoid formation and subsequently enhance the risk of and/or exacerbate conditions associated with acute and chronic diseases (i.e., cancers, cardiovascular disease, inflammation, neurological disorders, etc.). The following series of papers examines the impact of modifying dietary levels of linoleic acid on health outcomes. The authors were asked to start with current intakes of linoleic acid (adults) and determine if health outcomes would change if linoleic acid intake increased or decreased. The authors addressed changes in tissue arachidonic acid content and eicosanoid formation, cardiovascular disease, inflammation, and psychiatric disorders.

Estimated conversion of α‐linolenic acid to long chain n‐3 polyunsaturated fatty acids is greater than expected in non fish‐eating vegetarians and non fish‐eating meat‐eaters than in fish‐eaters

Background: It is believed that n‐3 polyunsaturated fatty acid (PUFA) status is important for cardiovascular health. However, the major sources of the essential dietary PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are fish and fish oil supplements. Limited conversion of α‐linoleic acid (ALA), found in plant foods (flaxseeds, walnuts, soya and rape‐seed oils), to EPA, DPA (docosapentaenoic acid) and DHA occurs in men (0.2–6% for EPA and DPA, ≤0.05% for DHA) but is greater in younger women (Burdge, 2006). Therefore, n‐3 PUFA status may be compromised in individuals not eating fish or fish‐oils, compared with fish‐eaters. An investigation into n‐3 PUFA status and estimated potential conversion of ALA in middle‐aged women with different dietary habits in the EPIC‐Norfolk population was conducted.Methods: Data were collected via a nurse examination between 1993 and 1997 (Welch, 2006). Circulating plasma phospholipid n‐3 PUFA were measured using gas liquid chromatography (HP 5980 gas chromatograph) (Welch, 2006). Diet was estimated using a 7‐day food diary and data were entered using the DINER data entry program (Welch, 2001). Only participants with dietary data and plasma fatty acids, who did not consume fish oils, were included in this study (n = 2256). Ethical permission was granted by the Norfolk and Norwich Ethics Committee. Participants were divided according to dietary habit into non‐fish‐eating vegetarians, non‐fish‐eating meat‐eaters and fish‐eaters (97% meat‐eaters). The ratio of circulating long chain n‐3 PUFA (LCn‐3PUFA are the total of EPA, DPA and DHA) to intake of ALA was calculated (PLCn‐3PUFA:DALA). A larger ratio implies greater conversion of ALA. Statistics were performed with STATA 10.0 and as ALA conversion may be affected by dietary EPA, DHA and linoleic acid, age, body mass index (BMI) and smoking habit, the ratio was adjusted for these covariates. The P for the difference between groups was calculated using anova.Results: Although intakes of total n‐3 PUFA were ≈30% lower in vegetarians and meat‐eaters than fish‐eaters, circulating plasma LCn‐3 PUFA were only 12% and 9% lower, respectively. The PLCn‐3PUFA:DALA was greater in vegetarians and meat‐eaters than in fish‐eaters. Population characteristics, diet, n‐3 PUFA status and the ratio of circulating long chain n‐3 PUFA to intake of dietary ALA (PLCn‐3PUFA:DALA) in 2256 women aged 39–78 years Vegetarian non‐fish‐eaters Meat eating non‐fish‐eaters Fish‐eaters P* N 56 309 1891 Mean SD Mean SD Mean SD Age 59.0 9.5 61.8 9.3 62.4 8.7 0.01 BMI (kg m−2) 25.7 4.1 27.0 4.7 26.7 4.4 0.09 Diet n‐3 PUFA g d−1 0.86 0.38 0.89 0.34 1.24 0.46 &lt;0.001 Plasma LCn‐3 PUFA μM 360 199 373 166 408 169 &lt;0.001 Mean 95% CI Mean 95% CI Mean 95% CI PLCn‐3PUFA:DALA† 0.149 0.123 0.171 0.142 0.133 0.152 0.129 0.125 0.133 0.002 PLCn‐3PUFA:DALA‡ 0.156 0.135 0.177 0.149 0.139 0.158 0.128 0.124 0.131 0.011 *Difference between groups. †Unadjusted data. ‡Adjusted for age, BMI, smoking habit, dietary EPA and DHA and circulating linoleic acid. Discussion: Although these are epidemiological findings and not the result of careful metabolic studies, the fact that the PLCn‐3PUFA:DALA ratio is ≈22% is higher in vegetarians and meat‐eaters than in fish‐eaters indicates that there is greater conversion of ALA than in fish‐eaters and may explain the smaller than expected differences in n‐3 PUFA status between fish and non‐fish consumers.Conclusions: If this finding were replicated in a controlled feeding study and it were confirmed that maintenance of n‐3 PUFA status was feasible from plant sources there could be implications for the requirements for fish intake.References Burdge, G.C. (2006) Metabolism of alpha‐linolenic acid in humans. Prostaglandins Leukot. Essent. Fatty Acids75, 161–168.Welch, A.A., Bingham, S.A., Ive, J., et al. (2006) Dietary fish intake and plasma phospholipid n‐3 polyunsaturated fatty acid concentrations in men and women in the European Prospective Investigation into Cancer‐Norfolk United Kingdom cohort. Am. J. Clin. Nutr. 84, 1330–1339.Welch, A.A., McTaggart, A., Mulligan, A.A., et al. (2001) DINER (Data Into Nutrients for Epidemiological Research) – a new data‐entry program for nutritional analysis in the EPIC‐Norfolk cohort and the 7‐day diary method. Public Health Nutr. 4, 1253–1265.

31 Dietary Linoleic Acid and the Aetiology of Ulcerative Colitis - a European Multi-Centre Prospective Cohort Study

31 Dietary Linoleic Acid and the Aetiology of Ulcerative Colitis - a European Multi-Centre Prospective Cohort Study

Effects of high fat diet on fecal contents of bile acids in rats.

The effects of dietary oils and fats used in Japan on the fecal contents of bile acids in rats were studied. F344/Du Crj female rats (8 weeks old) were fed on diet containing 20% corn oil, rape seed oil, sesame oil, soybean oil, lard, or tallow as high oil or fat diets or on 0.2% linoleic acid diet as a low fatty acid diet for 4 weeks, and then their feces were collected. Bile acids in the feces were partially purified and analyzed by high-performance liquid chromatography. Analyses showed that lard or tallow in the diet resulted in significant increases in the contents of bile acids in the feces, whereas sesame oil in the diet resulted in significant decreases in their contents.

The role of CD36 and Caveolin‐1 in atherosclerotic lesion formation

While CD36 has been found to have both positive and negative effects on the development of atherosclerosis, caveolin is thought to be cardioprotective. LDL receptor (LDLr) null mice form atherosclerotic lesions when fed a high fat (lard) diet. In this study, we examined the roles of CD36 and Caveolin‐1 (cav‐1) on the formation of atherosclerotic lesions in a LDLr null background. LDLr null, CD36/LDLr null, and Cav‐1/LDLr null mice were fed a high fat (lard) diet, myristic acid diet, linoleic acid diet, or a stearic acid diet for 9 – 13 weeks. At the end of the study, the mice were processed to quantify atherosclerotic lesions. On high fat (lard) diet, CD36/LDLr null mice had a dramatic increase in atherosclerotic lesions whereas the Cav‐1/LDLr null mice had a decrease compared to LDLr null mice. In contrast, on the myristic acid, linoleic acid, and stearic acid diets, the LDLr null mice produced significantly more lesions than both CD36/LDLr and Cav‐1/LDLr null mice. The stearic acid diet did not alter the extent of lesion formation between Cav‐1/LDLr and CD36/LDLr null mice however, the myristic acid and the linoleic acid diets increased lesion formation in the Cav‐1/LDLr null compared to the CD36/LDLr null mice. In conclusion, these data indicate that the role of CD36 in atherosclerosis is at least partially determined by the type of fat in the diets, whereas the absence of Cav‐1 seems to be protective.

How relevant is the ratio of dietary n-6 to n-3 polyunsaturated fatty acids to cardiovascular disease risk? Evidence from the OPTILIP study

There has been much debate over the practical utility of the dietary ratio of n-6 to n-3 polyunsaturated fatty acids in optimizing the benefits of n-3 fatty acids (C18-C22) on cardiovascular health. This review examines the supporting evidence from the OPTILIP study within the context of the emerging consensus on the value of this dietary metric. The question of whether the ratio of n-6/n-3 polyunsaturated fatty acids or total amounts of dietary polyunsaturated fatty acids is of more importance to cardiovascular health has been addressed recently in a randomly controlled trial (OPTILIP) and in a stable isotope tracer study. These two studies were independently unanimous in concluding that the ratio of n-6/n-3 polyunsaturated fatty acids is of no value in modifying cardiovascular disease risk. The latter study also showed that the absolute amounts of dietary linoleic acid and alpha-linolenic acid are of relevance to the efficiency of conversion of alpha-linolenic acid to eicosapentaenoic acid and docosahexaenoic acid. This review should help to settle any outstanding controversy over the dietary ratio of n-6/n-3 polyunsaturated fatty acids. It reinforces current recommendations to increase the consumption of preformed eicosapentaenoic acid/docosahexaenoic acid in fish, and supports dietary measures to increase and decrease intakes alpha-linolenic acid and linoleic acid, respectively, to promote the endogenous synthesis of these longer chain n-3 polyunsaturated fatty acids.

Salt Loading Increases Urinary Excretion of Linoleic Acid Diols and Triols in Healthy Human Subjects

Increased dietary linoleic acid has been associated with reduced blood pressure in clinical and animal studies possibly mediated by prostaglandins. Urinary linoleate and prostaglandin metabolite excretion were investigated in subjects exposed to a salt-loading/salt-depletion regimen. Twelve healthy subjects were recruited from the New Orleans population (before Hurricaine Katrina) and admitted to the Tulane-Louisiana State University-Charity Hospital General Clinical Research Center after a 5-day outpatient lead-in phase on a 160-mmol sodium diet. On inpatient day 1, the subjects were maintained on the 160-mmol sodium diet, and a 24-hour urine specimen was collected. On day 2, the subjects received 2 L of IV normal saline over 4 hours and continued on a 160-mmol Na(+) diet (total: 460 mmol of sodium). Two 12-hour urine collections were obtained. On day 3, the subjects received three 40-mg oral doses of furosemide, two 12-hour urine collections were obtained, and the subjects were given a 10-mmol sodium diet. Urinary oxidized lipids were measured by high-performance liquid chromatography-tandem quadrupole mass spectroscopy. The excretion of the urinary linoleate metabolites, dihydroxyoctadecamonoenoic acids, and trihydroxyoctadecamonoenoic acids increased significantly during intravenous salt loading as compared with day 1 and the salt-depleted periods. The urinary excretion of 6-keto- prostaglandin F1alpha was unaffected by salt loading but was dramatically increased 7- to 10-fold by salt depletion. Prostaglandin E2 excretion was positively correlated with sodium excretion. The salt-stimulated production of linoleic acid diols and triols may inhibit tubular sodium reabsorption, thereby assisting in the excretion of the sodium load.