Br J Nutr 2000 Apr;83(4):439-47

Br J Nutr 2000 Apr;83(4):439-47

Diets containing long-chain n-3 polyunsaturated fatty acids affect behaviour differently during development than ageing in mice.

Carrie I, Guesnet P, Bourre JM, Frances H

INSERM U. 26, Unite de Neuro-Pharmaco-Nutrition, Hopital. F. Widal, Paris, France. isabelle.carrie@lrb.ap-hop-paris.fr

The effect of a standard diet providing essential fatty acids enriched in fish oil or palm oil was studied in young, mature and old mice. Two groups of pregnant and lactating OF1 mice were fed on diets with or without high levels of long-chain n-3 polyunsaturated fatty acids. Offspring were maintained on these diets after weaning. The litter size did not differ. The weight increased more quickly in fish-oil-fed mice than palm-oil-fed mice. The fish-oil diet induced a significant increase in exploratory activity in young mice which was not found in mature and old mice. The level of locomotor activity was significantly higher in young, no different in mature, and lower in old fish-oil-fed mice than in controls. Habituation, the simpler form of learning, occurred to the same extent in the two diet groups. For the place learning protocol of the Morris water maze there was no difference between the two diet groups; however, in the probe trial, the mature fish-oil-fed mice remembered the situation well compared with the control mice. In the active avoidance test, on the first day of acquisition the young fish-oil-fed mice made more avoidances than control mice, whereas in contrast, mature and old-fish-fed mice made less avoidances than control mice. These results suggest a positive effect on arousal and learning ability of a diet enriched in long chain n-3 polyunsaturated fatty acids in young mice and a detrimental effect in old mice.

Br J Nutr 2000 Apr;83(4):371-9

Study of the effects of dietary fish intake on serum lipids and lipoproteins in two populations with different dietary habits.

Torres IC, Mira L, Ornelas CP, Melim A

Departamento de Quimica, Universidade da Madeira, Funchal, Portugal. isat@dragoeiro.uma.pt

Increased concentrations of n-3 polyunsaturated fatty acids (PUFA), namely eicosapentaenoic acid (20:5; EPA) and docosahexaenoic acid (22:6; DHA), have been shown to be beneficial in coronary artery disease (CAD). In the present study, the relationships between fish intake and concentrations of serum EPA and DHA and the effects of these fatty acids on serum lipids and lipoproteins were investigated. Two groups of men, one living in a fishing village and the other in a farming village, participated in this study. The daily fish consumption was ten times greater in the fishing village group than in the rural village group and the mortality from IHD in the rural village was four times higher. Serum concentrations of EPA and DHA were significantly higher in the fishing village group (P < 0.001). In this group, the serum concentration of arachidonic acid (20:4; AA), was significantly lower (P < 0.001), and the ratio EPA:AA was twice that of the rural village (P < 0.001). Moreover, in the fishing village group, the serum triacylglycerol and total cholesterol levels were significantly lower than those observed in the rural village (P < 0.01 and P < 0.05 respectively). In the fishing village group the serum LDL-cholesterol concentration was also lower, although the difference was not significant. Our results reinforce the hypothesis that a high intake of n-3 PUFA provides protection against CAD.

Teratology 2000 Jul;62(1):26-35

alpha-tocopherol and gamma-tocopherol attenuate ethanol-induced changes in membrane fatty acid composition in embryonic chick brains.

Miller RR Jr, Slathar JR, Luvisotto ML

Biology Department, Hillsdale College, Hillsdale, Michigan 49242-1205.

BACKGROUND: This project investigated whether or not EtOH-induced reductions in the levels of long-chain polyunsaturated membrane fatty acids could be attenuated by exogenous exposure to either alpha-tocopherol, gamma-tocopherol, or diallyl sulfide (DAS). METHODS: At 0 days of development, fertile chicken eggs were injected with a single dose of either saline supplemented with various concentrations of EtOH, alpha- or gamma-tocopherol and EtOH, or DAS and EtOH. At 18 days of development, brains were isolated and subjected to membrane analyses. RESULTS: When exposed to EtOH, concentrations ranging from 0-60.50 mum/Kg egg, dose-dependent decreases in the levels of brain 18:0, 18:1 (n-9), 18:2 (n-6), 18:3 (n-3), and 20:4 (n-6) were observed. These ethanol-induced changes in membrane fatty acid composition correlated with ethanol-induced reductions in brain mass, brain protein levels, acetylcholine esterase (AChE) activities and correlated with increased lipid hydroperoxide levels. Exposure to either 2.5 mum alpha-tocopherol/Kg egg and 6.050 mm EtOH/Kg egg, or 2.5 mum alpha-tocopherol/ Kg egg and 6.050 mm EtOH/Kg egg attenuated EtOH-induced changes in membrane fatty acid composition, brain mass, brain protein levels, AChE activities, and lipid hydroperoxide levels. Embryonic exposure to the cytochrome p450-2E1 inhibitor, diallyl sulfide (DAS), also attenuated EtOH-induced decreases in long-chain, unsaturated membrane fatty acids. However, embryonic exposure to DAS promoted abnormally low brain mass. CONCLUSION: EtOH-induced reductions in the levels of brain long-chain polyunsaturated fatty acid are caused by lipid peroxidation. Copyright 2000 Wiley-Liss, Inc.

Reprod Nutr Dev 2000 Mar-Apr;40(2):113-25

Effect of dietary polyunsaturated fatty acids on contractile function of hearts isolated from sedentary and trained rats.

Demaison L, Blet J, Sergiel JP, Gregoire S, Argaud D

Unite de Nutrition Lipidique, INRA, BV 1540, Dijon, France. demaison@dijon.inra.fr

Moderate physical training induced a decrease in arterial blood pressure in fish oil-fed rats as compared to sunflower seed oil-fed rats. The purpose of this study was to determine if these changes were due to modifications of the left ventricular function of the heart. Forty rats were fed a semi-purified diet containing either 10% sunflower seed oil or 10% fish oil (EPAX 3000TG, Pronova). Each dietary group was assigned to two sub-groups, one being constituted by sedentary animals and the other by trained animals. Training was achieved by daily running for 60 minutes at moderate intensity for three weeks. At the end of the training period, the animals were sacrificed and their hearts were immediately perfused according to the working mode. The phospholipid fatty acid composition and parameters of the left ventricular function were determined. Feeding fish oil markedly reduced the proportion of n-6 polyunsaturated fatty acids (PUFA, 18:2 n-6, 20:4 n-6, 22:4 n-6 and 22:5 n-6) in cardiac phospholipids. The n-6 PUFA were replaced by n-3 PUFA (mainly docosahexaenoic acid). In sedentary animals, the fluid dynamic (aortic and coronary flow, cardiac output) was not modified by the diet. The heart rate was reduced (-10%) in n-3 PUFA-rich hearts. Physical training did not markedly alter the polyunsaturated fatty acid profile of cardiac phospholipids. Conversely, it reduced the heart rate, aortic flow and cardiac output (-11, -21 and -14%, respectively) at a similar extent in the two dietary groups. In a second set of experiments, the training period was repeated in animals fed a commercially available diet (A103, UAR) which simultaneously provided n-6 and n-3 fatty acids. In these dietary conditions, neither the aortic flow nor the heart rate was decreased by physical exercise. These results suggest that both n-6 and n-3 PUFA in the diet are necessary to ensure a good cardiac adaptation to moderate physical training. Furthermore, the fish oil-induced decrease in arterial blood pressure in trained animals was not related to changes in cardiac contractility, but to a decrease in vascular resistances. Moderate physical training + dietary n-3 PUFA might be used to prevent hypertension and cardiovascular diseases.

Diabetes 2000 Jun;49(6):1033-41

Anti-modified LDL antibodies, LDL-containing immune complexes, and susceptibility of LDL to in vitro oxidation in patients with type 2 diabetes.

Mironova MA, Klein RL, Virella GT, Lopes-Virella MF

Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston 29403, USA.

We investigated the hypothesis that modified lipoproteins trigger an immune response leading to the production of autoantibodies and subsequently to the formation of atherogenic immune complexes (IC). We recruited 20 type 2 diabetic patients with macrovascular disease, 14 nondiabetic patients with coronary artery disease (CAD), and 34 healthy control subjects matched for age, sex, and race. Serum antibodies to oxidized and glycated LDL did not differ significantly among the 3 groups. Serum IC contained variable, but not statistically different, amounts of IgG, IgM, and IgA. In contrast, the content of cholesterol in IC isolated from diabetic patients was significantly higher than that in IC isolated from control subjects, and the content of apolipoprotein (apo)-B was significantly higher than that in IC isolated from control subjects and patients with CAD. Cholesteryl ester accumulation in human monocyte-derived macrophages incubated with IC, a measure of the atherogenic potential of IC, was significantly higher in macrophages incubated with red blood cell-adsorbed IC isolated from diabetic patients compared with IC isolated from control subjects (P < 0.03) or from patients with CAD (P < 0.04) and was strongly correlated with the content of apoB (r = 0.68, P < 0.001) and cholesterol (r = 0.61, P < 0.001) in IC. LDL from diabetic patients was more susceptible to oxidation in vitro, was significantly smaller, and contained significantly less alpha-tocopherol than LDL isolated from subjects in the other groups. In addition, the n-3 polyunsaturated fatty acid content of phospholipids and cholesteryl esters in LDL isolated from diabetic patients was significantly increased (P < 0.05) compared with that from patients with CAD or from control subjects. We postulate that LDL size, susceptibility to oxidation, and lipid fatty acid composition may play a critical role in the production of antibodies to oxidized LDL and consequently in the formation of LDL-containing IC in patients with type 2 diabetes.

J Nutr 2000 Jul;130(7):1800-1808

Depletion of alpha-Tocopherol and Astaxanthin in Atlantic Salmon (Salmo salar) Affects Autoxidative Defense and Fatty Acid Metabolism.

Bell JG, McEvoy J, Tocher DR, Sargent JR

Institute of Aquaculture, University of Stirling, Stirling FK9 4LA, Scotland, U.K.

Duplicate groups of Atlantic salmon post-smolts were fed four purified diets supplemented with both vitamin E and the carotenoid astaxanthin (Ax) (+E, +Ax), or supplemented with either vitamin E or Ax (-E, +Ax and +E, -Ax) or deficient in both vitamin E and Ax (-E, -Ax) for 22 wk. There were no effects of diet on growth rate, but an extensive lipoid liver degenerative lesion was observed in 15% of fish fed diets deficient in vitamin E. Tissue vitamin E concentrations varied in accordance with dietary vitamin E in liver, muscle, heart, plasma, brain and eye; levels were reduced to approximately 3% in liver but only to 40% in eye of fish fed diets deficient in vitamin E compared with those fed diets supplemented with vitamin E. An interactive sparing of Ax supplementation on tissue vitamin E concentration was observed, but only in brain. Dietary deficiency of both vitamin E and Ax significantly increased the recovery of desaturated and elongated products of both [1-(14)C] 18:3(n-3) and [1-(14)C] 20:5(n-3) in isolated hepatocytes, suggesting that conversion of fatty acids to their long-chain highly unsaturated products can be stimulated by a deficiency of lipid-soluble antioxidants. The antioxidant synergism of vitamin E and Ax was supported by their ability to reduce malondialdehyde formation in an in vitro stimulation of microsomal lipid peroxidation and to reduce plasma levels of 8-isoprostane. The results of this study suggest that both vitamin E and the carotenoid Ax have antioxidant functions in Atlantic salmon.

Lipids 2000 May;35(5):567-74

Blood fatty acid composition of pregnant and nonpregnant Korean women: red cells may act as a reservoir of arachidonic acid and docosahexaenoic acid for utilization by the developing fetus.

Ghebremeskel K, Min Y, Crawford MA, Nam JH, Kim A, Koo JN, Suzuki H

Institute of Brain Chemistry and Human Nutrition, The University of North London, United Kingdom. keb@kebgm.demon.co.uk

Relative fatty acid composition of plasma and red blood cell (RBC) choline phosphoglycerides (CPG), and RBC ethanolamine phosphoglycerides (EPG) of pregnant (n = 40) and nonpregnant, nonlactating (n = 40), healthy Korean women was compared. The two groups were of the same ethnic origin and comparable in age and parity. Levels of arachidonic (AA) and docosahexaenoic (DHA) acids were lower (P < 0.05) and palmitic and oleic acids higher (P < 0.0001) in plasma CPG of the pregnant women. Similarly, the RBC CPG and EPG of the pregnant women had lower AA and DHA (P < 0.05) and higher palmitic and oleic acids (P < 0.01). The reduction in DHA and total n-3 fatty acids in plasma CPG of the pregnant women was paralleled by an increase in docosatetraenoic (DTA) and docosapentaenoic (DPA) acids of the n-6 series and in DPA/DTA ratio. In the RBC phospholipids (CPG and EPG) of the pregnant women, DTA and DPA acids of the n-6 series and DPA/DTA ratio did not increase with the decrease of the n-3 metabolites (eicosapentaenoic acid, DPA, and DHA) and total n-3. Since pregnancy was the main identifiable variable between the two groups, the lower levels of AA and DHA in RBC CPG and EPG of the pregnant women suggest that the mothers were mobilizing membrane AA and DHA to meet the high fetal requirement for these nutrients. It may also suggest that RBC play a role as a potential store of AA and DHA and as a vehicle for the transport of these fatty acids from maternal circulation to the placenta to be utilized by the developing fetus.

Lipids 2000 May;35(5):561-6

Trans fatty acids in adipose tissue of French women in relation to their dietary sources.

Boue C, Combe N, Billeaud C, Mignerot C, Entressangles B, Thery G, Geoffrion H, Brun JL, Dallay D, Leng JJ

Laboratoire de Lipochimie Alimentaire, Universite Bordeaux 1, Talence, France.

This study reports the fatty acid composition of subcutaneous adipose tissue in French women with special emphasis on the content of trans fatty acids originating from two main dietary sources, ruminant fats and partially hydrogenated vegetable oils (PHVO). Adipose tissue trans fatty acid levels from 71 women, recruited between 1997 and 1998, were determined using a combination of capillary gas chromatography and silver nitrate thin-layer chromatography. Results indicate that on average cis monounsaturates accounted for 47.9% of total fatty acids, saturates for 32.2%, and linoleic acid for 14.4%. Cis n-3 polyunsaturates represented only 0.7%. Total content of trans fatty acids was 2.32 +/- 0.50%, consisting of trans 18:1 (1.97 +/- 0.49%), trans 18:2 (0.28 +/- 0.08%), and trans 16:1 (0.06 +/- 0.03%). Trans 18:3 isomers were not detectable. The level of trans fatty acids found in adipose tissue of French women was lower than those reported for Canada, the United States, and Northern European countries but higher than that determined in Spain. Therefore, trans fatty acid consumption in France appears to be intermediate between that of the United States or North Europe and that of Spain. Based on the equation of Enig et al., we estimated the mean daily trans 18:1 acid intake of French women at 1.9 g per person. The major trans 18:1 isomer in adipose tissue was delta11 trans, as in ruminant fats. Estimates of relative contribution of trans fatty acid intake were 55% from ruminant fats and 45% from PHVO. This pattern contrasts sharply with those established for Canada and the United States where PHVO is reported to be the major dietary source of trans fatty acids.

Br J Nutr 2000 Jun;83(6):637-43

Effect of whole linseed (Linum usitatissimum) in the diet of finishing pigs on growth performance and on the quality and fatty acid composition of various tissues.

Matthews KR, Homer DB, Thies F, Calder PC

Meat and Livestock Commission, Milton Keynes, UK. kim_matthews@mlc.org.uk

Pigs (n 144, 30 kg liveweight) were allocated to one of three diets differing in the level of whole linseed (Linum usitatissimum, also known as flaxseed). The diets contained 0, 50 and 100 g/kg for diets L0, L50 and L100 respectively, while containing a constant oil content (60 g/kg). Pigs were slaughtered at a liveweight of 77-87 kg. With the exception of a slight difference in feed intake, there was no effect of diet on production characteristics or carcass traits. Levels of alpha-linolenic acid were increased in all tissues studied as the amount of linseed in the diet increased. In the plasma, m. longissimus thoracis, liver and kidney eicosapentaenoic acid concentration increased markedly. Docosapentaenoic acid concentration increased in the muscle, liver and kidney, whereas in the plasma higher levels of docosahexaenoic acid were observed. None of the longer-chain fatty acids (C20 or longer) were detected in the subcutaneous fat. The changes in fatty acid composition resulted in marked changes to the n-6: n-3 and arachidonic: eicosapentaenoic acid ratios. Feeding whole linseed had no negative effect on the oxidative stability of the meat. Sensory panel results showed no significant differences by diet except for a reduction in abnormal odour (odour perceived by panellists to be abnormal in pigmeat) in the L50 diet and a reduction in the skatole odour (odour of 3-methylindole) in the pigs fed on diet L100. It is concluded that increasing the linseed content of pig diets up to 100 g/kg has no adverse effect on the carcass or meat quality whilst enhancing the levels of n-3 fatty acids which have a potentially positive health effect in man.

Carcinogenesis 2000 Aug;21(8):1513-1519

Morphodensitometric analysis of protein kinase C beta(II) expression in rat colon: modulation by diet and relation to in situ cell proliferation and apoptosis.

Davidson LA, Brown RE, Chang WC, Morris JS, Wang N, Carroll RJ, Turner ND, Lupton JR, Chapkin RS

Molecular and Cell Biology Section, Faculty of Nutrition and Department of Statistics, Texas A&M University, College Station, TX 77843, USA.

We have recently demonstrated that overexpression of PKC beta(II) renders transgenic mice more susceptible to carcinogen-induced colonic hyperproliferation and aberrant crypt foci formation. In order to further investigate the ability of PKC beta(II) to modulate colonocyte cytokinetics, we determined the localization of PKC beta(II) with respect to cell proliferation and apoptosis along the entire colonic crypt axis following carcinogen and diet manipulation. Rats were provided diets containing either corn oil [containing n-6 polyunsaturated fatty acids (PUFA)] or fish oil (containing n-3 PUFA), cellulose (non-fermentable fiber) or pectin (fermentable fiber) and injected with azoxymethane (AOM) or saline. After 16 weeks, an intermediate time point when no macroscopic tumors are detected, colonic sections were utilized for immunohistochemical image analysis and immunoblotting. Cell proliferation was measured by incorporation of bromodeoxyuridine into DNA and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling. In the distal colon, PKC beta(II) staining was localized to the upper portion of the crypt. In comparison, proximal crypts had more (P < 0.05) staining in the lower tertile. AOM enhanced (P < 0.05) PKC beta(II) expression in all regions of the distal colonic crypt (upper, middle and lower tertiles). There was also an interaction (P < 0.05) between dietary fat and fiber on PKC beta(II) expression (corn/pectin > fish/cellulose, fish/pectin > corn/cellulose) in all regions of the distal colonic crypt. With respect to colonic cell kinetics, proliferation paralleled the increase in PKC beta(II) expression in carcinogen-treated animals. In contrast, apoptosis at the lumenal surface was inversely proportional to PKC beta(II) expression in the upper tertile. These results suggest that an elevation in PKC beta(II) expression along the crypt axis in the distal colon is linked to enhancement of cell proliferation and suppression of apoptosis, predictive intermediate biomarkers of tumor development. Therefore, select dietary factors may confer protection against colon carcinogenesis in part by blocking carcinogen-induced PKC beta(II) expression.

Br J Nutr 2000 Jun;83(6):637-43

Effect of whole linseed (Linum usitatissimum) in the diet of finishing pigs on growth performance and on the quality and fatty acid composition of various tissues.

Matthews KR, Homer DB, Thies F, Calder PC

Meat and Livestock Commission, Milton Keynes, UK. kim_matthews@mlc.org.uk

Carcinogenesis 2000 Aug;21(8):1513-1519

Morphodensitometric analysis of protein kinase C beta(II) expression in rat colon: modulation by diet and relation to in situ cell proliferation and apoptosis.

Davidson LA, Brown RE, Chang WC, Morris JS, Wang N, Carroll RJ, Turner ND, Lupton JR, Chapkin RS

Molecular and Cell Biology Section, Faculty of Nutrition and Department of Statistics, Texas A&M University, College Station, TX 77843, USA.

Lipids 2000 Jul;35(7):745-55

Dietary n-3 long-chain polyunsaturated fatty acid deprivation, tissue lipid composition, ex vivo prostaglandin production, and stress tolerance in juvenile Dover sole.

Logue JA, Howell BR, Bell JG, Cossins AR

School of Biological Sciences, University of Liverpool, United Kingdom.

Larval Dover sole fed an Artemia diet supplemented with n-3 long-chain (C20 + C22) polyunsaturated fatty acids (PUFA) are known to be more resistant to low-temperature injury. Here we explore the relationship between tissue fatty acid composition and tolerance of stressful environmental conditions over the larval and early juvenile periods. Artemia nauplii supplemented with n-3 long-chain PUFA-deficient and PUFA-enriched oil emulsions were fed to two groups of larvae. Whole body tissue samples from the resulting PUFA-deficient and -enriched juveniles possessed 12.1 and 21.9% n-3 long-chain PUFA, respectively. These differences were at the expense of C18 PUFA, while proportions of saturated fatty acids, monounsaturated fatty acids, and total PUFA were unaffected. Brain and eye tissues from the PUFA-deficient fish contained lower levels of 22:6n-3, known to be important for optimal nervous system function, incorporating instead a range of fatty acids of lower unsaturation. PUFA-deprived juveniles showed substantially greater mortality when exposed to a combination of low temperature and low salinity, as well as to high temperature and to hypoxia. After adaptation to the different diets, both dietary groups were fed a common formulated feed high in n-3 long-chain PUFA. Tissue PUFA in both groups progressively increased to the same high value, with a consequent loss of the differences in cold-susceptibility. These correlated changes support a link between dietary manipulation of n-3 long-chain PUFA and development of a stress-sensitive phenotype. PUFA deprivation had no detectable effect upon static hydrocarbon order of purified brain membranes (as assessed by fluorescence polarization) but was associated with an increase in the whole-body content of prostaglandins. We conclude that susceptibility to environmental stress is responsive to dietary n-3 long-chain PUFA manipulation, possibly due to altered tissue development or the overproduction of eicosanoids.

J Infect Dis 2000 Sep;182 Suppl 1:S54-S61

Consumption of Eicosapentaenoic Acid and Docosahexaenoic Acid Impair Murine Interleukin-12 and Interferon-gamma Production In Vivo.

Fritsche KL, Anderson M, Feng C

Department of Animal Sciences and the Graduate Nutritional Sciences Program, University of Missouri, Columbia, MO 65211, USA. FritscheK@missouri.edu

In mice, individual dietary omega-3 polyunsaturated fatty acids n-3 (PUFA) were found to be sufficient to effect the changes in circulating interleukin (IL)-12 and interferon (IFN)-gamma levels that were previously seen in fish oil-fed mice. Weanling female C3H mice were fed one of five experimental diets. All five diets met all known nutritional requirements for mice and differed only in the fat source. After 4 weeks, mice were challenged with live Listeria monocytogenes or sterile PBS. Twenty-four hours after infection, n-3 PUFA-fed mice had significantly lower circulating IL-12 p70 and IFN-gamma than mice fed the control diet (P<.01). In addition, splenic cytokine mRNA for IL-12 p40, tumor necrosis factor-alpha, and IL-1beta were lower in infected mice fed n-3 PUFA-containing diets than in mice fed the olive oil ethyl esters control diet. The reduction of IL-12 and IFN-gamma production by n-3 PUFA may have important implications for host infectious disease resistance.

Metabolism 2000 Aug;49(8):977-83

Energy restriction dilutes the changes related to dietary fat type in membrane phospholipid fatty acid composition in rats.

Cha MC, Jones PJ

School of Dietetics and Human Nutrition, McGill University, Ste Anne de Bellevue, Quebec, Canada.

To investigate liver cell membrane phospholipid (PL) fatty acid (FA) composition in response to the consumption of different types of dietary fat and graded levels of energy intake, rats were fed for 10 weeks on a diet containing either fish oil, safflower oil, or beef tallow. Within each dietary fat group, subgroups were either provided free access to food or energy-restricted to 85% or 70% of the ad libitum intake by reducing the dietary carbohydrate content while keeping other macronutrient intakes constant. Higher (P < .05) proportions of docosahexaenoic acid, linoleic acid, and monounsaturated FA were observed in the membrane PL of the fish oil, safflower oil, and beef tallow groups, respectively, resembling the FA composition in the diets. However, such modifications of dietary FA composition in, membrane PL FA were influenced by body energy status. The higher docosahexaenoic acid and total n-3 FA content in phosphatidylcholine (PC), sphingomyelin (SPH), and phosphatidylserine (PS) of the ad libitum fish oil group compared with the other dietary groups no longer existed when energy supply was restricted. Therefore, reducing energy intake tended to dilute the changes of membrane PL FA composition occurring as a function of dietary FA composition. These data suggest that the influence of dietary fat type on cellular structure and perhaps function becomes increasingly important with progressively positive energy balance.

Clin Nutr 2000 Aug;19(4):271-276

Serum fatty acid imbalance in bone loss: example with periodontal disease.

Requirand P, Gibert P, Tramini P, Cristol JP, Descomps B

Faculty of Dentistry of Montpellier, Institute of Biology, Montpellier, France

Among the numerous factors of bone remodelling, the local action of arachidonic acid metabolites together with cytokines, is particularly important, especially that of prostaglandin PGE2. It has been suggested that the alveolar bone destruction in periodontal disease and osteoporosis can be treated by reducing the ratio of arachidonic acid in phospholipids, which would diminish prostaglandin production. The aim of this study was to evaluate the main serum polyunsaturated fatty acids and a possible alteration in the level of arachidonic acid in patients suffering from periodontal bone loss. Of the 105 patients who participated the study, 78 were suffering from periodontal bone loss and 27 served as a control group. The fatty acids were measured in serum by gas-chromatography. The results showed that the level of fatty acids of the n-6 pathway was higher in our patients with bone loss than in the control group, whereas the reverse was observed with fatty acids of the n-3 pathway. In conclusion, our patients' bone losses are linked with an imbalance between n-6 and n-3 fatty acids, which seems to justify a diet increase in 20- and 22-carbon fatty acids. Copyright 2000 Harcourt Publishers Ltd.

Clin Nutr 2000 Aug;19(4):265-269

Influence of enteral diets supplemented with key nutrients on lymphocyte subpopulations in Peyer's patches of endotoxin-boostered mice.

Manhart N, Vierlinger K, Akomeah R, Bergmeister H, Spittler A, Roth E

Department of Surgical Research, University of Vienna, Austria

Background and aims: This study was undertaken to compare the effect of different key nutrients on lymphocyte subsets of Peyer's patches (PP) and spleen in endotoxemic mice.Methods: Female Balb/c mice were fed over a period of 10 days either with an isocaloric and isonitrogenous control diet (Control), a glutamine enriched diet (Diet I) or a diet containing glutamine, arginine, glycine, and n-3 fatty acids (Diet II). On day 7 the mice were challenged intraperitoneally with 25mug LPS. The lymphocyte subpopulations (B cells, T cells, CD4+ and CD8+) of PP and spleen were analysed by flow cytometry. Glutathione content of small intestinal mucosa and spleen was determined by HPLC and luminal small intestinal IgA by ELISA.Results: Both experimental diets increased the number of B and T cells in the PP and that of T cells in the spleen (P<0.01). Glutathione content in PP and spleen was higher under administration of key nutrients (P<0.05). Diet II reduced luminal small intestinal IgA content in comparison to the two other groups.Conclusion: The addition of arginine, glycine and n-3 fatty acids to a glutamine supplemented diet does not enhance lymphocyte numbers in PP and spleen, but reduces intestinal IgA content. Copyright 2000 Harcourt Publishers Ltd.

J Am Diet Assoc 2000 Aug;100(8):955-60

Case problem: dietary recommendations to combat obesity, insulin resistance, and other concerns related to polycystic ovary syndrome.

McKittrick M

New York Presbyterian Hospital, USA.

For many years, PCOS has been misdiagnosed. It has only been in the recent past that there has been an increased awareness about the seriousness of this condition. As dietetics professionals, it is important that we become knowledgable about this condition so that we can educate patients on insulin resistance and the effects of hyperinsulinemia, and to be able to provide dietary recommendations to women with PCOS. The following are some dietary recommendations that I share with my patients who have PCOS: The bottom line is that you need to find a diet that works for you and one that you can live with. Select whole-grain starches instead of processed, refined starches. Foods high in fiber will cause a slower rise in blood sugar levels. Restrict foods high in sugar such as sweetened beverages and sweet desserts. Check food labels on fat-free desserts, as many are loaded with sugar. Include a lean protein as well as a heart-healthy fat at each meal. This will slow the rise in blood sugar levels. Avoid diets that promote ketosis. Space out the consumption of carbohydrates throughout the day. This will cause less of rise in blood sugar and insulin peak levels, compared with eating all carbohydrates at one meal. Consume vitamin/mineral supplements, such as: Calcium 1,000 mg to 1,500 mg (take 2 to 3,500-mg pills per day; be sure to ingest the pills at different times during the day to enhance absorption). Multivitamin with minerals (make sure it contains 400 micrograms folic acid if trying to get pregnant) For heart health, limit foods high in saturated and trans fats (e.g., fatty red meats, whole milk, butter and stick margarine, chicken skin, fried foods, and rich desserts). Select mainly monounsaturated fats (i.e., olive oil, canola oil, nuts) and n-3 fats (fatty fish such as salmon and bluefish, flaxseed, nuts), as these fats are heart healthy. Exercise on a regular basis. The benefits of aerobic exercise include: burns energy and aids in weight control; lowers blood pressure; raises HDL cholesterol levels; and may improve insulin resistance (proven in type 2 diabetics). Some benefits of resistance training are that it builds lean mass which will speed metabolism and it helps prevent osteoporosis.

Nutr Cancer 2000;37(1):65-72

Modulation of liver microsomal monooxygenase system by dietary n-6/n-3 ratios in rat hepatocarcinogenesis.

Kim Y, Ji SK, Choi H

Department of Food and Nutrition, Seoul National University, Korea.

This study was designed to determine the effects of dietary n-3/n-6 fatty acid ratios on preneoplastic foci and the microsomal monooxygenase system in rat hepatocarcinogenesis. Male Sprague-Dawley rats were fed four kinds of diets containing 15% (wt/wt) fat with different n-6/n-3 ratios: low ratio (> or = 1.0) with tuna oil, low ratio (> or = 1.0) with perilla oil, moderate ratio (< or = 4.0), and high ratio (< or = 10.0). Hepatocarcinogenesis was induced by diethylnitrosamine and partial hepatectomy. The moderate ratio diet decreased significantly the area and number of placental glutathione S-transferase-positive foci compared with the high ratio diet and low ratio diet with perilla oil. The fatty acid composition of microsomal membrane varied extensively, reflecting the dietary n-6/n-3 ratios. Liver microsomal lipid peroxidation was significantly decreased in the group fed the low ratio diet with tuna oil compared with the moderate and high ratio groups. Glucose-6-phosphatase activity, which reflects membrane stability, was significantly higher in the low ratio groups than in the high ratio group. The monooxygenase activities were increased significantly in the moderate ratio group compared with the high ratio group. These results suggest that a moderate n-6/n-3 ratio (< or = 4.0) may be the most effective in decreasing preneoplastic foci by elevating the monooxygenase activities and n-3 fatty acids in fish oil may have a protective effect by lowering the lipid peroxidation and stabilizing the microsomal membrane during rat hepatocarcinogenesis.

Nutr Cancer 2000;37(1):19-26

Mechanisms linking diet and colorectal cancer: the possible role of insulin resistance.

Bruce WR, Wolever TM, Giacca A

Department of Nutritional Sciences, University of Toronto, ON, Canada. wr.bruce@utoronto.ca

Diet is clearly implicated in the origin of colorectal cancer, with risk factors for the disease including reduced consumption of vegetables, fiber, and starch and increased consumption of red meat and animal fat. Several hypotheses have been developed to explain these associations. Most recently, McKeown-Eyssen and Giovannucci noted the similarity of the risk factors for colorectal cancer and those for insulin resistance and suggested that insulin resistance leads to colorectal cancer through the growth-promoting effect of elevated levels of insulin, glucose, or triglycerides. We briefly review the evidence from observational, epidemiological, and experimental animal studies linking diet with insulin resistance and colorectal cancer. The evidence suggests that diets high in energy and saturated fat and with high glycemic index carbohydrate and low levels of fiber and n-3 fatty acids lead to insulin resistance with hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. We then consider how insulin, the related insulin-like growth factors, triglycerides, and nonesterified fatty acids could lead to increased growth of colon cancer precursor lesions and the development of colorectal cancer. Finally, we consider the implications of this scheme on possible future research directions, including studies of satiety and clinical tests of the importance of insulin resistance in the colon carcinogenesis process.

Curr Cardiol Rep 2000 Sep;2(5):445-51

The gruppo italiano per lo studio della sopravvivenza nell'Infarto miocardio (GISSI)-prevenzione trial on fish oil and vitamin E supplementation in myocardial infarction survivors.

Stone NJ

Northwestern University School of Medicine, 211 E. Chicago Avenue; STE 1050, Chicago, Illinois 60611, USA. n-stone@northwestern.edu.

A recent large-scale, open-label, randomized, controlled trial in 11, 324 myocardial infarction (MI) survivors has shown low-dose fish oil, but not vitamin E, to reduce significantly the cumulative rate of all-cause death, nonfatal MI, and nonfatal stroke. Neither intervention significantly reduced the other primary endpoint, the cumulate rate of cardiovascular death, nonfatal MI, and nonfatal stroke. Analysis of secondary endpoints indicated that the benefits of the 875 mg fish oil capsules containing 850 to 882 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as ethyl esters was in reducing mortality and not in a reduction of nonfatal MI. It was a safe intervention. The internal validity and external validity of the data was examined and the findings placed in clinical perspective. Important questions remain about the benefits of increased plant sources of n-3 polyunsaturated fatty acids (PUFA) for those who cannot obtain or consume fish. Also the benefits of diet versus fish oil supplementation haven't been determined precisely. Although it seems reasonable to increase sources of n-3 PUFA in the diet for those at high risk of coronary heart disease, current data do not support a policy of promoting fish oil capsules for secondary prevention of coronary heart disease.

Biochem Soc Symp 1999;66:141-7

Mitochondria in heart ischaemia and aging.

Hansford RG, Tsuchiya N, Pepe S

Laboratory of Molecular Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.

We have examined the effect of dietary polyunsaturated fatty acids (PUFAs) upon mitochondrial Ca2+ content and dehydrogenase activation in the rat heart. Diets were either a conventional low-fat chow (Ref) or were rich in n-3 PUFAs from fish oils (n-3) or n-6 PUFAs from animal fat (n-6). We found that the n-3 diet minimized the rise in mitochondrial Ca2+ seen in response to positive inotropic intervention with noradrenaline, and also minimized the activation of pyruvate dehydrogenase, which is Ca2+ dependent. As the work output of all three groups of hearts was the same, this observation may explain the previous finding of increased thermodynamic efficiency of the n-3 heart relative to the n-6 heart. When hearts were subjected to low-flow ischaemia (15 min), followed by 5 min of reperfusion, increases of mitochondrial Ca2+ were less in the n-3 group than in the n-6 group. In more prolonged ischaemia and reperfusion, n-3 feeding may confer protection against mitochondrial Ca2+ overload, opening of the permeability transition pore and cell death. Notably, the effects of n-3 feeding on mitochondrial functioning were most apparent in hearts from senescent rats (23 months). This is consistent with our finding that the decrease in mitochondrial membrane cardiolipin content, and increase in phosphatidylcholine, which occurred with aging in the Ref and n-6 groups, was totally prevented by n-3 feeding. Thus there are a number of reasons to regard an n-3-rich diet as being protective of the heart in aging mammals.

Eur J Clin Nutr 2000 Sep;54(9):732-737

The associations of a marine diet with plasma lipids, blood glucose, blood pressure and obesity among the Inuit in Greenland.

Bjerregaard P, Pedersen HS, Mulvad G

National Institute of Public Health, Copenhagen, Denmark.

Objective: To analyse the associations between the intake of fish and marine mammals and risk factors for cardiovascular disease, ie lipid profile, fasting blood glucose, blood pressure and obesity, in a population whose average consumption of n-3 fatty acids is high compared with Western countries. Design: Information was obtained from a population survey in Greenland: interview data, clinical data and fasting blood samples were obtained from a random sample of Inuit from three towns and four villages. Subjects: Two-hundred and fifty-nine adult Inuit (74% of the sample). Results: Marine diet was positively associated with serum high-density lipoprotein (HDL) and blood glucose and inversely with very-low-density lipoprotein (VLDL) and triglyceride. Association with low-density lipoprotein (LDL), diastolic and systolic blood pressure, waist-hip ratio and body mass index were inconsistent and not statistically significant. The pattern was similar within groups with low, medium and high consumption of marine food. Conclusions: There are statistically significant associations between the consumption of marine food and certain lipid fractions in the blood also in this population with a very high average intake of marine food. The observation that blood glucose is positively associated with marine diet in a population survey is new and should be repeated. There was good agreement between the results for the reported consumption of seal and those for the biomarkers. Sponsorship: The study was financially supported by the Greenland Home Rule, Directorate of Health and Research, the Commission for Scientific Research in Greenland, and the Danish Medical Research Council. European Journal of Clinical Nutrition (2000) 54, 732-737

Eur J Clin Nutr 2000 Sep;54(9):690-694

The effect of low-dose fish oil supplementation on serum growth factors in healthy humans.

Wallace JM, McCabe AJ, Roche HM, Higgins S, Robson PJ, Gilmore WS, McGlynn H, Strain JJ

Northern Ireland Centre for Diet and Health (NICHE), University of Ulster, Coleraine, Northern Ireland, UK.

Objective: To examine the effect of low-dose fish oil supplementation on specific growth factors, purported to play a central role in lesion formation, and also on the total growth factor activity of serum, as assessed by the induction of DNA synthesis in cultured human arterial smooth muscle cells. Design: Randomized placebo-controlled double-blind intervention study. Setting: Free-living population. Subjects: Sixty-three healthy volunteers, 37 males and 26 females. Interventions: Four treatment regimes with subjects receiving 0, 0.3,0.6 or 0.9 g/day of n-3 PUFA for an 8 week period. Blood samples were taken at baseline and following the 8 week intervention. All samples were analysed in batch following completion of the study. Results: Consumption of fish oil had no effect on serum platelet-derived growth factor (PDGF), or transforming growth factor beta (TGFbeta) concentration. Furthermore, fish oil supplementation did not alter the total growth factor activity of serum. Conclusions: Results indicate that low-dose fish oil supplementation, equivalent to about two portions of fatty fish per week and providing less than 1 g n-3 PUFA/day, does not alter the levels of the major serum growth factors and does not modify total serum growth factor activity in healthy human volunteers. Sponsorship: European Union shared cost project (FAIR-CT-95-0085).

Comp Biochem Physiol B Biochem Mol Biol 2000 Aug;126(4):477-85

Lipids and fatty acids of two pelagic cottoid fishes (Comephorus spp) endemic to Lake Baikal.

Kozlova TA, Khotimchenko SV

Limnological Institute, SB RAS, Irkutsk, Russia. kozlovatat@usa.net

Matured females of two Lake Baikal endemic fish species, Comephorus baicalensis and Comephorus dybowski, have been investigated for lipid of the whole body and specific tissues (liver, muscles, ovaries), phospholipid classes and fatty acids of neutral and polar lipids. Total lipid in the body (38.9% fresh weight), liver (23.5%) and muscles (14.5%) of C. baicalensis were greater than those of C. dybowski (4.7, 8.7 and 2.6%, respectively); only their ovaries were similar (5.3 and 5.6% lipid, respectively). In both species, phosphatidylcholine and phosphatidylethanolamine were the major phospholipids, ranging from 60.7 to 75.1% of total phospholipid and 14.5-25.7%, respectively. In most cases, monounsaturated fatty acids (MUFA) were the major fatty acid group in C. baicalensis, whereas polyunsaturated fatty acids (PUFA) were the major group in C. dybowski. The MUFA 18:1(n-9) prevailed over other fatty acids in C. baicalensis and varied from 19% in polar lipids of muscles to 56.1% in neutral lipids of muscles. In polar lipid of C. dybowski, the PUFA 22:6(n-3) prevailed over other fatty acids in muscles and ovaries, while 16:0 dominated polar liver lipids and neutral lipids of all tissues. Other major fatty acids included 16:1(n-7), 18:1(n-7), and 20:5(n-3). Values of the (n-3)/(n-6) fatty acid ratio for neutral lipids of C. baicalensis (0.5-0.9) are well below the range of values characteristic either for marine or freshwater fish, while these values for polar lipids (1.6-1.8) are in the range typical of freshwater fish. Neutral lipid fatty acid ratios in C. dybowski (2.5-3.1) allow it to be assigned to freshwater fish, but polar lipids (2.8-3.7) leave it intermediary between freshwater and marine fish.

Lipids 2000 Sep;35(9):1011-5

Dietary docosahexaenoic acid affects stearic acid desaturation in spontaneously hypertensive rats.

Engler MM, Bellenger-Germain SH, Engler MB, Narce MM, Poisson JP

Laboratory of Cardiovascular Physiology, Department of Physiological Nursing, University of California, San Francisco 94143-0610, USA. marguerite.engler@nursing.ucsf.edu

Docosahexaenoic acid (DHA, 22:6n-3) is an n-3 polyunsaturated fatty acid which attenuates the development of hypertension in spontaneously hypertensive rats (SHR). The effects of DHA on delta-9-desaturase activity in hepatic microsomes and fatty acid composition were examined in young SHR. Two groups of SHR were fed either a DHA-enriched diet or a control diet for 6 wk. Desaturase activity and fatty acid composition were determined in hepatic microsomes following the dietary treatments. Delta-9-desaturase activity was decreased by 53% in DHA-fed SHR and was accompanied by an increase in 16:0 and a reduction in 16:1n-7 content in hepatic microsomes. The DHA diet also increased the levels of eicosapentaenoic acid (20:5n-3) and DHA. The n-6 fatty acid content was also affected in DHA-fed SHR as reflected by a decrease in gamma-linolenic acid (18:3n-6), arachidonic acid (20:4n-6), adrenic acid (22:4n-6), and docosapentaenoic acid (22:5n-6). A higher proportion of dihomo-gamma-linolenic acid (20:3n-6) and a lower proportion of 20:4n-6 is indicative of impaired delta-5-desaturase activity. The alterations in fatty acid composition and metabolism may contribute to the antihypertensive effect of DHA previously reported.

Lipids 2000 Sep;35(9):1001-9

The effect of low alpha-linolenic acid diet on glycerophospholipid molecular species in guinea pig brain.

Kurvinen JP, Kuksis A, Sinclair AJ, Abedin L, Kallio H

Banting and Best Department of Medical Research, University of Toronto,Ontario,Canada.

The changes in guinea pig brain (cerebrum) glycerophospholipid molecular species resulting from a low-alpha linolenic acid (ALA) diet are described. Two groups of six guinea pigs were raised from birth to 16 wk of age on either an n-3 deficient diet containing 0.01 g ALA/100 g diet or n-3 sufficient diet containing 0.71 g ALA/100 g diet. Molecular species of diradyl glycerophosphoethanolamine (GroPEtn), glycerophosphocholine, glycerophosphoserine, and glycerophosphoinositol were analyzed by high-performance liquid chromatography with on-line electrospray ionization mass spectrometry (HPLC/ESI/MS). Alkenylacyl GroPEtn species were determined by comparing spectra before and after mild acid treatment while diacyl- and alkylacyl species were distinguished by HPLC/ESI/MS. The proportions of phospholipid classes and of the diradyl GroPEtn subclasses were not altered by diet changes. The main polyunsaturated molecular species of diradyl GroPEtn subclasses and of phosphatidyl choline and phosphatidylserine (PtdSer) contained 16:0, 18:0, or 18:1 in combination with docosahexaenoic acid (DHA, 22:6n-3), docosapentaenoic (DPA, 22:5n-6), or arachidonic acid (ARA, 20:4n-6). A significant proportion of DPA containing species were present in both diet groups, but in n-3 fatty acid deficiency, the proportion of DPA increased and DHA was primarily replaced by DPA. The combined value of main DHA and DPA containing species in the n3 deficient group ranged from 91-111% when compared with the n-3 sufficient group, indicating a nearly quantitative replacement. The n-3 fatty acid deficiency did not lower the content of ARA containing molecular species of PtdSer of the guinea pig brain as reported previously for the rat brain. The molecular species of phosphatidylinositol were not altered by n-3 fatty acid deficiency. The present data show that the main consequence of a low ALA diet is the preferential replacement of DHA-containing molecular species by DPA-containing molecular species in alkenylacyl- and diacyl GroPEtn and PtdSer of guinea pig brain.

Lipids 2000 Sep;35(9):991-9

Response of plasma lipids to dietary cholesterol and wine polyphenols in rats fed polyunsaturated fat diets.

Fremont L, Gozzelino MT, Linard A

Laboratoire de Nutrition et Securite Alimentaire, INRA-CRJ, Jouy-en-Josas, France. Myriam.Defrance@jouy.inra.fr

This experiment was designed to evaluate the effects of dietary red wine phenolic compounds (WP) and cholesterol on lipid oxidation and transport in rats. For 5 wk, weanling rats were fed polyunsaturated fat diets (n-6/n-3 = 6.4) supplemented or not supplemented with either 3 g/kg diet of cholesterol, 5 g/kg diet of WP, or both. The concentrations of triacylglycerols (TAG, P < 0.01) and cholesterol (P < 0.0002) were reduced in fasting plasma of rats fed cholesterol despite the cholesterol enrichment of very low density lipoprotein + low density lipoprotein (VLDL + LDL). The response was due to the much lower plasma concentration of high density lipoprotein (HDL) (-35%, P < 0.0001). In contrast, TAG and cholesteryl ester (CE) accumulated in liver (+120 and +450%, respectively, P < 0.0001). However, the cholesterol content of liver microsomes was not affected. Dietary cholesterol altered the distribution of fatty acids mainly by reducing the ratio of arachidonic acid to linoleic acid (P < 0.0001) in plasma VLDL + LDL (-35%) and HDL (-42%) and in liver TAG (-42%), CE (-78%), and phospholipids (-28%). Dietary WP had little or no effect on these variables. On the other hand, dietary cholesterol lowered the alpha-tocopherol concentration in VLDL + LDL ( -40%, P < 0.003) and in microsomes (-60%, P < 0.0001). In contrast, dietary WP increased the concentration in microsomes (+21%, P < 0.0001), but had no effect on the concentration in VLDL + LDL. Cholesterol feeding decreased (P < 0.006) whereas WP feeding increased (P < 0.0001) the resistance of VLDL + LDL to copper-induced oxidation. The production of conjugated dienes after 25 h of oxidation ranged between 650 (WP without cholesterol) and 2,560 (cholesterol without WP) micromol/g VLDL + LDL protein. These findings show that dietary WP were absorbed at sufficient levels to contribute to the protection of polyunsaturated fatty acids in plasma and membranes. They could also reduce the consumption of alpha-tocopherol and endogenous antioxidants. The responses suggest that, in humans, these substances may be beneficial by reducing the deleterious effects of a dietary overload of cholesterol.

Clin Nutr 2000 Oct;19(5):313-318

Effects of dietary fish oil on survival rate, plasma amino acid pattern, and inflammatory-related mediators in diabetic rats with sepsis.

Chyi A, Yeh S

Institute of Nutrition and Health Science, Taipei, Taiwan, Republic of China

This study was designed to investigate the effects of dietary fish oil on survival rates, plasma amino acid profiles, and inflammatory-related mediators in diabetic rats with sepsis. Diabetes mellitus (DM) was induced in rats by streptozotocin. The DM rats were maintained for 4 weeks on medium fat (10%, w/w) diets containing either fish oil or safflower oil. After that, sepsis was induced by cecal ligation and puncture (CLP). There were 2 groups in this study: fish oil sepsis group (FOS) and safflower oil sepsis group (SOS). The survival rate was observed after CLP. Also, changes of the amino acid pattern as well as interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, prostaglandin (PG) E(2)at 6, 12, and 24 h after CLP were investigated. The results demonstrated that survival rates were not significantly different between the 2 groups. Plasma arginine levels were significantly lower in sepsis groups than that in the DM-chow group, regardless of whether the diabetic rats were fed fish oil or safflower oil. No significant differences were observed in plasma valine, leucine, isoleucine, glutamine, or arginine concentrations between the FOS and SOS groups at different time points. Concentrations of IL-1beta in peritoneal lavage fluid (PLF) at 6 h and TNF-alpha at 6 h as well as at 12 h after CLP in the FOS group were significantly higher than those in the SOS group. PGE(2)levels in PLF, by contrast, were lower in the FOS group at 6 and 12 h after CLP than in the SOS group. These results suggest that differences in IL-1beta, TNF-alpha, and PGE(2)levels in PLF in the early period of sepsis did not influence the survival rates and plasma amino acid profiles of the FOS and SOS groups. Compared with safflower oil, feeding diabetic rats with fish oil had no beneficial effects on survival rates and muscle protein breakdown. The immunologic impact of dietary n-3 polyunsaturated fatty acids on diabetic rats with sepsis requires further investigation. Copyright 2000 Harcourt Publishers Ltd.

Cochrane Database Syst Rev 2000;4:CD001283

Dietary marine fatty acids (fish oil) for asthma (Cochrane Review).

Woods RK, Thien FC, Abramson MJ

Department of Epidemiolgy and Preventative Medicine, Monash Medical School, Alfred Hospital, Commercial Road, Prahran, Victoria, AUSTRALIA, 3181. Rosalie.Woods@med.monash.edu.au

BACKGROUND: Epidemiological studies suggest that a diet high in marine fatty acids (fish oil) may have beneficial effects on inflammatory conditions such as rheumatoid arthritis and possibly asthma. OBJECTIVES: 1. To determine the effect of marine n-3 fatty acid (fish oil) supplementation in asthma. 2. To determine the effect of a diet high in fish oil in asthma. SEARCH STRATEGY: The Cochrane Airways Review Group register was search using the terms: marine fatty acids OR diet OR nutrition OR fish oil OR eicosapentaenoic acid OR EPA. Bibliographies of retrieved trials were searched and fish oil manufacturers contacted. SELECTION CRITERIA: Randomised controlled trials in patients with asthma more than two years of age were included. The study duration had to be in excess of 4 weeks. Double blind trials were preferred, but single-blind and open trials were also reviewed for possible inclusion. Three reviewers read each paper, blind to its identity. Decisions concerning inclusion were made by simple majority. Quality assessment was performed by all three reviewers independently. DATA COLLECTION AND ANALYSIS: The only comparison possible was between marine n-3 fatty acid supplementation and placebo. There were insufficient trials to examine dietary manipulation alone. MAIN RESULTS: Eight randomised controlled trials conducted between 1986 and 1998 satisfied the inclusion criteria. Six were of parallel design and two were cross-over studies. Seven compared fish oil with placebo whilst one compared high dose vs low dose marine n-3 fatty acid supplementation. None of the included studies reported asthma exacerbations, health status or hospital admissions. There was no consistent effect on any of the analyzable outcomes: FEV1, peak flow rate, asthma symptoms, asthma medication use or bronchial hyper reactivity. The single study performed in children also combined dietary manipulation with fish oil supplementation and showed improved peak flow and reduced asthma medication use. There were no adverse events associated with fish oil supplements. Updated Search conducted August 2000. No new trials were found. REVIEWER'S CONCLUSIONS: There is little evidence to recommend that people with asthma supplement or modify their dietary intake of marine n-3 fatty acids (fish oil) in order to improve their asthma control. Equally, there is no evidence that they are at risk if they do so.

Proc Soc Exp Biol Med 2000 Nov;225(2):128-135

Induction of Hepatic Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) in Rats by Dietary n-6 Polyunsaturated Fatty Acids.

Ghoshal AK, Xu Z, Wood GA, Archer MC

Departments of Nutritional Sciences and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5S 3E2.

The insulin-like growth factors (IGFs) are mitogenic polypeptides that have been linked to a variety of normal physiological processes as well as neoplasia. Overexpression of several components of the IGF system is associated with hepatocarcinogenesis in humans and rodents. In rat liver, diets rich in n-6 polyunsaturated fatty acid (PUFA) enhance the development of preneoplastic lesions and tumors. Therefore, the objective of this study was to determine the effect of these dietary fatty acids on the hepatic expression of the various components of the IGF system. The mRNA levels of IGF-1 and the type 1 receptor were not different in livers of rats fed a diet containing 20% corn oil (CO) compared with those fed 5% CO. Analysis of the IGF binding proteins revealed that insulin-like growth factor binding protein-1 (IGFBP-1) levels were altered by the amount and type of dietary fat. A 2.5-fold induction of IGFBP-1 mRNA occurred within 1 week after the animals were fed the 20% corn oil diet compared with those fed 5% CO and was further enhanced to over 6-fold after 1 month. Furthermore, IGFBP-1 protein was only detectable in the livers of animals fed the 20% CO diet. Induction of IGFBP-1 mRNA (4.5-fold) also occurred in rats fed a high-fat diet containing safflower (rich in n-6 PUFAs) compared with those fed a high-fat diet containing menhaden oil (rich in n-3 PUFAs). The induction of IGFBP-1 mRNA was independent of serum insulin levels and the development of insulin resistance. Since IGFBP-1 mRNA is upregulated in regenerating liver, we reasoned that the induction of IGFBP-1 mRNA may be associated with an increase in cell proliferation; however, no difference was observed in the hepatic labeling index of rats fed the 20% CO compared with the 5% CO diet. In summary, these studies show a striking induction by dietary n-6 PUFAs of hepatic IGFBP-1, a protein that has been implicated in liver cancer development.

Diabetologia 2000 Sep;43(9):1093-8

Use of cod liver oil during pregnancy associated with lower risk of Type I diabetes in the offspring.

Stene LC, Ulriksen J, Magnus P, Joner G

Section of Epidemiology, National Institute of Public Health, Oslo, Norway.

AIMS/HYPOTHESIS: To test whether cod liver oil or vitamin D supplements either taken by the mother during pregnancy or by the child in the first year of life is associated with lower risk of Type I (insulin-dependent) diabetes mellitus in children. METHODS: We carried out a population-based case control study in Vest-Agder county of Norway, evaluating the use of supplements by a mailed questionnaire. We received responses from 85 diabetic subjects and 1,071 control subjects. Odds ratios (OR) with 95% confidence intervals (CI) were estimated using logistic regression analyses. RESULTS: When mothers took cod liver oil during pregnancy their offspring had a lower risk of diabetes. The unadjusted OR was 0.30, 95% CI: (0.12 to 0.75), p = 0.01. This association changed very little and was still significant after adjusting for age, sex, breastfeeding and maternal education. Mothers taking multivitamin supplements during pregnancy [adjusted OR= 1.11, 95% CI: (0.69 to 1.77)], infants taking cod liver oil in the first year of life [adjusted OR = 0.82, 95 % CI: (0.47 to 1.42) and the use of other vitamin D supplements in the first year of life [adjusted OR = 1.27, 95 % CI: (0.70 to 2.31)] was significantly associated with the risk of diabetes. CONCLUSION/INTERPRETATION: We found that cod liver oil taken during pregnancy was associated with reduced risk of Type I diabetes in the offspring. This suggests that vitamin D or the n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid in the cod liver oil, or both, have a protective effect aginst Type I diabetes.

Biotechnol Bioeng 2000 Dec 5;70(5):587-591

Synthesis of glycerides containing n-3 fatty acids and conjugated linoleic acid by solvent-free acidolysis of fish oil.

Garcia HS, Arcos JA, Ward DJ, Hill CG Jr

UNIDA-Instituto Tecnologico de Veracruz. Apdo. Postal 1420, Veracruz, Ver. Mexico.

Menhaden oil, a rich source of n-3 fatty acids, was interesterified with conjugated linoleic acid (CLA) in a reaction medium composed solely of substrates and either free or immobilized commercial lipase preparations. Of five lipases tested, an immobilized preparation from Mucor miehei provided the fastest rate of incorporation of CLA into fish oil acylglycerols; however, and as observed with most of the lipases utilized, a significant proportion of the n-3 fatty acid residues were liberated in the process. A soluble lipase from Candida rugosa converted free CLA to acylglycerol residues while leaving the n-3 fatty acid residues virtually untouched. Even though the reaction rate was slower for this enzyme than for the other four lipase preparations, the specificity of the free C. rugosa lipase gives it the greatest potential for commercial use in preparing fish oils enriched in CLA residues but still retaining their original n-3 fatty acid residues. Copyright 2000 John Wiley & Sons, Inc.

Biochem J 2000 Nov 1;351(Pt 3):795-804

Bis(monoacylglycerol) phosphate in rat uterine stromal cells: structural characterization and specific esterification of docosahexaenoic acid.

Luquain C, Dolmazon R, Enderlin JM, Laugier C, Lagarde M, Pageaux JF

Laboratoire de Biochimie et Pharmacologie, INSA Lyon, INSERM U352, France.

In rat uterine stromal cells (U(III) cells), docosahexaenoic acid (DHA) was esterified extensively in alkenylacyl-glycerophosphoethanolamine and in an unknown phospholipid accounting for only 0.7% of the total phospholipid. The latter was identified as a bis(monoacylglycerol) phosphate (BMP) using MS. Incorporation studies using C(18:3)n-3 and C(20:5)n-3 demonstrated that BMP had a high specificity to incorporate DHA and C(22) polyunsaturated fatty acids of the (n-3) series. By contrast, polyunsaturated fatty acids of the (n-6) series were never incorporated into BMP. Incubation of U(III) cells with 5 muM DHA for 24 h increased the DHA content of BMP from 36 to 71% of the total acyl chains. [(3)H]DHA-labelled BMP purified as a single TLC spot was resolved into three peaks using HPLC. These peaks were also observed when cells were labelled with [(3)H]phosphatidylglycerol, an exogenous BMP precursor, and with [(33)P]P(i). Electrospray MS of BMP from control cells showed that the first two peaks contained the same molecular species (mainly C(22:6)n-3/C(22:6)n-3 and C(18:1)n-9/C(22:6)n-3) while the third peak mainly contained the C(18:1)n-9/C(18:1)n-9 species. The stereoconfiguration analysis of the compounds revealed an sn-glycero-3-phospho-1'-sn-glycerol configuration for the first peak and sn-glycero-1-phospho-1'-sn-glycerol configurations for the other two. BMP from rat testis was used to establish the positions of the acyl groups. More than 70% of its acyl chains were C(22:5) n-6. It was separated on HPLC into three peaks that co-migrated with the three peaks of BMP from U(III) cells. Lipase activity and NMR analysis of the second peak showed that fatty acids esterified the primary alcohol group on each glycerol moiety. We conclude that the three peaks are stereoisomeric compounds with different acyl-chain locations and may be the result of different metabolic fates depending on subcellular localization.

Mol Cell Biochem 2000 Aug;211(1-2):39-45

Selective inhibition of the non-enzymatic lipid peroxidation of phosphatidylserine in rod outer segments by alpha-tocopherol.

Terrasa A, Guajardo M, Catala A

Catedra de Bioquimica, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, Argentina.

In the present study it was investigated if alpha-tocopherol shows protection against in vitro lipid peroxidation of phospholipids located in rod outer segment membranes (ROS). After incubation of ROS in an ascorbate-Fe2+ system, at 37 degrees C during 160 min, the total cpm originated from light emission (chemiluminescence) was found to be lower in those membranes incubated in the presence of alpha-tocopherol. The fatty acid composition of total lipids isolated from rod outer segment membranes was substantially modified when subjected to non-enzymatic lipid peroxidation with a considerable decrease of docosahexaenoic acid (22:6 n-3). The incorporation of alpha-tocopherol (0.35 microlmol/mg protein) produce a 43.37% inhibition of the lipid peroxidation process evaluated as chemiluminiscence (total cpm originated in 160 min). The phospholipid species containing the highest amount of docosahexaenoic acid: phosphatidyletanolamine and phosphatidylserine were more affected than phosphatidylcholine during the lipid peroxidation process. Not all phospholipids, however, were equally protected after the addition of alpha-tocopherol to the incubation medium. Phosphatidylcholine and phosphatidyletanolamine, were not protected by alpha-tocopherol, the vitamin provides selective antioxidant protection only for phosphatidylserine. These results indicate that alpha-tocopherol may act as antioxidant protecting rod outer segment membranes from deleterious effect by a selective mechanism that diminishes the loss of docosahexaenoic acid from phosphatidylserine.

Am J Clin Nutr 2000 Nov;72(5):1202-1205

Breast-fed and formula-fed infants do not differ in immunocompetent cell cytokine production despite differences in cell membrane fatty acid composition.

Granot E, Golan D, Berry EM

Department of Pediatrics, Hadassah University Hospital, and the Department of Human Nutrition and Metabolism, Hebrew University-Hadassah Medical School, Jerusalem.

BACKGROUND: Breast-fed and formula-fed infants differ in the amount and type of polyunsaturated fatty acids consumed. The fatty acid composition of cell membranes is related to dietary fatty acids and, in adults, changes in membrane fatty acid composition are accompanied by changes in monocyte cytokine production and hence a modification of the immunologic response. OBJECTIVE: Our objective was to determine whether production by immunocompetent cells of the proinflammatory cytokines interleukin 1 (IL-1) and tumor necrosis factor (TNF) differs between breast-fed and formula-fed infants. DESIGN: Twenty-six healthy infants (13 breast-fed and 13 fed modified cow-milk formula) aged 2-4 mo were studied. The fatty acid composition of red blood cell (RBC) membrane phospholipids was measured by gas-liquid chromatography and IL-1 and TNF release were measured in whole blood culture in bacterial-endotoxin-stimulated and unstimulated cells. RESULTS: The infants' ages, weights, hemoglobin concentrations, and white blood cell counts did not differ significantly between groups. The percentage of n-3 fatty acids of total RBC phospholipid fatty acids was significantly higher in breast-fed than in formula-fed infants (6.31 +/- 2.5% compared with 2.98 +/- 0.97%); docosahexaenoic acid (22:6n-3) concentrations were also markedly higher in breast-fed infants (5.1 +/- 1.2% compared with 2.2 +/- 0.9%, P: < 0.001), but eicosapentaenoic acid (20:5n-3) and docosapentaenoic acid (22:5n-3) concentrations did not differ significantly between groups. The percentage of n-6 fatty acids was not significantly different between groups. The percentage of oleic acid (18:1) was higher in formula-fed than in breast-fed infants (16.2 +/- 0.7% compared with 20.6 +/- 1.1%; P: < 0.001). IL-1 and TNF release in whole blood culture did not differ significantly between groups. CONCLUSION: The release of proinflammatory cytokines by immunocompetent cells does not differ significantly in breast-fed and formula-fed infants despite differences in cell membrane fatty acid composition.

J Anim Sci 2000 Nov;78(11):2849-55

Fatty acid composition, including conjugated linoleic acid, of intramuscular fat from steers offered grazed grass, grass silage, or concentrate-based diets.

French P, Stanton C, Lawless F, O'Riordan EG, Monahan FJ, Caffrey PJ, Moloney AP

Teagasc, Grange Research Centre, Dunsany, Co. Meath, Ireland.

The effects of grazed grass, grass silage, or concentrates on fatty acid composition and conjugated linoleic acid (cis-9, trans-11-18:2; CLA) concentrations of i.m. fat of steers fed to achieve similar carcass growth rates were investigated. Fifty steers were divided into 10 blocks based on body weight and assigned at random from within blocks to one of five dietary treatments. The experimental rations offered daily for 85 d preceding slaughter were 1) grass silage for ad libitum intake plus 4 kg of concentrate, 2) 8 kg of concentrate plus 1 kg of hay, 3) 6 kg of grazed grass DM plus 5 kg of concentrate, 4) 12 kg of grazed grass DM plus 2.5 kg concentrate, or 5) 22 kg of grazed grass DM. The concentration of polyunsaturated fatty acids (PUFA) in i.m. fat was higher (P < .05) for steers offered ration 5 than for those given any other ration. Decreasing the proportion of concentrate in the diet, which effectively increased grass intake, caused a linear decrease in the concentration of i.m. saturated fatty acids (SFA) (P < .01) and in the n-6:n-3 PUFA ratio (P < .001) and a linear increase in the PUFA:SFA ratio (P < .01) and the conjugated linoleic acid concentration (P < .001). The data indicate that i.m. fatty acid composition of beef can be improved from a human health perspective by inclusion of grass in the diet.

Anticancer Res 2000 Sep-0Oct;20(5A):3195-203

N-3 polyunsaturated fatty acids accentuate B16 melanoma growth and metastasis through suppression of tumoricidal function of T cells and macrophages.

Salem ML, Kishihara K, Abe K, Matsuzaki G, Nomoto K

Department of Immunology, Kyushu University, Fukuoka, Japan. mohamed-84@hotmall.com

BACKGROUND: The antitumor effects of the n-3 polyunsaturated fatty acids (PUFAs) are still controversial and as yet undefined. MATERIALS AND METHODS: EPA-28, a fish oil enriched with n-3 PUFAs including eicosapentaenoic and docosahexaenoic acids, was administered subcutaneously into C57BL/6 mice before and after subcutaneous inoculation of B16 melanoma cells. The effects of EPA-28 on the antitumor activities of T cells and macrophages were investigated. RESULTS: The treatment of the mice with EPA-28 before and after the tumor inoculation enhanced the growth and metastasis of B16 melanoma and decreased the survival rate of the tumor-bearing mice. The treatment also decreased the number of CD4+ T cells in the spleen and tumor draining lymph nodes on day 14 after the tumor inoculation. Moreover, EPA-28 suppressed the antimelanoma cytolytic activity of T cells and macrophages of the tumor-bearing mice. CONCLUSION: The results suggest that EPA-28 treatment increased both the growth and metastasis of B16 melanoma cells by suppressing the cytolytic function of both T cells and macrophages.

Atherosclerosis 2000 Nov 1;153(1):129-138

The effect of concentrated n-3 fatty acids versus gemfibrozil on plasma lipoproteins, low density lipoprotein heterogeneity and oxidizability in patients with hypertrygliceridemia.

Stalenhoef AF, de Graaf J, Wittekoek ME, Bredie SJ, Demacker PN, Kastelein JJ

541 Department of Internal Medicine, University Hospital Nijmegen, PO Box 9101, 6500 HB, Nijmegen, The Netherlands

We evaluated in a double-blind randomized trial with a double-dummy design in 28 patients with primary hypertriglyceridemia, the effect of gemfibrozil (1200 mg/day) versus Omacor (4 g/day), a drug containing the n-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), on lipid and lipoprotein levels, low density lipoprotein (LDL) subfraction profile and LDL oxidizability. Both Omacor and gemfibrozil therapy resulted in a similar significant decrease in serum triglyceride (TG), very low density lipoprotein (VLDL) triglyceride and VLDL cholesterol concentrations and an increase in high density lipoprotein (HDL) and LDL cholesterol concentrations. The increase in LDL cholesterol was due to a significant increase in cholesterol content of the relatively buoyant LDL subfractions LDL1, LDL2 and LDL3, whereas the relative contribution of the dense LDL subfractions LDL4 and LDL5 to total LDL tended to decrease. So, both therapies resulted in a more buoyant LDL subfraction profile, reflected by a significant increase of the value of parameter K (+10.3% on Omacor vs +26.5% on gemfibrozil therapy, gemfibrozil vs Omacor P>0.05). Cu(2+)-induced oxidation of LDL was measured by continuous monitoring of conjugated dienes. After 12 weeks of Omacor treatment LDL appeared more prone to oxidative modification in vitro than LDL after gemfibrozil treatment, as measured by the significantly decreased lag time, preceding the onset of the lipid peroxidation. In both groups the rate of oxidation did not change with therapy. The amount of dienes formed during oxidation increased significantly on Omacor treatment, but not on gemfibrozil treatment. Plasma thiobarbituric acid reactive substances were higher after Omacor and lower after gemfibrozil treatment, although not significantly. We conclude that both Omacor and gemfibrozil have favorable effects on lipid and lipoprotein concentrations and the LDL subfraction profile. However, Omacor increased the susceptibility of LDL to oxidation, whereas gemfibrozil did not affect the resistance of LDL to oxidative modification in vitro. The clinical relevance of these changes remains to be established in the light of other postulated favorable effects of n-3 fatty acids on the course of cardiovascular disease.

Atherosclerosis 2000 Nov 1;153(1):47-57

Vascular smooth muscle cells preloaded with eicosapentaenoic acid and docosahexaenoic acid fail to respond to serotonin stimulation.

Pakala R, Pakala R, Sheng WL, Benedict CR

Department of Internal Medicine, Division of Cardiology, University of Texas Health Science Center-Medical School, 6431 Fannin, MSB 6.039, 77030, Houston, TX, USA

Epidemiological, animal and clinical studies indicate that n-3 fatty acids may benefit individuals with known history of cardiovascular disease or at risk of developing it. Though there is indirect evidence to suggest that the beneficial effects of n-3 fatty acids may be because of their ability to inhibit smooth muscle cell (SMC) proliferation, there are no studies that have examined this hypothesis. In this study, the mitogenic effect of serotonin (5HT) and platelet derived growth factor (PDGF), known mitogens for vascular SMC, on aortic SMCs preloaded with eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) is examined. 5HT and PDGF could only partially stimulate proliferation of SMC that were preloaded with EPA or DHA as compared to the control cells. gamma-Linolenic acid (LA) and oleic acid (OA) did not block the 5HT or PDGF induced 3[H]thymidine incorporation suggesting that the anti-proliferative effect was specific to n-3 fatty acids only. Further, when EPA and DHA were combined in the ratio they are present in fishoils, there was a synergistic interaction in inhibiting the proliferation of SMC. Further, SMC grown in the presence of EPA or DHA, when stimulated with 5HT, failed to show an increase in 5HT(2) receptor mRNA. One of the potential mechanism by which fish oils may prevent the development of atherosclerosis or restenosis could be inhibition of the mitogen induced SMC proliferation. Combination of EPA with DHA is likely to be more beneficial.

J Reprod Fertil 2000 Nov;120(2):257-264

Effect of long-term supplementation with arachidonic or docosahexaenoic acids on sperm production in the broiler chicken.

Surai PF, Noble RC, Sparks NH, Speake BK

Department of Biochemistry and Nutrition, Scottish Agricultural College, Auchincruive, Ayr KA6 5HW, UK.

The possibility was investigated that dietary supplementation of the male chicken with long-chain polyunsaturated fatty acids of the n-6 and n-3 series may prevent the decrease in sperm output that normally occurs by 60 weeks of age. From 26 weeks of age, birds were raised on wheat-based diets supplemented with either maize oil (rich in linoleic acid, 18&ratio;2n-6), arasco oil (rich in arachidonic acid, 20&ratio;4n-6) or tuna orbital oil (rich in docosahexaenoic acid, 22&ratio;6n-3). The effects of the last two oils were investigated at two levels of vitamin E supplementation (40 and 200 mg kg(-1) feed). By 60 weeks of age, there was a small increase in the proportion of the main polyunsaturate of chicken sperm phospholipid, docosatetraenoic acid 22&ratio;4n-6, in chickens fed arasco oil diet compared with chickens given the maize oil diet, an effect that was potentiated at the higher dietary intake of vitamin E. Supplementation with tuna orbital oil significantly reduced the proportions of 20&ratio;4n-6 and 22&ratio;4n-6 in the sperm phospholipid and increased the proportion of 22&ratio;6n-3. The diet supplemented with tuna orbital oil and the lower level of vitamin E markedly depleted vitamin E from the tissues of the birds and decreased the concentration of vitamin E in the semen; these effects were largely prevented by the higher level of vitamin E in the diet. The susceptibility of semen to lipid peroxidation in vitro was increased in chickens fed arasco and tuna orbital oils with 40 mg vitamin E kg(-1) feed, but was reduced when 200 mg vitamin E kg(-1) feed was provided in the diet. The number of spermatozoa per ejaculate decreased by 50% between 26 weeks and 60 weeks of age in the birds fed the maize oil diet. This age-related decrease in the number of spermatozoa was almost completely prevented by feeding the birds with the oils enriched in either 20&ratio;4n-6 or 22&ratio;6n-3. Testis mass at 60 weeks of age was approximately 1.5 times greater in birds given of the arasco and tuna orbital oil diets compared with those given the maize oil diet.