Showing papers on "Docosahexaenoic acid published in 1996"

Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants

Abstract: It is becoming clear that an adequate level of long-chain highly unsaturated fatty acids in the nervous system is required for optimal function and development; however, the ability of infants to biosynthesize long-chain fatty acids is unknown. This study explores the capacity of human infants to convert 18-carbon essential fatty acids to their elongated and desaturated forms, in vivo. A newly developed gas chromatography/negative chemical ionization/mass spectrometry method employing 2H-labeled essential fatty acids allowed assessment of this in vivo conversion with very high sensitivity and selectivity. Our results demonstrate that human infants have the capacity to convert dietary essential fatty acids administered enterally as 2H-labeled ethyl esters to their longer-chain derivatives, transport them to plasma, and incorporate them into membrane lipids. The in vivo conversion of linoleic acid (18:2n6) to arachidonic acid (20:4n6) is demonstrated in human beings. All elongases/desaturases necessary for the conversion of linolenic acid (18:3n3) to docosahexaenoic acid (22:6n3) are also active in the first week after birth. Although the absolute amounts of n-3 fatty acid metabolites accumulated in plasma are greater than those of the n-6 family, estimates of the endogenous pools of 18:2n6 and 18:3n3 indicate that n-6 fatty acid conversion rates are greater than those of the n-3 family. While these data clearly demonstrate the capability of infants to biosynthesize 22:6n3, a lipid that is required for optimal neural development, the amounts produced in vivo from 18:3n3 may be inadequate to support the 22:6n3 level observed in breast-fed infants.

Composition, accumulation and utilization of yolk lipids in teleost fish

Abstract: Lipid reserves in teleost eggs are stored in lipoprotein yolk and, in some species, a discrete oil globule. Lipoprotein yolk lipids are primarily polar lipids, especially phosphatidylcholine and phosphatidylethanolamine (PE), and are rich in (n−3) polyunsaturated fatty acids, especially 22:6(n−3) (docosahexaenoic acid, DHA). Oil consists of neutral lipids and is rich in monounsaturated fatty acids (MUFA). Egg lipids are derived from dietary fatty acid, fatty acid mobilized from reserves and possibly fatty acid synthesized de novo. There is selective incorporation of essential fatty acids, particularly DHA, into yolk lipids and discrimination against incorporation of 22:1(n−11). Lipid is delivered to the oocyte by vitellogenin, which is rich in polar lipids, and likely also by other lipoproteins, especially very low density lipoprotein, which is rich in triacylglycerol (TAG). All classes of lipid may be used as fuel during embryonic and larval development and MUFA are preferred fatty acids for catabolism by embryos. Catabolism of oil globules is frequently delayed until latter stages of development. In some species, DHA derived from hydrolysis of phospholipid may be conserved by transfer to the neutral lipid. Recent work has expanded knowledge of the role of DHA in membrane structure, especially in neural tissue, and molecular species analysis has indicated that PE containing sn-1 oleic acid is a prime contributor to membrane fluidity. The results of this type of study provide an explanation for the selection pressures that influence yolk lipid composition. Future work ought to expand knowledge of specific roles of individual fatty acids in embryos along with knowledge of the ecological physiology of ovarian recrudescence, environmental influences on vitellogenin and yolk lipid composition, and the control of yolk lipid accumulation and utilization.

A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until two months

Abstract: This was a randomized, double-blind trial to determine if a nutrient-enriched (preterm) formula supplemented with 0.2% docosahexaenoic acid (DHA, 22:6n-3) from a low eicosapentaenoic acid (0.06%) source of marine oil would enhance visual novelty preference and attention of preterm infants. Both the standard and experimental formulas contained 3% of total fatty acids as linolenic acid (18:3n-3) and were fed from approximately three days of age to two months past term. After two months, both diet groups were fed a commercially-available term formula with linolenic acid as the only source of n-3 fatty acid. At 12 mo visual recognition memory (novelty preference) and visual attention (number and duration of discrete looks) were determined with the Fagan Test of Infant Intelligence. The DHA-supplemented group compared with the control group had more and shorter duration looks in comparisons of familiar and novel stimuli, confirming earlier evidence that DHA can increase information processing speed of preterm infants who otherwise are receiving good intakes of linolenic acid. Because supplementation was stopped at two months and the effects seen at 12 mon, this study demonstrates for the first time that a relatively short period of DHA supplementation can produce significant effects on later visual attention.

Polyunsaturated fatty acids modulate sodium and calcium currents in CA1 neurons

Abstract: Recent evidence indicates that long-chain polyunsaturated fatty acids (PUFAs) can prevent cardiac arrhythmias by a reduction of cardiomyocyte excitability. This was shown to be due to a modulation of the voltage-dependent inactivation of both sodium (INa) and calcium (ICa) currents. To establish whether PUFAs also regulate neuronal excitability, the effects of PUFAs on INa and ICa were assessed in CA1 neurons freshly isolated from the rat hippocampus. Extracellular application of PUFAs produced a concentration-dependent shift of the voltage dependence of inactivation of both INa and ICa to more hyperpolarized potentials. Consequently, they accelerated the inactivation and retarded the recovery from inactivation. The EC50 for the shift of the INa steady-state inactivation curve was 2.1 +/- 0.4 microM for docosahexaenoic acid (DHA) and 4 +/- 0.4 microM for eicosapentaenoic acid (EPA). The EC50 for the shift on the ICa inactivation curve was 2.1 +/- 0.4 for DHA and > 15 microM for EPA. Additionally, DHA and EPA suppressed both INa and ICa amplitude at concentrations > 10 microM. PUFAs did not affect the voltage dependence of activation. The monounsaturated oleic acid and the saturated palmitic acid were virtually ineffective. The combined effects of the PUFAs on INa and ICa may reduce neuronal excitability and may exert anticonvulsive effects in vivo.

The very low birth weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acids from linoleic and linolenic acids.

Abstract: Infants fed formulas devoid of long-chain polyunsaturated fatty acids (LCP) exhibit low plasma LCP concentrations and have poorer retinal and neurologic development in comparison with their human milk-fed counterparts. It is not known whether the low plasma LCP concentrations result from an impaired biosynthetic capacity, a high need or a low dietary intake. With stable isotope technology and high sensitivity tracer detection using gas chromatography-isotope ratio mass spectrometry we measured the conversion of [13C]linoleic acid (C18:2n-6) and [13C]linolenic acid (C18:3n-3) into their longer chain derivatives in five 1-mo-old formula-fed preterm infants (birth weight 1.17 +/- 0.12.kg and gestational age 28.4 +/- 1.3 wk). Carbon-13-labeled linoleic acid and inolenic were mixed with the formula and administered continuously for 48 h. Both tracers were rapidly incorporated in plasma phospholipids, and their metabolic products including arachidonic acid (C20:4n-6) and docosahexaenoic acid (C22:6n-3) became highly enriched. We demonstrate that the preterm infant is capable of synthesizing LCP from their 18-carbon precursors, and our data do not support the hypothesis that a reduced delta 6 desaturation is a main factor leading to low arachidonic acid and docosahexaenoic acid levels.

Essential fatty acid requirements of cultured marine fish larvae

Abstract: Feeding of marine fish larvae is, in most cases, limited to the administration of two species of live prey. This reduction in the range of food available for the cultured larvae may occasionally lead to nutritional imbalances or deficiencies. A large amount of research has been recently devoted to the study of the essential fatty acid requirements of marine fish larvae. Studies on the biochemical composition of developing eggs and larvae, as well as the comparison of the patterns of loss and conservation during starvation, pointed out the importance of n-3 HUFA and arachidonic acid as essential fatty acids for larvae of marine fish. The biochemical composition of marine fish larvae, in terms of lipid content and fatty acid composition of total and polar lipids, is modified by dietary levels of essential fatty acids. Larval growth, survival and activity have also been reported to be affected by dietary levels of essential fatty acids. In addition, some pathological signs, such as hydrops or abnormal pigmentation, have been related to essential fatty acid deficiency in these fish. Based on these effects, the essential fatty acid requirements of marine larval fish have been reported to range between 0.3 and 55 g kg−1 n-3 HUFA on a dry weight basis, suggesting that quantitative requirements of fish larvae may differ from those of juveniles or adults. But quantitative requirements for larvae of the same species reported by various authors are often contradictory. These differences are discussed in relation to the dietary lipid content, ratio 20:5n-3/22:6n-3 and culture conditions used.

Visual acuity and fatty acid status of term infants fed human milk and formulas with and without docosahexaenoate and arachidonate from egg yolk lecithin

Abstract: Preterm infants fed formulas with docosahexaenoic acid (DHA, 22:6n-3) during the interval equivalent to the last intrauterine trimester and beyond have higher circulating DHA and transiently higher visual acuity compared with infants fed formulas containing linolenic acid. In term infants several nonrandomized studies of infants receiving DHA from human milk suggest a relationship between DHA status and acuity, but the evidence for a cause-and-effect relationship is mixed. In the present study, term infants were randomly assigned to a standard term formula (n = 20) or the same formula with egg yolk lecithin to provide DHA (0.1%) and arachidonic acid (AA, 20:4n-6, 0.43%) (n = 19) at levels reported in milk of American women. A third group of infants was breast fed for > or = 3 mo (n = 19). Grating visual acuity (Teller Acuity Card procedure) and plasma and red blood cell (RBC) phosphatidylcholine (PC) and phosphatidylethanolamine (PE) DHA and AA were determined at corrected ages of 2, 4, 6, 9 (acuity only), and 12 mo past term = 40 wk postmenstrual age (PMA). At 2 mo breast-fed infants and infants fed the supplemented formula had higher grating acuity than term infants fed standard formula. As in preterm infants, the increase was transient. Plasma PC DHA and AA and RBC PE AA increased by 2 mo in supplemented infants, but RBC PE DHA in supplemented infants was not higher than in controls until 4 mo and beyond. Despite normal intrauterine accumulation of DHA and AA, infants fed formula with 2% linolenic acid and 0.1% DHA had better 2-mo visual acuity than infants fed formula with 2% linolenic acid.

Effect of maternal docosahexaenoic acid (DHA) supplementation on breast milk composition

Abstract: OBJECTIVE To assess the effect of varying maternal intake of docosahexaenoic acid (DHA, 22 : 6n-3), in the absence of other dietary polyunsaturates, on breast milk fatty acids. DESIGN AND INTERVENTION Lactating mothers were randomised on day 5 post-partum to groups consuming equal numbers of capsules but containing either placebo or an oil containing DHA (43%) as its only polyunsaturate to receive 0, 0.2, 0.4, 0.9, 1.3 g DHA/day. Breast milk fatty acids as well as maternal plasma and erythrocyte phospholipids were assessed at 12 weeks post partum by capillary gas chromatography. RESULTS Breast milk DHA levels ranged from 0.2 to 1.7% of total fatty acids and increased in a dose dependent manner (r2 = 0.89, P < 0.01). Maternal plasma (r2 = 0.71, P < 0.01) and erythrocyte (r2 = 0.77, P < 0.01) phospholipid DHA levels increased and were also strongly associated with dietary dose of DHA. Increasing maternal dietary doses of DHA did not affect breast milk arachidonic acid (AA, 20 : 4n-6) levels or antioxidant status as measured by plasma vitamin A or E levels. CONCLUSIONS Our results have demonstrated that DHA in the diet has a strong, specific and dose-dependent effect on breast milk DHA.

High-fat diet-induced hyperglycemia and obesity in mice: Differential effects of dietary oils

Abstract: Mice fed a high-fat diet develop hyperglycemia and obesity. Using non-insulin-dependent diabetes mellitus (NIDDM) model mice, we investigated the effects of seven different dietary oils on glucose metabolism: palm oil, which contains mainly 45% palmitic acid (16:0) and 40% oleic acid (18:1); lard oil, 24% palmitic and 44% oleic acid; rapeseed oil, 59% oleic and 20% linoleic acid (18:2); soybean oil, 24% oleic and 54% linoleic acid; safflower oil, 76% linoleic acid; perilla oil, 58% alpha-linolenic acid; and tuna fish oil, 7% eicosapentaenoic acid and 23% docosahexaenoic acid. C57BL/6J mice received each as a high-fat diet (60% of total calories) for 19 weeks (n = 6 to 11 per group). After 19 weeks of feeding, body weight induced by the diets was in the following order: soybean > palm > or = lard > or = rapeseed > or = safflower > or = perilla > fish oil. Glucose levels 30 minutes after a glucose load were highest for safflower oil (approximately 21.5 mmol/L), modest for rapeseed oil, soybean oil, and lard (approximately 17.6 mmol/L), mild for perilla, fish, and palm oil (approximately 13.8 mmol/L), and minimal for high-carbohydrate meals (approximately 10.4 mmol/L). Only palm oil-fed mice showed fasting hyperinsulinemia (P < .001). By stepwise multiple regression analysis, body weight (or white adipose tissue [WAT] weight) and intake of linoleic acid (or n-3/n-6 ratio) were chosen as independent variables to affect glucose tolerance. By univariate analysis, the linoleic acid intake had a positive correlation with blood glucose level (r = .83, P = .02) but not with obesity (r = .46, P = .30). These data indicate that (1) fasting blood insulin levels vary among fat subtypes, and a higher fasting blood insulin level in palm oil-fed mice may explain their better glycemic control irrespective of their marked obesity; (2) a favorable glucose response induced by fish oil feeding may be mediated by a decrease of body weight; and (3) obesity and a higher intake of linoleic acid are independent risk factors for dysregulation of glucose tolerance.

The effect of docosahexaenoic acid on aggression in young adults. A placebo-controlled double-blind study.

Abstract: 41 students took either docosahexaenoic acid (DHA)-rich oil capsules containing 1.5-1.8 grams DHA/day (17 females and 5 males) or control oil capsules containing 97% soybean oil plus 3% fish oil (12 females and 7 males) for 3 mo in a double-blind fashion. They took a psychological test (P-F Study) and Stroop and dementia-detecting tests at the start and end of the study. The present study started at the end of summer vacation and ended in the middle of mental stress such as final exams. In the control group extraggression (aggression against others) in P-F Study was significantly increased at the end of the study as compared with that measured at the start (delta = +8.9%, P = 0.0022), whereas it was not significantly changed in the DHA group (delta = -1.0%). The 95% CI of differences between the DHA and control groups were -16.8 to -3.0%. DHA supplementation did not affect the Stroop and dementia-detecting tests. Thus, DHA intake prevented extraggression from increasing at times of mental stress. This finding might help understand how fish oils prevent disease like coronary heart disease.

Supplementation with an algae source of docosahexaenoic acid increases (n-3) fatty acid status and alters selected risk factors for heart disease in vegetarian subjects

Abstract: The purpose of this double-blind study was to investigate the influence of dietary supplementation with an algae source of docosahexaenoic acid [DHA; 22:6(n-3)], devoid of any eicosapentaenoic acid [EPA; 20:5(n-3)], on serum/platelet DHA status, the estimated retroconversion of DHA to EPA, and risk factors for heart disease in vegetarian subjects. Healthy vegetarians (12 male, 12 female) consumed nine capsules daily of either DHA (1.62 g/d) or corn oil for 6 wk. Consumption of DHA capsules increased DHA levels in serum phospholipid by 246% (from 2.4 to 8.3 g/100 g fatty acids) and in platelet phospholipid by 225% (from 1.2 to 3.9 g/100 g fatty acids). EPA levels increased in serum phospholipid by 117% (from 0.57 to 1.3 g/100 g fatty acids) and in platelet phospholipid by 176% (0.21 to 0.58 g/100 g fatty acids) via metabolic retroconversion; the estimated extent of DHA retroconversion to EPA was 11.3 and 12.0%, based on the serum and platelet analyses, respectively. Arachidonic acid [AA; 20:4(n-6)] levels in serum and platelet phospholipids decreased moderately during the trial period (DHA group) as did both docosapentaenoic acids [22:5(n-6) and 22:5(n-3)]. Although no significant changes were found in the total and LDL-cholesterol levels with DHA supplementation, the total cholesterol:HDL-cholesterol ratio showed a moderate decrease over time as did the LDL-cholesterol:HDL-cholesterol ratio and serum triglyceride concentrations. DHA supplementation did not alter the various thrombogenic factors measured. In conclusion, DHA supplementation markedly enhanced the DHA status (of serum and platelets), provided for the formation of substantial EPA, and lowered the total and LDL-cholesterol:HDL-cholesterol ratios.

Production of docosahexaenoic and docosapentaenoic acids bySchizochytrium sp. isolated from Yap Islands

Abstract: A marine microbe (strain SR21) from the coral reef area of the Yap Islands was isolated by a screening test for polyunsaturated fatty acids and was found to accumulate lipid that contained 22:5n-6 docosapentaenoic acid (DPA) as well as 22:6n-3 docosahexaenoic acid (DHA). Strain SR21 was identified as genusSchizochytrium in Labyrinthulomycota, owing to its ultrastructural character and life cycle, which is composed of vegetative cell, zoosporangium, and zoospore stages. After cultural optimization, both in flask and fermenter, the highest DHA and DPA productivities of 2.0 and 0.44 g/L per day, respectively, were obtained in a medium of 60 g/L glucose and corn steep liquor/ammonium sulfate in a half salt concentration of seawater in fermenter culture at 28°C and pH 4. This productivity was almost twice that obtained with flask culture, indicating its high resistance to mechanical stirring. The lipid extracted from the cell was about 50% of the dry cell weight and was composed of 93% triacylglycerol (TG). DHA content of the lipid was 34% of total fatty acids. The TG profile was simple, and the content of the most dominant TG, 1,3-dipalmitoyl-2-DHA-TG, was 27%. TG that contained DHA and n-6-DPA amounted to 57 and 17%, respectively, of total TG molecules. Strain SR21 was revealed to be an excellent source of microbial DHA and n-6 DPA.

Nutritional Enhancement of n‐3 and n‐6 Fatty Acids in Rotifers and Artemia Nauplii by Feeding Spray‐dried Schizochytrium sp.

Abstract: A docosahexaenoic acid (DHA), 22:6(n-3), rich strain of Schizochytrium sp. was used in a spray-dried form to evaluate the enhancement of highly unsaturated fatty acids (HUFAs) in Artemia franciscana nauplii (Utah biotype) and the rotifer Brachionus plicatilis. This heterotrophic microalga was selected because of its high concentration of the longest chain HUFAs in the n-3 and n-6 series, DHA and docosapentaenoic acid (DPA), 22:5(n-6), respectively. When 24-h-old Artemia nauplii were fed 400 mg/L of the algae for 24 h, the DHA content of the nauplii went from undetectable levels to 0.8% of dry weight and the omega-3 HUFA eicosapentaenoic acid (EPA), 20:5n-3, content went from 0.1% to 0.5% of dry weight in the nauplii. Similarly, 22:5(n-6) increased in the nauplii from undetectable levels to 0.4% of dry weight, with a concomitant increase in arachidonic acid, (20:4n-6), from trace to 0.3% of dry weight even though there was no arachidonic acid in the algal biomass. Similar enrichment patterns were observed in rotifers. The results suggest that spray-dried cells of Schizochytrium sp. are effective in enriching Artemia naupli and rotifers in both n-3 and n-6 HUFAs. The results also suggest that Artemia nauplii and rotifers are capable of readily retroconverting 22:6(n-3) to 20:5(n-3) and 22:5(n-6) to 20:4(n-6) through the process of β-oxidation, a well-known process in mammals.

Evidence that free polyunsaturated fatty acids modify Na+ channels by directly binding to the channel proteins

Abstract: The effects of free polyunsaturated fatty acids (PUFA) on the binding of ligands to receptors on voltage-sensitive Na+ channels of neonatal rat cardiac myocytes were assessed. The radioligand was [benzoyl-2,5-(3)H] batrachotoxinin A 20alpha-benzoate ([(3)H]BTXB), a toxin that binds to the Na+ channel. The PUFA that have been shown to be antiarrhythmic, including eicosapentaenoic acid (EPA; C20:5n-3), docosahexaenoic acid (DHA; C22:6n-3), eicosatetraynoic acid (ETYA), linolenic acid (C18:3n-3), and linoleic acid (C18:2n-6), inhibited [(3)H]BTXB binding in a dose-dependent fashion with IC50 values of 28-35 microM, whereas those fatty acids that have no antiarrhythmic effects including saturated fatty acid (stearic acid, C18:0), monounsaturated fatty acid (oleic acid; C18:1n-9), and EPA methyl ester did not have a significant effect on [(3)H]BTXB binding. Enrichment of the myocyte membrane with cholesterol neither affected [(3)H]BTXB binding when compared with control cells nor altered the inhibitory effects of PUFA on [(3)H]BTXB binding. Scatchard analysis of [(3)H]BTXB binding showed that EPA reduced the maximal binding without altering the Kd for [(3)H]BTXB binding, indicating allosteric inhibition. The inhibition by EPA of [(3)H]BTXB binding was reversible (within 30 min) when delipidated bovine serum albumin was added. The binding of the PUFA to this site on the Na+ channel is reversible and structure-specific and occurs at concentrations close to those required for apparent antiarrhythmic effects and a blocking effect on the Na+ current, suggesting that binding of the PUFA at this site relates to their antiarrhythmic action.

Role of essential fatty acids in the function of the developing nervous system

Abstract: The basis for n-3 fatty acid essentially in humans includes not only biochemical evidence but functional measures associated with n-3 deficiency in human and nonhuman primates. Functional development of the retina and the occipital cortex are affected by alpha-linolenic acid deficiency and by a lack of docosahexaenoic acid (DHA) in preterm infant formulas and, as reported more recently, in term diets. Functional effects of n-3 supply on sleep-wake cycles and heart rate rhythms support the need for dietary n-3 fatty acids during early development. Our results indicate that n-3 long-chain polyunsaturated fatty acids should be considered provisionally essential for infant nutrition. DHA may also be required by individuals with inherited metabolic defects in elongation and desaturation activity, such as patients with peroxisomal disorders and some forms of retinitis pigmentosa.

Plasma lipids, erythrocyte membrane lipids and blood pressure of hypertensive women after ingestion of dietary oleic acid from two different sources

Abstract: Objective To study the effect of a diet rich in monounsaturated fatty acids (MUFA), from high-oleic sunflower oil (HOSO) and olive oil, on plasma lipids, erythrocyte membrane lipids (including fatty acid composition) and blood pressure of hypertensive (normocholesterolaemic or hypercholesterolaemic) women. Methods There were 16 participants who were hypertensive women aged 56.2 ± 5A years. The participants ate a diet enriched with HOSO or olive oil for two 4-week periods with a 4-week washout period before starting the second type of MUFA diet At entry and during study of each diet, plasma lipids and apolipoproteins were measured by conventional enzymatic methods. Erythrocyte membrane lipid and fatty acid compositions were analysed by means of the latroscan thin-layer chromatography/flame ionization detection technique and by gas chromatography, respectively. Blood pressure was also measured. The statistical analysis was conducted by using Student's two-tailed paired t-test Results In both groups of hypertensive patients, there was a significant increase in plasma high-density lipoprotein (HDL) cholesterol concentration after the HOSO or olive oil diets, with regard to baseline. Additionally, a significant decrease in plasma HDL 2 cholesterol concentration and an increase in plasma HDL 3 cholesterol concentration were evident The membrane free-cholesterol concentration increased significantly and the phospholipid concentration decreased significantly in erythrocytes after the olive oil diet, though both MUFA diets produced a significant decrease in the concentration of membrane esterified cholesterol. Therefore, the molar ratio of cholesterol to phospholipids was raised significantly in the erythrocyte membrane of hypertensive women after the dietary olive oil, but not after the HOSO diet In the hypertensive and normocholesterolaemic group the HOSO diet significantly increased the content in the erythrocyte membrane of oleic, eicosenoic, arachidonic and docosapentaenoic acids, whereas the olive oil diet increased the content of palmitoleic acid and long-chain polyunsaturated fatty acids of the n-3 family besides, compared with baseline. A significant decrease in linoleic acid was also evident In the hypertensive and hypercholesterolaemic group, the HOSO diet resulted in significant increases in palmitoleic, oleic, eicosenoic and behenic acids, whereas the olive oil diet enhanced the content of arachidonic, docosapentaenoic and docosahexaenoic acids besides, with respect to baseline. In addition, there was a significant decrease in stearic acid, but only after dietary olive oil was there a decrease in linoleic acid. The most important differences between the two MUFA diets were the increase in n-3 fatty acids and the decrease in the n-6:n-3 fatty acids ratio after dietary olive oil in the erythrocyte membranes of hypertensive patients. Interestingly, a significant reduction in systolic and diastolic blood pressures was only evident after the ingestion of olive oil. Conclusion These data suggest that the beneficial effects of dietary olive oil on the plasma lipids and lipoprotein profile, lipid and fatty acid composition of erythrocyte membrane, and blood pressure in women with untreated essential hypertension are not found equally for the HOSO-rich diet, despite both vegetable oils providing a similar concentration of MUFA.

Eicosapentaenoic acid is primarily responsible for hypotriglyceridemic effect of fish oil in humans

Abstract: The aim of this study was to determine whether eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), or both, were responsible for the triglyceride (TG)-lowering effects of fish oil. EPA (91% pure) and DHA (83% pure), a fish oil concentrate (FOC; 41% EPA and 23% DHA) and an olive oil (OO) placebo (all ethyl esters) were tested. A total of 49 normolipidemic subjects participated. Each subject was given placebo for 2–3 wk and one of the n-3 supplements for 3 wk in randomized, blinded trials. The target n-3 fatty acid (FA) intake was 3 g/day in all studies. Blood samples were drawn twice at the end of each supplementation phase and analyzed for lipids, lipoproteins, and phospholipid FA composition. In all groups, the phospholipid FA composition changed to reflect the n-3 FA given. On DHA supplementation, EPA levels increased to a small but significant extent, suggesting that some retroconversion may have occurred. EPA supplementation did not raise DHA levels, however, FOC and EPA produced significant decreases in both TG and very low density lipoprotein (VLDL) cholesterol (C) levels (P<0.01) and increases in low density lipoprotein (LDL) cholesterol levels (P<0.05). DHA supplementation did not affect cholesterol, triglyceride, VLDL, LDL, or high density lipoprotein (HDL) levels, but it did cause a significant increase in the HDL2/HDL3 cholesterol ratio. We conclude that EPA appears to be primarily responsible for TG-lowering (and LDL-C raising) effects of fish oil.

Fish diet, fish oil and docosahexaenoic acid rich oil lower fasting and postprandial plasma lipid levels

Abstract: OBJECTIVE The present study was carried out to clarify the effects of fish diet, fish oil and docosahexaenoic acid (DHA) rich oil on fasting and postprandial lipid levels in healthy male students. DESIGN The study was a randomized single-blind study with a control and three study groups. SETTING The study was carried out in the Departments of Physiology and Clinical Nutrition of University of Kuopio. SUBJECTS Healthy male volunteers were recruited for the study from the university student population. Fifty-nine subjects entered and 55 completed the study. INTERVENTIONS For 15 weeks the subjects in the fish diet group ate 4.3 +/- 0.5 fish containing meals per week and those in the fish oil and DHA-oil groups ate 4 g oil per day. Fish diet provided 0.38 +/- 0.04 g eicosapentaenoic acid (EPA) and 0.67 +/- 0.09 g DHA, fish oil 1.33 g EPA and 0.95 g DHA and DHA-oil (EPA-free) 1.68 g DHA per day. RESULTS Fasting plasma triglyceride levels decreased in all test groups in 14 weeks when compared to the control group (P < 0.05). Total plasma cholesterol levels did not change but the HDL2/HDL3-cholesterol ratio increased in all test groups by over 50% (P < 0.05). The postprandial total and chylomicron triglyceride responses, measured as areas under the response curve, were lowered in 15 weeks by the fish diet and fish oil (P < 0.05), the same tendency (P < 0.1) being seen in DHA-oil group. CONCLUSIONS These results show that both fasting and postprandial triglyceride concentrations can be decreased with moderate intakes of long-chain n-3 fatty acids either from a fish diet or fish oil and that also pure DHA has a hypotriglyceridemic effect.

Increased Docosahexaenoic Acid Levels in Human Newborn Infants by Administration of Sardines and Fish Oil During Pregnancy

Abstract: In rhesus monkeys, maternal n-3 fatty acid deficiency during pregnancy produces infant monkeys deficient in n-3 fatty acids at birth. These results stimulated current experiments to find out if n-3 fatty acids from fish in the diets of pregnant women would influence the concentration of docosahexaenoic acid (DHA, 22:6 n-3) in the newborn human infant. Fifteen healthy pregnant women were enrolled to receive a 9-wk dietary supplementation of n-3 fatty acids from the 26th to the 35th wk of pregnancy. Sixteen pregnant women were not supplemented and served as controls. n-3 Fatty acid supplementation consisted of sardines and additional fish oil, which provided a total of 2.6 g of n-3 fatty acids per day (d) for the 9-wk period of supplementation. This included 1.01 g DHA. The end point of this study was the blood concentrations of DHA in the newborn infant. DHA in maternal red blood cells increased from 4.6% of total fatty acids to 7.15% at the end of the supplement period and at the time of delivery decreased (as expected) to 5.97% of total fatty acids. Maternal plasma showed a similar change from 2.12 to 3.51% of total fatty acids and then decreased to 2.35%. Levels of DHA in plasma and red blood cells of unsupplemented mothers did not change during the same time period. Levels of DHA in blood of newborn infants differed greatly in infants born from n-3-supplemented mothers compared with control infants. In red blood cells, DHA was 7.92% of total fatty acids compared with 5.86% (control infants). Plasma values showed a similar difference: 5.05% vs. 3.47% (controls). In n-3-supplemented infants, DHA concentrations were 35.2% higher than in control infants in red blood cells and 45.5% higher in plasma. These data indicate the importance of maternal dietary n-3 fatty acids and, in particular, maternal dietary DHA in promoting higher concentrations of DHA in the blood of the newborn infant.

Chronic administration of eicosapentaenoic acid and docosahexaenoic acid as ethyl esters reduced plasma cholesterol and changed the fatty acid composition in rat blood and organs

Abstract: Fish oils rich in n-3 fatty acids have been shown to decrease plasma lipid levels, but the underlying mechanism has not yet been elucidated. This investigation was performed in order to further clarify the effects of purified ethyl esters of eicosapentaenoic acid (EPA-EE) and docosahexaenoic acid (DHA-EE) on lipid metabolism in rats. The animals were fed EPA-EE, DHA-EE, palmitic acid, or corn oil (1 g/kg/d) by orogastric intubation along with a chow background diet for three months. At the end the animals were sacrificed. Plasma and liver lipids were measured, as well as lipid-related enzyme activities and mRNA levels. The fatty acid composition of plasma and different tissues was also determined. This study shows that, compared to the corn oil control, EPA-EE and DHA-EE lowered plasma cholesterol level, whereas only EPA-EE lowered the amount of plasma triacylglycerol. In liver peroxisomes, both EE preparations increased fatty acyl-CoA oxidase FAO activities, and neither altered 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activities. In liver microsomes, EPA-EE raised HMG-CoA reductase and acyl-CoAicholesterol acyltransferase activities, whereas DHA-EE lowered the former and did not affect the latter. Neither product altered mRNA levels for HMG-CoA reductase, low density lipoprotein-receptor, or low density lipoprotein-receptor related protein. EPA-EE lowered plasma triacylglycerol, reflecting lowered very low density lipoprotein secretion, thus the cholesterol lowering effect in EPA-EE-treated rats may be secondary to the hypotriacylglycerolemic effect. An inhibition of HMG-CoA reductase activity in DHA-EE treated rats may contribute to the hypocholesterolemic effect. The present study reports that 20∶5n-3, and not 22∶6n-3, is the fatty acid primarily responsible for the triacylglycerol lowering effect of fish oil. Finally, 20∶5n-3 was not converted to 22∶6n-3, whereas retroconversion of 22∶6n-3 to 20∶5n-3 was observed.

Relation of Smoking and Alcohol Consumption to Serum Fatty Acids

Abstract: To examine the relation of cigarette smoking and alcohol consumption to serum fatty acid levels, the authors conducted a cross-sectional study of 190 men who were enrolled in the Multiple Risk Factor Intervention Trial between 1973 and 1976. After controlling for dietary fat, cholesterol, energy intake, and other potential confounders, the authors found that smoking and alcohol intake were associated with the serum cholesterol ester and phospholipid levels of several fatty acids. As the number of cigarettes smoked per day increased, the levels of cholesterol ester and phospholipid palmitoleic acid (16:1) and oleic acid (18:1) and the levels of phospholipid dihomogammalinolenic acid (20:3) and omega-9 eicosatrienoic acid (20:3) increased (all p's < or = 0.01). Serum levels of phospholipid omega-3 docosahexaenoic acid (22:6) and cholesterol ester and phospholipid arachidonic acid (20:4) were inversely associated with smoking (all p's < or = 0.01). As the number of alcoholic drinks per week increased, levels of cholesterol ester and phospholipid palmitic acid (16:0) and oleic acid (18:1), cholesterol ester myristic acid (14:0), and phospholipid palmitoleic acid (16:1), adrenic acid (22:4), and omega-9 eicosatrienoic acid (20:3) increased (all p's < 0.05), whereas levels of cholesterol ester and phospholipid linoleic acid (18:2) and phospholipid stearic acid (18:0) and the serum polyunsaturated fat: saturated fat ratio decreased (all p's < or = 0.01). These results suggest that smoking and alcohol consumption may influence the absorption, synthesis, or metabolism of serum fatty acids. Studies that use serum fatty acid levels as indicators of dietary fat intake should control for the effects of cigarette smoking and alcohol consumption.

Effect of omega-3 fatty acids on the progression of metastases after the surgical excision of human breast cancer cell solid tumors growing in nude mice.

Abstract: We showed previously that a diet rich in linoleic acid (LA), an omega-6 fatty acid, stimulates the growth and metastasis of human breast cancer cells in athymic nude mice. In contrast, diets supplemented with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), omega-3 fatty acids, exert suppressive effects. We have now assessed EPA and DHA as adjuvant nutritional therapy in the nude mouse model and compared the responses when the intervention was commenced 1 week before ("neoadjuvant") or immediately after ("postoperative adjuvant") surgical excision of the primary tumor. Female nude mice received a high-fat, 8% LA diet beginning 7 days before 10(6) MDA-MB-435 human breast cancer cells were injected into a thoracic mammary fat pad. As the tumor surface areas approached 0. 7 cm2, the mice were assigned to either continue on the LA-rich diet or to commence one containing 8, 4, or 2% EPA or DHA. Seven days later, the mammary fat pad tumors were excised; the mice still consuming the 8% LA diet were then allocated sequentially to either continue this diet or commence one of the six postexcision omega-3 fatty acid dietary interventions. Eight weeks later, the mice were necropsied and evaluated for local recurrence and lung metastases. Although there were no differences in the incidence of local recurrence between groups, EPA and DHA both inhibited the development of lung metastases. When the dietary interventions were commenced 7 days before surgery, the severity of lung metastasis was reduced by the two omega-3 fatty acids in a dose-dependent manner; at all three levels, the suppressive effects were statistically significant (P < 0.05). Postexcision EPA treatment produced small, statistically insignificant effects, but lung involvement was reduced significantly by feeding DHA at the 2 and 4% levels (P < 0. 05). Overall, these results suggest that omega-3 fatty acids may have a place as adjuvant nutritional therapy in breast cancer and particularly as part of a neoadjuvant regimen.

The effect of parenteral fish oil on leukocyte membrane fatty acid composition and leukotriene-synthesizing capacity in patients with postoperative trauma.

Abstract: The incorporation of omega-3 and omega-6 fatty acids (FAs) into leukocyte membranes and the leukotriene (LT)B4-, LTB5 -, LTC4-, and LTCs-synthesizing capacity in stimulated leukocytes were measured following parenteral omega-3 FA nutrition in 20 postoperative patients. Total parenteral nutrition (TPN) over 5 days postoperatively was isonitrogenous (0.24 g N x kg-1 x d1) and isoenergetic (92 kJ/22 kcal x kg-1 x d-1), containing 0.15 g fish oil and 0.85 g soybean oil per kg-1 x d-1 (FO) or 1.0 g soybean oil x kg-1 x d-1 (SO). Following 5 days' FO administration, the content of eicosapentaenoic acid (EPA) was increased 2.5-fold, LTB5 1.5-fold, and LTC5 sevenfold. With SO nutrition, EPA and LTB5 generation remained unaltered, whereas LTC5 doubled. The production of LTB4 and LTC4 was not affected in any of the groups. We conclude that a 5-day parenteral fish oil supplementation has an immunomodulatory effect on lipid-mediator generation in human leukocytes in postoperative trauma.

(n-3) Polyunsaturated Fatty Acids Modulate the Expression of Functionally Associated Molecules on Human Monocytes in Vitro

Abstract: Diets rich in (n-3) polyunsaturated fatty acids (PUFA) are associated with suppression of the immune system, but the mechanisms are unclear. Specific immune responses are initiated by antigen-presenting cells. This study examines the in vitro effect of the (n-3) PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the expression of cell surface molecules required for normal antigen-presenting cell function on human blood monocytes. Monocytes were incubated with or without EPA or DHA for 48 h at 37 degrees C. Following incubation, expression of major histocompatibility complex (MHC) class II molecules (HLA-DR, -DP and -DQ) and adhesion molecules [intercellular adhesion molecule-1 (ICAM-1) and leucocyte function associated antigen-1] was quantified by flow cytometry. In the presence of EPA alone there was a significantly lower median intensity of expression of HLA-DR and ICAM-1 relative to incubations without EPA. In contrast, significantly greater median intensities of expression of HLA-DR and -DP were observed following incubation with DHA. In parallel experiments, where monocytes were simultaneously activated by the addition of interferon-gamma to the cultures, median expression intensities of HLA-DR, -DP and ICAM-1 were significantly lower in the presence of either EPA or DHA compared with incubations without the (n-3) PUFA. These findings support previous animal studies that suggest that (n-3) PUFA can influence immune reactivity by modulating antigen-presenting cell function.

Microalgae as a source of fatty acids

Abstract: Microalgae are a very diverse group of organisms that consist of both prokaryotic and eukaryotic forms. Although most microalgae are phototrophic, some species are also capable of heterotrophic growth. Some species of microalgae can be induced to overproduce particular fatty acids through simple manipulations of the physical and chemical properties of the culture medium. As a result of the profound differences in cellular organization and growth modes and the ability to manipulate their fatty acid content, microalgae represent a significant source of unusual and valuable lipids and fatty acids. The utilization of microalgal lipids and fatty acids as food components requires that these organisms be grown at large scale under controlled conditions. Several growth systems have been developed for large scale growth of phototrophic microalgae using either natural sunlight or artificial light, but their lack of control of culturing parameters or their high cost of operation have limited their utility for the production of food products. Instead, large scale cultivation of heterotrophic microalgae using classical fermentation systems provides consistent biomass produced under highly controlled conditions at low cost. Microalgae contain many of the major lipid classes and fatty acids found in other organisms. However, they are also the principal producers in the biosphere of some polyunsaturated fatty acids, especially docosahexaenoic acid (DHA). The high DHA content found in some algae is currently being utilized to supplement infant formula to enable it to more closely resemble human breast milk. Thus, the commercialization of DHA from microalgae demonstrates the value of these organisms as a source of useful fatty acids.