Effects of in vitro hyperthermia on fatty acids of red blood cells and plasma lipids from patients with multiple sclerosis

Heparinized blood from 43 patients with multiple sclerosis (MS) and 43 controls matched for age, sex and race were incubated at 42 degrees C for 24 h. The hematocrit values were determined before and after heating. The plasma and red blood cells (RBC) were separated and the plasma free fatty acids (FFA), total neutral lipids (NL; which included the triglycerides and cholesteryl esters), phospholipids (PL), and RBC lipids from 24 patients and 24 controls were isolated. The total amounts of the various FFA in the plasma and the relative percentage fatty acid compositions of the various FFA, NL, ester-linked fatty acids of plasma PL, RBC lipids as well as those of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) fractions of RBC lipids were determined by gas-liquid chromatography (GLC). The hematocrit values were significantly higher in heated samples from both MS and controls. The results of fatty acid analyses from 24 pairs of heated and unheated MS and controls showed that the concentrations of total FFA and most of the fatty acids increased significantly in the heated plasma of both MS and control samples, compared to the respective unheated plasma samples. When the FFA values were expressed as relative percentage compositions, the results showed significant increases in palmitic, arachidonic and adrenic acids and significant decreases in oleic, linoleic and linolenic acids in the heated samples from MS and controls compared to the corresponding unheated samples. In NL the relative percentages of linoleic and arachidonic acids were significantly higher in the heated samples from both MS and controls, while in the PL, the percentages of linoleic acid were lower in the heated samples from both MS and controls, when compared to the corresponding unheated samples. The fatty acid compositions of the RBC lipids showed highly significant increases in palmitic plus palmitoleic, stearic and oleic acids and significant decreases in linoleic and most of the polyunsaturated acids in the heated MS samples compared to the unheated MS samples. In contrast, the fatty acid compositions of the RBC lipids from heated controls showed significant increase in only palmitic plus palmitoleic acids and significant decreases in linoleic and arachidonic acids, compared to the values from unheated controls. The results show that the RBC membranes from MS were more affected by the heat than those of control RBC, indicating possible differences between blood from MS patients and controls.     

Increased thromboxane A2 generation and altered membrane fatty acid composition in platelets from patients with active angina pectoris

Lipid composition of platelet membranes and thromboxane A2 (TxA2) generation by platelets were investigated in eighty-seven anginal patients (forty-two with resting angina in active phase and forty-five with effort stable angina or rest angina in inactive phase) and in forty-five clinically healthy subjects of similar age. All subjects were on the same dietary regimen and the adherence to diet was checked by analysis of red blood cell lipids. Platelets from active angina patients produced more TxA2 than platelets from both inactive patients and controls (p less than 0.001). Moreover patients with active angina had higher arachidonic acid (AA, p less than 0.001) and lower eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) levels in phosphatidylcholine (PC, p less than 0.001), than inactive patients and controls. AA and EPA changes in membrane PC significantly correlated with TxA2 production (p less than 0.001) but not with coronary pathoanatomy. Plasma lipids, content of cholesterol, total phospholipids (and their saturated and unsaturated fatty acids) and the different phospholipid fractions in platelet membrane were not different in the three groups. Present results indicate that in platelets from anginal patients phospholipid fatty acid composition is at least in part independent of plasma composition and that in active angina there are modifications leading to increased TxA2 formation and possibly contributing to the occurrence of ischemic attacks.     

Lipid composition of cultured human endothelial cells

Primary cultures of endothelial cell monolayers (ECM) obtained from umbilical cord veins were grown in a medium containing fetal calf serum (FCS) and L-glutamine. Endothelial cells (EC) were harvested after fourth or fifth day of seeding. Lipid extracts were separated into neutral lipids and phospholipid fractions by thin layer chromatography (TLC). The fractions were analyzed by gas liquid chromatography (GLC) for fatty acid distribution. Free cholesterol was the major component of neutral lipids but the percentage was lower in EC than in platelets. Cholesterol ester (ChE) and free fatty acids (FFA) were found in equal percentages and higher than that observed in platelets. Triglycerides comprised 2.6 % of the total lipids. Palmitic, stearic and oleic acids were the main fatty acids of EC neutral lipids. Phosphatidyl choline (PC) was the largest (36.3 %) phospholipid fraction. Phosphatidyl ethanolamine (PE), and the combined phosphatidyl serine and phosphatidyl inositol fractions (PS + PI) were present in equal percentages (25.3 and 25.6 %). Each phospholipid fraction had a characteristic fatty acid pattern. Long chain polyunsaturated FA were present in high concentrations in all fractions. Arachidonic acid (AA) ranged from 4.0 – 18.3 % whereas linoleic acid and di-homo-γ-linolenic acid ranged from 1.9 – 7.3 % and 2.3 – 5.5 % respectively, in the various PL-fractions. EC examined immediately after collection from the umbilical cords, had significantly higher concentrations of linoleic and arachidonic acids in the total phospholipids than EC grown in culture medium for 4–5 days.     

Platelets and aging. II--Plasma lipoproteins and fatty acid profiles

Lipid composition of both plasma and platelets were investigated in sixteen old (78-94 years) and eight young (25-35 years) subjects. No age-related change was noted in plasma total and HDL cholesterol whereas a slightly increase of triglycerides was observed in the elderly population. Level of apo AI tended to decrease while apo AII decreased significantly in the elderly. These results led to a higher apo AI/apo AII ratio in elder subjects. However, no difference was detected in the level of apo B. In contrast, several modifications appeared in fatty acid composition of plasma lipids. Primarily, monounsaturated fatty acids content was increased while level of linoleic acid (and arachidonic acid in phospholipids) decreased in each class of plasma lipids of elderly subjects. In platelets from the elderly, we found an enhancement of monounsaturated fatty acids in phosphatidyl-inositol (PI), -ethanolamine (PE) and -choline (PC). The decrease of linoleic acid was detected in PC while the reduction of AA was noted in PE. These results indicate that modifications of fatty acid composition in both plasma and platelet lipids appeared with aging. They might be linked to the enhanced platelet activation in vivo observed in elderly people.     

The alkenylacyl class of ethanolamine phospholipid represents a major form of eicosapentaenoic acid (EPA)-containing phospholipid in the platelets of human subjects consuming a fish oil concentrate

A quantitative assessment was made of the distribution of arachidonic acid (AA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) among the individual sub-classes (diacyl, alkylacyl, alkenylacyl) of the various platelet phospholipids of human subjects consuming a fish oil concentrate (as MaxEPA) enriched in EPA plus DHA. This work was of interest since dietary fish oils provide for a pronounced enrichment of platelet phospholipid in EPA as well as DPA plus DHA to a lesser extent while reducing AA-phospholipid and platelet reactivity. After 42 days of MaxEPA supplementation (providing 3.6 g EPA and 2.4 g DHA per day), the majority of the mass of all four polyunsaturated fatty acids in the choline-containing phospholipid (PC) was found in the diacyl species (76-87% of total PC). In contrast, twice as much of the EPA in the ethanolamine-containing phospholipid (PE) resided in the alkenylacyl species (62.7% of total PE) relative to the diacyl species (32.3%) with minor amounts in the alkylacyl fraction (5.1%). The major single reservoir of total EPA-containing phospholipid was the alkenylacyl PE (38.2% of total) followed by diacyl PC (27.8%), diacyl PE (19.6%), with progressively lesser amounts in the alkylacyl PC, alkylacyl PE, diacyl PS (phosphatidylserine), alkenylacyl PC, and diacyl PI (phosphatidylinositol) at 6.7, 3.1, 2.3, 1.4, and 0.8% of the total mass, respectively. In contrast, only 27.1% of the total mass of AA-phospholipid was represented by the alkenylacyl PE with the bulk of the remainder being distributed in the diacyl species of PE, PC, PI, and PS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dietary fatty acid and antioxidant intake in community-dwelling patients suffering from schizophrenia

INTRODUCTION: Brain phospholipids are uniquely rich in polyunsaturated fatty acids (PUFAs). Most PUFAs such as alpha-linolenic acid 18:3(n-3), eicosapentaenoic acid 20:5(n-3), and docosahexaenoic acid 22:6(n-3) are essential and must be provided through the diet. PUFAs are also very sensitive to oxidative stress. Decreased essential fatty acid content has been observed in cell membranes of various tissue types of schizophrenia patients, including neural cell membranes. A number of mechanisms may account for these deficits, such as inadequate dietary supply or increased oxidation. It is known that patients with schizophrenia make poor dietary choices. However, whether their dietary fatty acid or antioxidant intake is insufficient and contributes to the observed deficiencies has not been assessed. METHODS: After obtaining informed consent, a 24-h diet recall was administered to elicit nutritional information in 146 outpatients with schizophrenia. Intake of fatty acids and antioxidants including vitamins A, C, and E was compared to U.S. population standards according to the National Health and Nutrition Examination Survey Cycle III (NHANES III) results. RESULTS: Saturated and polyunsaturated fatty acid (PUFA) intake was significantly higher in schizophrenia patients than in controls (p相似文献   

Maternal dietary fish oil enriches docosahexaenoate levels in brain subcellular fractions of offspring

Prompted by the speculated essentiality of docosahexaenoic acid (DHA) for neural development, this study was undertaken to investigate the incorporation of (n-3) fatty acids in the maternal diet into various phospholipids of infant rat brain subcellular fractions: microsomes (Ms), synaptosomes (Sy), myelin (My), and mitochondria (Mt). Two groups of infant rats were nourished by dams fed diets containing 20% of either corn oil (CO) or menhaden oil (MO) from 2 until 12 days of age. DHA but not eicosapen taenoic acid (EPA) was distributed to all subcellular fractions of infant rats in the CO group. The levels of DHA were higher in Ms and Mt than Sy and My, and higher in phosphatidylethanolamine (PE) and phosphatidylserine (PS) than phosphadylcholine (PC) and phosphatidylinositol (PI). The MO feeding enriched DHA in PE of all subcellular fractions, PS of all subcellular fractions, except My, PC of Sy, My and Mt, and PI of My. EPA was enriched in phospholipids in all subcellular fractions, except mitochondrial PS of the MO group. In the MO group, the ratios of EPA/ DHA, ranging from 0.01 to 0.85, in all subcellular phospholipids were markedly lower than that found in the mother-s milk (i.e., 1.5), suggesting an ability to elongate and desaturate EPA to DHA and/or disproportional uptake of the fatty acids by the brain. In PE of all subcellular fractions, the increased levels of DHA and EPA, with a concomitant reduction of arachidonic and/or linoleic acid, yielded higher ratios of total (n?3)/(n?6) fatty acids in the MO than the CO group. The inclusion of preformed DHA and EPA in the maternal diet provides an effective means to enrich these fatty acids in developing brains. © 1993 Wiley-Liss, Inc.     

Atherothrombogenic risk modulation by n-3 fatty acids was not associated with changes in homocysteine in subjects with combined hyperlipidaemia

Favourable effects of n-3 fatty acids on the atherogenic risk profile were recently demonstrated in subjects with combined (type IIb) hyperlipidaemia, not responding to a therapeutic diet. Re-examination of a previous patient material was performed to assess the influence of n-3 fatty acids on homocysteine and several coagulation factors. Subjects were randomly allocated to receive either a concentrated compound of 85% eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) (n = 28), or corn oil (n = 29), in a daily dose of 4g for 12 weeks. The intervention was double-blind. Homocysteine remained unchanged in both groups after 12-week treatment. N-3 fatty acids supplementation did not affect the levels of fibrinogen, coagulation factor VII or tissue factor pathway inhibitor (TFPI), while plasminogen activator inhibitor (PAI) increased significantly (Student's t-test; p <0.05). Total blood platelets were significantly reduced in subjects receiving n-3 fatty acids (Student's t-test; p <0.05), whereas bleeding times increased non-significantly.     

Omega-3 fatty acids on the forced-swimming test

OBJECTIVES: Based on the findings of epidemiological data and recent clinical trials, omega-3 fatty acids seem to have a preventive and therapeutic effect on depression. METHOD: We examined the effect of omega-3 fatty acids on the forced-swimming test (FST) in two groups of Sprague-Dawley rats after a six-week treatment with two different diets. Behavioral responses were observed and recorded during the 5-min test. The fatty acid composition from the whole brain tissue and the RBC membrane of the rats were analyzed. RESULTS: Comparing to control diet, omega-3 fatty acid diet significantly decreased the immobility time (218 +/- 16 vs. 183 +/- 19s, p = 0.001) and increased behaviors of swimming (32 +/- 7 vs. 45 +/- 9s, p = 0.012) and climbing (50 +/- 10 vs. 73 +/- 14s, p = 0.011) during the FST. The group in omega-3 fatty acid diet had higher levels of docosahexaenoic acid (DHA, 50% increase) and alpha-linolenic acid (ALA, 63% increase) in the brain, and of eicosapentaenoic acid (EPA, 27% increase) in the peripheral RBC membrane. The level of brain DHA is negatively correlated to the immobility time (r = -0.654, p = 0.006) and is positively correlated to the swimming time (r = 0.69, p = 0.003). CONCLUSION: The result shows that omega-3 fatty acids have a beneficial effect on preventing the development of depression-like behaviors in rats with the FST.     

Sialic acid and fatty acid concentrations in lymphocytes, red blood cells and plasma from patients with multiple sclerosis

Lipids and constituents of lipids were isolated from peripheral blood lymphocytes (PBL), red blood cells (RBC), plasma and sera from 51 patients with multiple sclerosis (MS) and 51 controls, matched for age, sex and race. The amount of sialic acid released by incubation of intact PBL from MS patients was significantly lower (P less than 0.02) than that of the sialic acid from control lymphocytes. The amounts of sialic acid released by neuraminidase from intact RBC, on the other hand, did not differ significantly between the MS group and the control group. The concentrations of ganglioside sialic acid in PBL from MS and control groups did not vary significantly. Similarly the concentration of ganglioside sialic acid in RBC from MS patients was not significantly different from that in the controls. Analyses of the fatty acids isolated after alkaline methanolysis of the lipids from the PBL of MS patients and controls showed a small but significant decrease (P less than 0.01) in the relative percentage of linoleic acid in patients with MS. Determination of the ester-linked fatty acids in RBC lipids from patients with MS showed a significant decrease (P less than 0.001) in the relative percentage of linoleic acid and an increase (P less than 0.01) in palmitic plus palmitoleic acids compared to control values. The fatty acid composition of the plasma neutral lipids plus free fatty acids showed a very significant decrease (P much less than 0.001) in the relative percentage of linoleic acid, a small decrease (P less than 0.05) in arachidonic acid and significant increases in palmitic (P less than 0.001) and oleic acids (P less than 0.001) in MS, compared to controls. These results are suggestive of possible differences in metabolism of lipids between patients with MS and controls.     

Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder.

BACKGROUND: Epidemiological surveys and peripheral tissue (red blood cells/plasma) fatty acid composition studies suggest that omega-3 fatty acid deficiency is associated with major depressive disorder (MDD) and suicide. It was hypothesized that patients with MDD would exhibit lower frontal cortical concentrations of docosahexaenoic acid (DHA), the principal omega-3 fatty acid in brain, relative to normal controls. METHODS: We determined the total fatty acid composition of postmortem orbitofrontal cortex (Brodmann's Area 10) from patients with DSM-IV-defined MDD (n = 15) and age-matched normal controls (n = 27) by gas chromatography. RESULTS: After correction for multiple comparisons, the omega-3 fatty acid DHA was the only fatty acid that was significantly different (-22%) in the postmortem orbitofrontal cortex of MDD patients relative to normal controls. Deficits in DHA concentrations were greater in female MDD patients (-32%) than in male MDD patients (-16%), and could not be wholly attributed to lifestyle factors or postmortem tissue variables. CONCLUSIONS: These results demonstrate a selective deficit in the omega-3 fatty acid DHA in the orbitofrontal cortex of patients with MDD. This finding adds to a growing body of evidence implicating omega-3 fatty acid deficiency as well as the orbitofrontal cortex in the pathophysiology and potentially pathogenesis of MDD.     

Influence of highly concentrated n-3 fatty acids on serum lipids and hemostatic variables in survivors of myocardial infarction receiving either oral anticoagulants or matching placebo

Forty patients with previous myocardial infarction were given 4 capsules with 1 g concentrated fish oil preparation daily for 4 weeks. No special diet was applied. The supplementation was equivalent to 3.4 grams of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) daily. Twenty-two of the 40 subjects received concomitant treatment with long-term oral anticoagulants (OAC). The fatty acid composition of serum after the supplementation period showed a significant increase in the proportion of EPA and DHA, while arachidonic acid (AA) remained essentially constant. This resulted in a rise of the EPA/AA ratio from 0.59 to 1.49 (p less than 0.001), confirming satisfying absorption of the concentrate. Blood lipids showed an overall decrease of triglycerides (TG) by 25% (p = 0.02), while total cholesterol rose by 5% (p = 0.03) and HDL-cholesterol was unaffected. Blood glucose and the TG associated factors plasminogen activator inhibitor and factor VII-phospholipid complex revealed trends towards reduction. Ivy bleeding time showed a significant prolongation, the median increasing from 240 to 270 seconds. A significant increase of fibrinogen was seen, as was a decrease of clotting time in the combined prothrombin test in patients receiving concomitant OAC. Thus, given for 4 weeks, the investigated concentrate of n-3 fatty acids exerts not merely beneficial effects as far as the risk profile for atherosclerotic disease is concerned. The results also point towards interactions with OAC that may be of clinical relevance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of high doses of essential fatty acids on the postviral fatigue syndrome

Sixty-three adults with the diagnosis of the postviral fatigue syndrome were enrolled in a double-blind, placebo-controlled study of essential fatty acid therapy. The patients had been ill for from one to three years after an apparently viral infection, suffering from severe fatigue, myalgia and a variety of psychiatric symptoms. The preparation given contained linoleic, gamma-linolenic, eicosapentaenoic and docosahexaenoic acids and either it, or the placebo, was given as 8 x 500 mg capsules per day over a 3-month period. The trial was parallel in design and patients were evaluated at entry, one month and three months. In consultation with the patient the doctors assessed overall condition, fatigue, myalgia, dizziness, poor concentration and depression on a 3-point scale. The essential fatty acid composition of their red cell membrane phospholipids was analysed at the first and last visits. At 1 month, 74% of patients on active treatment and 23% of those on placebo assessed themselves as improved over the baseline, with the improvement being much greater in the former. At 3 months the corresponding figures were 85% and 17% (p less than 0.0001) since the placebo group had reverted towards the baseline state while those in the active group showed continued improvement. The essential fatty acid levels were abnormal at the baseline and corrected by active treatment. There were no adverse events. We conclude that essential fatty acids provide a rational, safe and effective treatment for patients with the post-viral fatigue syndrome.     

Omega-3 fatty acids and risk of cognitive impairment and dementia

It has been suggested that the dietary intake of omega-3 polyunsaturated fatty acids could be inversely related to the risk of dementia and cognitive decline. This analysis examined the association between plasma concentration of omega-3 polyunsaturated fatty acids and prevalence and incidence of cognitive impairment and dementia. Data are reported on subjects 65 years or older who had a complete clinical evaluation at the first two waves (1991-1992 and 1996-1997) of the Canadian Study of Health and Aging. Main outcome measures were cognitive impairment and dementia by mean relative plasma concentrations of fatty acids in the phospholipid fraction at baseline. Results were adjusted for age, sex, education, smoking, alcohol intake, body mass index, history of cardiovascular disease, and apolipoprotein E e4 genotype. In the cross-sectional analysis, no significant difference in omega-3 polyunsaturated fatty acid concentrations was observed between controls and both prevalent cases of cognitive impairment and dementia. In the prospective analysis, a higher eicosapentaenoic acid (p < 0.01) concentration was found in cognitively impaired cases compared to controls while higher docosahexaenoic acid (p < 0.07), omega-3 (p < 0.04) and total polyunsaturated fatty acid (p < 0.03) concentrations were found in dementia cases. These findings do not support the hypothesis that omega-3 polyunsaturated fatty acids play a protective role in cognitive function and dementia.     

Linoleic acid levels in white blood cells, platelets, and serum of multiple sclerosis patients

We found a small but statistically significant reduction in the linoleic acid concentration of white blood cells and platelets in MS patients. The percent linoleic acid concentration (mean +/- S.D.) in the white blood cells if 24 MS patients was 8.8 +/- 1.8% as compared with 11.4 +/- 4.9 in 24 age and sex-matched controls (p less than 0.05). Platelet levels were 8.5 +/- 2.4% and 10.6 +/- 3.8% respectively (P less than 0.05). Serum linoleic acid levels were not significantly different in the two groups. The possible role of linoleic acid in the pathogenesis of MS has yet to be defined.     

Decreased erythrocyte and platelet phospholipids and fatty acids in juvenile neuronal ceroid-lipofuscinosis (Batten disease)

Total cellular and phospholipid fatty acids were analyzed in erythrocytes and platelets from six patients with juvenile neuronal ceroid-lipofuscinosis (Spielmeyer-Vogt, Batten disease, JNCL). The results were compared to those of age-matched controls. The amounts of total fatty acid and the phospholipid classes, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) were significantly decreased in patients when related to cellular protein. The reductions in total fatty acids were 27% in erythrocytes and 50% in platelets. Erythrocyte PC reduction was 36%, PE was 44% and PS 27%. There were no major qualitative differences in the phospholipid fatty acids, suggesting that the fatty acid composition of the reduced phospholipid was normal, and that there is a generalized phospholipid deficiency in these cells in JNCL. This was not related to nutritional status. The pathogenesis of Batten disease may be related to abnormal membrane function resulting from this marked phospholipid deficiency.     

Abnormal fatty acid pattern in the superior temporal gyrus distinguishes bipolar disorder from major depression and schizophrenia and resembles multiple sclerosis

This study investigated the fatty acid composition of the postmortem superior temporal gyrus (STG), a cortical region implicated in emotional processing, from normal controls (n=15) and patients with bipolar disorder (BD, n=15), major depressive disorder (MDD, n=15), and schizophrenia (SZ, n=15). For comparative purposes, STG fatty acid composition was determined in a separate cohort of multiple sclerosis patients (MS, n=15) and normal controls (n=15). Compared with controls, patients with BD, but not MDD or SZ, exhibited abnormal elevations in the saturated fatty acids (SFA) palmitic acid (16:0), stearic acid (18:0), the polyunsaturated fatty acids (PUFA) linoleic acid (18:2n-6), arachidonic acid (20:4n-6), and docosahexaenoic acid (22:6n-3), and reductions in the monounsaturated fatty acid (MUFA) oleic acid (18:1n-9). The total MUFA/SFA and 18:1/18:0 ratios were lower in the STG of BD patients and were inversely correlated with total PUFA composition. MS patients exhibited a pattern of fatty acid abnormalities similar to that observed in BD patients including elevated PUFA and a lower 18:1/18:0 ratio. Collectively, these data demonstrate that BD patients exhibit a pattern of fatty acid abnormalities in the STG that is not observed in MDD and SZ patients and closely resembles MS patients.     

Essential and other fatty acids in plasma in schizophrenics and normal individuals from Japan

Plasma phospholipid and cholesterol ester fatty acid levels were measured in samples from normal individuals, schizophrenics, and patients with affective and paranoid disorders in Japan. The schizophrenics were divided into groups with normal and reduced platelet sensitivity to the aggregation-inhibiting effects of prostaglandin (PG) E1. As in samples from schizophrenics in several other countries, linoleic acid levels were significantly below normal, as was the ratio of linoleic acid to its metabolites. Phospholipid fatty acid levels were normal in patients with paranoid or affective disorders. When the schizophrenics were divided into those with and without an abnormal response to PGE1, oleic acid was higher and eicosapentaenoic acid lower in those patients with an abnormal response. This study lends further support to the idea that schizophrenics may differ from controls in their essential fatty acid and eicosanoid metabolism.     

Supplementation with a combination of omega-3 fatty acids and antioxidants (vitamins E and C) improves the outcome of schizophrenia

Reduced levels of membrane essential polyunsaturated fatty acids (EPUFAs), namely, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acids (DHAs), and their association with psychopathology have been consistently reported in both chronic-medicated schizophrenic patients as well as in never-medicated patients soon after the first episode of psychosis. Past supplementation studies with either omega-6 or omega-3 or both EPUFAs generally in chronic-medicated-older patients have reported varying degrees of therapeutic effects, and have suggested that supplementation with primarily omega-3 EPUFAs (EPA>DHA) may be preferable. We report the supplementation with a mixture of EPA/DHA (180:120 mg) and antioxidants (vitamin E/C, 400 IU:500 mg) orally morning and evening to schizophrenic patients (N=33) for 4 months. The red blood cell (RBC) membrane fatty acid levels, plasma lipid peroxides and clinical measures were carried out by established procedures at pretreatment, posttreatment and after 4 months of postsupplementation period to determine the stability of treatment effects within patients. Levels of fatty acids and lipid peroxides were compared with their levels in normal controls (NC) (N=45).Posttreatment levels of RBC EPUFAs were significantly higher than pretreatment levels as well as levels in normal controls without any significant increase in plasma peroxides. Concomitantly, there was significant reduction in psychopathology based on reduction in individual total scores for brief psychiatric rating scale (BPRS) and positive and negative syndrome scale (PANSS), general psychopathology-PANSS and increase in Henrich's Quality of Life (QOL) Scale. The EPUFA levels returned to pretreatment levels after 4 months of supplementation washout. However, the clinical improvement was significantly retained. Future studies need be done in placebo-controlled trials and also with a comparison group supplemented with fatty acids alone in a larger number of patients, both chronic as well as never medicated, and for a longer duration of treatment while the dietary intake is monitored. This may establish the EPUFA supplementation a very effective treatment to improve the outcome for an extended period of time.     

Influence of a concentrated ethylester compound of n-3 fatty acids on lipids, platelets and coagulation in patients undergoing coronary bypass surgery.

Twenty patients accepted for coronary bypass surgery were randomized to receive either a concentrated ethylester compound of n-3 fatty acids, with a daily dose of 3.15 g of eicosapentaenoic acid (EPA) and 1.89 g of docosahexaenoic acid (DHA), or corn oil (controls) in a double blind study, to evaluate the effect on lipids, platelets and coagulation during the pre- and postoperative phase. Only patients with fasting triglyceride (TG) levels greater than or equal to 1.6 mmol/l at recruitment were eligible. The study was continued for 5 to 6 months. Surgery was usually performed at mid-intervention. Blood samples were collected during morning hours in fasting subjects, just prior to intervention, preoperatively and at final postoperative follow-up. Moreover, blood loss was accurately accounted for postoperatively. A threefold increase (p = 0.0001) of EPA was noted at pre- and postoperative follow-up. TG-levels were reduced 20 and 39%, respectively, in patients on n-3 fatty acids, reaching statistical significance at end of intervention (p = 0.034). TG-levels in controls remained largely unchanged. In patients on n-3 fatty acids, there was a statistically significant increase in serum total cholesterol preoperatively, but this change was no longer present at completion of the study. No significant changes were noted in platelet function, as judged by bleeding time, collagen induced platelet aggregation and release of TxB2 during aggregation. Parameters of extrinsic coagulation, including phospholipase C-sensitive factor VII (PLC-VII) and extrinsic pathway inhibitor (EPI), also remained essentially unchanged in both groups of patients. However, fibrinogen was significantly reduced in controls (p less than 0.05) at end of intervention.(ABSTRACT TRUNCATED AT 250 WORDS)