MATERIAL FOR MS-DIET KB FATTY ACIDS - 70's Title Polyunsaturated fatty acids in treatment of acute remitting multiple sclerosis. Author Bates D; Fawcett PR; Shaw DA; Weightman D Source Br Med J, 2: 6149, 1978 Nov 18, 1390-1 Abstract One hundred and sixteen patients with acute remitting multiple sclerosis (MS) took part in a double-blind controlled trial of treatment with polyunsaturated fatty acids and were randomly allocated to one of four groups. Two groups received linoleic acid, one alone as a spread and one with gamma-linolenic acid in capsules (Naudicelle); and two control groups received oleic acid, one as a spread and one in capsules. Rates of clinical deterioration and frequencies of attacks were not significantly different between treated and control groups. Exacerbations were shorter and less severe in patients receiving a high dose of linoleic acid than in controls, but those receiving a lower dose--that is, Naudicelle--showed no such difference. Thus supplementing the diet with 20 g linoleic acid marginally affected the duration and severity of relapses of MS but had no effect on overall disability. The dose of Naudicelle used provided insufficient supplementation. Language of Publication English Unique Identifier 79063229 Title Inhibitory effect of unsaturated fatty acids on lymphocyte-antigen interaction with special reference to multiple sclerosis. Author Field EJ; Shenton BK Source Acta Neurol Scand, 52: 2, 1975 Aug, 121-36 Abstract Using the macrophage electrophoretic mobility (MEM) test, the in vitro effects of oleic, linoleic and arachidonic acid, as well as Naudicell oil and methyl gamma-linolenate, on lymphocyte response to various antigens (PPD, thyroid antigen and EF) were studied in patients with mutiple sclerosis, patients with other neurological diseases, and in normal subjects. In all three groups, linoleic and arachidonic acid showed a significant inhibition; the latter was greater than the former, when tested at physiological concentrations, suggesting that unsaturated fatty acids may exert an immunoregulatory effect in vivo. The methylester of gamma-linolenate is the most powerful suppressing agent yet tested. The inhibitory activity of linoleic and arachidonic acids was consistently greater in MS than in other subjects and forms the basis of an in vitro test for the disease. The possible relationship of these findings to widespread alterations in the fatty acid composition of the tissues and to the pathogenesis of MS is discussed. Language of Publication English Unique Identifier 75221599 ) - 80's (Title ( A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis. ) Author Bates D; Cartlidge NE; French JM; Jackson MJ; Nightingale S; Shaw DA; Smith S; Woo E; Hawkins SA; Millar JH; et al Address Department of Neurology, University of Newcastle upon Tyne, UK. Source J Neurol Neurosurg Psychiatry, 52: 1, 1989 Jan, 18-22 Abstract A trial of n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis has been conducted over a 5 year period. Ambulant patients (312) with acute remitting disease were randomly allocated to treatment or placebo. Both groups were given dietary advice to increase the intake of n-6 polyunsaturated fatty acids and the treatment group in addition received capsules containing n-3 polyunsaturated fatty acids. Analysis of clinical outcome at the end of 2 years of treatment was made in terms of the duration, frequency and severity of relapses and the number of patients who had improved or remained unchanged. The results showed no significant difference at the usual 95% confidence limits but there was a trend in favour of the group treated with n-3 polyunsaturated fatty acids in all parameters examined. Language of Publication English Unique Identifier 89215866 ) (Title Biological effects of fish oils in relation to chronic diseases. Author Carroll KK Source Lipids, 21: 12, 1986 Dec, 731-2 Abstract The low incidence of cardiovascular disease in Greenland Eskimos appears to be due to their high intake of seal, whale and fish. The lipids of these marine animals lower serum triglyceride and cholesterol levels and help to prevent blood clotting. The latter effect has been related to a change in the balance of prostacyclin and thromboxane as a result of replacing n-6 polyunsaturated fatty acids in the body by n-3 polyunsaturated fatty acids present in marine lipids. Dietary fish oils have also been shown to inhibit development of mammary, pancreatic, intestinal and prostatic tumors in experimental animals. This effect may likewise be due to changes in the production of prostaglandins or related compounds. The involvement of prostaglandins and leukotrienes in immune responses has led to studies on the effects of fish oil on various chronic diseases associated with abnormalities of the immune system. Some of these diseases, such as multiple sclerosis and psoriasis, are also relatively uncommon in Eskimos. Preliminary results of these studies are encouraging, but more work is required to assess the usefulness of dietary fish oils in treatment of these diseases. In addition to their apparent therapeutic value, n-3 fatty acids are considered essential dietary components since they cannot be synthesized in the body and appear necessary for normal vision and probably other body functions. Language of Publication English Unique Identifier 87143517 ) Title: Alteration of lipid-phase behavior in multiple sclerosis myelin revealed by wide-angle x-ray diffraction. Author: Chia LS; Thompson JE; Moscarello MA Source: Proc Natl Acad Sci U S A, 81: 6, 1984 Mar, 1871-4 Abstract Wide-angle x-ray diffraction studies revealed that the lipid-phase transition temperature of multiple sclerosis (MS) myelin was about 20 degrees C lower than that of normal myelin, indicating differences in the physical organization of the bilayer. The transition temperature of liposomes prepared from total lipid extracts of normal myelin was 12 degrees C lower than that for corresponding intact myelin, demonstrating that the protein of normal myelin had a substantial ordering effect on the lipid bilayer. The transition temperature for liposomes of MS myelin lipid was essentially similar to that for isolated MS myelin. Because the protein/phospholipid ratio was higher in MS myelin, and no difference in degree of fatty acid saturation was observed, the inability of MS myelin protein to organize the lipid reflects a qualitative difference in the proteins. Language of Publication: English Unique Identifier: 84170405 Title Essential fatty acid and lipid profiles in plasma and erythrocytes in patients with multiple sclerosis. Author Cunnane SC; Ho SY; Dore-Duffy P; Ells KR; Horrobin DF Source Am J Clin Nutr, 50: 4, 1989 Oct, 801-6 Abstract This study was conducted to investigate the possible differences in erythrocyte lipid composition, which might account for the previously reported increase in erythrocyte membrane zinc levels in patients with multiple sclerosis (MS). Compared with healthy control subjects, plasma lipids in patients with MS contained less sphingomyelin but more phosphatidylserine and the cholesterol-phospholipid ratio was 42% higher in the plasma from MS patients (p less than 0.01). In erythrocytes from MS patients, phosphatidylinositol was lower and erythrocyte cholesterol per milligram protein was significantly lower than concentrations in healthy control subjects (p less than 0.01). Among the long-chain fatty acids, the omega-3 fatty acids were lower in plasma from MS patients and linoleic acid was lower in erythrocyte ghosts from MS patients (p less than 0.01). We conclude that altered levels of cholesterol in plasma and erythrocytes from MS patients may contribute to increased erythrocyte-membrane Zn in MS patients. It cannot be stated with certainty whether the altered fatty acid profiles in MS patients were a function of the disease or of altered fatty acid intake. Language of Publication English Unique Identifier 90023309 Title Linoleic acid levels in white blood cells, platelets, and serum of multiple sclerosis patients. Author Fisher M; Johnson MH; Natale AM; Levine PH Source Acta Neurol Scand, 76: 4, 1987 Oct, 241-5 Abstract 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. Language of Publication English Unique Identifier 88073124 Title Use of plasma for immediate diagnosis of multiple sclerosis (plasma-erythrocyte unsaturated fatty acid test): comparison with the erythrocyte-unsaturated fatty acid (E-UFA) test. Author Field EJ; Joyce G Source Neurol Res, 8: 1, 1986 Mar, 57-60 Abstract A labile factor in plasma (but not serum) of MS subjects confers MS like properties vis à vis effect of linoleic acid (LA) and arachidonic acid (AA), on the electrophoretic mobility of washed red blood cells (RBC) irrespective of their provenance. Plasma from anomalous MS relatives and other neurological diseases (OND) likewise confer corresponding properties on washed RBC. The magnitude of results produced by LA and AA on plasma coated cells is equal to that produced by LA and AA directly on the original cells and approximately twice that reported with latex particles. Language of Publication English Unique Identifier 86203944 Title The effect of nutritional counselling on diet and plasma EFA status in multiple sclerosis patients over 3 years. Author Fitzgerald G; Harbige LS; Forti A; Crawford MA Address ARMS Research Unit, Central Middlesex Hospital, Acton, London, UK. Source Hum Nutr Appl Nutr, 41: 5, 1987 Oct, 297-310 Abstract The dietary intake of 83 people with multiple sclerosis (MS) was assessed by the 7-day weighed intake method prior to dietary advice and at 6-monthly intervals thereafter up to 36 months. The P:S ratio of the diet increased from an initial value of 0.8 to 1.5 after 6 months and 1.34 at 36 months. Biochemical investigation of plasma essential fatty acid (EFA) status specifically linoleic, eicosapentanoic and docosahexanoic acids showed significant correlations with diet. Concurrent 6-monthly neurological and physiotherapy assessments were also carried out, the neurological results are discussed in relation to a nutrient scoring system. Language of Publication English Unique Identifier 88086125 Title Effects of dietary linoleic acid and gamma linolenic acid on platelets of patients with multiple sclerosis. Author Mcgregor L; Smith AD; Sidey M; Belin J; Zilkha KJ; McGregor JL Address Inserm Unit 63, Alexis Carrel Medical School, Lyon, France. Source Acta Neurol Scand, 80: 1, 1989 Jul, 23-7 Abstract The effects of dietary evening primrose oil (rich in linoleic acid and gamma-linolenic acid) were studied on platelets of multiple sclerosis (MS) patients and controls. It was found that platelet aggregation (ADP, thrombin and collagen), platelet fibrinogen binding and platelet glycoprotein (sialic acid and N-acetyl glucosamine) content were not significantly modified by evening primrose oil in MS patients and controls. Moreover, platelet fibrinogen binding and platelet glycoprotein (sialic acid and N-acetyl glucosamine) content were determined for the first time in MS patients and found similar to controls. Platelets of MS patients aggregated more to thrombin and collagen compared to controls, but the difference was only significant with thrombin aggregation after the oil treatment. This study does not show a significant effect of evening primrose oil on platelets of MS patients. Language of Publication English Unique Identifier 89389825 Title Plasma lipids and their fatty acid composition in multiple sclerosis. Author Navarro X; Segura R Source Acta Neurol Scand, 78: 2, 1988 Aug, 152-7 Abstract We report an extensive study of the plasma lipid profile and fatty acid composition in 61 multiple sclerosis (MS) patients compared with 61 normal subjects. The main abnormality in the MS was a reduction in the proportion of linoleic and arachidonic acids mostly evident in the HDL and in the cholesteryl esters fraction, with a compensatory increase in saturated acids. The fatty acid abnormalities correlated with the duration of the disease and the degree of disability. Thus, in the MS patients studied there was a deficiency in essential fatty acids, although this metabolic abnormality does not seem specific to MS. Language of Publication English Unique Identifier 89021877 Title Red blood cell fatty acids in multiple sclerosis. Author Navarro X; Segura R Address Department of Physiology, Autonomous University of Barcelona, Spain. Source Acta Neurol Scand, 79: 1, 1989 Jan, 32-7 Abstract The fatty acid (FA) composition of each phospholipid constituent of the red blood cells (RBC) was analyzed, by thin-layer and gas chromatography techniques, in 61 multiple sclerosis (MS) patients and 61 normal subjects, in whom the plasma lipid FA composition had previously been studied. The MS patients showed a significant decrease in the proportions of linoleic and arachidonic acids in most phospholipids, with a compensatory increase of saturated FA. Correlations between FA percentages in plasma and cell lipids demonstrated abnormalities in the MS patients, suggestive of a disturbance in the exchange between these compartments. The alterations reported in plasma and RBC in the MS patients are consistent with a relative deficiency of essential FA. Language of Publication English Unique Identifier 89189616 Title [Metabolic aspects of multiple sclerosis] Original Title Stoffwechselaspekte der Multiplen Sklerose. Author Neu IS Source Wien Med Wochenschr, 135: 1-2, 1985 Jan 31, 20-2 Abstract According to the present opinion multiple sclerosis (MS) is caused by a concurreance of various factors. This predisposing factor seem to be related to a disturbance of the lipid- and fatty acid metabolism, characterized by decreased concentrations of polyunsaturated fatty acids (PUFA) and essential fatty acids (EFA) in the plasma, the blood cells, the cerebrospinal fluid (CSF) and white matter of the brain in patients with MS. A disturbed absorption of EFA could be excluded. Now the question arises whether there is a disturbed utilisation of EFA with the consequence of biochemical changes in myelin and blood cells. According to lipid-chemical and lipolytic enzymological studies a disturbance of the fatty acid elongation system as well as primary increased activation of the phospholipase A1 is conceivable. According to the demonstrated results the conception of a metabolic immunological caused generalised defect of the biological membranes - especially those of the myelin sheath and platelets - as predisposing factor for the increased platelet aggregation is possible. Even though these ideas do not yet allow a concrete pathogenetic conclusion, the prostaglandins (PG) might be of importance because their precursors are fatty acids and influence the immune mechanisms. Possibly, new approaches follow from the synopsis of present working hypotheses for an extended biochemical-immunological model of multiple sclerosis. Further immunological and laboratory methods should concentrate on differentiating MS from other diseases of the central nervous system and on diagnosing the disease in its early stage. The results of this work are fully discussed in other publications. Separate prints can be requested from the author. Language of Publication German Unique Identifier 85144323 Title. Essential fatty acids in perspective. Author: Sinclair HM Source: Hum Nutr Clin Nutr, 38: 4, 1984 Jul, 245-60 Abstract There are two families of essential fatty acids, the linoleic and linolenic. Linoleic acid (C18:2n-6), found mainly in vegetable seed oils, is desaturated and elongated in the body, forming arachidonic acid (C20:4n-6). Linolenic acid (C18:3n-3), the main dietary source of which is leaves, is desaturated and elongated, forming two fatty acids that are prevalent in fish oils: timnodonic (C20:5n-3) and clupanodonic (C22:6n-3). EFA are very easily peroxidized in air, but vitamin E protects against this. There are three functions of EFA. - The most important is as part of phospholipids in all animal cellular membranes: in deficiency of EFA faulty membranes are formed. - A second is in the transport and oxidation of cholesterol: EFA tend to lower plasma cholesterol. - A third function is as precursors of prostanoids which are only formed from EFA. Deficiency of EFA in experimental animals causes lesions mainly attributable to faulty cellular membranes: sudden failure of growth, lesions of skin and kidney and connective tissue, erythrocyte fragility, impaired fertility, uncoupling of oxidation and phosphorylation. In man pure deficiency of EFA has been studied particularly in persons fed intravenously. A relative deficiency (that is, a low ratio in the body of EFA to long-chain saturated fatty acids and isomers of EFA) is common on Western diets and plays an important part in the causation of atherosclerosis, coronary thrombosis, multiple sclerosis, the triopathy of diabetes mellitus, hypertension and certain forms of malignant disease. Various factors affect the dietary requirement of EFA. Language of Publication English Unique Identifier 84288797 Title Multiple sclerosis: the lipid relationship. Author Swank RL; Grimsgaard A Address Department of Neurology, Oregon Health Sciences University, Portland 97201. Source Am J Clin Nutr, 48: 6, 1988 Dec, 1387-93 Abstract Between 1949 and 1984, 150 multiple sclerosis patients consumed low-fat diets. Fats, oils, and protein intakes; disability; and deaths were determined. On daily fat consumption of less than 20.1 g (average 17 g), 31% died and deterioration was slight. Daily intakes of greater than 20 g (average of either 25 or 41 g) were attended by serious disability and deaths of 79% and 81%, respectively. Oil intakes bore an indirect relationship to fat consumption. Treatment early and before severe disability developed improved prognosis, and females tended to do better than males. High sensitivity to fats suggests they are involved in the genesis of multiple sclerosis. Language of Publication English Unique Identifier 89074619 -90's Title Dietary lipids and multiple sclerosis. Author Bates D Address Department of Neurology, University of Newcastle upon Tyne, UK. Source Ups J Med Sci Suppl, 48:1990, 173-87 Abstract The epidemiological and biochemical evidence supporting a role of dietary lipids in Multiple Sclerosis is reviewed. The published controlled trials of omega six Polyunsaturated Fatty Acids including 172 patients with Acute Remitting multiple Sclerosis are discussed and the results of recent study with omega three Polyunsaturated Fatty Acids in a Double Blind controlled study involving 312 patients are presented. It appears that there is a trend suggesting that the addition of omega six and omega three Polyunsaturated Fatty Acids to the diet of patients with Multiple Sclerosis results in a reduction of the severity and frequency of relapses and in a mild overall benefit in a two year period. Language of Publication English Unique Identifier 91173535 Title Health implications of fatty acids. Author Borlak JT; Welch VA Address Department of Biochemistry and Physiology, School of Animal and Microbial Sciences, University of Reading, England. Source Arzneimittelforschung, 44: 8, 1994 Aug, 976-81 Abstract 1. Although dietary trans fatty acids can effect the fatty acid composition of tissues, they are not considered to be harmful, provided sufficient essential fatty acids are present in the diet. 2. A reduction in dietary saturated fatty acids (SFA) and dietary increases in mono- and polyunsaturated (PUFA) fatty acids are beneficial in reducing the risk of coronary heart disease. 3. There is only limited evidence of a beneficial effect on hypertension by reducing either total fat or SFA in the diet. 4. There is a little evidence of a role for dietary fat in the initiation of cancer but linoleic acid has been implicated in tumor promotion and chemical carcinogenesis. 5. Dietary PUFA might be beneficial in the treatment of certain autoimmune diseases such a multiple sclerosis. Language of Publication English Unique Identifier 95032296 Title Effects of in vitro hyperthermia on fatty acids of red blood cells and plasma lipids from patients with multiple sclerosis. Author Cherayil GD Address Department of Pathology, Medical College of Wisconsin, Milwaukee 53226. Source J Neurol Sci, 95: 2, 1990 Feb, 141-51 Abstract 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. Language of Publication English Unique Identifier 90218163 Title Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. Author Gallai V; Sarchielli P; Trequattrini A; Franceschini M; Floridi A; Firenze C; Alberti A; Di Benedetto D; Stragliotto E Address Neurological Clinic, University of Perugia, Italy. Source J Neuroimmunol, 56: 2, 1995 Feb, 143-53 Abstract To demonstrate the influence of n-3 PUFA supplementation on cytokine and eicosanoid production in peripheral blood mononuclear cells (PBMCs) of MS patients (MSP), we investigated the impact of a 6-month dietary supplementation with these fatty acids on the levels of interleukin-1 beta (IL-1 beta), IL-2, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the supernatants of stimulated PBMCs and serum soluble IL-2 receptors in a group of 20 relapsing-remitting (R-R) MSP and a group of 15 age-matched control individuals (CI). The production of PGE2 and LTB4 in the stimulated PBMCs was also assessed in patient and control groups supplemented with n-3 PUFAs. In both groups, n-3 PUFA supplementation led to a significant decrease in the levels of IL-1 beta and TNF-alpha, and this reduction was more pronounced in the 3rd and 6th month of supplementation. An analogous decrease was observed in the levels of IL-2 and IFN-gamma produced by stimulated PBMCs, and in the levels of serum soluble IL-2 receptors. n-3 PUFA supplementation also appeared to significantly affect prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production in PBMCs, both in MSP and the control group. The reduced production of these proinflammatory eicosanoids, and the decrease of some cytokines with an immunohenancing effect as a consequence of n-3 PUFA supplementation, could modulate some immune functions which have been demonstrated to be altered in MSP. Language of Publication English Unique Identifier 95164652 Title Lipids and neurological diseases. Author Marshall BH Source Med Hypotheses, 34: 3, 1991 Mar, 272-4 Abstract Neurological diseases, such as multiple sclerosis (MS), Sjögren-Larsson syndrome, Reye's syndrome, and Refsum's syndrome (herediopathica atactica polyneuroformis), and many others afflict millions of persons yearly and have no successful treatment available. A common aspect of these diseases appears to be a lipid imbalance involving the essential fatty acids (EFA), linoleic and linolenic, and trace fatty acids which result from faulty lipid metabolism. It is proposed that treatments for these diseases should be sought through diet and metabolic enzymes rather than drugs. Language of Publication English Unique Identifier 91287595 Title Linoleic-acid-dependent slowing of erythrocyte sedimentation in multiple sclerosis. Author Mayer M Address Department of Neurology, Medical Faculty of the Palacký University, Olomouc, Czechoslovakia. Source Prostaglandins Leukot Essent Fatty Acids, 44: 4, 1991 Dec, 257-8 Abstract The influence of linoleic acid upon the sedimentation of washed erythrocytes from multiple sclerosis patients and controls was investigated in the present study. Linoleic acid, especially in the concentration of 250 microM and 500 microM, caused slowing of erythrocyte sedimentation and this effect was significantly greater in multiple sclerosis than in controls. These findings with all probability reflect an unsaturated fatty acid-dependent membrane alteration in multiple sclerosis and are analogues to results obtained earlier by several authors by using cytopherometric measurements. Language of Publication English Unique Identifier 92270623 x Title Red blood cell and adipose tissue fatty acids in mild inactive multiple sclerosis. Author Nightingale S; Woo E; Smith AD; French JM; Gale MM; Sinclair HM; Bates D; Shaw DA Address Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne. Source Acta Neurol Scand, 82: 1, 1990 Jul, 43-50 Abstract The fatty acid profiles of phosphatidyl ethanolamine (PE) and phosphatidyl choline (PC) of the red blood cells of 30 patients with mild inactive multiple sclerosis (MS) and 30 healthy controls were studied by gas chromatography. The groups were well matched for factors likely to influence tissue lipid levels, including diet. The MS patients showed a significant reduction in PE eicosapentaenoic acid (p = 0.009) especially in women, and an increase in both PE dihomo-gamma-linolenic acid (p = 0.004) and PC stearic acid (p = 0.04). No reduction in linoleic acid was observed in either the PC or PE fractions of the MS subjects. A similar study of the fatty acid profile in adipose tissue in 26 MS and 35 healthy controls found no detectable eicosapentaenoic acid in either group. However, whereas docosahexaenoic acid was not detectable in any MS patient, 40% of the controls had measurable levels varying from to 0.1 to 0.3% of total estimated fatty acid (p = 0.0003). No reduction in linoleic acid in MS subjects was observed. Supplementation with oral fish body oil demonstrated that n-3 fatty acids were incorporated into red blood cells over 5 weeks and this occurred equally in MS and controls. The effects of oral supplementation on adipose tissue were studied after 1 and 2 years. Whereas many fatty acids such as linoleic acid were raised at 1 year, but did not rise subsequently, eicosapentaenoic acid and docosahexaenoic acid continued to rise through the 2-year period.(ABSTRACT TRUNCATED AT 250 WORDS) Language of Publication English Unique Identifier 91050356 x tle Multiple sclerosis: fat-oil relationship. Author Swank RL Source Nutrition, 7: 5, 1991 Sep-Oct, 368-76 Abstract Between 1949 and 1984, 150 patients with multiple sclerosis consumed low-fat diets. Fat, oil, and protein intakes; disability; and deaths were determined. - daily fat consumption`less than 20.1 g/day (av 17 g/day), 31% died, and average deterioration was slight. - daily intake greater than 20 g/day (av 25 or 41 g/day) was attended by serious disability and the deaths of 79 and 81%, respectively. Oil intake bore an indirect relationship to fat consumption. Minimally disabled patients who followed diet recommendations deteriorated little if at all, and only 5% failed to survive the 34 yr of the study, 80% who failed to follow diet recommendations did not survive the study period. The moderately disabled and severely disabled patients who followed diet recommendations carefully did far better than those who failed to follow the diet. In general, women tended to do better than men. Those patients treated early did better than those in whom treatment was delayed. High sensitivity to fats suggests that saturated animal fats are directly involved in the genesis of multiple sclerosis. Language of Publication English Unique Identifier 92208526 Title Evidence for increased lipid peroxidation in multiple sclerosis. Author Toshniwal PK; Zarling EJ Address Department of Neurology, Cook County Hospital, Chicago, Illinois. Source Neurochem Res, 17: 2, 1992 Feb, 205-7 Abstract Pentane and ethane are degradation products of unsaturated fatty acids which are released during lipid peroxidation. In order to assess whether multiple sclerosis is associated with lipid peroxidation, we measured pentane and ethane excretion by 16 patients with multiple sclerosis and compared them to healthy control subjects. Patients with acute exacerbation of multiple sclerosis had significantly higher concentrations of pentane (10.5 +/- 4.2 nmol/l)(p less than 0.01) compared to either patients in remission (4.5 +/- 1.7 nmol/l) or control subjects (4.9 +/- 1.1 nmol/l). The concentrations of ethane were not significantly different among these groups. Of the patients with acute exacerbation who later achieved remission, the pentane excretion also returned to normal (5.6 +/- 0.9 nmol/l). One patient ho failed to reachieve clinical remission continued to excrete large amounts of pentane. We conclude that oxygen free radical activity is enhanced during exacerbation of multiple sclerosis. Language of Publication English Unique Identifier 92168314 Title Lipid and fatty acid composition is altered in plaque tissue from multiple sclerosis brain compared with normal brain white matter. Author Wilson R; Tocher DR Address Department of Biological and Molecular Sciences, School of Natural Sciences, University of Stirling, Scotland, U.K. Source Lipids, 26: 1, 1991 Jan, 9-15 Abstract Plaques and white matter from brains of multiple sclerosis (MS) patients were analyzed for lipid content, class composition, and fatty acid composition of total lipid, together with the fatty acid composition of plaque glycerophospholipids, and the results were compared with white matter from normal brain. Plaques contained less than 30% of the lipid present in normal white matter. Plaque lipid was characterized by significantly increased proportions of glycerophospholipids and decreased cerebrosides and sulfatides. In addition, a subacute plaque contained approximately 10 times the proportion of steryl esters observed in chronic plaques or normal white matter. Total lipid from all the MS plaques showed significantly increased percentages of saturated fatty acids, n-6, n-3 and total polyunsaturated fatty acids and decreased percentages of monoenes and alk-l-enyl ethers in comparison with normal brains. These results were consistent with increased cellularity and astrogliosis associated with MS plaques. However, analysis of plaque glycerophospholipids showed that the fatty acid changes observed in total lipid were not simply due to the increased proportion of glycerophospholipids and decreased myelin lipids, but that the fatty acid composition of the individual glycerophospholipids was different. Language of Publication English Unique Identifier 91270016 GLUTEN Title Does cryptic gluten sensitivity play a part in neurological illness? Author Hadjivassiliou M; Gibson A; Davies-Jones GA; Lobo AJ; Stephenson TJ; Milford-Ward A Source Lancet, 347: 8998, 1996 Feb 10, 369-71 Abstract BACKGROUND: Antigliadin antibodies are a marker of untreated coeliac disease but can also be found in individuals with normal small-bowel mucosa. Because neurological dysfunction is a known complication of coeliac disease we have investigated the frequency of antigliadin antibodies, as a measure of cryptic gluten sensitivity, and coeliac disease in neurological patients. METHODS: Using ELISA, we estimated serum IgG and IgA antigliadin antibodies in 147 neurological patients who were divided into two groups. There were 53 patients with neurological dysfunction of unknown cause despite full investigation (25 ataxia, 20 peripheral neuropathy, 5 mononeuritis multiplex, 4 myopathy, 3 motor neuropathy, 2 myelopathy). The remaining 94 patients were found to have a specific neurological diagnosis (16 stroke, 12 multiple sclerosis, 10 Parkinson's disease, 56 other diagnoses) and formed the neurological control group. 50 healthy blood donors formed a third group. FINDINGS: The proportions of individuals with positive titres for antigliadin antibodies in the three groups were 30/53, 5/94, and 6/50 respectively (57, 5, and 12%). The difference in proportion between group 1 and the combined control groups was 0.49 (95% CI 0.35-0.63). Distal duodenal biopsies in 26 out of 30 antigliadin-positive patients from group 1 revealed histological evidence of coeliac disease in nine (35%), non-specific duodenitis in ten (38%), and no lesion in seven (26%) individuals. INTERPRETATION: Our data suggest that gluten sensitivity is common in patients with neurological disease of unknown caus e and may have aetiological significance. Language of Publication English Unique Identifier 96169974 Title Is there a role for gluten-free diets in multiple sclerosis? Author Hewson DC Source Hum Nutr Appl Nutr, 38: 6, 1984 Dec, 417-20 Abstract This brief paper presents findings of 17 (3.4 per cent) of the patients involved in the ARMS research programme which is investigating the role of nutrition and physiotherapy in the management of MS. These 17 were following gluten-free diets. Our findings support the view that there is no conclusive evidence that GF diets are universally beneficial in the management of MS. Language of Publication English Unique Identifier 85130306 MINERALS Title Selenium in chronic neurologic diseases. Multiple sclerosis and Batten's disease. Author Clausen J; Jensen GE; Nielsen SA Source Biol Trace Elem Res, 15:1988 Jan-Apr, 179-203 Abstract The selee4unium levels in whole blood and the activity of glutathione peroxidase in hematogenous Multiple sclerosis (MS) patients suffer from a chronic relapsing/remitting demyelinating disease. A theory explaining the pathogenesis of MS concerns increased stickiness of cellular plasma membranes, hampering normal vascular function of the brain. In agreement with that theory, the present communication demonstrates significantly lowered selenium values and lowered glutathione peroxidase activities of major types of hematogenous cells. In close agreement with these findings, hematogenous cells in MS show increased peroxidation rates. A nonblinded biochemical dietary experiment on MS patients showed that all abnormalities could be normalized by daily intake of selenium, vitamin E, and vitamin C. Language of Publication English Unique Identifier 91001225 ------------- Title Morphology of demyelination in the human central nervous system. Author Hauw JJ; Delaère P; Seilhean D; Cornu P Address Laboratoire de Neuropathologie R. Escourolle, Hôpital de la Salpêtrière, Paris, France. Source J Neuroimmunol, 40: 2-3, 1992 Oct, 139-52 Abstract The principles of the neuropathological classification of disorders of central nervous system myelin are recalled. They are illustrated by a few selected examples. Dysmyelination is characterized by the production of an abnormal and unstable myelin sheath; it is often associated with hypomyelination (paucity of myelin formation) and is due to metabolic disorders. It is the main process in leukodystrophies. Storage of different lipids (e.g. sulfatides, long-chain fatty acids) or associated pathology of various cell types (in Alexander's disease, for example) are used for classifying these disorders. Biochemical and genetic characterizations are presently ongoing. Demyelination is the destruction of apparently normal myelin. It is often followed by remyelination. Our present knowledge on the neuropathology of multiple sclerosis, the most common demyelinating disease, is summarized. Cell-mediated demyelination affects the myelin sheaths for an obscure reason. The causes of the multifocal and sharply demarcated plaques, and of the fading of the remyelination process at the edge of some plaques, are not clear. A few examples of demyelinating diseases of known etiology and of various mechanisms are given. The similarities between acute disseminated leukoencephalitis and experimental autoimmune encephalitis are stressed. In progressive multifocal leukoencephalopathy, chronic infection of oligodendrocytes by JC virus induces poorly defined areas of demyelination. In AIDS, the pathogenesis of the myelin change is unclear. Macrophages may be responsible. Toxic and vascular disorders provide also good models for the understanding of mechanisms of demyelination. Language of Publication English Unique Identifier 93055339 Title: Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. Author Hibbeln JR; Salem N Jr Address Laboratory of Membrane Biophysics and Biochemistry, DICBR, National Institute of Alcohol Abuse and Alcoholism, Rockville, MD 20852, USA. Source Am J Clin Nutr, 62: 1, 1995 Jul, 1-9 Abstract Recent studies have both offered and contested the proposition that lowering plasma cholesterol by diet and medications increases suicide, homicide, and depression. Significant confounding factors include the quantity and distribution of dietary n-6 and n-3 polyunsaturated essential fatty acids that influence serum lipids and alter the biophysical and biochemical properties of cell membranes. Epidemiological studies in various countries and in the United States in the last century suggest that decreased n-3 fatty acid consumption correlates with increasing rates of depression. This is consistent with a well-established positive correlation between depression and coronary artery disease. Long-chain n-3 polyunsaturate deficiency may also contribute to depressive symptoms in alcoholism, multiple sclerosis, and post-partum depression. We postulate that adequate long-chain polyunsaturated fatty acids, particularly docosahexaenoic acid, may reduce the development of depression just as n-3 polyunsaturated fatty acids may reduce coronary artery disease. Language of Publication English Unique Identifier 95321257 Title: On the causes of multiple sclerosis. Author: Hutter C Source: Med Hypotheses, 41: 2, 1993 Aug, 93-6 Abstract Evidence on aetiology in multiple sclerosis suggests that the prevalence depends on the interaction of two factors, diet and exposure to visible sunlight. The dietary features which may be beneficial include supplementation with fish oils, avoidance of saturated fats, and the associated intake of antioxidants with unsaturated fatty acids. Inhibition, by antioxidants, of the enzyme lipoxygenase inhibits leukotriene synthesis, and the presence of fish oils leads to the production of leukotrienes with less inflammatory properties. This is of particular importance in the retina where leukotrienes might be the underlying cause of retrobulbar neuritis. The antioxidant properties of vitamin A may also lead to inhibition of leukotriene synthesis. Visible solar radiation could be of benefit therefore by releasing vitamin A from visual pigment rhodopsin. The interaction of these two factors may explain the epidemiological observations on the prevalence of multiple sclerosis. Language of Publication: English Unique Identifier: 94049341 Periodical: JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY Title: Blood-brain barrier abnormalities in longstanding multiple sclerosis lesions. An immunohistochemical study. Name: Kwon EE Name: Prineas JW Abstract: Thirty-five randomly selected plaques from five patients with longstanding multiple sclerosis were examined immunohistochemically for evidence of extravascular serum proteins. One lesion showed histological evidence of active demyelination and 34 were inactive. In the one active lesion and in 26 of the 34 inactive lesions, serum proteins were detected outside blood vessels in a distribution consistent with leakage during life. The findings suggest that the blood-brain barrier (BBB) is permanently damaged in many old plaques, although to a degree not often detectable by current gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging (MRI). The findings also suggest that in patients with multiple sclerosis, a breached BBB is not by itself sufficient to induce active demyelination. Continuous exposure of demyelinated axons and glia to cytokines, antibody or other factors present in the circulation might be important, however, in preventing oligodendrocyte regeneration and new myelin formation in longstanding lesions. ISSN 0022-3069 Title: Comparison of membrane structure, osmotic fragility, and morphology of multiple sclerosis and normal erythrocytes. Author Kurantsin-Mills J; Samji N; Moscarello MA; Boggs JM Source Neurochem Res, 7: 12, 1982 Dec, 1523-40 Abstract Erythrocyte membranes from multiple sclerosis (MS) patients and normal individuals were studied by electron spin resonance spectroscopy, osmotic fragility tests, scanning electron microscopy (SEM) and fatty acid analysis of membrane lipids. There was no significant difference in the membrane fluidity between MS and normal erythrocytes using fatty acid spin labels with the nitroxide moiety on carbons 5, 12, or 16 from the carboxyl group. Linoleic acid, which has been reported to decrease the absolute electrophoretic mobility of only MS erythrocytes, increased the fluidity of MS and normal erythrocyte membranes to a similar extent. The osmotic fragility of MS erythrocytes obtained from outpatients was similar to normal control cells but the osmotic fragility of erythrocytes obtained from hospitalized MS patients was greater than normal. Scanning electron microscopy of MS erythrocytes revealed no gross abnormalities. Cells incubated with linoleic acid had transformed from discocytes into sphero-echinocytes with prominent membrane surface indentations but MS and normal erythrocytes appeared identical. Of the fatty acid content of the total lipid extract, erythrocytes from most, but not all, MS hospitalized patients and some patients with other demyelinating diseases had relatively less (P less than .001) 18:2 than the normal cells. These results indicate that at least some of the abnormalities reported in MS erythrocytes may only be found in hospitalized patients and may be due to other complications of the disease. They also indicate that the reported abnormal effects of linoleic acid on the electrophoretic mobility of MS erythrocytes may be caused by some other mechanism than an effect on the fluidity of the bilayer. Language of Publication English Unique Identifier 83192759 Title: Continual breakdown and regeneration of myelin in progressive multiple sclerosis plaques. Author Prineas JW; Kwon EE; Cho ES; Sharer LR Source Ann N Y Acad Sci, 436:1984, 11-32 Abstract Plaques with lipid macrophages and macrophages containing undigested myelin fragments from five multiple sclerosis patients were studied by light microscopy of epoxy-embedded tissue (five cases) and electron microscopy (one case). Cell counts determined electron microscopically revealed that oligodendrocytes were reduced in number in areas of commencing myelin breakdown. The major mechanism of myelin destruction was phagocytosis by macrophages of intact myelin sheaths in the presence of very small numbers of lymphocytes and plasma cells. When plaques were orientated to allow examination of whole myelin internodes, it was found that most lesions, including lesions known to have been present for less than ten months, contained remyelinating internodes, sometimes in numbers large enough to form shadow plaques. It is concluded that the two processes of sometimes massive remyelination and active demyelination frequently coexist in "fatty" subacute plaques filled with lipid-containing macrophages, and that myelin breakdown at the edges of progressive lesions includes destruction of remyelinating internodes. Language of Publication English Unique Identifier 85172992 Title: Nervonic acid and demyelinating disease. Author Sargent JR; Coupland K; Wilson R Address Department of Biological and Molecular Sciences, School of Natural Sciences, University of Stirling, UK. Source Med Hypotheses, 42: 4, 1994 Apr, 237-42 Abstract Demyelination in adrenoleukodystrophy (ALD) is associated with an accumulation of very long chain saturated fatty acids such as 26:0 stemming from a genetic defect in the peroxisomal beta oxidation system responsible for the chain shortening of these fatty acids. Long chain monoenoic acids such as erucic acid, 22:1(n-9), can normalise elevated serum levels of 26:0 in ALD by depressing their biosynthesis from shorter chain saturated fatty acids. Sphingolipids from post mortem ALD brain have decreased levels of nervonic acid, 24:1(n-9), and increased levels of stearic acid, 18:0. Increased levels of 26:0 are accompanied by decreased nervonic acid biosynthesis in skin fibroblasts from ALD patients. Sphingolipids from post mortem MS brain have the same decreased 24:1(n-9) and increased 18:0 seen in post mortem ALD brain. The 24:1(n-9) content of sphingomyelin is depressed in erythrocytes from multiple sclerosis (MS) patients. Defects in the microsomal biosynthesis of very long chain fatty acids including 24:1(n-9) in 'jumpy' and 'quaking' mice are accompanied by impaired myelination. An impairment in the provision of nervonic acid in demyelinating diseases is indicated, suggesting that dietary therapy with oils rich in very long chain monenoic acid fatty acids may be beneficial in such conditions. Language of Publication English Unique Identifier 94352240 Title : Blood-brain barrier: a definition of normal and altered function. Name: Pollay, M. Name: Roberts PA Imprint: United States : 1980 Jun Note: CAS Registry 0 (Amino Acids) JOURNAL ARTICLE REVIEW Review Article Refs. 68 Periodical : NEUROSURGERY 6(6):675-85 Abstract: The anatomical component of the blood-brain barrier (BBB) has been shown to be the cerebral capillary. These capillary endothelial cells are connected by continuous tight intercellular junctions and under normal conditions do not demonstrate transendothelial channels or pinocytotic vesicles. The rate that substances penetrate the BBB is related to molecular size, lipid solubility, and the presence of a specific carrier-mediated transport system. This latter mechanism for transendothelial passage is utilized for the movement of a wide variety of biologically important compounds such as sugars, amino acids, and organic acids. In certain pathological conditions, the permeability of the BBB is altered so that normally excluded plasma proteins and fluid enter the brain extracellular space, with the subsequent development of cerebral edema. In other abnormal conditions, alterations in the specialized transport systems operating across the cerebral capillary result in adverse changes in cerebral and neurotransmitter metabolism. An understanding of the unique properties of the BBB and of the changes that occur in pathological conditions has allowed the development of rational therapeutic strategies for a wide variety of diseases of the central nervous system. ISSN 0148-396X