ESSENTIAL FATTY ACIDS
TABLE OF CONTENTS
Effects of dietary supplementation on autoimmunity in the MRL/lpr mouse: A preliminary investigation
Dietary fats and coronary heart disease
Plasma lipids and their fatty acid composition in multiple sclerosis
Essential fatty acids in the serum and cerebrospinal fluid of multiple sclerosis patients
Clinical trials of unsaturated fatty acids in multiple sclerosis
Abnormality of fatty acid composition of plasma lipid in multiple sclerosis
Arachidonic and docosahexanoic acid content of bovine brain myelin: Implications for the pathogenesis of multiple sclerosis
Inhibition by acetylsalicylic acid, a cyclo‑oxygenase inhibitor, and p‑bromophenacylbromide, a phospholipase A2 inhibitor, of both cirrhosis and enzyme‑altered nodules caused by a choline‑deficient, L‑amino acid‑defined diet in rats
Vasodilating agents and platelet function: intracellular free calcium concentration, cyclic nucleotides, and shape‑change response.
Postischemic tissue injury by iron-mediated free radical lipid peroxidation
Increased TGF-beta and decreased oncogene expression by omega-3 fatty acids in the spleen delays onset of autoimmune disease in B/W mice
Role of omega-3 fatty acids in health and disease
Inhibitory effects of a novel platelet activating factor (PAF) antagonist (BN 52021) on antigen‑induced prostaglandin and thromboxane formation by the guinea‑pig lung
Fatty acid compositions of plasma lipids in atopic dermatitis/asthma patients.
Essential fatty acid metabolism in patients with essential hypertension, diabetes mellitus and coronary heart disease.
Differential effects of polyunsaturated fatty acids on chemosensitivity of NIH3T3 cells and its transformants
Demonstration of organotropic effects of chemopreventive agents in multiorgan carcinogenesis models.
Severe rheumatoid arthritis: current options in drug therapy.
Rationales for micronutrient supplementation in diabetes.
n‑3 Fatty acids decrease colonic epithelial cell proliferation in high‑risk bowel mucosa
Early enteral feeding in postsurgical cancer patients: Fish oil structured lipid‑based polymeric formula versus a standard polymeric formula
Inhibition of lipolysis and muscle protein degradation by EPA in cancer cachexia
The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer
Historical perspective and potential use of n‑3 fatty acids in therapy of cancer cachexia
ESSENTIAL FATTY ACIDS
Effects of dietary supplementation on autoimmunity in the MRL/lpr mouse: A preliminary investigation
Godfrey DG, Stimson WH, Watson J, Belch JF, Sturrock RD
Ann Rheum Dis (UK), 1986, 45/12 (1019-1024)
The effects of dietary fatty acid supplementation on various disease parameters in the spontaneously autoimmune MRL-mp-lpr/lpr mouse model of systemic lupus erythematosus before onset of disease were investigated. A fat deficient diet was supplemented with the following oils: olive oil, sunflower oil, evening primrose oil (EPO), fish oil, and a fish oil/EPO mixture. The mice receiving a diet enriched with EPO showed an increase in survival, as did those receiving a fish oil/EPO mixture. These results, taken together with those of the other parameters monitored, suggest that EPO may be of benefit in alleviating the murine form of the disease.
Dietary fats and coronary heart disease
Biomedicine and Pharmacotherapy (France), 1996, 50/6‑7 (261‑268)
The prevention and treatment of coronary heart disease (CHD) necessitates vigorous dietary intervention so as to lower the serum cholesterol level by at least 6%. Greater decreases in serum cholesterol can bring about reversal of atherosclerosis. The critical dietary change is the reduction in intake of saturated fat and cholesterol. Some of this fat may be replaced by unsaturated fats, especially monounsaturated fat (olive or canola oil). Fish and the omega‑3 fats they contain may also be useful for the prevention of CHD. The benefits of omega‑3 fats occur within a few months and probably involve an anti‑thrombotic effect. There is evidence that the intake of trans‑fatty acids formed by the hydrogenation of oils should be reduced as they are associated with CBD. Hypolipidaemic drugs may be useful for persons at very high risk of CHD but should generally be avoided for primary prevention.
Plasma lipids and their fatty acid composition in multiple sclerosis
Navarro X, Segura R.
Department of Physiology, Autonomous University of Barcelona, Spain
Acta Neurol Scand (Denmark), 1988, 78/2 (152‑157)
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.
Essential fatty acids in the serum and cerebrospinal fluid of multiple sclerosis patients
Neu IS
Acta Neurol Scand (Denmark), 1983, 67/3 (151‑163)
Statistical evaluation of essential fatty acids (determined by gas chromatography) in the serum and cerebrospinal fluid of patients with definite MS and acute CCT showed marked differences as compared to healthy subjects. It was also evident that the decrease of essential fatty acids in MS patients differed from that of CCT patients. Whereas the fatty acid levels in the serum of MS patients revealed only minor differences as compared to the controls and CCT patients, MS patients did show a clear decrease, especially of linoleic and arachidonic acids, in the CSF. This difference was most pronounced in cholesterol esters in the CSF. One absorption study with safflower oil demonstrated normal enteral absorption of essential fatty acids and the ability to cross the blood‑CSF barrier.
Clinical trials of unsaturated fatty acids in multiple sclerosis
IRCS Med Sci (England), 1981, 9/12 (1081)
The membrane of MS‑RBC (multiple sclerosis‑erythrocytes) is different from non‑MS. Until now it was believed that 6‑8 months treatment with gamma‑linolenate converted their abnormal properties into normal, as judged by electrophoretic measurements in the presence of LA (linoleic acid) and AA (arachidonic acid). Further experimentation has shown however, such conversion to non‑MS type is delayed until 21‑24 months after gamma‑linolenate feeding, when low doses of LA and AA begin to have the same effect on mobility as they do in normal cells. Thus any clinical trial of PUFA should begin about 2 years after it is instituted ‑ not concluded, as at present. This may account for the relative success of Swank's dietary treatment which spans over 20 years. The long term requirement for essential fatty acids (EFA) to restore membrane normality in MS must be taken into account in planning therapeutic trials.
Abnormality of fatty acid composition of plasma lipid in multiple sclerosis
Sato S, Shirakawa K, Tsubaki T, Sakuragawa N
Brain Nerve (Tokyo) (Japan), 1979, 31/8 (797‑801)
It has been reported that the composition of fatty acid is abnormal in the blood of European patients with multiple sclerosis (MS). The purpose of the present paper is to confirm such an abnormality in Japanese MS. The level of linoleic acid was decreased significantly in active stage at seven relapses in four cases of MS. While the level of plasma linoleic acid was decreased the non‑essential fatty acids oleate and palmitate showed significant increase in these relapses. In thirteen patients with MS who were in remission, the level of arachidonic acid was decreased. Clinical courses were correlated to linoleic acid levels in four cases of active MS. The level of linoleic acid was decreased at each relapse and returned to normal in remission.
Arachidonic and docosahexanoic acid content of bovine brain myelin: Implications for the pathogenesis of multiple sclerosis
Ansari KA, Shoeman DW.
Dept. of Neurology, U. of Minn. School of Medicine, Minneapolis
Neurochem Res (USA), 1990, 15/1 (7‑11)
Lipids were extracted from bovine brain myelin using a mixture of hexane and isopropanolol (3:2). Myelin lipids were resolved, using Sep Pak chromatography, into four fractions: Fraction 1 contained neutral lipids, fraction 2, free fatty acids, fraction 3, ethanolamine phospholipids and fraction 4, choline phospholipids. Docosahexanoic (DHA) and arachidonic (AA) acids in these fractions were measured by RPHPLC. Fraction 2 was analyzed directly, the other three fractions were subjected to alkaline hydrolysis before analysis for DHA and AA. DHA and AA were not found in fraction 1. Both DHA and AA were found in fractions 2 and 3. Only AA was consistently found in fraction 4. These results were confirmed by GC.
Inhibition by acetylsalicylic acid, a cyclo‑oxygenase inhibitor, and p‑bromophenacylbromide, a phospholipase A2 inhibitor, of both cirrhosis and enzyme‑altered nodules caused by a choline‑deficient, L‑amino acid‑defined diet in rats
Endoh T, Tang Q, Denda A, Noguchi O, Kobayashi E, Tamura K, Horiguchi K, Ogasawara H, Tsujiuchi T, Nakae D, Sugimura M, Konishi Y.
Department of Oncological Pathology, Cancer Center, Nara Medical University, Japan
Carcinogenesis (United Kingdom), 1996, 17/3 (467‑475)
Effects of inhibitors of arachidonic acid (AA) metabolism on the development of fatty liver, cirrhosis, glutathione‑S‑transferase placental form (GST‑P)‑positive nodules and the generation of 8‑hydroxydeoxyguanosine (8‑OHdG) and thiobarbituric acid‑reactive substances (TBARS), caused by a choline‑deficient, L‑amino acid‑defined (CDAA) diet, were examined in male Fischer 344 rats by feeding CDAA diets supplemented with the inhibitors for 12 and 30 weeks. Acetylsalicylic acid (ASA) (at doses of 0.1 and 0.2%) and p‑bromophenacylbromide (BPB) (0.1 and 0.2%) were used as inhibitors of, respectively, cyclo‑oxygenase and phospholipase A2, and quercetin (QU) (0.75 and 1.5%) and nordihydroguaiaretic acid (NDGA) (0.1 and 0.2%) as inhibitors of lipoxygenase. None of the inhibitors affected the development of fatty liver caused by the CDAA diet. ASA at a dose of 0.2% almost completely prevented the appearance of cirrhosis, GST‑P‑positive nodules, 8‑OHdG and TBARS in seven out of 11 (63.7%) rats. BPB at a dose of 0.2% also exerted inhibitory effects on all of these lesions but to a lesser extent than ASA. QU and NDGA exerted inhibitory effects limited to the GST‑P‑positive nodule case. The results indicate that a perturbed AA metabolism, particularly of the cyclo‑oxygenase pathway, derived secondarily from depletion of labile methyl groups or phosphatidylcholine, might play key roles in the cirrhosis, hepatocarcinogenesis and oxidative stress caused by a CDAA diet. The results also indicated a possible involvement of the lipoxygenase pathway in hepatocarcinogenic processes.
Vasodilating agents and platelet function: intracellular free calcium concentration, cyclic nucleotides, and shape‑change response.
Erne P, Mittelholzer E, Rogg H, Resink TJ, Buhler FR
J Cardiovasc Pharmacol (United States) 1986, 8 Suppl 8 pS102‑6
The adenylate‑cyclase activator forskolin, the guanylate‑cyclase stimulator sodium nitroprusside, the phosphodiesterase inhibitor Ro 15‑2041, different Ca‑entry blockers, as well as various vasodilators, and the atrial natriuretic peptide were tested for antiplatelet activity. Thrombin, vasopressin, ADP, arachidonic acid, and the dihydropyridine Ca agonist CGP 28392 were used as platelet activators. The physiological and biochemical parameters of platelet function studied included shape‑change reaction, intracellular free‑Ca modulation, and cyclic nucleotide formation. When inhibition of the shape‑change response occurred, it was accompanied by inhibition of the increase in intracellular free Ca. Furthermore, the results suggest a possible intracellular site of action of Ca entry blockers in platelets, and confirm the importance of modulation of cyclic nucleotides in the regulation of platelet function, regardless of the mechanism of platelet activation. Additional antiplatelet activity of antihypertensive agents may have a beneficial effect in reducing the associated risk of thrombo‑embolic complications in essential hypertension.
White BC, Krause GS, Aust SD, Eyster GE
USA Ann Emerg Med (USA), 1985, 14/8 (804-809)
Cell damage initiated during ischemia matures during reperfusion. Mechanisms involved during reperfusion include the effects of arachidonic acid and its oxidative products prostaglandins and leukotrienes, reperfusion tissue calcium overloading, and damage to membranes by lipid peroxidation. Lipid peroxidation occurs by oxygen radical mechanisms that require a metal with more than one ionic state (transitional metal) for catalysis. We have shown that cellular iron is delocalized from the large molecules where it is normally stored to smaller chemical species during postischemic reperfusion. Postischemic lipid peroxidation is inhibited by the iron chelator deferoxamine. Intervention in the reperfusion injury of membranes by chelation of transitional metals is a new and promising therapeutic possibility for protection of the heart and brain.
J Immunol (USA), 1994, 152/12 (5979-5987)
This study was designed to investigate the mechanisms by which marine lipids rich in long chain omega-3 fatty acids inhibit autoimmune disease and prolong the survival rate in female (NZB/NZW) F1 (B/W) mice, an animal model for human SLE. Nutritionally adequate semipurified diets containing at 10% either corn oil (CO) or fish oil (FO) were fed from 1 mo of age and were monitored for proteinuria and survival. Proteinuria was detected earlier and became progressively severe in CO-fed mice. The average life span was significantly shortened by the CO diet (266.7 days plus or minus 12.5), whereas FO extended the survival significantly (402.1 days plus or minus 26.1; p < 0.001). A cross- sectional study at 6.5 mo of age revealed an increased proliferative response to T cell mitogens including bacterial superantigens and decreased serum anti-dsDNA Ab titers in the FO group compared with the CO group. Furthermore, splenocytes from the FO group when stimulated with Con A had higher IL-2 and lower IL-4 production similar to that of young (3.5 mo) mice. Flow cytometric analyses of splenocytes revealed lower Ig+, higher lymphocyte endothelial cell adhesion molecule-1, and lower Pgp-1+ cells within CD4+ and CD8+ subsets in FO-fed mice. Also, elevated IL-2 and IL-4 and significantly higher TGF-beta1 and lower c-myc and c-ras mRNA expression and higher TGF-beta1 and significantly lower c-Myc and c-Ha-Ras proteins were detected in spleens of FO-fed mice. Fatty acid analysis revealed significantly higher linoleic (18:2omega-6) and arachidonic (20:4omega-6) acid levels in splenocytes of the CO- fed group and higher eicosapentanoic (20:5omega-3) and docosahexanoic (22:6omega- 3) acid levels in the FO-fed group, indicating that changes in membrane fatty acid composition may contribute to the altered immune function and gene expression during the development of murine SLE.
Nutr Res (USA), 1993, 13/SUPPL. 1 (S19-S45)
Dietary lipid interventions have an important role in modulating the onset of autoimmunity, cardiovascular diseases and cancer. Many studies carried out in the past have established the adverse effects of saturated fats in humans and in animal models. Based on these adverse effects, the consumption of vegetable oils containing both monounsaturated omega (omega)-9 and polyunsaturated fatty acids (rich in 18:2 omega-6) is rising significantly in the United States. The increased consumption of many vegetable oils particularly of omega-6 series is however to be viewed as pro-inflammatory and its suspected as one of the possible causes for the gradual rise in certain malignant tumors, rheumatoid arthritis and autoimmune diseases primarily due to the increased production of pro-inflammatory cytokines although its increased usage has reduced cardiovascular disease nearly 30% in the United States. Diets based on omega-6 enriched oils can increase the level of linoleic acid in tissue phosphoglycerides and are able to reduce cholesterol levels, yet these lipids usually tend to elevate excessive arachidonic acid (20:4 omega- 6) levels. In contrast, omega-3 fatty acid-enriched fish oil (FO) and/or omega-3 precursors from certain vegetable oils (linolenic acid, 18:3 omega-3) are found to provide protection against cardiovascular disease, rheumatoid arthritis, cancer and possibly against the severity of viral infections. Nutritional modification of cellular functions by dietary lipids with a balanced ratio of omega-6 and omega-3 fatty acids offers an attractive avenue to correct, modify and/or prevent many patho-physiological processes in health and disease state and to reduce toxicity of drugs in many patients. The mediation of such effects is thought to be primarily achieved through alterations of cellular membranes composition and other endogenous lipid stores which may modify the functional activity of various receptors on plasma membranes. In summary, the protective effects of omega-3 lipids have been explained based on changes in eicosanoid synthesis and the reduced risk of sudden death from cardiac arrhythmia, increased protection from ischemic myocardium, improved myocardial function and reduction of other cardiovascular and autoimmune disease risks. However, well-designed studies are still required to further define the key role of both combination of omega-6 and omega-3 fatty acids, from marine and vegetable sources, both as a supplement to infant nutrition specifically for optimizing the development of cognitive function, and also as preventive measure for reducing the incidence of diseases of aging in rapidly growing elderly populations.
Inhibitory effects of a novel platelet activating factor (PAF) antagonist (BN 52021) on antigen‑induced prostaglandin and thromboxane formation by the guinea‑pig lung
Harczy M, Maclouf J, Pradelles P, Braquet P, Borgeat P, Sirois P
Pharmacol Res Commun (UK), 1986, 18/SUPPL. (111‑117)
The effects of a new Platelet‑Activating Factor (PAF‑acether) antagonist (BN52021) extracted from Ginkgo biloba leaves have been studied on the release of metabolites of arachidonic acid in IgG‑dependent guinea pig pulmonary anaphylaxis in vitro. Prostaglandin Esub 2 (PGEsub 2) and thromboxane Bsub 2 (TxBsub 2) were assayed using a novel ELISA technique. The release of PGEsub 2 and TxBsub 2 from anaphylactic lungs reached a maximum 4‑5 min following the antigen challenge (about 3.2 and 31.0 ng/ml respectively) and decayed slowly during the following 25 min. BN52021 (1, 3 and 30 mug/ml) produced dose‑dependent decreases of the release of PGEsub 2 and TxBsub 2. These results suggest that there are some interactions between the release of icosanoids and PAF‑acether in anaphylaxis.
Sakai K, Okuyama H, Shimazaki H, Katagiri M, Torii S, Matsushita T, Baba S.
Faculty of Pharmaceutical Sciences, Nagoya City University
Arerugi. 1994 Jan. 43(1). P 37-43
The proportions of linoleic acid in total plasma lipids and phospholipids were significantly greater and those of oleic acid were lower in pre-puberal and puberal atopic patients as compared with age-matched healthy controls. The n-3/n-6 fatty acid ratio of the triacylglycerol fraction was also lower in atopic patients. However, no significant decreases in the proportions of dihomo-gamma-linolenic acid and arachidonic acid were observed in plasma lipids of atopic patients, suggesting that delta 6-desaturase activity is not impaired in atopic patients. We provide an explanation for the beneficial effects of raising the n-3/n-6 ratio of dietary oils in the context of suppressing allergic hyper-reactivity in humans.
Das UN.
Department of Medicine, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, India
Prostaglandins Leukot Essent Fatty Acids (Scotland) Jun 1995, 52 (6) p387-91
Mortality and morbidity from coronary heart disease (CHD), diabetes mellitus (DM) and essential hypertension (HTN) are higher in people of South Asian descent than in other groups. There is evidence to believe that essential fatty acids (EFAs) and their metabolites may have a role in the pathobiology of CHD, DM and HTN. Fatty acid analysis of the plasma phospholipid fraction revealed that in CHD the levels of gamma- linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are low, in patients with HTN linoleic acid (LA) and AA are low, and in patients with non-insulin dependent diabetes mellitus (NIDDM) and diabetic nephropathy the levels of dihomo-gamma-linolenic acid (DGLA), AA, alpha-linolenic acid (ALA) and DHA are low, all compared to normal controls. These results are interesting since DGLA, AA and EPA form precursors to prostaglandin E1, (PGE1), prostacyclin (PGI2), and PGI3, which are potent platelet anti- aggregators and vasodilators and can prevent thrombosis and atherosclerosis. Further, the levels of lipid peroxides were found to be high in patients with CHD, HTN, NIDDM and diabetic nephropathy. These results suggest that increased formation of lipid peroxides and an alteration in the metabolism of EFAs are closely associated with CHD, HTN and NIDDM in Indians.( ABSTRACT TRUNCATED AT 250 WORDS)
Differential effects of polyunsaturated fatty acids on chemosensitivity of NIH3T3 cells and its transformants
Tsai WS, Nagawa H, Muto T.
First Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan
International Journal of Cancer (USA), 1997, 70/3 (357‑361)
Polyunsaturated fatty acids (PUFAs) have been suggested, on the basis of animal‑model studies, to be related not only to cancer development but also to chemotherapeutic effects. Controversy persists, however, as to which types of PUFAs are beneficial in terms of chemosensitivity. In this study, we used the NIH3T3 cell line and its SIC (sigmoid colon cancer) oncogene transformants to investigate the effects of PUFAs on the chemosensitivity of non‑malignant and malignant cells in terms of cell proliferation. We also determined the fatty acid composition of cells by high‑performance liquid chromatography (HPLC). The results revealed that the sensitivity of SIC transformants to mitomycin C (MC) was lower than that of NIH3T3 cells cultured in 10% calf‑serum DMEM without PUFA supplementation. When cells were cultured in DMEM supplemented with eicosapentaenoic acid (EPA) at a concentration (2 microg/ml) that does not influence cell proliferation, the sensitivity of SIC transformants to MC increased, whereas that of NIH3T3 cells decreased in comparison with the sensitivity of cells cultured without PUFA supplementation (p < 0.05). There was no difference between the 2 cell lines in the chemosensitivity of cells cultured in medium supplemented with arachidonic acid (ARA). The SIC transformants contained more stearic acid (C:18) and less lauric acid (C:12) than NIH3T3 cells cultured without PUFA. Culturing the cells in medium supplemented with EPA or ARA modified the cellular fatty‑acid composition. EPA caused the relative combined percentage of lauric acid and myristic acid (C:14) in SIC transformants to decrease signifcantly, and the SIC transformants tended to accumulate additional EPA, in contrast to the NIH3T3 cells. We conclude that the alterations in fatty‑acid composition in malignant transformants caused by exogenous EPA differ from those in non‑malignant cells, and that these changes account for the increased chemosensitivity of malignant transformants. Although preliminary, these findings imply that EPA specifically enhances the chemosensitivity of malignant cells.
Demonstration of organotropic effects of chemopreventive agents in multiorgan carcinogenesis models.
Tsuda H; Iwahori Y; Asamoto M; Baba‑Toriyama H; Hori T; Kim DJ; Uehara N; Iigo M; Takasuka N; Murakoshi M; Nishino H; Kakizoe T; Araki E; Yazawa K
National Cancer Center Research Institute, National Cancer Center Hospital, Tokyo, Japan.
IARC Sci Publ (France) 1996, (139) p143‑50
Organotropic chemopreventive effects of three (pro)vitamins and three unsaturated fatty acids were examined using mouse and rat multiorgan carcinogenesis models. For the study of (pro)vitamins, male and female B6C3F1 mice were treated with N,N‑diethylnitrosamine (DEN) and N‑methyl‑N‑nitrosourea (MNU) during the first 11 weeks, then from weeks 12 to 32 they received alpha‑carotene (0.4 mg/mouse), beta‑carotene (0.4 mg/mouse) or alpha‑tocopherol (40 mg/mouse) three times a week by gavage; control mice received vehicle alone. In male mice, alpha‑carotene significantly reduced liver weights, representing a reduced tumour mass (P < 0.001), and alpha‑carotene, beta‑carotene and alpha‑tocopherol significantly reduced the numbers of liver tumours (adenomas a0.01) as compared with control mice, the effects being greatest with alpha‑carotene. In female mice, alpha‑carotene significantly decreased the number of liver tumours (P < 0.001). In the lung, alpha‑carotene and alpha‑tocopherol reduced the area of lesions (hyperplasias and adenomas combined) only in males (P < 0.05). For the study of unsaturated fatty acids, F344 male rats were treated with DEN, MNU, N‑butyl‑N‑hydroxybutylnitrosamine (BBN), 1,2‑dimethylhydrazine (DMH) and N,N‑bis(2‑hydroxy)propylnitrosamine during the first 5 weeks, then from weeks 6 to 36 they were given docosahexaenoic acid (C22:6), eicosapentaenoic acid (C20:5) or linoleic acid (C18:2) at 1.0 g/rat, three times a week by gavage; control rats were treated with oleic acid (C18:1) using the same protocol. All animals were fed a low linoleic acid and calorie‑adjusted basal diet during fatty acid administration. Docosahexaenoic acid and linoleic acid reduced tumours in the large and small intestines, respectively. However, they did not influence the yield of preneoplastic liver, lung, kidney, forestomach and urinary bladder lesions. The data thus provide evidence for organotropic effects of carotenoids and unsaturated fatty acids on carcinogenesis.
Kremer JM.
Division of Rheumatology, Albany Medical College, New York
Geriatrics (United States) Dec 1990, 45 (12) p43-8
Therapeutic advances have been made in rheumatoid arthritis (RA), but patients (and sometimes physicians) may become frustrated at the apparent lack of breakthrough treatments. The latest advances in the treatment of severe RA are discussed, along with what investigators are using experimentally both in combination with other drugs and alone to treat RA now and, possibly, in the future. These agents include methotrexate, cyclosporine, gamma-interferon, and omega-3 fatty acids. (21 Refs.)
Rationales for micronutrient supplementation in diabetes.
McCarty MF, Rubin EJ
Med Hypotheses (England) Feb 1984, 13 (2) p139-51
Available evidence--some well-documented, some only preliminary--suggests that properly-designed nutritional insurance supplementation may have particular value in diabetes. Comprehensive micronutrient supplementation providing ample doses of antioxidants, yeast-chromium, magnesium, zinc, pyridoxine, gamma-linolenic acid, and carnitine, may aid glucose tolerance, stimulate immune defenses, and promote wound healing, while reducing the risk and severity of some of the secondary complications of diabetes. (125 Refs.)
n‑3 Fatty acids decrease colonic epithelial cell proliferation in high‑risk bowel mucosa
Huang YC, Jessup JM, Forse RA, Flickner S, Pleskow D, Anastopoulos HT, Ritter V, Blackburn GL.
Cancer Research Institute, Deaconess Pathway Health Network, Department of Surgery, Harvard Medical School, Boston, Massachusetts 02215, USA
Lipids (USA), 1996, 31/3 SUPPL. (S313‑S317)
The n‑3 fatty acids (C20:5, eicosapentaenoic acid; C22:6, docosahexaenoic acid) may be important in the development, growth, and metastasis of colon cancer, a leading cause of death in North America. Patients who have had a bowel neoplasm have a high risk of developing a second neoplasm, and this risk is associated with a high percentage of cells correspond to the S phase of bromodeoxyuridine (BrdUrd) labeling in mucosal epithelial cells. To determine the effect of n‑3 fatty acid supplementation on DNA synthesis of rectal mucosa, patients with stage 1 or stage 2 colon carcinoma or adenomatous polyps were randomized to consume either 9 g/d n‑3 fatty acid capsules or 9 g/d placebo capsules. Plasma phospholipid fatty acid analysis and proctoscopic mucosal biopsies were performed ats were isolated from the mucosa, disassociated with enzymes, and incubated with BrdUrd, and %S phase was measured by flow cytometry. The plasma phospholipid n‑6/n‑3 ratio was determined by gas chromatography. Supplement compliance was assessed by plasma phospholipid n‑6/n‑3 ratio. Mean capsule consumption in these two group was 82%. Prior to supplementation, there were no significant differences in the %S phase and the plasma n‑6/n‑3 ratio between these groups. Patients whose colonic epithelial cells indicated hyperproliferation at baseline showed a strongly positive correlation to the %S phase of BrdUrd uptake and the n‑6/n‑3 ratio. There was no significant change after n‑3 treatment in patients with low baseline. Those in the placebo group showed no significant difference in n‑6/n‑3 ratio, although there was an increase in the %S phase of BrdUrd uptake at 6 mon. The n‑3 group did not have significant side effects, and polyps were not found after completing 12 mon of n‑3 fatty acid supplementation. This study suggests that n‑3 fatty acid may he a useful chemopreventive agent in some patients as reflected in a plasma biomarker of colon tumor growth and metastasis. A low plasma phospholipid n‑6/n‑3 fatty acid ratio may serve as a nutritional marker that is associated with colonic epithelial cell hyperproliferation in the n‑3‑supplemented group as compared with the placebo group. Characteristics of mucosal proliferation at baseline may be a crucial factor for the effect of n‑3 fatty acid supplementation.
Early enteral feeding in postsurgical cancer patients: Fish oil structured lipid‑based polymeric formula versus a standard polymeric formula
Kenler AS, Swails WS, Driscoll DF, DeMichele SJ, Daley B, Babineau TJ, Peterson MB, Bistrian BR.
Department of Surgery, Deaconess Hospital, Boston, Massachusetts 02215, USA
Annals of Surgery (USA), 1996, 223/3 (316‑333)
Objectives: The authors compared the safety, gastrointestinal tolerance, and clinical efficacy of feeding an enteral diet containing a fish oil/medium‑chain triglyceride structured lipid (FOSL‑HN) versus an isonitrogenous, isocaloric formula (O‑HN) in patients undergoing major abdominal surgery for upper gastrointestinal malignancies. Summary Background Data: Previous studies suggest that feeding with n‑3 fatty acids from fish oil can alter eicosanoid and cytokine production, yielding an improved immunocompetence and a reduced inflammatory response to injury. The use of n‑ 3 fatty acids as a structured lipid can improve long‑chain fatty acid absorption. Methods: This prospective, blinded, randomized trial was conducted in 50 adult patients who were jejunally fed either FOSL‑HN or O‑HN for 7 days. Serum chemistries, hematology, urinalysis, gastrointestinal complications, liver and renal function, plasma and erythrocyte fatty acid analysis, urinary prostaglandins, and outcome parameters were measured at baseline and on day 7. Comparisons were made in 18 and 17 evaluable patients based a priori on the ability to reach a tube feeding rate of 40 mL/hour. Results: Patients receiving FOSL‑HN experienced no untoward side effects, significant incorporation of eicosapentaenoic acid into plasma and erythrocyte phospholipids, and a 50% decline in the total number of gastrointestinal complications and infections compared with patients given O‑ HN. The data strongly suggest improved liver and renal function during the postoperative period in the FOSL‑HN group. Conclusion: Early enteral feeding with FOSL‑HN was safe and well tolerated. Results suggest that the use of such a formula during the postoperative period may reduce the number of infectious and gastrointesinal complications per patient, as well as improve renal and liver function through modulation of urinary prostaglandin levels. Additional clinical trials to fully quantify clinical benefits and optimize nutritional support should be undertaken.
Inhibition of lipolysis and muscle protein degradation by EPA in cancer cachexia
Tisdale MJ.
Pharmaceutical Sciences Institute, Aston University, Birmingham, United Kingdom
Nutrition (USA), 1996, 12/1 SUPPL. (S31‑S33)
Depletion of muscle and adipose tissue in cancer cachexia appears to arise not only from decreased food intake but also from the production of catabolic factors by certain tumours. Experiments with the cachexia‑inducing MAC16 tumour in mice showed that when part of the carbohydrate calories were replaced by fish oil, host body weight loss was inhibited. The effect occurred without an alteration of either the total calorie consumption or nitrogen intake. Instead, one of the polyunsaturated fatty acids (PUFA) in fish oil, eicosapentaenoic acid (EPA), was found directly to inhibit tumour‑ induced lipolysis. The effect was structurally specific, as two related PUFA, docosahexaenoic acid (DHA) and gamma‑linolenic acid (GLA), were without effect. The antilipolytic effect of EPA arose from an inhibition of the elevation of cyclic AMP in adipocytes in response to the lipid mobilizing factor. The increased protein degradation in the skeletal muscle of cachectic animals was also inhibited by EPA. This effect was due to the inhibition of the rise in muscle prostaglandin E2 in response to a tumour‑produced proteolytic factor by EPA. Thus, reversal of cachexia by EPA in this mouse model results from its capacity to interfere with tumour‑produced catabolic factors. Similar factors have been detected in human cancer cachexia.
The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer
Wigmore SJ, Ross JA, Falconer JS, Plester CE, Tisdale MJ, Carter DC, Fearon KC.
University Department of Surgery, Royal Infirmary of Edinburgh, UK
Nutrition (USA), 1996, 12/1 SUPPL. (S27‑S30)
Cachexia is common in patients with pancreatic cancer and has been associated with persistent activation of the hepatic acute phase response and increased energy expenditure. Fatty acids have been shown to have anticachectic effects in animal models and to reduce inflammatory mediators in healthy subjects and patients with chronic inflammatory disease. Eighteen patients with unresectable pancreatic cancer received dietary supplementation orally with fish oil capsules (1 g each) containing eicosapentaenoic acid 18% and docosahexaenoic acid 12%. Anthropometric measurement, body composition analysis, and measurement of resting energy expenditure and serum C‑reactive protein were performed before and after supplementation with a median of 12 g/day of fish oil. Patients had a median weight loss of 2.9 kg/month (IQR 2‑ 4.6) prior to supplementation. At a median of 3 months after commencement of fish oil supplementation, patients had a median weight gain of 0.3 kg/month (IQR 0.‑0.5) (p < 0.002). Changes in weight were accompanied by a temporary but significant reduction in acute phase protein production (p < 0.002) and by stabilisation of resting energy expenditure. This study suggests a component fish oil, perhaps EPA, merits further investigation in the treatment of cancer cachexia.
Historical perspective and potential use of n‑3 fatty acids in therapy of Karmali RA.
Bryan Cave, New York, New York, USA cancer cachexia
Nutrition (USA), 1996, 12/1:
A review of the current status of research on n‑3 polyunsaturated fatty acids, eicosapentannoic and docosahexaenoic, indicates that these fatty acids exhibit protective effects on: (i) the development of carcinogen‑induced tumors, the growth of solid tumors, cachexia, and metastatic diseases in experimental models; and (ii) accelerated proliferation of flat human rectal mucosal epithelial of risk for breast cancer‑leukocyte adenosine diphosphate ribosyl transferase activity and 16‑alphahydroxylated estrogen‑in women at risk for breast cancer. These research findings, along with epidemiological evidence of an inverse relationship between n‑3 fatty acid intake and incidence of some cancers, warrant clinical investigation in the potential benefit of n‑3 fatty acids in the prevention and therapy of cachexia in cancer patients.