DIETARY SUPPLEMENT AND METHOD OF MINIMIZING EFFECTS OF INFECTION THROUGH DIET

Abstract: A method of minimizing infection and minimizing the risks of infection in at risk animals and patients. A dietary supplement to accomplish this objective is also disclosed. The method includes the step of administering a diet rich in omega 3 fatty acids, for example by adding a substantial proportion of fish oils to the diet. The dietary supplement is particularly well suited to patients receiving total parenteral nutrition.

Description: DIETA Y SUPPLEMENT AND METHOD OF MINIMIZING EFFECTS OF INFECTION THROUGH DIET ACKNOWLEDGEMENT Funding for the research which led to this application was furnished, in part, by grant GM-30632 from the Institute of General Medical Sciences, National Institutes of Health. BACKGROUND OF THE INVENTION The present invention relates to a method of dietary control which reduces the effects of infection as well as minimizing the effects of subsequent infection in at risk animals, particularly human patients. A dietary supplement useful in the method of the invention is also disclosed. Animals can be infected by many agents which break down the natural defenses and cause illness. These agents include bacteria, viruses, parasites, and fungi. While a great number of drugs have been developed to combat these infectious agents, the primary defense is the body's own immune system. The effectiveness of the body's defensive system against infection depends on the level of certain chemicals, e.g., prostaglandins, in the blood and cell membranes. These chemicals are synthesized from precursor molecules, e.g., fatty acids, obtained in the diet. In fact, some antiinfection drugs work by modifying the levels of synthesis of these molecules. The amount and family of fatty acids in the diet is one of the keys to nutrition. There are three major families of polyunsaturated fatty acids: u3, uβ and u9. The names are based on the location of the closest double bond to the methyl end of the fatty acid; that is, if the closest double bond is between the third and fourth carbon atoms from the methyl group, the molecule is a ω3 fatty acid while if the double bond is between the sixth and seventh carbons, it is classified as a uβ fatty acid. Mammals can desaturate or elongate fatty acid chains but cannot interconvert fatty acids from one family to another. The most significant fatty acids are those which have been desaturated and elongated to the twenty carbon length. The u9 fatty acids are elongated to form eicosatrienoic acids (C20:3u9), the uβ fatty acids form arachidonic acid (C20:4ω6), and the ω3 fatty acids form eicosapentaenoic acid (C20:5u3) or docosahexaenoic acid (C22:6u3). The notation (C : ω ) gives the number of carbons in the chain, the number of double bonds and the class of the fatty acid, respectively. Most people in industrialized nations obtain a high proportion of their fatty acids from meat fats and vegetable oils. These fatty acid sources are high in uβ fatty acids and low in u3 fatty acids. Therefore, arachidonic acid is the predominant twenty carbon desaturated and elongated fatty acid in the plasma and membranes of these people. In countries where fish oil, which contains a high proportion of ω3 fatty acids, is the predominant fatty acid source, eicosapentaenoic acid is the major desaturated fatty acid found in the plasma and membranes. Part of the significance of the twenty carbon fatty acids is their ability to act as substrates in the prostanoid synthesis pathway which forms prostaglandins from fatty acids. The first enzyme in this pathway is cycl o-oxygenase whose primary substrate in mammals is arachidonic acid. In the platelets, arachidonic acid is modified by the enzymes of the ' pathway to form thromboxane Ag. a potent platelet aggregator and vasoconstrictor. In endothelial cells, arachidonic acid forms prostacyclin I 2» a vasodilator and platelet antiaggregator. Both thromboxane A« and prostacyclin I 2 are prostaglandins of the "2" series. However, the enzyme cyclo-oxygenase can also use eicosapentaenoic acid as a substrate. In the platelets, eicosapentaenoic acid is formed into thromboxane A,. Thromboxane A 3 is a weak vasoconstrictor but unlike thromboxane A« » 1t will not aggregate platelets. I * n endothelial cells, prostacylin I 3 , which has vasodilatory and platelet antiaggregating properties similar to prostacyclin I 2 , is formed from eicosapentaenoic acid. Thromboxane A 3 and prostacyclin I« are prostaglandins of the "3" series. If docosahexaenoic acid is formed upon chain elongation and desaturation, or since it is present in fish oils, it also can be used as a substrate for cyclo-oxygenase. This also decreases the level of series u Z n prostaglandin formation. The fact that both u3 and uδ fatty acids can act as substrates for the.prostanoid synthesis pathway led to the theory that dietary manipulation could modify the levels of type 2 and type 3 prostaglandins in the platelets and cell membranes. According to this theory, the availability of u3 fatty acids in the diet would cause a decrease in the level of type 2 prostaglandins in the plasma and 5 membranes through competitive inhibition for the enzymes which normally use uβ fatty acids as substrates. In one experiment on dietary manipulation, Sanders, Vickers and Haines, Clin. Sci. 61:317-324 (1981), investigated the effect on blood lOlipids and hemostasis in healthy young men by supplementing their diet with cod liver oil, an oil rich in u3 fatty acids. These researchers found that the ratio of u3 to uβ fatty acids and resulting products was increased in the platelets and 15 erythrocyte phosphoglycerides by this diet modification. In a series of papers by Dyerberg et al , e.g., Am. J. Clin. Nutr 28:958-966 (1975), Lancet 2:433-435 (1979), and Am. J. Clin. Nutr. 33:2657-2661 20 (1970)', the effects of diet high in u 3 fatty acids on heart disease were studied. The Greenland Eskimos, who have a low meat and high fish oil diet, were the test subjects. Since meat is high in uδ fatty acids while fish oils have significant quantities of u3 25 fatty acids, these studies provided a comparison between high u6 and high u3 diets. The Eskimos with the high u3 fatty acid diets had significantly lower incidence of heart disease than Eskimos who had high uβ fatty acid diets. The latter group were primarily 30 Eskimos who had moved to Denmark and changed their diet to have a substantial proportion of uβ fatty acids. These experiments showed that dietary manipulation could change the susceptibility to heart disease. So e hospitalized patients, particularly critically ill patients, receive total parenteral nutrition. Since most patients receiving parenteral nutritional systems have a high risk of infection, a diet which minimizes the risk of infection would be a substantial benefit to this class of patients. Parenteral nutrition diets include a source of fatty acids since fatty acids are necessary for adequate biochemical functioning. However, standard parenteral diets use fatty acids derived primarily from soybean or safflower oil which as with most plant oils, are high in uβ fatty acids but have little or no u3 fatty acid content. While some uβ fatty acids are essential to good health, somewhere between 2 and 4 percent of the total calorie content is all that is necessary. Conventional parenteral nutrition diets supply 10-15 percent, occasionally as high as 50 percent, of the calorie content as the uβ fatty acids, a clear excess. Lowering uβ fatty acids may lead to an increase in platelet thromboxane A 3 levels. One theory for the decreased heart disease among eskimoes is that the platelets are not as "sticky" if the thromboxane A 2 levels are lowered. Since the production of thromboxane A 3 is normally at the expense of thromboxane A 2 , a diet which lowers the uδ fatty acid levels might lead to a decrease in heart disease. Cook, Wise and Halushka, J. Clin. Invest. 65:227 (1980) investigated the thromboxane A 2 levels in rats challenged with endotoxin. They found endotoxin shock increases thromboxane A 2 levels in the platelets. Rats treated with i idazole (a thromboxane synthetase inhibitor), indomethacin (a fatty acid cyclo-oxygenase inhibitor), or those animals with essential fatty acid deficiency (uδ fatty acid deficiency) had higher survival rates to endotoxin shock than did normal rats. All of the groups of animals with higher survival rates exhibited lower thromboxane A 2 levels. Accordingly, an object of the invention is to provide a method of minimizing the effects of infection and minimizing the effects of subsequent infection in at risk animals, particularly humans, by administering a diet which promotes resistance to infection without interfering with essential bodily processes. Another object of the invention is to provide a dietary supplement which provides sufficient nutrition in animals while reducing the risk of infection. A further object of the invention is to provide a method of treating patients, primarily patients having high risk of infection, with a dietary supplement which provides essential fatty acids while assisting in resistance to infection. These and other objects and features of the invention will be apparent from the following description. SUMMARY OF THE INVENTION The present invention features a method of minimizing the effects of infection and minimizing the effects of subsequent infection in at risk animals. The invention Includes the step of administering a diet rich in u3 fatty adds, preferably by administration of oils rich in u3 fatty acids. Oils rich in u3 fatty acids are selected from a group consisting of fish oils, e.g., herring, anchovy, cod, and menhaden oil, and various unusual plant oils. The oils may be concentrated to provide a high percentage of u3 fatty acids per unit volume. The preferred animals for administration of the diet are humans, e.g., hospitalized patients. The 5 patients may have an infection at the time of administration of the diet or may be members of a class having a high risk of Infection. These high risk patients include those suffering with secondary i munosuppression due to chemotherapy or diabetes lOmellitus, protein-malnourished patients, or patients undergoing abdominal surgery. The infections may be wound infections, empyemas, bacteremias, abscesses, or septlcemias. These infections are caused by a variety of infectious agents including bacteria, 15 viruses, parasites, and fungi. The oils rich 1n u3 fatty acids may be administered orally or intravenously. The Invention also features a dietary supplement having 10 to 20 percent by weight of an 20 oily fraction rich in u3 fatty acids, 1-2 percent by weight of an emulsifier and sterile water. The emulsifier is selected from a group consisting of egg yolk phosphol ipids and soybean phosphol ipids. The dietary supplement may also include 1-3 percent of an 25 osmolality modifier such as glycerin. The oily fraction consists of a mixture of oils rich in u3 fatty acids and oils rich in u6 fatty acids , e.g., oils rich in Hnoleic acid. The oils rich in u3 fatty acids provide 10-90 percent of the total fatty 30 acids. Oils rich in u6 fatty acids include safflower, sunflower, and soybean oils while oils rich in u3 fatty acids include fish oils derived from herring, cod, anchovy and menhaden as well as unusual piant oil s. The invention further features a method of minimizing the effects of infection and minimizing the effects of subsequent infection in at risk patients by administration of a -dietary supplement. This supplement supplies all the essential fatty acids while providing resistance to infection by modification of the substrates for some enzyme processes. The dietary supplement of the Invention is useful in this method. DESCRIPTION The present invention relates to a method of using dietary control to minimize Infection and to minimize the risk of subsequent infection in high risk animals and patients. Mixtures of 1 ipid-containing oils replace the standard fatty acid portion of conventional dietary supplements, e.g., those used in parenteral feedings. By substituting u3 fatty acids for conventional u6 fatty acids, survival to challenge with infection is improved. Conventional dietary supplements have primarily soybean or safflower oil as their lipid or fatty acid source. Soybean oil has approximately 53 percent u6 fatty acids and only 8 percent u3 fatty acids while safflower oil has almost 78 percent u6 fatty acids and substantially no u3 fatty acids. In contrast, fish oils such as menhaden oil have 22 percent or more u3 fatty acids and only 2-5 percent u6 fatty acids. By replacing the predominantly u6 fatty acid-containing oils with u3 fatty acid-conta1ning oils, the levels of type 2 prostaglandins is reduced and the levels of type 3 prostaglandins increased. Since Infectious agents such as endotoxins increase the levels of type 2 prostaglandins, the lowering of type 2 prostaglandins by diet may improve chance of survival after challenge with these infections. For example, patients receiving parenteral dietary nutrition normally have lowered resistance due to immunosuppression. Infection is one of the major causes of complications, including death, i n this type of patient. By dietary modifications, survival and full recovery are promoted. The following non-limiting examples will show the efficacy of the present invention. EXAMPLE 1 This Example illustrates that animals fed a diet in which the primary lipid source are oils rich in u3 fatty acids rather than a diet containing oils rich 1n uβ fatty acids promotes survival when the animals are challenged with endotoxin. The animals were healthy, male Hartley strain guinea pigs from Elm Hill Breeding Laboratories in Chel sford, Mass. The weight of the animals at the initiation of the experiment were 200 to 250 grams. The animals were initially fed standard laboratory guinea pig chow made by Ral ston-Purina Company for one week and then switched to the experimental diets. Table 1 lists the ingredients of the diets used for both groups of guinea pigs. TABLE 1 DIET COMPOSITION: MODIFIED REID-BRIGGS SEMI-PURIFIED GUINEA PIG DIET INGREDIENT AMOUNT PER KILOGRAM (GRAMS) Casein 300 Corn Starch 200 Sucrose 89 Glucose 0 Cellulose 150 011 150 Arginine 3 Salt Mix 90 Vitamin Mix 10 Choi 1ne Chloride 4 Ascorbic Acid 4 1000 gm total The diets fed to the two groups of guinea pigs were identical except the control group received 150 gm of safflower oil while the second group received 145 gm of menhaden with 5 gm of safflower oil added to prevent linoleic acid deficiency. The diets are standard Reid-Briggs guinea pig diets except the oil content is raised so the diet contains 15 percent by weight of lipid as opposed to traditional 7.3 percent. This allows 36 percent of the dietary calories to be 1ipid-derived as compared with the standard 15 percent. Table 2 illustrates the lipid content of safflower oil and menhaden oil. TABLE 2 DIETARY OIL FATTY ACID COMPOSITION (IN PERCENT TOTAL FATTY ACIDS) FATTY ACID SAFFLOWER OIL MENHADEN OIL C14 0 Myrlstic .1 11.6 C16 0 Palmitic 6.5 13 C16 lu7 Palmitoleic 13.3 C18 0 Stearic 2.4 2.1 C18 lu9 Oleic 13.1 6.7 C18 lu7 3.3 C18 2u6 Linolelc 77.7 1.1 C20 4u6 Arachidonic .7 C20 4u3 1.9 C20 5u3 Eicosapentaenoic 17.3 C22 5u6 .4 C22 5u3 2.0 C22 6u3 8.2 C24 lu9 .4 Other .2 18 The animals were kept on these diets for six weeks prior to endotoxin challenge. Each of the groups were subdivided into two groups at 6 weeks and one of the subgroups received 1 cc of a 0.9 percent saline solution while the other half received 10 mg/kg body weight of the drug ibuprofen intra-peritoneally. Ibuprofen is a cyclo-oxygenase inhibitor. One hour after administration of the saline or ibuprofen, the animals all received 0.5 mg/lOOgm body weight of the endotoxin, an approximate LDJ- Q dosage for these animals. The endotoxin, a 1 ipopolysaccharide derived from E. coli, was obtained from Difco Laboratories. A portion of the animals was retained for four days to determine survival against endotoxin while another portion were sacrificed one hour after endotoxin administration for collection of plasma. The sacrificed animals were decapitated and the blood collected in EDTA tubes to which 25 cg/cc ibuprofen had been added. The blood was spun down, the plasma separated and frozen for subsequent fatty acid, thromboxane B 2 , and 6-keto-PGF< α analysis. One problem with this diet rich in u3 fatty acids was that over the six weeks of the experiment, the control group (uδ fatty acid rich diet) guinea pigs gained an average of 304 gms while the guinea pigs on the u3 fatty acids rich diet gained an average of only 113 grams. By Increasing the u6 fatty acids from 2 percent to 4 percent of the total intake, this weight gain differential might be obviated. Table 3 illustrates the survival of the two -groups of guinea pigs at 12, 24, 48, and 72 hours after endotoxin challenge. While both groups show substantially equal survival at 12 hours, from 24 hours on the group fed the diet rich in u3 fatty acids (menhaden oil) showed a threefold increase in survival . TABLE 3 SURVIVAL FROM LD 50 ENDOTOXIN DIET 12 HOURS 24H0URS 48 HOURS 72 HOURS n percent n percent n percent π percent Safflower Oil (n=30) 16 (53) 6 (20) 4 (13) 4 (13) Menhaden Oil (n=30) 20 (67) 18 (60) 15 (50) 14 (47) Clearly, replacing the u6 fatty acids by u3 fatty acids enhances survival to endotoxin shock. Table 4 illustrates the levels of thromboxane in the B 2 plasma of the two groups. Thromboxane B 2 is a stable metabolite of thromboxane A 2 so it was used for the measurement because of the rapid metabol ization of the thromboxane A 2 . While it is evident from Table 4 that ibuprofen and endotoxin challenge clearly affect the thromboxane B 2 level, it is not clear that the diet affects the thromboxane B 2 level. TABLE 4 PLASMA THROMBOXANE B 2 LEVELS DIET BUPROFEN BEFO RE AFTE R Safflower Oil no 172 +_26 45 03 Safflower Oil yes 64^9 78M 3 Menhaden 011 no 292^60 397^25 Menhaden Oil yes 98+28 211 +50 X^ SEM in pg/ l N=6 for all groups Several explanations of these results are possible. One possibility is that survival cannot be correlated to thromboxane A 2 or B 2 levels. Second, the testing for thromboxane B 2 Itself may cause an artifact. Measurements were made by a radioimmunoassay procedure and no studies have been done to differentiate between thromboxane B 2 and thromboxane B 3 , the stable metabolite of thromboxane A 3 . Since there is only a small structural difference between these type 2 and type 3 thro boxanes (one double bond), it is possible that there is significant cross reactivity between the thromboxanes so part of the measured thromooxane B 2 could actually be thromboxane B.,. Thromboxane A 3 should be produced from the u3 fatty acids. Table 5 shows the plasma 6-keto-PGF^ α levels for the various groups. 6-keto-PGF^ n is a stable metabolite of prostacyclin I 2 . TABLE 5 PLASMA 6-KET0-PGF χ α LEYELS ENDOTOXIN DIET IBUPROFEN BEFORE AFTER Safflower Oil no 43.7^11.3 544+179 Safflower Oil yes 58.3^14.0 71.6+10.4 Menhaden Oil no 81.0+10,7 502_+167 Menhaden Oil yes 55.7+_13.5 138.3+39.7 X +_ SEM in pg/ml n = 6 for al1 groups As with the thromboxane B 2 assay, cross reactivity with Δ 17-6 keto -PGF j α, the stable metabolite of prostacyclin I 3 , was not tested. This may account for the lack of a difference in the 6-keto-PGF, α levels among the groups, Δ 17-6 keto - PGF, α is produced from u3 fatty acids. What is evident from this experiment is that the diet modification promoted enhanced survival of the guinea pigs fed the diet rich in u3 fatty acids. The mechanism for enhanced survival is not clear, however. EXAMPLE 2 This Example illustrates one procedure for forming a dietary supplement for patients which will enhance resistance to infection. Patients who may benefit from such a supplement include those wi :h secondary immunosuppression due to diabetes mellitus or chemotherapy. In these latter patients, the total poly orphonuclear leukocyte count is normally less 3 than 1,000/ mm . Another group of patients who could benefit are protein-malnourished patients. In these patients, the serum albumin level in plasma is normally less than 3.2 gm/dl or recent weight loss of greater than 10 percent of original body weight has occurred. The oil emulsion is made as follows. For each liter of emulsion, 100-200 gm of refined and bleached oil rich in u3 fatty acids is mixed with 11 gms of an emulsifier, e.g., egg yolk phosphol ipids USP, 22.5 gms. of an os olality modifier, e.g., glycerin USP, and sterile water USP to bring the volume to a liter. Specifically, the oil is added to a high shear mixer such as a Waring mixer with steel blades operated at 1,600 RPM. The phosphol ipids are added slowly to the oil and mixed at high speed for 6 minutes. Eight hundred milllllters of sterile water is added in a s€eady stream to the phospholipid and oil mixture and emulsified for 20 minutes at 1600 RPM. The attainment of the oil-1n-water emulsion is confirmed by the "drop dispersion test." E u! sification is continued until the coarse oil emulsion disperses freely in water but not in oil. The coarse emulsion 1s then passed through a high speed homogenizer five times until particle size is less than 1 micron. At that time, five more passes through the high speed homogenizer are performed and with each pass, glycerin is added to the emulsion. During the last five passes, additional water is added to make the final emulsion volume up to the one liter batch. Normally, all volumes are multiplied ten-fold and a ten liter batch is mixed at once. Aliquots of the emulsion are set aside for 5measuring particle size which should be between 0.24 and 0.75 microns. The solutions are then passed through a five micron particle filter into sterile and pyrogen free evacuated containers The emulsion is then sterilized at low temperature (105°C.) for 25 lOmlnutes. The solutions are cooled to room temperature and stored in the dark at 9 * C. for one week. Prior to patient administration, the samples are retested for particle size and the presence of bacterial or endo.toxin contamination. If the 15 particle size is greater than 1 micron or the endotoxin concentration is greater than 1 ng, the batch of emulsion 1s discarded. As previously noted, this dietary supplement can be used in patients who may be susceptible to a 20 number of infectious agents. Examples of these infectious agents include E. coli, Pseudomonas, or Klebisiella for the gram negative bacteria, Staphylococcus aureus or albus for the gram positive bacteria, Herpes simplex or zoster for the viruses, 25 and fungi such as Candida. A variety of parasites can also be controlled by this type of supplement. While the method and dietary supplement disclosed herein will not necessarily prevent the onset of infection caused by these agents, it will 3θpromote survival of infected patients or animals. The specific method and dietary supplement set forth herein are purely Illustrative and those skilled in the art may determine other modifications and varlatlons of these procedures. Such other modifications and variations are included within the scope of the following claims. What is claimed is:

Claims: 1. A method of minimizing the effects of infection and minimizing the effects of subsequent infection in at risk animals comprising the step of: administering a diet rich in u3 fatty acids. 52. The method of claim 1 wherein said diet rich in u3 fatty acids comprises administration of oils rich in u3 fatty acids. 3. The method of claim 2 wherein said oils rich in u3 fatty acids are selected from a group 10 consisting of fish oils and plant oils. 4. The method of claim 3 wherein said fish oils are selected from a group consisting of oils derived from herring, anchovy, cod and menhaden. 5. The method of claim 2 wherein said oils rich 15 in u3 fatty acids comprise oils concentrated to provide a high percentage of u3 fatty acids per unit volume. 6. The method of claim 1 wherein said animals comprise humans. 207. The method of claim 6 wherein said humans comprise patients who have an infection at time of administration of said. diet. 8. The method of claim 7 wherein said patients are infected with infections selected from a group 25 consisting of wound infections, empyemas, bactere ias, abscesses, and septicemias. 9. The method of claim 6 wherein said infections are caused by infectious agents selected from a group consisting of bacteria, viruses, parasites, and fungi. 510. The method of claim 6 wherein said humans comprise patients who have a high risk of infection at time of administration of the diet. 11. The method of claim 10 wherein said patients at high risk of infection are selected from a group 0 consisting of patients with secondary immunosuppression due to chemotherapy or diabetes mellitus, protein-malnourished patients, and patients undergoing abdominal surgery. 12. The method of claim 6 wherein said oils rich 5 in u3 fatty acids are administered orally. 13. The method of claim 6 wherein said oils rich in u3 fatty acids are administered intravenously. 14. A dietary supplement comprising: 10-20 percent by weight of an oily fraction 0 rich in u3 fatty acids; 1-2 percent by weight emulsifier; and sterile water. 15. The dietary supplement of claim 14 wherein, said emulsifier is selected from a group consisting 5 of egg yolk phosphol ipids and soybean phosphol ipids. 16. The dietary supplement of claim 15 wherein said dietary supplement further comprises 1-3 percent by weight of an os olality modifier. 17. The dietary supplement of claim 16 wherein said os olality modifier comprises glycerin. 18. The dietary supplement of claim 14 wherein said oily fraction rich in u3 fatty acids comprise a 5 mixture of oils rich in u3 fatty adds and oils rich in uδ fatty acids. 19. The dietary supplement of claim 18 wherein said oils rich in u3 fatty acids comprise 10-90 percent by weight of said oily fraction rich in u3 10 fatty acids. 20. The dietary supplement of claim 18 wherein said oils rich in uδ fatty acid comprise oils rich In 1 inoleic acid. 21. The dietary supplement of claim 18 wherein 15 said oils rich in u6 fatty acid are selected from a group consisting of safflower, sunflower, and soybean oils. 22. The dietary supplement of claim 18 wherein said oils rich in u3 fatty acids comprise fish oils. 2023. The dietary supplement of claim 22 wherein said fish oils are selected from a group consisting of oils derived from herring, anchovy, cod, and menhaden, 24. A method of minimizing the effects of 25 infection and minimizing the effects of subsequent infection in at risk patients by administering a dietary supplement supplying essentially fatty acids, said dietary supplement comprising: 10-20 percent by weight of an oily fraction, said oily fraction containing a substantial proportion of u3 fatty acids; 1-2 percent by weight of an emulsifier; 1-3 percent by weight of an os olality modifier, and steril e water. 25. The method of claim 24 wherein said emulsifier is selected from a group consisting of egg yolks phosphol ipids and soybean phosphol ipids. 26. The method of claim 24 wherein said osmolality modifer comprises glycerin. 27. The method of claim 24 wherein said oily fraction comprises a mixture of oils rich in u3 fatty acids and oils rich in u6 fatty acids. 28. The method of claim 27 wherein said oils rich in u3 fatty acids comprise 10-90 percent of said oily fraction. 29. The method of claim 28 wherein said oils rich in u3 fatty acids are selected from a group consisting of fish oils and plant oils. 30. The method of claim 29 wherein said fish oils are selected from a group consisting of oils derived from herring, anchovy, cod and menhaden.

Inventors: BABAYAN VIGEN K, BISTRIAN BRUCE R, BLACKBURN GEORGE L, MASCIOLI EDWARD A, BABAYAN, VIGEN, K., BISTRIAN, BRUCE, R., BLACKBURN, GEORGE, L., MASCIOLI, EDWARD, A.
Applicants: NEW ENGLAND DEACONESS HOSPITAL
Application year: 1985
Main classification: A61K31
IPC codes: A23L1, A61K31, A61K35, A61K36, A61K38, A61P31, A61P33, A61P37, A61P43