Dietary control of arachidonic acid metabolism

Abstract

Compositions for the treatment of symptoms of inflammatory disorders may include gamma-linolenic acid or dihomogammalinolenic acid, an inhibitor of Δ 5 desaturase, and optionally stearidonic acid or ω-3 arachidonic acid. Preferred formulations may be in the form of a good tasting,.preferably milk or fruit based drink, or a dried powder. Compositions reduce inflammation and inhibit increase in serum arachidonic acid associated with gamma-linolenic acid.

1 . A method of treating an inflammatory disorder, or a disorder having an inflammatory component, in a mammalian subject in need of such treatment by administering to said subject an effective amount of a composition in unit dosage form for delivery of a daily dose of said composition, said composition consisting essentially of:
 (i) an effective amount of y-linolenic acid (GLA) for increasing dihomogammalinolenic acid (DGLA) levels in the inflammatory cells of said mammalian subject, thereby inhibiting the metabolism of arachidonic acid;   (ii) an effective amount of a Δ 5  desaturase inhibitor for inhibiting accumulation of arachidonic acid in the serum of said mammalian subject; and, optionally,   (iii) an effective amount of a competitive inhibitor of arachidonic acid metabolism.   
     
     
         2 . The method of  claim 1 , wherein the mammalian subject is a human subject. 
     
     
         3 . The method of  claim 1 , wherein said disorder is at least one of asthma, allergic rhinitis, allergic rhinoconjunctivitis, psoriasis, acute myocardial infarction, glomerulonephritis, Crohn's disease, inflammatory bowel disease, arthritis, breast cancer, colon cancer, prostate cancer, an autoimmune disease, systemic Lupus erythematosus, schizophrenia, depression, IgA nephropathy, sepsis, toxic shock, organ failure, organ transplant, coronary angioplasty, risk for Alzheimer's disease, cystic fibrosis, atherosclerosis, menstrual discomfort, cyclic breast pain, premature labor, gout, venous leg ulcers, coronic urticaria, primary dysmenorrhea, endometriosis, or Lyme disease. 
     
     
         4 . The method of  claim 1 , wherein said GLA is present in an amount from about 1 gram to about 10 grams. 
     
     
         5 . The method of  claim 4 , wherein said GLA is present in an amount from about 1.5 grams to about 3 grams. 
     
     
         6 . The method of  claim 1 , wherein the Δ 5  desaturase inhibitor is eicospentaenoic acid (EPA), sesamin, episesamin, sesaminol, sesamolin, curcumin, α-linolinic acid, heneicosapentaenoic acid, docosahexaenoic acid, alkyl gallate, propyl gallate, or p-isopentoxyaniline. 
     
     
         7 . The method of  claim 1 , wherein said 4 5  desaturase inhibitor is EPA. 
     
     
         8 . The method of  claim 7 , wherein said EPA is present in an amount from about 0.1 gram to about 10 grams, from about 0.25 gram to about 5 grams, or from about 0.5 gram to about 3 grams. 
     
     
         9 - 10 . (canceled) 
     
     
         11 . The method of  claim 7 , wherein the ratio of GLA to EPA is from 1:1 to 2:1. 
     
     
         12 . The method of  claim 11 , wherein said EPA is present in an amount from about 0.1 gram to about 10 grams, about 0.25 gram to about 5 grams, or about 0.5 gram to about 3 grams. 
     
     
         13 - 14 . (canceled) 
     
     
         15 . The method of  claim 11 , wherein said EPA is present in an amount of about 0.1 gram, about 0.25 gram, or about 0.5 gram. 
     
     
         16 - 17 . (canceled) 
     
     
         18 . The method of  claim 7 , wherein said composition comprises a 2:1 ratio of GLA:EPA. 
     
     
         19 . The method of  claim 1 , wherein said composition comprises stearidonic acid. 
     
     
         20 . The method of  claim 19 , wherein stearidonic acid is present in an amount from about 0.1 gram to about 15 grams. 
     
     
         21 . The method of  claim 1 , wherein said Δ 5  desaturase inhibitor is a free fatty acid, a fatty acyl ester, a diglyceride, a triglyceride, an ethyl ester, a phospholipid, a steryl ester, a sphingolipid, or a combination of the foregoing. 
     
     
         22 . The method of  claim 1 , wherein said composition comprises ω-3 arachidonic acid. 
     
     
         23 . The method of  claim 1 , wherein said composition is an emulsion wherein said Δ 5  desaturase inhibitor is EPA, which is present in an amount from about 0.1 gram to about 10 grams, and wherein said composition further includes an emulsifying agent, and at least one flavoring agent, sweetening agent, coloring agent or preservative. 
     
     
         24 . The method of  claim 23 , wherein said EPA is present in an amount from about 0.25 gram to about 5 grams or from about 0.5 grams to about 3 grams. 
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 1 , wherein the composition is a flavored drink, a powder, a tablet or a capsule. 
     
     
         27 - 28 . (canceled)