Disorders implicating PUFA oxidation
Some aspects of the invention provide for a method of treating hepatic disorders, lipidemias and cardiac-related risk factors using polyunsaturated fatty acids which are modified in certain positions to attenuate oxidative damage by Reactive Oxygen Species (ROS) and/or suppress the rate of formation of reactive products and toxic compounds.
1. A method of treating or inhibiting the progression of a hepatic disorder, comprising:
administering an effective amount of a polyunsaturated substance to a patient having alcoholic fatty liver disease, non-alcoholic fatty liver disease, steatohepatitis, or cirrhosis, and in need of treatment, wherein the polyunsaturated substance comprises a polyunsaturated fatty acid or fatty acid ester deuterated at one or more bis-allylic positions; wherein the amount of deuterated polyunsaturated fatty acid or fatty acid ester administered to or ingested by the patient is in the range of about 5% to about 75% of the total amount of polyunsaturated fatty acid or fatty acid ester administered to or ingested by the patient, wherein the polyunsaturated fatty acid or fatty acid ester is incorporated into the patient's body following administration in a concentration sufficient to reduce or prevent autoxidation and cancel toxicity of undeuterated fatty acid or fatty acid ester in the patient's body.
2. The method of claim 1 , wherein at least one deuterium atom in the deuterated polyunsaturated fatty acid or fatty acid ester is present at a level greater than 0.02%.
3. The method of claim 2 , wherein over the treatment period the deuterated polyunsaturated fatty acid or fatty acid ester comprises between about 10% and 50% of the total amount of fatty acids or fatty acid esters in the patient's body.
4. The method of claim 2 , wherein over the treatment period the deuterated polyunsaturated fatty acid or fatty acid ester comprises between about 10% and 30% of the total amount of fatty acids or fatty acid esters in the patient's body.
5. The method of claim 2 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is an omega-3 fatty acid or fatty acid ester, or an omega-6 fatty acid or fatty acid ester.
6. The method of claim 5 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is selected from the group consisting of 11,11-D2-linolenic acid, 14,14-D2-linolenic acid, 11,11,14,14-D4-linolenic acid, 11,11-D2-linoleic acid, 11-D-linolenic acid, 14-D-linolenic acid, 11,14-D2-linolenic acid, and 11-D-linoleic acid.
7. The method of claim 5 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is further deuterated at least one saturated methylene group that is adjacent to a second saturated methylene group.
8. The method of claim 1 , wherein the deuterated or undeuterated polyunsaturated fatty acid ester is a triglyceride, diglyceride, or monoglyceride.
9. The method of claim 1 further comprising co-administering an antioxidant.
10. The method of claim 9 , wherein the antioxidant is Coenzyme Q, idebenone, mitoquinone, mitoquinol, vitamin C, or vitamin E.
11. The method of claim 1 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is arachidonic acid or an ester thereof.
12. The method of claim 1 , wherein the deuterated fatty acid or fatty acid ester is eicosapentaenoic acid or an ester thereof.
13. The method of claim 1 , wherein the deuterated fatty acid or fatty acid ester is docosahexaenoic acid or an ester thereof.
14. The method of claim 1 , wherein the deuterated fatty acid or fatty acid ester is a linoleic acid or an ester thereof or linolenic acid or an ester thereof.
15. The method of claim 1 , wherein the deuterated fatty acid or fatty acid ester is an ethyl ester.
16. The method of claim 1 , wherein the amount of deuterated polyunsaturated fatty acid or fatty acid ester administered to or ingested by the patient is in the range of about 0.1 mg/kg to 100 mg/kg per day.
17. The method of claim 1 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is 11,11-D2-linoleic acid or ethyl ester thereof.
18. The method of claim 1 , wherein the deuterated polyunsaturated fatty acid or fatty acid ester is 11,11,14,14-D4-linolenic acid or ethyl ester thereof.