Alleviating oxidative stress disorders with PUFA derivatives
Some aspects of the invention provide for essential fatty acids which are substituted in specific positions to slow down oxidative damage by Reactive Oxygen Species (ROS), and to suppress the rate of consequent formation of reactive products, for the purpose of preventing or reducing the damage associated with oxidative stress associated diseases such as neurological diseases and age-related macular degeneration (AMD).
1. A method of treating a medical condition, comprising:
selecting a subject that has ataxia or a neurodegenerative disease; and
administering an effective amount of an isotopically modified polyunsaturated fatty acid or ester thereof to the subject;
wherein the amount of isotope in the isotopically modified polyunsaturated fatty acid or ester thereof is above the naturally-occurring abundance level, wherein the amount of isotopically modified polyunsaturated fatty acid or ester thereof ingested by or administered to the subject is at least about 5% of the total amount of polyunsaturated fatty acid or ester thereof ingested by or administered to the subject, and wherein the isotopically modified polyunsaturated fatty acid or ester thereof is selected from the group consisting of 11, 11-D2-linoleic acid; 11-D-linoleic acid; 11, 11, 14, 14, D4-linolenic acid; 11,14, D2-linolenic acid; 11, 11, D2-linolenic acid; 11-D-linolenic acid; 14-D-linolenic acid; 14, 14, D2-linolenic acid, and ester thereof.
2. The method of claim 1 ,
wherein the effective amount of the isotopically modified polyunsaturated fatty acid or ester is suitable for human consumption, and
wherein the isotopically modified polyunsaturated fatty acid or ester thereof is capable of retaining its chemical identity when incorporated in a bodily constituent of the subject following ingestion or uptake by the subject, or is capable of conversion into higher homolog of the polyunsaturated fatty acid in the subject.
3. The method of claim 1 , wherein the subject has a neurodegenerative disease.
4. The method of claim 1 , wherein the isotopically modified polyunsaturated fatty acid or ester thereof has an isotopic purity at a modified position of from about 10% to 100%.
5. The method of claim 1 , wherein the subject has a neurodegenerative disease associated with lipid peroxidation.
6. The method of claim 1 , wherein
the subject is administered a sufficient amount of an isotopically modified polyunsaturated fatty acid or ester thereof such that the subject maintains a sufficient concentration of isotopically modified polyunsaturated fatty acid to resist autooxidation.
7. The method of claim 1 , wherein the subject has ataxia.
8. The method of claim 1 , wherein the isotopically modified polyunsaturated fatty acid ester thereof is the ethyl or glyceryl ester of 11,11-D2-linoleic acid; 11-D-linoleic acid; 11-D-linoleic acid; 11,11,14,14-D4-linolenic acid; 11,14-D2-linolenic acid; 11,11-D2-linolenic acid; 11-D-linolenic acid; 14-D-linolenic acid; or 14,14-D2-linolenic acid.
9. The method of claim 1 , wherein the isotopically modified polyunsaturated fatty acid ester thereof is the ethyl ester of 11,11-D2-linoleic acid; 11-D-linoleic acid; 11,11,14,14-D4-linolenic acid; 1,14-D2-linolenic acid; 11,1l-D2-linolenic acid; 11-D-linolenic acid; 14-D-linolenic acid; or 14,14-D2-linolenic acid.
10. The method of claim 1 , wherein the isotopically modified polyunsaturated fatty acid ester thereof is the ethyl ester of 11,11-D2-linoleic acid or 11-D-linoleic acid.
11. The method of claim 1 , wherein the isotopically modified polyunsaturated fatty acid ester thereof is the ethyl ester of 11,11-D2-linoleic acid.
12. The method of claim 1 , wherein the isotopically modified polyunsaturated fatty acid or ester thereof is a ω-6 polyunsaturated fatty acid.
13. The method of claim 1 , wherein the isotopically modified polyunsaturated fatty acid or ester thereof is an ethyl ester.
14. A method of treating a medical condition, comprising
selecting a subject having a neurodegenerative disease associated with lipid peroxidation or an ataxia; and
administering an effective amount of an isotopically modified polyunsaturated fatty acid or ester thereof or mixture thereof to the subject;
wherein the isotopically modified polyunsaturated fatty acid or ester thereof has a structure of formula (2)
wherein:
R is H or C 3 H 7 ,
R 1 is H or alkyl,
each Y is independently H or Deuterium with at least one Y being deuterium,
each X is independently H or Deuterium,
m=1-10,
n=1-5, and
p=1-10.
15. The method of claim 14 , wherein the subject has an ataxia.
16. The method of claim 14 , wherein the subject has a neurodegenerative disease associated with lipid peroxidation.
17. The method of claim 14 , wherein the isotopically modified polyunsaturated fatty acid or ester thereof is a linoleic acid or ester thereof.
18. The method of claim 14 , wherein the isotopically modified polyunsaturated fatty acid or ester thereof is a linolenic acid or ester thereof.
19. The method of claim 14 , wherein the isotopically modified polyunsaturated fatty acid or ester thereof is an arachidonic acid or ester thereof.
20. The method of claim 14 , wherein the isotopically modified polyunsaturated fatty acid or ester thereof is an eicosapentaenoic acid or ester thereof.
21. The method of claim 14 , wherein the isotopically modified polyunsaturated fatty acid or ester thereof is a docosahexaenoic acid or ester thereof.
22. The method of claim 14 , wherein the isotopically modified polyunsaturated fatty acid or ester thereof or mixture thereof is a mixture having two or more selected from the group consisting of linoleic acid or ester thereof, linolenic acid or ester thereof, arachidonic acid or ester thereof, eicosapentaenoic acid or ester thereof, and docosahexaenoic acid or ester thereof.