METHODS OF INCREASING EPA BLOOD LEVELS
In various embodiments, the present invention provides methods of treating and/or preventing cardiovascular-related disease and, in particular, a method of blood lipid therapy comprising administering to a subject in need thereof a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof.
1 . A method of increasing a concentration of EPA in plasma or RBCs of a subject having baseline fasting triglycerides of at least about 500 mg/dl, the method comprising administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of EPA per day, wherein upon administering the composition to the subject daily for a period of 12 weeks, the subject exhibits an increase in the concentration of EPA in plasma and/or RBCs of at least 100% compared to a control subject who is not administered EPA, wherein the control subject also has baseline fasting triglycerides of at least about 500 mg/dl.
2 . The method of claim 1 wherein the increase is at least 200%, at least about 400%, or at least about 600%.
3 . The method of claim 1 , wherein the subject exhibits no increase, no significant increase in, or a decrease in a concentration of DHA in plasma and/or RBCs.
4 . The method of claim 1 , wherein the subject is administered about 2 g/day or about 4 g/day of EPA.
5 . The method of claim 1 , wherein the subject further exhibits no increase, no substantial increase, or a reduction in plasma and/or RBC levels of DHA compared to the control subject.
6 . A method of reducing a ratio of arachidonic acid to EPA (AA/EPA) in plasma or RBCs of a subject having baseline fasting triglycerides of at least about 500 mg/dl, the method comprising administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of EPA per day, wherein upon administering the composition to the subject daily for a period of 12 weeks, the subject exhibits a decrease in AA/EPA in plasma and/or RBCs of at least 50% compared to a control subject who is not administered EPA, wherein the control subject also has baseline fasting triglycerides of at least about 500 mg/dl.
7 . The method of claim 6 , wherein the decrease in AA/EPA in plasma and/or RBCs is at least 70% or at least 75%.
8 . The method of claim 6 , wherein the decrease includes a decrease in AA/EPA in plasma of at least 75% or at least 90%.
9 . The method of claim 6 , wherein the decrease includes a decrease in AA/EPA in RBCs of at least 80%, at least 90%, or at least 95%
10 . The method of claim 6 , wherein the subject is administered about 2 g/day or about 4 g/day of EPA.
11 . The method of claim 6 , wherein the subject further exhibits no increase, no substantial increase, or a reduction in plasma and/or RBC levels of DHA compared to the control subject.
12 . A method of reducing a ratio of omega-3 fatty acids to omega-6 fatty acids (n-3/n-6) in plasma or RBCs of a subject having baseline fasting triglycerides of about 200 mg/dl to about 500 mg/dl and on stable statin therapy, the method comprising administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of EPA per day, wherein upon administering the composition to the subject daily for a period of 12 weeks, the subject exhibits a decrease in n-3/n-6 in plasma and/or RBCs of at least 50% compared to a control subject who is not administered EPA, wherein the control subject also has baseline fasting triglycerides of at least about 500 mg/dl.
13 . The method of claim 12 , wherein the decrease in n-3/n-6 in plasma and/or RBCs is at least 60% or at least 100%.
14 . The method of claim 12 , wherein the decrease includes a decrease in n-3/n-6 in plasma of at least 60%, at least 100%, or at least 140%.
15 . The method of claim 12 , wherein the decrease includes a decrease in n-3/n-6 in RBCs of at least 60%, at least 80%, or at least 100%.
16 . The method of claim 12 , wherein the omega-3 fatty acids include one or more of: α-linolenic acid, stearidonic acid, eicosatrienoic acid, ω-3 arachidonic acid, eicosapentaenoic acid, ω-3 docosapentaenoic acid and docosahecaenoic acid.
17 . The method of claim 12 , wherein the omega-6 fatty acids include one or more of: linoleic acid, γ-linolenic acid, eicosadienoic acid, dihomo-γ-linolenic acid, ω-6 arachidonic acid, adrenic acid, and ω-6 docosapentaenoic acid.
18 . The method of claim 12 , wherein the subject is administered about 2 g/day or about 4 g/day of EPA.
19 . The method of claim 12 , wherein the subject further exhibits no increase, no substantial increase, or a reduction in plasma and/or RBC levels of DHA compared to the control subject.
20 . A method of increasing a ratio of omega-3 fatty acids to total fatty acids in plasma or RBCs of a subject having baseline fasting triglycerides of at least about 500 mg/dl, the method comprising administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of EPA per day, wherein upon administering the composition to the subject daily for a period of 12 weeks, the subject exhibits an increase in the ratio of omega-3 fatty acids to total fatty acids in plasma and/or RBCs of at least 20% compared to a control subject who is not administered EPA, wherein the control subject also has baseline fasting triglycerides of at least about 500 mg/dl.
21 . The method of claim 20 , wherein the increase is at least about 50%, at least about 60%, or at least about 130%.
22 . The method of claim 20 , wherein the increase includes an increase in the ratio in plasma of at least 60% or at least about 130%.
23 . The method of claim 20 , wherein the increase includes an increase in the ratio in RBCs of at least 20% or at least about 50%.
24 . The method of claim 20 , wherein the omega-3 fatty acids include one or more of: α-linolenic acid, stearidonic acid, eicosatrienoic acid, ω-3 arachidonic acid, eicosapentaenoic acid, ω-3 docosapentaenoic acid and docosahecaenoic acid.
25 . The method of claim 20 , wherein the total fatty acids include one or more of:
α-linolenic acid, stearidonic acid, eicosatrienoic acid, ω-3 arachidonic acid, eicosapentaenoic acid, ω-3 docosapentaenoic acid, docosahecaenoic acid, linoleic acid, γ-linolenic acid, eicosadienoic acid, dihomo-γ-linolenic acid, ω-6 arachidonic acid, adrenic acid, ω-6 docosapentaenoic acid, myristoleic acid, palmitoleic acid, cis-vaccenic acid, oleic acid, gondoic/gadoleic acid, erucic acid, nervonic acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid and lignoceric acid.
26 . The method of claim 20 , wherein the subject is administered about 2 g/day or about 4 g/day of EPA.
27 . The method of claim 20 , wherein the subject further exhibits no increase, no substantial increase, or a reduction in plasma and/or RBC levels of DHA compared to the control subject.
28 . A method of decreasing a ratio of omega-6 fatty acids to total fatty acids in plasma or RBCs of a subject having baseline fasting triglycerides of at least about 500 mg/dl, the method comprising administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of EPA per day, wherein upon administering the composition to the subject daily for a period of 12 weeks, the subject exhibits a decrease in the ratio of omega-6 fatty acids to total fatty acids in plasma and/or RBCs of at least 5% compared to a control subject on stable statin therapy without EPA, wherein the control subject also has baseline fasting triglycerides of about 200 mg/dl to about 500 mg/dl.
29 . The method of claim 28 , wherein the decrease is at least about 10%, at least about 13%, or at least about 17%.
30 . The method of claim 28 , wherein the decrease includes a decrease in the ratio in RBCs of at least 13% or at least about 17%.
31 . The method of claim 28 , wherein the omega-6 fatty acids include one or more of: linoleic acid, γ-linolenic acid, eicosadienoic acid, dihomo-γ-linolenic acid, ω-6 arachidonic acid, adrenic acid, and ω-6 docosapentaenoic acid.
32 . The method of claim 28 , wherein the total fatty acids include one or more of:
α-linolenic acid, stearidonic acid, eicosatrienoic acid, ω-3 arachidonic acid, eicosapentaenoic acid, ω-3 docosapentaenoic acid, docosahecaenoic acid, linoleic acid, γ-linolenic acid, eicosadienoic acid, dihomo-γ-linolenic acid, ω-6 arachidonic acid, adrenic acid, ω-6 docosapentaenoic acid, myristoleic acid, palmitoleic acid, cis-vaccenic acid, oleic acid, gondoic/gadoleic acid, erucic acid, nervonic acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid and lignoceric acid.
33 . The method of claim 28 , wherein the subject is administered about 2 g/day or about 4 g/day of EPA.
34 . The method of claim 28 , wherein the subject further exhibits no increase, no substantial increase, or a reduction in plasma and/or RBC levels of DHA compared to the control subject.