AMINO ACID COMPOSITIONS AND METHODS FOR THE TREATMENT OF LIVER DISEASES

1 .- 25 . (canceled)

26 . A method for improving mitochondrial function in a subject, wherein the method comprises administering to the subject an effective amount of a composition comprising:

(a) a leucine amino acid entity chosen from:

(i) L-leucine or a salt thereof,

(ii) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-leucine, or

(iii) β-hydroxy-β-methylbutyrate (HMB) or a salt thereof;

(b) an arginine amino acid entity chosen from:

(i) L-arginine or a salt thereof,

(ii) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-arginine,

(iii) ornithine or a salt thereof,

(iv) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising ornithine,

(v) creatine or a salt thereof, or

(vi) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising creatine;

(c) L-glutamine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine; and

(d) N-acetylcysteine (NAC) or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising NAC,

wherein when the composition is in powder form at least 50 wt. % of the total wt. of the composition is one or more amino acid entities in free form, and

wherein the total wt. % of (a)-(d) is greater than the total wt. % of other amino acid entities in the composition.

27 . The method of claim 1 , wherein the subject has non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH).

28 . The method of claim 1 , wherein the composition further comprises L-isoleucine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-isoleucine.

29 . The method of claim 1 , wherein the composition further comprises L-valine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-valine.

30 . The method of claim 1 , wherein the composition further comprises both of:

(e) L-isoleucine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-isoleucine; and

(f) L-valine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-valine.

31 . The method of claim 1 , wherein one or both of the arginine amino acid entity and the L-glutamine or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine are present at a higher amount (wt. %) than the leucine amino acid entity.

32 . The method of claim 1 , wherein the composition further comprises a serine amino acid entity chosen from L-serine or glycine.

33 . The method of claim 1 , wherein:

(1) the wt. % of the (c) in the composition is greater than the wt. % of the arginine amino acid entity of (b);

(2) the wt. % of the (c) in the composition is greater than or equal to the wt. % of the leucine amino acid entity of (a);

(3) the wt. % of the arginine amino acid entity of (b) in the composition is greater than the wt. % of the leucine amino acid entity of (a); or

(4) a combination of two or three of (1)-(3).

34 . The method of claim 1 , wherein (a)-(d) are each a free amino acid or a salt thereof, and wherein the composition further comprises L-isoleucine or a salt thereof and L-valine or a salt thereof.

35 . The method of claim 34 , wherein a ratio of the L-leucine or a salt thereof of (a), the L-isoleucine or a salt thereof, the L-valine or a salt thereof, the L-arginine or a salt thereof of (b), the L-glutamine or a salt thereof of (c), and the NAC or a salt thereof of (d) is, respectively, 1+/−15%:0.5+/−15%:0.5+/−15%:1.5+/−15%:2+/−15%:0.15+/−15% or 1+/−15%:0.5+/−15%:0.5+/−15%:1.5+/−15%:2+/−15%:0.3+/−15%.

36 . The method of claim 34 , wherein the composition further comprises a L-serine, and wherein a ratio of the L-leucine or a salt thereof of (a), the L-isoleucine or a salt thereof, the L-valine or a salt thereof, the L-arginine or a salt thereof of (b), the L-glutamine or a salt thereof of (c), the NAC or a salt thereof of (d), and the L-serine is, respectively, 12+/−15%:6+/−15%:3+/−15%:9+/−15%:12+/−15%:2.7+/−15%:18+/−15%.

37 . The method of claim 1 , wherein methionine, tryptophan, and cysteine are present at less than 2 wt. % of the composition when the composition is in powder form.

38 . The method of claim 1 , wherein methionine, tryptophan, or cysteine are absent in the composition.

39 . The method of claim 1 , wherein:

(1) the ratio of the leucine amino acid entity of (a) to the arginine amino acid entity of (b) is at least 1:4, and not more than 3:4;

(2) the ratio of the leucine amino acid entity of (a) to the L-glutamine or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine of (c) is at least 1:4, and not more than 3:4; or

(3) the ratio of the arginine amino acid entity of (b) to the L-glutamine or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine of (c) is at least 1:4, and not more than 6:7.

40 . The method of claim 1 , wherein the ratio of: (a) the leucine amino acid entity, (b) the arginine amino acid entity, (c) the L-glutamine or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine, and (d) the N-acetylcysteine (NAC) or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising NAC is: 1+/−15%:1.5+/−15%:2+/−15%:0.15+/−15%; 1+/−15%:1.5+/−15%:2+/−15%:0.3+/−15%; 1+/−15%:1.81+/−15%:2+/−15%:0.15+/−15%; or 1+/−15%:0.75+/−15%:1+/−15%:0.225+/−15%.

41 . A method for improving mitochondrial function in a subject, wherein the method comprises administering to the subject an effective amount of a pharmaceutical composition consisting essentially of:

(a) L-leucine or a salt thereof;

(b) L-arginine or a salt thereof;

(c) L-glutamine or a salt thereof,

(d) N-acetylcysteine (NAC) or a salt thereof,

(e) L-isoleucine or a salt thereof,

(f) L-valine or a salt thereof, and

(g) one or more pharmaceutically acceptable excipients.

42 . A method for improving mitochondrial function in a subject, wherein the method comprises administering to the subject an effective amount of a composition comprising:

(a) L-leucine or a salt thereof,

(b) L-arginine or a salt thereof,

(c) L-glutamine or a salt thereof,

(d) N-acetylcysteine (NAC) or a salt thereof,

(e) L-isoleucine or a salt thereof, and

(f) L-valine or a salt thereof.