AMINO ACID COMPOSITIONS AND METHODS FOR THE TREATMENT OF MUSCLE DISEASES AND DISORDERS

1 . A composition comprising:

a) a L-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 R-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;

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

e) an EAA chosen from:

i) L-histidine or a salt thereof,

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

iii) L-lysine or a salt thereof,

iv) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-lysine,

v) L-phenylalanine or a salt thereof,

vi) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-phenylalanine,

vii) L-threonine or a salt thereof, or

viii) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-threonine.

2 . The composition of claim 1 , wherein one, two, three, or four of methionine (M), tryptophan (W), valine (V), or cysteine (C) is absent, or if present, is present at less than 10 weight (wt.) % of the composition.

3 . The composition of claim 1 , wherein:

a) comprises a combination of L-leucine or a salt thereof and HMB or a salt thereof;

b) comprises a combination of two or three of L-arginine or a salt thereof, ornithine or a salt thereof, or creatine or a salt thereof; and/or

e) comprises a combination of two, three, or four of the EAAs.

4 . The composition of claim 1 , wherein:

f) a wt. % of the R-amino acid entity in the composition is greater than the wt. % of the L-glutamine or a salt thereof;

g) the wt. % of the L-glutamine or a salt thereof in the composition is greater than the wt. % of the L-amino acid entity;

h) the wt. % of the R-amino acid entity in the composition is greater than the wt. % of the L-amino acid entity;

i) the wt. % of the R-amino acid entity in the composition is greater than the wt. % of the EAA, or the combination of two, three, or four of the EAAs in (e);

j) the wt. % of the L-glutamine or a salt thereof in the composition is greater than the wt. % of the EAA or the combination of two, three, or four of the EAAs in (e);

k) the wt. % of the L-amino acid entity in the composition is greater than the wt. % of the EAA or the combination of two, three, or four of the EAAs in (e); or

l) a combination of two, three, four, five, or six of (f)-(k).

5 . The composition of claim 1 , wherein:

m) the ratio of the L-amino acid entity to the R-amino acid entity is at least 1:4, or at least 2:5, and not more than 3:4;

n) the ratio of the L-amino acid entity to the L-glutamine or a salt thereof is at least 1:4, or least 1:3, and not more than 3:4;

o) the ratio of the L-glutamine or a salt thereof to the R amino acid entity is at least 1:2, or least 3:4, and not more than 11:12;

p) the ratio of the EAA in (e), or the combination of two, three, or four of the EAAs in (e), to the L-amino acid entity is at least 1:4, or at least 2:5, and not more than 3:4;

q) the ratio of the EAA in (e), or the combination of two, three, or four of the EAAs in (e), to the L-glutamine or a salt thereof is at least 1:4, or at least 2:5, and not more than 3:4;

r) the ratio of the EAA in (e) to the R-amino acid entity is at least 1:5, or at least 1:3, and not more than 2:3; or

s) a combination of two, three, four, five, or six of (m)-(r).

6 . The composition of claim 1 , wherein the wt. ratio of the L-amino acid entity, the R-amino acid entity, the L-glutamine or a salt thereof, and the NAC or salt thereof is about 1+/−15%:1.5+/−15%:1.33+/−15%:0.15+/−15% or about 1+/−15%:1.5+/−15%:1.33+/−15%:0.3+/−15%.

7 . The composition of claim 1 , further comprising one or both of an isoleucine (I)-amino acid-entity and a valine (V)-amino acid-entity.

8 . The composition of claim 7 , wherein:

t) the wt. % of the L-amino acid-entity in the composition is greater than or equal to the wt. % of the I-amino acid-entity and the V-amino acid-entity in combination;

u) the wt. % of the L-amino acid-entity, the I-amino acid-entity, and the V-amino acid-entity in combination in the composition is greater than or equal to the wt. % of the L-glutamine or a salt thereof;

v) the wt. % of the L-amino acid-entity, the I-amino acid-entity, and the V-amino acid-entity in combination in the composition is greater than or equal to the wt. % of the R-amino acid entity;

w) the wt. % of the R-amino acid entity and the L-glutamine or a salt thereof in the composition is greater than the wt. % of the L-amino acid-entity, the I-amino acid-entity, and the V-amino acid-entity in combination;

x) the wt. % of the L-amino acid-entity, the I-amino acid-entity, and the V-amino acid-entity in combination is greater than the EAA in (e), or the combination of two, three, or four of the EAAs in (e), in the composition;

y) the wt. % of the I-amino acid-entity in combination with the L-amino acid entity or the V-amino acid-entity is greater than the EAA in (e), or the combination of two, three, or four of the EAAs in (e), in the composition;

z) the wt. % of the V-amino acid entity is greater than the EAA in (e), or the combination of two, three, or four of the EAAs in (e), in the composition; or

aa) a combination of two, three, four, five, six, or seven of (t)-(z).

9 . The composition of claim 7 , wherein:

bb) the ratio of the L-amino acid entity to the I-amino acid entity is at least 3:2, or at least 7:4, and not more than 5:2 or not more than 3:1;

cc) the ratio of L-amino acid entity to V-amino acid entity is at least 3:2, or at least 7:4, and not more than 5:2 or not more than 3:1;

dd) the ratio of the L-amino acid entity to the R-amino acid entity is greater than 1:3, greater than 1:2, and less than 3:4;

ee) the ratio of the L-amino acid entity to the L-glutamine or a salt thereof is greater than 1:4, greater than 3:8, and less than 5:6, or less than 6:7;

ff) the ratio of the EAA in (e), or the combination of two, three, or four of the EAAs in (e), to the L-amino acid is greater than 1:4, greater than 3:8, and less than 3:4, or less than 5:6; or

gg) a combination of two, three, four, or five of (bb)-(ff).

10 . The composition of claim 7 , wherein the wt. ratio of the L-amino acid entity, the I-amino acid entity, the V-amino acid entity, the R-amino acid entity, the L-glutamine or salt thereof, and the NAC or salt thereof is about 1+/−15%:0.5+/−15%:0.5+/−15%:1.5+/−15%:1.33+/−15%:0.15+/−15% or about 1+/−15%:0.5+/−15%:0.5+/−15%:1.5+/−15%:1.33+/−15%:0.3+/−15%.

11 . The composition of claim 1 , wherein at least one of (a)-(e) is a free amino acid.

12 . The composition of claim 1 , wherein at least one of (a)-(e) is in a salt form.

13 . The composition of claim 7 , wherein the composition comprises:

a) L-leucine or a salt thereof;

b) L-arginine or a salt thereof;

c) L-glutamine or a salt thereof;

d) NAC or a salt thereof;

e) L-histidine or a salt thereof, L-lysine or a salt thereof, L-phenylalanine or a salt thereof, and L-threonine or a salt thereof;

f) L-isoleucine or a salt thereof; and

g) L-valine or a salt thereof.

14 . The composition of claim 1 , wherein the composition is capable of one, two, three, four, or all of:

a) activating mTORC1;

b) one or both of activating protein synthesis or inhibiting protein catabolism;

c) improving insulin sensitivity or glucose tolerance;

d) reducing inflammation; or e) improving or increasing myogenesis.

15 . A composition comprising:

a) a L-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 R-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;

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

e) an EAA chosen from:

i) L-histidine or a salt thereof,

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

iii) L-lysine or a salt thereof,

iv) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-lysine,

v) L-phenylalanine or a salt thereof,

vi) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-phenylalanine,

vii) L-threonine or a salt thereof, or

viii) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-threonine,

wherein one or both of the R-amino acid entity and the L-glutamine or a salt thereof are present at a higher amount (wt. %) than the L-amino acid entity.

16 . The composition of claim 15 , wherein:

a) comprises a combination of L-leucine or a salt thereof and HMB or a salt thereof;

b) comprises a combination of two or three of L-arginine or a salt thereof, ornithine or a salt thereof, or creatine or a salt thereof; and/or

e) comprises a combination of two, three, or four of the EAAs.

17 . The composition of claim 15 , further comprising one or both of an I-amino acid-entity and a V-amino acid-entity.

18 . A composition comprising:

a) a L-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 R-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;

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

e) an EAA chosen from:

i) L-histidine or a salt thereof,

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

iii) L-lysine or a salt thereof,

iv) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-lysine,

v) L-phenylalanine or a salt thereof,

vi) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-phenylalanine,

vii) L-threonine or a salt thereof, or

viii) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-threonine,

wherein one or both of the R-amino acid entity and the L-glutamine or a salt thereof are present at a higher amount (wt. %) than the EAA of (e).

19 . The composition of claim 18 , wherein:

a) comprises a combination of L-leucine or a salt thereof and HMB or a salt thereof;

b) comprises a combination of two or three of L-arginine or a salt thereof, ornithine or a salt thereof, or creatine or a salt thereof; and/or

e) comprises a combination of two, three, or four of the EAAs.

20 . The composition of claim 18 , further comprising one or both of an I-amino acid-entity and a V-amino acid-entity.