Compositions and methods for increasing energy metabolism
Compositions and methods useful for inducing an increase in fatty acid oxidation or mitochondrial biogenesis, reducing weight gain, inducing weight loss, or increasing Sirt1, Sirt3, or AMPK activity are provided herein. Such compositions comprise a combination of a PDE 5 inhibitor, such as sildenafil or icariin, and resveratrol, and a branched amino acid such as leucine, or its metabolite.
1. A composition comprising:
(a) a synergistically effective amount of a phosphodiesterase 5 (PDE 5) inhibitor; and
(b) at least 500 mg of leucine and/or at least 200 mg of a leucine metabolite, wherein the PDE 5 inhibitor comprises sildenafil.
2. The composition of claim 1 , wherein the amount of phosphodiesterase 5 (PDE 5) inhibitor is a sub-therapeutic amount.
3. The composition of claim 1 , wherein the composition is formulated as a unit dosage.
4. The composition of claim 3 , wherein the unit dosage comprises a sub-therapeutic amount of component (a) that is between 0.1 and 20 mg of sildenafil.
5. The composition of claim 3 , wherein the unit dosage comprises a sub-therapeutic amount of component (a) that is between 0.1 and 10 mg of sildenafil.
6. The composition of claim 2 , wherein the sub-therapeutic amount of component (a) further comprises between 0.5-50 mg of avanafil, 0.05-10 mg of iodenafil, 0.25-25 mg of mirodenafil, 0.01-1.25 mg of tadalafil, 0.01-1.25 mg of vardenafil, 0.5-50 mg of udenafil, 0.5-50 mg of zaprinst, or 0.05-100 mg of icariin.
7. The composition of claim 1 , wherein the component (b) is free leucine.
8. The composition of claim 1 , wherein the component (b) comprises between 500 to 2000 mg of free leucine.
9. The composition of claim 1 , wherein the component (b) comprises at least 200 mg of a leucine metabolite comprising beta-hydroxymethylbutyrate (HMB).
10. The composition of claim 1 , further comprising an anti-diabetic agent.
11. The composition of claim 1 , further comprising a sub-therapeutic amount of an anti-diabetic agent.
12. The composition of claim 10 , wherein the anti-diabetic agent is a biguanide or thiazoladinedione.
13. The composition of claim 10 , wherein the anti-diabetic agent is metformin or rosiglitazone.
14. The composition of claim 10 , wherein the anti-diabetic agent comprises at least 25 mg of metformin.
15. The composition of claim 1 , further comprising resveratrol.
16. The composition of claim 10 , wherein component (a) comprises between 0.1 and 10 mg of sildenafil, component (b) comprises between 500 and 2000 mg of free leucine, and the anti-diabetic agent comprises at least 250 mg of metformin.
17. The composition of claim 1 , further comprising a pharmaceutically active agent other than the PDE 5 inhibitor and the leucine and/or the leucine metabolite.
18. The composition of claim 1 , wherein the composition further comprises less than 1% by weight of an amino acid selected from the group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine in free amino acid form.
19. The composition of claim 1 , wherein the composition further comprises less than 1% by weight of isoleucine and valine.
20. The composition of claim 1 , wherein the composition is free of isoleucine and valine.
21. The composition of claim 1 , wherein the composition is formulated in tablets or capsules.