Compositions and methods for increasing energy metabolism

Abstract

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 .- 47 . (canceled) 
     
     
         48 . A composition effective for enhancing energy metabolism comprising:
 a) an 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 icariin.   
     
     
         49 . The composition of  claim 48 , wherein the amount of phosphodiesterase 5 (PDE 5) inhibitor is a sub-therapeutic amount. 
     
     
         50 . The composition of  claim 48 , wherein the composition is formulated as a unit dosage. 
     
     
         51 . The composition of  claim 50 , wherein the unit dosage comprises a sub-therapeutic amount of component (a) that is between 0.05 and 100 mg of icariin. 
     
     
         52 . The composition of  claim 49 , 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, or 0.5-50 mg of zaprinst. 
     
     
         53 . The composition of  claim 48 , wherein the component (b) is free leucine. 
     
     
         54 . The composition of  claim 48 , wherein the component (b) comprises between 500 to 2000 mg of free leucine. 
     
     
         55 . The composition of  claim 48 , wherein the component (b) comprises at least 200 mg of a leucine metabolite comprising beta-hydroxymethylbutyrate (HMB). 
     
     
         56 . The composition of  claim 48 , further comprising an anti-diabetic agent. 
     
     
         57 . The composition of  claim 48 , further comprising a sub-therapeutic amount of an anti-diabetic agent. 
     
     
         58 . The composition of  claim 56 , wherein the anti-diabetic agent is a biguanide or thiazoladinedione. 
     
     
         59 . The composition of  claim 56 , wherein the anti-diabetic agent is metformin or rosiglitazone. 
     
     
         60 . The composition of  claim 56 , wherein the anti-diabetic agent comprises at least 25 mg of metformin. 
     
     
         61 . The composition of  claim 48 , further comprising resveratrol. 
     
     
         62 . The composition of  claim 59 , wherein component (a) comprises between 0.05 and 100 mg of icariin, component (b) comprises between 500 and 2000 mg of free leucine, and the anti-diabetic agent comprises at least 250 mg of metformin. 
     
     
         63 . The composition of  claim 48 , further comprising a pharmaceutically active agent other than the PDE 5 inhibitor. 
     
     
         64 . The composition of  claim 48 , wherein the composition comprises less than 1% 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. 
     
     
         65 . The composition of  claim 48 , wherein the composition comprises less than 1% of isoleucine and valine. 
     
     
         66 . The composition of  claim 48 , wherein the composition is free of isoleucine and valine. 
     
     
         67 . The composition of  claim 48 , wherein the composition is formulated in tablets or capsules.