Compositions, methods and kits for reducing lipid levels
Compositions, methods, and kits useful for treating hyperlipidemic conditions are provided herein. Such compositions can contain synergizing amounts of nicotinic acid, nicotinamide riboside and/or nicotinic acid metabolites in combination with leucine and/or a leucine metabolite, with or without resveratrol.
1. A method of lowering total cholesterol level or total lipid content in a subject in need thereof, the method comprising administering to the subject a dose of a one or two part composition comprising:
a) at least 250 mg of leucine and/or at least 25 mg of one or more leucine metabolites, wherein the leucine metabolite is selected from the group consisting of keto-isocaproic acid (KIC), alpha-hydroxy-isocaproic acid, and hydroxymethylbutyrate (HMB); and
b) at least 1 mg of nicotinic acid and/or nicotinamide riboside and/or one or more nicotinic acid metabolites, wherein the nicotinic acid metabolite is selected from the group consisting of nicotinyl CoA, nicotinuric acid, nicotinate mononucleotide, nicotinate adenine dinuecleotide, and nicotinamide adenine dinucleotide,
wherein each of (a) and (b) are free of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, lysine, methionine, phenylalanine, proline, serine,threonine, tryptophan, valine, isoleucine and tyrosine, and
wherein (a) and (b) are administered either simultaneously or in close temporal proximity.
2. The method of claim 1 , wherein the composition is substantially free of nicotinamide.
3. The method of claim 1 , wherein the component (a) in the composition is leucine and the component (b) in the composition is nicotinic acid.
4. The method of claim 1 , wherein the amount of leucine and/or one or more leucine metabolites in the composition is less than 1300 mg.
5. The method of claim 1 , wherein the amount of nicotinic acid and/or nicotinamide riboside and/or one or more nicotinic acid metabolites in the composition is less than 250 mg.
6. The method of claim 1 , wherein the amount of nicotinic acid and/or nicotinamide riboside and/or one or more nicotinic acid metabolites in the composition is between 1-100 mg.
7. The method of claim 1 , wherein the composition further comprises resveratrol.
8. The method of claim 1 , wherein a molar ratio of component (a) to (b) in the composition is greater than 5.
9. The method of claim 1 , wherein the composition is a tablet, a capsule, or a pill.
10. The method of claim 1 , wherein the composition further comprising one or more therapeutic agents selected from the group consisting of HMG-CoA inhibitor, fibrate, bile acid sequestrant, ezetimibe, lomitapide, phytosterols, CETP antagonist, orlistat, and any combination thereof.
11. The method of claim 1 , wherein the dose is a unit dose.
12. A method of reducing atherosclerotic plaque size in a subject in need thereof, comprising administering a one or two part composition comprising:
a) at least 250 mg of leucine and/or at least 25 mg, of one or more leucine metabolites, wherein the leucine metabolite is selected from the group consisting of keto-isocaproic acid (KIC), alpha-hydroxy-isocaproic acid, and hydroxymethylbutyrate (HMB); and
b) at least 1 mg of nicotinic acid and/or nicotinamide riboside and/or one or more nicotinic acid metabolites, wherein the nicotinic acid metabolite is selected from the group consisting of nicotinyl CoA, nicotinuric acid, nicotinate mononucleotide, nicotinate adenine dinucleotide, and nicotinamide adenine dinucleotide,
wherein each of (a) and (b) are free of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, valine, isoleucine and tyrosine, and
wherein (a) and (b) are administered either simultaneously or in close temproal proximity.
13. The method of claim 12 , wherein the amount of leucine and/or one or more leucine metabolites is less than 1300 mg.
14. The method of claim 12 , wherein the amount of nicotinic acid and/or nicotinamide riboside and/or nicotinic acid metabolites is less than 250 mg.
15. The method of claim 12 , wherein the amount of nicotinic acid and/or nicotinamide riboside and/or nicotinic acid metabolites is between 1-100 mg.
16. The method of claim 12 , wherein the amount of nicotinic acid and/or nicotinamide riboside and/or nicotinic acid metabolites is less than 25 mg.
17. The method of claim 12 , wherein the composition is administered to the subject for at least 1 year.
18. The method of claim 12 , wherein the dose is a unit dose.
19. A method of reducing a side effect of nicotinic acid and/or nicotinamide riboside and/or one or more nicotinic acid metabolites wherein the side effect is characterized by an increase in cutaneous vasodilation in a subject administered with nicotinic acid and/or nicotinamide riboside and/or the one or more nicotinic acid metabolites, comprising administering a one or two part composition comprising:
a) at least 250 mg of leucine and/or at least 25 mg of one or more leucine metabolites, wherein the leucine metabolite is selected from the group consisting of keto-isocaproic acid (KIC), alpha-hydroxy-isocaproic acid, and hydroxymethtlbutyrate (HMB); and
b) at least 1 mg of nicotinic acid and/or nicotinamide riboside and/or one or more nicotinic acid metabolites, wherein the nicotinic acid metabolite is selected from the group consisting of nicotinyl CoA, nicotinuric acid, nicotinate mononucleotide, nicotinate adenine dinucleotide, and nicotinamide adenine dinucleotide,
wherein each of (a) and (b) are free of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, valine, isoleucine and tyrosine, and
wherein (a) and (b) are administered either simultaneously or in close temporal proximity.
20. The method of claim 19 , wherein the composition is administered orally.
21. The method of claim 19 , wherein the effective amount comprises at least 500 mg of leucine and/or at least 200 mg of the one or more leucine metabolites.
22. The method of claim 19 , wherein the composition further comprising one or more therapeutic agents selected from the group consisting of HMG-CoA inhibitor, fibrate, bile acid sequestrant, ezetimibe, lomitapide, phytosterols, CETP antagonist, orlistat, and any combination thereof.
23. The method of claim 19 , wherein nicotinic acid and/or nicotinamide riboside and/or one or more nicotinic acid metabolites is in a sub-therapeutic amount if administered alone.
24. The method of claim 19 , wherein nicotinic acid and/or nicotinamide riboside and/or one or more nicotinic acid metabolites is in an amount that is less than 1 g.
25. The method of claim 19 , wherein nicotinic acid and/or nicotinamide riboside and/or one or more nicotinic acid metabolites is in an amount that is less than 250 mg.
26. The method of claim 19 , wherein the amount of nicotinic acid and or nicotinamide riboside and/or one or more nicotinic acid metabolites is between 1-100 mg.
27. The method of claim 19 , wherein the amount of nicotinic acid and or nicotinamide riboside and/or one or more nicotinic acid metabolites is capable of achieving a serum level of nicotinic acid and/or nicotinamide riboside and/or one or more nicotinic acid metabolites that is between about 1-100 nM.