Composition comprising ketone body and nicotinamide adenine dinucleotide modulator and methyl donor
The present invention provides a composition comprising a mixture of an exogenous ketone body, an exogenous NAD modulator and a methyl donor. Typically, exogenous NAD modulator is an exogenous nicotinamide adenine dinucleotide (NAD) precursor. The present invention also provides a method of using such a composition for treating various clinical conditions, including metabolic disorders and neurocognitive impairments. The compositions of the invention can also be used to improve human performance in various competitive or environmental conditions.
1. A composition comprising a therapeutically effective amount of: (i) an exogenous ketone body comprising 3-hydroxybutyrate (“BHB”) or an ester of BHB, (ii) exogenous nicotinamide adenine dinucleotide (“NAD”) modulator, and (iii) a methyl donor, wherein the composition is in a single unit form, and wherein said NAD modulator is present in an amount from 125 mg to 2000 mg, and the ratio (w/w) of the exogenous ketone body to the NAD modulator is from 160:1 to 10:1.
2. The composition according to claim 1 , wherein said exogenous ketone body comprises an ester of BHB.
3. The composition of claim 2 , wherein said ester of BHB is of the formula:
wherein
each of R 6 , R 7 and R 8 is independently selected from the group consisting of hydrogen,
BHB moiety or a hydroxyl protecting group;
provided at least one of R 6 , R 7 and R 8 is BHB moiety of the formula C(═O)CH 2 CH(OR 2 )CH 3 , wherein R 2 is H or a hydroxyl protecting group.
4. The composition according to claim 1 , wherein said exogenous NAD modulator comprises a nicotinamide adenine dinucleotide precursor.
5. The composition according to claim 4 , wherein said exogenous NAD precursor comprises nicotinoyl riboside or a derivative thereof.
6. The composition according to claim 1 , wherein said exogenous NAD modulator comprises nicotinamide riboside halide.
7. The composition according to claim 1 , wherein said exogenous NAD modulator is nicotinamide riboside chloride, nicotinamide mononucleotide or a combination thereof.
8. The composition according to claim 1 , wherein said methyl donor comprises choline, betaine, folate, vitamin B 12 , S-adenosylmethionine, or a mixture thereof.
9. The composition according to claim 1 , wherein the amount of said exogenous ketone body ranges from about 1 mg to about 50,000 mg in said single unit form.
10. The composition of claim 1 , wherein the exogenous ketone body comprises BHB.
11. The composition of claim 2 , wherein the ester of BHB comprises a glycerol ester of BHB.
12. The composition of claim 11 , wherein said glycerol ester of BHB comprises a compound of the formula:
wherein
at least one of R 3 and R 4 is BHB and the other is a C 4 -C 22 fatty acid moiety
R 5 together with the oxygen atom to which it is attached forms choline, serine, inositol, or ethanolamine moiety.