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 method of administering to a subject with a sign, symptom, or a diagnosis of cognitive impairment, the method comprising administering to the subject:
(i) an exogenous ester of β-hydroxybutyrate (BHB);
(ii) an exogenous nicotinamide dinucleotide (“NAD”) modulator, and
(iii) a methyl donor, wherein the methyl donor is betaine;
wherein the methyl donor is administered in an amount from 0.001 mg to 5,000 mg; and
wherein administration improves the neurocognitive function of the subject.
2. The method of claim 1 , wherein the methyl donor is administered in an amount from 150 mg to 1500 mg.
3. The method of claim 1 , wherein the exogenous ester of β-hydroxybutyrate and the exogenous NAD modulator are administered in a ratio of exogenous ester of β-hydroxybutyrate to exogenous NAD modulator from 1,000,000:1 to 1000:1.
4. The method of claim 1 , wherein the exogenous NAD modulator and the methyl donor are administered in a ratio of exogenous NAD modulator to methyl donor from 0.25:1 to 6.667:1.
5. The method of claim 1 , wherein the exogenous 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 a hydrogen, a BHB moiety and a hydroxyl protecting group;
provided at least one of R 6 , R 7 and R 8 is a BHB moiety of the formula —C(═O)CH 2 CH(OR 2 )CH 3 , wherein R 2 is H or a hydroxyl protecting group.
6. The method of claim 1 , wherein the exogenous NAD modulator is selected from the group consisting of nicotinoyl riboside, nicotinamide riboside, nicotinic acid mononucleotide, nicotinamide mononucleotide, and ß-nicotinamide ribose monophosphate.
7. The method of claim 1 , wherein the exogenous NAD modulator is administered in an amount from 125 mg to 2000 mg.
8. The method of claim 1 , wherein the exogenous ester of BHB is administered in an amount from 1 gram to 20 grams.
9. The method of claim 1 , wherein the exogenous ester of BHB is administered in an amount from 10 grams to 20 grams.
10. The method of claim 1 , wherein the exogenous NAD modulator is in a salt form.
11. The method of claim 10 , wherein the salt form is a halide.
12. The method of claim 11 , wherein the halide is selected from the group consisting of iodide, bromide, and chloride.
13. The method of claim 1 , wherein the exogenous NAD modulator is a nicotinamide riboside halide.
14. The method of claim 1 , wherein the exogenous NAD modulator is nicotinamide riboside, and wherein the nicotinamide riboside comprises a protecting group selected from the group consisting of an acetyl group (CH 3 C(═O)—), an acetoacetyl group, formate, benzoate, and carbamate.
15. The method of claim 1 , wherein the exogenous ester of BHB is a glycerol ester of BHB.
16. The method of claim 1 , wherein (i), (ii) and (iii) are administered in a solid powder form.
17. The method of claim 1 , wherein (i), (ii), and (iii) are dissolved in an aqueous medium prior to administration.