Leucine-enriched ketogenic formulations
Described herein are nutritional compositions, such as ketogenic compositions, leucine-enriched amino acid mixtures, etc., useful, for example, for dietary management of intractable epilepsy. In some embodiments, the disclosure relates to methods of inhibiting epileptic seizures in a subject comprising administering to the subject a leucine-enriched amino acid mixture.
1. A ketogenic composition comprising: fat, a protein source, and carbohydrate, wherein: (a) the fat provides 60-90% of total calories of the composition and medium chain triglycerides (MCTs) provide between 10-40% of total calories of the composition; (b) the protein source comprises a non-casein protein and a leucine-enriched amino acid mixture; (c) and the ratio of calories fat to calories combined protein and net carbohydrate ranges from about 2:1 to about 4:1,
wherein the leucine-enriched amino acid mixture comprises L-leucine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, and L-valine, and comprises leucine at a molar ratio between 30% and 70% with respect to total essential amino acids in the mixture.
2. The ketogenic composition of claim 1 , wherein the protein source comprises a non-casein protein isolate, non-casein protein concentrate, non-casein protein hydrolysate, or a combination of the foregoing, optionally wherein the protein source is nutritionally complete.
3. The ketogenic composition of claim 1 , wherein the leucine-enriched amino acid mixture comprises leucine at a molar ratio between 35% and 60% with respect to total essential amino acids in the mixture.
4. The ketogenic composition of claim 1 , wherein each of the amino acids in the composition is present at the following molar composition ratio (%) with respect to total of essential amino acids in the composition: 0.1% to 5% of L-histidine, 5.0% to 15% of L-isoleucine, 30% to 70% of L-leucine, 8.0% to 25% of L-lysine, 2.0% to 10% of L-methionine, 2.5% to 8.0% of L-phenylalanine, 7.0% to 20% of L-threonine, 5.0% to 15% of L-valine, and 0.1% to 4.0% of L-tryptophan.
5. The ketogenic composition of claim 1 , wherein the molar ratio of leucine to isoleucine ranges from about 1:1 to 4:1, the ratio of leucine to valine ranges from about 1:1 to about 4:1, or a combination of the foregoing.
6. The ketogenic composition of claim 1 , wherein the fat comprises about 40% to about 50% MCTs by weight.
7. The ketogenic composition of claim 1 further comprising one or more vitamins and one or more minerals, optionally wherein the one or more vitamins comprise vitamin D, vitamin K1, and/or vitamin K2, and/or wherein the one or more minerals comprise calcium, magnesium and/or phosphorous.
8. The ketogenic composition of claim 1 , wherein the composition is a solid, optionally wherein the solid is a powder.
9. The ketogenic composition of claim 1 , wherein the composition is a liquid, optionally wherein the liquid is an aqueous liquid.
10. The ketogenic composition of claim 1 , wherein the composition is nutritionally complete.
11. A method for dietary management of a disease or condition associated with clinical improvement after Ketogenic diet administration, the method comprising administering to the subject an effective amount of the composition of claim 1 .
12. The method of claim 11 , wherein the disease or condition is intractable epilepsy.
13. The method of claim 11 , wherein the subject is following or has previously followed a ketogenic diet.
14. The method of claim 11 , wherein the subject has been determined to be refractory to treatment with anti-epileptic drugs (AEDs).
15. The method of claim 11 , wherein the subject is determined to have an improvement in clinical outcomes after administration of the ketogenic diet.
16. A method for treating intractable epilepsy in a subject comprising administering to the subject a leucine-enriched amino acid mixture comprising L-leucine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, and L-valine, wherein
(i) the leucine is present at a molar ratio between 30% and 70% with respect to total essential amino acids in the mixture; and
(ii) the molar ratio of leucine to isoleucine ranges from about 1:1 to 4:1 or the ratio of leucine to valine ranges from about 1:1 to about 4:1.
17. A method for reducing epileptic seizures in a subject comprising administering to the subject a leucine-enriched amino acid mixture comprising L-leucine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, and L-valine, wherein
(i) the leucine is present at a molar ratio between 30% and 70% with respect to total essential amino acids in the mixture; and
(ii) the molar ratio of leucine to isoleucine ranges from about 1:1 to 4:1 or the ratio of leucine to valine ranges from about 1:1 to about 4:1.
18. The method according to claim 16 , wherein the intractable epilepsy is the epilepsy that is refractory to treatment with one or more anti-epileptic drugs (AEDs).
19. The method according to claim 16 , wherein the subject has previously been administered a ketogenic formula or is currently following a ketogenic diet.
20. The method according to claim 16 , wherein the subject is in a state of ketosis.
21. The method according to claim 16 , wherein the leucine-enriched amino acid mixture accounts for between 1.0% and 6.0% of the subject's daily caloric intake.
22. A method for clinical dietary management of a disease or disorder of a subject on a ketogenic diet, comprising administering to the subject a leucine-enriched amino acid mixture comprising L-leucine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, and L-valine, wherein
(i) the leucine is present at a molar ratio between 30% and 70% with respect to total essential amino acids in the mixture; and
(ii) the molar ratio of leucine to isoleucine ranges from about 1:1 to 4:1 or the ratio of leucine to valine ranges from about 1:1 to about 4:1.
23. A method for inducing ketogenesis in a subject comprising administering to the subject a leucine-enriched amino acid mixture comprising L-leucine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, and L-valine, wherein
(i) the leucine is present at a molar ratio between 30% and 70% with respect to total essential amino acids in the mixture; and
(ii) the molar ratio of leucine to isoleucine ranges from about 1:1 to 4:1 or the ratio of leucine to valine ranges from about 1:1 to about 4:1.
24. The method according to claim 23 , wherein the method further comprises administering a ketogenic diet to the subject.
25. A non-therapeutic method of inducing ketogenesis in a subject comprising administering to the subject a leucine-enriched amino acid mixture comprising L-leucine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, and L-valine, wherein
(i) the leucine is present at a molar ratio between 30% and 70% with respect to total essential amino acids in the mixture; and
(ii) the molar ratio of leucine to isoleucine ranges from about 1:1 to 4:1 or the ratio of leucine to valine ranges from about 1:1 to about 4:1.
26. The method according to claim 25 , further comprising administering a ketogenic diet to the subject.
27. The method according to claim 25 , wherein the non-therapeutic method is cosmetic or athletic performance-enhancing.
28. A method for treating disease or disorder in a subject selected from traumatic brain injury (TBI), neurodegenerative disease, cancer, obesity, diabetes, and diseases related to certain inborn errors of metabolism, comprising administering to the subject a mixture comprising L-leucine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, and L-valine, wherein
(i) the leucine is present at a molar ratio between 30% and 70% with respect to total essential amino acids in the mixture; and
(ii) the molar ratio of leucine to isoleucine ranges from about 1:1 to 4:1 or the ratio of leucine to valine ranges from about 1:1 to about 4:1.
29. The method according to claim 28 , wherein the diseases related to inborn errors of metabolism are selected from glucose transporter syndrome and pyruvate dehydrogenase deficiency (PDH).
30. The method according to claim 28 , wherein the cancer is selected from brain tumors.