IP Library Granted Patent US 9,138,420
Granted Patent B2
US 9,138,420 · App. 14/455,385 · Granted Sep 22, 2015

Compositions and methods for producing elevated and sustained ketosis

Inventors: Dominic Paul D'Agostino (Tampa, FL); Patrick Arnold (Champaign, IL); Shannon Kesl (Tampa, FL)
Assignee: University of South Florida
A61K31/23A23L2/52A61K31/19A61K31/20A23V2002/00
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Quick Facts
Patent No.
US 9,138,420
App. No.
14/455,385
Granted
Sep 22, 2015
Kind
B2
Abstract

Beta-hydroxybutyrate mineral salts in combination with medium chain fatty acids or an ester thereof such as medium chain triglycerides were used to induce ketosis, achieving blood ketone levels of (2-7 mmol/L), with or without dietary restriction. The combination results in substantial improvements in metabolic biomarkers related to insulin resistance, diabetes, weight loss, and physical performance in a short period of time. Further, use of these supplements to achieve ketosis yields a significant elevation of blood ketones and reduction of blood glucose levels. Use of these substances does not adversely affect lipid profiles. By initiating rapid ketosis and accelerating the rate of ketoadaptation, this invention is useful for the avoidance of glucose withdrawal symptoms commonly experienced by individuals initiating a ketogenic diet, and minimizes the loss of lean body mass during dietary restriction.

Claims (52)

1. A composition, comprising:

at least one medium chain fatty acid or ester thereof in an amount between about 5 grams and about 50 grams; and

at least one beta-hydroxybutyrate compound in an amount between about 2 grams and about 50 grams, wherein the at least one beta-hydroxybutyrate compound is comprised of a beta-hydroxybutyrate salt.

2. The composition of claim 1 , wherein the at least one beta-hydroxybutyrate compound comprises one or more of a beta-hydroxybutyrate salt comprising sodium beta-hydroxybutyrate, arginine beta-hydroxybutyrate, potassium beta-hydroxybutyrate, calcium beta-hydroxybutyrate, magnesium beta-hydroxybutyrate, lithium beta-hydroxybutyrate, lysine beta-hydroxybutyrate, histidine beta-hydroxybutyrate, omithine beta-hydroxybutyrate, creatine beta-hydroxybutyrate, agmatine beta-hydroxybutyrate, or citrulline beta-hydroxybutyrate.

3. The composition of claim 1 , wherein the at least one beta-hydroxybutyrate compound comprises a salt mixture comprising a plurality of sodium beta-hydroxybutyrate, potassium beta-hydroxybutyrate, calcium beta-hydroxybutyrate, or magnesium beta-hydroxybutyrate.

4. The composition of claim 1 , wherein the at least one beta-hydroxybutyrate compound is comprised of (i) a beta-hydroxybutyrate salt and 1,3-butanediol, (ii) a beta-hydroxybutyrate salt and ethyl acetoacetate, (iii) a beta-hydroxybutyrate salt and ethyl beta-hydroxybutyrate, (iv) a salt mixture of beta-hydroxybutyrate salts and 1,3-butanediol, (v) a salt mixture of beta-hydroxybutyrate salts and ethyl acetoacetate, or (vi) a salt mixture of beta-hydroxybutyrate salts and ethyl beta-hydroxybutyrate.

5. The composition of claim 1 , wherein the at least one beta-hydroxybutyrate compound is racemic DL-beta-hydroxybutyrate or the single isomer R-beta-hydroxybutyrate.

6. The composition of claim 1 , wherein the at least one beta-hydroxybutyrate compound is included in an amount between about 5 grams and about 30 grams.

7. The composition of claim 1 , wherein the at least one beta-hydroxybutyrate compound is included in an amount between about 10 grams and about 20 grams.

8. The composition of claim 1 , wherein the at least one medium chain triglyceride or ester thereof is included in an amount between about 10 grams and about 40 grams.

9. The composition of claim 1 , wherein the at least one medium chain triglyceride or ester thereof is included in an amount between about 15 grams and about 30 grams.

10. The composition of claim 1 , wherein the at least one beta-hydroxybutyrate compound is included in an amount between about 5 grams and about 30 grams and the at least one medium chain triglyceride or ester thereof is included in an amount between about 10 grams and about 40 grams.

11. The composition of claim 1 , wherein the at least one beta-hydroxybutyrate compound is included in an amount between about 10 grams and about 20 grams and the at least one medium chain triglyceride or ester thereof is included in an amount between about 15 grams and about 30 grams.

12. The composition of claim 1 , wherein the at least one medium chain fatty acid or ester thereof is selected from the group consisting of medium chain triglycerides, coconut oil, coconut milk powder, fractionated coconut oil, palm kernel oil, isolated hexanoic acid, isolated octanoic acid, isolated decanoic acid, ethoxylated triglyceride, enone triglyceride derivatives thereof, aldehyde triglyceride derivatives thereof, monoglyceride derivatives thereof, diglyceride derivatives thereof, triglyceride derivatives thereof, or an alkyl ester thereof.

13. The composition of claim 1 , further comprising at least one additional component selected from the group consisting of amino acids, amino acid metabolites, vitamins, minerals, coconut milk powder, electrolytes, NADH, tetrahydrobiopeterin, alpha-ketoglutaric acid, alpha lipoic acid, nutritional co-factors, calcium beta-methyl-beta-hydroxybutyrate, arginine alpha-ketoglutarate, sodium R-alpha lipoic acid, thiamine, riboflavin, niacin, pyridoxine, ascorbic acid, citric acid, malic acid, sodium benzoate, potassium sorbate, acesulfame K, aspartame, xanthan gum, and combinations thereof.

14. The composition of claim 11 , further comprising at least one additional component selected from the group consisting of amino acids, amino acid metabolites, vitamins, minerals, coconut milk powder, electrolytes, NADH, tetrahydrobiopeterin, alpha-ketoglutaric acid, alpha lipoic acid, nutritional co-factors, calcium beta-methyl-beta-hydroxybutyrate, arginine alpha-ketoglutarate, sodium R-alpha lipoic acid, thiamine, riboflavin, niacin, pyridoxine, ascorbic acid, citric acid, malic acid, sodium benzoate, potassium sorbate, acesulfame K, aspartame, xanthan gum, and combinations thereof.

15. The composition of claim 14 , wherein the at least one beta-hydroxybutyrate compound comprises a salt mixture comprising a plurality of sodium beta-hydroxybutyrate, potassium beta-hydroxybutyrate, calcium beta-hydroxybutyrate, or magnesium beta-hydroxybutyrate.

16. The composition of claim 1 , wherein the at least one medium chain fatty acid or ester thereof and the at least one beta-hydroxybutyrate compound are each included in an effective amount so as to induce ketosis in a mammal for at least 240 minutes.

17. A composition for inducing sustained ketosis in a mammal, comprising:

at least one medium chain fatty acid or ester thereof; and

at least one beta-hydroxybutyrate compound, wherein the at least one beta-hydroxybutyrate compound is comprised of a beta-hydroxybutyrate salt,

wherein the at least one medium chain fatty acid or ester thereof and the at least one beta-hydroxybutyrate compound are included in an effective amount so as to induce ketosis in a mammal for at least 240 minutes.

18. The composition of claim 17 , wherein the at least one beta-hydroxybutyrate compound is included in an amount between about 5 grams and about 30 grams.

19. The composition of claim 17 , wherein the at least one beta-hydroxybutyrate compound is included in an amount between about 10 grams and about 20 grams.

20. The composition of claim 17 , wherein the at least one medium chain triglyceride or ester thereof is included in an amount between about 10 grams and about 40 grams.

21. The composition of claim 17 , wherein the at least one medium chain triglyceride or ester thereof is included in an amount between about 15 grams and about 30 grams.

22. The composition of claim 17 , wherein the at least one beta-hydroxybutyrate compound is included in an amount between about 5 grams and about 30 grams and the at least one medium chain triglyceride or ester thereof is included in an amount between about 10 grams and about 40 grams.

23. The composition of claim 17 , wherein the at least one beta-hydroxybutyrate compound is included in an amount between about 10 grams and about 20 grams and the at least one medium chain triglyceride or ester thereof is included in an amount between about 15 grams and about 30 grams.

24. The composition of claim 17 , wherein the at least one beta-hydroxybutyrate compound comprises one or more of a beta-hydroxybutyrate salt comprising sodium beta-hydroxybutyrate, arginine beta-hydroxybutyrate, potassium beta-hydroxybutyrate, calcium beta-hydroxybutyrate, magnesium beta-hydroxybutyrate, lithium beta-hydroxybutyrate, lysine beta-hydroxybutyrate, histidine beta-hydroxybutyrate, omithine beta-hydroxybutyrate, creatine beta-hydroxybutyrate, agmatine beta-hydroxybutyrate, or citrulline beta-hydroxybutyrate.

25. The composition of claim 17 , wherein the at least one beta-hydroxybutyrate compound comprises a salt mixture comprising a plurality of sodium beta-hydroxybutyrate, potassium beta-hydroxybutyrate, calcium beta-hydroxybutyrate, or magnesium beta-hydroxybutyrate.

26. The composition of claim 17 , wherein the at least one beta-hydroxybutyrate compound is comprised of (i) a beta-hydroxybutyrate salt and 1,3-butanediol, (ii) a beta-hydroxybutyrate salt and ethyl acetoacetate, (iii) a beta-hydroxybutyrate salt and ethyl beta-hydroxybutyrate, (iv) a salt mixture of beta-hydroxybutyrate salts and 1,3-butanediol, (v) a salt mixture of beta-hydroxybutyrate salts and ethyl acetoacetate, or (vi) a salt mixture of beta-hydroxybutyrate salts and ethyl beta-hydroxybutyrate.

27. The composition of claim 17 , wherein the at least one medium chain fatty acid or ester thereof is selected from the group consisting of medium chain triglycerides, coconut oil, coconut milk powder, fractionated coconut oil, palm kernel oil, isolated hexanoic acid, isolated octanoic acid, isolated decanoic acid, ethoxylated triglyceride, enone triglyceride derivatives thereof, aldehyde triglyceride derivatives thereof, monoglyceride derivatives thereof, diglyceride derivatives thereof, triglyceride derivatives thereof, or an alkyl ester thereof.

28. The composition of claim 17 , further comprising at least one additional component selected from the group consisting of amino acids, amino acid metabolites, vitamins, minerals, coconut milk powder, electrolytes, NADH, tetrahydrobiopeterin, alpha-ketoglutaric acid, alpha lipoic acid, nutritional co-factors, calcium beta-methyl-beta-hydroxybutyrate, arginine alpha-ketoglutarate, sodium R-alpha lipoic acid, thiamine, riboflavin, niacin, pyridoxine, ascorbic acid, citric acid, malic acid, sodium benzoate, potassium sorbate, acesulfame K, aspartame, xanthan gum, and combinations thereof.

29. A method of promoting or sustaining ketosis in a mammal, comprising:

administering the composition of claim 1 to a mammal to promote or sustain ketosis.

30. The method of claim 29 , wherein the at least one beta-hydroxybutyrate compound is included in an amount between about 5 grams and about 30 grams and the at least one medium chain triglyceride or ester thereof is included in an amount between about 10 grams and about 40 grams.

31. The method of claim 29 , wherein the at least one beta-hydroxybutyrate compound is included in an amount between about 10 grams and about 20 grams and the at least one medium chain triglyceride or ester thereof is included in an amount between about 15 grams and about 30 grams.

32. The method of claim 29 , wherein the at least one beta-hydroxybutyrate compound comprises a salt mixture comprising a plurality of sodium beta-hydroxybutyrate, potassium beta-hydroxybutyrate, calcium beta-hydroxybutyrate, or magnesium beta-hydroxybutyrate.

33. The method of claim 29 , wherein the at least one medium chain fatty acid or ester thereof is selected from the group consisting of medium chain triglycerides, coconut oil, coconut milk powder, fractionated coconut oil, palm kernel oil, isolated hexanoic acid, isolated octanoic acid, isolated decanoic acid, ethoxylated triglyceride, enone triglyceride derivatives thereof, aldehyde triglyceride derivatives thereof, monoglyceride derivatives thereof, diglyceride derivatives thereof, triglyceride derivatives thereof, or an alkyl ester thereof.

34. The method of claim 29 , wherein the composition further comprises at least one additional component selected from the group consisting of amino acids, amino acid metabolites, vitamins, minerals, coconut milk powder, electrolytes, NADH, tetrahydrobiopeterin, alpha-ketoglutaric acid, alpha lipoic acid, nutritional co-factors, calcium beta-methyl-beta-hydroxybutyrate, arginine alpha-ketoglutarate, sodium R-alpha lipoic acid, thiamine, riboflavin, niacin, pyridoxine, ascorbic acid, citric acid, malic acid, sodium benzoate, potassium sorbate, acesulfame K, aspartame, xanthan gum, and combinations thereof.

35. The method of claim 29 , wherein the composition is administered at least once a day for between one and two weeks, and wherein the method further comprises the mammal restricting intake of carbohydrates and protein.

36. A method of suppressing appetite or promoting weight loss in a mammal, comprising

administering the composition of claim 1 to a mammal to promote or sustain ketosis.

37. The method of claim 36 , wherein the at least one beta-hydroxybutyrate compound is included in an amount between about 5 grams and about 30 grams and the at least one medium chain triglyceride or ester thereof is included in an amount between about 10 grams and about 40 grams.

38. The method of claim 36 , wherein the at least one beta-hydroxybutyrate compound is included in an amount between about 10 grams and about 20 grams and the at least one medium chain triglyceride or ester thereof is included in an amount between about 15 grams and about 30 grams.

39. The method of claim 36 , wherein the at least one beta-hydroxybutyrate compound comprises a salt mixture comprising a plurality of sodium beta-hydroxybutyrate, potassium beta-hydroxybutyrate, calcium beta-hydroxybutyrate, or magnesium beta-hydroxybutyrate.

40. The method of claim 36 , wherein the at least one medium chain fatty acid or ester thereof is selected from the group consisting of medium chain triglycerides, coconut oil, coconut milk powder, fractionated coconut oil, palm kernel oil, isolated hexanoic acid, isolated octanoic acid, isolated decanoic acid, ethoxylated triglyceride, enone triglyceride derivatives thereof, aldehyde triglyceride derivatives thereof, monoglyceride derivatives thereof, diglyceride derivatives thereof, triglyceride derivatives thereof, or an alkyl ester thereof.

41. The method of claim 36 , wherein the composition further comprises at least one additional component selected from the group consisting of amino acids, amino acid metabolites, vitamins, minerals, coconut milk powder, electrolytes, NADH, tetrahydrobiopeterin, alpha-ketoglutaric acid, alpha lipoic acid, nutritional co-factors, calcium beta-methyl-beta-hydroxybutyrate, arginine alpha-ketoglutarate, sodium R-alpha lipoic acid, thiamine, riboflavin, niacin, pyridoxine, ascorbic acid, citric acid, malic acid, sodium benzoate, potassium sorbate, acesulfame K, aspartame, xanthan gum, and combinations thereof.

42. The method of claim 36 , wherein the composition is administered at least once a day for between one and two weeks, and wherein the method further comprises the mammal restricting intake of carbohydrates and protein.

43. A composition, comprising:

a medium chain fatty acid or ester thereof in an amount between about 15 grams and about 30 grams, the medium chain fatty acid or ester thereof consisting of a medium chain triglyceride; and

at least one beta-hydroxybutyrate compound in an amount between about 10 grams and about 20 grams, wherein the at least one beta-hydroxybutyrate compound comprises a salt mixture comprising a plurality of sodium beta-hydroxybutyrate, potassium beta-hydroxybutyrate, calcium beta-hydroxybutyrate, or magnesium beta-hydroxybutyrate.

Assignments (2)
CONFIRMATORY LICENSE Recorded Jul 16, 2015
From: SOUTH FLORIDA, UNIVERSITY OF
To: NAVY, SECRETARY OF THE UNITED STATES OF AMERICA
Reel/Frame 036132/0783 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 16, 2014
From: D'AGOSTINO, DOMINIC PAUL; ARNOLD, PATRICK; KESL, SHANNON
To: UNIVERSITY OF SOUTH FLORIDA
Reel/Frame 033961/0407 →
Continuity (4)
Continuation PCTUS2014031237 · Mar 19, 2014
Provisional Application 61926664 · Jan 13, 2014
Provisional Application 61803203 · Mar 19, 2013
Related Publication 20140350105A1 · Nov 27, 2014