Ketone bodies and ketone body esters as blood lipid lowering agents
The subject disclosure provides compositions for reducing serum cholesterol and/or triglyceride levels in subjects. These compositions can comprise racemic β-hydroxybutyrate or D-β-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic β-hydroxybutyrate or D-β-hydroxybutyrate, esters of D-β-hydroxybutyrate, oligomers of D-β-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol or R-1,3 butandiol alone and can be, optionally, administered in conjunction with a low fat diet to a subject. Alternatively, compositions comprising racemic β-hydroxybutyrate or D-β-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic β-hydroxybutyrate or D-β-hydroxybutyrate, esters of D-β-hydroxybutyrate, oligomers of D-β-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol, R-1,3 butandiol or combinations thereof can be formulated as nutritional supplements (also referred to as nutritional compositions) or incorporated into therapeutic compositions containing a) anti-hypertensive agents; b) anti-inflammatory agents; c) glucose lowering agents; or d) anti-lipemic agents) which are administered to a subject, optionally in combination with a low fat diet, in order to cause a reduction or lowering of: serum cholesterol levels; triglyceride levels; serum glucose levels, serum homocysteine levels, inflammatory proteins (e.g., C reactive protein) and/or hypertension in treated subjects. Alternatively, compositions disclosed herein can be administered alone, or in combination with other therapeutic agents to prevent or reverse vascular disease.
1. A method for lowering serum glucose levels in a diabetic subject in need thereof comprising the oral administration of a composition comprising an R-1,3-butanediol ester of monomeric D -β-hydroxybutyrate alone, or in combination with an additional therapeutic agent, to a subject so as to raise blood D -β-hydroxybutyrate plus acetoacetate from between 0.1 to 20 mM.
2. The method according to claim 1 , wherein said composition is administered in the form of the subject's diet.
3. The method according to claim 1 , wherein said method comprises the administration of a first composition comprising the R-1,3-butanediol ester of monomeric D -β-hydroxybutyrate in combination with a second composition comprising a therapeutic agent, wherein said first and second compositions are administered separately, sequentially or together and each composition is in unit dosage form.
4. The method according to claim 3 , wherein said therapeutic agent is selected from glucose/blood sugar lowering agents, lipid lowering (anti-lipemic) agents, blood pressure lowering agents (anti-hypertensive agents), or agents that reduce inflammation (anti-inflammatory agents).
5. The method according to claim 1 , wherein said method lowers blood sugar in a diabetic subject without inducing insulin shock and comprises administering the said composition in unit dosage form or feeding the diabetic subject a diet containing the said composition.
6. The method according to claim 1 , wherein said method lowers or reduces elevated blood homocysteine and comprises administering the said composition in unit dosage form or feeding the diabetic subject a diet containing the said composition.
7. The method according to claim 1 , wherein said method lowers or reduces serum C-reactive protein levels and comprises administering the said composition in unit dosage form or feeding the diabetic subject a diet containing the said composition.
8. The method according to claim 1 , wherein said method lowers or reduces blood pressure levels in a subject and comprises administering the said composition in unit dosage form or feeding the diabetic subject a diet containing the said composition.
9. The method according to claim 1 , wherein the dietary intake of fat by said subject is reduced.
10. The method according to claim 1 , wherein the R-1,3-butanediol ester of monomeric D -β-hydroxybutyrate is administered in an amount that a) provides for blood levels of D -β-hydroxybutyrate plus acetoacetate ranging from between 0.1 to 25 mM, between 0.4 to 10 mM or between 0.6 and 3 mM in an individual; or b) ranges from 2-100% of the total caloric intake of an individual, 5-70% of the total caloric intake of an individual, or 5-30% of the total caloric intake of the individual.
11. The method according to claim 1 , wherein said method raises blood D -β-hydroxybutyrate plus acetoacetate from between 0.5 and 10 mM.
12. The method according to claim 1 , wherein said method raises blood D -β-hydroxybutyrate plus acetoacetate from between 1 to 3 mM.
13. A method of reducing serum glucose levels in a diabetic subject in need thereof, comprising administering an R-1,3-butanediol ester of monomeric D -β-hydroxybutyrate in combination with a therapeutic agent selected from:
a) anti-lipemic agents;
b) anti-hypertensive agents;
c) glucose lowering agents; or
d) anti-inflammatory agents
to a diabetic subject.