Ketone Bodies as A Therapeutic for Alzheimer’s Disease: Future Treatments in Alzheimer’s Disease
S. T. Henderson1, J. L. Vogel1, L. J. Barr1, F. Garvin1. 1.Clinical Research, Accera Inc., Broomfield, United States
25th International Conference of Alzheimer’s Disease International (ADI), March 10-13, 2010, Greece.
Objectives and Study: The rationale and results for the use of ketone bodies as a therapy for Alzheimer’s disease (AD) is reviewed. An early feature of AD is region specific declines in cerebral glucose metabolism. One therapeutic approach is to supplement the brain’s normal glucose supply with ketone bodies.
Methods: An oral ketogenic compound, AC-1202, was tested in subjects with mild to moderate AD in two clinical studies to examine the cognitive effects of induced ketosis. Acute administration of AC-1202 was tested in 20 AD participants in a blinded, randomized, crossover study. Chronic administration of AC-1202 was tested in 152 AD subjects in a US-based, 90-day, randomized, double-blind, placebo-controlled, parallel-group study. In both studies, subjects were on a normal diet, most were taking approved AD medications, and results were stratified by APOE4 carriage status.
Results: In both acute and chronic dosing, AC-1202 significantly induced ketosis 2 hours after administration. After acute dosing, non-E4 carriers demonstrated a significant difference in the ADAS-Cog test compared to E4 carriers (p=0.039). After chronic dosing, non-E4 carriers demonstrated a significant difference between AC-1202 and Placebo in mean change from Baseline in ADAS-Cog score on Day 45 (4.77 point difference, p=0.0005) and Day 90 (3.36 point difference, p=0.0148). In the dosage compliant population, non-E4 carriers receiving AC-1202 differed in ADAS-Cog from Placebo by 6.26 points at Day 45 (p=0.0011) and 5.33 points at Day 90 (p=0.0063). In addition, significant correlations between serum ketone bodies and cognitive performance were found in both studies.
Conclusions: AC-1202 rapidly elevated serum ketone bodies in AD patients and resulted in significant differences in ADAS-Cog scores compared to the Placebo. Effects were most notable in APOE4(-) subjects who were dosage compliant.
Note: AC-1202 is a dietary supplement made from MCTs derived from coconut oil. MCTs are metabolized into ketone bodies in the liver.