Indications and Usage

Alzheimer's Disease as a Metabolic Deficiency

Under normal conditions, glucose is the primary energy source for the brain. Imaging studies have shown decreased utilization of glucose in the brains of AD patients early in the disease, before clinical signs of cognitive impairment occur. This decrease in glucose metabolism (hypometabolism) worsens as clinical symptoms develop and the disease progresses. ^1,2 Hypometabolism may not be solely an artifact of cell atrophy since it occurs in asymptomatic patients at risk for AD, such as patients homozygous for the epsilon 4 variant of the apolipoprotein E gene (APOE4, a genetic risk factor for AD), as well as in familial forms of AD. Thus, AD is a disease with distinctive metabolic and nutritional requirements. ^3,4

Given that hypometabolism is an early and progressive event in AD and may precipitate downstream pathological events, it is reasonable to target the improvement of neuronal energy states for the management of AD. Studies in animals and human subjects have shown that increasing blood glucose levels facilitates memory.⁵ However, due to the impracticality of maintaining chronically elevated glucose levels, a safer alternative is required. Ketone bodies provide an alternative energy substrate that can be utilized by the brain to improve cognition and memory.

Ketone bodies are naturally produced from fat stores as an alternative to glucose during periods of sustained hypoglycemia, such as during fasting or very low carbohydrate intake. In a controlled clinical study in human subjects experiencing hypoglycemia, the infusion of ketones was shown to improve cognitive function compared with control subjects, suggesting that increased ketones can substitute for glucose as an energy source for the brain.^6,7

In vitro data indicate that the ketone body ß-hydroxybutyrate (BHB) can substitute for a large fraction of glucose as an energy substrate, and preserves neuronal integrity and stability.⁸ Ketone bodies feed directly into the tricarboxylic acid (TCA) cycle in neurons and generate adenosine triphosphate (ATP), as well as increasing pools of acetyl-CoA and succinate. Ketones are neuroprotective against several types of toxic insults,⁹ and also reduce neuropathological changes, such as ß-amyloid levels in animal models of AD.¹⁰

Axona is designed to safely elevate serum ketone levels to assist with the clinical dietary management of the metabolic processes and nutritional requirements associated with mild to moderate AD.