In recent years, clinicians have utilized a somewhat surprising tool to treat their patients with refractory epilepsy-diet. The majority of people with epilepsy can become free from seizures with the use of antiepileptic medications, but in about 20-30% of people with epilepsy, medications fail to completely control their symptoms. Clinicians and researchers have found the ketogenic diet is an effective way to treat these patients; it is at least as successful as the most recent anticonvulsant drugs designed to treat refractory epilepsy. Researchers have also started exploring the therapeutic potential of the diet in other neurological conditions, including Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis (ALS), among others.

The ketogenic diet is low in carbohydrates, adequate in protein, and high in fat, and sometimes partially restricted in calories. When following this diet, the brain shifts its main source of energy from glucose to fat. Fats are broken down into ketones, and these ketones are utilized by the brain as its main energy source. This shift in energy source is thought to be related to decreased seizures, though exactly how this happens is not yet clear. Researchers have proposed that the diet may work by altering neurotransmitter function, synaptic transmission, regulation of reactive oxygen species, and mitochondrial dysfunction — pathological mechanisms thought to play a role in a number of neurological diseases.

In Alzheimer’s disease, for example, results from clinical studies have been inconclusive but promising. In one randomized double-blind study, Alzheimer’s patients on a ketogenic diet showed significant cognitive improvement compared to patients not following the diet. In cell cultures, ketone bodies have been shown to be effective against the toxic effects of beta-amyloid, a key pathological feature of the disease. The diet may also help reduce oxidative stress and enhance mitochondrial function.

Mitochondrial dysfunction is also thought to play a contributory role in Parkinson’s disease, with its characteristic movement and cognitive impairment. In one small clinical trial of five patients with Parkinson’s disease, patients on the diet reduced their scores on the Unified Parkinson’s Disease Rating Scale by 43.4%.

The diet may also prove helpful in the treatment of Amyotrophic Lateral Sclerosis, or ALS. Mitochondrial dysfunction is also likely to play role in this devastating disease of the motor neurons. Though human studies have not yet been performed, mouse models of the condition have yielded promising results. In these mouse models, animals given a ketogenic diet showed significant motor improvements compared to animals on a normal diet.

Researchers speculate that the diet may prove helpful in even more neurological conditions, such as recovery from stroke and brain injury. Though the diet is an accepted treatment for refractory epilepsy, in other neurological conditions more clinical trials are needed to see if the diet is truly efficacious. If borne out, the diet may open another therapeutic avenue for the treatment of these diseases.

References

Griggs RC. Epilepsy. In Andreoli TE, Carpenter CC, Griggs RD, Benjamin IJ, eds. Andreoli and Carpenter’s Cecil Essentials of Medicine. 7th Ed. Philadelphia, PA: Elsevier; 2005: 1120-1128.

Henderson ST, Vogel JL, Barr LJ, Garvin F, Jones JJ, & Costantini LC (2009). Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutrition & metabolism, 6 PMID: 19664276

Huffman J, & Kossoff EH (2006). State of the ketogenic diet(s) in epilepsy. Current neurology and neuroscience reports, 6 (4), 332-40 PMID: 16822355

Lee M (2012). The use of ketogenic diet in special situations: expanding use in intractable epilepsy and other neurologic disorders. Korean journal of pediatrics, 55 (9), 316-21 PMID: 23049588

Mackay MT, Bicknell-Royle J, Nation J, Humphrey M, & Harvey AS (2005). The ketogenic diet in refractory childhood epilepsy. Journal of paediatrics and child health, 41 (7), 353-7 PMID: 16014140

Stafstrom CE, & Rho JM (2012). The ketogenic diet as a treatment paradigm for diverse neurological disorders. Frontiers in pharmacology, 3 PMID: 22509165

VanItallie, T., Nonas, C., Di Rocco, A., Boyar, K., Hyams, K., & Heymsfield, S. (2005). Treatment of Parkinson disease with diet-induced hyperketonemia: A feasibility study Neurology, 64 (4), 728-730 DOI: 10.1212/01.WNL.0000152046.11390.45

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