Ketogenic Therapy for Other Conditions

Ketogenic therapy has been successfully used to treat intractable epilepsy for many years, and is also the treatment of choice in neurometabolic disease.  More recently there is an increasing scientific literature on the use of this type of diet as a treatment for neurological cancers and a wider range of disorders. This insight discussed the evidence for these other conditions.

The metabolic changes that occur with ketogenic therapy, such as enhancement of mitochondrial function and impact on glucose use, have led to suggestions that it may be beneficial in disorders of neuro-degeneration such as Parkinson’s disease, Alzheimer’s disease, and Amyotrophic lateral sclerosis (1). There is also increased interest into the effect that it could have on the normal aging process in the brain (2). The calorie-restrictive properties of this type of diet may also provide benefits via the regulation of a family of proteins called sirtuins which are involved in mediating the anti-aging process (1, 3). The increased essential fatty acid intake provided by a high fat dietary regime may also improve cognitive dysfunction (4).

Parkinson’s disease is characterised by the progressive death of brain dopaminergic neurons caused by mitochondrial dysfunction. Ketones could provide a fuel source for these at-risk neurons, alternatively the ketone-induced enhancement of mitochondrial function may protect cells against insults that demand a high energy supply (1). A feasibility study on use of the ketogenic diet in 7 patients with Parkinson’s disease reported a decrease in the average disease rating score in the 5 patients who completed the study (5), and benefits were also seen in studies on mice (6).

A number of metabolic abnormalities are associated with Alzheimer’s disease, in particular the formation of extracellular plaques containing amyloid protein. Ketogenic diet therapy may protect against amyloid deposition; this has been shown in studies on mice (7). In a  randomized, double blind study of 152 patients with mild to moderate Alzheimers disease, the group treated with a medium chain triglyceride ketogenic compound showed significant improvement in cognitive function compared with controls (8), although the benefit of the diet was only seen in patients lacking a particular genotype (APOε4 – a risk factor for the disease).

Amyotrophic lateral sclerosis is a progressive motor neuron disease.  Results from animal studies indicate that ketogenic dietary therapy may help slow the progressive loss of these neurons (9), although there are no published results from clinical studies.

Although there is clearly future potential for using ketogenic dietary therapy within the management of neurodegenerative disorders, further studies are needed before it can be incorporated into clinical practice in order to clarify who would benefit from this type of treatment and how best it should be implemented. There is also some evidence from animal studies suggesting that ketogenic dietary therapy may have a role in protecting the brain from trauma and ischaemia, with the injured brain preferring to use ketones as a fuel (1); again further studies are needed.

One small study which treated autistic children with an intermittently-applied modified medium chain triglyceride diet has suggested that ketogenic dietary therapy may be of benefit in this group (10). However the study design and choice of outcome assessment tool have been questioned (1), and further studies are needed before any recommendations can be made. Other reports have suggested a modified Atkins style ketogenic diet could be used to treat headache (11), narcolepsy (12) and alternating hemiplegia of childhood (13).

References

  1. Barañano KW, Hartman AL. The ketogenic diet: uses in epilepsy and other neurologic illnesses. Curr Treat Options Neurol. 2008 Nov;10(6):410-9.
  2. Balietti M, Casoli T, Di Stefano G, Giorgetti B, Aicardi G, Fattoretti P. Ketogenic diets: an historical antiepileptic therapy with promising potentialities for the aging Ageing Res Rev. 2010 Jul;9(3):273-9.
  3. Qin W, Yang T, Ho L, Zhao Z, Wang J, Chen L, Zhao W, Thiyagarajan M, MacGrogan D, Rodgers JT, Puigserver P, Sadoshima J, Deng H, Pedrini S, Gandy S, Sauve AA, Pasinetti GM.   Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction.  J Biol Chem. 2006 Aug 4;281(31):21745-54..
  4. Kotani S, Sakaguchi E, Warashina S, Matsukawa N, Ishikura Y, Kiso Y, Sakakibara M, Yoshimoto T, Guo J, Yamashima T. Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction. Neurosci Res. 2006 Oct;56(2):159-64.
  5. Vanitallie TB, Nonas C, Di Rocco A, Boyar K, Hyams K, Heymsfield SB. Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study Neurology. 2005 Feb 22;64(4):728-30.
  6. Tieu K, Perier C, Caspersen C, Teismann P, Wu DC, Yan SD, Naini A, Vila M, Jackson-Lewis V, Ramasamy R, Przedborski S. D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. J Clin Invest. 2003 Sep;112(6):892-901.
  7. Van der Auwera I, Wera S, Van Leuven F, Henderson ST. A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease. Nutr Metab (Lond). 2005 Oct 17;2:28.
  8. Henderson ST, Vogel JL, Barr LJ, Garvin F, Jones JJ, Costantini LC. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond). 2009 Aug 10;6:31.
  9. Zhao Z, Lange DJ, Voustianiouk A, MacGrogan D, Ho L, Suh J, Humala N, Thiyagarajan M, Wang J, Pasinetti GM. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis. BMC Neurosci. 2006 Apr 3;7:29.
  10. Evangeliou A, Vlachonikolis I, Mihailidou H, Spilioti M, Skarpalezou A, Makaronas N, Prokopiou A, Christodoulou P, Liapi-Adamidou G, Helidonis E, Sbyrakis S, Smeitink J. Application of a ketogenic diet in children with autistic behavior: pilot study. J Child Neurol. 2003 Feb;18(2):113-8.
  11. Kossoff EH, Huffman J, Turner Z, Gladstein J. Use of the modified Atkins diet for adolescents with chronic daily headache. Cephalalgia. 2010 Aug;30(8):1014-6.
  12. Husain AM, Yancy WS Jr, Carwile ST, Miller PP, Westman EC. Diet therapy for narcolepsy. Neurology. 2004 Jun 22;62(12):2300-2.
  13. Roubergue A, Philibert B, Gautier A, Kuster A, Markowicz K, de Villemeur TB, Vuillaumier-Barrot S, Nicole S, Roze E, Doummar D. Excellent Response to a Ketogenic Diet in a Patient with Alternating Hemiplegia of Childhood. JIMD Rep. 2014 Feb 16. [Epub ahead of print]