A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis.

 Abstract

BACKGROUND:

The cause of neuronal death in amyotrophic lateral sclerosis (ALS) is uncertain but mitochondrial dysfunction may play an important role. Ketones promote mitochondrial energy production and membrane stabilization.

RESULTS:

SOD1-G93A transgenic ALS mice were fed a ketogenic diet (KD) based on known formulations for humans. Motor performance, longevity, and motor neuron counts were measured in treated and disease controls. Because mitochondrial dysfunction plays a central role in neuronal cell death in ALS, we also studied the effect that the principal ketone body, D-beta-3 hydroxybutyrate (DBH), has on mitochondrial ATP generation and neuroprotection. Blood ketones were > 3.5 times higher in KD fed animals compared to controls. KD fed mice lost 50% of baseline motor performance 25 days later than disease controls. KD animals weighed 4.6 g more than disease control animals at study endpoint; the interaction between diet and change in weight was significant (p = 0.047). In spinal cord sections obtained at the study endpoint, there were more motor neurons in KD fed animals (p = 0.030). DBH prevented rotenone mediated inhibition of mitochondrial complex I but not malonate inhibition of complex II. Rotenone neurotoxicity in SMI-32 immunopositive motor neurons was also inhibited by DBH.

CONCLUSION:

This is the first study showing that diet, specifically a KD, alters the progression of the clinical and biological manifestations of the G93A SOD1 transgenic mouse model of ALS. These effects may be due to the ability of ketone bodies to promote ATP synthesis and bypass inhibition of complex I in the mitochondrial respiratory chain.

 

High-fat and ketogenic diets in amyotrophic lateral sclerosis. 

Abstract

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease. Epidemiologic data suggest that malnutrition is a common feature in amyotrophic lateral sclerosis and being overweight or obese confers a survival advantage in this patient population. In amyotrophic lateral sclerosis mouse models, a high-fat diet has been shown to lead to weight gain and prolonged survival. However, little research has been conducted to test whether nutritional interventions might ameliorate the disease course in humans. Here we review the currently available evidence supporting the potential role of dietary interventions as a therapeutic tool for amyotrophic lateral sclerosis. Ultimately, determining whether a high-fat or ketogenic diet could be beneficial in amyotrophic lateral sclerosis will require large randomized, placebo-controlled clinical trials.

Reference:
  • 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. PubMed PMID: 16584562;
  • Paganoni S, Wills AM. High-fat and ketogenic diets in amyotrophic lateral
    sclerosis. J Child Neurol. 2013 Aug;28(8):989-92. doi: 10.1177/0883073813488669.
    Epub 2013 May 10. PubMed PMID: 23666040
 

About the author: Dr. Mordy Levy

 

Dr. Mordy Levy, ND, DC, HOM, is possibly the only Canadian doctor to have graduated from three first professional doctorates in separate and distinct health care professions: Chiropractic Medicine (DC)-1997, Allopathic Medicine (MD)-2006, Naturopathic Medicine (ND)-2011, graduated Summa Cum Laude, from the prestigious National University of Health Sciences (Chicago, IL) and was the valedictorian of his graduating class.

Dr Levy's first undergraduate degree (BSc) was in Biology and Psychology from York University, and his second undergraduate degree (BMSc) was in Human Biology and Biomedical sciences from National University of Health Sciences (Chicago, IL)

Dr. Levy is a registered member in good standing with three distinct health professions in Ontario, namely the College of Chiropractors of Ontario, the College of Naturopaths of Ontario, in addition to the College of Homeopaths of Ontario. Dr. Levy is a professional member of the Institute of Functional Medicine, the Canadian Society of Orthomolecular Medicine, American College of Nutrition, in addition to the Ontario Association of Naturopathic Doctors, the Ontario Chiropractic Association and the Ontario Homeopathic Association. Always an avid lifelong learner, Dr. Levy completed numerous postgraduate certifications in Functional Medicine, Clinical Nutrition, Medical Acupuncture, Homeopathic Medicine, in addition to Prolotherapy regenerative medicine. His clinical interests are in Neurological, Autoimmune and Gastrointestinal Dysfunctions.
On a personal noted: Dr. Levy enjoys spending time with his three boys, practicing TaeKwonDo and reviewing research articles.

Website: http://www.DrLevy.ca