Neurological Disorders, the Ketogenic Diet and Practical Implications

According to the World Health Organization (2016) neurological disorders are diseases affecting the central and peripheral nervous system.  This encompasses the brain, the spinal cord, cranial and peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscles.  Disorders in relation to these organs and tissues include Parkinson’s disease, Alzheimer disease, epilepsy, stroke, other dementias, migraines, neuro-infections, brain tumours, multiple sclerosis, stroke, and neurological disorders due to malnutrition.

There are many viral, bacterial, fungal, and parasitic infections that can cause havoc on the nervous system, leading to serious illness or permanent damage.  Such examples include mycobacterial tuberculosis, human immunodeficiency virus, West Nile virus, aspergillus fungus, and malaria.  Symptoms may occur due to the infection itself or due to an immune response.

Putting it in perspective, more than 6 million people die of stroke each year.  More than 50 million people have epilepsy worldwide.  It is estimated 47.5 million people with dementia with 7.7 million new cases every year.  Alzheimer’s disease is the most common cause of dementia and contributes to approximately 60-70% of cases.  There is currently no cure, only early detection and management via pharmaceutical intervention.  If dietary changes could make huge impacts, both preventatively and throughout the course of treatment, then would it not be worth a try?

Researchers have begun to investigate the therapeutic effects of a ketogenic diet in relation to neurological disorders.  A ketogenic diet is a low carbohydrate, high fat diet.  The carbohydrate restriction forces the body into a metabolic state called ketosis, where the body burns compounds known as ketones (formed via the break down of fatty acids).  The body becomes more efficient in metabolising fat, and it also turns fat into ketones in the liver, which can supply energy to the brain.

Storoni & Plant (2015) reviewed evidence in support of a ketogenic diet in the treatment for multiple sclerosis.  The authors recognised that while both inflammation and neurodegeneration are both responsible for disease progression and disability, the neurodegenerative component may play a more significant role.  Multiple sclerosis is a disease characterised by the destruction of the myelin sheath, a layer of fatty tissue that surrounds and protects nerve cells.  As stated by Storoni & Plant (2015), “Axonal degeneration is a prominent feature of MS and is notably present even in the absence of local demyelination.  Animal models suggest that mitochondrial injury may be a necessary step preceding axonal degeneration”.  The mitochondria is responsible for ATP (energy production) within our cells.

So how does the ketogenic diet fit into the picture?

Some studies have shown that there may be a shift taking place with regards to neural metabolism, prior to the onset of signs of clinical degeneration, where glucose uptake and utilisation has been reduced.  This decrease in glucose utilisation may reflect a decline in mitochondrial function (Storoni & Plant, 2015).  According to Storoni & Plant (2015) “This shift has been observed to occur long before the onset of clinical signs of neurodegeneration, suggesting the possibility that glucose hypometabolism may be the initial step leading to axonal atrophy and neural loss through a reduction in ATP availability”.  Here, the importance of using not only the ketogenic diet to manage and treat the symptoms of those already diagnosed with MS, but the use of the ketogenic diet in prevention measures is critical in understanding diet and its relevance in the realm of therapeutics.

When the body is subjected to carbohydrate restriction, the central nervous system cannot directly use fat as a source of energy, thus, fat is converted into ketone bodies.  Ketone bodies bypass the glycolytic pathway and directly enter the Tricarboxylic Acid Cycle (TCA) within the mitochondria, contributing to energy production.  Ketoacidosis induced by diet is different to ketoacidosis as a complication of diabetes.  In the diet induced scenario, ketones do not exceed 8 mmol/L; in diabetic ketoacidosis, levels can exceed 20 mmol/L (Storoni & Plant, 2015).

The mechanism behind the positive effects of a ketogenic diet on the mitochondria appears to be via the reduction of reactive oxygen species through its effect on uncoupling proteins.  Uncoupling proteins are transporters present in the inner membrane of the mitochondria.  Their job is to carry a proton across the membrane to provide energy for oxidative phosphorylation.  A ketogenic diet appears to protein the activity of uncoupling proteins with a corresponding decline in ROS.  Furthermore, authors of this study found a ketogenic diet increases ATP (energy production), suppresses pro-inflammatory cytokines, and provides neuro-protective effects by stabilising ATP-potassium channels (located on the cell surface of neurons), thereby stabilising neuron excitability (Storoni & Plant, 2015).

A study by Zhu et al., (2016) aimed to determine the impact of a ketogenic diet on neurobehavioural development when used to treat children with intractable epilepsy, confirming the efficacy of a ketogenic diet, as well as the correlation between early eletroencephalography (EEG) changes in the early stages with treatment efficacy.

Intractable epilepsy refers to seizures that persist to be uncontrolled, despite treatment with two or more anti-epileptic drugs.  Results of the study demonstrated a ≥50% reduction in seizure frequency in 69.0% (29/42), 54.8% (23/42), 40.5% (17/42), and 33.3% (14/42) patients after 3, 6, 12, and 18 months of KD treatment, respectively (Zhu et al., 2016).  Authors made note the improvement is more significant with prolonged treatment using a ketogenic diet.

References

Storoni M & Plant G. The therapeutic potential of the ketogenic diet in treating multiple progressive sclerosis. Mult Scler Int. 2015;2015:681289. Doi: 10.1155/2015/681289. Retrieved from http:// http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709725/.

Zhu D, Wang M, Wang J, Yuan J, Niu G, Zhang G, Sun L, Xihong H, Xie M, Zhao Y. Ketogenic diet effects on neubehavioural development of children with intractable epilepsy: a prospective study. 2016;(55):87-91. Doi: http://dx.doi.org/10.1016/j.yebeh.2015.12.011.

World Health Organisation. What are neurological diseases? (2016). Retrieved from http:// http://www.who.int/features/qa/55/en/.

 

 

 

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