Impact of Ketogenic Diet on Neurological Disorders

Primary Category

Nutrition

P-Category

Secondary Category

S-Category

Authors:

Tasneem Kousar MBBS,
Abeer Sarwar MBBS,
Junaid Kalia MD

Introduction

Ketogenic diet is a diet rich in fats, moderate proteins and low on carbohydrates.

The diet was initially developed to treat epilepsy in children

Over the years, a number of researches are in place to establish its role in neurological function and pathologies

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Ketones bodies are an important source of energy

They are water soluble lipids that contain ketones groups

They are produced in the mitochondria of liver during breakdown of fatty acids

Ketones are used as an energy source during periods of low glucose like fasting

Studies show ketones also have anti-inflammatory, anti-oxidant, epigenetic, enhancing mitochondrial function properties

Goal of Ketogenic Diet

To mimic the biochemical model of fasting

To utilize the neuroprotective effect of ketones in various brain pathologies

To decrease overall on inflammatory response to the body and brain.

Types of Ketogenic Diet

Classic Ketogenic diet

Targeted Ketogenic diet

Modified Atkin's diet

Medium chain triglyceride oil (MCT)

Effects on Brain health

Ketone bodies are able to cross the blood-brain barrier

In normal circumstances, glucose is utilized by the body for ATP production. During periods of fasting or starving, ketone bodies become the source of energy

After crossing the blood brain barrier they can be a source of energy and provide ATP replacing the function of glucose

Figure 1: Three types of ketone bodies

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There are 3 ketones bodies

Beta-Hydroxybutyrate

Acetone

Acetoacetate

Epilepsy

Ketogenic diet are well established as a treatment option in pharmacologically resistant epilepsy especially in children

A ketone diet is started after unresponsiveness to at least 2 epileptic drugs

The exact anti-epileptic properties of ketone bodies are still unknown

Many in vivo and in vitro studies are currently studying different molecular targets of ketones bodies. Some of the targets being studied include

GABA
Glutamate receptors and transporters
Histone Deacetylation
ATP Potassium channels

The role of ketone bodies is diverse, as it exerts anti-inflammatory, anti-oxidant and mitochondrial effects. It also affects the gut microbe. All of the above can contribute to its anti-epileptic effects.

Neurodegenerative disease

Glucose Metabolism in brain

Studies have also shown reduced glucose uptake in Alzheimer's disease.
The BENEFIC (Brain ENErgy, Fitness, Imaging and Cognition) Trial was conducted to assess the ketones and glucose metabolism via PET (Positron Emission Tomography). The study concluded that ketogenic drink for 6 months showed increased ketone uptake in white matter bypassing glucose deficit and improvement in cognitive function.

Mitochondrial involvement in brain disease

The neurodegenerative diseases like Alzheimer's are linked to B-Amyloid protein accumulation in brain that can ultimately causes mitochondrial dysfunction resulting in decreased ATP and eventually cell death.
Ketogenic diet causes an upregulation of mitochondrial genes as well as genes utilized in metabolism while stimulating the increase in mitochondrial mass.
This ensures the supply of ATP. The availability of ATP and enhanced mitochondrial function contribute to improved axonal survival and prevents demyelination.
β-hydroxybutyrate Improves mitochondrial function by decreasing the production of Reactive Oxygen Species (ROS)

The role of ketones in myelin preservation is still under investigation

Traumatic Brain Injury

Traumatic brain injury's can results in disruption of the neuronal flow and glucose metabolism. The cerebral cells increase their glucose uptake to maintain the neuronal flow also known as hyperglycolysis.

Hyperglycemia in the acute recovery phase of brain injury plays detrimental effect.

It has been proposed that further investigation into the ketogenic diet is needed to understand its potential benefits for traumatic brain injuries and its role with neuro Protection.

Ischemic stroke

Ketone diet exerts neuroprotective effect by selectively protecting neurons and prolonging their survival from mechanisms that precipitate excitotoxicity and death,

Ketones also protects from free radical injury in ischemic stroke.

Neuroinflammation

Migraine is an inflammatory disorder.

It is characterized by a sterile meningeal neurogenic inflammation which stimulates trigeminal afferent nociceptive neurons and activates mast cells and macrophages which in turn release cytokines, serotonin, histamine and proteases

KD decreases TNFa (tumor necrosis factor alpha) levels and NFjB (nuclear factor j B) nuclear translocation, inhibits COX2 (cyclooxygenase 2) and microsomal prostaglandin E(2) synthase-1 expression

Neurological Tumors

Tumor cells have a high demand for glucose and posses limited ability to oxidize ketone bodies.

Ketones produced with intake of ketogenic diet are able to bypass glucose metabolism and provide ATP to brain cells. The depletion of glucose can starve the tumor cells causing cell death.

Studies done on patients with brain tumours shows that ketogenic diet have certain benefits that include improved response of the tumor to standard treatment (chemotherapy/radiation) and improvement in quality of life measures (alertness)

Adverse effects of ketogenic diet

Common side effects include, Flu-like symptoms, headaches and muscle aches. This is also known as keto flu. The treatment of keto flu is hydration and over the counter electrolytes

Other side effects are kidney stones, vitamin and mineral deficiencies, and gastrointestinal distress.

Increased intake of saturated fat can lead to dyslipidemia and coronary artery diseases.

Bibliography

Arora, N., & Mehta, T. R. (2020). Role of the ketogenic diet in acute neurological diseases. Clinical Neurology and Neurosurgery, 192, 105727. https://doi.org/10.1016/j.clineuro.2020.105727

Barbanti P;Fofi L;Aurilia C;Egeo G;Caprio M; (n.d.). Ketogenic diet in Migraine: Rationale, findings and perspectives. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. Retrieved October 24, 2021, from https://pubmed.ncbi.nlm.nih.gov/28527061/.

Hartman, A. L., Gasior, M., Vining, E. P. G., & Rogawski, M. A. (2007, May). The neuropharmacology of the ketogenic diet. Pediatric neurology. Retrieved October 13, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1940242/.

Ketogenic diet in children with malignant or recurrent/refractory brain tumor - full text view. Full Text View - ClinicalTrials.gov. (n.d.). Retrieved December 2, 2021, from https://clinicaltrials.gov/ct2/show/NCT03328858.

Kossoff EH, Zupec-Kania BA, Auvin S, Ballaban-Gil KR, Christina Bergqvist AG, Blackford R, Buchhalter JR, Caraballo RH, Cross JH, Dahlin MG, Donner EJ, Guzel O, Jehle RS, Klepper J, Kang HC, Lambrechts DA, Liu YMC, Nathan JK, Nordli DR Jr, Pfeifer HH, Rho JM, Scheffer IE, Sharma S, Stafstrom CE, Thiele EA, Turner Z, Vaccarezza MM, van der Louw EJTM, Veggiotti P, Wheless JW, Wirrell EC; Charlie Foundation; Matthew's Friends; Practice Committee of the Child Neurology Society. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open. 2018 May 21;3(2):175-192. doi: 10.1002/epi4.12225. PMID: 29881797; PMCID: PMC5983110.

Pinto, A., Bonucci, A., Maggi, E., Corsi, M., & Businaro, R. (2018, April 28). Anti-oxidant and anti-inflammatory activity of ketogenic diet: New Perspectives for neuroprotection in alzheimer's disease. Antioxidants (Basel, Switzerland). Retrieved December 2, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981249/.

Roy, M, Fortier, M, Rheault, F, et al. A ketogenic supplement improves white matter energy supply and processing speed in mild cognitive impairment. Alzheimer's Dement. 2021; 7:e12217. https://doi.org/10.1002/trc2.12217

U.S. National Library of Medicine. (2020, October 2). LDL: The "bad" cholesterol. MedlinePlus. Retrieved October 23, 2021, from https://medlineplus.gov/ldlthebadcholesterol.html

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