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Neurological Disorders and The Ketogenic Diet

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  Published on January 13th, 2021
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  Last modified April 15th, 2021
neurological disorders

Neurological disorders, such as epilepsy, Alzheimer’s disease, Parkinson’s disease, sleep disorders, brain cancer, autism, pain, multiple sclerosis, and various types of headaches, are often insufficiently treatable using pharmacological therapies. To make things worse, lots of medications have side effects. Hence, many patients look for more natural treatments, and luckily, research has begun to support the relationship between diet and various health conditions. In the future, the ketogenic diet could become the “natural” support for treatment for a variety of general health and neurological disorders.

A great example is drug-resistant epilepsy. The ketogenic diet has been successfully used as an epilepsy treatment for decades. Although the mechanisms behind anticonvulsant effects are not yet clear, there have been enough experimental studies carried out to confirm its efficacy.

 

What About Other Neurological Disorders?

Admittedly, we are still lacking a sufficient amount of clinical data. Still, the literature supporting the broad use of the ketogenic diet and its variants against a variety of neurological conditions has been emerging in the past decades.

Lately, researchers in this field have been identifying mechanisms through which the ketogenic diet may provide neuroprotective activity. They speculate that the main factors for this activity are the ketone body production and the reduction in blood glucose levels. [1,2]

 

Aging and Longevity

Research suggests that the ketogenic diet may slow down some degenerative processes that occur in the aging brain cells. The ketogenic diet is likely to involve some neuroprotective mechanisms, especially in the context of pathological neurodegeneration. For example, studies, conducted on rats, have shown that medium-chain triglycerides (MCT) have a protective effect on some of the age-related intracellular dysfunctions. [3,4]

 

Alzheimer’s disease

The ketogenic diet might also play a beneficial role in patients with Alzheimer’s disease (AD). So far, clinical studies have demonstrated some promising results. Namely, a certain type of AD patients has shown significant improvement in various memory and learning tasks after being on an MCT ketogenic diet for a while.

What is more, even diets such as the Mediterranean have shown some promise with AD. This suggests there something about a high intake of healthy fats and a low intake of carbohydrates that acts neuroprotective. [5,6,7,8,9]

 

Parkinson’s Disease

Research suggests that ketone bodies may provide neuroprotective benefits in the case of Parkinson’s disease (PD). By providing the brain with an alternative fuel source (ketone bodies), disrupted glucose uptake can be bypassed. This prevents neuron degradation from starvation and thus helps prevent further motor dysfunctions from motor neuron death.[6,10]

 

ALS

If you are familiar with Amyotrophic lateral sclerosis (ALS), you know that it is a rapidly progressive disease that leaves the affected individual profoundly weak despite retained cognitive functioning. Again, animal models of ALS have shown some improvement after administration of the ketogenic diet. However, the survival time was not extended in these animals.

Investigators have been wondering whether the timing of intervention is crucial for a protective effect of the ketogenic diet treatment. In fact, this question is applicable to all neurodegenerative diseases. [11,12]

 

Cancer

Theoretically, depriving cancer cells of their usual fuel supply (e.g. glucose) by use of the ketogenic diet could be clinically therapeutic. Studies, conducted on both humans and animals with brain tumors, have led to some interesting findings. The brain tumor growth rates decreased on the ketogenic diet.

There are several human cases with improved brain tumors on the ketogenic and MCT-based diets. Moreover, the diet seems to improve the general quality of life in some patients. [13, 14, 15]

 

Psychiatric and Developmental Disorders

The ketogenic diet may also have mood-stabilizing properties. Specifically, studies on depression, schizophrenia, and bipolar disorder seemed to get beneficial effects on the diet, comparable to monoamines and other mood-stabilizing medications. [16,17, 18, 19, 20]

Lately, limited clinical research has even raised the intriguing possibility that the ketogenic diet might help ease some of the deviant behaviors, seen in children with an autism spectrum disorder

. This is a neurodevelopmental disorder that affects mostly language and social function. Some children seem to show significant behavior improvement on a ketogenic diet variant, consisting of MCT. On the downside, many children with autism don’t tolerate changes in dietary and other routines too well. [21, 22, 23, 24]

 

Chronic Headaches & Migraines

Let us end this list of possible benefits of the ketogenic diet in neurological disorders with one of the most common headache disorders: migraines. Scientists have come to some good theoretical reasons to consider the ketogenic diet for chronic migraines.

The idea for this petition nutritional therapy comes from a potential overlap of migraines and epilepsy, although the intrinsic mechanisms, underlying both phenomena, differ in many aspects.

If you happen to be one of the chronic migraine sufferers, you might be aware that doctors can prescribe certain antiepileptic drugs for this specific form of headaches. Interestingly, the first report of using the ketogenic diet to treat migraine came as early as in the 1920s, soon after the diet’s first use for epilepsy. [25, 26, 27]

 

Concluding Thoughts on the Ketogenic Diet and Neurological Conditions

To conclude, we need more clinical data to support a definite conclusion, but preliminary studies show that the metabolic shifts that occur on the ketogenic diet might lead to neuroprotective actions. If you or someone close to you suffers from any neurological disorder, do consult with the treating doctor before trying the diet. Anyhow, if you are a migraine sufferer, and otherwise healthy, studies suggest that there is no harm in giving the ketogenic diet a try.

 

References

1. Gasior, M., Rogawski, M. A., & Hartman, A. L. (2006). Neuroprotective and disease-modifying effects of the ketogenic diet. Behavioural pharmacology17(5-6), 431–439. https://doi.org/10.1097/00008877-200609000-00009

2. W?odarek D. (2019). Role of Ketogenic Diets in Neurodegenerative Diseases (Alzheimer’s Disease and Parkinson’s Disease). Nutrients11(1), 169. https://doi.org/10.3390/nu11010169

3. Roberts, M. N., Wallace, M. A., Tomilov, A. A., Zhou, Z., Marcotte, G. R., Tran, D., Perez, G., Gutierrez-Casado, E., Koike, S., Knotts, T. A., Imai, D. M., Griffey, S. M., Kim, K., Hagopian, K., McMackin, M. Z., Haj, F. G., Baar, K., Cortopassi, G. A., Ramsey, J. J., & Lopez-Dominguez, J. A. (2017). A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice. Cell metabolism26(3), 539–546.e5. https://doi.org/10.1016/j.cmet.2017.08.005

4.Gano, L. B., Patel, M., & Rho, J. M. (2014). Ketogenic diets, mitochondria, and neurological diseases. Journal of lipid research55(11), 2211-2228.

5. Stafstrom, C. E. & Rho, J. M. (2012). The ketogenic diet as a treatment paradigm for diverse neurological disorders. Frontiers in Pharmacology, 3, 1–8. doi: 10.3389/fphar.2012.00059

6. Kashiwaya, Y., Takeshima, T., Mori, N., Nakashima, K., Clarke, K., & Veech, R. L. (2000). d-?-Hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease. Proceedings of the National Academy of Sciences97(10), 5440-5444.

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. doi: 10.1186/1743-7075-2-28. PMID: 16229744; PMCID: PMC1282589.

8. Yao J, Chen S, Mao Z, Cadenas E, Brinton RD. 2-Deoxy-D-glucose treatment induces ketogenesis, sustains mitochondrial function, and reduces pathology in female mouse model of Alzheimer’s disease. PLoS One. 2011;6(7):e21788. doi: 10.1371/journal.pone.0021788. Epub 2011 Jul 1. PMID: 21747957; PMCID: PMC3128612.

9. 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. doi: 10.1186/1743-7075-6-31. PMID: 19664276; PMCID: PMC2731764.

10. Phillips MCL, Murtagh DKJ, Gilbertson LJ, Asztely FJS, Lynch CDP. Low-fat versus ketogenic diet in Parkinson’s disease: A pilot randomized controlled trial. Mov Disord. 2018 Aug;33(8):1306-1314. doi: 10.1002/mds.27390. Epub 2018 Aug 11. Erratum in: Mov Disord. 2019 Jan;34(1):157. PMID: 30098269; PMCID: PMC6175383.

11. 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. doi: 10.1186/1471-2202-7-29. PMID: 16584562; PMCID: PMC1488864.

12. Paganoni, S., & Wills, A. M. (2013). High-fat and ketogenic diets in amyotrophic lateral sclerosis. Journal of child neurology28(8), 989–992. https://doi.org/10.1177/0883073813488669

13. Seyfried, T. N., & Mukherjee, P. (2005). Targeting energy metabolism in brain cancer: review and hypothesis. Nutrition & metabolism2, 30. https://doi.org/10.1186/1743-7075-2-30

14. Seyfried TN, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P. Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? Epilepsy Res. 2012 Jul;100(3):310-26. doi: 10.1016/j.eplepsyres.2011.06.017. Epub 2011 Aug 31. PMID: 21885251.

15. Nebeling LC, Miraldi F, Shurin SB, Lerner E. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr. 1995 Apr;14(2):202-8. doi: 10.1080/07315724.1995.10718495. PMID: 7790697.

16. Hartman, A. L., Gasior, M., Vining, E. P. G., & Rogawski, M. A. (2007). The neuropharmacology of the ketogenic diet. Pediatric Neurology36(5), 281-292. DOI: 10.1016/j.pediatrneurol.2007.02.008

17. Bostock, E. C. S., Kirkby, K. C., & Taylor, B. V. M. (2017). The current status of the ketogenic diet in psychiatry. Front Psychiatryhttps://doi.org/10.3389/fpsyt.2017.00043

18. Murphy, P., Likhodii, S., Nylen, K., & Burnham, W. M. (2004). The antidepressant properties of the ketogenic diet. Biological Psychiatry56(12), 981-983. DOI: 10.1016/j.biopsych.2004.09.019

19. Hallbook, T., Ji, S., Maudsley, S., & Martin, B. (2012). The effects of the ketogenic diet on behavior and cognition. Epilepsy Research100(3), 304-309. https://doi.org/10.1016/j.eplepsyres.2011.04.017

20. Patrick, R. P., & Ames, B. N. (2015). Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: Relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. FASEB Journal29(6), 2207-2222. DOI: 10.1096/fj.14-268342

21. Ruskin, D. N., Svedova, J., Cote, J. L., Sandau, U., Rho, J. M., Kawamura, Jr, M., Boison, D., & Masino, S. A. (2013). Ketogenic diet improves core symptoms of autism in BTBR mice. PLoS One8(6), doi: 10.1371/journal.pone.0065021

22. Napoli, E., Duenas, N., & Giulivi, C. (2014). Potential therapeutic use of the ketogenic diet in autism spectrum disorders. Frontiers in Pediatrics, https://doi.org/10.3389/fped.2014.00069

23. Zarnowska, I., Chrapko, B., Gwizda, G., Nocun, A., Mitosek-Szewczyk, K., & Gasior, M. (2018). Therapeutic use of carbohydrate-restricted diets in an autistic child: A case report of clinical and 18FDG PET findings. Metabolic Brain Disease33, 1187-1192. https://doi.org/10.1007/s11011-018-0219-1

24. Newell, C., Bomhof, M. R., Reimer, R. A., Hittel, D. S., Rho, J. M., & Shearer, J. (2016). Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder. Molecular Autism7(37), https://doi.org/10.1186/s13229-016-0099-3

25. Gross, E. C., Klement, R. J., Schoenen, J., D’Agostino, D. P., & Fischer, D. (2019). Potential protective mechanisms of ketone bodies in migraine prevention. Nutrients, 11(4), 811. DOI: 10.3390/nu11040811

26. Barbanti, P., Fofi, L., Aurilia, C., Egeo, G., & Caprio, M. (2017). Ketogenic diet in migraine: Rationale, findings, and perspectives. Neurol Sci, DOI: 10.1007/s10072-017-2889-6

27. Di Lorenzo, C., Coppola, G., Bracaglia, M., Di Lenola, D., Evangelista, M., Sirianni, G., Rossi, P., Di Lorenxo, G., Serrao, M., Parisi, V., & Pierelli, F. (2016). Coritcal functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: A multimodal evoked potentials study. J Headache Pain, DOI: 10.1186/s10194-016-0650-9

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