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Ketosis. It has become one of the most popular words of the 21^st century. Often connected to weight loss plans, “ketosis” is also strongly associated with epilepsy: the ketogenic diet was first introduced by clinicians as a treatment for epilepsy in the 1920s. Over the last decade, researchers have been studying the effect of ketosis on other neurological disorders, with promising results.

In ketosis, the mitochondria burn fat instead of glucose for energy metabolism. Ketosis can be achieved through periods of fasting or by restricting the intake of carbohydrates in the diet, leading the body to break down fatty acids to produce higher-than-normal levels of the so-called ketone bodies—acetoacetate, ?-hydroxybutyric acid, and acetone—through a process called ketogenesis, which occurs principally in the mitochondrial matrix in the liver. Research studies suggest that the “state of ketosis” and ketone bodies may exert a neuroprotective action and support brain metabolism.^1,2

Neuroprotection, Mitochondria, and Contraindications

Human studies have demonstrated a reduction of Alzheimer’s disease and Parkinson’s disease symptoms in participants following a clinical ketogenic diet.^3-5 These improved symptoms included cognitive as well as motor symptoms and overall disease ratings. Therapeutic ketogenic diets have also been studied by IFM educator Terry Wahls, MD, IFMCP, with the specific aim of reversing the symptoms of multiple sclerosis. Such diets have been shown to stimulate mitochondrial biogenesis, improve mitochondrial function, and reduce oxidative stress.^2,6,7 Dr. Wahls has used ketogenic diets in her clinical practice for a wide variety of health issues that result from mitochondrial disease. In the following IFM video, Dr. Wahls talks about the importance of diet for patients with neurological disease symptoms like fatigue.

Although the ketogenic diet is seen by many as a promising therapy for diverse neurological diseases, the long-term effects of this kind of diet in humans remains uncertain. To this end, some researchers continue to study the effects of intermittent metabolic switching for optimizing brain function and resilience.^8,9 Metabolic switching describes the body’s change of fuel source from glucose to fat and ketones after fasting or prolonged exercise^8,10 and may impact multiple signaling pathways believed to support neuroplasticity and overall brain health.⁸

Contraindications

Since ketogenic diets are restrictive in nature, application of this diet strategy to the elderly population or patients with neurodegenerative disorders should be done with caution regarding sufficient nutrient intake and maintaining a healthy appetite. There are a range of other populations with contraindications for a ketogenic diet, including, but not limited to, patients who have type 1 diabetes, who are pregnant or breastfeeding, who have kidney, liver, or heart failure, or who have an eating disorder.^11,12 In addition, the APOE4 allele is the primary genetic risk factor for Alzheimer’s disease, and APOE4 carriers may have increased risk of unfavorable lipid profiles.¹³ This creates additional considerations for this population when developing a personalized nutritional approach to disease treatment or prevention that may or may not include a ketogenic diet.¹⁴

Conclusion

Ketogenic diets have been found to have a positive impact on some neurological conditions; however, this therapeutic approach may not be appropriate for all populations. The functional medicine approach uses patient-centered care to create personalized interventions and prevention strategies to support brain health. IFM tools include therapeutic food plans that support metabolic switching while emphasizing foods and nutrients that benefit mitochondria.

Research studies continue to enhance our understanding of how ketogenic therapies work and what effects they have on both mitochondrial function and neurological disorders. Learn more about the latest research as well as clinical applications at IFM’s upcoming Bioenergetics Advanced Practice Module (APM).

Related Articles

Neurodegenerative Disease: Improving Outcomes Through Nutrition

Emerging Concepts: Type 2 Diabetes and the Ketogenic Diet

Fasting and Mitochondrial Health

References

1. Jensen NJ, Wodschow HZ, Nilsson M, Rungby J. Effects of ketone bodies on brain metabolism and function in neurodegenerative diseases. Int J Mol Sci. 2020;21(22):8767. doi:3390/ijms21228767
2. Tao Y, Leng SX, Zhang H. Ketogenic diet: an effective treatment approach for neurodegenerative diseases. Curr Neuropharmacol. 2022;20(12):2303-2319. doi:2174/1570159X20666220830102628
3. Pavón S, Lázaro E, Martínez O, et al. Ketogenic diet and cognition in neurological diseases: a systematic review. Nutr Rev. 2021;79(7):802-813. doi:1093/nutrit/nuaa113
4. Grammatikopoulou MG, Goulis DG, Gkiouras K, et al. To keto or not to keto? A systematic review of randomized controlled trials assessing the effects of ketogenic therapy on Alzheimer disease. Adv Nutr. 2020;11(6):1583-1602. doi:1093/advances/nmaa073
5. Wu L, Chu L, Pang Y, et al. Effects of dietary supplements, foods, and dietary patterns in Parkinson’s disease: meta-analysis and systematic review of randomized and crossover studies. Eur J Clin Nutr. 2024;78(5):365-375. doi:1038/s41430-024-01411-1
6. Yang H, Shan W, Zhu F, Wu J, Wang Q. Ketone bodies in neurological diseases: focus on neuroprotection and underlying mechanisms. Front Neurol. 2019;10:585. doi:3389/fneur.2019.00585
7. Brocchi A, Rebelos E, Dardano A, Mantuano M, Daniele G. Effects of intermittent fasting on brain metabolism. Nutrients. 2022;14(6):1275. doi:3390/nu14061275
8. Mattson MP, Moehl K, Ghena N, Schmaedick M, Cheng A. Intermittent metabolic switching, neuroplasticity, and brain health. Nat Rev Neurosci. 2018;19(2):63-80. doi:1038/nrn.2017.156
9. Mishra S, Singh B. Intermittent fasting and metabolic switching: a brief overview. Biomed Pharmacol J. 2020;13(3). doi:13005/bpj/2030
10.  Wilhelmi de Toledo F, Grundler F, Sirtori CR, Ruscica M. Unravelling the health effects of fasting: a long road from obesity treatment to healthy life span increase and improved cognition. Ann Med. 2020;52(5):147-161. doi:1080/07853890.2020.1770849
11.  Watanabe M, Tuccinardi D, Ernesti I, et al. Scientific evidence underlying contraindications to the ketogenic diet: an update. Obes Rev. 2020;21(10):e13053. doi:1111/obr.13053
12.  Muscogiuri G, El Ghoch M, Colao A, et al. European guidelines for obesity management in adults with a very low-calorie ketogenic diet: a systematic review and meta-analysis. Obes Facts. 2021;14(2):222-245. doi:1159/000515381
13.  Dunk MM, Li J, Liu S, et al. Associations of dietary cholesterol and fat, blood lipids, and risk for dementia in older women vary by APOE genotype. Alzheimers Dement. 2023;19(12):5742-5754. doi:1002/alz.13358
14.  Norwitz NG, Saif N, Ariza IE, Isaacson RS. Precision nutrition for Alzheimer’s prevention in ApoE4 carriers. Nutrients. 2021;13(4):1362. doi:3390/nu13041362