Ketogenic Diets for White Matter Disease

Estimated reading time: 8 minutes

The brain is mostly made up of gray matter and white matter. The gray matter covers the outside of our brain, which is called the cortex, meaning the bark. White matter is mostly on the inside. White matter consists of nerve fibers that connect different parts of the brain, and it’s covered in a myelin sheath. This protective sheath appears white because it’s made up exclusively of fat, along with a few other types of molecules. White matter’s role is to conduct information and move it from one part of the brain to another.

Chronic ischemic brain disease, CNS small vessel disease, leukoaraiosis, white matter hyperintensities, white matter lesions, lacunar infarcts, microvascular disease, or small vessel disease are all names that refer to the same thing. They are all White Matter Diseases.

What causes White Matter Disease?

White matter disease means that the blood vessels supplying the white matter have either closed up, broken off, or swollen under pressure, leading to insufficient oxygen and micronutrient supply to nerve cells. Tiny blood vessels die off, which reduces or entirely eliminates the energy source for the brain cells supplied by that particular blood vessel. White matter disease is a term referring to sustained damage to a specific part of the brain caused by reduced blood flow.

In the brain, these things typically happen in the periventricular spaces, which is the center of the brain. The reason for this is that the blood vessels in this part of the brain have the smallest diameter, as small as a strand of hair. Hence, even a small amount of damage in this area can lead to issues. Inflammation causes this damage.

What’s causing neuroinflammation?

Newly discovered functional subsets of microglia have been found to contribute to the white matter response in CNS disease onset and progression. Microglia show different molecular patterns and morphologies depending on the disease type and brain region, particularly in white matter. In the later stages of the disease, overactive microglia can perpetuate disease progression in white matter diseases through their pro-inflammatory, oxidative, and excitotoxic effects, impairing myelin repair and inducing neurodegeneration.

Let me give an example of what this looks like. Some microglia get put on overdrive in a highly inflammatory environment and start chomping down on things they shouldn’t. They start to munch (phagocytosis) cells and structures that are not dead yet. Some of that is myelin in white matter. And if we had chilled the immune system out, much myelin might have been saved.

Do you know what makes microglia happy, calm, and functioning? A ketogenic diet. Think I am making this stuff up? I am not. Keep reading.

How can a ketogenic diet help reduce the neuroinflammation causing White Matter Disease?

In this study, researchers explored the therapeutic effects of the ketogenic diet (KD) on depressive-like behaviors in rodent models. The results revealed that the ketogenic diet significantly improved depressive-like behaviors. They reported that the symptoms were likely mediated through the restoration of microglial inflammatory activation and neuronal excitability.

Altogether, we demonstrated the therapeutic effects of KD on depressive-like behaviors, which are probably mediated via the restoration of microglial inflammatory activation and neuronal excitability.

Guan, Y. F., Huang, G. B., Xu, M. D., Gao, F., Lin, S., Huang, J., … & Sun, X. D. (2020). Anti-depression effects of ketogenic diet are mediated via the restoration of microglial activation and neuronal excitability in the lateral habenula. Brain, Behavior, and Immunity88, 748-762.

In this next study, researchers looked at the protective and anti-inflammatory effects of the ketogenic diet in a mouse model of Parkinson’s disease. They used a neurotoxin that selectively destroys dopaminergic neurons in the substantia nigra, a region of the brain involved in movement control. The resulting damage to these neurons leads to motor dysfunction and other symptoms that closely resemble Parkinson’s disease in humans. The results showed that when the mice were given the ketogenic diet before being exposed to the neurotoxin, their motor problems improved. The diet also helped protect the brain cells responsible for producing dopamine, which is typically damaged in Parkinson’s disease. The ketogenic diet reduced the activation of certain immune cells (microglia) in the brain and lowered the levels of inflammation-causing molecules (proinflammatory cytokines) in the affected area.

The data showed that pretreatment with KD alleviated the motor dysfunction induced by MPTP (neurotoxin).

Yang, X., & Cheng, B. (2010). Neuroprotective and anti-inflammatory activities of ketogenic diet on MPTP-induced neurotoxicity. Journal of molecular neuroscience42, 145-153.

This next comprehensive review delves into the molecular mechanisms that control how microglia, the brain’s immune cells, behave in different ways. Microglia can either adopt harmful, inflammation-causing states or helpful, inflammation-fighting states that protect the brain. The review also examines a wealth of preclinical data, which suggests that following a ketogenic diet (KD) can lead to a series of beneficial changes in microglial cells.

These changes seem to stem from the inhibition of pathways that would otherwise push microglia toward harmful, pro-inflammatory states. By doing so, the ketogenic diet could potentially promote helpful, anti-inflammatory states in microglia, which may ultimately benefit individuals with various neurological conditions.

In addition, a wide array of preclinical data indicates that following a KD an orchestrated set of mechanisms take place in microglial cells. Those mechanisms appear to result in the inhibition of pathways governing the acquisition and maintenance of predominantly pro-inflammatory microglial states/phenotypes…

Morris, G., Puri, B. K., Maes, M., Olive, L., Berk, M., & Carvalho, A. F. (2020). The role of microglia in neuroprogressive disorders: mechanisms and possible neurotherapeutic effects of induced ketosis. Progress in Neuro-Psychopharmacology and Biological Psychiatry99, 109858.

Sorry. Do you need some more scientific evidence to feel convinced? No problem. I got you! How about this next article, It’s titled, The Therapeutic Role of Ketogenic Diet in Neurological Disorders.

This review emphasizes that the ketogenic diet may offer therapeutic benefits for patients with neurological issues, particularly by addressing neuroinflammation, a key contributing factor in these conditions. By examining scientific literature, it’s clear that the ketogenic diet could impact not only the course of these neurological disorders but also the effectiveness of their treatment. The authors suggest that a ketogenic diet should be a part of the treatment for those with neurological issues.

For the moment, it seems that KD can provide therapeutic benefits in patients with neurological problems by effectively controlling the balance between pro- and antioxidant processes and pro-excitatory and inhibitory neurotransmitters, and modulating inflammation or changing the composition of the gut microbiome.

Pietrzak, D., Kasperek, K., Rękawek, P., & Piątkowska-Chmiel, I. (2022). The therapeutic role of ketogenic diet in neurological disorders. Nutrients14(9), 1952.


So why is a mental health counselor interested in brain health writing about White Matter Disease and making sure you know a ketogenic diet is a possible treatment? Because some of you (or your loved ones) will have the mood, memory, and balance symptoms that come with various White Matter Diseases. And when they are found on a scan, they will be given ineffective treatment options.

Current treatments, as you can imagine, are uninspired—physical therapy, medicating hypertension and diabetes, and watching your cholesterol. You can read about these conventional treatment options here:

Maybe instead of telling people not to worry about the white matter damage being picked up on scans as “aging” and to not worry about it, we could have neurologists offer a ketogenic diet.

Maybe a neurologist could explain to someone that a ketogenic diet, in one fell swoop, can stop, slow, or even reverse their white matter disease by directly addressing metabolic and immune system dysfunction.

Why aren’t microglial activation and function targeted with a ketogenic diet as a potential therapeutic strategy for treating white matter diseases?

As you can see, the scientific evidence is already there.

If you need help learning how to implement a ketogenic diet for white matter disease or other neurological issues, you may inquire regarding my online program below:


Alber, J., Alladi, S., Bae, H.-J., Barton, D. A., Beckett, L. A., Bell, J. M., Berman, S. E., Biessels, G. J., Black, S. E., Bos, I., Bowman, G. L., Brai, E., Brickman, A. M., Callahan, B. L., Corriveau, R. A., Fossati, S., Gottesman, R. F., Gustafson, D. R., Hachinski, V., … Hainsworth, A. H. (2019). White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 5, 107–117.

de Groot, M., Ikram, M. A., Akoudad, S., Krestin, G. P., Hofman, A., van der Lugt, A., Niessen, W. J., & Vernooij, M. W. (2015). Tract-specific white matter degeneration in aging: The Rotterdam Study. Alzheimer’s & Dementia, 11(3), 321–330.

Guan, Y.-F., Huang, G.-B., Xu, M.-D., Gao, F., Lin, S., Huang, J., Wang, J., Li, Y.-Q., Wu, C.-H., Yao, S., Wang, Y., Zhang, Y.-L., Teoh, J., Xuan, A., & Sun, X.-D. (2020). Anti-depression effects of ketogenic diet are mediated via the restoration of microglial activation and neuronal excitability in the lateral habenula. Brain, Behavior, and Immunity, 88, 748–762.

I CARE FOR YOUR BRAIN with DR. SULLIVAN (Director). (2022, December 14). White Matter Disease.

Morris, G., Puri, B. K., Maes, M., Olive, L., Berk, M., & Carvalho, A. F. (2020). The role of microglia in neuroprogressive disorders: Mechanisms and possible neurotherapeutic effects of induced ketosis. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 99, 109858.

Pietrzak, D., Kasperek, K., Rękawek, P., & Piątkowska-Chmiel, I. (2022). The Therapeutic Role of Ketogenic Diet in Neurological Disorders. Nutrients, 14(9), Article 9.

Sweeney, M. D., Montagne, A., Sagare, A. P., Nation, D. A., Schneider, L. S., Chui, H. C., Harrington, M. G., Pa, J., Law, M., Wang, D. J. J., Jacobs, R. E., Doubal, F. N., Ramirez, J., Black, S. E., Nedergaard, M., Benveniste, H., Dichgans, M., Iadecola, C., Love, S., … Zlokovic, B. V. (2019). Vascular dysfunction—The disregarded partner of Alzheimer’s disease. Alzheimer’s & Dementia, 15(1), 158–167.

Wardlaw, J. M., Smith, C., & Dichgans, M. (2019). Small vessel disease: Mechanisms and clinical implications. The Lancet Neurology, 18(7), 684–696.

Yang, X., & Cheng, B. (2010). Neuroprotective and Anti-inflammatory Activities of Ketogenic Diet on MPTP-induced Neurotoxicity. Journal of Molecular Neuroscience, 42(2), 145–153.

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