multiple sclerosis

Ketogenic diet: can it play a role in treating symptoms of Multiple sclerosis?

Virginia Thornley, M.D., Neurologist, Epileptologist
September 19, 2018
Multiple sclerosis has no cure at this current moment. It is unclear what is the exact etiology otherwise there would be a cure. Based on research, genetic and environmental factors play a role. Based on MRI observations, there are inflammatory and degenerative components to the pathogenesis.
What is the ketogenic diet and how does it pertain the brain
The ketogenic diet was initially found to be effective in treatment of medically refractory seizures. But the underlying concept might be applied to other diseases as well.
Instead glucose as the energy substrate, ketones are utilized, If the supply of glucose is reduced, the energy source is shifted towards the beta-oxidation of fatty acids into ketone bodies. These ketones become the new source of energy and allows increased ATP formation which is the source of energy in the mitochondria, which is the powerhouse of the cell where energy is formed.
Different lines of thinking regarding pathogenesis of Multiple Sclerosis
There are lines of thought that Multiple sclerosis can be inflammatory versus neurodegenerative. Because of this many agents are directed towards the autoimmune component of the disease process. It is commonly thought that the autoimmune process results in the neurodegeneration seen on MRI.
As evidenced by the “black holes” seen on MRI after acute attacks, there is evidence there is a neurodegenerative aspect. This other line of thinking suggests that it is a degenerative process that triggers the inflammatory response.
It’s been found  that degenerating axons have abnormal mitochondria.
Ketogenic diet and inflammation
In one animal study, it was found that the ketogenic diet reduced inflammatory cytokines after 14 days in animals (2).
Ketogenic diet and increased ATP
In one animal model with a control group and a group on ketogenic diet, after 3 weeks it was found that those on the ketogenic diet had a higher ATP/ADP ratio which is speculated to contribute towards neuronal stability.

How can the ketogenic diet help with Multiple Sclerosis?
The ketogenic diet reduces the formation of reactive oxygen species. It preserves ATP production when the mitochondria fails. The thought is that the axons start to degenerate once the mitochondria are dysfunctional (1).
In summary
There are no human clinical studies on ketogenic diet and the improvement of multiple sclerosis. Based on pre-clinical studies, there is indication that ketogenic diet may help improve the ATP stores when the mitochondria becomes dysfunctional which may potentially slow neurodegeneration of axons.
The ketogenic diet might reduce inflammation which is thought to be triggered by a neurodegenerative process in Multiple Sclerosis. However, more studies are needed especially human clinical trials. Currently there is not enough evidence to support this based on the available studies as pre-clinical studies do not always correlate in human trials. More studies are needed.

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  1. Storoni, M., Plant, G. The therapeutic potential of the ketogenic diet in treating progressive multiple sclerosis. Mult. Scler. Int. 2015. doi 10.1155/2015/681289
  2. Dupuis, N., Curatolo, N., Benoist, J.F., Auvin, S., Ketogenic diet exhibits anti-inflammatory properties. Epilepsia, 2015. 56(7):e95-98
  3. DeVivo, D.C., Leckie, M.P., Ferrendell, J.S., McDougal, D.B., Jr. Chronic ketosis and cerebral metabolism. Ann Neurol. 1978, Apr. 394):331-337

Ketogenic diet and its variants modifed Atkins diet, low glycemic index treatment: effectiveness, side effect profile in patients with epilepsy and incidental weight loss

Virginia Thornley, M.D., Neurologist, Epileptologist, February 26, 2018

Doctors first took notice of the ketogenic diet working in patients with epilepsy in the 1920’s. But the exact mechanism remains unclear. One study elucidated that the ketone bodies are one of the reasons why the ketogenic diet works in patients with epilepsy. Ketosis occurs during a natural fasting state. In the ketogenic diet using high fat, the by-products of beta-oxidation of fatty acids which are beta-hydroxyacetate and acetoacetate in the blood do not correlate with patients who are doing better. Medium chain triglyceride fatty acids, which are a part of a variation of the ketogenic diet, are shown to suppress the AMPA receptors which subserve the excitatory neurotransmitter glutamate and may change energy use of the cell through mitochondrial processes (1).


Ketogenic diet and adverse effects

Some patients have difficulty adhering to the diet which makes it difficult to use. Common side effects because of the high-fat content are diarrhea, constipation, nausea, transient increase in lipemic values. Variations of the ketogenic diet are sometimes used to offset these side effects and reduce the non-compliance.

Some ketogenic variants

Ketogenic diet variants include modified Atkins diet, low glycemic index treatment, and medium chain diet. The ketogenic diet consists of 4:1 ratio of fat to carbohydrates shifting metabolism to the use of ketone bodies as a source of energy. A lower ratio is sometimes employed called the modified ketogenic diet with a 3:1 or 2:1 ratio of fat to carbohydrates. In the modified ketogenic diet, the palatability is improved and avoids the gastrointestinal symptoms associated with the ketogenic diet such as nausea. With the modified Atkins diet, carbohydrates are restricted to 10-20 grams a day, or a 1-2:1 ratio of protein to fat plus carbohydrates. In the low glycemic index treatment, carbohydrates are limited to 40-60 grams while 50-60% of the diet is fat and 20-30% is from protein. The medium-chain triglyceride diet employs oils as a supplement such as coconut oil. The palatability of these diets improve patient compliance and lessen the side effects of the ketogenic diet. Some patients also used the diets to incidentally lose weight in addition to treating seizures (2).


Effectiveness of the ketogenic diet and ketogenic diet variants

One study summarizing studies on patients using the classic ketogenic diet found that 50% of patients out of 206 had a >50% reduction of seizures using the classic ketogenic diet. Older patients seemed to benefit less. In the modified Atkins diet, seizures were reduced in younger patients with more frequent seizures. Patients tended to drop out because of the side effects, lack of perceived effectiveness and because of the restrictions in the diet. Patients greater than 12 years old were less adherent to the diet (3).

It is possible that the protective effects of the ketogenic diet are related to the medium chain triglyceride fatty acids and not the ketone bodies.




1. Augustin, et al, “Mechanism of action for medium-chain triglyceride ketogenic diet and metabolic disorders,” Lancet Neurology, 2018, Jan., 84-93.

2. McDonald, et al, “Ketogenic diets for adults with highly refractory epilepsy,” Epilepsy Currents, 2017, Nov.-Dec., 17(6):346-350.

3. Payne, et al, “The ketogenic and related diets in adolescents and adults-a review,” Epilepsia, 2011, Oct., 52(11):1941-1948.