UPDATED BY FRANZISKA SPRITZLER, RD, CDE
The ketogenic diet first became known as a therapeutic treatment in the 1920s, when it showed positive effects for children suffering from pediatric epilepsy. But does the diet help treat other neurological disorders, too? Studies continue to explore the extent of which the ketogenic diet can be used as therapy regarding neurological disorders.
What are Neurological Disorders?
Neurological disorders are a class of diseases that impact the brain, spine, and nerves. There are over 600 different diseases of the nervous system, many of which are increasing in frequency and lacking in effective treatment modalities.
Brain Diseases and Glucose
While every neurological disorder has its own characteristics, one theme that most have in common is impaired cerebral glucose metabolism, or the inability of the brain to get enough energy from glucose.
There are several key contributors to impaired cerebral glucose metabolism, but aging is one of the biggest.
However, glucose is not the only fuel source that can be used by the brain. Ketone bodies – fat-derived compounds created via carbohydrate restriction or severe calorie restriction – can also be used by the brain. In fact, research shows that ketone bodies, or ketones, are the preferred fuel source of the human brain, meaning that when both glucose and ketones are present, the brain will preferentially use ketones. Additionally, ketones are considered a “cleaner” fuel source because they produce less oxidative stress when they are metabolized compared to glucose. Finally, research has demonstrated that brain ketone uptake does not diminish with age, meaning this superior fuel source can still provide energy to the brain when glucose cannot.
Although using ketones for energy is just one way the keto diet can affect brain diseases, it provides a compelling reason to consider the ketogenic diet for several neurological disorders.
Keto and Epilepsy
Epilepsy is one of the most common serious neurological conditions in the world and is characterized by abnormal brain cell activity that results in recurrent seizures.
Interestingly, fasting recommendations for health were first recorded back in 500 BC and eventually became the primary therapeutic approach for epilepsy. Interestingly, fasting as a health recommendation dates back to 500 BC and later became the main treatment for epilepsy. But in the 1920s, researchers discovered that a high-fat, low-carb diet could replicate the seizure-controlling effects of fasting while allowing individuals to continue eating. Just like that, the ketogenic diet was born.
However, as the creation and use of anti-epileptic drugs increased, the ketogenic diet became a forgotten option. Now the most popular treatment options for epilepsy are pharmaceutical medications, surgery, and vagal nerve stimulation, the latter two being more medically invasive.
But using such treatments, especially medication, can lead to side such as dizziness, nausea, vertigo, and fatigue among many others. Additionally, 25 percent of children do not respond to antiepileptic drugs, and those who do typically build up resistance to the drug, requiring frequent switching of medication, only to develop resistance that requires them to switch again.
This begs the question, how successful is the ketogenic diet for epilepsy? Medical literature suggests a greater than 50% percent success rate in patients utilizing the keto for seizure control. This is especially good news considering the ketogenic diet is not met with the same side effects and resistances to anti-epileptic drugs.
It’s not completely understood why the ketogenic diet helps prevent seizures, but the belief is that the change in metabolism that occurs on the diet plays a major role in the anti-convulsant effect. Additionally, along with creating more available energy for the brain, the keto diet has demonstrated the ability to increase the synthesis of GABA, a neurotransmitter in the brain that reduces excitability of brain cells thus reducing seizure risk.
As a result, it’s believed that keto may also help manage other conditions that result in seizures such as Rett syndrome, infantile spasms, Dravet syndrome, and tuberous sclerosis complex, GLUT1 deficiency syndrome, and Doose syndrome; however, much more research is needed in these specific cases.
Keto and Alzheimer’s Disease
An estimated 5.8 million Americans currently have Alzheimer’s disease (AD). Alzheimer’s disease is a progressive neurodegenerative disorder that is characterized by a decline in memory and language. Those suffering from AD demonstrate an accumulation of amyloid plaques (clumps of beta-amyloids, which destroy connections between nerve cells) and tau protein tangles (neurofibrillary tangles, a common AD marker) within the brain; together, they play a major role in the progression and symptoms of the disease. It’s currently thought that AD results from a combination of environmental, lifestyle, and genetic factors. It’s also believed that a ketogenic diet can have positive effects on AD patients.
One of the most common and earliest signs of AD is an energy deficit in the brain. Those suffering from AD have brain insulin resistance, which causes impaired glucose metabolism, leading to a brain energy deficit. This characteristic of AD has led many to refer to the disease as “type III diabetes.”
This characteristic of AD is also one of the biggest reasons why a ketogenic diet should be considered for people with Alzheimer’s. As mentioned above, ketones can provide energy for the brain through pathways that are independent of insulin’s action. That means these ketones can provide fuel even to the insulin-resistant brain.
However, the power of a ketogenic diet for AD is not just a result of mitigating the energy deficit. Animal research has demonstrated that the ketogenic diet can reduce levels of the amyloid plaques that characterize AD. However, much more research is needed to determine if this occurs in humans. We also know that ketones are neuroprotective, meaning they can help reduce inflammation, which is important for preventing or slowing mental deterioration over time.
Keto first gained traction for the treatment of Alzheimer’s thanks to Dr. Mary Newport, author of The Complete Book of Ketones, who found that inducing ketosis through a keto diet and the use of coconut oil, MCT oil, and exogenous ketones, all drastically improved her husband’s AD symptoms.
Since then, the ketogenic diet has been used in research much more frequently and has demonstrated a strong correlation between ketosis and improvements in cognitive performance in individuals suffering from AD.
In a 2021 randomized crossover trial, 21 patients with Alzheimer’s disease on a 12-week modified ketogenic diet showed improvements in daily function and quality of life compared to those who ate a low-fat diet. In addition, the ketogenic diet was shown to be safe, nutritional ketosis was sustained (beta-hydroxybutyrate levels averaged 0.95 mmol/L), and the trial retention rate was extremely high at 81%.
It’s important to note that we need much more human research to determine the best use of the keto diet and ketogenic compounds for reducing the risk of and/or treating Alzheimer’s disease. It’s also not fully understood if the ketogenic diet can demonstrate improvements for all individuals.
Keto and Parkinson’s Disease
Parkinson’s disease (PD) is another neurodegenerative disease that manifests through impaired movement and affects 1 to 2 percent of people over the age of 65.
PD is caused by the death of neurons in the substantia nigra (a layer of midbrain gray matter) and creates immense motor problems affecting daily life, including slow, jittery movement and disruption to the basal ganglia (thalamus-linked structures in the base of the brain involved in movement coordination).
Early symptoms of PD include rigid motions, trembling or shaking, and slow movement. Advanced symptoms include dementia, depression, and impaired walking and talking.
The basal ganglia control the “autopilot” functions of the brain, such as walking or basic motor tasks, thus explaining many of the symptoms of PD. The death of neurons in the substantia nigra is caused by the impairment of mitochondrial complex 1 activity, which compromises mitochondrial activity and results in an energy deficit.
Since impaired mitochondrial activity and reduced brain energy are hallmarks of Parkinson’s disease, the ketogenic diet is being investigated as a potential treatment option.
Research on the ketogenic diet for this condition is limited but growing. A small study published in 2005 found that subjects who were able to adhere to the ketogenic diet for 28 days experienced significant improvements on the unified Parkinson’s disease rating scale. A larger 2018 trial compared a ketogenic diet to a low-fat diet in patients with Parkinson’s disease. Although both diets significantly improved symptoms, the ketogenic diet led to greater improvements in nonmotor symptoms such as urinary problems, pain, fatigue, daytime sleepiness, and cognitive impairment. Seven participants from the previous trial who followed a ketogenic diet for 24 weeks experienced improvements in health biomarkers, cognitive function, mood, and symptoms, as well as reductions in pain and anxiety.
These promising studies offer hope in the treatment of Parkinson’s disease and warrant further exploration of the use of the ketogenic diet.
Keto and Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis (ALS), also referred to as Lou Gehrig’s disease, is a progressive neurodegenerative disease affecting motor neurons and ultimately leading to paralysis and death.
Death from ALS typically occurs 2 to 5 years from symptom onset and currently, the only FDA approved therapy for ALS extends survival by a measly 2 to 3 months.
About 6,000 people in the U.S. are diagnosed with ALS each year, and so far, no cure has been found. Symptoms of ALS include loss of motor function, impaired breathing, loss of or difficulty speaking, trouble eating, and muscle wasting.
While researchers are still working to determine the exact cause of ALS, it appears that like epilepsy, Alzheimer’s, and Parkinson’s disease, dysfunctional brain metabolism plays a big role.
While the available research is very sparse, keto’s ability to reduce inflammation and improve energy balance in the brain gives reason to consider its use in the treatment of ALS.
In a recent case study, a 64-year-old man who followed a ketogenic diet for 18 months experienced improvements in ALS-related function, respiratory measures, mood, and quality of life, with only minor declines in physical function and respiratory pressures, and remained functionally independent 45 months after symptom onset.
Keto and Multiple Sclerosis
Multiple Sclerosis (MS) has traditionally been viewed as an autoimmune-mediated inflammatory disease resulting in damage to the myelin (protective sheaths that cover nerve cells) of neurons. Myelin damage is thought to be a primary contributor to the symptoms of MS, which are numbness, impaired muscle function and coordination, impaired speech, poor vision, and severe fatigue.
Most people have the relapsing-remitting form of MS, where their symptoms appear, resolve, and then come back, usually getting a little worse each time they return.
Researchers have identified that mitochondrial dysfunction plays a role in the progression of MS. There is now ongoing research on a ketogenic diet for MS by Dr. Terry Wahls, and a recent review article featured emerging evidence supporting ketogenic interventions for MS, including evidence from clinical trials. In one of those trials, researchers found that a Modified Atkins ketogenic diet was safe, well-tolerated, and effective in improving fatigue, reducing depression, and promoting loss of excess body fat in patients with MS. In a 2022 trial, researchers reported that a ketogenic diet led to reductions in serum neurofilament light chain levels (sNfL), a marker of neuroaxonal damage, in MS patients. In a subsequent study, another group of researchers found that significant declines in sNfL only occurred in those with higher ketone levels (≥1.0 mmol/L), suggesting that the degree of ketosis may enhance neuroprotection.
Keto and Autism
Autism is a developmental disorder that affects the nervous system. While there is a spectrum of symptoms for autism, the disorder is most notably characterized by repetitive and compulsive behaviors. Additionally, people with autism often display impaired mitochondrial function.
Again, published studies are very limited, but what exists is promising. For instance, a 2002 pilot trial examined the effects of a ketogenic diet on 30 children with autism, ages 4 to 10. While seven of the children had difficulties tolerating the diet and five were only able to adhere for 2 months,18 children were able to follow the ketogenic diet for six months. Two of the patients experienced significant improvements on the childhood autism rating scale, eight patients experienced average improvements, and eight patients experienced mild improvements.
Despite the study’s small sample size, the results indicate that more research should be conducted on ketogenic therapies for autism, especially since keto can improve gut health, which is often impaired in children with autism.
Keto and Traumatic Brain Injury
Traumatic brain injuries (TBI) are common in contact sports as well as car and workplace accidents. TBI is associated with impaired cerebral energy production as well as with increased free radical production. As with the other conditions listed in this article, TBI may also respond positively to a ketogenic diet.
When head trauma occurs, it creates a major energy deficit in the brain. To compensate for the loss, the brain upregulates glycolysis and metabolizes glucose at an accelerated rate. This eventually leads to insulin resistance in the brain, which creates both an energy deficit and stimulates inflammation.
A 2021 review suggests that while ketones show promise as a therapeutic strategy for improving recovery from TBI by addressing brain energy deficits and reducing inflammation, oxidative stress, and neurodegeneration, further research is needed to evaluate their effectiveness in humans and to address optimal usage conditions and individual factors.
Keto and Migraines
Migraines are characterized by recurrent neurovascular pain attacks triggered by genetic or environmental factors or both. While the exact cause of migraines is not known, it is believed that overexcited neurons, lack of adequate energy, and an imbalance in brain chemicals all play a role.
Several researchers believe that by serving as alternative brain fuel and signaling molecules, ketones may positively affect pathways related to migraine pathophysiology, such as mitochondrial function, oxidative stress, cerebral excitability, inflammation, and the gut microbiome.
A 2017 review examining the effects of a ketogenic diet on migraine in over 150 patients reported that six out of seven studies demonstrated that the ketogenic diet was effective at reducing the frequency and intensity of migraines. The researchers who conducted the review suggested that although more research is needed, preliminary data suggest that the stabilizing effects of the ketogenic diet may provide relief from migraine-related symptoms.
While the research is still in its infancy, there are some individuals who are not waiting to start making an impact with the ketogenic diet, including Dr. Angela Stanton, who has developed her own migraine protocol that includes a modified ketogenic diet.
The Final Word
There’s a lot of evidence that suggests the ketogenic diet could be promising in the treatment of neurological disease, but we need more research before it becomes part of the standard of care or adjuvant therapy.
The mechanisms by which ketosis can insert its benefits into the many conditions we mentioned in this article are great for getting the conversation started; however, it will take many more clinical trials before physicians will start prescribing the diet for these various disorders. We look forward to more research and results to better spread awareness on the increasingly popular topic of the ketogenic diet for neurological disorders.
