Seizures, which are characterized by transient behavioral changes, are due to abnormal electrical activity within the brain. Epilepsy is a neurological disorder denoted by the periodic occurrence of seizures; numerous types of epilepsy have been described.
Approximately 3 million people experience epilepsy in the United States and there are 200,000 cases diagnosed each year. Epilepsy most commonly begins in children under the age of 2 or adults over the age of 65. Roughly 3 percent of the general population will experience epilepsy by age 75 (Epilepsy Foundation 2010).
Conventional treatment for epilepsy is primarily based on anti-epileptic drugs (AEDs), and often, epilepsy patients must endure significant clinical experimentation to find a regimen that works for them. Most importantly, not all patients will respond well to AEDs, either due to a lack of effectiveness or due to side effects.
Research has shed light on aspects of epilepsy that remain underappreciated by the conventional establishment. For example, special dietary regimens, such as the ketogenic diet, have the capacity to provide benefit for epilepsy patients and represent a potential adjuvant to mainstream therapies.
Moreover, magnesium is a well-known anticonvulsive agent, and studies show that magnesium deficiency is associated with epilepsy; intravenous magnesium can effectively control different types of seizures as well (Oladipo 2003; Sinert 2007; Oliveira 2011). However, the efficacy of supplemental magnesium has historically been limited in the context of conditions involving the central nervous system due to the inability of most types of magnesium to efficiently cross the blood-brain-barrier. Recently, though, scientists at the Massachusetts Institute of Technology have develop a groundbreaking new form of supplemental magnesium, called magnesium-L-threonate, that elevates brain magnesium levels more than conventional types of magnesium (Slutsky 2010).
Other important contributors to epilepsy include oxidative stress and mitochondrial dysfunction (Rahman 2012). Recent evidence indicates that supplementation with mitochondrial protectants like ubiquinol (CoQ10) and pyrroloquinoline quinone (PQQ) can target these underlying pathological features of epilepsy and may complement the effects of conventional anti-epileptic drugs (Tawfik 2011; Stites 2006).
In this protocol, you will learn how irregular electrical activity in the brain causes seizures, and how several variables influence neuronal excitability. You will also read about several novel and underutilized treatment strategies and scientifically-studied natural compounds with the potential to modulate the overactive neural network of the epileptic brain.
Epileptic seizures range in severity from mild sensory disruption to a short period of staring or unconsciousness to convulsions. Seizures can manifest in a variety of symptoms, including repetitive motions, changes in breathing rate, flushing, sudden lapses in consciousness, hallucinations, rhythmic twitching of muscles or a generalized loss of muscle control (NINDS 2012).
People with epilepsy have a substantially higher mortality rate than the general population. This is attributable to a phenomenon known as sudden unexplained death in epilepsy patients (SUDEP). SUDEP is unexpected and non-traumatic and occurs in approximately 1 percent of epileptics (Jehi and Najm 2008). It has no clear anatomical or toxicological cause, although it may be due to cardiac arrhythmias sometimes triggered by epileptic electrical activity. In the United States, SUDEP may account for 8 to 17 percent of all deaths in individuals with epilepsy, with greater incidence in younger individuals. Major risk factors for SUDEP include epilepsy occurring earlier in life, lying in bed in a face down position, having poorly controlled epilepsy, and being male. In fact, the male-to-female ratio can be as high as 1.75:1 (Nouri S et al 2004). One of the most important things that epileptics can do to lower their risk of SUDEP is to improve the control of their disease, which for many patients can be achieved by changing their diet and taking supplements in addition to taking their anti-epileptic drugs. Sleeping on your back may also lower your risk of SUDEP (Nashef et al. 2007).
Neurobiology of epilepsy
The brain contains billions of neurons, which are in constant communication with one another. During nerve cell signaling, or "firing," chemicals called neurotransmitters are released into the space between neurons (synapse) to carry the signal. Neurotransmitters influence the action of neurons, either by triggering (exciting) or discouraging (inhibiting) a neuron's firing. The firing of neurons is mediated by electrical signals; as a result, abnormal electrical activity can cause uncontrolled neuron firing, leading to seizures.
Epileptic seizures are caused by a disruption in electrical activity among neurons in the cerebral cortex, the most highly developed part of the human brain. Comprising about two-thirds of the brain's mass, the cortex is responsible for thinking, perception and the production and understanding of language. The cortex is also responsible for processing and interpreting the five senses.
The nervous system has two major divisions: the central nervous system and the peripheral nervous system. The central nervous system consists of the brain and the spinal cord. The peripheral nervous system also has two parts: the somatic nervous system and the autonomic nervous system (which is further divided into three parts: sympathetic, parasympathetic, and enteric). The autonomic nervous system exercises control over automatic or involuntary functions in the body, such as heart rate and respiration, among others. Although seizures emanate from the brain, there is a complex interaction between the autonomic nervous system and the central nervous system with regard to seizures.
Some seizures have a preliminary phase, known as an aura. An aura is a brief electrical discharge in the brain that can alert a person with epilepsy that a larger seizure is imminent. Epilepsy auras can range from a nonspecific strange or peculiar sensation to feelings of extreme fear or euphoria to the experience of strange lights or strange sounds. (Epilepsy auras are different from migraine headache auras.) The auras are actually small focal seizures that do not affect consciousness. Researchers have also developed techniques that allow them to identify the type of brain activity that occurs in auras in the hopes of learning more about how these focal electrical disturbances contribute to more generalized seizure activity (Fukao et al. 2010).
Causes of epilepsy and common seizure triggers
There are multiple different health problems that can cause epilepsy. For example, brain tumors, either benign or malignant, brain trauma, autoimmune irregularities, and neurological diseases such as stroke and Alzheimer's can lead to seizures (Vincent et al. 2011). These represent forms of epilepsy that are acquired and have a distinct cause.
Idiopathic epilepsy describes epilepsies with no identifiable cause. Genetics are thought to play a role in many cases of idiopathic epilepsy, as close relatives of an epileptic are five times as likely to develop epilepsy themselves (Bhalla et al. 2011).
In susceptible individuals, seizures can be precipitated by the presence of certain factors referred to as triggers, which include low blood sugar (hypoglycemia), dehydration, fatigue, lack of sleep, stress, extreme heat or cold, depression, and flashing or flickering lights. Food and environmental sensitivities may trigger seizures in some people.
Electrolyte Imbalances: Electrolytes are minerals, such as sodium and potassium, which have an electrical charge when dissolved in the body's fluids. The human brain relies on these minerals to generate the electrical currents needed for neurons to function and communicate. Consequently, alterations in the levels of these electrolytes can severely affect the electrical activity in the brain and trigger seizures in epileptics. Diminished sodium levels (hyponatremia) were associated with increased frequency of seizures in a cross-sectional study of 363 patients in a county hospital (Halawa 2011). New onset epileptic seizures in a 54 year old woman who consumed a large amount of a soft drink were described in a case report; her seizures were attributed to a sudden drop in sodium levels due to excessive fluid consumption (Mortelmans et al. 2008). Magnesium and calcium deficiencies can also trigger or exacerbate seizures in epileptics (Castilla-Guerrera et al. 2006).
Caffeine and Methylxanthines: Methylxanthines, including caffeine, are a family of natural stimulants that can be found in many foods and beverages, including coffee, tea, and chocolate. Methylxanthines increase activity in the central nervous system and can increase the excitability of neurons. There have been case reports of increasing seizure frequency, even in patients with formerly well-controlled epilepsy, following heavy coffee consumption. In one case, 4 cups of coffee a day was associated with an increase in seizure frequency from two per month to several per week, and in another, 5 to 6 cups daily caused two seizures in a month in a young epileptic with well-controlled epilepsy (Blaszczyk 2007; Kaufman 2003; Bonilha 2004). Experimental models indicate that caffeine lowers the seizure threshold, thus making anti-epileptic drugs less effective (Chrościńska-Krawczyk et al. 2011). After thoroughly reviewing the available evidence and conducting some animal model experiments, one group of investigators said that "the existing clinical data confirm the experimental results in that caffeine intake in epileptic patients results in increased seizure frequency. It may be concluded that epileptic patients should limit their daily intake of caffeine" (Jankiewicz 2007).
Stress: A 2003 study revealed that emotional stress exacerbated seizures in 64% of epileptics (Haut 2003). Other studies have corroborated these findings (Gilboa 2011; Maggio and Segal 2012). Similarly, fatigue and a lack of sleep can also trigger seizures (Frucht et al. 2000, Nakken et al. 2005).
Reactive Oxygen Species: Free radicals may play a role in epilepsy (Waldbum and Patel 2010, Pieczenik and Neustadt 2007). These compounds have the ability to damage proteins, DNA and the membranes of cells, potentially causing neurons to fire erratically leading to a seizure. Many factors can induce production of free radicals, including head trauma and neurodegenerative diseases as well as normal cellular metabolism (Halliwell B 2001). Mitochondria, the cellular energy cores in which adenosine triphosphate (ATP) production takes place, are the primary source of free radicals within the body. As we age, the efficiency and integrity of these vital organelles begins to falter, leading to increasing oxidative stress and cellular deterioration. With regard to epilepsy, a relevant consequence of age-related mitochondrial dysfunction is cellular membrane damage, which can impair cellular communication, potentially leading to seizures. Indeed, experimental models indicate that animals genetically prone to a poor ability to quench mitochondrial free radicals are more likely to have seizures than normal animals (Liang 2004). Moreover, in humans, heritable defects in the mitochondrial genome cause a subclass of epilepsy called mitochondrial epilepsy (Rahman 2012).
Mitochondrial energy metabolism can be targeted with some natural compounds; in particular, coenzyme Q10 (CoQ10) and pyrroloquinoline quinone (PQQ). Studies indicate that both of these nutrients quell mitochondrial oxidative stress and promote overall mitochondrial vigor; PQQ even stimulates the growth of new mitochondria via a process called mitochondrial biogenesis (Sourris 2012; Stites 2006). In a well-designed animal model, researchers recently showed that CoQ10 reduced the severity of seizures and quelled the seizure-induced increase in oxidative stress that is responsible for epilepsy-related neuronal damage (Tawfik 2011). Most important, CoQ10 augmented the effects of phenytoin, a conventional anti-epileptic drug, and spared cognitive function in rats that had seizures (Tawfik 2011). In other words, when seizure-prone animals were given CoQ10 plus phenytoin, their seizures were less severe than in animals receiving the anti-epileptic drug alone.
Aspartame. Phenylalanine, a metabolite of aspartame, can be neurotoxic at high concentrations. Therefore, it is plausible that very high doses of aspartame may trigger seizures, though this has not been observed in controlled clinical studies. In a study of people who anecdotally reported that aspartame triggered their seizures, no seizures were produced under controlled conditions of aspartame exposure (Rowan 1995). Another study of children with a particular type of seizure called petit mal seizures, however, did demonstrate changes in brain electrical activity after very high oral doses of aspartame, though none of the subjects had an actual seizure (Camfield PR et al 1992). In this study, the dose administered was 40 mg/kg, or about 2,800 mg for a 70 kg (154 lbs) human. For perspective, a can of diet soda typically contains about 180 mg of aspartame; therefore, the dose of aspartame administered to the children in the study was equivalent to over 15 cans of diet soda for an adult. In contrast, an intensive review published in 2002 found that there was no conclusive scientific evidence linking aspartame to epilepsy (Butchko et al 2002).
Similarly, the food additive monosodium glutamate (MSG) has been alleged to cause seizures. However, evidence implicating the amounts of MSG commonly encountered in food in the pathology of seizures is primarily, though not exclusively, anecdotal in nature. Monosodium glutamate can indeed induce seizures in animal models, but the dose required is equivalent to several thousand grams of MSG for a grown human - a dose highly unlikely to be attainable through dietary means alone. Nonetheless, some older reports suggest that MSG might lower seizure threshold in sensitive children (Shovic 1997).
Even though peer-reviewed evidence that directly implicates these dietary excitotoxins in necessarily triggering seizures among adult humans is lacking, some innovative doctors have noted substantial, though anecdotal, benefit when their seizure patients have been advised to carefully avoid food containing MSG. Therefore, it may be prudent for seizure patients, especially children, to avoid ingestion of aspartame and MSG.
Environmental toxins. Many environmental toxins, including some pesticides and heavy metals, are known to trigger seizures. For instance, mercury and lead are associated with seizures (Landrigan 1990, Brenner 1980, Istoc-Bobis 1987). For more information on the health impact of heavy metals, refer to the Heavy Metal Toxicity protocol. Also, insecticides known as organophosphates increase brain activity and can cause seizures (Sanborn 2002, Simpson 2002). Additional information is available in the Metabolic Detoxification protocol.
Diagnosis and standard medical treatment
Epilepsy is usually diagnosed on the basis of a combination of clinical findings, including patient history, physical examination, and laboratory testing. During an office visit, a patient will typically undergo a standard neurological examination, which includes evaluation of orientation, reflexes, motor control, nerve function, coordination, and sensory perception. It is often helpful for a physician to examine the person as soon after seizure activity as possible.
The most common diagnostic test to detect epilepsy is the electroencephalogram (EEG), which monitors electrical activity in the brain. However, brain activity may be normal between seizures, so a normal EEG does not rule out a diagnosis of epilepsy. Other brain imaging studies, including magnetic resonance imaging (MRI) and computed tomography (CT) scanning, are sometimes used to identify physical causes of seizures, such as tumors or malformations in the brain's vasculature (aneurysms).
Standard conventional treatments for epilepsy often rely on anti-epileptic drugs (AEDs), which may need to be taken for many years. Anti-epileptic drugs are grouped by their mechanism of action (many of the drugs listed below have multiple mechanisms of action):
Drug selection is based on clinical diagnosis as well as characteristics of the AED and its side effects. The choice of drug also depends on the personal preferences and experiences of the treating physician as well as the clinical context (e.g., in an emergency room, intravenous administration would be a typical approach). Sometimes the type of epilepsy can also guide the choice of drug. For example, the medication valproic acid is often more effective in treating generalized epilepsy than other AEDs (Marson et al. 2007). On the other hand, ethosuximide, another AED, is sometimes more effective for absence seizures. In an outpatient setting, many choices are available.
The optimal treatment outcome is complete cessation of seizures with one AED, also known as monotherapy. In general, almost 50 percent of adult patients and 66 percent of pediatric patients will become seizure free with the first drug that they try (Kwan and Brodie 2001, Prunetti and Perucca 2011). If the first AED fails or causes intolerable side effects, another one can be selected; many physicians will opt for an AED with a different mechanism of action. If the first AED fails because of intolerable side effects, a second trial of AEDs will be successful in approximately 50 percent of patients; however, in patients for whom the first drug was not effective, a second AED will be effective less than 15 percent of the time (Kwan and Brodie 2000).
When successful seizure control with monotherapy cannot be achieved, other AEDs are added to the treatment regimen. Polypharmacy (the use of multiple AEDs for epilepsy) is based on a combination of the various known mechanisms of action (Ochoa JG et al 2005). Each medication should be titrated upward in dosage until either seizures are eradicated or side effects become intolerable. Certain individuals with intractable seizures can be treated with as many as four different AEDs concomitantly.
Most AEDs have some side effects that can be intolerable for patients. As a result, although AED therapy is one of the mainstays of epilepsy treatment, other options may provide significant relief with fewer or milder side effects. In most instances, careful blood monitoring must be performed to determine the blood levels of each AED especially when a patient is taking multiple AEDs or other pharmaceuticals that alter metabolism.
Surgery for epilepsy is a very highly specialized operation and is typically reserved for patients who do not respond well to anti-epileptic drugs (AEDs). It should be performed only by the most experienced teams of neurosurgeons, epileptologists (neurologists specializing in epilepsy), and other physicians in major academic centers. Successful surgery for epilepsy is dependent on finding a "focal lesion," an abnormality that can be seen on a radiological imaging scan. Common examples of focal lesions include masses; less common focal lesions include scars or fibrosis. The best surgical outcomes occur in individuals who have a diagnosis of temporal lobe epilepsy, a well-circumscribed focal lesion, or abnormal EEG data that are focal in nature to match the imaging abnormality.
In these cases, the success rate, defined as patients that become seizure-free, ranges from 80 to 90 percent. For individuals who do not have matching lesions on EEG and imaging, the success rate falls to about 50 percent (still considered favorable). Complications are few and insignificant compared to the improved quality of life as a result of seizure reduction (Alarcon G et al 2006). However, surgery is not the only procedure that can provide significant relief for epileptics.
Other Neurological Procedures
Vagal nerve stimulation. The vagus nerve, which relays information to and from the brain, has many connections to neurological areas that are instrumental in seizures. Vagal nerve stimulation (VNS) is the only form of electrical treatment for epilepsy approved by the United States Food and Drug Administration (FDA). Vagal nerve stimulation was approved by the FDA in July 1997 as an adjunctive treatment for partial-type seizures in adults and adolescents older than 12 who did not respond well to anti-epileptic drugs (AEDs). In vagal nerve stimulation, a small electrical device, about the size of a pocketwatch, is implanted under the skin along with a connecting wire in the left upper chest area. Small leads are attached to the vagus nerve on the left side of the neck. The implantation takes about two hours. After implantation, the stimulator device is programmed to deliver electrical stimulation automatically 24 hours a day (usually every few minutes) (Karceski 2011).
Not only can vagal nerve stimulation reduce the severity and frequency of seizures, but it can also abort a seizure after it starts. Although the mechanism of vagal nerve stimulation therapy is still unclear, researchers think that it is able to increase inhibitory signals in the brain, helping to prevent the electrical activity that leads to seizures. Vagal nerve stimulation has been found to be safe and effective. Patients that have their seizure frequency reduced by 50 percent or more are classified as "responders." With long term use, between 50 and 80 percent of patients who receive vagal nerve stimulation treatment will become responders, depending on the seizure type. (Qiabi et al. 2011, De Herdt et al. 2007, Shawhan et al. 2009, Milby et al. 2008, Elliott et al. 2009). Reduction of AED use was reported in 43 percent of patients following vagal nerve stimulation for intractable epilepsy, and subjective improvement in quality of life occurred in 84 percent (McLachlan RS et al 2003).
Deep Brain Stimulation (DBS) is another novel therapy that may provide significant benefits for epileptics. This treatment involves the placement of electrodes in the brain using minimally invasive surgery that can then be used to send mild electrical currents to particular regions of the brain, such as the thalamus, the cerebellum and other deep regions in the brain. This technique was initially developed in the 1980s as a way to reduce tremors in patients with Parkinson's disease and has gained support for treating other movement disorders, such as dyskinesia. Its effects on these other neurological issues have spurred interest using deep brain stimulation to treat epilepsy (Pereira et al 2012, Lega et al. 2010, Wakerley et al. 2011).
Early clinical studies on deep brain stimulation have found that it is generally safe, with the adverse effects being transient and mild. Some patients have experienced side effects such as episodic nystagmus (uncontrollable eye movements), auditory hallucinations, and lethargy (Lega et al. 2010). However, one of the advantages of deep brain stimulation is that it can be switched off if side effects appear and the entire procedure is reversible. Early results from multiple clinical trials of deep brain stimulation have found that it can reduce seizures in a significant portion of patients, depending on its placement (Janszky et al. 2011).
Transcranial Magnetic Stimulation is a noninvasive technique that uses electromagnetic currents to alter the electrical activity in the brain. This therapy has shown great promise for reducing seizures in epileptics by reducing neuronal excitability. Some of the earliest studies found that transcranial magnetic stimulation can induce a prolonged period of protection from the types of electrical activity that cause seizures (Chen et al. 1997). Case studies have found that this technique can reduce seizure frequency by over 60 percent in patients (Sun et al. 2011). The most serious side effect associated with transcranial magnetic stimulation is a headache, though there is a small risk of seizure during this treatment (Bae et al. 2007). However, this risk is low and this technique is considered to be safe; in addition, as transcranial magnetic stimulation technology advances and is combined with EEGs, this therapy can be used in a more targeted and safer way (Rotenberg 2010).
Novel and emerging drug strategies
The pharmaceutical industry continues to make new anti-epileptic drugs to provide additional options for controlling epilepsy while also minimizing side effects. One new anti-epileptic drug (AED), known as levetiracetam, has recently been approved for monotherapy. Though the specific mechanisms are unclear, levitiracetam works by inhibiting synaptic conductance in ways different than traditional AEDs, so it may be effective for the treatment of epilepsies that have not responded well to other medications (Lysing-Williamson 2011). Other novel AEDs are only approved for adjunctive treatment, which means they can be added onto already existing drug regimens. Three of the newest AEDs that are approved for adjunctive therapy are eslicarabzepine acetate, lacosamide and retigabine.
Eslicarbazepine acetate works using a similar mechanism to an already established AED, carbemazapine, but it has less neurotoxicity (Benes et al 1999, Ambrósio et al. 2000) Eslicarbazepine also has fewer reported side effects than a similar AED, oxcarbazepine and can be taken once per day. As a result, eslicarbazepine acetate is being used as an additional AED for patients who do not have adequate control of their epilepsy with other medications (Fattore 2011). Another recently developed AED is lacosamide (Prunetti and Perucca 2011). This drug has been shown to reduce electrical seizure activity in the brain without affecting other aspects of brain function (Duncan GE et al 2005). Lacosamide works on a different part of neurons than other AEDs, so its novel mechanism may allow it to be more effective in patients that have not responded well to other AEDs (Errington et al. 2008, Curia et al. 2009). Similarly, the new medication retigabine also has a different mechanism than other AEDs and so it can be added onto the treatment regimens of epileptics who are still having frequent seizures with less of a concern of impaired effectiveness (Bialer 2007).
Together, these new medications, as well as other new drugs like stiripentol (Diacomit®) and rufinamide (Banzel®), have the potential to treat previously intractable cases of epilepsy or to reduce side effects. Some researchers have also noted that diuretics, such as furosemide and bumetanide, may also be able to reduce seizures by affecting the levels of water and ions in the brain (Maa et al 2011). Although there have not been any recent clinical studies of the effects of diuretics on epilepsy, studies examining the effects of these medications in tissue and animal models of epilepsy have been promising, and one small clinical study published in 1976 found that diuretics were able to significantly reduce seizure frequency in some patients (Ahmad et al. 1976).
Hormone imbalances may play a role in epilepsy. Female epileptics often have an exacerbation of their condition at specific points during their menstrual cycle, which is sometimes called catamenial epilepsy. Seizures in women often increase during periods of low progesterone (El-Khayat et al. 2008). Research has found that estrogen increases neuronal excitability and progesterone reduces neuronal activity, which suggests that an imbalance between estrogen and progesterone could increase seizure frequency (Finocchi and Ferrari 2011). Lower progesterone levels are also associated with more frequent seizures in women, and elevated estrogen levels during perimenopause also appear to exacerbate epilepsy (Murialdo et al. 2009; Erel 2011).
Progesterone restoration therapy has been studied as a possible treatment of epilepsy and initial results have been promising (Stevens and Harden 2011). The effects of hormones on epilepsy still needs to be better elucidated, as some studies have suggested that estrogen can have pro-epileptic and anti-epileptic properties, depending on its levels (Veliskova et al 2010). Women are not the only patients that can have their epilepsy affected by sex hormone levels; testosterone and its metabolites also have anti-seizure effects (Frye et al. 2009, Reddy 2010). Indeed, in a case report of a man with posttraumatic seizures, testosterone therapy caused his seizures to lessen and nearly disappear (Tan 2001). These findings suggest that maintaining optimal testosterone levels may ameliorate seizure disorders in men. Free testosterone is a good indicator of testosterone activity; optimal levels are 20 – 25 pg/mL.
Dietary Management: The Ketogenic Diet and Others
The idea that diet can affect epilepsy was first postulated by Hippocrates, who noticed that fasting could prevent convulsions (Kelley and Hartman 2011). Currently there are four different dietary treatments that can be used for epilepsy: the ketogenic, medium chain triglyceride, modified Atkins, and low-glycemic index diets.
The most widely used dietary treatment for epilepsy is the ketogenic diet. The ketogenic consists of high intake of fats (80 percent) and low intake of protein and carbohydrates; it was developed in the 1920s (Francois LL et al 2003; Stafstrom CE et al 2003). The ketogenic diet requires patients to be very careful about what they eat for it to be effective (Sheth et al 2002; Mady MA et al 2003).
The ketogenic diet is carefully designed so that fats, primarily in the form of long-chain fatty acids, provide the main source of calories in the diet. Typically patients need to consume three to four times as much fat by weight compared to carbohydrates and proteins; this means that with this diet, over 90 percent of the calories come from fat. This high fat diet changes the body's metabolism, causing it to generate chemicals known as ketones, which can then be burned for energy. This diet is also designed to provide approximately 1g of protein for every kg of body weight to ensure adequate protein intake. The ketogenic diet typically begins with a brief fasting period, though this is not necessary and is often based on the clinician's preferences (Kosoff et al. 2009).
The way that the ketogenic diet prevents seizure is still under investigation. One of the prevailing theories is that the ketones produced by the diet are able to enter into the brain. From there, the ketones are able to increase the levels of chemicals that decrease neuron activity, reduce levels of reactive oxygen species and make the brain use energy more efficiently, resulting in fewer seizures (Bough 2007, Kosoff et al. 2009).
The ketogenic diet has consistently been proven to be an effective treatment for epilepsy. Reviews have found that over 50 percent of children undergoing the ketogenic diet have a greater than 50 percent reduction in their seizure frequency, with over 30 percent experiencing a decrease in seizure frequency of over 90 percent and more than 15 percent becoming completely seizure free (Lefevre and Aronson 2000). These numbers are even greater for children that maintain the ketogenic diet for three months: over half of the children have their seizures reduced by 90 percent or more and over 30 percent become completely seizure free (Henderson et al. 2006). The benefits of the ketogenic diet have also been confirmed by the randomized control trial, which is the most rigorous of clinical trials. (Neal et al. 2008).
Although the ketogenic diet has traditionally been recommended for children, it may also be used with great success in adolescents and adults. Clinical studies examining the effects of the ketogenic diet on older patients have shown that the diet can produce a significant reduction in seizure frequency in this population as well (Mady et al. 2003, Mosek et al 2009, Klein et al. 2010). One of the main obstacles for adolescents and adults trying the ketogenic diet is patient compliance, because the diet can be so restrictive. As a result, multiple similar diets have also been designed to try to take advantage of the concept behind the ketogenic diet without significantly reducing its effectiveness. The medium chain triglyceride diet is based on the idea that shorter fat molecules, such as medium-chain triglycerides, produce more ketones and thus allow for more protein and carbohydrate in the diet. Other diet plans, including the modified Atkins Diet and the low-glycemic index treatment, have also been developed to allow more flexibility. The Modified Atkins Diet allows for 10-30 g of carbohydrates each day and has no restrictions on protein or caloric intake. The Low-Glycemic Index Treatment allows a higher amount of carbohydrates (40-60 g per day) as long as they have a glycemic index of less than 50. Both of these modified ketogenic diets have also proven beneficial in the treatment of epilepsy (Payne et al. 2011).
The ketogenic diet and related metabolic treatments for epilepsy can cause some side effects and nutritional deficiencies. The most common side effects are gastrointestinal issues, such as diarrhea, constipation, nausea, vomiting and increases acid reflux.
This diet can also raise the levels of cholesterol and other lipids in the blood. Patients undergoing the ketogenic diet may also have an increased risk of a vitamin D deficiency, leading to reduced bone strength, as well as kidney stones, selenium deficiency and increased bruising. As a result, vitamin supplementation and careful monitoring may be needed during the ketogenic diet. (Kang HC et al.. 2004, Groesbeck et al. 2006, Bergqvist et al. 2007, McNally et al. 2009, Bank et al 2008)