A Functional Medicine Protocol for Epilepsy: Testing, Supplements, and Nutrition

Epilepsy is a brain disorder that results in recurring seizures. An estimated 5 million new cases of epilepsy are diagnosed annually, with a total of 50 million people affected worldwide. There are many types of seizures, and a single episode does not guarantee that you have epilepsy.

Treatment of epilepsy requires an understanding of the type and cause of seizures. A conventional neurological workup is needed for the preliminary evaluation of epilepsy and prevention of seizures. However, a functional medicine doctor can also be a valuable team member for those with epilepsy. Specialty labs can identify underlying factors contributing to seizures not detectable on standard labs and imaging. Therapeutic dietary modifications and supplemental interventions can be added to pharmaceutical therapy to improve treatment outcomes and quality of life.

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What is Epilepsy?

Epilepsy is a neurologic brain disorder that causes recurring seizures. Seizures result from sudden, temporary bursts of electrical activity in the brain, resulting in involuntary body movements, functions, sensations, behaviors, and awareness. It is important to remember that not all seizures are caused by epilepsy. (1)

People with epilepsy have a lower seizure threshold than people without. You may be diagnosed with epilepsy if you've experienced two unprovoked seizures or one unprovoked seizure with a high risk of more. Epilepsy is a spectrum disorder characterized by seizure type and cause, age of onset, the affected part of the brain, seizure severity and frequency, and lab and imaging findings. (1)

Epilepsy Signs & Symptoms

Recurring seizures are the predominant symptom of epilepsy. Different types of seizures have various characteristics and may appear differently from one another. Signs and symptoms of seizures include the following (2-4):

• Temporary loss of awareness and consciousness
• Uncontrolled muscle movements and jerking
• Loss of muscle tone
• Blank stare
• Temporary confusion, slowed thinking, and problems with talking or comprehension
• Changes in hearing, vision, taste, smell
• Numbness or tingling
• Lip-smacking, chewing, rubbing hands, and finger motions
• Change in emotion: fear, anxiety, deja vu
• Loss of bowel or bladder control

Immediate medical care is required in the following scenarios (4):

• A seizure lasting more than five minutes
• A person isn't breathing after the seizure stops
• A second seizure follows immediately after a first
• A seizure accompanied by heat exhaustion
• Seizure in pregnant and diabetic patients
• Seizure results in injury

What Causes Epilepsy?

Many different factors can cause epilepsy. The underlying cause is unknown for about half of people with diagnosed epilepsy.

Central nervous system infection is a major risk factor and the most common cause of epilepsy worldwide, especially in developing countries. Infections that can cause epilepsy include neurocysticercosis, cerebral malaria, toxoplasmosis, rubella/German measles, cytomegalovirus, herpes simplex, bacterial and viral meningitis, tuberculosis, and HIV. (5)

About 30-40% of epilepsy is caused by genetic predisposition. Some types of epilepsy are hereditary, and genes are passed from parent to child; first-degree relatives of people with inherited epilepsy have a two- to four-fold increased risk of epilepsy. However, not all genetic epilepsy is inherited, and some genetic mutations can occur spontaneously in a child without any history of epilepsy in the family. (6)

Autoimmunity occurs when the immune system begins forming proteins called antibodies that inappropriately target and damage the body's tissues. If antibodies target the brain, autoimmune epilepsy can occur. The most common antibodies associated with autoimmune epilepsy include N-methyl-d-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein 1 (LGI1), glutamic acid decarboxylase 65 (GAD65), and folate receptor. (7)

There exist over 750 metabolic disorders that result from deficient enzyme activities, leading to poor digestion and metabolism of nutrients and energy generation. Epilepsy can result from metabolic disorders due to accumulations in cellular waste products, overstimulation of neural tissues, energy and cofactor deficiencies, imbalances in excitatory and inhibitory neurotransmitters, and structural brain malformations. Although rare, inborn errors in metabolism should always be ruled out as a cause of seizures and epilepsy in children. (8, 9)

Congenital or acquired (through trauma/injury) structural changes to the brain can cause epilepsy and other neurological deficits.

Functional Medicine Labs to Test for Root Cause of Epilepsy

Functional medicine labs help practitioners personalize treatment options for their patients. Below are some of the most common labs ordered for patients who have epilepsy.

Neurological Autoimmune Reactivity

Cyrex's Array 7X is an autoimmune panel that detects immune reactivity by measuring IgA, IgG, and IgM antibodies to tissues in the central and peripheral nervous tissues. It can help with the early detection of neuroinflammatory and neurodegenerative disorders and aid in monitoring the effectiveness of related treatment protocols.

The blood-brain barrier (BBB) is a relatively impermeable network of blood vessels and tissues that limit the transport of most substances to the brain as a protective mechanism. Permeability of the BBB can lead to neurologic defects that lower the seizure threshold and predispose to epilepsy. Cryex's Array 20 is complementary to Array 7X; it measures antibodies that, if present, indicate a breakdown and increased permeability of the BBB due to trauma or environmental triggers.

Organic Acids

An organic acids test (OAT) measures cellular metabolic byproducts excreted in urine to screen for metabolic disorders and other functional variations in the gut microbiome, micronutrient and neurotransmitter deficiencies and imbalances, inflammation, and exposure to environmental toxins.

Micronutrient Panel

Vitamin and mineral deficiencies can impair energy and neurotransmitter metabolism, increase neuroinflammation by reducing antioxidant pathway efficiency, and alter the electrical activity of brain cells and neurons. Additionally, many nutrient deficiencies are associated with the use of antiepileptic drugs (AEDs), including, but not limited to, folate, vitamin B12, vitamin D, calcium, and vitamin K. A micronutrient test can detect clinical and functional nutrient deficiencies contributing to the development of epilepsy and resulting as a side effect from AEDs.

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Conventional Treatment for Epilepsy

Conventional treatment of epilepsy mainly relies upon anticonvulsant medications, such as carbamazepine, phenobarbital, phenytoin, topiramate, and valproic acid. The choice of AED should be made in consultation with a neurologist and based on other medications, comorbidities, lifestyle, and patient preference.

Functional Medicine Treatment Protocol for Epilepsy

A personalized treatment plan can be prescribed based on an extensive intake and lab results. Below is an example of a sample treatment protocol for patients with epilepsy.

Therapeutic Diet and Nutrition Considerations for Epilepsy

The ketogenic diet is a high-fat, low-carbohydrate diet that shifts the body into a fat-burning metabolic state, called ketosis, so that the body relies on ketone bodies instead of glucose as its primary fuel source. The ketogenic diet was initially developed in the 1920s to treat epilepsy in children, and has since become popularized in the context of other health conditions. Lack of dietary carbohydrates mimics a fasting state, causing ketogenesis and increased production of ketone bodies, especially beta-hydroxybutyrate. Research has continued to demonstrate the beneficial effects of the ketogenic diet, notably reduced seizure frequency, in patients with epilepsy. Four variations of the ketogenic diet are widely used as effective dietary therapy amongst the epilepsy population. (10, 11)

Classic Ketogenic Diet

The classic keto diet uses a 4:1 ratio of fat to protein and carbs. Foods are weighed out so that patients eat 90% of their calories from fat, 6% from protein, and 4% from carbohydrates. Long-term compliance and eating the right foods to meet dietary intake goals can be challenging. Because of this, working with a trained dietician or nutritionist is recommended for best results.

Medium-Chain Triglyceride (MCT) Diet

The MCT diet is a less restrictive variation of the keto diet, developed by Dr. Peter Huttnelocher in the 1970s. It allows more variety because of its more lenient macronutrient ratio of 1.9:1, and relies upon 60% of daily calories from MCT supplementation. Coconut oil is the most common source of MCTs; other MCTs include caproic acid, caprylic acid, capric acid, and lauric acid.

Modified Atkins Diet (MAD)

The original Atkins diet is a low-carbohydrate diet developed for weight loss. Doctors at Johns Hopkins Hospital developed the MAD, a hybrid classic keto and Atkins diet, in the early 2000s.

The MAD emphasizes a 0.8:1 macronutrient ratio; it limits carbohydrates, encourages fat, and does not limit protein intake. Carbohydrates should only be eaten when accompanied by a fat source. Research has shown improved seizure control in 45% of patients following the MAD. Fewer food restrictions and higher caloric intake make compliance with this dietary variation easier than the classic keto diet. (12, 13)

Low Glycemic Index Treatment (LGIT)

LGIT is a less structured diet designed as an alternative to the ketogenic diet. It allows for increased intake of low glycemic carbohydrates, with a macronutrient ratio of 2:3 and a daily carbohydrate goal of 40-60 grams. Food quantities are not weighed but are based on portion sizes to allow more flexibility. High-fat foods, like meats, oils, and dairy, are still emphasized in this diet. Research shows that after six months, LGIT results in greater than 90% seizure reduction in 34% of patients, 50-90% reduction in 20% of patients, and no change in seizure frequency in 26% of patients. (14, 15)

Supplements Protocol for Epilepsy

Many dietary supplements are indicated for patients with epilepsy. Supplemental protocols can reduce epilepsy severity by addressing underlying causes of seizures, preventing/treating pharmacotherapy-associated nutrient deficiencies, and improving patient quality of life. Supplement choice, in part, will depend on seizure type. Supplement-drug interactions must also be considered before initiation. Summarized below are well-documented supplement options to consider in patients with epilepsy.

Fish Oil

Omega-3 polyunsaturated fatty acids found in fish oil are essential fats that maintain the integrity of nervous tissue and modulate neuronal and brain inflammation and excitability. Clinical research suggests omega-3 fatty acids through fish oil supplementation significantly reduce seizure frequency in children and adults.  

Dose: 1,200 mg daily

Duration: at least 3 months

Magnesium L-Threonate

Magnesium acts as a natural calcium channel blocker, the same mechanism of action as some AEDs. Magnesium deficiency is associated with seizures, and supplementation has been proven effective as an adjunctive treatment of seizures. Magnesium L-threonate is a form of magnesium that can cross the blood-brain barrier and has a high affinity for the brain and nervous system.

Dose: 2,000 mg (contains 144 mg of elemental magnesium) once daily

Duration: at least 6-12 weeks

Vitamin B6

Vitamin B6 deficiency has been found in a high percentage of patients with epilepsy. A mutation in the ALDH7A1 gene may cause vitamin B6 deficiency. Correction of vitamin B6 status with intravenous or oral administration of vitamin B6 (pyridoxine) has been shown to benefit patients with B6-dependent and independent epilepsy.

Dose: 25-50 mg daily

Duration: at least 4-6 weeks

Cannabidiol (CBD)

Research favorably supports the use of CBD in the treatment of epilepsy. CBD interacts with the endocannabinoid system, influencing neurotransmitter function and seizure threshold. More recent research has revealed that CBD blocks neurological signals carried by a molecule called lysophosphatidylinositol (LPI), which reduces neuronal excitation involved in seizure initiation. Positive clinical outcomes of CBD include improved quality of life, reduced psychiatric symptoms (i.e., anxiety, depression), better sleep, and increased efficacy of AEDs in epileptic patients.

Dose: 5mg/kg body weight twice daily

Duration: at least 3-12 months

When to Retest Labs

Patients should be advised to follow up in 1-3 month increments depending on the severity of epilepsy, patient response to intervention, and their need for doctor support. Frequent follow-up may be more necessary for monitoring therapeutic dietary modifications than for dietary supplements. Seizure frequency, severity, and other cognitive and emotional symptoms should be monitored as indicators of treatment efficacy. Micronutrient deficiencies identified on baseline testing can be remeasured after 4-6 weeks of nutrient therapy to ensure proper dosages are being administered. If indicated, repeat autoimmune and organic acids testing could be considered 6-12 months after baseline.

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Summary

A seizure is a change in neurologic function caused by dysfunctional electrical activity in the brain. Epilepsy is the umbrella term for recurrent seizures. An integrative and functional approach to epilepsy emphasizes nutritional interventions that can be implemented in conjunction with antiepileptic drug therapy that supports brain and neurological function.