Many natural compounds also affect the brain and may be able to influence epilepsy; natural compounds will likely be most beneficial as adjuvants to conventional therapies.
Vitamins and Minerals
Epilepsy patients should also be aware that long-term use of anti-epileptic drugs (AEDs) can negatively affect their vitamin and mineral status. For instance, patients taking anti-epileptic drugs (AEDs) have significantly lower levels of vitamin D in their blood (Menon and Harinarayan 2010, Shellhaas and Joshi 2010, Pack 2004, Valsamis et al. 2006, Mintzer S et al 2006). This is because many AEDs increase the activity of a liver enzyme known as cytochrome P450, which also breaks down vitamin D. Vitamin D is essential for the absorption of calcium; consequently, patients taking AEDS absorb less calcium in their diet, which increases their risk of developing osteoporosis. Patients who are taking AEDs may need to take vitamin D and calcium supplements (Fong et al. 2011).
Anti-epileptic drugs have also been shown to reduce levels of several B vitamins, including folate and vitamins B6 and B12 (Sener et al. 2006, Linnebank et al. 2011) These vitamins are critical for controlling metabolism in the body; low levels of these vitamins can also lead to low red blood cell levels, causing fatigue and pallor. One of the most serious consequences of the low folate levels caused by AEDs is high levels of the compound homocysteine, a risk factor for heart disease (Sener et al. 2006; Kurul et al 2007, Apeland et al 2001). Elevated levels of homocysteine have been implicated in the increased risk of heart disease seen in epileptics. Moreover, some studies have indicated that elevated homocysteine may contribute to AED resistance or increase seizures in epileptics (Diaz-Arrastia 2000). Based on these findings, some researchers call for routine supplementation with the B vitamins, especially the metabolically active form of folic acid, L-methylfolate, to reduce homocysteine levels (Morrell MJ 2002). Folate deficiencies can also lead to seizures, particularly in infants. Impaired folate transport in the body can be a cause of seizures that do not respond well to typical treatments (Djukic A 2007). In addition, epileptics often have reduced folic acid levels, possibly due to the use of AEDs (Asadi-Pooya 2005). Doctors of epileptics should routinely monitor folic acid, vitamin B12 and homocysteine levels in patients to help prevent an increased risk of cardiovascular disease that could otherwise be treated.
Some forms of epilepsy are directly linked to vitamin B6 deficiencies; these convulsions, known as pyridoxine-dependent seizures, can only be treated with high doses of vitamin B6 (Asadi-Pooya 2008). Low vitamin B6 levels are also associated with general epilepsy. Even in patients without pyridoxine-dependent seizures, low levels of pyridoxine might increase seizure sensitivity, although more research needs to be done to determine if pyridoxine can treat seizures (Gaby 2007). Some types of seizures cannot be treated with pyridoxine, but they can be effectively managed with pyridoxal-5-phosphate, the biologically active form of vitamin B6 (Tamura et al. 2000, Jiao et al. 1997, Wang et al. 2005).
Antioxidants, such as vitamin E, vitamin C and selenium are able to mitigate mitochondrial oxidative stress in the brain and other tissues, lowering seizure frequency in various types of epilepsy (Tamai et al. 1988, Zaidi et al. 2004, Savaskan et al. 2003, Yamamoto et al. 2002, Ogunmekan et al. 1979, 1989 and 1985). Animal models have shown that alpha-tocopherol alone is able to prevent several types of seizures (Levy et al 1990; Levy et al 1992). Epileptics are also more likely to have low vitamin E levels, though this may be a result of taking anti-epileptic drugs (Higashi et al. 1980).
Magnesium helps maintain connections between neurons. It has been shown to suppress EEG activity and limit seizure severity in animal models, and magnesium deficiency is associated with seizures in humans (Oladipo 2007; Nuytten et al 1991, Borges et al. 1978). Within the body, ionic magnesium acts as a natural calcium channel blocker, offsetting the excitatory influence of ionic calcium in a manner similar to the calcium channel blocker class of conventional AEDs (Touyz 1991). Moreover, magnesium levels decline sharply following seizures in patients with idiopathic epilepsy (Gupta 1994). In fact, intravenous or intramuscular magnesium is often administered to women to safely prevent eclampsia, a pregnancy-associated disorder characterized by seizures (Bhattacharjee 2011).
A recently developed form of magnesium, known as magnesium-L-threonate, may be particularly effective in epilepsy and other neurological disorders. This form of magnesium appears to be better at penetrating the blood-brain barrier and thus is more efficiently delivered to brain cells (Slutsky et al. 2010, Abumaria et al. 2011). In fact, in an animal model, magnesium-L-threonate boosted magnesium levels in spinal fluid by an impressive 15% compared to virtually no increase with conventional magnesium. Moreover, oral magnesium-L-threonate was able to modulate learning and memory, indicating that it does indeed impact the central nervous system (Abumaria 2011).
Thiamine, manganese and biotin are often low in epileptics as well (Gaby 2007).
Melatonin plays an important role in the brain, particularly in regulating the brain’s sleep-wake cycle. It also exerts a calming effect at the neuronal level by reducing glutaminergic (excitatory) signaling and augmenting GABAergic (inhibitory) signaling (Banach et al. 2011). Melatonin is widely used as a sleep aid and to treat jet lag; the side effects of taking melatonin are mild and it is one of the most commonly used supplements in the United States. Animal models have shown that melatonin can be effective in reducing epileptic seizures (Lima et al. 2011, Costa-Latufo et al. 2002). Melatonin has also been beneficial in humans with epilepsy and is particularly effective in the treatment of cases of juvenile epilepsy that do not respond well to anti-epileptic drugs (AED’s) (Banach et al. 2011). Due to its widespread use and minimal side effects, melatonin has potential to improve control of epilepsy (Fauteck et al. 1999).
Polyunsaturated Fatty Acids (PUFAs), such as omega-3 fatty acids, are a type of essential fat that play an important role in maintaining central nervous system health. Animal studies have suggested that PUFAs, including omega-3 and some omega-6 fatty acids, may be able to modulate neuronal excitability (Blondeau et al. 2002, Taha et al. 2010). This is further supported by the fact that children on the ketogenic diet often have higher levels of PUFAs in their cerebrospinal fluid, which suggests that increased PUFA levels is one of the ways that the ketogenic diet prevents seizures (Xu et al. 2008, Auvin 2011). Clinical trials in adults have yielded mixed results. In one such study, 57 epileptic patients were given 1 g EPA and 0.7 g DHA daily. Seizure activity was reduced over the first six weeks, although the effect was temporary. The researchers called for more in-depth studies, with larger doses and larger observational groups (Yuen AW et al 2005). However, a randomized controlled trial did not find that fish oil reduced seizure frequency; although, the study did find, that PUFAs reduced seizures when administered in an open-label format, meaning when subjects knew that they were not receiving a placebo (Bromfeld et al. 2008). An ongoing National Institutes of Health-sponsored trial is examining the effects of fish oil on cardiac health in epileptics (ClinicalTrials.gov).
Life Extension suggests that the omega-6 to omega-3 ratio should be kept below 4 to 1 for optimal health. More information on testing and optimizing your omega-6 to omega-3 ratio can be found in the Life Extension Magazine article entitled “Optimize Your Omega-3 Status“.
Resveratrol, derived from red grapes and Japanese knotweed (Polygonum cuspidatum), and the plant Bacopa monnieri both appear to be promising in the management of seizure-related neurotoxicity. Resveratrol and bacopa-derived compounds have been extensively studied in experimental settings and consistently shown to guard against neuronal damage (Jyoti 2007; Hosamani 2009; Kanthasamy 2011; Chung 2011). In the context of epilepsy, numerous mechanisms by which resveratrol might prevent seizures have been proposed (Shetty 2011), and, indeed, in an animal model resveratrol prevented chemical-induced seizures (Wu 2009); though studies on epileptic humans have yet to be performed. Likewise, bacopa has been the subject of several animal model experiments, many of which have revealed a clear benefit relating to seizure frequency and post-seizure brain cell damage (Pandey 2010; Mathew 2010; Krishnakumar 2009). Nonetheless, bacopa also has yet to be studied in a controlled manner in a population of epileptic humans.
Phytocannabinoids (pCBs), which are compounds found in marijuana that closely resemble chemicals the body produces naturally called endocannabinoids, have shown great potential in the treatment of epilepsy. Phytocannabinoids can affect both the central and peripheral nervous system because neurons have receptors that respond directly to binding by cannabinoids. One of the major effects of pCBs is to reduce neuronal excitability by modulating electrical activity around synapses; as a result, these chemicals are sometimes referred to as potential “circuit breakers” for neurological disorders, including epilepsy (Wallace et al. 2003, Katona and Freund 2008). Therefore, researchers have been studying the effects of tetrahydrocannabinol (THC) and other phytocannabinoids on the brain to try to develop new mechanisms for treating epilepsy (Hoffman and Frazier 2011, Hill et al 2012). One small clinical trial found that the phytocannabinoid, cannabidiol, did reduce seizures in epileptics who were already taking AEDs (Cunha et al 1980). Another study that was largely based on epidemiology found an association between marijuana use and decreased risk of seizure (Ng et al 1990). Moreover, it has been reported that patients treated for epilepsy subjectively feel that marijuana use helps eases their epilepsy (Gross et al 2004). More research is needed to determine the efficacy and safety of natural and synthetic cannabinoids for the treatment of seizures. A comprehensive review of studies examining the effects of cannabinoids on seizure frequency in humans is currently being carried out by the Cochrane Epilepsy Group (Gloss and Vickrey 2011). Marijuana is illegal except as a prescribed treatment for medical problems in certain states; Life Extension does not recommend consuming illegal drugs as a treatment for epilepsy. However, the benefits of these phytocannabinoids do suggest that marijuana-derived compounds may soon become an accepted form of therapy for epilepsy and other neurological disorders.
Seizure Interruptions. Although auras do not occur in all individuals with seizure disorders, some people are aware of a change in their sensory perception (whether auditory, olfactory, sensory, visual, or gustatory, sometimes involving malaise, vertigo, or the sense of deja vu) that signals the onset of a seizure. Anecdotal reports indicate that some people have learned to interrupt their seizure process by replacing the aura-induced perception with another. In these individuals, the aura is a known signal of seizure onset. For example, if the aura is a smell or unpleasant odor, these individuals can often interrupt the seizure by immediately smelling something else (in general, something with a more pleasing smell than the aura).
Some people are able to take the interruption technique a step further. By simply relying on mental imagery (e.g., remembering a pleasant, positive smell), they can arrest a seizure. Some find that anger can effectively interrupt a seizure; they are able to arrest their seizures by yelling at them. Other individuals who have seizures with an observable onset pattern enlist a support person to shout at them or give them a quick shake when the pattern commences. The techniques that successfully “interrupt” an aura vary from patient to patient and must be performed at a specific time to stop the seizure (Wolf 1994). However, the use of aura interruption may be able to help reduce or eliminate seizures (Elsas et al. 2011).
Stress Reduction Getting a good night’s sleep on a regular basis is a very important component of seizure prevention. Some scientists hypothesize that one major function of REM sleep is to reduce the brain’s susceptibility to epileptogenic influences (Jaseja H 2004). Stress reduction and relaxation techniques such as meditation may also aid in reducing seizures (Swinehart 2008).
Physical exercise can also be an important way to relieve stress that may be particularly beneficial for epileptics. Not only can exercise reduce stress, improve social integration and improve quality of life, regular physical exercise may directly help reduce seizure frequency (Arida et al. 2010). Physical exercise may “desensitize” neurons to emotional stress, helping avert seizures brought on by other triggers (Arida et al. 2009).
Biofeedback, another relaxation technique, can also be helpful. When the autonomic nervous system (or the involuntary nervous system) is in a state of overarousal, the likelihood of seizure activity can increase. Biofeedback is a technique that uses displays of some form of biological monitoring, such as an EEG, to help patients identify how their body responds to certain situations. By observing changes in EEG readings, patients are able to learn how to partially control the electrical activity in their brains and can develop the ability to reduce their risk of having seizures. Although most clinical trials involving biofeedback have been small (Tozzo CA et al 1988; Andrews DJ et al 1992; Ramaratnam S et al 2001), a comprehensive review of many studies found that biofeedback can provide significant relief for epileptics, particularly those that have not had success with anti-epileptic drugs (AEDs) (Tan et al. 2009). On average, almost 75 percent of people who try EEG biofeedback for epilepsy will experience fewer seizures. Biofeedback using other biologic responses, such as slow cortical potential feedback and galvanic skin response has also been promising (Nagai 2011).
Other behavioral interventions may reduce seizure frequency as well. Yoga can improve quality of life and result in fewer seizures (Lundgren et al. 2008, Khan et al. 2010) Acupuncture may also be helpful in seizure prevention. A thorough review of published trials found that acupuncture may be beneficial, but that more and better designed studies need to be done (Cheuk 2008). Studies of the benefits of other relaxation techniques and cognitive behavioral therapy have also found a possible benefit (Ramaratnam 2004).