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From the Townsend Letter
February/March 2015

Migraine Headache
by Life Extension

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Conventional Treatment
Most migraine treatment plans involve both acute and preventive strategies (Braun 2010).

Acute Treatment
The goal of acute or abortive treatment is to relieve the intensity and/or duration of an imminent or ongoing migraine as quickly as possible (Hershey 2011).

First tier options for acute migraine management may include nonsteroidal anti-inflammatory drugs (NSAIDs) and/or mild analgesics (e.g., acetaminophen or aspirin; Hershey 2011; Bajwa 2012). Caffeine, due to its vasoconstrictive properties, is sometimes combined with aspirin and/or acetaminophen as well (Aukerman 2002). However, these options may not be sufficient for treating severe migraines, in which case a variety of drugs in the triptan class may be considered (Hershey 2011).

The triptan drugs (e.g., sumatriptan, rizatriptan, eletriptan, and almotriptan) act on several specific mechanisms of a migraine headache, such as promoting vasoconstriction and blocking pain pathways in the brainstem. Triptans mediate these effects by activating certain serotonin receptors in cranial blood vessels (Bajwa 2012).

Although the triptans are arguably the most effective treatment for acute relief of a migraine headache (i.e., the "gold standard"), they have a number of side effects (Cady 2011). For example, triptans should be avoided (when possible) in patients who are at risk for cardiovascular events and stroke (i.e., patients with heart disease). Furthermore, triptans require careful monitoring because they are known to interact with a large number of other commonly used medications (Bajwa 2012).

Other drugs that may be used to treat migraine include ergot alkaloids, which cause blood vessel constriction; opioids; and, less commonly, corticosteroids (MD Consult 2011).

Medicating as early as possible during migraine increases the chances of successfully aborting an attack or reducing its intensity (Aukerman 2002).

Preventive Treatment
The main goals of preventive therapy are to reduce migraine frequency, severity, and duration, as well as improve responsiveness to acute treatment(s). Preventive treatment options include headache trigger avoidance, daily medication, physical therapy, and/or behavioral therapy (Braun 2010).

Drugs used to prevent migraines include blood pressure medications (e.g., beta blockers, calcium channel blockers, ACE inhibitors, and angiotensin receptor blockers), tricyclic antidepressants (e.g., amitriptyline [Elavil]), and anticonvulsants (e.g., valproate [Depakote], gabapentin [Neurontin], and topiramate [Topamax]). These drugs should be started at low doses and given adequate time to reach peak effectiveness. Therefore, depending upon the chosen medication, a proper drug trial could take anywhere from four weeks to three months to take effect (Bajwa 2010).

Unfortunately, taking too much migraine prevention medication for too long can lead to "medication overuse headache." Medication overuse headache can become a chronic, self-perpetuating condition called "chronic daily headache," in which patients experience daily headaches caused by medication overuse, but continue to use medication to relive the headaches. To prevent medication overuse headache, migraine patients should (on average) limit use of NSAIDs to 15 or fewer days a month and limit triptan or over-the-counter combination analgesic use to 9 or fewer days a month (Garza 2012; Young 2001).

Lifestyle Considerations
Although there are a wide variety of acute and preventive drugs available for treating migraines, many patients will not experience significant symptom relief unless healthful lifestyle modifications are made (Sun-Edelstein 2009a). The following lifestyle interventions may prevent migraines (Chaibi 2011b; Gallagher 2012; Linde 2009; Honaker 2008, Hauge 2011):

  • avoidance of caffeine, nicotine, red wine, and other migraine triggers
  • stress reduction
  • improving sleep hygiene
  • massage therapy
  • chiropractic manipulation
  • acupuncture
  • getting sufficient exercise
  • frequent stretching

Dietary Interventions
A significant association between dietary intake and migraine incidence exists; one out of every four migraine patients report that certain foods can trigger an attack (Mueller 2007). Furthermore, the avoidance of food allergies and/or sensitivities may reduce or eliminate migraine symptoms for some patients (Ross 2011).

Common nutritional migraine triggers include (Mueller 2007):

  • monosodium glutamate (MSG), a commonly used flavor-enhancer found in some soups and Chinese food
  • nitrites, preservatives found in processed meats such as hot dogs
  • tyramines, natural compounds found in wines and aged foods (e.g., cheeses)
  • phenylethylamine, a stimulant compound found in chocolate, garlic, nuts, raw onions, and seeds

Many of these nutritional migraine triggers have vasoactive properties (causes constriction or dilation of blood vessels; Gallagher 2012), which is why they may contribute to migraine attacks.

Other potential dietary triggers include cow's milk, wheat, eggs, alcohol, artificial sweeteners, citrus fruits, pickled products, and vinegar (Mueller 2007; Ross 2011).

It is important to note that not all migraine patients are susceptible to the aforementioned nutritional triggers, thus the complete elimination of these items is not always necessary (Mueller 2007). In order to identify nutritional triggers, experts suggest the use of food diaries because they are simple, inexpensive, and removal of trigger foods is associated with a reduction in migraine headaches (Sun-Edelstein 2009a).

Also, food allergy and sensitivity testing to measure immunologic reactivity to foods may allow for identification of potential migraine triggers (Ross 2011; Arroyave Hernandez 2007; Mylek 1992).

In addition to the above triggers, dietary fasting for longer than 4 hours should also be avoided (when possible) since it has been linked to an increased risk of migraine (Gallagher 2012; Fukui 2008).

Integrative Interventions
Natural therapies (e.g., dietary supplements) are well tolerated, and many have been shown to reduce migraine symptoms (O'Brien 2010; Schiapparelli 2010).

Butterbur root: Butterbur (Petasites hybridus) is a plant that flourishes in moist conditions, and has been used for a wide range of medicinal purposes in Europe since ancient times (Pothmann 2005). Butterbur extracts possess analgesic, anti-inflammatory, anti-spasmodic, and vasodilatatory properties, which may explain their efficacy for migraine prevention (Pothmann 2005; Oelkers-Ax 2008). Butterbur root extract (standardized to 15% petasins) has been shown to be both safe and effective for the prevention of migraines (Diener 2004; Lipton 2004; Pothmann 2005). In one study, researchers split 245 patients into three groups to receive: 75 mg of butterbur extract twice a day, 50 mg of butterbur extract twice a day, or placebo. At the end of a four-month treatment period, those taking the 75 mg dosage experienced a whopping 48% reduction, on average, in the frequency of migraine attacks (Lipton 2004).

Butterbur is so effective for reducing the frequency and severity of migraine attacks, that the American Academy of Neurology (AAN) and the American Headache Society (AHS) have recommend it as an effective treatment for migraine (Holland 2012).

Coenzyme Q10: Coenzyme Q10 (CoQ10) is a potent antioxidant (Ross 2007) and an important component of cellular energy production. Researchers have found that organs with high metabolic rate, such as the brain, appear to quickly deplete CoQ10 stores, potentially leading to a deficiency (Ross 2011).

CoQ10 (at doses of 100–300 mg daily) has been shown to be beneficial for preventing and reducing the frequency of migraine attacks among adults (Schiapparelli 2010; Slater 2011). These actions are attributed to CoQ10's potential to interfere with inflammatory mechanisms and mitochondrial dysfunction, both of which have been implicated in the migraine process (Slater 2011).

Riboflavin: Riboflavin (i.e., vitamin B2) contributes to cell growth, enzyme function, and energy production (AMR 2008). High quality data indicate that riboflavin is effective for the prevention of migraine among both children and adults (Condo 2009; Boehnke 2004), and may decrease the need for traditional rescue medications (Boehnke 2004). It is believed that riboflavin's beneficial effects are due to its ability to enhance mitochondrial energy production (Brenner 2010), this is based on data indicating that riboflavin is especially effective among migraine patients with mitochondrial genetic abnormalities (DiLorenzo 2009).

One study involving 23 participants showed that supplementation with 400 mg riboflavin daily reduced headache frequency by an impressive 50% at three months, with improvement persisting through six months (Boehnke 2004). Riboflavin is also cost-effective and has a minimal side effect profile (Condo 2009).

Feverfew: Feverfew (Tanacetum parthenium) is a small, daisylike flower with a distinctively strong, bitter odor (Goodyear-Smith 2010). Recent evidence has revealed that feverfew inhibits the production of several inflammatory mediators that may be involved in migraine including arachidonic acid, cyclooxygenase-2, TNF-α, IL-1, MCP-1. Due to these anti-inflammatory properties, feverfew's use in the management of migraine attacks is promising (Goodyear-Smith 2010; Saranitzky 2009; Chen 2007). However, a review of randomized controlled trials revealed mixed results for the effectiveness of feverfew (Pittler 2004). For example, a study that used dried leaf revealed a decrease in the frequency of migraines while another using a CO2 extract did not show significant benefit (Pittler 2004). A combination of ginger and feverfew has also been shown to be effective for migraine prevention with minimal side effects (Cady 2011; Ernst 2000). A dosage of 100-300 mg up to 4 times daily is recommended (Pareek 2011).

Magnesium: Magnesium modulates many important neural and vascular processes involved in the development of a typical migraine attack. Migraine patients commonly exhibit low magnesium levels (in the serum, tissue, and lymphocytes), especially during an attack (Qujeq 2012; Talebi 2011; Sun-Edelstein 2009b). Furthermore, magnesium deficiency can trigger cortical spreading depression (CSD), platelet aggregation, vasoconstriction, and substance P release; all of which are have been implicated in migraine pathology (Sun-Edelstein 2009b). A dosage of 600 mg of magnesium daily has been shown to be effective for the prevention of migraine attacks (Koseoglu 2008), and is inexpensive and well-tolerated (Sun-Edelstein 2009b). In combination with CoQ10, vitamin B2, and ginkgo, magnesium has been shown to significantly decrease the amount of migraine headaches (Esposito 2011). Although not yet proven in clinical trials, a form of magnesium called magnesium-L-threonate may be ideal for people with migraine because experimental data indicate that it enters the central nervous system more efficiently than other forms of magnesium (Slutsky 2010).

Melatonin: Melatonin is a natural compound produced by the pineal gland that helps regulate the sleep-wake cycle (i.e., circadian rhythms), and has been clinically shown to possess potent antioxidant and analgesic properties (Wilhelmsen 2011). Since melatonin is often found in lower-than-normal levels among migraine patients (especially during an attack), it is thought that it may play an important role in migraine pathology (Masruha 2008; Masruha 2010).

Some researchers hypothesize that migraines are triggered by an irregularity in pineal gland function (Gagnier 2001). When this imbalance is corrected through melatonin supplementation, some migraine patients experience an improvement in symptoms (Vogler 2006). In one clinical study, melatonin supplementation trended toward a two-thirds reduction in number of migraine attacks (Alstadhaug 2010). This response rate may have been more statistically significant if the researchers used a larger dose of melatonin (3 mg instead of 2 mg), and if treatment was extended for a longer period of time (12–16 weeks, instead of 8 weeks; Peres 2011). Melatonin has been found to be safe and associated with little or no side effects (Gagnier 2001).

S-adenosylmethionine (SAMe): SAMe is a nutritional supplement derived from the amino acid methionine and adenosine triphosphate, a nucleic acid (De Silva 2010). It is a naturally occurring substance produced by the body to perform a variety of important biochemical processes, especially involving the central nervous system (CNS; Carpenter 2011). Some data suggest that long-term supplementation with SAMe may relieve pain among migraine sufferers, possibly due to its ability to increase serotonin (Gatto 1986; Fetrow 2001).

L-tryptophan: The amino acid L-tryptophan is a precursor to serotonin. Several lines of evidence indicate that low serotonergic signaling within the brain may precipitate migraine (Hamel 2007). Therefore, supporting serotonin synthesis by providing precursors such as L-tryptophan may help avoid physiological conditions that promote migraine headache. Indeed, in an older clinical trial, supplementation with 2 to 4 g of L-tryptophan daily was as effective at preventing migraine attacks as the medication methysergide (Sicuteri 1973). Also, a more recent trial found that dietary tryptophan depletion caused exacerbation of migraine symptoms (Drummond 2006).

Miscellaneous Beneficial Ingredients: The following list of natural ingredients may also be useful for managing migraine symptoms, though definitive clinical data are lacking:

  • Ginkgo biloba (Schiapparelli 2010)
  • Lipoic acid (Sun-Edelstein 2009a)
  • Vitamin B6 (Ross 2011)
  • Ginger (Mustafa 1990)

Suggestions

  • Butterbur root; standardized extract: 150 mg daily
  • Riboflavin: 400 mg daily
  • Ginger root, standardized extract: 250 mg daily
  • Coenzyme Q10 (as ubiquinol): 100–300 mg daily
  • Feverfew (dried leaf): up to 1200 mg daily in divided doses
  • Magnesium: 140 mg daily as magnesium-L-threonate; 320 mg daily as magnesium citrate
  • Melatonin: 0.3–5 mg before bed (sometimes up to 10 mg)
  • S-adenosylmethionine (SAMe): 200–1200 mg daily
  • Ginkgo biloba; standardized extract: 120 mg daily
  • R-lipoic acid: 300–600 mg daily
  • Vitamin B6 (as pyridoxal-5-phosphate): 100 mg daily
  • L-tryptophan: 500–2000 mg daily

In addition, the following blood tests may provide helpful information:

  • Food Safe Allergy Test
  • Magnesium (RBC)
  • Male Basic Hormone Panel
  • Female Basic Hormone Panel
  • Male Comprehensive Hormone Panel
  • Female Comprehensive Hormone Panel

More information on the integrative interventions and lab tests mentioned in this article is available from Life Extension, an organization dedicated to scientific innovation. To receive a free copy of Life Extension magazine, visit www.lifeextension.com/Book6 or call toll-free 866-606-9803 and mention discount code DPT506A.

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