The third most common disease in the world behind dental caries and tension-type headache, migraine has an estimated global prevalence of 14.7%. That equates to approximately one in every seven people who are affected and in need of respite from the often-debilitating symptoms that don’t consistently respond to current drug treatment.
A study conducted in mice that employed dimethyl fumerate (DMF), a drug typically prescribed for relapsing-remitting multiple sclerosis (MS) and examined its effectiveness in reducing migraine. Specifically, the study investigated the role of DMF, as an activator of Nrf-2/ARE pathway in nitroglycerin (NTG)-induced hyperalgesia and its underlying mechanisms. It has been demonstrated that NTG administration produces attacks similar to spontaneous migraine attacks and sensitizes trigeminal and cortical structures that underlie migraine allodynia.
1. High levels of oxidative stress are involved in migraine pathogenesis along with genetic and environmental factors.
2. NrF2 is the master gene regulator of oxidative stress and among many things, Nrf-2 signaling cascade modulates both inflammation and oxidative stress.
3. DMF was discovered to impact the anti-oxidative stress cell machinery promoting the transcription of genes downstream to the activation of Nrf-2.
4. Another recent study demonstrated that activation of the Nrf-2/ARE pathway inhibited the activation of trigemino vascular system (TGVS) and prevented the induction of hyperalgesia, however without specifying the underlying mechanisms of migraine.
5. Patients with migraine have a threefold higher incidence of depression and patients with depression have a threefold higher incidence of migraine (I believe this is due to all the factors that lead to immune dysregulation and chronic neuro-inflammation in the brain).
6. Activation of NF-κB in the trigeminal cervical complex (TNC) is reported to be involved in the pathogenesis of migraine; the nuclear factor NF-κB pathway has long been considered a prototypical pro-inflammatory signaling pathway, largely based on the role of NF-κB in the expression of pro-inflammatory genes including cytokines, chemokines, and adhesion molecules. It’s been shown that upregulation of inflammatory a few different gene transcripts occurs in those with migraine (there is ongoing cross talk between the NF-kB gene and the Nrf-2 gene that allows a balance in neuro-inflammation). DMF induced Nrf-2 expression suppresses the NF-κB mediated inflammatory pathway.
b. In other words, in response to inflammatory and oxidative stimuli, upregulation of Nrf-2 signaling inhibits the overproduction of pro-inflammatory cytokines and chemokines as well as limiting the activation of NF-κB.
7. In headache, neurogenic inflammation is responsible of the characteristic symptoms as pain and sensitization, because mast cells that reside close to primary nociceptive neurons are capable of triggering local inflammation.
In summary: DMF treatments markedly upregulated the antioxidant enzymes, demonstrating its important role in the reduction of oxidative stress related to migraine and leading study investigators to conclude that this drug may be able to impact migraine incidence.
BUT…is there a more natural way to treat migraine?
So do all patients necessarily need a drug to prevent and treat migraine? What else can we do to reduce oxidative stress and up regulate NrF2 pathways?
Oxidative stress occurs when there is an imbalance between the production of free radicals and the body’s ability to counteract their damaging effects through neutralization with antioxidants. Oxidative damage is the harm sustained by cells and tissues that are unable to keep up with free radical production.
No doubt, as I’ve said many times, our brain is only as healthy as our body (and gut) and that any measures to reduce systemic inflammation (diet, lifestyle modifications, stress reduction, sleep regulation, exercise and more) will help.
1. Lower your toxic load – that includes chemicals, toxins, GMO's, pesticide-laden produce - and address infectious triggers.
2. Real food is the best source of antioxidants, so eat a healthy well balanced diet and ideally focus on non-GMO, organic choices and avoid all processed foods.
Foods rich in antioxidant nutrients include:
Vegetables: Broccoli, bell peppers, spinach
Fruits: Oranges, apples, berries
Whole-grains: Oats, quinoa, brown rice
Beans: Kidney, pinto, red beans
Nuts: Walnuts, pecans, almonds
Drinks: Coffee, tea
Avoid foods that are produced with rancid vegetable oils.
3. Don’t smoke; if you do, quit!
4. Supplements, while not a replacement for the benefit of nutrients from real foods, include
Vitamin A, E, C, selenium, resveratrol, alpha lipoic acid, pyridoxal-5-phosphate (P5P), endothelial cell growth supplement (ECGS), N-acetyl cysteine (NAC).
* Note Vitamin B complex and Magnesium (600 mg / day) are helpful migraine preventers
5. Restorative sleep.
6. Lower stress and stress management techniques.
7. Consistent form of exercise.
8. Heal your gut: previous studies have already found an association between gastrointestinal disorders and migraines because of the gut-brain connection.
Always remember that our brain is only as healthy as our body. So if we can heal the body, we can heal the brain.
Dr. Suzy Gazda
Dr. Suzanne Gazda, Integrative Neurology