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Science of Migraine

GABA, or gamma-aminobutyric acid, is a popular supplement for the relief of anxiety and insomnia. Until recently, I was not recommending it to my patients. There are no scientific studies showing that it works. So why did I start recommending it? A report by a single patient, or as we say in scientific literature, an N of 1.

This 65-year-old woman had been suffering from anxiety from a young age. When her summer camp friends would write down everyone’s most common sayings, hers was, “I am so nervous”. This sense of anxiety persisted throughout her life. She is a successful career woman with a loving family. After a death in her family, she started seeing a psychologist who suggested taking GABA for insomnia. Within days, she was overcome by a sense of calmness she never experienced in her life. It’s been several months now and she remains calmer than ever before.

Certainly, this could be a placebo effect. In addition to the lack of controlled clinical trials, it is not even clear if GABA gets into the brain by crossing the so-called blood-brain barrier (BBB). It is possible, however, that it does not have to cross BBB. There is evidence that GABA may work through the enteric nervous system (ENS) – nerve endings lining the intestines. Both GABA and its receptors are widely distributed in the gut. Certain probiotics such as Lactobacillus and Bifidobacterium were found to increase GABA concentrations in the ENS. Probiotics have been shown to improve mood. This effect may be occurring through the vagus nerve. Vagus nerve is a large nerve that connects the intestines and all internal organs with the brain. It was somewhat of a surprise that vagus nerve stimulation at the neck level was proven (and FDA-approved) to relieve refractory depression and epilepsy.

GABA has been a popular supplement for many years. This obviously does not prove that it really works. However, it is very safe and relatively inexpensive. I would consider trying it before taking a prescription drug for anxiety or insomnia. Those can have significant side effects and in a 65-year-old may increase the risk of Alzheimer’s disease. And I always recommend regular exercise and meditation before any supplements.

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Thank you, Lisa Robin Benson for a kind review of my book. This is a video review on the Migraine.com website.

Many of my colleagues have written very positively about my book. It is even more gratyfing to hear that patients and patient advocates also find it useful.

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Opportunities & Challenges in the Management of Headache is one of the two annual courses organized by the Diamond Headache Clinic Research & Educational Foundation. This year, it will be held in San Diego from February 16th through February 19th.

The other annual event, Headache Update 2023 will be held in Orlando, Fl from July 13th through July 16th. Both courses have been always well attended and have been receiving very high marks from the attendees.

It’s been my privilege to participate in these annual courses over the past 25 years. This year I will be speaking on February 17th on Nutritional Approaches and Alternative Therapies in Migraine.

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Holidays are again upon us. There are many reasons why people experience more migraines this time of year. Family drama, all the delicious unhealthy food, and alcohol. A report just published in the journal Headache brings some good news. Scientists proved that alcohol does not trigger migraines.

The researchers evaluated the digital diaries of 493 migraine sufferers who reported drinking alcohol. They used sophisticated statistical analysis including standard deviations, Bayesian statistics, Markov Chain Monte Carlo simulations, and the like, to show that there was no correlation between drinking alcohol and developing a migraine the next day.

If you still insist that alcohol gives you migraines, to paraphrase Groucho Marx, who are you going to believe, the scientists or your own lying eyes?

Another amusing paper comparing red wine with vodka as a trigger of migraines was published years ago by British researchers in The Lancet 

Migraine patients who believed that red wine but not vodka triggered their attacks were challenged either with red wine or vodka. It was a blinded study – patients were not told what they were drinking. Vodka was diluted to equivalent alcohol content, and both were “consumed cold out of dark bottles to disguise colour and flavour”. And indeed, only wine triggered a migraine attack. A group of French doctors responded to this study in a letter to the editor. They stated that the only thing this study proved was that the Brits can’t tell wine from vodka.

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Riboflavin (vitamin B2) has been a popular supplement for the prevention of migraine headaches. The evidence for its efficacy is limited. Only one small double-blind, placebo-controlled trial showed that a very high dose of riboflavin (400 mg daily) is better than a placebo. The study included only 55 patients, which makes the results not very reliable. Besides, the difference between the riboflavin and the placebo groups appeared only in the third month. There was no difference during the first two months. This study was published over 20 years ago and my clinical impression over this long period of time has been fairly negative.

A study just published in the journal Headache examined dietary intake of riboflavin and thiamine (vitamin B1) and correlated it with the occurrence of migraines or severe headaches. The researchers used the data from 13,439 adult participants in the National Health and Nutrition Examination Survey conducted between 1999 and 2004 in the United States. They found that people with a high intake of thiamine were significantly less likely to suffer from severe headaches or migraines. This was more pronounced in women. They found no such association for riboflavin.

Supplements with the most evidence in treating migraines are magnesium and CoQ10. I recommend riboflavin, folate (vitamin B9) and vitamin B12, to patients with an elevated homocysteine level. Excessive amounts of this amino acid are damaging to blood vessels and may be responsible for the increased risk of strokes in patients who have migraine with aura. It is worth checking homocysteine levels in all patients who have migraine auras, even if the auras occur infrequently.

“B complex” is a popular combination of various B vitamins. This latest paper is making me consider adding B complex rather than individual B vitamins to magnesium and CoQ10 in all of my migraine patients.

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It was an honor to speak in Israel at the 6th Annual International Headache Symposium along with past presidents of the International Headache Society, Drs. Messoud Ashina and Alan Rapaport, the current IHS president, Cristina Tassorelli, the president-elect, Dr. Rami Burstein, and other leading headache experts. The symposium was organized by the President of the Israeli Headache Association, Dr. Oved Daniel, and by Dr. Arieh Kuritzky.

 

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Regular exercise has been proven to prevent migraine headaches in many studies. A Swedish study of 91 patients established that exercising for 40 minutes 3 times a week is as effective as relaxation training or taking a preventive migraine drug topiramate. Topiramate, however, caused significant side effects. Another study by the same group of researchers of 46,648 people found a strong inverse correlation between physical activity and the frequency of headaches.

A report by German researchers in the September 13 issue of the journal Neurology provides strong evidence that physical activity leads to larger brain volumes. This was a rigorous study that included 2,550 participants. The physical activity was measured using an accelerometer, a device similar to a fitness tracker.

The authors discovered that “Physical activity dose and intensity were independently associated with larger brain volumes, gray matter density, and cortical thickness of several brain regions.” The most notable change occurred in people who went from a sedentary lifestyle to a modest amount of low-intensity exercise when compared with those who already engaged in at least moderate amounts of physical activity. And this trend continued – very high frequency and intensity of training did not offer any additional benefits.

Two other reports of various benefits of exercise were published this month.

One was a study published in JAMA Neurology. This study also used accelerometers to count the steps made by 78,430 people. The researchers found that a higher number of steps prevented the development of dementia. The optimal dose was just under 10,000 steps and a higher speed had an additional benefit.

The second report in JAMA Internal Medicine analyzed the same group of 78,430 people and discovered that accumulating more steps per day (up to 10,000) may be associated with a lower risk of all-cause, cancer, and cerebrovascular disease mortality and incidence of cancer and cerebrovascular disease. Here they also found that a higher step intensity may provide additional benefits.

 

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Last week I spoke to Dr. Amelia Scott Barrett, a neurologist and headache specialist based in Denver. She shares my interest in combining medications with various non-drug therapies. In our first conversation, we discussed the role of magnesium in treating migraines.

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The 6th Annual International Headache Symposium in Israel will be held at Daniel Hotel, Herzliya (8 miles from Tel Aviv), on October 27, 2022. THe symposium is organized by the President of the Israeli Headache Association, Dr. Oved Daniel and by Dr. Arieh Kuritzky.

I am honored to have been invited to speak alongside the President of the International Headache Society Dr. Messoud Ashina, Dr. Rami Burstein of the Harvard Medical School, and other leading headache experts. The topic of my presentation will be “What to do when nothing works”. Other topics to be discussed include, Molecular signaling pathway in migraine: update, (Messoud Ashina), Connecting the line between dizziness, occipital headache, muscle tenderness and the cerebellum (Sait Ashina), Open-label studies: do they have any value? (Cristina Tassorelli), and others.

You can see the full program and registration information on this website.

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I recently saw a 32-year-old woman who never suffered from headaches until a year ago when she was given an injection of a COVID vaccine (J&J). Her headache started the day after vaccination and it has persisted unabated. Besides severe daily headaches, she developed profound fatigue, muscle aches, and brain fog, making her unable to work. Her headaches had all the features of chronic migraines and I recommended trying Botox injections along with a migraine medication that she has not yet tried.

I’ve seen a few dozen patients who developed less devastating headaches or whose preexisting migraines worsened after vaccination. Some developed a headache after the first or second shot and a few had it only after the booster. I am not suggesting that people should avoid the COVID vaccine. I’ve had three shots myself. I am writing about this because of a study just published by European researchers in the Journal of Headache and Pain“Headache onset after vaccination against SARS-CoV-2: a systematic literature review and meta-analysis.”

They examined the results of 84 scientific reports that included 1.57 million participants, 94% of whom received Pfizer or Oxford-AstraZeneca vaccines. They discovered that vaccines were associated with a doubling of the risk of developing a headache within 7 days from the injection compared to people who received a placebo injection. They did not find a difference between the two different vaccine types. Some people developed a headache within the first 24 hours. In approximately one-third of the cases, headache had migraine-like features with pulsating quality, phonophobia, and photophobia. In 40 to 60% the headache was aggravated by physical activity, which is another migraine feature.

The majority of patients used some medication to treat their headaches. People reported that the most effective drug was aspirin, although the details about various treatments were not provided. We do know that in Europe doctors are much less likely to prescribe medications, including triptans. It is likely that early and aggressive treatment can prevent these headaches from becoming chronic and disabling.

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I am happy to announce that you can attend the Migraine World Summit free of charge. It is back on March 16-24, 2022 for its 7th annual virtual event. As one of the former presenters, I can tell you that you may greatly benefit from learning about the latest research on how to best manage migraine.

Migraine World Summit is a 9-day event where 32 of the world’s leading experts on migraine and headache research are interviewed on topics voted on by real patients. These interviews are online and can be accessed from anywhere in the world, but are only available free during the 9-day event.

Get your ticket today at MigraineWorldSummit.com

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Worsening of headaches in children is one of many deleterious effects of the pandemic and measures to control it. A survey of children in a headache clinic at the Children’s National Hospital in Washington DC by Dr. DiSabella and his colleagues showed that 46% of children had worsening of their migraine headaches during the pandemic.

They also reported much higher rates of anxiety, depression, and stress. Two-thirds of children reported that they exercised less. This could be one of the contributing factors since exercise has been shown to reduce the frequency and the severity of headaches.

What this survey did not explore is the effect of family stress and the presence of child abuse. Reports of child abuse have actually declined during the pandemic because most of these reports come from teachers. Chronic migraines and chronic pain are much more common in patients with a history of being physically, emotionally, or physically abused. PTSD from other causes has a similar predisposing effect and many children and adults have been traumatized by the pandemic.

Some children (as well as adults) report improvement of their headaches during the pandemic. My patients tell me that because they do not have to commute, they have more time to exercise, meditate, cook healthy meals, and get more sleep. I see this in a small proportion of patients. A larger group did worse with additional factors being worsening of headaches due to COVID and in a very small number, COVID vaccines.

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