Summary on Migraine prophylaxis
Riboflavin - also known as vitamin B-2 - is an "essential" vitamin; that is, the body doesn't produce the vitamin on its own, so it must be provided in the diet. Riboflavin assists in the metabolism of energy by processing protein, fats and carbohydrates. Benefits of riboflavin intake include healthy vision and skin, and a possible preventive effect against migraines.
As reported in the European Journal of Neurology 1 , researchers at the Humboldt University of Berlin recruited 23 people (aged 20 to 65) who experienced frequent migraine headaches. All of the subjects took 400 mg of riboflavin for six months. Questionnaires recorded the subjects' rates of migraine frequency, duration, intensity and the use of analgesic drugs at the outset of the trial, after three months, and again at six months.
Half way through the trial, the average frequency of migraines had been cut in half for the entire group. The rate of analgesic usage was nearly cut in half as well. Over the course of the trial, subjects reported no change in the duration or intensity of headaches that still occurred none of the subjects reported any adverse reactions.
Foods that contain good amounts of riboflavin include leafy green vegetables, whole grains, meat, eggs, yoghurt, cheese and milk. However, alcohol consumption and oral contraceptives may cause a riboflavin deficiency.
Riboflavin is not always efficiently absorbed by the digestive tract, so anyone who puts it to use for migraine prevention may also want to try other natural preventive agents such as magnesium (many migraine patients have been shown to have magnesium deficiencies). Magnesium and Riboflavin may act synergistically.
BACKGROUND
Although its exact mechanism of action in migraine prophylaxis has not been elucidated, the beneficial effects of riboflavin have been ascribed to increased energy production in the mitochondria, a mitochondrial dysfunction may be a factor in migraine pathogenesis. Based on this premise, riboflavin intake may provide migraine relief in patients with reduced energy production within the mitochondria of brain.
CLINICAL TRIALS
Open-Pilot Study
In a study by Schoenen and colleagues 2 , 49 subjects diagnosed with migraine with and without aura, received 400 mg of riboflavin per day as a single oral dose.
Efficacy was determined in terms of migraine severity and was assessed after three to five months of treatment.
Migraine severity score decreased in all subjects, with mean improvement at 68.2%. The number of migraine days per month decreased significantly from 8.7 to 2.9
The authors reported that high-dose riboflavin could provide an effective and satisfactory preventive approach for migraine.
Riboflavin- randomised placebo controlled study
Schoenen et al. 3 conducted a double-blind, randomized, parallel-group study of high-dose riboflavin versus placebo in patients ages 18 to 65 years. Fifty-five patients were randomized to three-month treatment with 400 mg of riboflavin (n = 28) or placebo (n = 27).
The primary efficacy parameter was the change of migraine attack frequency during month 4 when compared to the frequency of migraine attack during baseline month 1
Secondary efficacy parameters were reduction of migraine headache days; mean duration and severity of migraine; migraine index (headache days plus mean severity); number of days with nausea/vomiting; and mean number of tablets, suppositories, or injections taken per day for the acute treatment of the attacks.
There was a statistically significant decrease in migraine attack frequency in the riboflavin group compared to placebo. Patients in the riboflavin group had an average of two fewer migraines per month ( P = .0001). The change from baseline to month 4 in attack frequency—the primary outcome variable—was in favour of 400 mg of riboflavin. The response rate was 19% in the placebo group versus 56% in the riboflavin group ( P = .002). Beneficial effects of riboflavin were observed after one month, and the frequency of attacks declined further during the last month of follow-up. The difference between treatment groups at month 4 became statistically significant in advantage of riboflavin. Attack frequency and headache days were lower in the riboflavin group. Additionally, days with nausea were lower in month 4 in comparison to month 1.
Regarding safety, there were no significant changes in blood pressure or body weight (placebo, +0.4 kg; riboflavin, +0.2 kg) among study groups. Only three adverse effects were reported during the study. One subject in the riboflavin group experienced diarrhoea two weeks after starting treatment and subsequently withdrew from the study. Another subject in the riboflavin group reported polyuria but completed the study. One subject in the placebo group reported recurrent abdominal cramps of moderate intensity but did not withdraw.
The beneficial effects of riboflavin were most prominent on migraine frequency and the number of migraine-free days. The efficacy of riboflavin over placebo was marginal for headache severity, duration, the use of rescue medications, and migraine-associated gastrointestinal symptoms.
Pertaining to its good efficacy and tolerability profiles, the authors concluded that riboflavin provides a potential option for migraine prophylaxis.
The field of pharmacologic management of migraine continues to evolve. A wide range of migraine preventive therapies is available. However, the therapeutic gain of such treatments against placebo is low (30% to 40%). Additionally, the use of established migraine prophylactic therapies has been linked to adverse effects. Specifically, central nervous system adverse effects are associated with beta-blockers, and anticholinergic adverse effects are associated with tricyclic antidepressants.
Riboflavin has been evaluated in a number of trials and was shown to be effective in decreasing frequency and severity of migraine attacks. Also, high-dose riboflavin appears to be safe and with relatively few and benign adverse effects. Major adverse effects of riboflavin include gastrointestinal upset.
1. Boehnke C, Reuter U, Flach U, Schuh-Hofer S, Einhäupl KM, Arnold G. High-dose riboflavin treatment is efficacious in migraine prophylaxis: an open study in a tertiary care centre. Eur J Neurol. 2004;11:475-7.
2. Schoenen J, Lenaerts M, Bastings E. High-dose riboflavin as a prophylactic treatment of migraine: results of an open pilot study. Cephalalgia . 1994;14:328-329.
3. Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology . 1998;50:466-470.
Magnesium
Magnesium is a mineral found naturally in foods such as green leafy vegetables, nuts, seeds, and whole grains and in food supplements.
Magnesium is needed for more than 300 biochemical reactions. It helps regulate blood sugar levels and is needed for normal muscle and nerve function, heart rhythm, immune function, blood pressure, and for bone health.
Several studies have evaluated the effectiveness of magnesium for migraine and have had promising results. In one study, oral magnesium (600 mg per day) or a placebo were given to 81 people with migraines 1 . At the third month, the frequency of migraines was reduced by 41.6 percent in the group taking magnesium, compared to 15.8 percent in the group taking the placebo. The only reported side effects were diarrohea in 18.6 percent of people and digestive irritation in 4.7 percent.
Other studies have found that magnesium reduces the severity and frequency of migraine.
An increasing number of doctors believe that some of the most severe cases of migraines may actually be caused by an imbalance of key minerals such as magnesium and calcium.
"Not all headaches are produced by this imbalance, but we now know that 50 to 60 percent of migraines are magnesium-linked. And that's probably why no prescription therapy on the market successfully treats headaches across the board.
The weight of evidence for magnesium's use in the treatment of migraines is building. To understand why magnesium might do the trick, it helps to take a look at how migraines happen.
Migraines are thought to be caused by vascular changes, or changes in the blood vessels, that reduce blood or oxygen flow in the scalp and brain. What causes these vascular changes? Things such as muscle contractions during times of stress and biochemicals called catecholamines and serotonin, which are circulating in the blood. Too much serotonin can cause blood to flow too slowly; too little can cause blood to move too rapidly.
While researchers have long known that changes in serotonin and catecholamine levels cause migraine pain, stopping these changes has been a hit-or-miss proposition.
Without enough magnesium, serotonin flows unchecked, constricting blood vessels and releasing other pain-producing chemicals such as substance P and prostaglandins. Normal magnesium levels not only prevent the release of these pain-producing substances but also stop their effects.
It's very likely that magnesium deficiency is a widespread cause of migraines. Studies show that many people don't even come close to getting the Daily Value of magnesium, which is 400 milligrams.
It is estimated that about 50 to 60 percent of migraine patients have low magnesium levels.
1. Peikert A, Wilimzig C, Köhne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia. 1996;16:257-63.
