FYI re MIGRAINE AND LIFESTYLE: (please also see Radio New Zealand podcast of interview witih Dr Carol Hungerford, Australian GP who wrote a book on this subject 2014) also

STEP 1: Diary keeping: There are lots of potential triggers and they can vary from one person to another. We should investigate the most common triggers. Migraine sufferers find it helps to keep a personal diary of when headaches occur and suspected triggers to learn the best way to avoid them in the future. It's all about knowing your own body. Some people have strange feelings 24,48 or even 72hrs before their migraines, reminding us that although rapid reactions to foods are more common, that one may need to look back up to 72hrs for unusual foods in some cases. The challenge may be that a migraine is only triggered by a product (such as red wine) only if the person also eats another product (e.g. cheese), or also is dehydrated or stressed. Hence such overlapping triggers make it more difficult to find the culprit. A diary will help tease these complexities out. If you then identify a trigger, try eliminating this completely for a few months (long enough to be sure a change in migraine has occurred because of your change, not just by random chance).

STEP 2: A role of certain foods/lifestyle factors? A craving for certain foods is likely to be a symptom of an imminent migraine approaching rather than a cause of the migraine. A recent review of research evidence concluded these suspect foods could not be shown to trigger attacks or that a diet avoiding these foods will not stop people having migraines. Some migraine sufferers do individually report good results when they avoid some foods. As a result some specialists will recommend people cut these out of their diets. The following 4 approaches can be tried sequentially if diary keeping to identify the triggers has been unsuccessful.

Environmental triggers: Various environmental factors are thought to precipitate or trigger migraines. Some migraines are totally unpredictable, occurring for no apparent reason. Common examples of triggers include:

Undue stress or relaxation after a stressful period of time ("stress letdown")
Exposure to chemicals such as paints, varnishes and strong cleaning solutions
Hormone levels during the menstrual cycle
Bright or glaring lights
Unusual weather conditions
Too little sleep or too much sleep (sleeping in)
Missing a regular meal, causing excessive hunger

Nutrition triggers:
The most commonly identified culprits are:

Caffeine withdrawal
Coffee tea chocolate, or other caffeine based products
Artificial sugars

Foods containing histamine, tyramine, nitrates, nitrites and sodium glutamate:
eliminate from diet / lifestyle for a few months.

Aged cheddar, blue and white rind cheeses
Smoked and cured foods, eg salami, pepperoni
Fermented foods, eg soy sauce, miso, sauerkraut, beer, sherry, ginger beer, vinegar, yoghurt, sour milk
Salted and dried foods e.g. bacon, anchovies
Pickled foods, eg olives, gherkins
Broad or fava beans
Yeast extract, eg Marmite, Vegemite, soup mixes
Meat tenderiser

Other trigger foods?: definitely identified by some include

  • oranges, bananas, tomatos, nuts, other citrus, alcohol, various specific alcohol types (one patient might be "cheap beers" another red wine), excessive fizzy drinks, lollies, specific lollies (eg "fruit bursts"), red food colouring.
  • Gluten and Lactose elimination may assist for some people.
STEP 3 nutritional supplements: Various vitamins, minerals and herbs have been considered useful in Migraine. This includes the following levels of evidence as categorised by American Academy Neurology 2012. Level A evidence: "proven to be effective": butterbur, a native American remedy; daisy extract Petasites. Level B evidence: "probably effective": Vitamin B2 (Riboflavin), Magnesium, Feverfew, One down side is that toxicity of these products is also less well studied than with medications. Riboflavin (B2, 200mg twice daily) and Magnesium come combined (Clinician's brand Migradol at your chemist), and a special source of the herb Feverfew (Puracol's Feverfew or Nature's Way Mygrafew). Uncertain efficacy. Based on a single (statistically significant) pilot study suggesting effectiveness with B vitamins in some patients: Vitamin B12, Vitamin B6 (pyridoxine) and Folate (Vitamin B9). B12 can be supplemented sublingually.

1.Homocysteine, B6, B12 and folate: Some patients are relatively deficient in B12 and Pyridoxine and Folate, with elevated Homocysteine which can badly affect blood vessels. In these patients supplementing these vitamins leads to a 30% reduction in average migraine disability. These supplements should not be used in patients with problematic angina (heart pains), and there has been concern regarding the use of Folate in smokers but this remains unfounded. A randomized, double-blind placebo, controlled trial of 6 months of daily vitamin supplementation (i.e. 2000 mcg of folic acid, 25 mg vitamin B6, and 400 μg of vitamin B12) in 52 patients diagnosed with migraine with aura has recently been published. Vitamin supplementation reduced homocysteine by 39% (approximately 4 μmol/l) compared with baseline and better then placebo (P=0.001). Vitamin supplementation also reduced the prevalence of migraine disability from 60% at baseline to 30% after 6 months (P=0.01), whereas no reduction was observed for the placebo group (P>0.1). Headache frequency and pain severity were also reduced (P<0.05), whereas there was no reduction in the placebo group (P>0.1). In this patient group the treatment effect on both homocysteine levels and migraine disability was associated with MTHFRC677T genotype whereby carriers of the C allele experienced a greater response compared with TT genotypes (P<0.05). The effect appeared limited to those whose Homocysteine levels were above the study median (ie 9.2 micomol/l). This pilot study provides some early evidence that lowering homocysteine through vitamin supplementation reduces migraine disability in a subgroup of patients. Larger trials are now warranted to establish whether vitamin therapy is a safe, inexpensive and effective prophylactic option for treatment of migraine and whether efficacy is dependant on MTHFRC677T genotype. The influence of dietary ie food folate intake on migraine has been unclear. A study in Headache: The Journal of Head and Face Pain (Vol 55, Iss 2,p301–309, Feb 2015) reports the association of dietary folate intake in the form of dietary folate equivalent, and total food folate (TFF) on migraine frequency, severity, and disability in 141 adult white females having migraine with aura and tested for MTHFR C677T gene variant. A weak but significant inverse relation was observed between dietary folate p= .045, and 'any folate' p= .036 and migraine frequency. In the subset with the MTHFR C677T gene, migraine frequency was also significantly but weakly linked to folate consumption p= .029, The main factors to reduce Homocysteine are B-vitamins. Vitamin B12 is very difficult for some patients to absorb from the stomach, so treatment either under the tongue, or by injection may be needed, and blood levels should rise to the upper end of the normal range.

  • Folate 5mg tablet 3 days per week (prescribed or OTC)
  • Pyridoxine (B6) 100mg 3 days per week (prescribed or OTC)
  • Vitamin B12 at 1000mcg po or s/l 3 days per week. Find a dose which pushes their B12 level to upper range and corrects homocysteine. Oral formulations Methylcobalamin are not funded.
  • oSources: B12 spots (New Hope/Twinlabs sublingual pastille "spot" 500mcg ~$37 for 100). B12 tablets (New Hope/Twinlabs 1000mcg ~$23 for 60). eg New Hope/Twin Labs products in "Hardy's Health Stores" to date, a chain across NZ. Methylcobalamin (B12) 1000mcg sublingual "Source Naturals" (~$23 for 60)
  • oIf B12 does not climb into high-normal range, lowering homocysteine, patients need…
  • Vitamin B12 injections by the GP
  • Gastric parietal cell antibodies for atrophic gastritis
  • Intrinsic factor antibodies
  • Remove proton pump inhibitors
  • Helicobacter serology (possible cause of impaired B12 absorption, treatable)
  • Upper GI endoscopy, especially if no reversible factor found or GPC Abs +ve
  • Food sources of the B-vitamins:
  • B12: Fish, poultry, meat, fortified cereals, yeast extracts (brewers' yeast, Marmite). Other good sources include: asparagus, broccoli, spinach, bananas, potatoes, dried apricots, dates and figs, milk, eggs, cheese, yoghurt, nuts and pulses, fish, brown rice, wheat germ, wholegrain cereals. B6 (pyridoxine) Fortified cereals, fortified soy products, organ meats, Vitamin B6 is found in most foods, so deficiency is rare. Sources also include avocado, herring, salmon, sunflower seeds and walnuts, Folate: Dark, leafy vegetables; enriched and whole grain breads; fortified cereals. Liver contains the greatest amount of folic acid, with lower levels found in beef, lamb and pork and a range of green vegetables and citrus fruits. Other sources of folate are dried beans, fresh orange juice, tomatoes, wheat germ (wholemeal bread and cereal) and wholegrain products (pasta and brown rice).
  • Please note: If Homocysteine does not respond to the above supplementation with the B-vitamins, it may indicate a deficit in Riboflavin (vitamin B2) and zinc, and may be assisted by supplementation of both +/- Trimethylglycine, and N-acetylcysteine. This entire combination (unproven to help clinically, but convenient and not expensive) can be obtained from single products such as on
  • Solgar's Gold Specifics Homocysteine Modulators ($22 for 1 months (2 daily), but no zinc included)
  • Higher Nature's "H factors" ($85 for 3 months (2 daily), zinc included)
2.Magnesium levels tend to be lower in those with migraine headaches, including children and teenagers, when compared to those with tension headaches or no headaches at all. In addition, a few clinical studies suggest that magnesium supplements may decrease the length of time that one suffers from a migraine and reduces the amount of medication needed. Some experts suggest that oral magnesium may be an appropriate alternative to prescription medication for people who suffer from migraine headaches. Magnesium sulfate seems to be less effective than prescription medications for preventing migraines in those who have 3 or more headaches per month. The only exception to this may be women who get migraine headaches around the time of their menstrual period. In addition, magnesium supplements may prove to be a welcome option for migraine sufferers who cannot tolerate medications due to side effects or who can't take migraine medications due to pregnancy or heart disease. These issues are under scientific investigation. Migraine patients may benefit if they consume at least 6 mg magnesium per day for each kilogram of body weight. An even higher intake of 10 mg/day per Kg of body weight may be desirable provided that it does not trigger a laxative effect. Breaking the dosage into three or four parts taken at different times of day helps prevent laxative effect.

3.Feverfew gained popularity in Great Britain in the 1980s as an alternative to conventional medications for migraine headaches. A survey of 270 migraine sufferers in Great Britain revealed that more than 70% of individuals felt substantially better after ingesting an average of 2 - 3 fresh feverfew leaves daily. Several controlled human trials have been conducted using feverfew for migraine prevention and treatment. Overall, these studies suggest that feverfew taken daily as dried leaf capsules may reduce the incidence of attacks in patients who experience long-term migraine headaches. A clinical study used a combination of feverfew with Salix alba (white willow). White willow contains components similar to aspirin. The product was given twice daily for 12 weeks. The frequency of migraine attacks and the pain intensity and duration were significantly reduced in patients taking the combination. Another study found that a carbon dioxide extract of feverfew decreased the frequency of migraine attacks from 4.76 per month to 1.9 per month. A 3 month study in 49 subjects found that a combination of feverfew with magnesium and vitamin B2 provided a 50% decrease in migraine attacks. Some studies in humans have not been positive. Whether feverfew helps improve migraine pain may also depend on which feverfew supplement you take.

4.Riboflavin (Vitamin B2): Several studies indicate that people who get migraines may decrease the frequency and duration of the headache by taking riboflavin. One double-blind, placebo-controlled study showed that taking 400 mg of riboflavin a day (eg 200mg twice daily) cut the number of migraine attacks in half.

5.Butterbur (Petasites) is a daisy extract that has been shown in several small randomised controlled trials to prevent migraines. Effect has been shown from 25mg twice daily, and optimal at 75mg twice daily. Based on this data it has been approved, as proven, for migraine by the American Food and Drug Administration (quite an impressive feat). The most convincing trial was a three-arm, parallel-group, randomized trial comparing Petasites extract 75 mg bid, Petasites extract 50 mg bid, or placebo bid in 245 patients with migraine. Eligible patients met International Headache Society criteria for migraine, were ages 18 to 65, and had at least two to six attacks per month over the preceding 3 months. The main outcome measure was the decrease in migraine attack frequency per month calculated as percentage change from baseline over a 4-month treatment period.

  • i.Results: Over 4 months of treatment, in the per-protocol analysis, migraine attack frequency was reduced by 48% for Petasites extract 75 mg bid (p = 0.0012 vs placebo), 36% for Petasites extract 50 mg bid (p = 0.127 vs placebo), and 26% for the placebo group. The proportion of patients with a ≥50% reduction in attack frequency after 4 months was 68% for patients in the Petasites extract 75-mg arm and 49% for the placebo arm (p < 0.05). Results were also significant in favor of Petasites 75 mg at 1, 2, and 3 months based on this endpoint. The most frequently reported adverse reactions considered possibly related to treatment were mild gastrointestinal events, predominantly burping.
  • ii.Conclusions: Petasites extract 75 mg bid is more effective than placebo and is well tolerated as a preventive therapy for migraine. Petasites 50 mg PO bid was not significantly more effective than placebo on the primary study endpoints.
  • iii.Medsafe, Ministry of Health warning June 2012 about the potential liver risks of Butterbur assumed to be related to plant-based pyrrolizidine alkaloids being in the product. 40 cases have been reported in the literature of liver toxicity; 9 were acute hepatitis and 2 were profound. Most of the published studies of butterbur extract used a single commercial product, known as Petadolex®. This product had been considered to be free of pyrrolizidine alkaloids. The manufacturer stands by its claim that the product is free of detectable pyrrolizidine alkaloids. Close monitoring of liver function is advised. Butterbur is sold as Solaray from Health2000 (certified free of the pyrrolizidine alkaloids). 60caps $32.00.
STEP 4: The following are sometimes heralded as important in migraine, however there is no supportive evidence for this. They are generally harmless and not expensive so I do not discourage their use.

1.Fish or flaxseed oils, are sometimes promoted for migraines; unproven

2.A general supplement of multi-vitamins and minerals, plus vitamin C; unproven

3.Niacin 100-250mg daily (50 and 500mg tabs can be prescribed) (nicotinic acid, Vitamin B3, but NOT nicotinamide or inositol) may be of help. Niacin can be purchased cheaply from the chemist (but can certainly be prescribed) at this dose and comes in 50 and 100mg tabs; unproven. It can cause flushing. It can improve sleep, even dramatically in some cases. It is therefore best taken just before getting into bed for sleep

STEP 5: Consider a link to hormonal cycles. For menstrual migraine to consider using

  • 1.trial usual migraine lifestyle and prophylactic agents first
2.consider long cycle (9 weeks on 1 week off) low dose (20-30mcg estrogens) Combined oral contraceptive pills. These are more likely to cause worsening (20% of cases) than improvement (10% of cases) if they have any effect at all (70% will notice no change). There is some associated risk of thrombosis in classical migraine cases, so if any complicated migraine occurred hormones are avoided.

3.acetazolamide 125mg mane, pre-menstrually to cover all the days often affected by Migraine in her cycle

4.danazol 200mg bd if refractory to acetazolamide trial

5.natural progesterones intermittently, day 15 to day 25 each month

topical skin product from chemist or health store

rectal or vaginal 200-400mg 1-2x/day (cost ~$16.50 per month for lowest dose (plus GST plus P&H)).

Menstrual migraines are distinct from menstrual-related migraines. Menstrual-related migraines occur most typically 3-7 days before day 1 of the cycle. Other associated symptoms are fatigue, irritability or depression, labile mood, appetite changes, bloating, and breast tenderness. True menstrual migraines occur during the perimenstrual period, beginning two days before the menstrual cycle through day 3 of the cycle. Menstrual migraines appear to be more severe, longer in duration, and more resistant to standard acute and prophylactic treatments than other migraine headaches. The cause of the severity of menstrual migraines is multifold. The difference between menstrual and nonmenstrual migraines reflects the relationship that exists between estrogen and menstrual migraines. The level of estrogen is not the sole concern in a nonmenstrual migraine attack. In contrast, menstrual migraines are related to estrogen withdrawal, the rate and extent of declining estrogen levels, and interactions between estrogen and other biochemicals. One hypothesis is that the fall in estrogen levels during the late luteal phase of the menstrual cycle primes the blood vessels to be more susceptible to other biochemicals involved in producing migraines and causing the associated pain. These biochemicals include serotonin, pineal hormones, substance P, noradrenaline, dopamine, endorphins, prolactin, and progesterones. The optimal treatment for menstrual migraines should differ from the treatments for other migraines, including menstrual-related migraines, for several reasons. First, the pathophysiology of menstrual migraines differs from that of other migraines in that the premenstrual fall of estrogen plays an important role. In addition, the menstrual attack is especially resistant to treatment, and its predictable recurrence may provide an opportunity for effective prophylactic therapy in short perimenstrual courses. Another difference is that the triggers of other types of migraines, such as stress, some foods, excessive sleep, and fasting, are of little importance in menstrual migraine, and patients gain little from avoiding these triggers. Finally, comorbidity with the premenstrual syndrome requires additional therapeutic measures. Given that the multifactorial causes of menstrual migraine have yet to be fully elucidated, it is not surprising that the disorder is difficult to treat and control. Menstrual migraines impose a significant burden on women as well as the economy. Since menstrual migraines are often refractory to traditional migraine abortive therapy, hormonal treatments may be appropriate for prevention.

Oral Contraceptives: Despite the controversy concerning the therapeutic role of oral contraceptives and the various effects of these agents on migraines and migraineurs, some women may improve with this therapy. In keeping with the theory that estrogen withdrawal and fluctuations in estrogen levels during the luteal phase are the major contributing factors to menstrual migraines, maintaining a low level of estrogen for an extended duration of time may alleviate or improve menstrual migraines. Studies have addressed the acceptance of extended-duration oral contraception use in women and the need for regimens that delay the pill-free week. An open-label, randomized, crossover study investigated the effect of oral contraceptives on migraine headaches. The study involved 40 women with histories of moderate or severe migraine with associated nausea, vomiting, photophobia, sensory symptoms, or a combination of these symptoms, which usually are not related to true menstrual migraine. Twenty patients were randomized to receive an oral contraceptive for 2 months, whereas the second group of 20 patients did not receive hormonal treatment. After 2 months, the second group received hormonal treatment and the first group received no hormonal treatment. Hormonal treatment consisted of a Monophasic combination oral contraceptive pill (norgestrel 0.5 mg-ethinyl estradiol 0.05 mg [Ovral]). Patients kept a self-rating card to record the number and severity of headaches, and the amount, kind, and success of therapy for each attack. The results showed an increased frequency of moderate and severe headaches during the 2 months in which patients received oral contraceptives. Frequency of mild headaches also increased, but to a lesser extent than moderate and severe headaches. Twelve of the 40 patients reported improvement of their headaches while taking the oral contraceptive. Twenty-eight patients reported worsening of their headaches while receiving therapy. This study identified three distinct groups of patients: those with migraine headaches aggravated by oral contraceptives (28/40), those whose migraines decreased in severity or frequency when taking oral contraceptives (12/40), and those whose migraines were unaffected by oral contraceptives. In a retrospective study involving 451 women with histories of migraine headaches. The study involved 295 participants who previously had taken oral contraceptives and had been diagnosed with migraine headaches. Of these patients, 201 reported no change in migraine status when taking oral contraceptives, whereas 74 patients reported worsening symptoms, and 24 patients reported improvement in migraine symptoms. The comparative analysis between those who worsened and those who improved indicated that these outcomes are unpredictable. A 12-month study of a low-dose oral contraceptive (ethinyl estradiol 30 µg-desogestrel 150 µg) compared extended therapy (9 wks on, 1 wk off) with traditional therapy (3 wks on, 1 wk off). This was a randomized, multicenter study involving 300 women. The only symptom that significantly differed between the two groups was headache. In the extended-treatment group, 9.7% of women complained of increased headache symptoms compared with 17.3% in the traditional group (p<0.05). This does not measure how good it was as a treatment for migraine. Conclusions: some women will benefit from oral contraceptive therapy, whereas more women may not. However, patients who fail nonmenstrual migraine therapy and are naïve to oral contraceptives or are stable on oral contraceptive therapy may improve their menstrual migraine symptoms or reduce the number of attacks/year by starting low-dose monophasic estrogen oral contraceptive pills perhaps with an extended-duration regimen.

Danazol: Unlike the therapies described above, danazol is an androgen derivative that downregulates estrogen receptors, thereby suppressing the pituitary-ovarian axis, inhibiting ovarian steroidogenesis, and preventing the rise of both estrogen and progesterone during the luteal phase of the menstrual cycle. Averting the rise in estrogen levels is of key importance in menstrual migraines; for that reason, danazol has been evaluated as a possible treatment modality. The agent is indicated for treatment of endometriosis and cystic diseases of the breast. Only a single prospective study has addressed the efficacy of danazol in the control of "hormonal migraine." The study's investigators defined hormonal migraine as a headache occurring from 7-10 days before menstruation through the second day of menses. The study involved 131 women (aged 20-51 yrs) with hormonally related migraines that were unresponsive to standard drug therapy. Participants maintained daily diaries to verify headache occurrence, frequency, and intensity (as rated on a 4-point scale), and to document drug therapy to relieve headaches. The study consisted of four phases; each of the first three were 2 months long, and the fourth phase lasted 6 months. Phase I consisted of dietary restriction with addition of acetazolamide 125 mg/day after the first month. In phase II, danazol 200 mg twice/day was added to the treatment regimen for 25 days/month, beginning on the third day of menses. In phase III, danazol was discontinued, although diet and acetazolamide were continued. In phase IV, danazol 200 mg twice/day was restarted for 25 days/month in those who had improved while receiving danazol in phase II and whose headaches had worsened while in phase III (diet and acetazolamide alone). The first 6 months of the study were completed by 131 patients. Eighty-three patients reported a 75% decrease (which was the authors' a priori definition of treatment success) in headache index (the monthly sum of daily headaches as graded on a 1-4 severity scale). Twenty-seven patients had no improvement, and 21 patients withdrew from the study due to side effects from danazol. The percentage of women obtaining headache relief was greater among women over 40 years compared with women younger than 30 (75% vs 31.8%, p=0.0165). According to patients' reports of "helpfulness," danazol was most effective for women whose migraines occurred 1 week before menses or during menstruation. All 83 women whose migraines were improved by danazol reported a return of migraines during phase III. Sixty-seven (82.6%) reported positive outcomes (headaches relieved and no side effects) during phase IV. Fourteen patients experienced side effects, two of which were severe and included joint pain and acne. This study included women with migraines associated with ovulation and cessation of menses; that is, it was not limited to true menstrual migraineurs.

Progesterone for Migraine: Progesterone and/or its metabolites as well as synthetic progestin-only hormones can have a variable effect on migraine. There is preliminary evidence to suggest that mid-luteal elevations of progesterone and/or its metabolites could be preventative for migraine when compared to other times of the cycle. Past studies have also reported that daily oral progestins could be preventative for migraine headache in premenopausal women. Their preventative effect in premenopausal women may be secondary to induction of anovulation along with a preventative benefit of the particular progestin used. Side effects such as breakthrough bleeding and mastalgia may, however, limit their use. Injectable depot medroxyprogesterone and levonorgestrel implants, which are contraceptive agents, can trigger headache as a side effect in susceptible patients. Progestins administered episodically for 10 to 12 days each month along with estrogen replacement therapy have been reported to trigger migraine in some postmenopausal women. Therefore, progesterone and progestins can prevent or trigger migraines in different clinical situations. There are advocates for Progesterone suppositories, vaginal pessaries, and progesterone creams applied to the skin for migraine, although the level of scientific evidence for these is limited. Progesterone pessaries (Utrogestan) are available on prescription but are not subsidised (ex-manufacturor $10.61 for pack of 30). Absorption rates vary but a starting dose of 200 or 400 mg once or twice a day for suppositories (rectal= good absorption) or the same pills can be used as pessaries (vaginal = good absorption). The usual dose is from day 15 to day 25 of the menstrual cycle each month. Treatment is well tolerated; a few patients have transient fatigue and depression. A sample regimen is

200 mg twice daily for days 15 to 25

100 mg twice daily for days 26, 27

50 mg twice daily for day 28, then discontinue

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