Health Research Technical Bulletin 585-0

Migratrol TM

By Robert Thiel, Ph.D., Naturopath

This product is intended to promote a better quality of life for people who tend to get migraine headaches. Since it contains the herbs feverfew and dong quai, it is not recommended during pregnancy. It is recommended that Migratrol be included as part of a program involving avoidance of caffeine and dairy. Suggestion, 2-4 per day or as recommended by your health care professional.

Copyright 1998. Doctors’ Research, Inc. All rights reserved. It is unlawful to copy this document.

Statement of Nutritional Support (SNS)

Current and historical references suggest that substances contained within the ingredients in Migratrol can help promote a better quality of life for people who suffer from migraine headaches.

Ingredients Each tablet contains: Natural Food Complex Magnesium 280 mg (Contains 14mg of Elemental Magnesium), Borage Seeds Borago officinalis 50mg, Dong Quai Root Angelica sinensis 50mg, Natural Food Complex Niacinamide 42mg (Contains 10 mg of Niacinamide), Feverfew Leaves Tanacetum parthenium 25mg, Vacuumed-Dried Bovine Thyroid 25mg, Vacuum-Dried Bovine Adrenal 15mg, Natural Food Complex Vitamin B-2 17mg (Contains 1.7mg of Vitamin B-2), Freeze-Dried Bovine Liver 10mg, Natural Food Complex Chromium GTF 5mg (Contains 10mcg of Elemental Chromium), Vacuum-Dried Bovine Pituitary 200mcg. Also contains vegetable lubricant.

“Contains no dairy products, no USP vitamins/minerals, and no preservatives.”

Evidence to Substantiate Statements of Nutritional Support

Adrenal Glandulars
Adrenal glandulars are a natural food complex which has been used for decades by nutrition-oriented doctors when certain headaches are present. It has been recently noted that plasma norepinephrine levels have been found to be lowered in patients who suffer from cluster headaches [1]. These types have been called “adrenal headaches” [2,3] with an etiological background of “overwork, exhaustion, worry, tension, tuberculosis” [2]. If one “has chronic, severe migraines, especially migraines which are resistant to pain medicines, it is likely that adrenal dysfunction exists. This disorder is known medically as adrenal insufficiency or hypoadrenalism” [4].

Dr. Cass Igram has also written, “As for migraine, the real problem goes back to the sudden drops in blood sugar levels which may occur several times during the day. When this happens, great stress is placed on all organs, particularly the brain. The brain uses 80% of the glucose consumed by the body. A sudden migraine attack is often the end result of this stress. When a rapid decline in blood sugar occurs, the body attempts to rectify the problem by raising blood sugar levels to normal. This is where the adrenal glands normally play an important role. Healthy adrenal glands “kick in” by secreting the appropriate hormones to bring blood sugar levels back to normal. The weaker the adrenals are, the longer it takes for this mechanism to come into play. The result may be a prolonged battle with a severe migraine headache” [4]; Dr. Goodheart also reached essentially the same conclusion [5]. It should be noted that it is generally accepted that hypoadrenalism results in “increasing the frequency of hypoglycemia” as well as “hypothyroidism” [6].

Foods containing caffeine appear to be at least a trigger for migraine headaches for some people [4,7-9]. It is interesting to note that it has been reported that caffeine consumption can cause sodium depletion that can lead to hypoadrenalism [5]. Another doctor reported that low intakes of sodium salts can often cause headaches [10]. Salt craving is a common symptom of hypoadrenalism [11]. Adrenal glandular products are a natural food complex believed by their proponents to provide nutritional support for the adrenal gland [2,12-22]. Adrenal glandular containing-products have been recommended to help people suffering from various types of headaches [2,3].

Borage Seeds Borago officinalis Borage seeds are a natural food complex source of essential fatty acids. Platelet aggregation appears to be altered in migraine headaches and that platelet aggravating factor may be involved in the pathogenesis of migraine headaches [23].

Although it has been reported that reducing fat consumption while increasing consumption of carbohydrates resulted in the reduction and intensity of headaches [24], it seems that the types of fats consumed is more important than the quantity of fats. Certain fatty acids may become substrates for lipoxygenase which can help induce the formation of leukotrine B5 which has less platelet aggravating effect than leukotrine B4 which is formed from arachidonic acid [25]. It has been found that prophylactic use of foods high in gamma-linolenic and alpha-linolenic acid can, after several months, reduce the severity and frequency of migraine headaches [26]. This may be because gamma-linolenic acid competes with arachidonic acid for the active site of cyclooxygenase and it appears to reduce the production of inflammatory leukotrines [27].

Borage seed oil contains 47.2% of linoleic acid and 23.1% of gamma-linolenic acid [25]. According to Dr. Igram, “GLA (gamma-linolenic acid) is an essential fatty acid...It helps stabilize the nerves, making them less susceptible to disease and inflammation...It helps diminish PMS, thus reducing the occurrence of PMS-induced headaches. GLA should form a part of the anti-migraine nutritional regimen, especially in the case of menstruating women” [4]. Animal research suggests that borage oil seems to suppress the levels of proinflammatory eicosanoids [28,29]. One researcher has reported significant improvement for migraine sufferers with prophylactic use of 600mg or more of evening primrose oil (and other nutrients) per day (evening primrose oil contains 10% GLA [30]) [24]. A study done by Dr. Thiel utilizing essential fatty acids for people with migraine headaches suggested that they may have played a role in reducing symptom severity, frequency, and/or duration [7]. One study which linked certain migraine headaches to Candida albicans found that a daily dosage of 300mg of various fatty acids resulted in clinical improvement of 13 of 17 migraine sufferers [31].

Bovine Glandulars, General Bovine glands, such as adrenal, liver, thyroid, and pituitary have been consumed as nutritional support for decades; they have been part of the human diet for much longer [32]. Glandulars are a natural food complex which contain nutritional peptides, enzymes (when freeze or vacuumed-dried), and substances believed to be hormone precursors [18,19]. Everything about nutrition is not known [33], thus there may be other substances contained within the glandulars which have mechanisms for supporting human nutrition that are not yet understood [20]. It should be noted that many substances contained within animal tissues are the same or similar to their human counterparts [33-35], including certain enzymes [34], and even T cell gene regions [35]. Oral supplementation with bovine thymus has been shown to enhance T-lymphocyte activity, probably due to thymosin-like activity [22]. Early research indicated that ruminant source glandulars (bovine, ovine) were better for humans than simian, feline, or rodent sources [36,37].

Although it is believed by some that the oral consumption of dried glandulars is no different than consuming any other protein-containing food, this is not completely true. This incomplete belief appears to be based on the fact that since the stomach breaks down proteins into their constituent amino acids, there is no benefit from consuming foods containing specific peptides. Evidence suggests that with oral consumption of glandular extracts, a small percentage (5-10%) of their peptides are not broken down, but remain available for intact absorption in the small intestine [20,21]. A small amount of these absorbed peptides then circulate and some of them appear to provide nutritional support in performing various anabolic and catabolic processes [12-22]. Howell and others have reported that the amount of enzymes which pass through the stomach is even higher (nearly 50%) [38]. Howell has reported that many people benefit from the nutrition enzymes provide [38]. A study in the journal Surgery showed that oral pancreatic supplementation resulted in improved enzyme and growth levels for children who had a pancreaticoduodenectomy [39]. Enzymes encourage a variety of metabolic processes, including anabolic (rebuilding) reactions.

Peptides provide materials from which to rebuild. Hormone precursors provide materials which can be converted into hormones. Glandulars supply these and other substances which are believed to provide nutritional support for their human counterparts [12-22]. The thyroid, adrenal, liver, and pituitary glands all play important roles in human metabolism [40].

Dong Quai Root Angelica sinensis Dong quai has anticoagulation properties like coumadin and has been used to help regulate the menstrual cycles [41]. It is a natural food complex which contains phyto-estrogen like compounds [42], but used alone the effects appear to be quite weak [43]. However, it is reportedly “useful for all female problems” and “male migraines” [44]. The root contains about 1% angelica oil [45]. It is also considered to be a tonic [46,47]. “These [tonics] are plant remedies that either strengthen or enliven a specific organ or the whole body. They are truly Nature’s gifts to a suffering humanity” [48]. Dong quai root “tones the blood and invigorates the circulatory system” [47].

Feverfew Leaves Tanacetum parthenium Schulz-Bip. synonymous with Chrysanthemum p., Leucanthemum p. and Pyrethrum p. Feverfew leaves are a commonly used natural food complex by people with migraine headaches, especially prophylactically [49-51]. Feverfew natural food complex which is rich in sesquiterpene lactones, the principal one being parthenolide [51]. Parthenolides inhibit phospholipase A2, have antiplatelet activity, and have anti-white cell activity [50]. Feverfew may be able to prevent the release of arachoidonic acid and inhibit in vitro aggregation of platelets stimulated by ADP or thrombin [50]. Serotonin may be involved in migraine headaches [52]. Feverfew has been shown to inhibit serotonin release from platelets and polymorphonuclear leukocyte granules, so much so that “Feverfew may produce an antimigraine effect in a manner similar to methysergide maleate” [50] (Methysergide maleate, Sansert is a known serotonin antagonist [52]). Parthenolide does not appear to be the sole pharmacologically active constituent; there appear to be other similar soluble substances which are similar to parthenolide (canin, secotanapartholide A, artecanin, and 3-beta-hydroxyparthenolide) which may also be involved [50,53]. These other sesquiterpenes have been shown to possess spasmolytic activity through an inhibition of the influx of extracellular calcium into vascular smooth muscle cells [50]. Feverfew’s natural food complex also contains several flavonoid glycosides, the main ones being luteolin and apigenin [50,51]. Canada’s Health Protection branch recommends 125mg of feverfew leaf per day for the prevention of migraines [51]. Some naturopathic doctors recommend 25mg of feverfew twice daily as a preventative measure [8]. One study involving 270 subjects, found that 70% reported that feverfew reduced the frequency and/or intensity of their attacks [8].

Liver Glandulars Nutritionally-oriented practitioners sometimes find that the liver can cause some headaches and recommend glandulars containing liver [2,3,17]. Liver contains IgA; people with allergies have low IgA; people with low IgA tend to get Candidiasis [4]. Allergies [4,7-10], as well as Candidiasis [31], can contribute to migraine headaches. “The evidence is clear: migraine headaches and food allergies are inseparable”[4]; “The more overloaded the liver is with infection or inflammation, the less capable it is of preventing food antigens from gaining entry into the bloodstream. Liver diseases of all types make an individual more vulnerable to allergy, and therefore, migraine” [4]. Other liver functions, such as its involvement in blood sugar regulation, may influence the frequency, intensity, or duration of migraines. “As for migraine, the real problem goes back to the sudden drops in blood sugar levels which may occur several times during the day. When this happens, great stress is placed on all organs, particularly the brain. The brain uses 80% of the glucose consumed by the body. A sudden migraine attack is often the end result of this stress. When a rapid decline in blood sugar occurs, the body attempts to rectify the problem by raising blood sugar levels to normal” [4]. This is where the liver may play an important role in migraines. The liver is the chemical factory of the body. It is involved in blood sugar regulation, conversion of T4 to T3, and a variety of enzymes [40]; problems in any of those areas can contribute to migraines [4]. Liver glandulars are naturally rich in IgA [4]. Liver glandular products are a natural food complex believed by their proponents to provide nutritional support for the liver [12-22].

Natural Food Complex Chromium Natural Food Complex chromium is the result of Saccharomyces cerevisiae (baker’s yeast) fed high amounts of chromium. It contains .2% chromium by weight; chromium is considered to be the probable active ingredient. Inorganic chromium “is very difficult to absorb”, but organically-bound chromium “is more easily absorbed” [4,54]. This may be because, “Chromium always appears in foods as part of a complex, usually with nicotinic acid” (niacinamide) [55]. “Chromium is generally accepted as an essential nutrient that potentiates insulin action...Moreover, inadequate chromium intake probably is of special concern to people exposed to stressors such as diets high in simple sugars, physical trauma, and infection, which apparently enhance the need for chromium” [54]. “Chromium may help reduce the length and severity of a migraine, especially if the migraine is due to hypoglycemia and/or emotional stress” [4]. It may be that the body sometimes produces vascular constriction to reduce the flow of blood which contains too much glucose (which occurs in hypoglycemics and diabetics) when insulin action is inadequate to reduce it after high glycemic foods/meals are consumed; vascular constriction in the forms of arteriosclerosis and thickening of basal lamina (often associated with hypothyroidism) are often present in diabetics as is pain in the cranial and other nerves [56]. Dr. Cass believes it takes up to six months of supplementation with chromium to replenish the levels the nervous systems of migraine sufferers have depleted [4]. A double-blind trial showed that chromium can play a role in reducing the frequency and intensity of chronic headaches [57]. Natural Food Complex chromium appears to reduce serum glucose much more than inorganic chromium (16.8% reduction vs. 6.0% reduction) [58] and thus may be more effective in this application.

Natural Food Complex Magnesium Natural Food Complex magnesium is the result of Saccharomyces cerevisiae fed high amounts of magnesium. It contains 5% magnesium by weight; magnesium is considered to be the probable active ingredient. Magnesium is reduced in the blood, saliva, cerebral spinal fluid, and brain when migraine headaches are present [59-63]. Interestingly, one study found that one of the leading symptoms in certain hypomagnesemic children was recurring headaches [64]. “Magnesium is known as ‘the tranquilizing mineral’ due to its effect on reducing irritability of the nerve cells” [65]. Magnesium is needed by the pituitary gland and a deficiency can result in adrenal and thyroid problems due to how they are affected by the pituitary gland [65]. Reduced brain concentrations of magnesium can result in migraine headaches; reduced amounts of magnesium in mononuclear blood cells has been found in patients while experiencing migraines or auras associated with their occurrence [59]. It has been speculated that migraines may respond to magnesium because decreases in serum ionized magnesium appear to 1) increase the affinity for serotonin cerebral muscle receptors, 2) potentate cerebral vasoconstriction induced by serotonin, and 3) facilitate tryptophan release from neuronal storage sites [60]. A similar theory is that since magnesium is required for normal neuron and cellular function, it probably plays a role in modulating serotonin levels to a point that it helps relieve pain in migraine sufferers [66]. Another theory is that 1) low magnesium levels increase sensitivity of NMDA receptors (of which magnesium has a gating function), 2) this hyperexcitabilty may increase the susceptibility of the cerebral cortex to spontaneous depolarization and depression, and 3) this depression spreads due to low magnesium concentrations and may cause the migraine or the migraine aura [61].

Many others have found that magnesium can reduce the frequency and duration of migraine headaches [4,29,66-69]. A study involving 600mg of magnesium per day found that migraine frequency reduced by 41.6% [67]. A study involving intravenous application of magnesium found a 50% pain reduction within 15 minutes in 35 of 40 patients (lasting for 24 hours for most) [68]. Magnesium has been found to be helpful for headaches associated with PMS [70]. “Recent studies done by doctors at the University of Tennessee showed that supplemental magnesium in a dose of 200 milligrams per day brought significant relief, particularly in women. Some 80% of the women tested found their migraines to be completely gone shortly after beginning the supplements. Magnesium was so effective that it was used to stop migraines once they occurred. Many of the subjects discovered that if they took magnesium within half an hour of the migraine onset, the symptoms would abate entirely”[4]. Supplemental magnesium has also been found to be helpful when PMS triggers migraine headaches [70]. One small double-blind study involving 1000mg of magnesium found it to have no favorable effect for migraine sufferers [71]; side effects noted included increased diarrhea [71]. Magnesium deficiencies are difficult to assess, but up to 3/4 of Americans may suffer from them [69]. It has been claimed that “Magnesium is difficult to absorb” [4]. A better way to state that is magnesium is not consistently well absorbed. “Absorptive studies have been conducted in which the amounts of magnesium ingested have varied from very small to very large amounts utilizing the same healthy subjects” [72]. A human excretion study indicates that Natural Food Complex magnesium is utilized 1.45 times more than magnesium amino acid chelate, 1.83 times more than magnesium oxide, and 2.08 times more than magnesium glycinate [73].

Natural Food Complex Vitamin B-2 Natural Food Complex vitamin B-2 is the result of a Saccharomyces cerevisiae extract nutrient activated with high amounts of riboflavin. It contains 10% vitamin B-2 by weight; vitamin B-2 is considered to be the probable active ingredient. Suboptimal consumption of riboflavin appears to be common. One study found that 77% of healthy individuals had subclinical deficiencies of riboflavin [74]. Another study found that consuming a daily single high dose (400mg per day) of riboflavin (vitamin B2) improved average headache scores for migraine sufferers by about two-thirds, which was the same as aspirin [75]. It may not be necessary to use this much vitamin B-2/riboflavin. The capacity of the human gastrointestinal tract to absorb orally administered riboflavin may be less than 20mg in a single dose” [76], thus using high quantities may be unnecessary. When riboflavin was used in Dr. Thiel’s study lower dosages were used (1mg-300mg) [7]. This investigator believes that vitamin B-2 tends to be indicated for certain people who wake up with headaches [7]. An animal study suggested that Natural Food Complex vitamin B-2 is absorbed 1.49 times more than USP riboflavin and retained in the liver 1.92 times more than USP riboflavin [77].

Natural Food Complex Niacinamide Natural Food Complex niacinamide (also known as vitamin B-3) is the result of a Saccharomyces cerevisiae extract nutrient activated with high amounts of nicotinamide. It contains 25% vitamin B-3 by weight; vitamin B-3 is considered to be the probable active ingredient. Nicotinamide is a vasodilator [78]. Nutrition-oriented practitioners have used vitamin B-3 to help people with migraines [4,8,17]. Tryptophan reportedly can “cure” some migraine headaches [4]. Vitamin B-3 consumption can help keep tryptophan from being converted into niacin when low niacin intakes are encountered [79]. Depressed individuals tend to have less l-tryptophan availability than non-depressed individuals [80]; supplementation with tryptophan has been found to reduce depression in some women [81]. An animal study suggested that Natural Food Complex niacinamide is absorbed 3.94 times more than USP niacinamide and retained in the liver 1.7 times more than USP niacinamide [82].

Pituitary Glandulars The pituitary is a master endocrine gland that exerts control on most other endocrine glands including the thyroid and adrenal glands [40,83]. It also plays a role in blood sugar regulation [40,83]. Research strongly suggests that the pituitary gland is associated with headaches of many types [1,4,84,85]. “Often, with migraine patients, doctors view x-rays for evidence of swollen pituitary glands which can easily be defined in this restricted region. As stated in Harrison’s Textbook of Internal Medicine, ‘Enlargement...is frequently encountered in routine skull [x-rays] obtained in patients complaining of headaches...’ The swelling places pressure on the nerves in the cranium and this causes pain” [4]. “In untreated or inadequately treated myxedema caused by primary disease of the thyroid, hypertrophy and hyperplasia of the thyrotrophs lead to an enlargement of the pituitary” [86]; conversely hypopituitarism can cause noncongenital hypothyroidism [87]. Doctors have long used pituitary glandulars for headaches [88]. More recent research has shown that the pituitary can be involved in migraine [4,84] and cluster headaches [1,85]. They are probably due to an imbalance of hormones [1]. Pituitary glandular products are a natural food complex believed by their proponents to provide nutritional support for the pituitary gland [12-22].

Thyroid Glandulars Low thyroid function appears to play a role in migraine headaches [4,7,17], but “The precise reason the thyroid is so involved in migraine is unknown” [4]. “The thyroid gland exerts significant control over the circulatory system, and this is one reason disorders of the thyroid gland are related to migraine”...Poor circulation with resultant reduced blood supply to the brain increases the risk for migraines [4]. Interestingly, both migraine headaches and thyroid problems are much more common in women than in men [83,89]. The thyroid produces hormones which speed metabolism (such as thyroxine) and affect concentrations of calcium (calcitonin) [83,89]. Thyroid problems, clinical and/or subclinical, are exceptionally common [4,90-93]. The fact that between 10-48% of senior citizens are suspected of having subclinical hypothyroidism [91,92] and 11% of the population appears to have a clinical thyroid condition [93], suggests to this investigator that thyroid problems in migraine sufferers are often missed, even when they have been medically tested for. In other words, since thyroid blood tests do not always reveal that thyroid may be involved, actual symptoms can be much more significant factors in determining whether a nutritional intervention may be effective; other doctors have reached similar conclusions [4,93]. One doctor reported that low intakes of sodium salts can often cause headaches [10]; it may be because most commerical sodium salts consumed contain iodine which is used by the body to make thyroid hormones [94].

Caffeine is believed to help some with migraine headaches [55,95]. Others cite foods containing it as at least a trigger for migraine headaches [4,7-10]. Withdrawal reactions occur in 25-100% of coffee consumers and includes severe headaches, depressed mood, anxiety, and fatigue [96]. Caffeine withdrawal headache symptoms usually occur between 13 to 23 hours of discontinuing caffeine and occur most frequently with heavy consumers of caffeine [97]. Just like thyroxine [82,89], caffeine increases the metabolic rate [98]. This investigator speculates that people who need nutritional thyroid support will often use caffeine in an attempt to compensate for the positive feeling of increased metabolism caffeine can provide. Unfortunately, caffeine does not actually nutritionally-support the thyroid gland. Cold extremities, depression, and menstrual disturbances which can be a symptom of low thyroid function [82] are also associated with migraines [85,95].

Oral contraceptives (birth control pills) can trigger and even be the cause of migraine headaches [4,17]. This investigator believes this is because they raise estrogen levels to the point they negatively affect estrogen-thyroid hormone balance (these hormones seem to work together in a manner which affects behavior [99]) and that this subsequent imbalance ultimately results in migraine headaches. “In untreated or inadequately treated myxedema caused by primary disease of the thyroid, hypertrophy and hyperplasia of the thyrotrophs lead to an enlargement of the pituitary” [86]; conversely hypopituitarism can cause noncongenital hypothyroidism [87]. Headache expert, Dr. Cass Ingram (D.O.), has written that synthetic approaches to thyroid problems (such as Synthyroid), have little, if any, effect on headaches; he prefers natural glandulars “Standardized raw (all-natural) thyroid extract is more effective in blocking and/or preventing headaches. This extract is made from the thyroid glands of animals” [4]. Other doctors have historically preferred natural food complex thyroid glandulars over the synthetic counterparts [12,100].

Natural food complex thyroid glandulars contain peptides, enzymes, and hormone precursors which are believed by some to help the thyroid gland nutritionally [12-22]. “Thus a patient given thyroid concentrate will manifest improvement in thyroid panels and other tests that demonstrate thyroid activity. Apparently the body is able to ‘recognize’ the specific ‘blueprints’ (nucleoproteins including DNA and RNA coding), protein configuration and other aspects of the specific gland or organ, and receptors of the target gland (i.e. thyroid) pick up the substances from the circulation” [12]. Thyroid glandulars have been used by migraine headache sufferers since at least the 1930s [88]. Dr. D.A. Versendaal (D.C.) recommends thyroid glandular supplements for people with migraine headaches [17].

Evidence to Substantiate Safety

Borage Seeds Borago officinalis Borage seeds are a food. According to the American Herbal Products Association, the seed oil is in safety class 1: “Herbs which can be safely consumed when used appropriately” [101]. They also report, “The seeds themselves contain only a small amount of the saturated (non-toxic) pyrrolizidine alkaloid, thesinine” [101]. Borage leaves may have toxic properties, but the seeds and the seed oil do not [101].

Bovine Glandulars Animal glands have been consumed since the beginning of history [32]. “Glandular products have been produced and used in the U.S. for over 60 years with absolutely no reports of microbial contamination or resultant illness” [12]. They are consumed in many countries, including the U.S. as food [12,32]; they may even contain substances to reverse diseases associated with Western diets [32]. “Since hormones are not part of the substance, overdosing is not a concern. Even when excess amounts have been ingested, the body can easily deaminize them” [12]. A search of the literature found one report (in a letter to the editor) outside the U.S. of a single, temporary complaint (it raised thyroid hormones levels which normalized when consumption was discontinued), from using a thyroid glandular product combined with lithium, but the daily consumption (45 tablets) was in excess of any reasonable consumption (daily quantity of thyroid hormones present: 0.5 T4 and .09mg of T3) [102]. Glandular suppliers provide products which are not contaminated with Bovine Spongiform Encephalopathy (BSE) and have been collected under USDA inspection [i.e.103]. The USDA has announced that no BSE has ever been detected in cattle in the U.S. [104]. No long-term, negative, side effects from taking glandular supplements is known [12].

Dong Quai Root Angelica sinensis Angelica has been used for centuries [105]. Canadian authorities do not recommend dong quai (a product ingredient) for pregnant women unless recommended by a qualified health care professional [101]; U.S. authorities have not felt that any restrictions are necessary. Nor have the Chinese who apparently have used it for centuries [101]. According to the American Herbal Products Association, it is in safety class 2b: “Not to be used during pregnancy” [101].

Feverfew Leaves Tanacetum parthenium “It is interesting to note that it (toxic mechanism) is not present in the commercially derived leaves” (of feverfew) [106]. According to the American Herbal Products Association, the seed oil is in safety class 2b: “Not to be used during pregnancy” [101]. “Occasional side effects, such as mouth ulceration or gastric disturbance have been observed in 6-15% of users, usually in the first week of use...There are no known adverse effects in long-term consumption” [101].

Natural Food Complex Chromium “Chromium toxicity through oral ingestion, however, is not a practical concern...Trivalent chromium only becomes toxic at extremely high amounts” [54]. An animal toxicity study concluded that natural food complex chromium was “virtually non-toxic” whereas inorganic chromium was found to be “highly toxic” [107]. Generally speaking, GTF chromium and other trivalent forms appear to be safe [54], whereas hexavalent forms have higher potential for toxicity (Natural Food Complex chromium is in the GTF form). The amount of elemental chromium in each supplement is 10mcg; the total in 8 tablets (twice the maximum recommended daily consumption) is 80mcg. The upper limit on the estimated safe and adequate daily amount for Americans is 200mcg, with many consuming less than 40mcg from dietary sources [54].

Natural Food Complex Magnesium “The normal kidney is capable of excreting large amounts of absorbed or injected magnesium ion so rapidly that serum levels usually do not rise to dangerous levels” [72]. The RDA for magnesium in adult females is 280mg; adult males 350mg. The amount of elemental magnesium in each supplement is 12mg; the total in 8 tablets (twice the maximum recommended daily consumption) is 96mg. Since the average American consumes 208mg of magnesium per day [72], the additional amount associated with consuming Migratrol is not only safe, it may help prevent some problems associated with magnesium deficiencies.

Natural Food Complex Vitamin B-2 “Toxicity from ingestion of excess riboflavin by experimental animals or humans is doubtful. The capacity of the human gastrointestinal tract to absorb orally administered riboflavin may be less than 20mg in a single dose” [76]. Single high doses of riboflavin in the amount of 400mg per day was found to be effective in reducing migraine headaches and did not have any side effects [75]. The amount of riboflavin in each supplement is 1.7mg; the total in 8 tablets (twice the maximum recommended daily consumption) is 13.5mg. There is no known danger consuming the amount of riboflavin people who take Migratrol are likely to take [76]. Natural Food Complex Niacinamide Although high amounts (1-3gm per day) of niacin can having temporary side effects, such as flushing [78,79], “niacinamide does not have a similar effect” [79]. The amount of niacinamide in each supplement is 10mg; the total in 8 tablets (twice the maximum recommended daily consumption) is 80mg. Lethal levels in rats using nicotinamide were found in the daily amount of 3.5g per kilogram (or the equivalent of 192.5gm for 121lb human) [79]. Even if niacinamide was dangerous at these levels (which it has not proven to be), this would require a person to consume 19,250 Migratrol per day to get to this concentration.

Saccharomyces Cerevisiae Saccharomyces cerevisiae, otherwise known as “baker’s yeast”, has been consumed in foods by humans for 1,000s of years. It has been consumed in food supplement form (such as in Migratrol) for approximately 30 years. One foreign study involving patients with Crohn’s disease taking 8,500mg of Saccharomyces cerevisiae per day speculated that some of the participants may have had a hypersensitivity reaction to it [108]. Each Migratrol contains approximately 300mg of enzymatically processed Saccharomyces cerevisiae; 8 per day (twice the maximum recommended amount) contains approximately 2,400mg (less than the amount used in the study). Also, the form in Migratrol has been enzymatically processed in such a manner (this process inactivates any yeast) that this reaction would appear to be less likely.

According to the PDR, Saccharomyces cerevisiae “is antibacterial and stimulates phagocytosis” is used for the common cold, cough/bronchitis, dyspeptic complaints, eczema, furuncles, acne, fevers, inflammation of the mouth and pharnyx, loss of appetite, and tendency to infection [109]. “The average daily dosage is 6gm” and “health risks or side effects following the proper administration and dosage are not recorded”, although “the simulataneous use intake of monoamine oxidase inhibitors can cause an increase in blood pressure” [109]. All of the enzymatically processed Saccharomyces cerevisiae in Migratrol is free of flavors, colors, dyes, binders, lubricants, fillers, preservatives, pesticides, insecticides, and time releasing agents (this has been authenticated by gas chromatography (GC)) [110]. Studies show nutritional benefits from intake and/or absorption of the vitamins and minerals (to be found in Migratrol) complexed in Saccharomyces cerevisiae [i.e. 58,73,83,77].

Risk/Benefit

Since migraine attacks are often frequent, some traditional health professionals believe that they require management with prophylactic agents to reduce their occurrence [4,95,111]. While this researcher concurs with this belief in many cases, is it necessary that these agents be synthetic? Although there is no doubt that some medical intervention can be helpful, there is no medical cure for migraine headaches [95]. This investigator is concerned that some migraine medications (such as Cafergot and several types of Excedrin) contain caffeine [95].

This investigator is also concerned that most of the other medicines used to treat headaches (migraines or otherwise) have potentially serious side effects: “Daily or nearly daily use of symptomatic medications, whether over-the-counter (OTC) or prescription are not recommended in the long-term management of patients with migraine headaches for the following reasons:
1. Chronic long-term use of acetaminophen or non-steriodal anti-inflammatory drugs (NSAIDS) has been associated with liver and/or kidney disease.
2. Chronic long-term use of analgesic products has been associated with analgesic nephropathy.
3. Chronic long-term use of caffeine, opiates (including propoxphene, butorphanol, codeine, meperidine), butalbital, ergotamine tartrate can lead to habituation or overuse.
4. Chronic long-term use of caffeine, opiates, butabital, and ergotamine tartrate can be associated with the establishement of a pharmacologically maintained pattern of pain referred to as rebound headache.
5. Chronic long-term use of abortive therapies may suggest the need for prophylaxis. Eliminating drugs that are causing analgesic rebound heachace may reduce the need for prophylactic medication in some individuals.” [95]

Since migraine headaches are a long-term problem and long-term use of the medications used to manage them is potentially dangerous [95], it seems reasonable that other interventions should be considered (at least as an adjunct). Prophylactic use of natural substances such as magnesium [4,7,66-68], vitamin B-2 [7,75], fatty acids [4,7,56], glandulars [4,7,11], and herbs [4,7,29] has been shown to be effective to reduce the severity of and frequency of migraine headaches. Natural interventions administered by properly trained professionals tend to have fewer negative consequences (pregnancy and other cautions, including allergies, though do apply) than the synthetic counterparts offered by some practitioners. They also appear to be cheaper than the prescriptions ordinarily used to treat migraines [112]. Food and nutritional problems do contribute to causing migraine headaches [4,7-9,11,29,56,58-64]. Migraines have negative effects on those that suffer from them [95] and on those associated with migraine sufferers (such as loved ones and employers) [95]. This researcher encourages doctors and health researchers to be willing to challenge long-standing misconceptions regarding migraines and to work toward cooperative interventions to help these people improve and lead as normal lives as possible. Migratrol represents a step in that direction.

REFERENCES

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