MIGRA-LIEVE　（TM）

BACKGROUD　AND　EDUCATIONAL　DATA

著者等の説明：省略

これより本文
この出版物について
このCondition-Specific　Monographのなかで述べられている知識や情報は専門家教育向けであり、今までに出版された研究、論文、書物から採られている。この最新の情報は疾病の診断と治療において有資格の健康管理専門家が行う管理や処置にとって替わるものとなるように意図されたものではない。

片頭痛への自然医学の臨床応用
片頭痛は5000年以上に亘ってよく知られた医学上の問題であり、頭部の痛みのなかで最もよく研究されているもののなかのひとつである。大規模な研究によると合衆国では女性の１８％、男性の６％が片頭痛を病んでいるという。12歳以上の1800万人の女性と、560万人の男性がこの病気ということになる。The　Center　for　Disease　Controlによれば、片頭痛は1981年から1989年にかけて60％増加した。片頭痛のもたらす経済的打撃はとんでもないもので、年間コストは180億ドルにも達する。

片頭痛の原因
片頭痛の基礎原因はまだ分かっていない。遺伝がある程度関係しており、片頭痛患者の50－70％が家族発生であるが、患者の親族にはっきりした生化学的もしくは生理学的特徴は認められない。

身体的機能的問題
何が片頭痛を起こさしめるのか、片頭痛が起こっているとき何がわれわれに起こっているのかについて、いくつかの理論が提唱されている。これらの理論のうちのあるものは、脳のいくつかの動脈が収縮して脳の視中枢の血流を減少させるということを言っている。この血流の低下は片頭痛のときに随伴する視覚異常やその他の症状を生ぜしめるという。

この理論は更にこれらの症状に引き続いて起こる痛みは頸動脈の拡張と動脈壁内の神経への圧迫の結果であるということを示唆している。しかし別の理論は、脳内の神経細胞が機能を失いそれが血流量を減らし,それがマグネシウム濃度を減らし、それが順に神経細胞の機能を低下させ、そしてこの機能不全が波打ちながらすべての関連領域に広がっていく。多くの研究者は重要な脳の化学物質であるセロトニンが片頭痛を増悪させるかも知れないと感じている。血液の成分である血小板は血液内に正常に存在する一連のセロトニンすべてを有しており、血小板が凝集するとセロトニンが放出され、血管を収縮させる。

徴候と症状
最も重要なふたつのカテゴリーは前兆のない片頭痛（普通型片頭痛）と前兆のある片頭痛（典型的片頭痛）である。前兆のない片頭痛は患者が特異的な基準を満たすかどうかによって診断される。患者は4－72時間続く同じような症状を過去に５回経験していなくてはならない。また次の特徴的な症状のうち２つを有していなければならない。（１）１側の頭痛、（２）痛みは拍動性もしくは鼓動性、（３）働けないほどひどい痛みを経験したことがある、（４）痛みは日常の労作で悪化する。更に,次の症状のうち１つを持っていなければならない。（１）嘔気・嘔吐（２）光や音で症状悪化。対照的に、前兆ありの片頭痛は以下の例外を除いて通常型の片頭痛の診断基準と同じである。患者は過去に２回同様の症状を経験していれば良く、また以下の４つの基準のうち３つを満たしていなくてはならない。（１）１回以上前兆を経験していること、（２）前兆症状は４分以上かけて完成すること、（３）前兆は６０秒以内に治まること、（４）頭痛は前兆が治まって６０分以内に始まること。前兆は幾つかの視覚異常の形をとり、暗いもしくは黒い点が視野に出現し,場合によってはそれが視野いっぱいに拡大し、見えなくなることもある。黒い点はジグザグの線状に光に取り囲まれることもある。典型的片頭痛の患者には、一方の手、腕、顔に脳卒中様の症状が表われるかもしれない。片頭痛の患者は、幾つかの特徴的な頭痛を体験することが多く、その中には、労作によって引き起こされる強い拍動性の頭痛（労作性頭痛）；穿刺頭痛と呼ばれるアイスピック様痛みもしくは電撃痛；そして片側性の激烈な眼球痛がある。

治療
片頭痛の患者に対しては、薬理学的ならびに非薬理学的を問わず多彩な治療法がある。しかし、実際的な理由で、２つのカテゴリーに分けられる。抑制的と予防的である。片頭痛の抑制的治療というのは、薬を用いて単に症状を処理しようというものである。軽い片頭痛に対する最初の治療には通常アスピリンか他の非ステロイド性抗炎症薬（例えば、イブプロフェンやナプロキサン）が用いられる。これらの痛みの緩和薬を飲んで、吐き気止めを用い、頭に氷のパックを乗せ、静かな暗い部屋で睡眠をとれば良い。

動脈を収縮させるある種の薬はある程度の効果と副作用をもたらす。あなたの薬局はあなたの相談に乗ってくれるでしょう。この種の薬のいくつかは良く効くが、往々にしてリバウンド頭痛や他の副作用をもたらす。

他の薬、例えばスマトリプタン（Imitrex）は中程度以上の片頭痛の痛みの強さを軽くすることが分かっている。この形式の薬の副作用にはちくちく、重さ、圧迫感などがある。抑制的治療とは対照的に、予防的薬剤による治療計画は、片頭痛の発作の頻度が高い場合にたてられる。プロプラノロールは片頭痛の予防治療のために合衆国ではよく処方される。片頭痛の予防には効果的であることが分かっているけれども、その副作用には易疲労性、うつ状態、精力減退、不眠、めまい、四肢の冷感などがある。drug　interventionのように薬を用いない予防的治療も有効であることがある。これらには、ストレスマネージメント、バイオフィードバック、エクササイズ、鍼、トリガーポイントへの注射、多くの理学療法（すなわち、マッサージ、マニピュレーション、経皮的神経刺激）がある。

医用植物に関して考慮すべき事柄

なつしろぎく
なつしろぎく（Tanacetum　parthenium）はひなぎく（Asteraceae）の一種で、背の低い、藪状に茂る多年草で、野原や道端に生育する。その黄緑色の葉と黄色の花はカミツレのそれに似ており、ときどき間違われる。

花は7月から10月に咲く。葉は医学用に供せられる。なつしろぎくの名はラテン語から来ている。"熱を追っ払う"の意である。ギリシア文学のなかでは生理時の痙攣や炎症や腫れの治療薬として述べられている。なつしろぎくはイギリスの薬草医により発熱や関節炎の治療のときに鎮痛剤として広く用いられたが、いつのまにか消えてしまった。

なつしろぎくはカナダ政府とイギリス政府によって片頭痛に有効だと認められたために、過去2世紀に亘って、再び盛んに使用された。

活性成分：最も重要な成分はparthenolideである。1960年に初めて同定されたのであるが、parthenolideはなつしろぎくの抗片頭痛作用のもととなっている葉っぱに含まれる。市販されているなつしろぎく製品でもっとも注意しなくてはいけないことは、含まれるparthenoideの量に大きなばらつきがみられることである。カナダでのなつしろぎく製品のある分析では約半数で事実上この物質が含まれていないに等しいことがあきらかになった。最低基準として、カナダ厚生省のHealth　Protection　Branchではなつしろぎく製品は少なくとも0.2%のparthenolideを含んでいなくてはならないとしている。

健康管理の職にある者はparthenolideはとても不安定であることをよく認識し、この問題に対処済みのなつしろぎく製品を手に入れようとしなければならない。parthenolideの含有量がはっきりしているなつしろぎく製品は数少ないが、あなたが相談した薬剤師はその中の一つを知っていたのだ。。

作用機序：なつしろぎく、とくにparthenolideは血小板の凝集を抑制し、（覚えているかもしれませんが、血小板の凝集はセロトニンを放出して、片頭痛を更にひどくする）、またヒスタミンの放出も抑制する。また、血小板からのセロトニンの放出も抑えることが、示されてきた。これにより片頭痛の痛みの強度、持続時間、そして頻度を減らし、血管の緊張度を改善させると信じられている。

臨床応用：なつしろぎくを用いた臨床研究は、主として片頭痛の治療と予防に関して行なわれており、最初の研究は英国で行なわれた。一連の研究でなつしろぎくは片頭痛の長期管理に有用であることが示された。

最初の研究は数年にわたりなつしろぎくを服用している片頭痛の患者を対象に行なわれた。症例は17例でなつしろぎく（1日あたり50mg）かプラセボのどちらかが与えられた。8例はそのままなつしろぎくを服用し続け、6ヵ月以上にわたって、片頭痛の持続的緩解を経験した。プラセボを与えられた9例は片頭痛がほとんど三倍近くに増悪した。頭痛の多くは耐えられないもので、不安、不眠、そして筋肉と関節の痛みが生じたと報告された。この報告により、なつしろぎくを急にやめるとどうなるか、多くの興味をひいた。2番目の研究は72例の片頭痛患者を対象にしたものである。彼らは1日82mgのなつしろぎくかプラセボを投与された。

なつしろぎくを用いた4ヵ月間の治療で片頭痛の頻度と痛みの強さがが軽減した。なつしろぎくはまた、片頭痛の発作時の嘔吐と視覚障害を軽減させた。副作用は軽微（主として軽い消化器症状とイライラ）で治療を中止するほどではなかった。

推奨用量：片頭痛を予防するためのなつしろぎくの適切な量はparthenolideの含有量に基いて決められている。カナダのHealth　Protection　Branchはなつしろぎくに薬剤認識番号（DIN）を与えた。片頭痛の予防には最低0.2%のparthenolideを含有する本当のなつしろぎく（Tanacetum　parthenium）からとられた乾燥なつしろぎくの葉を1日125mgとることを薦めている。これはparthenolideに換算すると１日最低250mcgということになる。これは効力を発揮する最低量と思われる。未発表の研究の結果では0.7%のparthenolideを含むなつしろぎくの抽出物を1日100mgとるのがよいということである。（ラベルにどういうことが書いてあったとしてもなつしろぎく抽出物の半数以上はわずかもしくは全くparthenolideを含有していないということを覚えておいてください。あなたの薬剤士はこの問題を回避できるよう助言してくれるでしょう。少なくとも4－6週の連続服用が推奨されている。

副作用／禁忌：上記の臨床研究で挙げられていた副作用に加えて、なつしろぎくで最もよくみられる副作用は口腔内の潰瘍である。これは主として、良質な標準化された抽出物ではなく葉っぱそのものを噛む患者にみられる。皮膚炎の報告も散見される。今のところ、長期毒性については調べられていない。なつしろぎくは妊娠中もしくは授乳中の女性には禁忌であり、２才以下の子供には使用すべきではない。

他の薬草に関して考慮すべき事柄

生姜
生姜（Zingiber　officinale）は血小板の凝集を阻止する成分を含有している。これらの作用のすべてが生姜が片頭痛に有用であるということを示しているが、コントロール臨床試験は行われていない。Journal　of　Ethnopharmacologyに４２才の片頭痛の女性患者が４日間４時間ごとに500‐600mgの生姜の粉末と水を混ぜたものを摂り、緩解を得たと発表された。患者は視覚的前兆が始まると生姜を摂り始めるよう言われていた。著者らは生姜を摂り始めて30分以内に軽快し始めたと報告している。また生姜を継続して用いたその女性は片頭痛の頻度も痛みの程度も軽減したと言っている。

イチョウ（ginkgo　biloba）の抽出物
イチョウの抽出物（GBE）はフランスの2つの小規模な臨床試験で、片頭痛の管理にある程度有効であることが示された。１日量は120‐240mgである。GBEを片頭痛に使うにはもっと多くの治験が必要である。

栄養補助食品に関して考慮すべき事柄

マグネシウム
片頭痛を誘発することが分かっているいくつかの要素（すなわち、ストレス、妊娠、生理、飲酒、ある種の利尿剤）はマグネシウムを涸渇させる。さらに、マグネシウムは片頭痛の予防や治療に有用とされる薬品の作用の多くを持っている。これらの作用とは（１）スパスムの阻止、（２）血小板凝集の阻止、（３）細胞膜の安定化、（４）炎症物質の合成、放出、ならびに作動の阻害、そして（５）脳血管緊張の改善である。さらに、片頭痛患者の発作中の脳内マグネシウム濃度は健常人のそれより19%低い。これらの所見はマグネシウムが片頭痛の予防や治療に関係していることを示唆している。臨床治験はこの可能性を支持している。オープントライアルで普通型もしくは典型的片頭痛の患者3000人以上がマグネシウム（通常1日200mg）を摂取した。患者のほとんどすべてが女性でまたほとんどが出産可能年齢であった。有効率は30%と報告されたが、有効とする基準はあきらかにされていない。

CONDITION-SPECIFIC　MONOGRAPH　SERIES

片頭痛
非コントロールスタディに引き続き、月経前片頭痛の患者20人が1日360mgのマグネシウムかプラセボを投与されるという二重盲験治験が行なわれた。治療は2ヵ月間続けられ、月経周期の15日目に開始され、月経まで続けられた。治療期の終わりには"Pain　Total　Index"（これにより片頭痛の持続時間と痛みの強さを測定する）がプラセボ群よりマグネシウム群が有意に低かった。頭痛の起こった日数はマグネシウムを投与された患者で有意に減っていたが、プラセボを投与された患者ではそうではなかった。治療の開始前は、片頭痛の患者では白血球（WBC）のマグネシウム濃度が健康人より低かった。

マグネシウムで治療すると、WBCのマグネシウム濃度は有意に上昇する。このデータはマグネシウムの欠乏が月経前片頭痛の機能不全に関係していることを示唆している。別の二重盲験治験では、18歳から65歳の片頭痛（平均月に3.6回の発作）の患者81人がアトランダムにマグネシウム（毎朝600mg）かプラセボを12週間にわたって投与されるよう割り振られた。マグネシウム群での発作の頻度はプラセボ群に比べて有意に減少（41.6%vs15.8%、p<0.05）した。発作の持続時間と痛みの強さもプラセボ群に比べて減少傾向をみせたが、統計学的に有意とはいえなかった。マグネシウムを投与された患者の18.6%に下痢が、4.7%に胃部不快感がおこった。ある報告では片頭痛の予防にマグネシウムが有益な作用をもつことを見出せなかった。その研究では、片頭痛の患者69人がマグネシウム（242mgを1日2回）かプラセボかを12週間投与されるようアトランダムに2重盲験で割り振られた。治療に対する反応はInternational　Headache　Societyの基準（片頭痛の持続時間か痛みの強さのどちらかで少なくとも50%の軽減を認めること）に基いて評価された。この基準を用いるとそれぞれの群で約30%の患者が反応ありとされ、両群には有意の差は認められなかった。しかし、この否定的結果は注意深く解釈されなければならない。International　Headache　Societyのプロトコールに従って、症状の改善を測定した研究はとても少なく、そのほとんどが治療の有効性を示せなかった。β－ブロッカー（片頭痛の再発を予防すると考えられている薬品）でさえInternational　Headache　Societyの基準でテストされると無効であった。マグネシウムを投与された（ただ、患者の11%にしかプラセボは投与されていないのであるが）患者の33%は以前に受けた片頭痛の薬より優れていると感じたということは注目に値する。こういうわけで、この研究の結果はマグネシウムの有効性を報告しているこれまでの論文と矛盾してはいない。

マグネシウムはまた片頭痛の急性発作を治療するために静脈内にも投与される。急性の発作を起こしている患者40人が1gの硫酸マグネシウム（10%溶液）を5分以上かけて注射された。注射15分後35人（87.5%）は痛みが少なくとも50%以上軽くなった。9人（22.5%）は痛みが完全にとれた。35人の患者のうち21人で24時間もしくはそれ以上痛みは軽減したままだった。マグネシウムの効果は治療前のマグネシウムの血清濃度と相関していた。この研究はマグネシウムの静脈内投与が急性の片頭痛発作に対して有効な治療法で、特に、血清マグネシウム濃度が低い患者にはそうであることを示している。これらの研究は片頭痛の予防のために経口的にマグネシウムを補うことへの理論的根拠を与えている。

妥当な用量は１日あたり200‐600mg（たくさんの量を摂取する場合には、できるだけ下痢をしないようにするために、何回かに分けて食事と共に摂らなければならない）である。マグネシウムの静脈内投与はまた片頭痛の急性発作の抑制的治療の一方法として考慮されて良いかもしれない。血清中のイオン化されたマグネシウムを測定することは、どの患者がマグネシウムの静脈内投与にもっともよく反応するかをはっきりさせるのに有用かもしれないが、この検査はまだ商品化されていない。

マグネシウムの静注による治療の試みは、医師がこの物質の扱いに慣れていれば、十分可能である。ニューヨーク頭痛診療所のAlexander　Mauskop医師はマグネシウムの使用の研究を主導し、この件でパテントを取った。Mauskop医師は片頭痛を含めてすべての頭痛に関して指導的専門家の一人であると国際的にも認められている。彼の著作"The　Headache　Alternative"はDell　Publishing、N.Y.　N.Y.から手にいれることができる。

リボフラビン（ビタミンB2）
片頭痛を繰り返す49人の患者が400mg/dayのリボフラビンを食事とともに少なくとも3ヵ月投与された。片頭痛発作の平均回数は67％低下し、片頭痛の平均強度は68％軽減した。耐えがたい胃症状のために一人の患者が治療を止めたが（この患者は一緒に少量のアスピリンを飲んでいた）、これ以外には副作用は報告されていない。この研究はリボフラビン補充が片頭痛の再発頻度を減らすかもしれないということを示唆している。

L-トリプトファン
片頭痛は脳内のセロトニンの欠乏と関係があるといわれてきた。従って、セロトニンの前駆物質であるL-トリプトファンは片頭痛の予防にある役割を果たしているのかもしれない。

この仮説を検証するために、治療抵抗性の8人の片頭痛の患者が6時間ごとに500mgのL-トリプトファンかプラセボ（L-ロイシン）を2重盲験クロスオーバー法で3ヵ月間投与された。平均頭痛指数（発作回数×発作強度）は、L-トリプトファンの方がプラセボに比べて32.8％低かった。この差は統計学的には有意ではなかったが、頭痛指数はL-トリプトファン治療中は患者8人中4人でプラセボに比べて著明に低かった。これらの結果はL-トリプトファンがある種の片頭痛に一定の価値を有する可能性のあることと矛盾しない。ある二重盲験試験で片頭痛患者は3g/dayのL-トリプトファンかプラセボを1ヵ月間投与された。

L-トリプトファンを投与された60人の患者はプラセボを投与された患者に比べて片頭痛が有意に少なく持続時間も短かった。この所見はL-トリプトファンが片頭痛患者の一部に対しては予防的価値を持っていることを示唆している。L-トリプトファンは重大な副作用をひきおこすとは報告されていない。しかし、1989年不純物の混じったL-トリプトファンがeosinophilia　myalgia　syndromeとして知られる重篤な、場合によっては死亡することもある疾患の原因であるとされた。一方、不純物の入っていないL-トリプトファンはこの疾患とは関係がない。現在、不純物のないL-トリプトファンは処方箋があれば調剤薬局から手に入れることができる。

魚油
魚油と片頭痛の関連性に対する興味は、片頭痛患者が健康な人に比べて、血小板や赤血球膜のオメガ-3脂肪酸の濃度が有意に低いという発見が引き金となって、持たれるようになった。オメガ-3脂肪酸（主として、魚油、亜麻仁油そしてその他のある種の植物油や木の実油にみつかっている）は血小板の凝集を阻止することが知られている。この作用により多分、血小板のセロトニン放出を減少させ、さらには脳動脈の攣縮と片頭痛の発作を軽減させるものと思われる。

抗片頭痛薬に反応しない片頭痛の患者15人にアトランダムに魚油濃縮物（植物油）が6週間2重盲験クロスオーバー法で投与された。プラセボに比べて油による治療は平均頭痛強度を有意に低下させた。魚油濃縮物は副作用として胃腸症状を起こしうるが、そうでない限り、普通は耐えられないものではない。オメガ-3脂肪酸を含んだ他の物質（例えば、亜麻仁油）も有効と思われる。

食餌療法に関して考慮すべき事柄
片頭痛の患者のうちの一部は、古くなったチーズやヨーグルト、ビール、ぶどう酒、レバー、酵母、そしてそのほかある種の食物に見出される化学物質であるチラミンに反応するということは一般によく知られている。こういう患者ではチラミンを含んだ食品を避けるということがしばしば片頭痛の再発を防止することになる。片頭痛の患者のなかには糖代謝の異常を示すものがいる。ある研究で午前の中頃や午後の中頃に片頭痛を経験した74人の患者に5時間糖負荷試験がなされた。6人（8%）が糖尿病に分類され、56人（76%）が反応性低血糖（食後血糖値の大幅な低下）と矛盾しないパターンを示した。低蔗糖で6回食の食餌療法を行うと、糖尿病の血糖曲線を示していた患者全員と反応性低血糖の患者の56%が片頭痛の頻度と強度において75%以上の改善を示した。

食品アレルギーもまた片頭痛の重要な原因と考えられてきた。ある研究で平均約20年にわたって頻繁に片頭痛を起こしている60人の患者が5日間除外食を摂取した。この間、たった２種類の低リスクの食物（通常、子羊肉と洋なし）と涌き水だけを摂った。5日目までにほとんどの症例で片頭痛が消失した。患者は引き続き、反応をみるために、１ないし3種類の一般的な食物を摂った。症状を引き起こす食品の平均的な数は患者1人あたり10品目（範囲は1‐30）であった。最も頻繁に症状を誘発したり脈拍の変化をもたらす食品は小麦（78%）、オレンジ（65%）、卵（45%）、紅茶とコーヒー（それぞれ40%）、チョコレートとミルク（それぞれ37%）、牛肉（35%）、とうもろこし、さとうきび糖、そして酵母（それぞれ33%）、マッシュルーム（30%）そしてえんどう豆（28%）であった。害を及ぼす食物を避けるとすべての患者が良くなった。このグループの頭痛の数は一月あたり４０２回から６回にまで低下し、患者の85%が頭痛を起こさなくなった。この研究は、アレルギーを起こす食品を同定し、避けることが慢性的な反復性の片頭痛患者の多数にとって効果的な方法であることの強力な証拠を提供している。反復する片頭痛患者は血糖値の異常と食物アレルギーの検索をされるべきである。これらの異常のどちらかがみつかった場合、適切な食事の献立を作らなければならない。さらに、低チラミン食を考慮しなければならない。

あなたの薬剤師に話してください
上記の事柄を読むと、片頭痛に役立つかもしれないと多くの成分が候補に上げられ、研究されてきたことが明らかになる。ひとつの成分がひとりの患者に有益だと分っても、他の人には、わずかしかもしくはまったく役立たないかもしれない。

往々にして、ある成分の作用機序は他のものとは異なっている。伝統的中国医学では、お互い助け合い共働し合うことが分かっている成分が、何世紀にもわたって伝えられ、今日現代の中国の医師達によって用いられている伝統的な処方に則って、一緒に混ぜ合わせられる。彼らは何千もの年数、研究、実験を通して、これらの組み合わせの方が、ただ一つで替わりを果たすような成分よりも、大多数の人々にとってより良い結果をもたらすことを発見してきた。あなたの薬剤師は、この文書であなたのために要約された科学的データを吟味した。彼もしくは彼女は、あなたの抱える問題にとってもっとも有益でありそうな成分の組み合わせを選んでくれた。どうぞ、あなたの薬剤師に相談して、上記の知見にもっともよく合致する彼もしくは彼女のお勧めを教えてもらってください。

以下は原文

BACKGROUND AND EDUCATIONAL DATA

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Clinical Applications of Natural Medicine
Migraine
Donald Brown, N.D.
Alan Gaby, M.D.
Ronald Reichert, N.D.

Published by Natural Product Research Consultants

Series Editor
Donald Brown, N.D.

Dr. Brown is the founder and director of Natural Product Research Consultants and the editor of the Quarterly Review of Natural Medicine. He is a faculty member of Bastyr University in Seattle, Washington, where he teaches herbal medicine and therapeutic nutrition. Dr. Brown's book, Herbal Prescriptions for Better Health, was published in February 1996 by Prima Publishing.

CONTRIBUTORS

Alan Gaby, M.D.
Dr. Gaby is past-president of the American Holistic Medical Association and medical editor of The Townsend Letter for Doctors. He served on the Ad Hoc Advisory Panel of the National Institutes of Health Office of Alternative Medicine. He is the author of Preventing and Reversing Osteoporosis and B6: The Natural Healer.

Ronald Reichert, N.D.
An expert in European phytotherapy, Dr. Reichert resides in Vancouver, B.C., where he has an active medical practice. Dr. Reichert contributes regular articles to lay and professional publications in Canada. In addition to his regular herbal research columns, Dr. Reichert provides professional review of German translations for the Quarterly Review of Natural Medicine.

Copyright (c) 1997
All rights reserved by:
NPRC, Inc.
600 First Avenue, Suite 205
Seattle, WA 98104

No part of this publication may be reproduced in any form without permission from NPRC, Inc. and its representatives.

ABOUT THIS PUBLICATION

The information presented in this Condition-Specific Monograph is intended for professional education and is obtained from published research, articles and books. This update is not intended to replace the care of a licensed health professional in the diagnosis and treatment of illness.

CLINICAL APPLICATIONS OF NATURAL MEDICINE MIGRAINE

Migraine has been a well known medical problem for over 5,000 years and represents one of the most investigated types of head pain. Research on large groups of people has shown that in the U.S. 18% of women and 6% of men suffer from migraine.1 This extrapolates to approximately 18 million females and 5.6 million males over the age of 12 with this disorder.2 The prevalence of migraine, according to the Center for Disease Control, has increased 60% from 1981 to 1989.3 4 The economic impact of migraine is staggering, with annual cost of the disease estimated at 18 billion dollars.5

CAUSES OF MIGRAINES

The basic cause of migraine is still unknown. Although genetics may play a role, with 50 to 70% of migraine sufferers reporting a familial occurrence, no consistent biochemical or physiological characteristic can be recognized in the relatives of those afflicted with the condition.6

PHYSICAL AND FUNCTIONAL CONCERNS

There are several theories as to what causes a migraine and what happens to us when they occur. One of these theories suggests that certain arteries in our brain contract and cause a reduction blood flow to the visual area of our brain. It is suggested that this reduction of blood flow results in the visual and other symptoms that accompany a migraine.

This theory further suggests that the pain that often follows these symptoms was the result of dilation (expansion) of the carotid artery and pressure on the nerves in the artery wall. Yet another theory proposes that nerve cells in the brain begin to lose function which causes a reduction blood flow, which reduces levels of magnesium, which in turn adds to decreasing nerve cell function and that this dysfunction spreads in a wave like fashion to all effected areas.7 Many researchers feel that serotonin, an important brain chemical may fuel migraines.8 9 10 11 12 13 Platelets (components of our blood) contain all of the serotonin normally present in blood, and, after they aggregate, (clump together) serotonin is released, resulting in a potent constricting effect on the arteries.14 15 16 17

SIGNS AND SYMPTOMS

The two most important categories are migraine without aura (common migraine) and migraine with aura (classic migraine). A diagnosis of migraine without aura is made if the patient fulfills specific criteria. The patient must have a history of five previous similar episodes, with pain lasting between 4 and 72 hours. Additionally, they must meet two of the following four characteristic symptoms: (1) unilateral head pain; (2) pain must be throbbing or pulsing; (3) an experience of moderate to severe pain which inhibits or restricts the ability to function;(4) pain is made worse by routine physical activity. Furthermore, they must have one of the following two symptoms present: (1) nausea and/or vomiting; (2) adverse reactions to light or sound.18 In contrast, migraine with aura employs the same diagnostic criteria as common migraine with the following exceptions. Patients only need a history of two prior migraine attacks and must fulfill three of the following four criteria: (1) one or more aura symptoms; (2) aura symptoms that develop over more than 4 minutes; (3) aura lasts less than 60 seconds; (4) headache follows within 60 minutes of the aura ending. Auras represent several forms of visual disturbances that are described as dark or black point(s) that may or may not expand and obscure the patient's vision. The black spot may be surrounded by lights with zigzag lines. Patients with classic migraine symptoms may exhibit stroke-like symptoms including symptoms affecting one hand, arm, or side of the face.19 It is interesting to note that migraine sufferers are more likely to experience specific headache variants including intense throbbing head pain, brought on by exertion (exertional headache); ice-pick-like pains or electrical jabs, called stabbing headaches; and unilateral, intense eye pain.20 21

TREATMENT

For the migraine sufferer, there is a wide variety of therapeutic approaches both pharmacologic and non-pharmacologic. However, for practical reasons the management of migraine can be divided into two categories; abortive and preventative. As abortive treatment of migraine simply address the symptoms,via the use of drugs. Initial therapy for mild migraine headache is usually aspirin or other non-steroidal anti-inflammatory agents (e.g. ibuprofen and naproxen sodium). These pain relievers, along with sleep in a quiet, dark room, an ice pack on the head and an anti nausea drug.22 23

Certain drugs that constrict arteries are used with varying degrees of success and side effects. Your pharmacist can discuss them with you. Some of these drugs, though effective frequently result in rebound headache and other side effects.24 25

Another drug, sumatriptan (Imitrex(r)),has been shown to reduce the intensity of moderate to severe migraine headaches.27 Side effects from this type of drug include, tingling, heaviness, and a sensation of pressure. In contrast to abortive therapy, preventative drug strategies can be employed if the frequency of migraine attacks is sufficiently high. Propranolol is widely prescribed in the United States as a treatment for migraine prevention. Although it has proven to be effective in migraine prevention, its side effects include fatigue, depression, impotence, insomnia, dizziness, and cold extremities.28 Like drug intervention, non-pharmaceutical preventive therapies may also be effective. These include behavioral modification techniques such as stress management, biofeedback, exercise, acupuncture, trigger point injections and numerous physical therapy techniques (e.g. massage, manipulation and transcutaneous nerve stimulation).29

PHYTOMEDICINE CONSIDERATIONS

FEVERFEW
Feverfew (Tanacetum parthenium) is a member of the daisy family (Asteraceae) and is a short, bushy perennial that grows along fields and roadsides. Its yellow-green leaves and yellow flowers resemble those of chamomile, for which it is sometimes confused.

The flowers bloom from July to October. The leaves are used in medicinal preparations.30 The name "feverfew" is derived from the Latin for "chase away fevers." It is mentioned in the Greek literature asa remedy for inflammation and swelling as well as menstrual cramps. Feverfew enjoyed wide use by British herbalists as an analgesic in the treatment of fevers and arthritis, but faded into obscurity.

Feverfew has enjoyed a revival over the past two decades due to approval of its use for treatment of migraine by both the Canadian and British governments.

ACTIVE CONSTITUENTS: The most important of these compounds is parthenolide . First identified in 1960, parthenolide is the portion of the leaf believed to be responsible for feverfew's anti-migraine activity.31 A critical consideration in commercial feverfew products has been the highly variable content of parthenolide. An analysis of commercial feverfew products in Canada found about half are virtually devoid of this compound.32 As a minimal standard, the Health Protection Branch of the Health and Welfare Department of the Canadian Government has proposed that feverfew preparations should contain at least 0.2% parthenolide content.

Health care practitioners should also be aware that parthenolide is highly unstable and seek feverfew extracts that address this issue. Your pharmacist has identified one of the few sources of feverfew where the parthenolide content is assured.

MECHANISM OF ACTION: Feverfew, and specifically parthenolide,inhibits platelet aggregation (which if you remember can release serotonin which may fuel migraines) and histamine release. It has also been shown to inhibit release of serotonin from platelets 33,34 This is believed to reduce the severity, duration and frequency of migraine headaches and lead to an improvement in blood vessel tone.35,36 37

CLINICAL APPLICATIONS: Clinical studies with feverfew have focused on the treatment and prevention of migraine and have primarily taken place in Great Britain. These studies indicate the efficacy of feverfew as a useful tool in the long-term management of migraines.

The initial clinical study enrolled migraine patients who had been using feverfew for several years.38 Seventeen patients were enrolled and given either feverfew (50 mg daily) or placebo. Eight patients, who remained on feverfew, experienced continued relief of migraines over a six month period. The nine receiving placebo had an almost three-fold increase in migraines. Many of these headaches were incapacitating, and anxiety, insomnia and muscle and joint soreness were also reported. This has prompted some concern at the abrupt cessation of feverfew therapy. A second study enrolled 72 migraine sufferers.39 They received either 82 mg of feverfew daily or placebo.

Treatment with feverfew for four months led to a decreased incidence and severity of migraines. Feverfew also led to less vomiting attacks and fewer visual disturbances during migraine attacks. Adverse events were mild (primarily mild gastrointestinal upset and nervousness) and did not result in discontinuation of treatment.

RECOMMENDED DOSAGE: Appropriate dosing of feverfew leaf for migraine prevention is based on parthenolide content. The Canadian Health Protection Branch has granted a Drug Identification Number (DIN) for feverfew.40 They recommend a daily dosage of 125 mg of a dried feverfew leaf preparation from authentic Tanacetum parthenium containing a minimum of 0.2% parthenolide for migraine prevention. This translates to a daily parthenolide dosage of at least 250 mcg. This should be considered a minimum amount for efficacy. Results from studies that are not yet published indicate that 100 mg. per day of feverfew extract at .7% parthenolide content may be desirable. (Remember that over 50% of most feverfew extracts have little or no parthenolide content regardless of their label claims. Your pharmacist can help to avoid this problem. Continuous use for at least four to six weeks is recommended.

SIDE EFFECTS/CONTRAINDICATIONS: In addition to the adverse events listed in the clinical studies above, the most common side effect reported with feverfew has been mouth ulceration.41 This has predominantly been found in individuals chewing the leaves not with higher quality standardized extracts. Scattered reports of dermatitis have been reported with use of feverfew. To date, no long-term toxicity studies have been performed. Feverfew is contraindicated for pregnant or lactating women and should not be used in children under the age of two years.

OTHER HERBAL CONSIDERATIONS

GINGER
Ginger (Zingiber officinale) contains constituents that inhibit platelet aggregation.42,43 44,45 While all of these actions point to the potential use of ginger with migraine, controlled clinical trials are lacking. One case study published in the Journal of Ethnopharmacology reported on a 42 year old female migraine sufferer who found relief taking 500 to 600 mg of ginger powder mixed with water every four hours for four days.46 The patient was instructed to begin ginger at the onset of visual aura. The authors report improvement within 30 minutes of beginning ginger. They also note that continued use of ginger by the woman led to decreased frequency and intensity of migraines.

GINKGO BILOBA EXTRACT
GBE has been shown to offer some promise for the management of migraines in two small French clinical trials.47 48 49 The daily dose ranged from 120 to 240 mg. Clearly, more research is needed on the potential use of GBE for migraine.

NUTRITIONAL SUPPLEMENT CONSIDERATIONS

MAGNESIUM
It has pointed out that various factors which are known to trigger migraines (namely stress, pregnancy, menstruation, alcohol ingestion, and some diuretics) also promote magnesium depletion.50 In addition, magnesium exerts many of the same effects as drugs that are helpful in the prevention or treatment of migraines.51 These effects include: (1) inhibition of spasm; (2) inhibition of platelet aggregation; (3) stabilization of cell membranes; (4) interference with the synthesis, release or action of inflammatory compounds; and (5) improvements in cerebral vascular tone. In addition, brain magnesium concentrations were significantly lower by 19% in patients during a migraine attack than in healthy controls. These observations suggest that magnesium may play a role in the prevention and/or treatment of migraine. Clinical trials have supported that possibility. In an open trial, more than 3,000 patients with common or classical migraine received magnesium (usually at a dose of 200 mg/day).52 Almost all of the patients were women and most were of childbearing age. The "success rate" was reported to be 80%, but the criteria for determining success were not specified.

CONDITION-SPECIFIC MONOGRAPH SERIES

MIGRAINE
That uncontrolled study was followed by a double-blind trial in which 20 patients with perimenstrual migraine received 360 mg/day of magnesium or a placebo.53 The treatments were given for two months, starting on the 15th day of each menstrual cycle and continuing until menstruation. At the end of the treatment period, the "Pain Total Index" (which measures duration and intensity of migraines) was significantly lower in the magnesium group than in the placebo group. The number of days with headaches was significantly reduced in patients receiving magnesium, but not in those given placebo. Prior to the start of treatment, white-blood-cell (WBC) magnesium concentrations were lower in the migraine patients than in healthy controls.

Magnesium treatment was followed by a significant increase in WBC magnesium levels. These data suggest that magnesium deficiency contributes to the dysfunction of perimenstrual migraine. In another double-blind study, 81 patients aged 18 to 65 years with migraines (mean attack frequency, 3.6 per month) were randomly assigned to receive magnesium (600 mg every morning) or a placebo for 12 weeks. 54 The frequency of attacks was significantly reduced in the magnesium group, compared with the placebo group (by 41.6%vs. 15.8%; p < 0.05). The duration and intensity of attacks also tended to decrease compared to placebo, but the difference was not statistically significant. Diarrhea occurred in 18.6% and gastric irritation in 4.7% of patients receiving magnesium. One study failed to find a beneficial effect of magnesium for migraine prevention. 55 In that study, 69 patients with migraines were randomly assigned to receive magnesium (242 mg twice daily) or a placebo, in double-blind fashion, for 12 weeks. Response to therapy was assessed according to the criterion of the International Headache Society; i.e. a reduction of at least 50% in the duration or intensity of migraines. Using that criterion, approximately 30% of patients in each group were considered responders, with no significant difference between groups. However, this negative finding should be interpreted cautiously. Only a few studies have measured improvement according to the protocol of the International Headache Society and most of those studies showed no significant benefit from the treatment being tested. Even beta-blockers (a class of drugs known to prevent migraine recurrences) were ineffective when tested by the International Headache Society criteria. It is noteworthy that 33% of patients receiving magnesium (but only 11% of patients given placebo) felt that their treatment was superior to previously used migraine medications. Thus, the results of this study are not inconsistent with previous reports of a beneficial effect of magnesium.

Magnesium has also been given intravenously to treat acute episodes of migraine.56 Forty patients with an acute migraine attack were given 1 g of magnesium sulfate (in a 10% solution) over five minutes. Fifteen minutes after the infusion, 35 patients (87.5%) experienced at least a 50% reduction in pain. Nine patients (22.5%) had complete relief of pain. In 21 of the 35 patients who improved, relief persisted for 24 hours or more. The effectiveness of magnesium was related to the pre-treatment serum concentration of magnesium. This study suggests that intravenous administration of magnesium is an effective treatment for acute migraine attacks, particularly in patients whose serum magnesium concentrations are low. These studies provide a rationale for oral magnesium supplementation for migraine prophylaxis.

A reasonable dosage is 200 to 600 mg/day (the larger amounts should be taken in divided doses with meals to reduce the risk of diarrhea). Intravenous administration of magnesium may also be considered as a method of aborting acute migraine attacks. While measurement of serum ionized magnesium might be useful to predict which patients are most likely to respond to intravenous magnesium, this test is not yet commercially available.

A therapeutic trial with intravenous magnesium is usually acceptable, provided that the physician is trained in proper administration of this compound. Dr. Alexander Mauskop of the New York Headache clinic has lead the research in the use of magnesium and has been issued a patent on the subject. Dr. Mauskop is considered internationally to be one of the leading experts on all types of headaches including migraines. His book "The Headaches Alternative" is available from Dell Publishing, N.Y, N.Y.

RIBOFLAVIN
49 patients with recurrent migraines were given riboflavin, 400 mg/day with breakfast, for at least three months.57 The mean number of migraine attacks fell by 67% and mean migraine severity improved by 68%. One patient stopped treatment because of gastric intolerance (that person was also taking small amounts of aspirin), but no other side effects were reported. This study suggests that riboflavin supplementation may reduce the recurrence rate of migraines.

L-TRYPTOPHAN
It has been suggested that migraines are related to a deficiency of serotonin in the brain.58 As the precursor to serotonin, L-tryptophan might therefore play a role in migraine prevention.

To test that hypothesis, eight migraine patients who had been resistant to therapy received 500 mg of L-tryptophan every six hours or a placebo (L-leucine), each for three months, in a double-blind, crossover trial.59 The mean headache index(number of attacks multiplied by the intensity) was 32.8% lower with L-tryptophan than with placebo. Although that difference was not statistically significant, headache indices were markedly lower in four of the eight patients during L-tryptophan treatment, compared to placebo treatment. These results are consistent with the possibility that L-tryptophan is of value for a subset of migraine patients. In a double-blind study, migraine patients received 3 g/day of L-tryptophan or a placebo for one month.

60 Patients receiving L-tryptophan had significantly fewer migraines of significantly shorter duration than did patients receiving placebo. These observations suggest that L-tryptophan may have preventive value for a portion of migraine patients. L-tryptophan has not been reported to cause any severe side effects. However, in 1989 a contaminated batch of L-tryptophan was implicated as the cause of a severe and sometimes fatal disorder known as eosinophilia myalgia syndrome. Uncontaminated L-tryptophan, on the other hand, has not been associated with this disorder. Currently, uncontaminated L-tryptophan is available by prescription from compounding pharmacists.

FISH OIL
Interest in the relationship between fish oil and migraines was triggered by the observation that migraine patients had significantly lower concentrations of omega-3 fatty acids in platelet and red blood cell membranes, compared with healthy individuals.61 Omega-3 fatty acids (which are found primarily in fish oils, flaxseed oil and some other vegetable and nut oils) are known to inhibit platelet aggregation. This effect would presumably decrease platelet serotonin release, with an accompanying reduction in cerebral artery spasm and migraine attacks.

Fifteen patients with migraines that had failed to respond to anti-migraine drugs received (in random order) a fish-oil concentrate (vegetable oil) for six weeks, in a double-blind, crossover trial.62 Compared with placebo, treatment with the oils resulted in a significant reduction in mean headache intensity. Fish-oil concentrates can cause gastrointestinal side effects, but are otherwise usually well tolerated. Other sources of omega-3 fatty acids (such as flaxseed oil) might conceivably have a beneficial effect, as well.

DIETARY CONSIDERATIONS
It is generally accepted that a small proportion of migraine patients will react to tyramine, a chemical found in aged cheese, yogurt, beer, wine, liver, yeast and certain other foods. In these patients, avoidance of tyramine-containing foods will often prevent recurrences of migraine. Abnormal glucose metabolism has been identified in some patients with migraines. In one study, a five-hour glucose tolerance test was performed on 74 patients who experienced migraines in the mid-morning or mid-afternoon.63 Six patients (8%) were classified as diabetic and 56 (76%) had a pattern consistent with reactive hypoglycemia (a large drop in blood sugar after a meal). Following dietary therapy with a low-sucrose, six-meal regimen, all patients with a diabetic glucose curve and 56% of those with reactive hypoglycemia (low blood sugar) had an improvement of greater than 75% in the frequency and severity of migraines.

Food allergy has also been implicated as an important factor in migraine. In one study, 60 patients who had been suffering from frequent migraines for a mean duration of about 20 years followed an exclusion diet for five days.64 During that time, only two low-risk foods (usually lamb and pears) and spring water were consumed. Migraines disappeared in most cases by the fifth day. Each patient then tested one to three common foods per day, looking for reactions. The mean number of foods causing symptoms was 10 per patient (range, 1 to 30). The foods most frequently causing symptoms and/or pulse changes were wheat (78%), orange (65%), egg (45%), tea and coffee (40% each), chocolate and milk (37% each), beef (35%), corn, cane sugar and yeast (33% each), mushrooms (30%), and peas (28%). When the offending foods were avoided, all patients improved. The number of headaches in the group fell from 402 to 6 per month, with 85% of the patients becoming headache free. This study provides strong evidence that identification and avoidance of allergy causing foods is an effective procedure for a large proportion of patients with chronic recurrent migraines. Patients with recurrent migraines should be evaluated for possible blood-sugar abnormalities and food allergies. When either of these abnormalities is found, appropriate dietary modifications should be made. In addition, a trial of a low-tyramine diet should be considered.

SPEAK TO YOUR PHARMACIST:
After reading the above information, it becomes clear that many ingredients have been considered and researched as to their benefits for migraine. Though one ingredient may prove to be beneficial for one person, it may be of little or no benefit to another individual.

Often times the method of action for one ingredient may be different from the method of another. In Traditional Chinese Medicine [CM) many ingredients that have been found to support and synergize one another are blended together in age old formulas that are passed down from century to century and used to this day by modern Chinese physicians. They have found over thousands of years or research and experimentation that these combinations often provide better results, to a larger population of people, than single ingredient alternatives. Your pharmacist has reviewed the scientific data that has been summarized for you in this document. He or she has chosen combinations of the above mentioned ingredients that are most likely to be of benefit for your concerns. Please consult your pharmacist about his or her recommendations on how to best implement the above information.

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References:
1 Rapoport AM, Scheftell ED. Headache Disorders: A Management Guide for Practitioners. Philadelphia: WB Saunders Co., 1996, 1.
2 Noack H, Rothrock JF. Migraine: definitions, mechanisms, and treatment. South Med J 1996; 89: 762.
3 Rapoport AM, Scheftell ED. Headache Disorders: A Management Guide for Practitioners. Philadelphia: WB Saunders Co.,1996, 4.
4 Theisler CW. Migraine Headache Disease. Gaithersburg, MD: Aspen Publishers Inc., 1990, 2.
5 Noack H, Rothrock JF. Migraine: definitions, mechanisms, and treatment. South Med J 1996; 89: 762.
6 Ziegler DK, Friedman AP. Migraine. In: Rowland LP, ed. Meritt's Textbook of Neurology, 8th ed. Philadelphia: Lea and Febiger, 1989, 773.
7 Rapoport AM, Scheftell ED. Headache Disorders: A Management Guide for Practitioners. Philadelphia: WB Saunders Co., 1996, 1, 37.
8 Campbell JK, Caselli RJ. Headache and other craniofacial pain. In: Bradley WG, Daroff RB, Fenichel GM, Marsden CD, eds. Neurology in Clinical Practice, Vol II. Boston: Butterworth-Heinemann, 1991: 1525_6.
9 Theisler CW. Migraine Headache Disease. Gaithersburg, MD: Aspen Publishers Inc., 1990, 42.
10 Campbell JK, Caselli RJ. Headache and Other Craniofacial Pain. In: Bradley WG, Daroff RB, Fenichel GM, Marsden CD,eds. Neurology in Clinical Practice, Vol II. Boston: Butterworth-Heinemann, 1991: 1526.
11 Noack H, Rothrock JF. Migraine: definitions, mechanisms,and treatment. South Med J 1996; 89: 764.
12 Rapoport AM, Scheftell ED. Headache Disorders: A Management Guide for Practitioners. Philadelphia: WB Saunders Co., 1996, 44.
13 Noack H, Rothrock JF. Migraine: definitions, mechanisms, and treatment. South Med J 1996; 89: 764.
14 Theisler CW. Migraine Headache Disease. Gaithersburg, MD: Aspen Publishers, 1990, 30_32.
15 Campbell JK, Caselli RJ. Headache and Other Craniofacial Pain. In: Bradley WG, Daroff RB, Fenichel GM, Marsden CD, eds. Neurology in Clinical Practice, Vol II. Boston: Butterworth-Heinemann, 1991: 1526.
16 Noack H, Rothrock JF. Migraine: definitions, mechanisms, and treatment. South Med J 1996; 89: 765.
17 Rapoport AM, Scheftell ED. Headache Disorders: A Management Guide for Practitioners. Philadelphia: WB Saunders Co., 1996, 39_40.
18 Rapoport AM, Scheftell ED. Headache Disorders: A Management Guide for Practitioners. Philadelphia: WB Saunders Co.,1996, 7_10.
19 Ziegler DK. Headache syndromes. In: Rosenberg RN, ed. Comprehensive Neurology. New York: Raven Press Ltd., 1991, 290.
20 Rapoport AM, Scheftell ED. Headache Disorders: A Management Guide for Practitioners. Philadelphia: WB Saunders Co., 1996, 12_13.
21 Ziegler DK, Friedman AP. Migraine. In: Rowland LP, ed. Meritt's Textbook of Neurology, 8th ed. Philadelphia: Lea and Febiger, 1989, 776_7.
22 Campbell JK, Caselli RJ. Headache and Other Craniofacial Pain. In: Bradley WG, Daroff RB, Fenichel GM, Marsden CD, eds. Neurology in Clinical Practice, Vol II. Boston: Butterworth-Heinemann, 1991: 1528.
23 Spierings ELM. Migraine: diagnosis, pathogenesis, and treatment. In: Rapoport AM, Scheftell ED, eds. Headache: A Clinician's Guide to Diagnosis, Pathophysiology and Treatment Strategies. Costa Mesa, CA: PMA Publishers, 1993, 92.
24 Campbell JK, Caselli RJ. Headache and other craniofacial pain. In: Bradley WG, Daroff RB, Fenichel GM, Marsden CD, eds. Neurology in Clinical Practice, Vol II. Boston: Butterworth-Heinemann, 1991: 1528.
25 Rapoport AM, Scheftell ED. Headache Disorders: A Management Guide for Practitioners. Philadelphia: WB Saunders Co., 1996, 84.
26 Noack H, Rothrock JF. Migraine: definitions, mechanisms, and treatment. South Med J 1996; 89: 767.
27 Spierings ELM. Migraine: diagnosis, pathogenesis, and treatment. In: Rapoport AM, Scheftell ED, eds. Headache: A Clinician's Guide to Diagnosis, Pathophysiology and Treatment Strategies. Costa Mesa, CA: PMA Publishers, 1993, 93_4.
28 Rapoport AM, Scheftell ED. Headache Disorders: A Management Guide for Practitioners. Philadelphia: WB Saunders Co., 1996, 91_2.
29 Rapoport AM, Scheftell ED. Headache Disorders: A Management Guide for Practitioners. Philadelphia: WB Saunders Co., 1996, 105_6.
30 Feverfew. Lawrence Review of Natural Products, September, 1994.
31 Awang DVC. Herbal medicine, feverfew. Canadian Pharm J 1989; 122: 266_70.
32 Heptinstall S, Awang DVC, Dawson BA, et al. Parthenolide content and bio-activity of feverfew (Tanacetum parthenium). Estimation of commercial and authenticated feverfew products. J Pharm Pharmacol 1992; 44: 391_5.
33 Heptinstall S, White A, Williamson L, Mitchell JRA. Extracts of feverfew inhibit granule secretion in blood platelets and polymophonuclear leukocytes. Lancet 1985; I:1071_4.
34 Makheja AN, Bailey JM. A platelet phospholipase inhibitor from the medicinal herb feverfew (Tanacetum parthenium). Prostagland Leukortrienes Med 1982; 8:653_60.
35 Pugh WJ, Sambo K. Prostaglandin synthetase inhibitors in feverfew. J Pharm Pharmacol 1988; 40:743_5.
36 Sumner H, Salan U, Knight DW, Hoult JRS. Inhibition of 5-lipoxygenase and cyclo-oxygenase in leukocytes by feverfew.Biochem Pharmacol 1992; 43:2313_20.
37 Pattrick M, Heptinstall S, Doherty M. Feverfew in rheumatoid arthritis: a double-blind, placebo-controlled study. Ann Rheumatic Dis 1989; 48:547_9.
38 Johnson ES, Kadam NP, Hylands DM, Hylands PJ. Efficacy of feverfew as prophylactic treatment of migraine. BritishMed J 1985; 291:569_73.
39 Murphy JJ, Heptinstall S, Mitchell JRA. Randomized double-blind placebo-controlled trial of feverfew in migraine prevention. Lancet 1988; ii:189_92.
40 Awang DVC. Feverfew fever. HerbalGram 1993; 29:34.
41 Bradley PR, ed. British Herbal Compendium, Volume 1. Bournemouth, Dorset: British Herbal Medicine Association, 1992, 96_8.
42 Kiuchi F, Ikwakami S, Shibuya M, et al. Inhibition of prostaglandin and leukotriene bio-synthesis by gingerols and diarylheptanoids. Chem Pharm Bull 1992; 40:387_91.
43 Verma SK, Singh J, Khamersa R, Bordia A. Effect of ginger on platelet aggregation in man. Indian J Med Res 1994; 98:240_2.
44 Kawai T, Kinoshita K, Koyama K, Takahashi K. Anti-emetic principles of Magnolia obovata bark and Zingiber officinale rhizome. Planta Med 1994; 60:17_20.
45 Onogi T, Minami M, et al. Capsaicin-like effect of (6)_shogaol on substance P containing primary afferentsin rats: A possible mechanism of its analgesic action. Neuropharmacol1992; 31:1165_9.
46 Mustafa T, Srivastava KC. Ginger (Zingiber officinale) in migraine headache. J Ethnopharmacol 1990; 29:267_73.
47 Kovacs K, Herman F, Filep J, et al: Platelet aggregation of migraineurs during and between attacks. Cephalagia 1990;10:161_5.
48 Lamant V, Mauco G, et al. Inhibition of the metabolism of platelet activating factor (PAF-acether) by three specific antagonists from Ginkgo biloba. Biochem Pharmacol 1987; 36:2749_52.
49 DeFeudis FV. Ginkgo biloba Extract (EGb 761): Pharmacological activities and Clinical Applications. Paris: Elsevier, 1991, 142.
50 Altura BM. Calcium antagonist properties of magnesium: implications for anti-migraine actions. Magnesium 1985; 4:169_75.
51 Ramadan NM, Halvorson H, Vande-Linde A, et al. Low brain magnesium in migraine. Headache 1989; 29:590_3.
52 Weaver K. Magnesium and migraine. Headache 1990; 30:168.
53 Faccinetti F, Sances G, Borella P, et al. Magnesium prophylaxis of menstrual migraine: effects on intra-cellular magnesium. Headache 1991; 31:298_304.
54 Peikert A, Wilimzig C, Kohne-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_263.
55 Pfaffenrath V, Wessely P, Meyer C, et al. Magnesium in the prophylaxis of migraine a double-blind, placebo-controlled study. Cephalalgia 1996; 16:436_440.
56 Mauskop A, Altura BT, Cracco RQ, et al. Intravenous magnesium sulphate relieves migraine attacks in patients with low serum ionized magnesium levels: a pilot study. Clin Sci 1995; 89:633_6.
57 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_9.
58 Salmon S, Fanciullacci M, Bonciani M, et al. Plasma tryptophan in migraine. Headache 1978; 17:238_241.
59 Kangasniemi P, Falck B, Langvik V-A, et al. Levotryptophantreatment in migraine. Headache 1978; 18:161_6.
60 Steardo L, Sorge F, Florio C. Trattamento con L-triptofanonelle cefalee essenziali: dati preliminari. Acta Neurologica1977; 32:613.
61 Carswell H. On a scale of 1 to 10 vs. a variety of ills,fish oil maybe a 5. Med Tribune, July 16, 1986, 3. 62 McCarren T, Hitzemann R, Smith R, et al. Amelioration of severe migraine by fish oil (omega-3) fatty acids. Am JClin Nutr 1985; 41:874.
63 Dexter JD,Roberts J, Byer JA. The five hour glucose tolerance test and effect of low sucrose diet in migraine. Headache1978; 18:91_4.
64 Grant ECG. Food allergies and migraine. Lancet 1979;i:966_9.

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About Migra-LieveTM ・ Order Migra-LieveTM ・ Survey ・ Adverse Effects
Side Effects ・ Contact Us ・ Home

以下は貼付文書です。

A DIETARY SUPPLEMENT SUPPORTING CEREBROVASCULAR TONE*

ormulated by leading researchers in the fields of natural medicine and nutrition, FMigra-Lieve" is the first comprehensive supplement for the support of cerebrovas-cular tone.* Using a botanical extract and nutritional supplements in the amounts shown beneficial in scientific studies, Migra-Lieve' provides the health care profes-sional with a valuable tool for patients seeking a dietary supplement to help support normal cerebrovascular tone.*

Migra-Lieve' is a unique combination of herbal and nutri-tional supplements aimed at supporting cerebrovascular tone, and reducing platelet aggregation and the production of pro-inflammatory mediators.* The herbal and nutrition-al ingredients in Migra-Lieve' are used in the amounts
shown to be beneficial in scientific studies.

- Commonly recommended for its ability to support cere-brovascular tone, feverfew (Tanacetum parthenium) is rich in compounds known as sesquiterpene lactones. The most important of these compounds is parthenolide, which
represents 85% of the sesquiterpene lactone content in
feverfew leaf extracts. Particularly important in feverfew extracts is the parthenolide content as well as the stability of this important constituent. Migra-Lieve' is not only
standardized to a high parthenolide content of 0.7% but

TWO CAPLETS PROVIDE: AMOUNT % Of U.S. RDA* Feverfew (Tonacetum parthenium) Extract ...................... I 00 mg.
(Standardized to 0.7% Parthenolide)
Magnesium ((itrate/Oxide 1:1 ) ............................... 300 mg ................ 75
Riboflavin (Vitamin B-2) ..................................... 400 mg ............ 23,525

*Percentage of U.S. Re(ommended Daily Allowance
(ontoins no yeost, milk, corn, wheat, gluten, soy, sodium, salt, sugar, flavorings, preservofives, orfificial colors.

also measures the
stability of partheno-lide. Standardization insures the optimal dosage of partheno-lide in an extract that

will not lose its potency over time. Scientific studies have
found that parthenolide inhibits platelet aggregation and the release of serotonin from platelets and polymorphonuclear leukocyte granules.* It has also been shown to inhibit pro-inflammatory prostaglandin synthesis and the release of
arachadonic acid.* European studies have shown the benefits of a feverfew extract, standardized on parthenolide content, on the long-term support of cerebrovascular tone.*

- Magnesium is a nutritional supplement with numerous effects that support vascular tone.* These include: 1) inhibi-tion of platelet aggregation; 2) interference with synthesis, release, and action of inflammatory mediators; 3) direct
alterations of cerebrovascular tone; 4) inhibition of vaso-
spasm; and 5) stabilization of cell membranes.* Some per-sons with poor cerebrovascular tone have been found to
have low brain levels of magnesium.* Recommended daily dosages of magnesium typically range from 200 to 600 mg to compensate for this deficiency.*

- Riboflavin (vitamin B-2) is a precursor of flavin adenine dinucleotide (FAD). This coenzyme is an important compo-nent of the electron-transport chain. A deficiency of mitro-chondrial energy reserves has been observed in some persons exhibiting poor cerebrovascular tone. This defect may theo-retically be corrected by a compound such as riboflavin that improves the activity of the electron-transport chain.*

RECOMMENDED USE

Take one caplet twice daily. Migra-Lieve"
is designed to provide benefits within four to six weeks. Once results are noted, Migra-Lieve" may be used for several months as
part of a daily supplement regime and com-prehensive wellness program.

CONTRAINDICATIONS, ADVERSE REACTIONS OR INTERACTIONS

Side effects due to any of the ingredients in Migra-Lieve T' are rare. Mild gastrointestinal upset and loose stools may occur in some
persons using magnesium. This product is not recommended for use during pregnancy or lactation and should not be used in chil-dren under the age of two years. Persons tak-ing potassium-sparing diuretics or with renal failure should not use this product.

SELECTED REFERENCES

Brown D, Gabv A, Reichert R. Clinical
Applications of Natural Medicine-Migraine.
NPRC Condition-Specific Monograph Series, 1997.

Feverfew. Lawrence Review of Natural
Products, September 1994.

Awang DVC. Herbal medicine, feverfew.
Canadian Pharm 1 1989; 122:266-70.

Heptinstall S, Awang DVC, Dawson BA,
et al. Parthenolide content and bioactivity of feverfew (Tanacetum partheiiium). Estima-tion of commercial and authenticated fever-few products. I Phartn Pharmacol 1992; 44: 391-5.

Pugh Wj, Sambo K. Prostaglandin syn-
thetase inhibitors in feverfew. I Pharm
Pharmacol 1988; 40:743-5.

Heptinstall S, White A, Williamson L,
Mitchell JRA. Extracts of feverfew inhibit granule secretion in blood platelets and
polymophonuclear leukocytes. Lancet
1985; i:1071-4.

Makheia AN, Bailey JM. A platelet phos-
pholipase inhibitor from the medicinal herb feverfew (Tanacetum parthenium). Prosta-
gland Leukotrienes Med 1982; 8:653-60.

Sumner H, Salan U, Knight DW, Hoult JRS.
Inhibition of 5-lipoxygenase and cyclo-oxy-genase in leukocytes by feverfew. Biochem Phannacol 1992; 43:2313-20.

Johnson ES, Kadam NP, Hylands DM,
Hylands Pj. Efficacy of feverfew as prophy-lactic treatment of migraine. British Med 1 1985; 291:569-73.

Murphy Jj, Heptinstall S, Mitchell JRA.
Randomized double-blind placebo-controlle( trial of feverfew in migraine prevention.
Lancet 1988; ii:189-92.

Altura BM. Calcium antagonist properties of magnesium: implications for antimigraine actions. Magnesium 1985; 4:169-75.

Ramadan NM, Halvorson H, Vande-Linde A, et al. Low brain magnesium in migraine.
Headache 1989; 29:590-93.

Weaver K. Magnesium and migraine.
Headache 1990; 30:168.

Faccinetti F, Sances G, Borella P, et al.
Magnesium prophylaxis of menstrual
migraine: effects on intracellular magnesium Headache 1991; 31:298-304.

Peikert A, Wilimzig C, Kohne-Volland R.
Prophylaxis of migraine with oral magne-sium: results from a prospective, multi-cen-ter, placebo-controlled and double-blind
randomized study. Cephaialgia 1996;
16:257-63.

Pfaffenrath V, Wessely P, Meyer C, et al.
Magnesium in the prophylaxis of migraine-a double-blind, placebo-controlled study.
Cephalaigia 1996; 16:436-40.

Schoenen -1, Lenaerts M, Bastings E. High-dose riboflavin as a prophylactic treatment of migraine: results of an open pilot study.
Cephaialgia 1994; 14:328-9.

NSCA products are available only through licensed health care professionals.
To order this product or for information on other NSCA Condition-Specific Products, call NSCA at (800) 758-8746.

MIGRA-LIEVE （TM）

以下は原文

以下は貼付文書です。

MIGRA-LIEVE　（TM）