2008年12月27日 星期六

保健與補健 - Dr. George Ku


保健與補健
我一向鼓吹「補健」。有一位朋友告訴我,他曾在辭典中找「補健」這個詞,但找不到,只能找到「保健」和「保健食品」。我說,據我所知,「保健」一詞不見於古籍,中國人一向說的是「進補」、「補養」、「補品」。日本有「保健所」,是處理地區居民健康和公共衞生事務的政府機關,所以「保健」可能是源自日本的外來語。單單看「保健」一詞,可以將它解作「保持健康」,其中的「保」字,有「不讓它受到損害」的味道,例如用於「保護」、「保衞」、「保存」、「保固」;其中的含意,是屬「維護」性質的。但一般所謂「保健」的食物,其用途並不在於消極地、蓋括性地維護健康,而是進取地、針對性地補充日常食物之不足,希望能將尚未達標的身體狀況,帶到健康的水平;因此,用「補」字是更貼切。我提議他試查看維基百科中這個名詞的中英對照,其中「保健食品」一詞並沒有自己的條目,若以這四個字搜索,走出來的課題會是「膳食補充劑」,英文是Dietary Supplement,可見「保健」云云,並不適當。還有,「保」字本身會引致一個美麗的誤會,因為好像是一個承諾,吃了「保」會帶來「健」康,令人產生「安枕無憂」的錯覺,偏離了應有的意義。我把「保」更正為「補」,乃實事求是之舉;表示身體缺乏了某些東西,於是輔以補健食品,「補」其不足,只此而已。這位朋友來自國內,說普通話,對這兩個字的分別馬上能察覺到,因為讀音迥然不同;若用廣東話,發音一樣,意義上的重大分別,很容易就忽略了。

尚有值得注意的,「補」是指「幫補」、「補遺」,換言之,是協助性的。相對來說,與其他另一些「補」的功能,大異其趣,各有所謀。首先,這不是「補給」。一個人的生存條件之一,是需要有不停的補給,包括氧氣、水分和食物,這差使是補健食品擔當不來的,也就是說,不能拿補健食品當飯吃。

清朝時有品級的官員官服上有繡章,綴在前胸與後背,文官繡鳥,武官繡獸;官職大小依此辨別。文官一品繡的是仙鶴,二品繡的是錦雞;武官一品則是麒麟,二品是獅子。這些繡章叫「補子」,又叫「補服」,所以官服有「補掛朝珠」之稱。補子的功能其實不在於「補」,因為不是用來掩蓋衣服的破爛部分,而是用來顯示訊息,也令衣服更華麗,乃是錦上添花。補健食品的用意不在此。

尚有一個很重要的功能,補健食品也是不幹的,此乃「修補」。身體中大至五臟四肢,小至每一個細胞,都會有損傷之虞;傷了自須修理。修理前者的方法,用的是藥,也可用外科手術;一些器官若是再修不好,還可更換零件,是為器官移植。在細胞的層面,則有一套天然的機制。

培補元氣
我爸爸姓顧,我自須姓顧;爸爸給我的名字叫「小培」。老實說,我曾想過改另一個名,因為自從覺得自己已是「大」人後,就開始感到這「小」字十分彆扭,加上英文讀法是將姓氏放在後面,普通話發音的「小培顧」,竟成為「小屁股」。像是冥冥中早有注定,爸爸原來有先見之明。我在三十四年前去美國讀書,本想讀醫科,最終以細菌學結業,之後在異邦做研究,兜兜轉轉,今天回歸香港,做的工作,正與我名字配合,乃是幫大眾「培補」身體。這個「培」,可不是什麼大事,只是吃一些普通到再不能更普通的健康食品,每天吃一點點,花費的金額也小,因此是「小培」。連着的「顧」字,原來另有典故。《戰國策》中有道:「見兔而顧犬未為晚也,亡羊而補牢未為遲也」,引申出來的成語「顧犬補牢」,比喻在事情緊急或出了差錯時才設法補救,「未為晚也」;雖然發現自己身體有衰敗的狀況,但開始「小培補健」,尚來得及:你說是否湊巧得緊?而且「顧」的英文拼音是Ku,恰恰正是替細胞做「修補」工作的蛋白質,它修補的層面,在於細胞中的遺傳物質 DNA,也是小到不能再小,換言之,亦可以稱之為替細胞「小培」的Ku。

DNA的形狀像扭麻花,其中是互繞的兩條長鏈,我們分別稱之為「正」、「負」。每一條長鏈上是一連串的遺傳密碼,密碼基本上只有四種,在學術研究中,我們分別用四個英文字母(C、G、A、T)來稱呼它們。如果「正」的一條攜帶的遺傳密碼是ATGC……等等,在「負」條的相對位置上,必然會是TACG……(A和T、G和C,分別相對,永遠如是)。所以,若任何一條因某種原因(比方,紫外線的侵害)而遺失了一截,細胞可以憑另一條上面A、T、G、C的排列,把缺失了的那一段重造出來,也就是修補失落了的部分。可是,假若「打孖」的DNA在同一位置斷了一截,要修補便十分棘手。好有一比,辦公室有一個重要檔案,必須保存,為了不想它失落,我們用照相機將它逐頁照下來。照完後,我們存有完整的兩套,一套是原文正本,另一套是菲林負片。在正本中的黑色,負片上見到的是白色;正本上的白色,負片上則是黑色。假如正本中有一頁遺失或損壞了,我們可以憑負片的同一頁,把缺失的一頁重新造出來。但假如正本的第二十一頁不見了,同時負片中的第二十一頁也找不到時,那就棘手了。可是,即使棘手也得修補;這個任務,落在一個特殊的蛋白質身上,這個蛋白質,我們稱之為Ku。Ku有兩種,分別叫Ku70和Ku80。兩者的分別,在於它們個別的分子量(70kDa與80kDa)不同。Ku如何修補DNA?方法是兩者合在一起,像一個兜,兜在斷成兩截DNA的折斷處,也就是尾端。

細胞的修補
1932年9月,美國的洛克菲勒大廈剛建到第六十九層,《紐約時報》派了二十七歲的攝影師Charles Clyde Ebbets去到建築地盤,為當時這幢數一數二的高廈(全高七十層)拍攝一些足以留存紀念的照片。Ebbets曾做過飛機特技表演員,有膽子在飛行中的飛機機翼上走動,完全不畏高。他爬上建造中的最高層,蹲在一條懸空的鋼樑上,在他面對着的另一條鋼樑上面,坐着十一個建築工人,他替他們照了一張照片,其後在10月2日刊登出來,這就是著名的Lunchtime atop a Skyscraper(在摩天大廈上的午膳時間)。照片可見鋼樑約兩呎寬,是鋼架上孤單單的一條,十一人大家排排坐在上面,每人的腳都吊在空中,背景是紐約市的天空,可見稀疏的雲層,遠處是房子的屋頂;工人們正在午膳,雖在極高處,身上卻無安全帶,談笑自若,像是坐在公園長椅上。每次看這照片,手心都不禁冒汗。真不知道他們怎樣練成這本領。正如我們的搭棚工人,能在棚架上爬上爬落,捷如猿猴。

搭棚可以說是國技,外國人第一次見到,瞠目結舌。棚的功用大矣哉,不但建築中需用到,平常的外牆修補工作,也少不了它。在細胞的層面,若是DNA有了創傷,亦須有「搭棚工人」修補,這些工人由一類叫Ku 的蛋白質擔當,其中包括兩個不同的成員,按它們的分子量,分別叫Ku70和Ku80。兩者合在一起,像一個兜,兜在斷成兩截的DNA折斷處,也就是尾端。除了形狀像兜,它們也能沿着DNA的鏈條攀下去,像織補衣服一樣,把缺失的部分織回來。

織補後能否完全回復舊觀?當然不能,但至少衣服尚可繼續穿。細胞雖然還能活下去,但功能肯定打了折扣;此乃細胞衰老的原因之一。如果Ku70和Ku80不相救,細胞會引發一個自滅機制,因而死亡。具體的情況:一旦細胞的DNA變質,例如斷了兩截,一個叫BAX的蛋白質會在細胞內的粒線體(火爐)身上鑽一個洞,令粒線體內的火種(細胞色素C)漏到細胞核,「一把火」把細胞核內的遺傳物質燒熔殆盡。在這方面,Ku在幫手修補DNA的同時,會抑制BAX,防止細胞「一時想唔開」而自殺。有一種癌叫 Neuroblastoma,多在兒童身體中出現,患上了九死一生;一組日本北海道大學的學者發現,可以藉着刺激一個叫SIRT1的蛋白質,令這些癌細胞內的Ku和BAX脫鈎,從而令癌細胞集體自殺(Proc. Natl. Acad. Sci. USA, Vol.105, pp.15599-15604)。什麼東西能刺激SIRT1?答案是葡萄中的Resveratrol。但須注意,要吃的話,須服食正牌的葡萄子素(冒牌貨叫花青素Anthocyanin),純度要高,還有,須與五羥黃酮(Quercetin,來自洋葱)同服,否則徒勞無功,因為肝會擺烏龍,把 Resveratrol當作毒排出體外。

葡萄子素
聽說在阿拉伯國家,偷東西的人一旦定罪,受的刑罰是斬手。這當然是太嚴厲了,何況縱是失去雙手,也並非沒有能力去偷。以「制止犯罪者再次干犯同樣罪行」的目標而言,宮刑顯然有效得多。男人若失去性器官,可沒有能力犯強姦罪。

藥廠發展新藥,目的是要針對肇事的兇徒,例如病毒、細菌,把它們趕盡殺絕,不得姑息。若要能劍及屨及,必須從一些生物指標找線索或靈感。歷史上最好的一類藥,是為抗生素Antibiotics,因為憑它的機制,可以有專攻的目標。但有一利必有一弊,有些細菌,對某些抗生素能產生抗藥性,原因也可能是目標太明顯了,令抗生素要攻擊者能「側側膊」避過。因此,一個好藥必須具備選擇性(Selectivity)的能力,同時要能針對目標物最易受重傷的一環,一舉置之於死地。

舉一個例。很多抗癌的化療藥,的確有能力干擾癌細胞增生的機制,破壞癌細胞內最重要的遺傳物質DNA。可是,化療藥並沒有好的「選擇性」能力,大小通吃,好歹不分,殃及池魚,把骨髓內的正常細胞也一併殺死,令病人失去製造紅血球、白血球的能力。不過,現在可能有一個方法,能選擇性地殺死癌細胞。

細胞既有自然死亡的程序,也能自滅(Apoptosis)。自滅是細胞內的一個「既定的」機制,在某些情況下,要細胞自殺,自動消滅自己。正常的細胞自滅,例如胎兒在成長中,手中部分細胞自動消失,令五隻手指能成形,是必須有的身體機能之一。這機能若太亢進,可造成體內新陳代謝紊亂;太遲鈍,則不能掃走一些「作反」的細胞,後果之一,是產生惡性腫瘤,也就是癌。

在1993年,哈佛大學有一位博士後(Post-Doctoral)研究員,名叫袁鈞英,發現了一個令細胞自滅的酶,稱之為Caspase-1(C-1)。這開始了自滅酶(Caspase)的熱門研究。現在學者已把整個引發細胞自滅的機制找出來,其中涉及多個自滅酶,次序是C-8、C-1、C-3。這個C-3可能便是一個抗癌的關鍵。

原來,癌細胞拚命在增生時,為了要衝過細胞控制增生的一個關卡(叫G2/M Check Point),需要用到C-3。但由於C-3可以引起細胞自滅,癌細胞會很小心,先只是累積C-3的前身(叫Pro-C-3),到需要時,才把一點點夠用的Pro-C-3,轉成C-3(Apoptosis Vol.11 pp.765-771;Nature Chem. Biol. Vol.2 pp.543-550)。因此,癌細胞內已有的Pro-C-3,若能將其「引爆」,便可以在不影響正常細胞下,引致癌細胞自滅。什麼東西可以令Pro-C-3轉為C-3?葡萄子素(Resveratrol)是也。

協同補健
在公司與公司之間的收購合併活動中,經常提到的一個名詞是「協同效應」(Synergy),意思是指兩者併在一起之後,會有額外的好處;若用通俗概括的方式形容,乃是「一加一等於三」。在營商及股市而言,我屬門外漢,但對「協同效應」這詞,我卻覺得有些時候被濫用了,言過其實,令人產生「美麗的誤會」。例如兩家巴士公司合併,好處是管理集中,人手精簡,重疊的支出可以省了,也不須在競爭方面耗費資源;但這只是「管家」式的「打算盤」開源節流而已。再進一步,置地收購牛奶公司,把後者的土地,由養牛改為建房子,將公司利潤大大提高,也只屬互補長短;這裏的「協同」之功,與土地儲備量同進退。我心目中最能產生協同效應的例子,乃是四會合併;結果把香港股票市場提升到國際地位,與紐約、倫敦鼎足而立,遠遠超逾了「開源節流」和「取長補短」的境界。
我經常提及葡萄中的寶物白藜蘆醇(Resveratrol),我稱之為葡提子素。很多人都知道,若將它與五羥黃酮(Quercetin)一起服用,對身體更有益;這可說是協同效應。具體做法是一杯紅酒加一碗洋葱湯,也有人用紅酒浸洋葱。
五羥黃酮是補健食品Dietary Supplement之一,可以在市面上買得到膠囊製品。若要發揮更大功效,可加入橙汁內服用。橙汁中的Naringenin與五羥黃酮,是一個「一加一等於三」的美妙配合,能大大抑制乳癌細胞增生(Nutr. Cancer, Vol. 26, pp.167-181)。那麼,可否改用西柚汁Grapefruit?千萬不可。曾有科學家在五萬多位更年期女士的身上,做過一個測試,叫她們每天吃四分之一個西柚,結果發覺西柚汁能干擾肝的一個排毒生物催化劑(叫CYP 3A4),可令雌激素的作用增高,從而增加患乳癌的機率(Br. J. Cancer, Vol. 97, pp.440-445)。
五羥黃酮的好處與綠茶素各有千秋。若患有濕疹或哮喘,五羥黃酮能藉着干擾一個組胺酸脫羧酶(Histidine Decarboxylase),大大降低引發濕疹╱哮喘的組織胺(Neuroimmuno Modulation, Vol. 13, pp.179-186)。綠茶素則能黏在肥大細胞(Mast Cell)表面,阻止一些(可以導致敏感的)E型抗體,觸發肥大細胞去分泌組織胺。所以要控制濕疹或哮喘,大可服用一個五羥黃酮和綠茶素的複方。
現在不少人都知道須補健,但到底怎樣做才真的能對身體有好處,卻不甚了了。我早幾天曾提過「適量」補健,也談到「輔承」補健(輔助食物及藥物之不足),今天說的是「協同」補健,以複方提升效益。我尚有其他五大重點,包括「自然補健」、「精準補健」、「互動補健」、「平民補健」、「開心補健」,往後再詳述。

文章來源:Dr. George Ku

2008年10月28日 星期二

綠茶素的好處 - Dr George Ku - 2008年10月28日

有眼不識好東西 - Dr George Ku - 2008年10月28日


我已年過半百,在年輕人的眼中,我已屬「上一代」,因此應有代溝。有「溝」不足為忤,例如現在流行的髮型,我不覺得有什麼好看,頭髮根根豎起,像是剛從床上爬起來,但人家喜歡,犯不到我,與我無關;更何況「悅目」本無一定的準則。不過,有不少從前的好東西,因為種種原因,時移世易,先則失寵,後則不常見,頗覺可惜。例如毛衣,在物資匱乏的年代,人人珍而重之,質地較好者例如用羊絨做的(香港人叫茄士咩),更是小心處理,冬季一過,包起來好好收藏,明年拿出來再穿,不但溫暖,亦顯然念舊,物盡其用。現在物質供應充裕,一般人再無珍惜之心,追求者乃是時尚,舊衣服穿得次數多了,每每有「寒酸」的顧忌。帶來的後果之一,是注重款式更甚於品質。在百貨商店中,再不見有樸實無華羊絨毛衣的專櫃。這種代溝,我卻是耿耿於懷的。

唯靈兄撰文談食,經常提起一些出品一絲不苟的老字號,可惜,只靠口碑,不會做宣傳,加上與年輕人追求新潮的趨向不合拍,終於難逃淘汰的命運。反觀一些例如迴轉壽司的食店,質素難望其項背,卻門外大排長龍,能不唏噓?在健康食品而言,最令我感慨者乃是綠茶素(Epi-Gallo-Catechin-Gallate, EGCG)。我從前曾在香港兩大健康及衞生產品連鎖店中,見過綠茶素片。在種種原因下,最近這兩大連鎖店已再沒有出售綠茶類的補健產品。原因之一,可能是很多人以為每天飲幾杯綠茶便有足夠的綠茶素,因此不須服用;另一原因,可能在於一些誤解,以為綠茶中含多量的鹼性物(例如咖啡因〔Caffeine〕),故此從茶中取得之「素」,不宜多吃;廣東人更有傳統的中藥藥理思想,可能感覺這東西太「涼」了,不適宜「寒」底的人。這反映消費者一般都不知道綠茶素片並不等於綠茶;出售健康食品的商人,在商言商,既然沒有生意經,不妨將它從貨架上拿走。另一方面,藥廠也對這類貨品沒有興趣,因為凡是天然物質都不能取得專利權。在沒有專利保護下,藥廠不能「獨市」,何必掘井供大眾一起從中取水喝?

美國UCLA大學學者曾找來志願者參與試驗,一部分人服綠茶,另一部分人服用綠茶素;之後,比較各人血液中的EGCG分量。結果發現,即使吃進口中的EGCG分量相同,進入體內後,兩組參試者血液中的EGCG百分比,竟有很大的差別。這是因為一杯綠茶中的成分主要是水,EGCG分布其中,濃度太低,吸收也隨着偏低(Am. J. Clin. Nutr., Vol.80, pp.1558-1564)。所以,即使每天喝二十杯綠茶,血液中所得的EGCG,也不及一片綠茶素片帶來的多。至於鹼,由於綠茶素片來自去了咖啡因(De-caffeinated)的綠茶,鹼的含量一定比綠茶中的少。

綠茶素的好處
中國最後一次的科舉考試,是在1904年舉行的,此後八股文作為法定考試文體的地位,也就廢除了,學子再不須在這格式上面下工夫。寫文章如果有體裁上的限制,不免會因為形式而犧牲內容;在這方面考慮,八股文自是不可取。若單單只看其中「表達」的安排,並非完全沒有道理。例如文章一開始,先有「破題」,將題目字面意義破釋,也就是告訴看文章的人「我這篇文章的主題內容是什麼」,這是十分重要的。不然人家看了老半天,不知作者想說什麼,更無法領略其論點。論述性質的文章與消閒小說不一樣,從讀者的角度來看,愈早知道文章內容扼要,愈能明白作者要說的話。因此有人提倡,在看一本書之前先看一遍目錄,來一個「鳥瞰」,正如剛進入迪士尼樂園尚未開始遊覽,不妨先研究樂園的平面圖,知道每一部分的設施,如何分布,然後才開步走,逐一作更深入的探討。

昨天談綠茶素(Epi-Gallo-Catechin-Gallate, EGCG),其中有發掘不完的優點。今天做一個鳥瞰,看看綠茶素的多種好處,這像看一本書的目錄,若要得到進一步的詳情,可根據每一條註腳再深入了解。 EGCG可以殺死多樣性骨髓癌的癌細胞,對正常的細胞則沒有影響(Blood Vol.108, pp.2804-2810),它對其他血癌也有殺傷力,包括急性白血球血癌(Life Sci., Vol.60, pp.135-142)、急性骨髓血癌(Haematologica, Vol.90, pp.317-325)。在其他身體器官而言,EGCG能促使多種癌細胞自滅,例如乳癌(Cancer Biol. Ther., Vol.6, pp.1938-1943);胰臟癌(Front. Biosci., Vol.12, pp. 5039-5051);肝癌(J. Hepatol., Vol.44, pp.1074-1082);大腸癌(Cancer Lett., Vol.247, pp.115-121);肺癌(Biochem.Biophys.Res.Commun.,Vol.360,pp.233-237);腎癌(Biofactors, Vol.20, pp.235-249);頭頸癌(Anticancer Res., Vol.25, pp.63-67);黑色素癌(Int. J. Cancer, Vol.114, pp.513-521)及腦癌(Brain Res., Vol.1071, pp.1-9)。對於消化系統,EGCG能殺死寄居在胃的幽門螺旋菌(Curr. Microbiol., Vol.47, pp244-249)、防止肝硬化(Lab. Invest., Vol.86, pp.697-709)、抑制腸瘜肉(Mutat. Res., Vol.506, pp.121-127)。在心血管系統方面,它能防止高血壓及心臟肥大(J. Cardiovasc. Pharmacol., Vol.43, pp.200-208)。EGCG能減低IgE引起的敏感反應,包括鼻敏感、哮喘和濕疹(J. Agric. Food Chem., Vol. 50, pp.5729-5734)。在骨骼的層面,它可以減少破骨細胞(Biochem. Biophys. Res. Commun., Vol. 292, pp.94-101)。還有,它能紓緩類風濕關節炎(Proc. Natl. Acad. Sci. USA, Vol.105, pp.14692),又能減低乙型澱粉樣蛋白引起的老人癡呆徵狀(Brain Res., Vol.1214, pp.177-187)。

2008年10月10日 星期五

Glow2Thione Skin Whitening and Age Defying Supplement





Have you ever longed for that celebrity skin? 
Do you have a dark complexion and uneven skin tone
Do you want to lighten your skin, improve your health and defy age?

This is the New Age of Advanced Skin Science!

Although beauty maybe in the eyes of the beholder, it does not mean that what they see through is the same as what we feel from within.
We live in a society where we are being judged by our appearance yet attraction also comes from one’s perception of physical beauty. Let’s admit it, we all want to look good and we want people to appreciate it. Therefore, it is essential that we take utmost care of our bodies, our skin.

The largest organ of the body, the skin is the first line of defense against disease. Unlike other organs, our skin surrounds and protects us. And when something goes wrong, the results are readily apparent. A self-repairing organ, the skin is constantly affected by both internal body conditions and the environment. Aging and disease can cause various signs and symptoms, including dryness, loss of elasticity and darkness.
With the new age of advance skin science, you can now have a celebrity skin and put an end to DARKness!
Glow2Thione™ Skin Whitening and Age Defying Supplement, with revolutionary L-glutathione: the Body’s Master Antioxidant, Detoxifier and Tyrosinase Inhibitor.
Now you can easily achieve the complexion you have always wanted 


It works by targeting unstable molecules called free-radicals, and oxidants which causes the cells in our body to be damaged. By eliminating these harsh elements, over-all health will be revitalized, the process of aging will slow down and appearance of the skin will be radiantly glowing. Glow2Thione’s L-glutathione inhibits and blocks Tyrosinase, the enzyme responsible for the production of dark melanin pigments. Continuous and consistent supplementation will result into gradual skin lightening until you reach the skin tone you desire. 
Glow2Thione™ contains the most powerful antioxidants which works synergistically to create what Scientists call as the Antioxidant Cycling. It is a process in which antioxidants work together to extend each others’ lives and make each other more powerful. That’s the reason why Glow2Thione™ is very potent and effective in bringing results.
Glow2Thione™ doesn't only bring beauty but also the gift of wellness. It is evident in most scientific studies that these powerful antioxidants like L-glutathione, Vitamin C, Alpha Lipoic Acid and Grape Seed Extract aids in boosting the body's immune system and fights certain types of Cancer and other Neurodegenerative diseases.

Your health is very important to us and so we guarantee you that Glow2Thione only uses the best ingredients and manufactured in a facility of standard and excellence. Our product's authenticity and purity is proven after it passed the Laboratory Analysis or the Assay.



About Glow2Thione
We have always believed that no matter how fair your skin is nor how good-looking you are, if it only exists superficially, the true essence of beauty is still far fetched. Many people are unhappy with their lives for certain reasons and one of them is because they do not like what they see in the mirror. Appearance truly is important for most people since it gives esteem and confidence to go on with their lives. Skin color is one of the biggest issues most people wants to resolve. Since it is the largest organ of the body, it cannot be easily hidden nor concealed and how people perceives you has something to do with the way you look, and in this case your skin, therefore having a fair and flawless skin has been essential nowadays. We do not say that only people with lighter complexion are beautiful and darker ones aren't, we believe all is beautiful in their own right whatever their skin color is, however, we, as individuals have the right to choose and the freewill to decide what's best for us. If you feel that having a lighter complexion will make you happy, complete and boosts your confidence, then you have all the right to embrace it. It is the new age and science has again brought us another solution in achieving a brand new skin....the new you. 

SkiNova aka SUPER WHITENING PILLS has been distributing skin whitening supplements on the internet since 2004 catering to people of diverse ethnicities who want to lighten their complexion. Based in the Philippines, our products are directly manufactured and imported in the USA and distributed from Manila  to be sold worldwide. We started in the business having a few clients, mainly our friends which became our first living testimonials. Now on our 7th year, we will strive harder to serve you better.

Our goal is to bring you superior quality when it comes to the supplements that we sell. We do not settle for any product just for the sake of profit but we make sure it is worth buying and using. We only sell and distribute supplements after we have tested and proven its efficacy and authenticity.

Since our product is an oral kind of skin lightener we have done studies and research to make sure that it is safe and will not compromise the user's health even in the long term use.

We believe that it is a paramount consideration that what we claim and tell people is scientifically true, that whatever comes from us, was derived from a reputable source and that its information is accurate.

Moreover, we value our customer's feedbacks and comments. It is an integral part which serves as our guideline whenever we do things. You are the reason why we are existing and so it is only rightful to always hear your voice and for us to listen, evaluate, advise and improve.

Finally, the most important thing we would like to ensure is safetiness. Having a a beautiful skin is senseless if you do not have a healthy body nor you possess an illness. We always make you sure that we do not sell anything unless it is certifiably safe, genuine and fresh from the manufacturer. It has always been our job to know first the customer's condition before advising him/her to use our product. Whenever there are certain cases related to health and disease, we forcefully advise our customers to seek for an opinion from a professional health care practitioner.




How It Works

This is the inner layer of the skin called Dermis and the outer surface which is visible in our eyes is the Epidermis. The primary determinant of variability in human skin color is the Melanin and Melanocyte is a cell that synthesizes it. L-glutathione,Glow2Thione's  main component, starts the lightening process in the Dermis working its way out to the surface.


This is the point where the metabolic pathway of Melanin begins. As you see in the diagram GSH(Reduced Glutathione) intervenes the metabolism. There are certain kinds of compounds that inhibits the Tyrosinase Activity and L-glutathione is one of them.


The oral use of Reduced Glutathione(L-glutathione) inhibits the Tyrosinase Activity. Once it has been inhibited, the metabolic pathway then reverses its course going to the synthesis of light pigmented melanin called Phaeomelanin instead of synthesizing dark pigmented melanin called Eumelanin. The cycle continously flow as long as the presence of L-glutathione co-exist in the metabolic pathway of melanin. Finally, light skin will reveal to the surface gradually changing your complexion.





Ingredients
Glutathione - "Glutathione is the body’s master antioxidant and best kept secret to maintaining health." - Theodore Hersh, M.D., Harvard graduate, Professor of Medicine, Emeritus, Emory University.

Glutathione is a small molecule made up of three amino acids, which exists in almost every cell of the body. The presence of Glutathione is required to maintain the normal function of the immune system. Glutathione is involved in detoxification, it binds to toxins, such as heavy metals, solvents, and pesticides, and transforms them into a form that can be excreted in urine or bile. Glutathione is also an important antioxidant. In preliminary research, Glutathione intake has been associated with protection against some forms of cancer, higher Glutathione levels have also been associated with good health in older adults.

Glutathione neutralizes the harmful effects of free radicals. Glutathione helps to protect the mitochondria (the cell's energy production unit) and the cell membrane. Glutathione also helps to protect against DNA damage. Glutathione are necessary for supporting the immune system, glutathione is required for replication of the lymphocyte immune cells.

Studies show that Glutathione acts as a Tyrosinase Inhibitor. Tyrosinase is an enzyme that catalyzes the biosynthesis of melanin which is the culprit for skin darkening.
Vitamin C - (ascorbic acid) is a water-soluble vitamin, which is necessary in the body to form collagen in bones, cartilage, muscle, and blood vessels, and aids in the absorption of iron. Dietary sources of vitamin C include fruits and vegetables, particularly citrus fruits such as oranges.

Many uses for vitamin C have been proposed, but few have been conclusively demonstrated as being beneficial in scientific studies. In particular, research in asthma, cancer, and diabetes remain inconclusive, while no benefits have been found in the prevention of cataracts or heart disease.

Vitamin C effects pigmentation in two ways: The creation of melanin is an oxidative process and so a powerful antioxidant like vitamin C could counteract the oxidative process required to create melanin. Ascorbic acid also has a role to play as an inhibitor Tyrosinase. Tyrosinase is essential for the formation of melanin, so if it is inhibited then the action of pigmentation is reduced.

Alpha Lipoic Acid - helps break down sugars so that energy can be produced from them through cellular respiration. In addition, recent research has discovered that Alpha Lipoic Acid plays a truly central role in antioxidant defense. It is an extraordinarily broad spectrum antioxidant able to quench a wide range of free radicals in both aqueous (water) and lipid (fat) domains. Moreover, it has the remarkable ability to recycle several other important antioxidants including vitamins C and E, glutathione and coenzyme Q10, as well as itself! For these reasons, alpha lipoic acid has been called the universal antioxidant.

In addition to serving as the hub of the body's antioxidant network, Lipoic Acid is the only antioxidant that can boost the level of intracellular Glutathione. Besides being the body's primary water-soluble antioxidant and a major detoxification agent, glutathione is absolutely essential for the functioning of the immune system. Scientists have known for a decade that maintaining a high cellular level of glutathione is critical for life and crucial for health.

In a number of experimental and clinical studies, Lipoic acid has now been shown to be useful in the treatment of such conditions as diabetes, ischemia-reperfusion damage, neurodegeneration, heavy-metal poisoning, radiation damage and HIV infection and may offer significant protection against stroke, heart disease and cataracts (Packer L et al., 1995). It is likely that much of the beneficial effect of Lipoic Acid may be attributed to its ability to increase levels of Glutathione, chelate metals (such as iron and copper), quench diverse free radicals, and recycle antioxidants.

Grape Seed Extract - is a natural plant constituent (bioflavonoid) which strengthens and protects living tissue. The OPC components in Grape Seed Extract are 50 times stronger than Vitamin E and 20 times stronger than Vitamin C. Grape Seed Extract is an antiallergenic, antihistamine, anti-inflammatory, and antioxidant. It strengthens blood vessels, improves skin, and aids in circulation.

Grape Seed Extract contains natural bioflavonoids called proanthocyanidins which help strengthen and protect cell membranes from oxidative damage caused by free radicals. Catechins, components of Grape Seed Extract, help reduce allergic responses by inhibiting enzymes involved in the formation of histamine (helping reduce symptoms of allergies and excess histamine in the stomach which may lead to further stomach problems).

Grape Seed Extract provides cardiovascular protection by preventing oxidation of lipoproteins (LDL), making them less likely to stick to blood-vessel walls. It also makes the linings of the arteries more resistant to damage and helps control excessive clotting. GSE strengthens the capillaries ensuring a good supply of oxygen and nutrients to the brain and throughout the body. It also affects enzymes that influence blood-fluid balances and therefore may be helpful in lowering blood pressure. the body. It also affects enzymes that influence blood-fluid balances and therefore may be helpful in lowering blood pressure.




Skin Tone Chart
You need not suffer and be unhappy just because you weren't blessed with the the complexion you desire. You can now achieve it while promoting better health safely. Use this page to know the skin tone type and shade you possess. It will help you to have an idea about the results you will achieving. Match your skin tone from the chart below. Each square represents a shade. If you're skin tone is #15, then 3 shades lighter will be #12 - this is very possible and realistic. You can achieve by as much as 5-6 shades lighter in long term usage of Glow2Thione. Remember, that result varies and it is essential that you consistently and continuously stick to the program to achieve great results. 




Questions

1. How long before I really see the results?
As we have been telling to people “Don’t expect a beauty miracle”, it takes time to grow and in this case it also takes time to have a lighter skin. Initial changes need not to be skin lightening immediately. Initial change can be smoothening of the skin or if you suffer from acne, it will gradually clear up in a matter of weeks. These are manifestations that Glutathione is starting to take it's course. Skin lightening generally begins in 2-4 months of usage. Since result varies from user to user, it is most likely that some users will be able see results as early as a month or two, others may need longer time.
2. How white can I get?
Initial phase of the program can give as much 1-3 shades lighter. Long term usage can lighten your skin by as much as 5-6 shades lighter or more. It will depend on how the supplement reacts to your body. Please refer to our skin tone chart

3. Will I look like Michael Jackson?
Definitely not. Results are gradual and natural. Its not dramatic nor drastic after just taking it in a few weeks. Also, it would be impossible to be extremely white since the skin has it's limits as to how light it can get.

4. Why is it that some people tend to see results earlier compared to other users?
For the simple reason that people have different metabolism and body chemistry, weight is also a factor. The fact that some people see results early means that their bodies have absorbed the components well. There are alot of factors (stress, lifestyle, diet, etc.) that can affect the results and so you should take that into consideration in taking Glow2Thione.

5. What is the recommended dosage in able to achieve visible results?
Standard dosage is 3 capsules a day. The maximum you can take is 4 capsules a day. You also need to take additional vitamin c when taking Glow2Thione. For every Glow2Thione capsule you take, you need 1000mg additional vitamin c in tablet form. If your skin is already light and you only want to even out your complexion, then 2 capsules a day is sufficient. Once you have already achieved the skin tone you desire, you may take 1 capsule a day as maintenance dose.

6. Is it safe to take high dosage of Glow2Thione whitening pills everyday?
It is very safe. Taking high dose of L-glutathione from these whitening pills are needed in order for it to work. Did you know that primarily Glutathione is given at a daily dose of 5000mg to certain patients? L-Glutathione and other components (Vitamin C, Alpha Lipoic Acid and Grapeseed Extract) are all supplements; they are actually good for the body. Moreover, they are water-soluble which just means that if there’s anything in excess, it will be just excreted through urine or bile.

7. Do I really need to take additional Vitamin C when taking this supplement? Why is it important?
Vitamin C is essential when taking these supplements because it helps Glutathione to stay in its usable form when it enters the body. It is most likely that Glutathione will be oxidized when taken, and so Vitamin C's role is to reverse the oxidation process making Glutathione remain in its reduced form suitable to achieve it's skin lightening property.

Vitamin C should be double the dosage of L-glutathione. And so, for every Glow2Thione capsule you take, you need additional 1000mg of Vitamin C.

“Glutathione is too large a molecule to effectively pass through the intestine into cells, so supplementing with glutathione alone is not helpful. But when taken with Vitamin C, which protects it from oxidative damage, Glutathione becomes effective.”
Monika Klein, C.N.,
Malibu, Cali

“Some people with darker skin tone report that taking Glutathione capsules along with vitamin C for three to six months or more actually lightens the color of their skin.”
website © 2004 www.Gluta.com

8. Why is Alpha Lipoic Acid important? What are its effects?
Alpha Lipoic Acid is another powerful anti-oxidant which has anti-aging properties and it is needed since it helps the body manufacture it's natural-occurring Glutathione, thus enhancing the full potential of skin lightening process.

Again, let’s take it from the experts:
“Take alpha-lipoic acid, an antioxidant that turns up the production of glutathione, your liver's head janitor. Glutathione latches on to toxic gunk and makes it water-soluble enough to be flushed out through your kidneys. For maximum liver scrubbing, take a 50 milligram alpha-lipoic acid tablet (sold in drugstores) twice a day.”
By Zachary Veilleux
Men’s Health Abc News

“lipoic acid is the only antioxidant that can boost the level of intracellular glutathione”
“Moreover, it has the remarkable ability to recycle several other important antioxidants including vitamins C and E, glutathione and coenzyme Q10, as well as itself!”
LE Magazine December 1999
STAYING YOUNG FOREVER
Karin Granstrom Jordan, M.D Ph.D.

9. What makes Glow2Thione different compared to other whitening pill?
What makes it different and powerful is the synergy between its various components. They are not only powerful individually, but also work together in what is known as antioxidant cycling. Antioxidant cycling is the term that describes how antioxidants work together to extend each others’ lives and make each other more powerful. And that’s also the reason why it is so effective to really whiten the skin in it’s long term use.

10. Is it just ok to continue using some whitening creams or gels while using it?
Yes. There is no problem if you still continue using your regular skin care regimen (creams, lotions) but once the skin lightening process has started you might not need to buy any creams to apply to your skin, the whitening pill itself alone is ok and you will see it for yourself.

11. How does the whitening process starts? Can it give me an equal skin tone all over?
The reason why are skin becomes white in using this whitening pill is because it reverses the dark melanin pigments turning to a light pigments and inhibits the enzyme Tyrosinase which catalyzes the production of melanin. Less melanin, a whiter skin. L-glutathione’s whitening process starts inside the skin (dermal layer) going outside (epidermal layer), that’s the reason why it takes time to be able to see initial change in your skin tone. The lightening process goes head to foot meaning that you will have an even skin tone throughout your body.

12. How can I consider this pill? It is a drug, vitamin or supplement? Is it just ok to take it with all my other medications and vitamins? Is there anything to avoid when taking this whitening pill?
L-Glutathione and its components (Vitamin C, ALA and Grape Seed Extract) can be considered as food/dietary supplement, they are also called powerful antioxidants. It is not a drug and so there are no known contradictions and precautions to be taken into consideration. However, L-Glutathione shouldn’t be taken by people taking anti-psychotic drug and chemotherapeutic drug. You should also not take it if you just recently undergone an operation or an organ transplant. Avoid drinking alcoholic beverages, the presence of alcohol in the stomach is one reason for your body to not fully absorb the whitening pill.

13. Once I have achieved the skin tone I want, is it just ok to stop taking the pills or should I continue it?
It is advisable to still continue taking the pills even though you have achieved the skin tone you want. Take 1 capsule a day as maintenance. We know that L-Glutathione is very good to our health and so taking it in long term will not only make us lighter but also it will promote better health.

14. Are the whitening effects of these whitening pills permanent? Will my skin tone go back to its original color once I stop using it?
Its whitening effects are permanent only if you will maintain (by avoiding exposure to sunlight) and take care of your skin. You won’t go back to your original skin color even if you stop taking these pills, however, there is a tendency for you to tan or darken your skin if you expose yourself to the sun and other harsh elements.

16. What If I am taking the pills but most of the time I am exposed to the sun, what will I do?
Use sunblock or sunscreen lotion that has an SPF of 45-60. It will protect you from the harmful effects of the sun. But of course its still best to avoid sun exposure if you can since there is no guarantee that your sunblock can totally protect your skin.

17. Is this whitening pill (L-Glutathione) safe in the liver?
Let’s hear what a renowned doctor says about it:
“The level of glutathione in the liver is critically linked to the liver’s ability to detoxify. The higher the glutathione content, the greater the liver’s capacity to detoxify harmful chemicals. Typically, when we are exposed to chemicals to which can damage the liver including alcohol, the concentration of glutathione in the liver is substantially reduced. This reduction makes the liver susceptible to damage.”
Nature’s Potent Liver Remedy
Dr. Murray

18. Is there any untoward side-effect from the long-term use of these whitening pills?
There are no known side effects or interactions known with oral administration of L-Glutathione even in its prolonged use. The side-effect, we all know, is the skin lightening itself.

19. Why do you say that this whitening pill is really effective? Is there any assurance for that?
Before using this whitening pill we have already tried and tested other brands which only gave us disappointment. The results took very long to see and the worst part is they have been the cause for my some acne breakouts and gaining of weight. That’s the time when we went on research and found out this whitening pill which we are now selling. The reason why we am very confident with this product is because we are the living proof that it really does work and also does wonders. In 3 weeks time we have experienced acne clearing and felt very radiant for the reason that it cleanses the body too. We, together with thousands of users have seen results and not disappointment. Now we recommend it to everyone to experience its power to really whiten the skin in the shortest period of time, thus, promoting better health. That’s what we call assurance.

20. I am in a hurry to see the results and also I want to be slim while I am taking the pills, is it ok to take slimming pills or other products?
Like I have mentioned before the whitening pill (L-Glutathione) is considered as a supplement and therefore safe to be taken with other medications, vitamins or supplements. However, we recommend people using whitening pills to just use slimming creams or whitening creams so as letting the whitening pill work solely in your body. If you are in a hurry and at the same want to be slim, I recommend you to use natural kind of weight reducing supplements such as green tea extract.

21. Is it safe to be taken even by young teens who wants to be fair?
L-glutathione is considered as a supplement. It is very safe to use and will not cause any harmful effects to the user even at a young age, however, we would recommend that the user should be at least 18 years of age. We want to make sure that the user is mature and responsible enough when taking the program. It's important to us that he/she is aware and understands how to take the regimen correctly in able to achieve results and not waste time and money.

22. Is it true from what I’ve heard that whitening of the hair is a side-effect in taking these whitening pills (L-glutathione)?
It is not true. The side effect in taking L-glutathione is the lightening of the skin already. There is no such thing as the “side effect of a side effect”, it doesn’t make sense. Moreover, we have also heard about that and the reason why they say some of there hair turned white might be because they have used a formulation containing Tyrostat (L Tyrosine). There have been reports about that.

23. Is it better to take the whitening pill with an empty stomach or should I eat my meal first before taking it?
Based on our studies, it’s much better to take the whitening pills with an empty stomach. Your body will most likely absorb the highest possible amount because it is only concentrated in just one substance unlike if have eaten already or had intake something, there might be a tendency for your body not to fully absorb it because there are already substances present in your stomach that might hinder the process of absorption.

24. Can pregnant or nursing women take the product?
No. Glutathione play an important role in the development and growth of the fetus, maintenance of a healthy pregnancy and even before pregnancy, in fertility and conception. It also protects both mother and fetus from the damaging effects of free radicals and oxidative stress. However, Alpha Lipoic Acid is not recommended to pregnant women. Therefore, pregnant and even nursing women who wishes to use the product must wait until they have already given birth or have already finished their nursing period.

25. Does the product work on people with certain illness?
No. People who have Thyroid-related illness(Hypo/Hyperthyroidism) will most likely not to benefit from the skin lightening effects of Glutathione. Other than that, the product works with most people.

26. Do you offer money-back guarantee?
No. Even if we are highly positive about the product's effectivity and safetiness, we cannot offer a money-back guarantee since there are factors that can be a reason for the product not to work and we have no control over that. An example would be a user who exposes him or herself to the sun very often or a user who is not taking the right dosage as advised. It would be hard for both parties to prove whether the product did really work or not. There is no exact science to measure whether the product will work, has worked and will not work for you.

27. Is it FDA approved?
L-Glutathione is considered as a dietary supplement and it is also categorized as GRAS(generally recognized as safe) by the FDA . It doesn't necessarily require a FDA approval since only manufactured drugs, foods, medical devices and cosmetics undergo this kind approval.

28. Is it BFAD registered?
Yes, Glow2Thione is registered from the Bureau of Food and Drugs with registration number FR-82502.
29. How can you guarantee that this product is safe, authentic and effective?
Glow2Thione passed the laboratory analysis or the ASSAY done a duly accredited laboratory by the Health Bureau. We have a great track record as an online distributor for almost 4 years now. Lastly, our unsolicited customer feedbacks and reviews only assures that truly our product is indeed safe, genuine and effective.

30. How can I become an online distributor, regional dealer or buy in bulk?
Please contact us and tell us your profile as well as your target market and quantity.




All About the Skin
Many people suffer from various discolorations of the skin as a result of locally increased skin pigment production. The pigment in the skin responsible is melanin, which also helps to protect us from the harmful effects of strong sunlight etc.

A variety of different influences, including the environment around us, or some internal factor, can cause some parts of the skin to produce more melanin. This results in hyper (excessive) pigmented skin spots or areas, such as: pregnancy mask, (often seen post pregnancy on the jaw line and other facial areas), liver-spots, age-spots and even hyper pigmentation after local skin damage, due to such things as acne or burns.e levels of Glutathione, chelate metals (such as iron and copper), quench diverse free radicals, and recycle antioxidants. 

Pigment Types

Skin colour is normally the result of the combination of 4 pigments:

In the epidermis (upper layer of the skin)
Melanin produced in the skin (brown-maroon);
Carotenoids which are taken into the skin from external sources (yellow)
In the dermis (lower layer of the skin)
Red blood cells containing oxygenated red pigment (haemoglobin) in the capillaries (small arteries)
Red Blood cells containing de-oxygenated blue pigment (haemoglobin) in the venules (small veins)
Melanin
Among these pigments, melanin, which made in cells in the lower layer of the skin called melanocytes, is the main pigment causing differences in skin colour.

The definition of melanin is difficult and the exact chemical structures have not yet been fully worked out. However, the melanin in humans is divided into two main groups:

Eumelanin - Brown/black pigment, prevalent in persons with dark complexions and hair

Pheomelanin - yellow-reddish pigment, prevalent in persons with fair complexions, freckles and red hair

Manufacture of Melanin
The special melanin producing cells called melanocytes are located in the lower region of the epidermis, (the upper layer of the skin). These are cells equipped with special arm like projections (dendrites), which project both sideways and upwards towards other cells called keratinocytes.
In the fluid (cytoplasm) inside these melanocytes are special structures (organelles) called "melanosomes", which store the melanin as it is produced (melanin packets).

The melanocytes also make the enzyme called tyrosinase, which is taken up into the melanosomes (melanin packets). This enzyme is needed to make melanin.

Once the melanin is made in the melanosomes (melanin packets), it is transferred to the keratinocytes by a special mechanism: the keratinocytes take in (surround) the special arm like projections on the melanocytes, which are full of melanin containing melanosomes.

This is done by combining the cell membranes between the melanocyte projection and the keratinocyte, so that the melanin is transferred into the keratinocytes.

Each epidermal melanocyte transfers melanin to around 36 nearby keratinocytes, Together they constitute a biological unit called melanin-epidermal unit

Exposure to ultraviolet rays (in sunlight) accelerates the formation and passage of the melanosomes to the keratinocytes, bringing about sun tanning.

These keratinocytes containing melanin grow and develop and slowly move up towards the surface of the epidermis. The melanin is gradually broken down by other enzymes and as the dead surface layer of the skin sloughs away through normal wear and tear any melanin pigment left is also lost. So, pigmentation is not a static process but one undergoing constant renewal.

The differences in pigmentation of the various skin types are not due to a different number of melanocytes but in the way in which melanin is built up. The melanosomes (melanin packets) in black skin are larger (longer and wider) and when they are transferred to the keratinocytes they remain independent of each other i.e. they don't group together as do the melanin packets in white skin, which are also smaller.

Biochemistry of Melanogenesis 
Both the eumelanins and pheomelanins are made from the amino acid tyrosine. 
The process starts with tyrosine, which goes through a number of chemical reactions creating a variety of intermediate chemicals before it eventually becomes melanin. This entire process can be divided into two important phases:
The first few stages are controlled by an enzyme called tyrosinase and is called the Enzyme Phase The second stage consists of rapid changes to the molecule through reactions involving oxygen until you finally end up with melanin. This is called the 'Non Enzymatic Phase'.

Factors Influencing Melanin Production 
Our colouration can vary on different areas of the body. There are three main factors which determine the level of melanin production and consequently our skin colouration:

Genes

Exposure to sunlight

Hormonal factors

Our Constitutional colour is our 'native' colour. Our genes are the main influence in determining our skin colour in the absence of exposure to the sun or other influences.

Our Optional colour is the pigmentation taken on by the skin in relation to other influences - usually exposure to the sun or hormonal factors. Optional colour is also influenced genetically.

Hormones such as oestrogen have a pigmentogenic (pigment stimulating) action. Testosterone also stimulates melanin production. Changes in pigmentation occur during pregnancy (pregnancy mask, chloasma). Changes in hormone levels due to such things as oral contraceptives, ovary disturbances or Addison's disease can also change the rate of melanin production.

Pigment Disorders 
Disorders linked to alterations in melanin pigmentation are divided into two groups:

1. The hyper-melanoses or hyper-chromias, characterised by a localised or a more widespread increase of melanin in the skin, which creates a darker colour than normal in the epidermis and excess pigment may be present in the dermis with a greyish or blue colour.

2. The hypomelanoses or hypochromias, characterised by a reduction in skin pigment so the skin appears whiter or lighter than its normal colour.

Due to there being many variations of cutaneous pigment disorder, diagnosis is better facilitated using a source of UV rays (Woods light).

Pigmentation alterations happen in many different ways as a result of multiple genetic and environmental factors. Hyper-pigmentation classification:

There are a very high number of conditions that may cause hyper-pigmentation. They are not easy to classify. They may be of genetic origin (e.g. ephelis, freckles, nevomelanoma etc.) or of acquired origin as previously mentioned.

Hyper pigmentation of cosmetic importance - Acquired Hypermelanoses

Cause
Brown colour(melanodermia)
Grey, slate or blue colour(cerulodermia)
Metabolic
Hepatic Illnesses
Haemochromatosis,
Pericholangiolitic cirrhosis
Haematoporphyria
Haemochromatosis
Macular cutaneous amiloidosis
Endocrine
Pregnancy mask
Addison disease
Contraceptives and
Therapy with oestrogen's
Pregnancy mask
Addison disease
Contraceptives and
Therapy with oestrogen
Chemical
Arsenic
Bisulfan,
Bleomycin
Cyclophosphamide
Adrimycin
Psoralens
Berloque's dermatitis
Phyto photo-dermatitis
Minocycline
Fixed eruption from medications,
barbiturates.
Phenothiazines
Chlorpromazine
Phenolphalein etc
Chlorpromazine
Physical
Ultra violet light
Ionising radiation
Traumas

Nutritional
Pellagra
Vit.B12 deficiency
Kwashiorkor
Chronic nutritional deficiency
Post-Inflammatory
Eczema
Lichen planus, lupus erythematosus
Lichen and macular amiloidosis
Systemic / morphea sclerosis
Pinta
Dyschromic erythema perstans
Tumours
Acantosis nigricans
Malignant tumours
Metastatic melanoma with melanogenuria




HYPERPIGMENTATION OF COSMETIC IMPORTANCE

Epidermal (MELANODERMIA)
Dermal (CERULODERMIA)
Melasma
Sun lentigo
Freckles induced by PUVA therapy
Berloque’s dermatitis
Post-inflammatory hypermelanosis traumas, excoriated acne, lichen planus
Lupus erythematosus, post-dermal abrasion
Post laser, post-infections, fixed eruption from pharmaceuticals
Riehl melanosis: occupational melanosis
Hyper pigmentation induced by pharmaceuticals
Minocycline, phenothiazine, silver
Clotazimine, carolenorjerrnia
Tattoos
Erythema ab igne
Dermal melasma
Oral contraceptives
Post-inflammatory
Excoriated acne



MELASMA

Melasma is usually a brown or sometimes grey-brown area on the face, the neck and the forearms. The pigmentation may be in a line (a band running down from the cheeks) or confetti (patchy spots) like pigmented marks.
Three areas of melasma are identified: centre-facial, cheek or jaw. The colour is generally a uniform light or dark brown. However, there may be a variegated brown colour. It manifests on photo-exposed areas: the forehead, in arches above the eyebrows, on the bridge of the nose, on the cheeks with a butterfly aspect, on the upper lip like a moustache, on the chin (sometimes extending to the V of the neck) and on the back of the forearms.

There may also be only one area, but usually they are set out symmetrically on the face, it is most common in women of Hispanic origin and people who live in places where exposure to UV rays is higher.


Causes of Melasma

Hormonal factors
Genetic factors (family)
Pregnancy (multiple)
Melasma exacerbated by the sun
Oestrogen / progesterone alterations
Cosmetic ingredients
Oral contraceptives
Pharmaceuticals and photo-toxic agents  
Thyroid disturbances (auto immune and not)  




The most important factors in the pathogenesis of melasma are a genetic predisposition and exposure to the sun. Melasma may not be resolved after giving birth or after the interruption of oral contraceptives.

Classification of Melasma 
Melasma can be divided into 3 types:

Epidermal - There is an increase in melanin in the basal and super-basal layers and in the horny layer. Under Wood's light (a test) the hyper pigmented maculae are more distinct and pigmentation is intensified.
Dermal - There is an increase of melanophages (macrophages full of melanin) in the surface and deep dermis. Pigmentation does not intensify under Wood's light. The maculae become less visible and their edges less distinct.

Mixed - Pigment in the epidermis and dermis.

SUN LENTIGO
These are brown coloured marks of about 1cm, which appear in photo-exposed areas (face, back, hands).

POST- PUVA THERAPY FRECKLES
These appear in exposed areas in more than 2% of patients after 2-3 years of prolonged therapy with photo chemotherapy, Psoralens and PUVA. They appear as star-shaped freckles, particularly evident in the elderly and in persons with fair complexions (photo-type I and II).

BERLOQUE'S DERMATITIS 
This is a modest skin reaction, which generally appears as a delayed reaction and it is rare to remember the cause that triggered it. The name refers to the pendent or drop form of the marks. It arises due to contact with cosmetics (cologne, perfumes, and after-shave lotions).
The sides of the neck and the upper limbs are most affected; the shape matches the area of application. Susceptibility to its development is individual. Heat, humidity and exfoliation all increase absorption.

POST-INFLAMMATORY HYPERPIGMENTATION 
Any acute or chronic inflammatory process may cause hyper pigmentation; it is more intense and persistent in dark skin. The response is due to the nature of the dermatosis rather than to the intensity of the inflammation. They usually appear in conditions in which there is damage to the keratinocytes of the basal layer.
Post-inflammatory hyper pigmentation may follow physical traumas, chemical peeling, excoriated acne and dermal abrasion in dark skinned persons.A particular form is erythema ab igne, which may break out in any area chronically exposed to a source of heat (warmer, hot-water bottle etc.).

RIEHL'S MELANOSIS 
This is more frequent in women, probably due to a more extensive use of cosmetic products. Often the patient will give a positive patch test to cosmetic ingredients exhibiting a local contact dermatitis. The pigmentation is brown greyish, involves almost the whole face, in particular forehead and temples, and may also affect the neck, chest, scalp and sometimes hands and forearms. Horny taproots till the follicles and peeling also appears. The melanosis reduces in some months if contact with cosmetics is avoided. Sometimes the cause is unknown.

OCCUPATIONAL MELANOSIS 
(Toxic melano-dermatitis)
Workers in contact with tar derivatives such as pitch, asphalt and mineral oils may develop diffuse melanosis in the parts exposed to the action of anthracene, phenanthrene and other photo-dynamic action substances

What is Glutathione?
Glutathione is already a substance that exists in your body. It’s just that until recently we didn’t know how to raise glutathione levels. Now when I talk about glutathione to a medical convention, for example, I’ll put a slide on the wall with 20 or 30 different things that glutathione does inside of your cell. But for most people, if they could remember three things, using the acronym A I D, then they can really start to understand why this has such an impact on so many different pathologies. The A stands for antioxidants, the I part stands for the immune system boosters and finally D, this area of detoxification. 

So let’s take a look at each of these key functions separately. First, Glutathione as an antioxidant. Because glutathione is the major antioxidant produced naturally in the body, many scientists will refer to it as the ‘master antioxidant’. In fact, most of the antioxidants most people are familiar with, such as vitamin C or E would not be able to work properly if it were not for glutathione. To understand how an antioxidant works, it’s important to understand a little bit about free radicals and the damage they can have on the body, also known as oxidative stress.

A good example of oxidative stress that everybody understands is that if you get a piece of metal and take the protective coating off the metal, that metal oxidizes. And pretty soon, if you leave it alone, that metal will get rusted and it’ll bore a hole right through that metal, or if you get a brand new apple and you take the peel off that apple, oxidative stress occurs-that apple will turn brown. Well, if you come back a week later, that apple will be a bit mushier, and if you come back a month later, there may not be an apple there. And so that’s all mediated by free radical damage. That’s what we call oxidative stress. 

These are very damaging substances which can destroy cell components in a matter of micro seconds. So it’s very important then, that these be quenched or neutralized right away and this is one of the important rules of glutathione. 

The second most important role of glutathione is to boost the immune system. Now science still has a lot to learn about the immune system, but one thing we’ve come to understand is how to fuel it. Glutathione has been described, literally, as food for the immune system.

To have a food product, which I think is the most important development we’ve offered to people and their health, their wellness issue, probably since penicillin, so 60 years. And I don’t say that lightly because I think it’s very exciting to re-tool and let the body do it’s own healing. Because that’s almost always, including intensive care, what we’re able to offer. We offer support systems until the body heals itself. Now we are providing it with extra building blocks. 

And finally, glutathione is a safe and natural detoxifier. It works in the body to eliminate toxins and helps support individual cells and organs. 

The way it operates, it detoxifies, it links with the poison through an enzyme called conjugate and when they link the poison become soluble and if a poison is soluble it is no longer poison, it leaves the body through the urine for example lead, carbon and also carcinogen. We would raise glutathione levels in an emergency setting in people who are suffering from certain overdoses. And what the glutathione would do in that case is to allow the person to get rid of these toxins themselves, from their body. Now I knew that this was good in acetaminophen overdose, but what most people don’t understand is that glutathione is also critical for getting rid of heavy metals like mercury, like lead, like pesticides, like herbicides, like the break down products of cigarette smoke, like automobile exhaust, and a dozen other well known carcinogens in our environment.

Health Benefits of Glutathione Supplementation

Has anti-aging properties.
Helps the body fight almost any disease, because it is a powerful antioxidant that helps maintain cellular health and helps prevent oxidative stress.
New studies suggest that it helps in alleviating the effects of neurodegenerative diseases like Alzheimer's, Parkinson's and Multiple Sclerosis.
Compelling evidence to suggest a crucial role for glutathione in the prevention and treatment of certain cancers.
Acts as an antioxidant and free radical scavenger protecting us against the damaging effects of pollutants and free radicals.
Helps normalize blood pressure in people with diabetes and hypertension.
Increase sperm counts in men with low sperm counts.
Prevents clots formation in the blood.
Plays a vital role in liver detoxification and helps improve it's function.
Helps combat acne by cleansing the body and getting rid of impurities that causes it.


What Doctors and Experts Say About Glutathione

Glutathione has been called the "master antioxidant", and regulates the actions of lesser antioxidants such as vitamin C, and vitamin E within the body. "We literally cannot survive without this antioxidant," Earl Mindell, R.Ph., Ph.D. "What You Should Know about the Super Antioxidant Miracle"
"No other antioxidant is as important to overall health as glutathione. It is the regulator and regenerator of immune cells and the most valuable detoxifying agent in the human body. Low levels are associated with hepatic dysfunction, immune dysfunction, cardiac disease, premature aging, and death." The Immune System Cure, Lorna R. Vanderhaeghe & Patrick J.D. Bouic, Ph.D.
Glutathione is the major endogenous antioxidant produced by the cell. Glutathione participates directly in the neutralization of free radicals, reactive oxygen compounds, and maintains exogenous antioxidants such as vitamins C and E in their reduced (active) forms. In addition, through direct conjugation, glutathione plays a role in the detoxification of many xenobiotics (foreign compounds) both organic and inorganic.
Research suggests that abnormally low glutathione levels may increase your risk for Heart Attack. Eric Topol, MD, New England Journal of Medicine.
"Glutathione has potent anti-viral properties - if tissue and serum glutathione levels are significantly increased, the replication of most pathogens are slowed or stopped. Conversely, glutathione deficiency produces a pro-viral effect." Paul Cheney, M.D., Ph.D. and expert in the treatment of Chronic Fatigue Syndrome.
As we age, there is a precipitous drop in Glutathione levels. Lower glutathione levels have been implicated in many diseases associated with aging. Journal of Clinical Epidemiology 47: 1021-28 1994
Antioxidants are well documented to play vital roles in health maintenance and disease prevention. Glutathione is your cells' own major antioxidant. Biochemical Pharmacology 47: 2113-2123 1994
Glutathione plays a role in eliminating many carcinogens as well as maintaining immune function. Cancer Letters 57: 91-94 1991
Strong muscular activity, such as that experienced by athletes, generates oxyradicals [free radicals] leading to muscle fatigue and poorer performance. Glutathione neutralizes these radicals. Sport Medicine 21: 213-238, 1996 leading to muscle fatigue and poorer performance. Glutathione neutralizes these radicals. Sport Medicine 21: 213-238, 1996
Glutathione detoxifies many pollutants, carcinogens, and poisons, including many in fuel exhaust and cigarette smoke. It retards damage from radiation such as seen with loss of the ozone. Annual Reviews of Biochemistry 52:711-780 1983
According to Lester Packer, Ph.D., maintaining high levels of glutathione is critical for life low glutathione levels are a marker for death at an early age. Glutathione diminishes as we age and cannot be boosted significantly through supplements.
Researchers have found that people over the age of 60 who have high blood levels of glutathione have fewer illnesses, lower cholesterol and blood pressure and healthier weights than people with lower levels. People over 69 with low blood levels of glutathione are more likely to have diabetes, arthritis and heart disease.


Science Journals and Articles

Glutathione Depletion Increases Tyrosinase Activity in Human Melanoma Cells

Véronique del Marmol1, Francisco Solano2, André Sels3, Georges Huez3, Anita Libert1, Ferdinand Lejeune1 and Ghanem Ghanem1

1L.O.C.E, Faculty of Medicine, University of Brussels, Belgium
2Department of Biochemistry, Faculty of Medicine, University of Murcia, Spain
3Department of Molecular Biology, University of Brussels, Belgium
Received 16 October 1992; Accepted 10 July 1993. Journal of Investigative Dermatology (1993) 101, 871–874; doi:10.1111/1523-1747.ep12371709

Abstract

The aim of the present work was to estimate the effect of intracellular glutathione depletion on melanogenesis in human melanoma cells. We determined tyrosine hydroxylation activity, the rate-limiting step of the pathway, and 14C-melanin formation, an assay reflecting the global eumelanogenic pathway. Intracellular glutathione was depleted by treatment with buthionine-S-sulfoximine, a well-known inhibitor of glutamylcysteine synthetase.

The intracellular depletion of glutathione was substantial after 20 h of incubation with 50 M buthionine-S-sulfoximine, although a significant effect could be observed after 6 h. Tyrosine hydroxylase activity increased in parallel with glutathione depletion, to reach 160% with respect to the control values during 24 h of buthionine-S-sulfoximine treatment. We have found the response to buthionine-S-sulfoximine to be dose dependent and the two different human cell lines HBL and LND1 to have similar, if not identical, responses. 14C-melanin formation assay revealed even greater activation, up to 400% of the control values. This indicates that glutathione depletion may have two distinct effects: first, a direct one on tyrosinase activity and, second, an effect on the promotion of eumelanogenesis. The stimulation of tyrosine hydroxylase can be explained by a possible inactivation of the enzyme by endogenous thiol compounds rather than by a direct effect of buthionine-S-sulfoximine itself on tyrosinase. The data suggest that thiol compounds may play a role for stimulation of melanogenesis by ultraviolet radiation.


Glutathione as a Depigmenting Agent: An Overview

C. D. Villarama*,*School of Medicine, University of California, San Francisco, CA, USACollege of Medicine, University of the Philippines Manila, Philippines and
H. I. Maibach**School of Medicine, University of California, San Francisco, CA, USA
*School of Medicine, University of California, San Francisco, CA, USA and †College of Medicine, University of the Philippines Manila, Philippines
International Journal of Cosmetic Science

Volume 27 Issue 3 Page 147-153, June 2005

To cite this article: C. D. Villarama, H. I. Maibach (2005) 
Glutathione as a depigmenting agent: an overview 
International Journal of Cosmetic Science 27 (3), 147–153. 
doi:10.1111/j.1467-2494.2005.00235.x

Abstract

Glutathione is an ubiquitous compound found in our bodies. Aside from its many ascribed biologic functions, it has also been implicated in skin lightening. We review in vitro and in vivo studies that show evidence of its involvement in the melanogenic pathway and shed light on the its anti-melanogenic effect. Proposed mechanisms of action include: (a) direct inactivation of the enzyme tyrosinase by binding with the copper-containing active site of the enzyme; (b) mediating the switch mechanism from eumelanin to phaeomelanin production; (c) quenching of free radicals and peroxides that contribute to tyrosinase activation and melanin formation; and d) modulation of depigmenting abilities of melanocytotoxic agents. These concepts supported by the various experimental evidence presented form basis for future research in the use of glutathione in the treatment of pigmentary disorders.

Opposite Regulation of Tyrosinase and Glutathione Peroxidase by Intracellular Thiols in Human Melanoma Cells

Journal Archives of Dermatological Research 
Publisher Springer Berlin / Heidelberg
ISSN 0340-3696 (Print) 1432-069X (Online)
Issue Volume 289, Number 6 / May, 1997 
Category Original Paper
DOI 10.1007/s004030050202 
Pages 341-346
Subject Collection Medicine 
SpringerLink Date Thursday, February 19, 2004

Authors 
M. Benathan1 
Department of Dermatology, Centre Hospitalier Universitaire Vaudois (CHUV), 1011 Lausanne, Switzerland Fax 21-3140-378

Abstract

Conditions of oxidative stress lead to downregulation of glutathione (GSH) and glutathione peroxidase (GPO), which could be responsible for tyrosinase induction in pigment cells. To address this question, the effects of selective modulation of GSH metabolism on melanogenic parameters of slightly and highly melanized melanoma cells were examined. Under standard culture conditions (100 7M cystine, 100 7M tyrosine), the levels of GSH and the activities of glutathione reductase (GR) and GPO were found to be directly related to the pigmentation of melanoma cells. Exposure to 50 7M buthionine sulfoximine for 72 h decreased tyrosinase activity by 30-50% and GSH levels by more than 95%. In contrast, inhibition of GR activity with bis(chloroethyl)nitrosourea or stimulation of GPO activity with sodium selenite did not affect tyrosinase activity nor pigment formation in the melanoma cells tested. Since cysteine (CysH) is a precursor of the GSH tripeptide, the modulation of tyrosinase and GPO activity by the extracellular cystine concentration was also examined. When the cystine concentration was increased from 0 to 200 7M, a dose-dependent decrease in tyrosinase activity was associated with dose-dependent increases in GPO activity and in cell levels of CysH and GSH. The results indicate that cellular thiols coregulate the activities of tyrosinase and GPO in opposite directions. These interdependent processes could provide melanoma cells with protection against oxidative stress at low as well as at high thiol concentration.


"Glutathione has been used in skin lightening compositions. Reduced form of glutathione has a dual role in the depigmentation of colored skin. The mechanism of action may involve competitive binding with the color forming precursors of tyrosine (dopaquinone) to form less-colored phaeomelanin"
http://appft1.uspto.gov/netacgi/nphParser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040166069%22.PGNR.&OS= DN/20040166069&RS=DN/20040166069

"In the presence of cysteine or glutathione, dopaquinone is converted to cysteinyl DOPA or glutathione DOPA. Subsequently, pheomelanin, a yellow-red pigment, is formed."
http://www.emedicine.com/derm/topic528.htm

"Pheomelanogenesis also starts with dopaquinone; this is conjugated to cysteine or glutathione to yield cysteinyldopa and glutathionyldopa, for further transformation into pheomelanin"
http://physrev.physiology.org/cgi/content/full/84/4/1155

"The observed differences in the glutathione and glutathione-related enzyme content between black and yellow (or red) skin provide evidence that the increase of glutathione-reductase activity in the environment of the melanocytes may stimulate the pigment cells to produce phaeomelanin instead of eumelanin pigment."
http://www.nature.com/jid/journal/v79/n6/abs/5615319a.html