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維他命C

出自維基百科,自由嘅百科全書
維他命C
藥嘅種類
維他命C結構
ATC代碼A11CC

維他命C英文Vitamin C)係1種存在喺柑橘類生果、漿果同蔬菜裏面嘅水溶性維他命。維他命C係人體必須嘅營養素,呢樣嘢用對人體十分重要嘅抗壞血酸英文Chemistry of ascorbic acidAscorbic acid形式嚟存在,對參與組織嘅修復、膠原蛋白嘅形成,仲有某啲神經遞質酵素合成都好重要。呢樣嘢對免疫系統嘅功能亦都好重要。呢樣嘢亦都抗氧化劑嘅作用。大部分動物可以自己合成維他命C。不過,包括人類呢啲高等靈長類動物、大部分蝙蝠豚鼠、某啲魚類同某啲因為佢哋嘅基因喺合成維他命C嘅酶裏面發生咗突變而搞到冇咗嗰個功能,所以佢哋一定要喺食物裏面攞到維他命C[1]

維他命C可以用嚟預防同治療1種由唔夠維他命C而引起嘅壞血病。呢樣嘢亦都係1種通用處方藥英文Generic drug,喺有啲國家用嚟做非處方嘅營養補充劑噉去賣。維他命C可以口服,亦都可以透過肌肉注射、皮下注射或者靜脈注射嚟畀藥。基於唔同嘅健康講法英文Health claim話,維他命C嘅中度缺乏存在住會增加罹患各種疾病風險嘅假設,例如係普通感冒癌症、或者係新冠肺炎[2](pxi)。仲有啲講法話,對於唔被睇成係缺乏維他命C嘅人嚟講,補充超過參考膳食攝取量英文Dietary Reference Intake嘅維他命C都有益處。維他命C嘅耐受性一般都好好,大劑量可能會搞到腸胃病英文Gastrointestinal disease、頭痛、瞓唔著同埋皮膚發紅英文Flushing (physiology)美國國家醫學醫學院英文National Academy of Medicine建議唔好大量噉服用[2]:155–165

維他命C喺1912年畀人發現,1928年被分離出嚟,仲喺1933年做咗第1個化學合成嘅維他命。阿爾伯特·聖捷爾吉英文Albert Szent-Györgyi憑住佢嘅發現而攞咗1937年嘅諾貝爾生理學或醫學獎

來源

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雖然其他植物性食物都含維他命C,不過生果同蔬菜係維他命C最豐富嘅天然來源[3][4]。維他命C亦都係最廣泛服用嘅營養補充劑[4]

植物來源

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  假如你想揾嘅係關於粟米、稻米同小麥等等10種成日見主要食物裡面嘅維他命C含量,請睇「主食§營養英文Staple food#Nutrition」。

下面嘅表係近似值,仲顯示咗唔同植物原料入面嘅相對含量[3][4][5]

份量係用每100克生果或蔬菜嘅食用部份嘅毫克嚟計:

植物來源嘅源材料[6] 含量(mg)
(每100克)
費氏欖仁英文Terminalia ferdinandiana[7]1,000-5,300
卡姆果英文Myrciaria dubia[8]2,800
針葉櫻桃英文Malpighia emarginata[9]1,677
油柑子[10][11]445
玫瑰果英文Rose hip426
海沙棘英文Common sea-buckthorn[12]400
番石榴果228
黑加侖子200
甜椒(黃)183
甜椒(紅)128
羽衣甘藍120
西蘭花90
奇異果90
甜椒(綠)80
椰菜仔80
紅加侖子羅甘莓英文Loganberry80
雲莓英文Rubus chamaemorus接骨木elderberry60
士多啤梨60
木瓜60
檸檬53
椰菜花48
菠蘿48
鈔皮瓜40
熱情果紅桑莓30
西柚青檸30
椰菜菠菜30
芒果28
黑啤梨木薯21
薯仔20
哈密瓜20
番茄14
蔓越莓13
藍莓提子10
杏桃布冧西瓜10
牛油果8.8
洋蔥7.4
車厘子7
蘋果6
紅蘿蔔露筍6

動物來源

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動物性食物嘅維他命C含量通常都唔高,就算有都會喺烹煮嘅過程裏面畀高溫破壞到冇晒。例如,每100克嘅生雞肝就含有17.9毫克嘅維他命C,但喺煎炸過之後,維他命C含量會跌到每100克只係得2.7毫克。母乳裏面嘅維他命C含量係每100克就有5毫克;牛奶裏面嘅維他命C含量係每100克就有1.0毫克,不過巴斯德消毒法嘅高溫會破壞咗牛奶裏面嘅維他命C含量[13]

準備食物

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維他命C喺某啲條件下會發生化學分解反應,裏面好多分解可能發生喺食物嘅烹飪過程入面。各種食物裏面嘅維他命C濃度會隨住儲存時間嘅延長而降低,降低嘅程度而且同儲存溫度成正比[14]。烹調可以令蔬菜裏面嘅維他命C含量降低大約60%,可能係因為增強咗酵素破壞嘅作用搞成噉[15]。長啲嘅烹調時間都可能會加重咗呢種影響[16]。另1個食物裏面維他命C流失嘅原因係浸出英文Leaching (chemistry),即係維他命C轉移落到去用嚟煮嘢食啲水裏面,呢啲水最後會畀人倒咗去而唔係食落肚[17]

食品強化

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各國透過強化食物裏面嘅營養成份嚟解決已知嘅營養缺乏問題[18]。雖然好多國家都強制或實施自願計劃去強化小麥粉、粟米粉或稻米入面嘅維他命含量[19],不過呢啲計劃裏面都未包括維他命C[19]。好似喺1997年嘅《食物援助商品入面嘅維他命C強化Vitamin C Fortification of Food Aid Commodities》所講嘅噉,美國向國際糧食救濟計劃提供配額,呢啲計劃後嚟喺《糧食換和平法案英文Food for Peace》嘅支持,同埋人道主義援助局the Bureau for Humanitarian Assistance嘅指導下開展[20]。維他命C後嚟喺每100克粟米大豆混合物同小麥大豆混合物嘅產品裏面加入40毫克(仲有礦物質同其他維他命)。呢啲高強化混合食物嘅補充配額提供畀難民營裏面嘅難民同流離失所嘅人,仲有主要針對媽咪同細路嘅發展援助計劃嘅受益者[17]。嗰份報告補充話:「維他命C(L-抗壞血酸)嘅穩定性係令人關注嘅,因為呢個係食物裏面其中一種最唔穩定嘅維他命。呢樣嘢喺加工同儲存過程入面嘅損失主要係由氧化引起,而由光照、氧氣、高溫、pH值升高、高水分含量(水活性),同埋銅鹽或亞鐵鹽嘅存在都會加速氧化。為咗減少氧化,維他命C用喺商品強化就會用2.5%嘅乙基纖維素做塗層。食物加工同調製過程中亦會發生氧化損失,而如果額外嘅維他命C溶解成煮食液體然後被丟棄,就可能會流失額外嘅維他命C[17]。」

補充劑

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維他命C補充劑。

維他命C嘅營養補充劑有片劑、膠囊、飲品混合包裝、複合維他命/礦物質配方、抗氧化劑配方,沖劑同埋結晶粉末等幾種形式[21]。有啲果汁同果汁飲品裏面都加咗維他命C。片劑同膠囊嘅含量範圍喺每份25毫克去到1,500毫克。最成日用嘅補充劑成分係抗壞血酸ascorbic acid抗壞血酸鈉sodium ascorbate,同埋抗壞血酸鈣calcium ascorbate[21]。維他命C分子亦都可以同棕櫚酸脂肪酸結合而形成抗壞血酸棕櫚酸酯英文Ascorbyl palmitate,又或者被包住喺脂質體裏面[22]

飲食

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建議攝取量

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唔同國家嘅機構都已經制定咗成年人對維他命C嘅建議攝入量:

2000年,《北美膳食參考攝取量英文Dietary Reference Intake》入面更新咗關話維他命C嘅章節,畀出嚟嘅參考每日攝入量英文Reference Daily Intake(RDA),成年男性係每日90mg,而成人女性係每日75mg,而成年人每日可耐受最高攝入量英文Dietary_Reference_Intake#Parameters(UL)係每日2,000mg[2]:134–152。下面個表列咗美國同加拿大細路、大肚婆同哺乳期婦女嘅RDA出嚟[2]:134–152,仲有成年人嘅UL值。

美國維生素C建議攝取量(毫克/日)[2](pp134–152)
1-3歲細路嘅RDA 15
4–8 歲細路嘅RDA 25
9–13歲細路嘅RDA 45
14–18歲女仔嘅RDA 65
14–18歲男仔嘅RDA 75
成年女性嘅RDA 75
成年男性嘅RDA 90
懷孕期女性嘅RDA 85
哺乳期女性嘅RDA 120
成年女性嘅UL 2,000
成年男性嘅UL 2,000

對於歐盟嚟講,歐洲食品安全局英文European Food Safety Authority(EFSA)幫成年人同細路設定咗高啲嘅建議攝取量:1-3歲細路每日20mg;4-6歲細路每日30mg;7-10歲細路每日45mg;11-14 歲青少年每日70mg,15-17歲男性每日100mg,15-17歲女性每日90mg;孕婦每日100mg;哺乳期婦女每日155mg[28]

吸煙者同接觸二手煙嘅人,佢哋嘅血清維他命C水平低過非吸煙者[29]。推論係吸入煙霧會搞到有氧化損傷,跟住消耗晒呢種抗氧化維他命[2](pp152–153)。美國醫學研究所估計,吸煙者每日需要比非吸煙者攝取多35mg嘅維他命C,但仲未正式制訂吸煙者更高嘅RDA[2](pp152–153)

美國國家健康統計中心每兩年做1次嘅全國健康與營養調查NHANES去評估美國成年人同細路嘅健康同營養狀況,部分嘅調查結果就喺《我哋喺美國食嘅嘢What We Eat In America》入面發表。2013-2014年嘅調查報告指出,對於廿歲以上嘅成年人嚟講,男性平均每日攝入量係83.3mg,而女性每日攝入量係75.1mg。噉即係話,呢個意味住有一半嘅女性同超過一半嘅男性都未達到維他命C嘅RDA[30]。同1項調查亦都指出,大約30%嘅成年人話佢哋食維他命素C營養補充劑或含有維他命C嘅多種維他命/礦物質補充劑,而呢啲人嘅總消耗量係每日300-400mg之間[31]

可耐受最高攝入量

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2000年,美國國家科學院醫學研究所將成年人維他命C嘅UL設定喺每日2000mg。揀呢個劑量嘅原因係因為人體試驗報告過話每日攝入量超過3,000mg就會出現肚屙同埋其他腸胃道唔舒服。呢個係最低觀察到嘅不良反應水平(LOAEL),即係話喺攝入量更高嘅情況下都會觀察到其他不良反應。對於年紀越嚟越細嘅小朋友嚟講,UL值會隨著年齡嘅增加而逐漸噉降低[2]:155–165。EFSA喺2006年亦都指出咗喺嗰個劑量水平下可能會出現嘅不良反應,不過最終得出嘅結論係,認為冇足夠嘅證據去設定維他命C嘅UL[32],就好似日本國立健康營養研究所喺2010年所做嘅嘢噉樣[27]

食物標籤

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對於美國食品同膳食補充劑嘅標籤目的,1份嘅份量係用每日價值嘅百分比(%DV)嚟表示。對於維他命C標籤嘅目的,每日價值嘅100%係60mg,但係由2016年5月27號起被修訂做90mg,令佢同RDA保持一致[33][34]。新舊成人每日攝取量對照表請參閱「參考每日攝取量英文Reference Daily Intake」嗰頁。

歐盟法規要求食物標籤上註明嘅能量、蛋白質、脂肪、飽和脂肪、碳水化合物、糖同埋鹽嘅含量。如果某啲營養素含量顯著嘅話都可以自願噉標示出嚟。食物標籤上面嘅營養素含量唔採用每日參考值(DV)嘅話,就係用參考攝取量(RI)嘅百分比嚟表示。例如,2011年嘅100%維他命C嘅參考攝取量設定做80mg[35]

食物保存添加劑

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抗壞血酸同呢樣嘢嗰啲係食物入面常見嘅添加劑,例如係罐頭生果,主要係為咗減慢氧化同埋酶促褐變英文Food browning[36][37]。呢樣嘢可能用嚟做整麪麵團改良劑英文Dough conditioner[38]。作為食物添加劑,呢啲添加劑被分配個E編號,呢啲嘢嘅安全評估同批准都係由歐洲食品安全局英文European Food Safety Authority(EFSA)負責[39]。相關嘅E編號係:

維他命C嘅立體異構體就算喺食物裏面有類似嘅作用,不過呢啲物質對人類壞血病冇療效。呢啲立體異構體包括異抗壞血酸英文Erythorbic acid同埋佢嘅鈉鹽(E315同E316)[40]

缺乏症

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血漿維他命C係而家應用得最廣泛嘅維他命C狀態測試方法[44]。充足嘅維他命C含量定義係接近每升50個 μmol。維他命C嘅維他命缺乏症英文Ascorbyl palmitate定義係低過23 μmol/L,而維他命C缺乏症就係低過11.4 μmol/L[29]。根據2017-2018年美國國家健康與營養調查英文National Health and Nutrition Examination Survey嘅數據,廿歲或以上嘅人平均血清維他命C嘅濃度係每升有53.4個μmol,裏面有5.9%嘅人被報告係缺乏維他命C[45]。喺全球,維他命C缺乏症喺低收入同中等收入國家比較常見,喺高收入國家亦都唔係罕見。喺高收入國家,男性嘅維他命C缺乏症嘅盛行率高過女性[46]

當維他命C透過每日攝取量達到100-200mg嗰時,血漿濃度大約係65 μmol/L嗰時就達到飽和,呢個水平遠高過建議攝取量。就算口服攝入量高啲都唔會進一步噉提升血漿同組織濃度,因為吸收效率會降低,任何過量吸收嘅維他命C都會跟住尿液排走[44]

診斷測試

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血漿裏面嘅維他命C含量係用嚟決定維他命嘅狀態。為咗研究嘅目的,可以評估白血球同埋組織入面嘅維他命C濃度,呢啲細胞同組織入面嘅維他命C濃度通常比血漿裏面嘅濃度高1級,呢個係透過能量依賴性轉運系統嚟維持嘅;喺飲食缺乏嗰段時間,呢啲細胞同組織裏面嘅維他命C濃度消耗速度慢過喺血漿裏面;喺飲食補充嗰陣,呢啲細胞同組織入面維他命C濃度嘅恢復速度比起血漿裏面嘅快[2](pp103–109)。但係,呢啲分析好難去測量,所以唔屬於標準診斷檢測嘅一部分[44][47]

化學

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維他命C嘅3D化學結構
抗壞血酸(還原劑英文Reducing agent

「維他命C」呢個名通常指嘅係抗壞血酸嘅對映異構體英文Enantiomer,同埋呢樣嘢嘅氧化還原反應形式—脫氫抗壞血酸DeHydroAscorbate (DHA),所以除非另有說明之外,營養學文獻裏面嘅「抗壞血酸ascorbate」同「抗壞血酸ascorbic acid」分別係指L-抗壞血酸l-ascorbate同埋L-抗壞血酸l-ascorbic acid。抗壞血酸係1種弱糖酸英文Acid_strength#Weak_acids,呢樣嘢嘅結構同葡萄醣有關。抗壞血酸喺生物系統裏面淨係存在喺低pH值嘅條件下,不過喺pH值高過5嘅溶液入面,呢樣嘢主要係用電離嘅形式—抗壞血酸ascorbate嘅形式存在[44]

而家已經開發咗好多分析方法嚟檢測抗壞血酸。例如果汁呢啲食物樣本嘅維他命C含量,可以透過檢測DCPIP英文Dichlorophenolindophenol溶液脫色所需嘅樣本體積,然後透過同已知濃度嘅維他命C去做比較嚟校準結果,嚟去計果汁呢啲食物樣本裏面嘅維他命C含量[48][49]

合成

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大部分動植物都能透過一系列酵素驅動嘅步驟去合成維他命C,呢啲步驟將單醣轉化做維他命C。酵母菌合成唔到L-抗壞血酸,而係合成佢嘅立體異構體英文Stereoisomerism異抗壞血酸英文Erythorbic acid[50]。維他命C喺植物裏面嘅中合成係透過將甘露糖英文Mannose半乳醣轉化做抗壞血酸嚟實現嘅[51][52]。喺動物裏面嘅起始原料係葡萄醣。某啲喺肝臟合成抗壞血酸嘅物種(包括哺乳動物雀形目)裏面,葡萄糖都係由肝醣裏面提取嘅;抗壞血酸嘅合成係個依賴糖原分解嘅過程[53]。喺人類同動物身上都唔能夠合成維他命C,催化生物合成最後一步嘅L-古洛糖酸內酯氧化酶英文L-gulonolactone oxidaseGULO發生高度突變而冇咗個功能[54][55][56][57]

動物合成

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有啲關於能夠合成維他命C嘅動物物種維持嘅血清維他命C濃度嘅資料。有一項針對幾個犬種做嘅研究報告話,平均濃度係35.9個μmol/L[58]。另一份關於山羊、綿羊同牛嘅報告顯示,報告嘅範圍分別喺100-110、265-270同160-350個μmol/L[59]

脊椎動物嘅抗壞血酸嘅生物合成係由UDP-葡萄糖醛酸glucuronic acid嘅形成開始。當UDP-葡萄糖glucose經歷兩次由UDP-葡萄糖6-脫氫酶glucose 6-dehydrogenase催化嘅氧化嗰陣時,就會形成UDP-葡萄糖醛酸glucuronic acid。UDP-葡萄糖6-脫氫酶係用輔助因子NAD+嚟做電子受體。轉移酶UDP-葡萄醣醛酸焦磷酸化酶glucuronate pyrophosphorylase會去除1個單磷酸尿苷英文Uridine monophosphate同埋葡萄醣醛酸激酶英文Glucuronokinase,而輔因子ADP一齊去除最終嘅磷酸鹽,令到D-葡萄糖醛酸英文[[:en:Glucuronic acid}|Glucuronic acid}]]出現。呢種化合物嘅醛基會用葡萄糖醛酸還原酶英文Glucuronate reductase同輔因子NADPH還原做伯醇primary alcohol,產生L-古洛糖酸gulonic acid。跟住喺C1位置上面嘅羰基同C4位置上面嘅羥基之間發生內酯化反應,嗰個反應就利用水解酶葡萄糖酸內酯酶英文Gluconolactonase去完成。L-古洛糖酸內酯然後就同氧氣發生反應,嗰個反應由L-古洛糖酸內酯氧化酶(嗰種酶喺人類同其他簡鼻亞目靈長類動物裏面冇嘅功能;睇睇單一假基因英文Pseudogene#Unitary_pseudogenes)同輔因子FAD+嘅催化。呢個反應會產生2-氧代古洛糖酸內酯oxogulonolactone(2-酮基古洛糖酸內酯keto-gulonolactone),呢樣嘢自發性發生烯醇化英文Enol反應產生抗壞血酸[52][60][61]。爬蟲類同埋古老啲嘅雀喺腎臟入面合成抗壞血酸;新啲嘅雀同大部分哺乳動物都會喺佢哋嘅肝臟入面製造抗壞血酸[52]

非合成者

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有啲哺乳動物已經冇咗合成維他命C嘅能力,包括猿猴眼鏡猴英文Tarsier,佢哋一齊構成咗兩個主要嘅靈長目之一嘅簡鼻亞目。人類亦都屬於呢個亞目群組。其他比較原始嘅靈長類動物(原猴亞目)天生就有合成維他命C嘅能力。例如係天竺鼠水豚呢啲豚鼠科英文Caviidae嘅物種係冇合成維他命C嘅能力,不過例如大鼠英文Rat小鼠英文Mouse就有呢種能力[62]

大多數蝙蝠嘅物種都冇合成維他命C嘅能力[63],但至少有兩種蝙蝠—食果蝙蝠棕果蝠同埋食蟲蝙蝠大蹄蝠英文Great roundleaf bat都保留咗(或者重拾咗)佢哋合成維他命C嘅能力[64][65]。有啲雀形目嘅鳥類都冇合成維他命C嘅能力,但並唔係所有鳥類都係噉樣,而且冇呢種能力嘅鳥類之間嘅親緣關係並唔明確;有人提出,鳥類嘅呢種能力曾經獨立喪失過好多次[66]。特別係,合成維他命C嘅能力被推定係喪失咗,然後後嚟喺至少兩個情況下重新得到[67]。大約有96%嘅現存魚類英文Neontology#Extant_taxa_versus_extinct_taxa[68]真骨魚[67])都冇咗合成維他命C嘅能力。血吸蟲英文Schistosoma(寄生扁形動物)本身冇辦法合成維他命C,一定要喺宿主嗰度攞到維他命C先至可以產卵;喺天竺鼠[69]同基因改造到冇辦法合成維他命C嘅老鼠[70]裏面,缺乏維他命C都可以阻止血吸蟲繁殖。另外,喺小鼠身上亦發現到,缺乏維他命C(就算係間歇性)都可以阻止到血吸蟲致病[70]

以每公斤體重消耗嘅毫克嚟計,非合成者物種嘅猿猴所攝入嘅維他命份量係政府建議人類攝取量嘅10-20倍[71]。呢種差異構成咗人類建議飲食攝取量爭議定得太過低嘅一啲基礎[72]。不過,猿猴嘅消耗唔代表猿猴嘅需求。默克嘅獸醫手冊Merck's veterinary manual指出,非人靈長類動物每公斤體重每日攝取3-6mg嘅維他命C可以預防壞血病[73]。相比之下,好多國家建議嘅成年人維他命C膳食攝取量係每公斤體重1-2mg嘅範圍裏面。

動物合成嘅進化

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抗壞血酸係哺乳類動物身體裏面1種成日都見嘅酵素輔因子英文Cofactor (biochemistry),參與膠原蛋白嘅合成,同時亦都係1種強效嘅還原劑英文Reducing agent,可以好快噉清除幾種活性氧英文Reactive oxygen speciesROS。鑑於抗壞血酸有呢啲重要嘅功能,令人驚訝嘅係,合成呢種分子嘅能力並唔係一直得以保留。事實上,類人猿靈長類動物、天竺鼠真骨魚、大部分蝙蝠同埋一啲雀形目鳥類都獨立冇咗喺腎臟或者喺肝臟裏面合成維他命C嘅能力[74][67]。喺所有對抗壞血酸做嘅營養缺陷型英文Auxotrophy基因組分析嘅案例裏面,發現呢種變化源於編碼L-古洛糖酸-γ-內酯氧化酶嘅基因發生功能缺失突變,嗰種酵素係催化上面講到嘅抗壞血酸合成途徑最後一步嘅酶[75]。合成維他命C嘅能力反覆冇咗嘅1個解釋係,呢個係基因漂變嘅結果;假設飲食裏面含有豐富嘅維他命C,自然選擇就唔會發揮作用嚟保留呢種能力[76][77]

就類人猿呢啲靈長類動物嚟講,有人認為佢哋冇咗合成維他命C嘅能力可能發生喺遠過晒人類甚至比猿類出現得更加早嘅進化史上面,因為佢哋明顯係喺第1批靈長類動物出現之後冇幾耐發生,但係又喺早期靈長類動物分裂成兩個主要亞目之後嘅某個時候出現,嗰兩個亞目係冇辯法合成維他命C嘅簡鼻亞目,同埋保留咗製造維他命C能力嘅姊妹亞目—非眼镜猴嘅原猴[78]。根據分子鐘測年法,呢兩個靈長類亞目嘅分支大約喺6,300萬-6,000萬年前分開去走[79]。大約300萬-500萬年之後(5,800萬年前),喺進化角度嚟睇,只係喺之後嘅短時間,眼鏡猴亞目跗形目英文Tarsiiformes——佢唯一倖存嘅科係喺其他簡鼻猴類裏面分化出嚟嘅眼鏡猴科英文Tarsier[80][81]。由於眼鏡猴亦都冇辦法合成維他命C,呢個意味住突變已經發生咗,所以一定發生喺呢兩個標記點之間(6,300萬-5,800萬年前)[78]

亦都有人指出,冇咗合成抗壞血酸能力同唔能夠分解尿酸有相似得驚人嘅地方,而冇咗尿酸分解能力亦都係靈長類動物嘅其中1個特徵。尿酸同抗壞血酸都係好強嘅還原劑英文Reducing agent。呢個導致有個講法,喺高等靈長類動物身上,尿酸已經取代咗抗壞血酸嘅部分功能[82]

植物合成

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維他命C喺植物嘅生物合成。

植物入面存在幾種唔同嘅抗壞血酸生物合成途徑。大部分途徑都係涉及透過葡萄醣解產物同埋其他代謝途徑英文Metabolic pathway,例如其中一個途徑係利用植物細胞壁聚合物[54]。植物入面主要嘅抗壞血酸生物合成途徑似乎係經由L-半乳糖。L-半乳糖脫氫酶英文L-galactose 1-dehydrogenase催化L-半乳糖氧化英文Organic redox reaction內酯英文Lactone,仲將內酯異構化做C4-羥基,產生L-半乳糖酸-1,4-內酯L-galactono-1,4-lactone[60]L-半乳糖酸-1,4-內酯跟住就同粒線體黃素酶L-半乳糖酸-1,4-內酯L-galactono-1,4-lactone[83]去產生抗壞血酸[60]。喺菠菜入面,L-抗壞血酸對L-半乳糖脫氫酶有負面嘅回饋作用[84][b]

所有植物都能夠自己合成抗壞血酸。抗壞血酸用嚟做光合作用相關酵素嘅輔因子,參與植物激素嘅合成,仲用嚟做抗氧化劑同其他抗氧化劑嘅再生劑[86]。植物利用幾種途徑去合成維他命C。主要途徑係用葡萄糖、果糖甘露糖英文Mannose(全部都係單醣)嚟做起始底物,產生L-半乳糖、L-半乳糖酸內酯同埋抗壞血酸[86][87]。呢種生物合成過程受晝夜節律嚟調控[87]。當中午嘅陽光強度需要高抗壞血酸濃度嗰陣,酶嘅表達會喺朝早達到最高峰嚟支持生物合成[87][88]。有啲次要嘅途徑可能淨係存在喺植物嘅特定部位;呢啲途徑可以同脊椎動物途徑相同(包括GLO酵素),亦都可以喺肌醇開始,然而經由L-半乳糖酸轉化做L-半乳酮內酯galactonolactone[86]

工業合成

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維他命C可以透過兩種主要途徑由葡萄糖產生。而家已經唔再利用喺1930年代開發嘅賴希斯坦法英文Reichstein process,嗰個方法係用單次發酵,然後再做純化學途徑合成。現代嘅兩步驟發酵過程最初喺1960年代响中國大陸開發,透過額外嘅發酵步驟嚟取代部分後續嘅化學合成階段。賴希斯坦法同現代嘅兩步發酵過程都係用葡萄糖嚟做起始原料,將佢轉化做山梨糖醇英文Sorbitol在先,然後再用發酵轉化做山梨糖英文Sorbose[89]。兩步驟發酵法跟住透過另一次發酵步驟將山梨糖經過另一個發酵步驟轉化做2-酮-L-古洛糖酸(KGA),避免咗額外嘅中間產物。兩種方法都可以喺葡萄糖起始原料入面產生大約60%嘅維他命C[90]。研究人員正喺度探索緊單步發酵嘅方法[91][92]

中國生產咗大約佔70%嘅全球維他命C市場,其餘嘅部分就由歐盟、印度同北美去瓜分。預計到2024年,全球市場規模就嚟超過14.1萬公噸[93]。每噸(1,000公斤)維他命C嘅成本用美金去計,喺上海嘅價錢係$2,220,喺漢堡就係$2,850,喺美國就係$3,490[94]

藥理學

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藥效學

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藥效學英文Pharmacodynamics包括維他命C用嚟做輔因子嘅酵素,呢啲酵素喺缺乏狀態下嘅功能可能受損;同埋口服或注射維他命C嘅劑量超過正常需求嘅話,任何酵素嘅輔因子或者其他生理功能都會受影響。喺正常生理濃度底下,維他命C作為1種酵素底物英文Substrate (chemistry)#Biochemistry,同埋輔因子英文Cofactor (biochemistry)仲有電子供體英文Electron donor抗氧化劑嚟發揮作用。佢嘅酵素功能包括膠原蛋白肉鹼英文Carnitine同埋神經遞質嘅合成;酪氨酸嘅合成同分解代謝英文Catabolism,仲有微粒體英文Microsome嘅代謝。喺非酵素功能入面,為咗保持鐵同銅原子喺佢哋嘅還原狀態,維他命C會用嚟充當做還原劑,向氧化分子提供電子嚟防止氧化[44]。喺靜脈注射達到非生理濃度嗰陣時,維他命C可能會起到促氧化劑英文Pro-oxidant嚟發揮作用,對癌細胞產生治療毒性[95][96]

維他命C有以下嘅嘅輔因子[44]

用嚟做1種抗氧化劑嘅抗壞血酸,呢樣嘢可以清除活性氧同氮化合物,噉樣就可以中和呢啲自由基化合物潛在嘅組織損傷。佢嘅氧化形式脫氫抗壞血酸跟住之後就會畀例如係穀胱甘肽英文Glutathione嘅內源性抗氧化劑還原做抗壞血酸[2]:98–99。喺眼入面,抗壞血酸被認為可以保護對眼唔好受到光解產生嘅自由基損傷;血漿入面嘅抗壞血酸水平越高,患白內障嘅風險越低有關[97]。抗壞血酸亦都可以透過將例如係α-生育酚英文α-Tocopherol嘅其他生物抗氧化劑再生返去活性狀態嚟間接去提供抗氧化保護[2]:98–99。另外,抗壞血酸亦都用嚟做微粒體藥物代謝系統入面混合功能氧化酶嘅非酵素還原劑,令到例如係藥物同環境致癌物嘅幾種底物冇咗活性[2]:98–99

藥物動力學

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抗壞血酸喺人體裏面嘅吸收途徑包括主動輸送同被動擴散[98]。當每日喺食物來源同中等劑量嘅營養補充劑,例如食幾種維他命/礦物質產品)入面攝取30-180mg維他命C嗰時,大約有70%-90%嘅維他命C係透過主動輸送嚟吸收嘅。不過,當大量噉攝取維他命C(例如係補充劑)嗰陣時,主動輸送系統就會去到飽和,而當吸收嘅總量隨住劑量而係噉加上去嗰陣,吸收效率就會跌到低過50%[3]。主動輸送係由抗壞血酸鈉 Sodium-Ascorbate Co-Transporter proteins共轉運蛋白(SVCTs)和己糖轉運蛋白(GLUTs)負責。SVCT1英文SLC23A1SVCT2英文SLC23A1會穿過細胞膜輸送抗壞血酸[99]。葡萄糖轉運蛋白GLUT1英文GLUT1GLUT3英文GLUT3GLUT4英文GLUT4淨係係轉移維他命C嘅氧化脫氫抗壞血酸(DHA)形式[100][61]。喺正常條件下,喺血漿同組織入面發現DHA嘅量都係低嘅,因為細胞會好快噉將DHA還原做抗壞血酸[101]

抗壞血酸鈉共轉運蛋白嘅主動輸送係人體裏面運送維他命C嘅主要系統[99]。例如維他命C合成者嘅大鼠,同埋例如係非合成者嘅人類,喺佢哋嘅細胞裏面,抗壞血酸嘅濃度都高過晒血漿裏面大約每公升50個μmol嘅濃度好多。

例如,腦垂體腎上腺嘅抗壞血酸含量可以超過每公升2,000個μmol,而肌肉裏面嘅含量係喺每公升200-300個μmol[102]。抗壞血酸嘅已知輔酶功能並唔需要噉高嘅濃度,所以可能存在其他仲未發現嘅功能。所有呢啲器官裏面高濃度嘅抗壞血酸含量嘅一個結果係,血漿維他命C冇辦法好好噉反映全身嘅維他命C狀況,所以呢樣嘢唔係唔係全身狀態嘅好指標,而就算飲食裏面嘅維他命C含量極低,唔同嘅人出現維他命C缺乏症症狀嘅所需時間都可能會有唔同[102]

維他命C主要係透過尿液嘅形式嚟排泄出抗壞血酸同埋嗰樣嘢嘅代謝物。仲未代謝嘅抗壞血酸形式排泄出去嘅部分會隨住增加攝入量而增加。另外,抗壞血酸會(可逆噉)轉化做DHA,而DHA又唔可逆轉噉變成2,3-二酮古洛糖酸酯2,3-diketogulonate,然後再轉化做草酸鹽oxalate,呢3種代謝物亦都會透過尿液排出。喺飲食攝入量低嗰陣時,維他命C會畀腎臟重新吸收而唔係排泄出去。呢種回收嘅過程可以延緩維他命C缺乏症嘅發生。人類比天竺鼠更加擅長去將DHA轉化返去做抗壞血酸,所以要耐好多先至會出現維他命C缺乏症[61][44]

健康影響

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Rows and rows of dietary supplement bottles on shelves
喺美國藥房嘅其他膳食補充劑入面包括維他命C補充劑。

維他命C對預防同治療1種由缺乏維他命C而引起嘅病—壞血病有絕對嘅作用。除此之外,維他命C喺預防或去醫唔同病方面嘅作用仍然存在住爭議,相關嘅評論結果成日都互相矛盾。而家仲未有證據顯示維他命C補充對整體死亡率有影響[103]。維他命C被列入咗去世界衛生組織基本藥物標準清單英文WHO Model List of Essential Medicines[104]同埋世界衛生組織示範藥物指南裏面[105]。2023年,維他命C係美國第226種最常見嘅處方藥物,處方量超過100萬張[106][107]

阿茲海默症

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有報告話,認知障礙症病人嘅血漿維他命C濃度會低啲。評論裏面冇提供到介入嘅臨床試驗報告[108][109]

血壓

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有報告話,同去,高血壓病人嘅血清維他命C比正常血壓嘅人低15.13 μmol/L。維他命同收縮壓Systolic Blood Pressure(SBP)仲有舒張壓Diastolic Blood Pressure(DBP)都有逆向關係。口服維他命C補充劑會令到高血壓病人嘅SBP出現輕微嘅下降,喺統計學意義上明顯噉落到去非常適中嘅位置[110][111]。可能嘅解釋係,維他命C可以提高細胞裏面四氫生物蝶呤英文Tetrahydrobiopterin嘅濃度,呢樣嘢係內皮一氧化氮合酶英文Nitric oxide synthase嘅輔因子,可以促進一氧化氮呢種強效血管擴張劑嘅產生。維他命C補充劑亦都可能逆轉一氧化氮合酶抑制劑NG-單甲基-L-精氨酸1英文MethylarginineNG-monomethyl-L-arginine 1,而且亦都有證據話,維他命C可以直接噉加強一氧化氮嘅生物活性[110]

普通傷風

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1955 black-and-white photo of Nobel Prize winner, Linus Pauling.
諾貝爾獎得主鮑林1970年出版嘅著作英文Vitamin C and the Common Cold (book)入面提倡服用維他命C嚟醫傷風

傷風入面嘅維他命C研究主要集中喺預防、持續時間同嚴重程度嘅影響呢3方面。長期每日口服超過200mg嘅維他命C對預防普通傷風冇效果。就算將分析限制喺每日至少用1,000mg嘅試驗亦都發現唔到有任何預防嘅效益。不過,定期服用維他命C補充劑確實可以令成年人平均病情嘅持續時間縮短咗8%,而細路就縮短咗14%,仲減輕咗傷風嘅嚴重性[112]。定期服用維他命C可以減少嚴重症狀嘅持續時間,但對輕度症狀嘅持續時間就冇影響[113]。治療性用藥,即係話喺出現傷風嘅初期症狀嗰陣時先至開始服用維他命C,對病情嘅持續時間或者嚴重程度都冇影響[112]

新冠肺炎

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2020年3-7月,維他命C因為聲稱可以用嚟預防同埋/或者治療COVID-19嘅成份比起任何其他成分都要多而收到美國FDA嘅警告信[114]。2021年4月,美國美國國家衛生院英文National Institutes of Health(NIH)嘅COVID-19治療指南話,「而家仲未有足夠嘅數據去支持或者反對去用維他命C嚟預防或治療COVID-19[115]。」喺2022年12月發布嘅更新入面,NIH嘅立場保持唔變:

  • 新冠肺炎治療指南小組(以下簡稱做「小組」)冇足夠的證據去建議或者反對用維他命C去醫非住院嘅新冠肺炎病人;
  • 小組冇足夠嘅證據去建議或反對用維他命C嚟醫住院嘅新冠肺炎病人[116]

針對因為嚴重COVID-19而住院嘅病人,有報告話,相對於唔食維他命C,食維他命C會顯著噉降低全因死亡風險同住院死亡率。兩組病人喺呼吸通氣發生率、留院時間或留喺重症加護病房(ICU)嘅時間方面冇顯著嘅差異。大部分納入呢啲元分析嘅試驗都係採用咗靜脈注射維他命C[117][118][119]。用咗維他命C治療嘅病人嚟講,急性腎損傷嘅發生率低啲。因為維他命而引起嘅其他副作用嘅發生率亦都冇差異[119]。結論係,喺發布更新嘅指引同建議之前,需要做更多大規模嘅研究嚟確認呢樣嘢對降低死亡率嘅好處[117][118][119]

癌症

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維他命C攝取高啲似乎可以降低患肺癌嘅風險[120]。冇證據話補充維他命C可以減低前列腺癌[121]結腸癌[122],或者乳癌嘅風險[123]

心血管疾病

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雖然血液循環維他命C水平或者飲食嘅維他命C攝取量高啲可能同中風風險低啲有關[124],不過而家仲未有證據話補充維他命C可以降低心血管疾病嘅風險[125]。當每日食嘅劑量大過500mg嗰陣,維他命C對內皮功能障礙英文Endothelial dysfunction有正面嘅作用(內皮係1層喺血管裏面嘅表面排列嘅細胞[126])。

眼睛健康

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飲食裏面嘅維他命C攝入量高啲同年齡相關嘅白內障風險低啲有關[97][127]。維他命C補充劑並唔能夠預防年齡相關嘅眼部黃斑病變[128]

缺鐵

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鐵缺乏性貧血嘅其中1個原因係鐵質嘅吸收減少。鐵質嘅吸收可以透過攝取含鐵嘅嘢食或補充劑嘅同時一齊補充維他命C嚟增強。維他命C有助鐵質還原喺亞鐵狀態,呢種狀態嘅溶解度更高,亦都更容易被吸收。呢樣嘢仲會將鐵螯合英文Chelation成可溶性複合物[129][130],呢樣嘢特別幫到手去吸收非血紅素鐵[131],非血紅素鐵存在喺非肉類來源入面,仲透過DMT1英文Natural resistance-associated macrophage protein 2受體嚟吸收[129]

牙周病

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維他命C攝入量低同血清濃度低同牙周病嘅進展有更加大嘅關係[132][133]

壞血病

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内文:壞血病

壞血病係1種由缺乏維他命C而引起嘅病。如果冇呢種維他命,身體製造嘅膠原蛋白就會太唔穩定,冇辦法發揮佢嘅功能,而身體裏面其他幾種酵素就冇辦法正常噉運作。缺乏維他命C嘅早期症狀係唔舒服同埋冇精神,跟住發展到呼吸短促、骨痛同埋容易有瘀傷。隨住病情發展,呢種病嘅特徵係皮膚上面會出現斑點英文Hyperkeratosis皮下出血,牙齦亦都會出血。皮膚病變最常見喺大髀腳膼。病人睇落去面色蒼白,覺得抑鬱,同埋活動受限而唔郁。壞血病晚期嘅病人會出現發燒、舊傷口可能會裂開同有、甩、抽搐,最後會死亡。因為健康嘅膠原蛋白會用維他命C補充嚟取代有缺陷嘅膠原蛋白,所以呢種病嘅損傷直到病嘅後期都係可以逆轉嘅[4][21][134]

第二次世界大戰嗰陣,英國對良心拒服兵役者英文Conscientious objector做咗1項關於實驗誘發壞血病嘅出名人體飲食研究;而喺1960年代尾去到1980年代,美國愛荷華州監獄亦都對囚犯做咗類似嘅研究。監獄研究入面嘅男性喺開始冇維他命C飲食之後大約4個禮拜之後就出現咗第1個壞血病嘅跡象,而喺早期嘅英國研究入面需要6-8個月嘅時間,呢個可能係因為呢個組別喺開始壞血病飲食之前持續6個禮拜每日預先補充咗70mg嘅維他命C補充劑。兩項研究入面嘅男性喺佢哋出現壞血病跡象嗰陣時,血液裏面嘅抗壞血酸水平低到冇辦法可以準確測量得到。呢兩項研究報告都話,只要每日補充10mg嘅維他命C,所有明顯嘅壞血病症狀都可以完全逆轉[135][136]。壞​​血病嘅治療方法包括食用含維他命C嘅嘢食,或者係透過膳食補充劑又或者係注射[21][2](p101)

敗血症

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内文:敗血病

敗血症病人可能會有包括維他命C濃度低嘅微量營養素缺乏[137]。靜脈注射嘅劑量高過RDA好多,敗血症病人似乎需要每日攝取3克或以上嘅維他命C先至可以維持正常嘅血漿濃度,因為炎症反應同埋氧化壓力英文Oxidative stress會加強,令到身體對維他命C嘅需求可能會大幅噉增加[138][139][140]。靜脈注射維他命C可能會降低敗血症嘅死亡率[141][142]

維他命C可以喺高濃度下好快噉分佈去到免疫系統嘅細胞裏面,促進自然殺傷細胞英文Natural killer cell嘅活性,同促進淋巴細胞嘅增殖,而且喺感染嗰陣好快就消耗晒,呢啲作用表明呢樣嘢喺免疫系統功能入面發揮重要嘅作用[143]歐洲食品安全局英文European Food Safety Authority得出結論話,成年人同3歲以下細路嘅維他命C攝取量同正常免疫系統嘅功能之間存在住因果關係[144][145]

2型糖尿病

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有啲評論係矛盾嘅。由1個角度嚟睇,維他命C補充係唔可以建議用嚟管理2型糖尿病英文Type 2 diabetes[146]。不過,另一份報告話,補充高劑量嘅維他命C可以降低血糖英文Glucose test胰島素同埋糖化血紅蛋白A1c英文Glycated hemoglobin[147]

副作用

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口服攝入超過需要量嘅維他命C補充劑係會吸收得唔好[3],而血液入面過量嘅維他命C會好快噉經過喺尿液度排出嚟,所以維他命C嘅急性毒性就會低啲[4]。口服超過2-3克嘅維他命C可能會引起反胃、腹部絞痛同埋肚痾。呢啲症狀歸因喺未吸收嘅維他命C經過腸道嗰陣時嘅滲透作用[2]:156。理論上,高劑量嘅維他命C攝入可能會搞到鐵質嘅過量吸收。一項針對健康受試者嘅補充評論摘要冇報告過呢個問題,但係對於遺傳性血色素沉著症英文Iron overload病人可能會受到副作用影響嘅可能性,嗰份評論未做進一步研究[2]:158

喺20世紀,啲人曾經認為過,過量嘅維他命C補充劑會增加患腎石嘅風險[148]。不過,更加近期嘅有《關於過量攝取抗壞血酸導致腎結石形成只限於腎病患者的報告》[2]:156–157。2003年嘅一份評論指出「流行病學研究嘅數據唔支持過量嘅抗壞血酸攝入量同表面上健康嘅個體形成腎結石之間嘅關係」[149]。1篇2022年嘅評論發現,淨係得有限嘅證據顯示維他命C補充可以會搞到有腎結石[150]

有廣泛嘅研究指出話關於維他命C靜脈注射對醫敗血症[139]、嚴重新冠肺炎[117][118],同埋癌症[151]都有潛在嘅好處。評論列出咗每日劑量高達24g嘅試驗[117]

對於有可能出現嘅不良反應嘅擔憂係,高劑量嘅維他命C靜脈注射會搞到維他命C超出生理水平,跟住氧化降解產生脫氫抗壞血酸,因為噉而產生酸鹽,從而增加咗草酸鈣腎結石同埋草酸鹽腎病嘅風險。因為腎臟會有效噉排出多餘咗嘅維他命C,所以腎衰竭嘅人風險可能會高啲。第2,對於蠶豆症病人,佢哋應該避免去用維他命C嘅高劑量治療,因為呢樣嘢會搞到急性溶血。第3,因為維他命C同葡萄醣都有相似嘅分子結構,治療可能會干擾咗血糖計測量血糖水平嘅準確性,可能搞到會出現假性嘅血糖讀數偏高。就算有呢啲擔憂,但係對重症加護病房裏面嘅敗血症、敗血性休克、新冠肺炎同其他急性病症病人嘅元分析報告話,對於接受短期高劑量靜脈注射維他命C嘅病人嚟講,新發作嘅腎結石、急性腎損傷或者需要腎臟替代治療都冇增加到。呢個表明咗維他命C靜脈注射喺呢啲短期應用下係安全嘅[152][153][154]

歷史

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有「西方醫學之父」稱號嘅希波克拉底知道壞血病嘅存在,喺佢嘅《先知書Prorrheticorum》第2卷,同埋《論內在情感Liber de internis affectionibus》入面都有形容,詹姆斯·林德James Lind都引用過[155]老普林尼亦都形容過壞血病嘅症狀:(i) 普林尼Pliny嘅《自然史Naturalis historiae》第3輯第49頁;(ii)斯特拉波Strabo,《地理誌Geographicorum》第16輯,引自1881年嘅《國際外科百科全書International Encyclopedia of Surgery[156]

海上嘅壞血病

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1747年,英國皇家海軍嘅外科醫生占士·林德英文James Lind喺第1個記錄到嘅其中一個對照實驗入面,發現到生果嘅某種質素可以預防壞血病[157]

1497年,啲人响達伽馬嘅遠航裏面已經了解到柑橘類生果嘅療效[158]。喺1500年代,葡萄牙水手停靠喺聖海倫娜島,利用島上種植嘅菜園嚟種蔬菜同野生果樹[159]。當局偶爾會建議食用植物性食物嚟預防長途海上航行嘅壞血病。英國東印度公司嘅第1位外科醫生約翰·伍德英文John Woodall喺佢1617年出版嘅書《外科醫生助手The Surgeon's Mate》入面,推薦用檸檬汁用嚟做預防同治療嘅作用[160]。1734年,荷蘭作家約翰‧巴赫斯特倫英文Johann Bachstrom提出咗明確嘅意見話:「壞血病只係因為完全唔食新鮮蔬菜同綠葉菜造成嘅[161][162]。」喺長途海上航行入面,壞血病一早已經做咗水手嘅其中1種主要死因[163]。根據莊拿芬·蘭姆Jonathan Lamb嘅講法,「1499年,達伽馬喺170個船員裏面冇咗116個人;喺1520年,麥哲倫喺230個船員裏面冇咗208個;全部主要都係壞血病[164]。」

青檸、檸檬同埋橙係早期被識別做預防或者用嚟醫長途航行壞血病嘅嘢食。

最早試過喺科學角度解釋呢種病嘅病因係英國皇家海軍嘅船醫占士·林德。1747年5月,林德喺海上航行嗰陣,除咗正常嘅糧食之外,每日仲畀啲船員兩個橙同1個檸檬,而另1班船員就繼續同時食用正常嘅糧食,仲會飲蘋果酒硫酸水或者海水。呢個係世界上最早嘅其中1個對照實驗[157]。結果顯示柑橘可以預防呢個病。林德喺1753年响佢嘅《壞血病論Treatise on the Scurvy》發表咗佢嘅研究成果[165]

新鮮生果要擺喺船上面儲存成本好高,而將呢啲嘢煮成汁雖然方便儲存,但係就會將維他命破壞咗(尤其係喺銅壺裏面煮滾嗰陣時)[16]。直到1796年,英國海軍喺海上先至將檸檬汁用嚟做標準海上配給。1845年,西印度群島嘅船開始供應青檸汁,1860年,青檸汁開始喺皇家海軍全面噉去用,噉樣亦都令美國人起咗「酸橙味英文Glossary of names for the British#LimeyLimey」呢個花名畀英國人[157]占士曲船長之前已經證明咗喺1772-75年帶住佢嘅船員去太平洋航行,而佢冇因為壞血病而失去任何1個船員,騷到帶咗德國酸菜上船嘅好處[166]。1776年,英國皇家學會憑住佢關於呢個方法嘅報告而頒授予咗科普利獎章英文Copley Medal畀佢[167]

抗壞血antiscorbutic」呢個名喺18世紀同19世紀用嚟做已知可以預防壞血病嘅嘢食。呢啲嘢食包括檸檬、青檸、橙、德國酸菜、捲心菜、麥芽同埋便攜式湯英文Portable soup[168]。1928年,加拿大北極人類學家維爾赫亞爾穆爾·斯特凡臣英文Vilhjalmur Stefansson嘅研究話,伊努熱人因為佢哋嘅飲食以生肉為主嚟避免患壞血病。後來對加拿大北部嘅育空地區原住民甸尼人英文Dene、伊努熱人同埋梅蒂人嘅傳統飲食做嘅研究話,佢哋每日嘅維他命C平均攝入量係喺每日52-62mg之間[169]

發現

[編輯]
想知多啲:維他命 § 歷史

維他命C喺1912年被發現,喺1928年分離出嚟,喺1933年被合成,令到呢樣嘢做咗第1個被合成出嚟嘅維他命[170]。之後冇幾耐,塔德烏什·賴希施泰因成功噉透過而家所謂嘅賴希斯坦法英文Reichstein process嘅工藝成功噉批量合成咗維他命C[171]。呢個令到維他命C嘅低成本大規模生產成為有可能嘅事。1934年,羅氏大藥廠買咗賴希斯坦法工藝嘅專利,用維多C英文Redoxon嚟註冊做合成維他命C嘅商標牌子,仲開始將呢樣嘢用嚟做膳食補充劑去推廣嚟賣[172][173]

1907年,挪威醫生阿克塞爾·霍爾斯特英文Axel Holst西奧多·弗羅利希英文Theodor Frølich喺研究船上嘅腳氣病英文Thiamine deficiency嗰陣意外發現英文Serendipity咗個幫到手去鑑定抗壞血因子嘅實驗動物模型,佢哋用穀物同麵粉嚟做實驗飼料去餵天竺鼠,佢哋好驚訝噉發現結果係天竺鼠患嘅係壞血病而唔係腳氣病。當時啲人唔知道嘅係,豚鼠(一種豚鼠科動物英文Caviomorpha)本身冇辦法自己去合成維他命C,而大鼠同小鼠就得[174]。1912年,波蘭生化學家卡西米爾·芬克英文Casimir Funk提出咗維他命嘅概念,其中1種被認為就係抗壞血病因子。1928年,雖然呢樣嘢嘅化學結構仲未確定得到,呢種因子就被叫做「水溶性Cwater-soluble C[175]

Albert Szent-Györgyi was awarded the Nobel Prize in Medicine in part for his research on vitamin C
呢張相係阿爾伯特·聖捷爾吉喺1948年影嘅,佢憑住喺生物燃燒過程方面嘅發現,特別係維他命C同埋反丁烯二酸(fumaric acid)嘅催化而攞到1937年嘅諾貝爾醫學獎[176]

喺1928年—1932年,阿爾伯特·聖捷爾吉英文Albert Szent-Györgyi約瑟夫·L·斯維爾貝利Joseph L. Svirbely嘅匈牙利團隊,仲有查理斯·格蘭·京英文Charles Glen King嘅美國團隊,佢哋識別咗抗壞血病因子出嚟。聖捷爾吉喺動物腎上腺入面將己糖醛酸分離出嚟,仲懷疑呢啲就係抗壞血因子[177]。喺1931年年尾,聖捷爾吉將佢最後1種喺腎上腺衍生嘅己醣醛酸交咗畀斯維爾貝利,仲暗示呢樣嘢可能係抗壞血病因子。

去到1932年春天,京嘅實驗室證實呢個事實,但係發表結果嗰陣時就冇歸功畀聖捷爾吉。呢個引發咗1場關於優先權嘅激烈爭議[177]。1933年,諾文·哈禾夫英文Norman Haworth透過化學驗證嘅方法鑑定出呢種維他命係L-己醣醛酸l-hexuronic acid,仲喺同年透過合成實驗嚟證實咗呢1點[178][179][180][181]。哈禾夫同聖捷爾吉提出將L-己醣醛酸命名做α-抗壞血酸,化學上嘅名係L-抗壞血酸,嚟紀念呢樣嘢對抗壞血病嘅功效[181][170]。呢個術語嘅詞源嚟自拉丁語,「a-」意思係「離開」或者「脫離」,而「-scorbic」就嚟自同壞血病有關嘅中世紀拉丁語「scorbuticus」,同埋古北歐語「skyrbjugr」、法語「scorbut」、荷蘭語「scheurbuik」,同埋低級德文「scharbock」同源[182]。聖捷爾吉憑住呢項發現而榮獲1937年嘅諾貝爾醫學獎[176],而哈禾夫亦都分享咗嗰年嘅諾貝爾化學獎[183]

1957年,J·J·伯恩斯Burns發現某喺哺乳動物容易患壞血病,因為佢哋嘅肝臟冇辦法產生1種叫做L-古洛糖酸內酯氧化酶英文L-gulonolactone oxidase酵素,呢個係合成維他命C嘅4種酶鏈入面嘅最後1種[184][185]。美國生物化學家歐文‧史東英文Irwin Stone係第1個利用維他命C嘅食品防腐特性嘅人。佢後來發展出1個諗法,即係人類擁有1種l- 古洛內酯氧化酶編碼基因嘅突變形式[186]。史東向萊納斯·保林Linus Pauling介紹咗呢個理論,即係為咗達到最佳嘅健康狀態,人類需要嘅維他命C攝取遠高過當時建議嘅每日攝取量[187]

2008年,研究人員發現人類同其他靈長類動物嘅紅血球已經進化出1個將氧化咗嘅L-脫氫抗壞血酸(DHA)重新轉化做抗壞血酸嘅機制嚟畀身體再用,噉樣就可以更加有效率噉利用身體入面存在嘅維他命C。呢個機制並冇發現喺自身合成維他命C嘅哺乳類動物身上出現[188]

高劑量療法

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高劑量維他命C係指攝取或者注射維他命C嘅劑量,相當或者高過晒能夠自身合成維他命C嘅哺乳類動物肝臟所產生嘅量。呢個論點雖然唔係實際嘅用語,不過鮑林喺1970年嘅1篇文章入面闡述咗支持呢個觀點嘅論點。簡單嚟講,佢嘅觀點係,為咗達到最佳嘅健康狀態,人類應該每日攝取至少2,300mg嘅維他命C嚟彌補自身冇辦法合成維他命C嘅不足。呢個建議亦都同1種同人類親緣關係近啲但都係自身冇辦法合成維他命C嘅大猩猩嘅攝取量範圍相符[72]。第2個支持高攝入量嘅論點係,血清抗壞血酸濃度會跟住攝取量嘅增加而升高,直到當攝取量超過1,250mg之後,濃度就會穩定喺大約190-200個μmol/L嘅水平[189]。正如上面所指出嘅噉,政府建議嘅劑量範圍喺每日40-110mg,而正常血漿嘅濃度大約喺每升50個μmol,所以「正常」濃度大約係口服劑量喺建議嘅高劑量範圍裏面可以達到嘅25%。

鮑林喺1970年普及咗高劑量維他命C用嚟預防同埋去醫普通傷風嘅概念,佢喺幾年之後提出維他命C可以用嚟預防心血管疾病,而最初每日10g噉靜脈注射維他命C,之後口服,可以醫得好末期癌症[190]。高劑量噉去服用抗壞血酸都有其他支持者,包括化學家歐文‧史東[187]同埋好有爭議性嘅馬蒂亞斯‧拉夫英文Matthias Rath同埋帕德里克‧霍福德英文Patrick Holford,佢哋兩個曾經都被指控喺為咗去醫癌症同HIV感染而提出冇證實過嘅治療療法[191][192]。就算喺鮑林嘅開創性論文發表咗之後大約卌年之後,大劑量嘅抗壞血酸靜脈注射可以改善末期癌症嘅結果又或者改善化療嘅毒性—呢個諗法仍然被認為係未經證實,仍然需要去做高質素嘅研究嚟驗證[193][194][151]

研究方向

[編輯]

癌症研究

[編輯]

有研究正喺度調查高劑量嘅維他命C靜脈注射用嚟做聯合治療係咪可以抑制癌症幹細胞英文Cancer stem cell,而呢啲癌症幹細胞負責腫瘤復發、轉移同化療抗藥性嘅罪魁禍首[195][196]

皮膚老化研究

[編輯]

目前亦都有持續關於局部應用維他命C用嚟預防皮膚老化跡象嘅研究正喺度做緊。 人體皮膚生理上含有少量維他命C,可以促進膠原蛋白嘅合成,減少膠原蛋白嘅降解,仲有助抗氧化保護,抵抗紫外線引起嘅光老化,包括光致癌作用英文Carcinogenesis。呢啲知識成日被用嚟做維他命C做局部「精華」成份去做推廣嘅理據,用喺預防或醫面部皮膚老化、黃褐斑英文Melasma(色素沉著斑)同埋皺紋;不過,呢啲講法冇證據支持,亦都得唔到目前為止做嘅研究去支持;局部治療相對於口服嘅所謂療效仲係唔太清楚[197][198]。局部應用維他命C對減慢皮膚老化嘅所謂機制就係,維他命C有抗氧化作用,可以中和嚟自陽光照射、空氣污染物,或者正常代謝過程嘅自由基英文Free-radical theory of aging[199]。臨床試驗文獻畀人認為唔夠去支持呢啲健康聲稱;其中1個原因係「所有研究都係用維他命C同其他成份或治療機制結合嚟用,所以搞到任何關於維他命C療效嘅具體結論都會變得複雜[200][201]。」

肺炎

[編輯]

需要進一步研究去確定預防性維他命C嘅治療係咪對預防或者治療肺炎有幫助[202]

[編輯]
  1. 雙子葉植物淨係運送亞鐵英文Ferrous離子(Fe²⁺),但如果鐵用三價鐵離子英文Ferric絡合物(Fe³⁺)嘅形式循環,就一定要做還原先至能夠主動運輸。植物胚胎會分泌大量嘅抗壞血酸,抗壞血酸能夠將三價鐵喺三價鐵絡合物還原返出嚟[85]
  2. 雙子葉植物胚胎排出嘅抗壞血酸係鐵還原嘅1種公認嘅機制,亦都係鐵吸收嘅必要步驟[a]
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