維他命C
| 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
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,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、頭痛、瞓唔著同埋皮膚發紅,美國國家醫學醫學院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·聖捷爾吉憑住佢嘅發現而攞咗1937年嘅諾貝爾生理學或醫學獎。
來源
[編輯]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
[編輯]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[7] | 1,000-5,300 |
| 卡姆果[8] | 2,800 |
| 針葉櫻桃[9] | 1,677 |
| 油柑子[10][11] | 445 |
| 玫瑰果 | 426 |
| 海沙棘[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 | 80 |
| 雲莓、 | 60 |
| 士多啤梨 | 60 |
| 木瓜 | 60 |
| 橙、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、桃 | 7 |
| 蘋果 | 6 |
| 紅蘿蔔、露筍 | 6 |
動物來源
[編輯]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
[編輯]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,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
[編輯]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《
補充劑
[編輯]
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
飲食
[編輯]建議攝取量
[編輯]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:
- 世界衞生組織[23]:每日40mg/每個禮拜300mg;
- 印度海德拉巴國家營養研究所[24]:每日40mg;
- 歐洲委員會
營養標籤理事會 [25]:每日80mg; - 2007年加拿大衛生部[26]:(男性)每日90mg;(女性)每日75mg;
- 美國國家科學院[2]:134–152:(男性)每日90mg;(女性)每日75mg;
- 日本國立健康營養研究所[27]:每日100mg;
- 歐洲食品安全局[28]:(男性)每日110mg;(女性)每日95mg;
2000年,《北美膳食參考攝取量》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(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(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(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
可耐受最高攝入量
[編輯]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
[編輯]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」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
[編輯]抗壞血酸同呢樣嘢嗰啲鹽同酯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[36][37]。呢樣嘢可能用嚟做整麪包嘅麵團改良劑[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(EFSA)負責[39]。相關嘅E編號係:
- 已經批准喺英國[40]、美國[41]、加拿大[42]、澳洲同紐西蘭[43]用嚟做食物添加劑:E300 抗壞血酸;
- 已經批准喺英國[40]、美國[41]、加拿大[42]、澳洲同紐西蘭[43]用嚟做食物添加劑:E301 抗壞血酸鈉;
- 已經批准喺英國[40]、美國[41]、加拿大[42]、澳洲同紐西蘭[43]用嚟做食物添加劑:E302 抗壞血酸鈣;
- 已經批准喺澳洲同紐西蘭[43],但未喺英國、美國或加拿大攞到批准:E303 抗壞血酸鉀;
- 已經批准喺英國[40]、美國[41]、加拿大[42]、澳洲同紐西蘭[43]用嚟做食物添加劑:E304
抗壞血酸脂肪酸酯 ,例如抗壞血酸棕櫚酸酯。
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同埋佢嘅鈉鹽(E315同E316)[40]。
缺乏症
[編輯]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
[編輯]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
[編輯]
「維他命C」呢個名通常指嘅係抗壞血酸嘅對映異構體,同埋呢樣嘢嘅氧化還原反應形式—
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
[編輯]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—異抗壞血酸[50]。維他命C喺植物裏面嘅中合成係透過將甘露糖或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(包括哺乳動物同雀形目嘅雀)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-
動物合成
[編輯]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-
非合成者
[編輯]有啲哺乳動物已經冇咗合成維他命C嘅能力,包括猿猴同眼鏡猴,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。例如係天竺鼠同水豚呢啲豚鼠科嘅物種係冇合成維他命C嘅能力,不過例如大鼠同小鼠就有呢種能力[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[68](真骨魚[67])都冇咗合成維他命C嘅能力。血吸蟲(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。
動物合成嘅進化
[編輯]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,參與膠原蛋白嘅合成,同時亦都係1種強效嘅還原劑,可以好快噉清除幾種
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——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[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。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
[編輯]
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,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-半乳糖脫氫酶催化L-半乳糖氧化成內酯,仲將內酯異構化做C4-羥基,產生
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、果糖或甘露糖(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-
工業合成
[編輯]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,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在先,然後再用發酵轉化做山梨糖[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
[編輯]藥效學
[編輯]藥效學包括維他命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,同埋輔因子仲有電子供體抗氧化劑嚟發揮作用。佢嘅酵素功能包括膠原蛋白、肉鹼同埋神經遞質嘅合成;酪氨酸嘅合成同分解代謝,仲有微粒體嘅代謝。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嚟發揮作用,對癌細胞產生治療毒性[95][96]。
- 喺膠原蛋白嘅合成過程裏面,脯氨酸同賴氨酸嘅羥基化需要3組酵素,包括脯氨酸羥化酶、脯氨酸-4-羥化酶同埋賴胺酸羥化酶。呢啲反應透過脯氨酸羥化酶同賴胺酸羥化酶將氫氧化物加到去膠原蛋白分子入面嘅脯氨酸或者賴氨酸上面,而呢兩種酵素都需要維他命C用嚟做輔因子。維他命C用嚟做輔因子嘅作用係將脯氨酸羥化酶同賴氨酰羥化酶由Fe2+氧化成Fe3+,同埋將佢由Fe3+還原成Fe2+。羥基化令到膠原蛋白分子形成3重螺旋結構,因此維他命C對於疤痕組織、血管同軟骨嘅形成同維持係必要嘅。
- 肉鹼嘅合成需要兩種酵素:三甲基賴氨酸雙加氧酶同埋γ-丁基甜菜鹼雙加氧酶。肉鹼係將脂肪酸輸送去到粒線體入面,係產生三磷酸腺苷嘅必要條件。
- 缺氧誘導因子—脯胺酸羥化酶(同工型:EGLN1、EGLN2同EGLN3)令到細胞可以對低濃度氧氣做出生理反應。
- 多巴胺β羥化酶參與多巴胺生物合成去甲腎上腺素嘅過程。
- 肽酰甘氨酸α-醯胺化單加氧酶係透過喺佢哋嘅C尾端甘氨酸殘基裏面整走乙醛酸殘基,令到肽類激素酰胺化。噉樣會增加肽激素嘅穩定性同活性。
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
[編輯]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,腦垂體同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
健康影響
[編輯]
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[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
[編輯]血壓
[編輯]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
普通傷風
[編輯]
對傷風入面嘅維他命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
[編輯]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(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
[編輯]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
[編輯]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
[編輯]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
[編輯]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受體嚟吸收[129]。
牙周病
[編輯]壞血病
[編輯]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同皮下出血,牙齦亦都會出血。皮膚病變最常見喺大髀同腳膼。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膿、甩牙、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]。
喺第二次世界大戰嗰陣,英國對良心拒服兵役者做咗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
[編輯]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
[編輯]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[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、胰島素同埋糖化血紅蛋白A1c[147]。
副作用
[編輯]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
[編輯]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《
海上嘅壞血病
[編輯]
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·伍德喺佢1617年出版嘅書《

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、醋、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《
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「
「
發現
[編輯]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·霍爾斯特同西奧多·弗羅利希喺研究船上嘅腳氣病嗰陣意外發現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)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「

喺1928年—1932年,阿爾伯特·聖捷爾吉同
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·哈禾夫透過化學驗證嘅方法鑑定出呢種維他命係
1957年,J·J·
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
[編輯]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‧拉夫同埋帕德里克‧霍福德,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,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。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(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[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]。
註
[編輯]- ↑ 雙子葉植物淨係運送亞鐵離子(Fe²⁺),但如果鐵用三價鐵離子絡合物(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]。
- ↑ 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]。
- ↑ Lykkesfeldt J, Carr AC (January 2024). "Vitamin C". Advances in Nutrition. 15 (1). doi:10.1016/j.advnut.2023.100155. PMC 10716693. PMID 37992968.
{{cite journal}}: Unknown parameter|article-number=ignored (help) - 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Institute of Medicine (US) Panel on Dietary Antioxidants Related Compounds (2000). "Vitamin C". Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: The National Academies Press. pp. 95–185. doi:10.17226/9810. ISBN 978-0-309-06935-9. PMID 25077263. 原先內容歸檔喺September 2, 2017. 喺September 1, 2017搵到.
- 1 2 3 4 "Vitamin C: Fact sheet for health professionals". Office of Dietary Supplements, US National Institutes of Health. March 26, 2021. 原先內容歸檔喺July 30, 2017. 喺25 February 2024搵到.
- 1 2 3 4 5 "Vitamin C". Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR. July 1, 2018. 原先內容歸檔喺July 12, 2019. 喺June 19, 2019搵到.
- ↑ "NDL/FNIC food composition database home page". USDA Nutrient Data Laboratory, the Food and Nutrition Information Center and Information Systems Division of the National Agricultural Library. 原先內容歸檔喺January 15, 2023. 喺30 November 2014搵到.
- ↑ "USDA national nutrient database for standard reference legacy: vitamin C" (PDF). U.S. Department of Agriculture, Agricultural Research Service. 2018. 原著 (PDF)喺November 18, 2021歸檔. 喺September 27, 2020搵到.
- ↑ Brand JC, Rae C, McDonnell J, Lee A, Cherikoff V, Truswell AS (1987). "The nutritional composition of Australian aboriginal bushfoods. I". Food Technology in Australia. 35 (6): 293–6.
- ↑ Justi KC, Visentainer JV, Evelázio de Souza N, Matsushita M (December 2000). "Nutritional composition and vitamin C stability in stored camu-camu (Myrciaria dubia) pulp". Archivos Latinoamericanos de Nutricion. 50 (4): 405–8. PMID 11464674.
- ↑ Vendramini AL, Trugo LC (2000). "Chemical composition of acerola fruit (Malpighia punicifolia L.) at three stages of maturity". Food Chemistry. 71 (2): 195–8. doi:10.1016/S0308-8146(00)00152-7.
- ↑ Begum RM (2008). A textbook of foods, nutrition & dietetics. Sterling Publishers Pvt. Ltd. p. 72. ISBN 978-81-207-3714-3.
- ↑ Sinha N, Sidhu J, Barta J, Wu J, Cano MP (2012). Handbook of fruits and fruit processing. John Wiley & Sons. ISBN 978-1-118-35263-2.
- ↑ Gutzeit D, Baleanu G, Winterhalter P, Jerz G (2008). "Vitamin C content in sea buckthorn berries (Hippophaë rhamnoides L. ssp . rhamnoides) and related products: A kinetic study on storage stability and the determination of processing effects". J Food Sci. 73 (9): C615–C20. doi:10.1111/j.1750-3841.2008.00957.x. PMID 19021790.
- ↑ Clark S (8 January 2007). "Comparing milk: human, cow, goat & commercial infant formula". Washington State University. 歸檔時間January 29, 2007. 喺February 28, 2007搵到.
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{{cite web}}: CS1 maint: unfit URL (link) - ↑ Zhou M, Bi Y, Ding M, Yuan Y (2021). "One-step biosynthesis of vitamin C in Saccharomyces cerevisiae". Front Microbiol. 12. doi:10.3389/fmicb.2021.643472. PMC 7947327. PMID 33717042.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Lbban E, Kwon K, Ashor A, Stephan B, Idris I, Tsintzas K, Siervo M (December 2023). "Vitamin C supplementation showed greater effects on systolic blood pressure in hypertensive and diabetic patients: an updated systematic review and meta-analysis of randomized clinical trials". Int J Food Sci Nutr. 74 (8): 814–25. doi:10.1080/09637486.2023.2264549. PMID 37791386. S2CID 263621742. 原先內容歸檔喺January 21, 2024. 喺December 23, 2023搵到.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Stratton J, Godwin M (June 2011). "The effect of supplemental vitamins and minerals on the development of prostate cancer: a systematic review and meta-analysis". Family Practice. 28 (3): 243–52. doi:10.1093/fampra/cmq115. PMID 21273283.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Al-Khudairy L, Flowers N, Wheelhouse R, Ghannam O, Hartley L, Stranges S, Eres K (March 2017). "Vitamin C supplementation for the primary prevention of cardiovascular disease". The Cochrane Database of Systematic Reviews. 2017 (3). doi:10.1002/14651858.CD011114.pub2. PMC 6464316. PMID 28301692.
{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Ashor AW, Lara J, Mathers JC, Siervo M (July 2014). "Effect of vitamin C on endothelial function in health and disease: a systematic review and meta-analysis of randomized controlled trials". Atherosclerosis. 235 (1): 9–20. doi:10.1016/j.atherosclerosis.2014.04.004. PMID 24792921.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - 1 2 DeLoughery TG (March 2017). "Iron Deficiency Anemia". The Medical Clinics of North America (Review). 101 (2): 319–332. doi:10.1016/j.mcna.2016.09.004. PMID 28189173.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Heffernan A, Evans C, Holmes M, Moore J (2017). "The Regulation of Dietary Iron Bioavailability by Vitamin C: A Systematic Review and Meta-Analysis". Proceedings of the Nutrition Society. 76 (OCE4). doi:10.1017/S0029665117003445.
{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Mi N, Zhang M, Ying Z, Lin X, Jin Y (January 2024). "Vitamin intake and periodontal disease: a meta-analysis of observational studies". BMC Oral Health. 24 (1). doi:10.1186/s12903-024-03850-5. PMC 10799494. PMID 38245765.
{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Tada A, Miura H (July 2019). "The relationship between vitamin C and periodontal diseases: A systematic review". Int J Environ Res Public Health. 16 (14): 2472. doi:10.3390/ijerph16142472. PMC 6678404. PMID 31336735.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Berger MM, Oudemans-van Straaten HM (March 2015). "Vitamin C supplementation in the critically ill patient". Curr Opin Clin Nutr Metab Care. 18 (2): 193–201. doi:10.1097/MCO.0000000000000148. PMID 25635594. S2CID 37895257.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Wintergerst ES, Maggini S, Hornig DH (2006). "Immune-enhancing role of vitamin C and zinc and effect on clinical conditions" (PDF). Annals of Nutrition & Metabolism. 50 (2): 85–94. doi:10.1159/000090495. PMID 16373990. S2CID 21756498. 原先內容歸檔 (PDF)喺July 22, 2018. 喺August 25, 2019搵到.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Goodwin JS, Tangum MR (November 1998). "Battling quackery: attitudes about micronutrient supplements in American academic medicine". Archives of Internal Medicine. 158 (20): 2187–91. doi:10.1001/archinte.158.20.2187. PMID 9818798.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ O'Connor EA, Evans CV, Ivlev I, Rushkin MC, Thomas RG, Martin A, Lin JS (June 2022). "Vitamin and Mineral Supplements for the Primary Prevention of Cardiovascular Disease and Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force". JAMA. 327 (23): 2334–2347. doi:10.1001/jama.2021.15650. PMID 35727272.
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- ↑ Shrestha DB, Budhathoki P, Sedhai YR, Mandal SK, Shikhrakar S, Karki S, Baniya RK, Kashiouris MG, Qiao X, Fowler AA (October 2021). "Vitamin C in critically ill patients: An updated systematic review and meta-analysis". Nutrients. 13 (10): 3564. doi:10.3390/nu13103564. PMC 8539952. PMID 34684565.
- ↑ Holford P, Carr AC, Zawari M, Vizcaychipi MP (November 2021). "Vitamin C intervention for critical COVID-19: A pragmatic review of the current level of evidence". Life. 11 (11): 1166. Bibcode:2021Life...11.1166H. doi:10.3390/life11111166. PMC 8624950. PMID 34833042.
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As they sailed farther up the east coast of Africa, they met local traders, who traded them fresh oranges. Within six days of eating the oranges, da Gama's crew recovered fully
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On returning, Lopes' ship had left him on St Helena, where with admirable sagacity and industry he planted vegetables and nurseries with which passing ships were marvelously sustained. [...] There were 'wild groves' of oranges, lemons and other fruits that ripened all the year round, large pomegranates and figs.
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Succus Limonum, or juice of Lemons ... [is] the most precious help that ever was discovered against the Scurvy[;] to be drunk at all times; ...
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... sed ex nostra causa optime explicatur, que est absentia, carentia & abstinentia a vegetabilibus recentibus, ... ( ... but [this misfortune] is explained very well by our [supposed] cause, which is the absence of, lack of, and abstinence from fresh vegetables, ...
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{{cite journal}}: CS1 maint: DOI inactive as of 7月 2025 (link) - ↑ Correia G, Magina S (July 2023). "Efficacy of topical vitamin C in melasma and photoaging: A systematic review". J Cosmet Dermatol. 22 (7): 1938–45. doi:10.1111/jocd.15748. PMID 37128827. S2CID 258439047.
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{{cite journal}}: Unknown parameter|article-number=ignored (help)