維他命D
| 維他命D | |
|---|---|
| 藥嘅種類 | |
膽鈣化醇(維他命D3) | |
| 點用 | 佝僂病、骨質疏鬆、軟骨病、維他命D缺乏症 |
| 生物目標 | 維他命D受體 |
| ATC代碼 | A11CC |
| 拎 | |
| MeSH | D014807 |
| AHFS/Drugs.com | MedFacts 天然產品 |
維他命D(英文:Vitamin D)係1組結構相關嘅脂溶性維他命,呢種化合物負責促進腸道對鈣同磷酸鹽嘅吸收,幫手去調節身體裡面嘅鈣同磷嘅含量,仲有好多其他生物學功能[1][2]。呢群化合物喺人類身上最重要嘅係維他命D2(麥角鈣化醇)同埋維他命D3(膽鈣化醇)[2][3]。人類可以透過曬太陽,身體裡面就會自動合成維他命D。
維他命D唔似其他12種維他命,呢樣嘢只係飲食入面有條件噉樣必需,因為當皮膚充分噉暴露喺陽光嘅輻射成份—紫外線B(UVB)嗰陣時,皮膚表皮深層先至可以化學合成鈣化醇。維他命D亦都可以透過飲食、食品強化同埋營養補充劑嚟攞到[2]。對於大部分人嚟講,皮膚合成嘅貢獻比飲食來源嘅仲要多[4]。喺美國,奶類同植物奶替代品都加咗維他命D3落去,仲有好多早餐穀物都係噉樣。鑑於城市生活可能會搞到唔夠陽光照射,喺戶外嗰陣時揀去着幾多衫嘅文化,同埋因為擔心陽光照射嘅安全而去搽防曬霜,美國飲食指南因為噉而一般都假設一個人所有嘅維他命D都係嚟自口服。
膽鈣化醇喺肝臟會轉化做骨化二醇(又叫做
類型
[編輯]| 種類 | 化學物 | 結構 |
|---|---|---|
| 維他命D1 | 麥角鈣化醇同埋光固醇比例1:1嘅分子化合物混合物。 | |
| 維他命D2 | 由麥角固醇轉化成嘅麥角鈣化醇。 | |
| 維他命D3 | 由皮膚入面嘅7-脫氫膽固醇轉化成嘅膽鈣化醇。 | |
| 維他命D4 | 22-二氫麥角鈣化醇 | |
| 維他命D5 | 由7-脫氫谷固醇轉化成嘅種子鈣化醇。 |
維他命D存在幾種形式嘅維他命異構體,其中兩種主要形式係維他命D2嘅麥角固醇,同埋維他命D3嘅膽鈣化醇[1]。「維他命D」呢個成日用嘅術語所指嘅係維他命D2同維他命D3,呢兩種物質分別喺1931年同1935年做咗化學表徵出嚟。維他命D3係由7-脫氫膽固醇經過紫外光照射而產生嘅。雖然喺1981年推薦過用維他命D形式嘅化學命名法[5],不過其他名仍然係成日用嘅[3]。
喺化學角度嚟睇,各種形式嘅維他命D都係開環甾類化合物,呢樣嘢意味住甾類環入面嘅1個鍵斷裂咗[6]。維他命D2同維他命D3嘅結構差異就喺側鏈:維他命D2喺22號同23號碳原子之間有個雙鍵,喺24號碳原子上面就有個甲基。維他命D類似物亦都已經被合成出嚟[3]。
美國膳食指南一般都會因為城市生活可能搞到唔夠陽光照射,文化因素影響啲人喺戶外活動嗰時著衫量,同埋因為擔心陽光照射嘅安全(包括皮膚癌風險)而去搽防曬,所以佢哋通常會假設一個人所需嘅維他命D全部都係嚟自口服[2][7]:362–394。
膳食攝取
[編輯]食物來源
[編輯]好少食物裡面天然含有維他命D。用嚟做營養保充劑嘅魚肝油,每茶匙就含有450個國際單位(IU)。脂肪豐富嘅魚類(而唔係例如吞拿魚呢啲瘦魚)係維他命D3嘅最好嘅天然食物來源,而牛肝、雞蛋同芝士都含有適量嘅維他命D。蘑菇因為可以透過紫外線處理嚟大大噉提高含量,所以蘑菇提供嘅D2含量都唔同[8][9]。喺某啲國家,早餐穀物、奶製品同植物奶製品都係強化嘅。嬰兒配方奶粉每升加入400-1000個IU嘅維他命D[2][10],呢個對於足月嬰兒出生頭1個月之後嘅正常攝取量嚟講係個正常嘅含量[11]。煮食只會減少維他命嘅含量[10]。
| 食物來源[2] | 劑量 (IU/每份) |
|---|---|
| 3盎士養殖虹鱒(已煮熟) | 645 |
| 3盎士三文魚(紅鮭)(已煮熟) | 570 |
| 1/2 杯經紫外線照射嘅菇(120毫升) | 366[8] |
| 1/2 杯未經紫外線照射嘅菇(120毫升) | 7[8] |
| 1杯2%嘅乳脂強化牛奶 | 120 |
| 1杯強化植物奶 | 100–144 |
| 1份即食強化穀物 | 80 |
| 1隻大蛋,炒蛋 | 44 |
| 3盎司牛肝(已煮熟) | 42 |
| 1.5盎司車打芝士 | 17 |
食物強化
[編輯]喺1930年代初,美國同北歐嘅國家開始用維他命D嚟強化牛奶去消滅佝僂病。呢個動作,加上醫學建議畀嬰幼兒曬多啲太陽,有效年噉遏止咗佝僂病嘅高患病率。維生素D嘅健康益處已經得到證實之後,令到好多食物都可以加強,甚至係包括熱狗同埋啤酒呢類睇落去唔太啱嘅食物。喺1950年代,由於有啲高血鈣症同先天缺陷個案被廣泛報道咗出嚟,維他命D強化食物嘅生產變得受管制,而喺某啲國家甚至亦停止使用呢種做法[12]。截至2024年,分別有15個同10個國家政府建立咗授權或自願性嘅食物強化計劃喺對抗維他命D缺乏症[13]。根據唔同國家嘅規定[13],用維他命D2或維他命D3強化嘅加工食品包括乳製品奶同埋其他乳製品,果汁同果汁飲品,代餐食物棒,大豆蛋白飲品,小麥粉或者粟米粉製品、嬰兒奶粉、穀類早餐同植物奶[14][15][16],最後1種被形容做由大豆、杏仁、大米、燕麥同其他植物來源製成,目的係用嚟替代乳製品嘅飲品[17]。
建議攝取量
[編輯]| 英國 | ||
| 年齡組 | 攝取量 (μg/日) |
最大攝取量 (μg/日)[18] |
|---|---|---|
| 母乳餵哺嬰兒(0-12 個月) | 8.5–10 | 25 |
| 配方奶粉餵哺嬰兒(每日<500毫升) | 10 | 25 |
| 1–10歲細路 | 10 | 50 |
| >10歲細路同成年人 | 10 | 100 |
| 美國 | ||
| 年齡組 | RDA (每日IU)[7] |
每日μg |
| 0-6個月大嬰兒 | 400* | 10 |
| 6-12個月大嬰兒 | 400* | 10 |
| 1–70歲 | 600 | 15 |
| > 70歲成年人 | 800 | 20 |
| 懷孕/哺乳期婦女 | 600 | 15 |
| 年齡組 | 可耐受最高攝取量 (每日IU)[7] |
每日μg |
| 0-6個月大嬰兒 | 1,000 | 25 |
| 6-12個月大嬰兒 | 1,500 | 37.5 |
| 1–3歲細路 | 2,500 | 62.5 |
| 4–8歲細路 | 3,000 | 75 |
| 9歲以上 | 4,000 | 100 |
| 懷孕/哺乳期婦女 | 4,000 | 100 |
| 加拿大 | ||
| 年齡組 | RDA (每日IU)[19] |
可耐受最高攝取量(IU)[19] |
| 0-6個月大嬰兒 | 400* | 1,000 |
| 7–12個月大嬰兒 | 400* | 1,500 |
| 1–3歲細路 | 600 | 2,500 |
| 4–8歲細路 | 600 | 3,000 |
| 9–70歲細路同成年人 | 600 | 4,000 |
| >70歲成年人 | 800 | 4,000 |
| 懷孕/哺乳期婦女 | 600 | 4,000 |
| 澳洲同紐西蘭 | ||
| 年齡組 | 充足攝入量 (μg)[20] |
攝入量上限 (μg)[20] |
| 0-12個月大嬰兒 | 5* | 25 |
| 1–18歲細路 | 5* | 80 |
| 19–50歲成年人 | 5* | 80 |
| 51–70歲成年人 | 10* | 80 |
| >70歲成年人 | 15* | 80 |
| 歐洲食品安全局 | ||
| 年齡組 | 充足攝入量 (μg)[21] |
可耐受上限 (μg)[22] |
| 0–12個月大嬰兒 | 10 | 25 |
| 1–10歲細路 | 15 | 50 |
| 11–17歲細路 | 15 | 100 |
| 成年人 | 15 | 100 |
| 懷孕/哺乳期婦女 | 15 | 100 |
| * 攝取量充足,但仲未確定RDA/RDI。 | ||
各國嘅政府機構對維他命D嘅參考每日攝入量都提出咗唔同嘅建議。呢啲建議會因應年齡、懷孕或者哺乳期,同埋對皮膚合成嘅假設程度而有唔同[2][18][19][21][20]。舊嘅建議攝取量比較低啲。例如,1997年美國嘅維他命D充足攝入量建議嬰兒、兒童、50歲以下同埋懷孕或哺乳期嘅婦女係每日200個國際單位(IU);51-70歲嘅人每日係400個IU,而71歲以上嘅人每日600個IU[23]。
換算:1個μg = 40個IU[18]。
政府機構出於膳食建議同食品標籤嘅目的,佢哋認為維他命D2同維他命D3係生物等效物[7][18][19][21][20]。
英國
[編輯]英國國民保健服務(NHS)建議,有維他命D缺乏風險嘅人、母乳餵哺嘅嬰兒、每日攝入唔超過500毫升嬰兒配方奶粉嘅嬰兒,同埋6個月至4歲嘅細路,佢哋應該全年每日噉去食維他命D補充劑嚟確保有足夠嘅攝入量[18]。呢啲包括皮膚合成維他命D能力有限嘅人,例如唔會成日做戶外活動、平時著遮住大部分皮膚嘅衫、體弱多病、臥床不起、住喺護養院嘅人,又或者例如係有非洲、非洲裔加勒比或者南亞裔背景嗰啲膚色比較深嘅人。而其他人可能可以喺4-9月透過充足嘅陽光照射下合成足夠嘅維他命D。NHS同英格蘭公共衛生署建議所有人,包括懷孕同餵哺緊母乳嘅女性,可以考慮喺秋冬期間每日服用含有10個μg(400個IU)嘅維他命D補充劑,因為嗰段期間陽光唔夠用嚟合成維他命D[24]。
美國
[編輯]喺2015年改名做美國國家醫學院嘅
喺美國,對於食品同膳食補充劑嘅標籤目的,每份含量係用每日數值嘅百分比(%DV)嚟表示。對於維他命D標籤嘅目的,每日價值嘅100%係400個IU(10個μg),不過喺2016年5月,呢個數字被修訂做800個IU(20個μg),令到呢個數字同建議膳食攝取量(RDA)保持一致[25][26]。喺參考每日攝入量嗰度提供咗個新舊成年人每日數值嘅列表。
加拿大
[編輯]澳洲同紐西蘭
[編輯]澳洲同紐西蘭喺2006年發表咗營養參考值,入面包括膳食維他命D攝入量嘅指引[20]。大約有1/3嘅澳洲人缺乏維他命D[27][28]。
歐盟
[編輯]歐洲食品安全局(EFSA)喺2016年檢討咗目前嘅證據,發現血清25(OH)D嘅濃度同肌肉骨骼健康結果之間嘅關係有好大嘅差異。佢哋認為冇辦法得出維他命D嘅平均需求量同埋人口參考攝入量,仲認為血清25(OH)D嘅濃度喺每升50個nmol係個啱啱好嘅參考值。對於所有1歲以上嘅人,包括大肚婆同哺乳期嘅女性,佢哋將維他命D嘅每日充足攝入量定咗喺每日15個μg(600個IU)[21]。
另一方面,歐盟委員會將
EFSA喺2012年檢討咗安全攝入量水平[22],將成年人嘅可耐受嘅上限設定做每日100個μg(4,000個IU),呢個結論同美國醫學研究所(IOM)嘅相似。
瑞典國家食品局建議,小朋友至75歲以下嘅成年人每日攝取10個μg嘅維他命D3,而75歲以上嘅成年人就建議每日攝入20個μg(800個IU)[30]。
歐洲嘅非政府組織都提出咗佢哋各自嘅建議。德國嘅營養學會建議每日攝取20個μg嘅維他命D[31]。
不足
[編輯]全球超過10億人[33],包括嬰幼兒、小朋友、成年人同老人家[34]——都可能被睇成係缺乏維他命D,報告嘅具體比例取決於用咩測量方法去定義「缺乏」[35]。2023年發表喺《
血清25 (OH) D嘅濃度被用嚟做維他命D缺乏症嘅生物標記。呢樣嘢嘅測量單位喺ng/mL或者nmol/L,1個ng/mL等於2.5個nmol/L。而家對於維他命D嘅缺乏、唔夠、充足,又或者對健康嘅所有方面最佳嘅攝取量都仲未有共識[35]。根據美國醫學研究所膳食參考攝取量委員會嘅數據,血清25 (OH) D嘅濃度低過每升30個nmol會顯著噉增加咗嬰幼兒因為維他命D缺乏症而患佝僂病嘅風險,仲將膳食鈣嘅吸收率由正常範圍嘅60-80%降低到去15%;而高過每升40個nmol就需要預防老人家骨質疏鬆症嘅骨質流失,同埋超過每升50個nmol就夠晒去滿足所有健康需要[7]:75–111。其他來源嘅文獻將缺乏症嘅定義係維他命D低過每升25個nmol,唔夠嘅定義係每升30-50個nmol[45],而最理想嘅水平定義係每升高過75個nmol[46][47]。部分爭議係因為研究報告顯示咗唔同種族之間嘅血清25 (OH) D嘅水平存在差異,而研究指出話呢啲變化背後存在遺傳同埋環境因素。非洲裔美國人嘅血清25 (OH) D水平低過同齡嘅白人人口,不過喺佢哋喺所有年齡層都有優越嘅鈣吸收率,同埋嘅骨骼礦物質密度高啲,而且作為老人家,患骨質疏鬆症同骨折嘅風險低啲[7](pp439–440)。理論上,喺呢個族群裡面補充嚟達到建議嘅「標準」濃度可能會引起有害嘅血管鈣化[48]。
利用25 (OH) D嘅檢測法嚟做一般健康人口嘅篩選工具去識別同治療某個人,呢個被認為唔及政府強制推行嘅維他命D強化計劃噉有成本效益。相反,有建議話嗰個計劃應該將檢測範圍淨係限制喺出現維他命D缺乏症,又或者已知會引起維他命缺乏症健康狀況嘅人[4][41]。
成因
[編輯]喺皮膚合成維他命D得唔夠嘅原因,包括因為住喺高緯度地區,所以唔夠接觸陽光裡面嘅UVB(距離赤道遠啲,冬天嘅日照時間短啲)。血清裡面維他命D嘅濃度喺冬季結束嗰時,可能會比夏季結束嗰時低1/3到一半[7]:100–101,371–379[4][12]。維他命D缺乏症嘅盛行率會隨住年齡嘅增長而增加,呢個係因為皮膚裡面嘅7-脫氫膽固醇嘅合成會少咗,同埋腎臟將骨化二醇轉化做骨化三醇嘅能力下降而造成[49],後者喺慢性腎病患者裡面更加明顯[50]。就算存在呢啲年齡因素嘅影響,如果皮膚接觸到足夠嘅UVB照射,老人家仍然可以合成到足夠嘅骨化三醇。如果唔係嘅話就建議食補充劑[49]。其他搞到合成唔夠嘅原因包括陽光畀空氣污染阻擋[51];城市/室內生活;長期住院同埋住喺長期護理設施入面;文化或宗教生活方式傾向揀去著啲防曬嘅衫;建議去用防曬嘅衣物或者搽防曬霜嚟減低患皮膚癌嘅風險;同埋最後深膚色對UVB嘅阻擋性質[40]。
喺冇咗皮膚合成嘅情況下,單靠食用天然含有豐富維他命D嘅食物,好少可以夠晒去維持建議嘅25(OH)D嘅血清濃度。維他命D嘅來源大致係:20%飲食,80%日照[4]。比起雜食者,純素食者嘅維他命D膳食攝取量會少啲,同埋血清25(OH)D水平低啲,而蛋奶素食者因為蛋黃同強化乳製品裡面含有嘅維他命含量,佢哋嘅維他命D水平就介乎於兩者之間[52]。目前,已經分別有15個國家強制推行食品強化計劃,同埋10個國家自願實施食品強化計劃嚟連接呢個差距[13]。美國係其中1個少數強制推行食品強化計劃嘅國家。最初嘅強化做法喺1930年代初開始,淨係局限喺牛奶,呢個對降低嬰幼兒佝僂病嘅發病率有好大嘅影響。喺2016年7月,FDA批准咗喺植物奶飲品裡面加入維他命D,而呢啲飲品係用嚟做牛奶替代品,例如由大豆、杏仁、椰子同燕麥製成嘅飲品[14]。喺個人層面嚟講,啲人可以揀去食複合維他命/礦物質產品,又或者淨係食含維他命D嘅產品[53]。
有好多病況、醫學治療同埋藥物都會將人推到去維他命D缺乏症嘅風險。增加維他命D缺乏症風險嘅慢性疾病包括腎衰竭[50]同肝衰竭、克隆氏症、發炎性腸道疾病,同埋例如囊性纖維化、仲有副甲狀腺功能亢進或減退呢啲吸收不良綜合症[40]。肥胖會將維他命D儲存喺脂肪組織入面嚟降低血清濃度[54],不過用嚟治療肥胖嘅減重手術會干擾咗膳食維他命D嘅吸收,亦都會令到維他命D缺乏[55]。影響維他命D相互代謝作用嘅藥包括抗逆轉錄病毒藥物、抗癲癇藥物、糖皮質激素、例如係
治療
[編輯]每日劑量嘅方案係首選過按時間表上每個禮拜或者每個月嘅高劑量方案,維他命D3可能會好過維他命D2,但係對於最好嘅類型、劑量、持續時間,又或者要衡量啲咩先可以叫做成功仍然仲係冇咩共識。除咗嬰兒之外,每日劑量大約係4,000個IU嘅方案對25(OH)D喺缺乏裡面恢復嘅影響會大啲,而且副作用風險會低啲,而每個禮拜或者每個月1次嘅高劑量方案(後者嘅劑量高到去100,000個IU)效果就會更加好。單劑劑量方案嘅唯一優點可能係病人嘅依從性好啲,因為單劑劑量通常由醫護人員畀藥,而唔係由病人自己去食藥[4]。雖然有啲研究發現維他命D3可以更快噉提高血液裡面25(OH)D嘅水平,仲喺身體裡面保持活性得更耐[57][58],不過有其他研究認為維他命D2嘅生物利用度仲有療效同維他命D3差唔多,都可以有效噉提高同維持25(OH)D嘅水平[8][59]。如果消化障礙影響吸收,高到去100,000個IU嘅維他命D3嘅肌肉注射係有治療作用[4]。
嬰兒嘅缺乏症
[編輯]喺啲哺乳媽咪身上做嘅比較研究顯示,母乳入面維他命D含量嘅平均值係每升有45個IU[60]。呢種維他命D含量太過低,低到冇辦法去滿足幾個政府機構建議嘅每日400個IU嘅維他命D攝取量需求(...因為母乳並唔係維他命D嘅有效來源)[7]:385。同樣呢啲嘅政府機構建議餵哺母乳嘅婦女每日要攝取600個IU嘅維他命D[2][18][19][21],不過呢個數量唔夠去提高母乳入面嘅維他命D含量嚟令呢樣嘢達到建議嘅攝取量[60]。有證據話母乳入面嘅維他命D含量可以提高,但因為維他命由哺乳媽咪嘅血清轉移去到乳汁係冇效率嘅,所以就需要去要求佢哋每日去食超過政府設定安全上限每日4,000個IU嘅維他命D膳食補充劑[60]。鑑於呢種唔夠,建議食母乳嘅嬰兒喺出生之後嘅頭1年每日就要畀佢哋食400個IU嘅維他命D膳食補充劑[60]。如果唔係食母乳嘅,嬰兒配方奶粉嘅設計係為咗每日食1公升配方奶粉嘅嬰兒提供400個IU嘅維他命D[61]—呢個係足月嬰兒出世頭1個月之後嘅正常飲奶量[11]。
深膚色嘅缺乏症風險
[編輯]黑色素,特別係真黑色素亞型,呢樣嘢係1種由氧化氨基酸酪氨酸分子連接而成嘅生物分子。呢樣嘢係由1種叫做黑素細胞嘅細胞喺叫做黑色素生成嘅過程入面產生。喺皮膚入面,黑色素係喺皮膚表皮嘅最底層(基底層)。黑色素可以永久噉融入皮膚搞到有深色皮膚,或者係因為接觸紫外線而引發呢樣嘢嘅合成,令到皮膚暫時變黑,形成曬黑。真黑色素係1種有效嘅光吸收劑;呢種色素可以吸收超過99.9%嘅紫外線輻射[62]。啲人因為呢種特性而認為真黑色素可以保護皮膚細胞唔使受到陽光入面嘅紫外線A(UVA)同紫外線B(UVB)輻射嘅損傷,嚟降低皮膚組織葉酸耗盡嘅風險,防止皮膚過早老化,仲降低曬傷同皮膚癌嘅風險[63]。黑色素會抑制皮膚裡面UVB促進嘅維他命D合成。喺世界上離赤道唔遠嘅地區,全年都有陽光充足照射意味住就算係膚色深啲嘅人喺皮膚上都可以攞到足夠嘅維他命D合成[64]。不過,當深膚色嘅人因為文化或者氣候原因而著衫遮住身體嘅大部分,或者主要喺城市嘅室內生活,又或者生活住喺冬天日照少啲嘅高緯度地區嗰陣時,佢哋就要面對維他命D缺乏症嘅風險[40][65]。最後1種情況叫做「緯度同膚色唔夾」[64]。
喺美國,維他命D缺乏症特別成日見到喺非白人西班牙裔同埋非裔美國人族群裡面[64][45][66]。不過,就算非裔美國人嘅平均25(OH)D嘅血清濃度低過每升50個nmol嘅充足水平,但係同歐洲裔嘅人去比,佢哋嘅骨質密度高啲,骨折風險低啲。可能嘅機制包括高啲嘅鈣保留量、低啲嘅鈣排泄量,同埋對甲狀腺副激素嘅骨骼抵抗力強啲[64][66][67],另外,遺傳因素亦都可能令到血清維他命D結合蛋白水平低啲,亦都係遺傳上降低血清維他命D結合蛋白,嚟到就算總血清25(OH)D嘅水平低啲,不過都可以保證到25(OH)D有足夠嘅生物利用度[68]。骨質密度同骨折風險之間嘅呢種矛盾現象未必會延續去到例如動脈鈣化、癌症、糖尿病或者全因死亡率呢啲非骨骼嘅健康狀況。而家有相反嘅證據話,喺非洲裔美國人口裡面,目前定義嘅「缺乏症」會增加非骨骼健康狀況嘅風險,而有啲證據話,補充反而會增加風險[64][66],包括有害嘅血管鈣化[48]。非裔美國人,同埋其他深膚色嘅黑人,可能需要對維他命D缺乏、不足同充足去做唔同嘅定義[48]。
過量
[編輯]對於維他命D可能會造成傷害嘅攝入量水平,到而家都仲未有統一嘅共識。根據IOM嘅評論,「每日劑量低過10,000個IU通常唔會同毒性有關,而維持幾個禮拜或者幾個月嘅每日劑量等同或者超過50,000個IU就會成日同毒性副作用有關,包括已經確診嘅高鈣血症[7]:427。」成年人血液裡面嘅25-羥基維他命D嘅正常濃度範圍喺每毫升有20-50個毫微克(ng/mL;相當於每公升50-125個nmol)。成年人引起不良反應所需要嘅血液濃度據認為係高過大約每毫升150毫微克[7](pp424–446)。
過量嘅維他命D會引起高血鈣症(血液裡面鈣濃度過高),呢個可能會令到骨骼同軟組織(包括動脈、心臟同腎臟)過度鈣化。如果唔醫唔醫嘅話,噉樣可能會搞到冇得逆轉嘅腎臟衰竭。維他命D中毒嘅症狀可能包括以下:口渴增加、尿量增加、噁心、嘔、肚屙、食慾下降、易嬲、便秘、攰、肌肉冇力、同埋失眠[73][74][75]。
2011年,美國國家醫學院修訂咗維他命D嘅可耐受攝取量上限(UL)嚟防止維他命D中毒。喺修訂之前,9歲以上嘅UL係每日50個μg(每日2,000個)[7]:424–445。根據修訂之後嘅定義係:「UL係指『一般人群裡面幾乎所有人攝取嘅某種營養素,而且嗰個攝取量唔太可能會對健康造成唔好影響風險嘅最高平均每日攝取量』[76]」。
美國按年齡劃分嘅男性同女性嘅UL,下面會用微克(mcg或μg)同國際單位(IU)嚟表示:
- 0-6個月:每日25個μg(每日1,000個IU);
- 7–12個月:每日38個μg(每日1,500個IU);
- 1–3歲:每日63個μg(每日2,500個IU);
- 4–8歲:每日75個μg(每日3,000個IU);
- 9歲以上:每日75個μg(每日3,000個IU);
- 孕婦期同埋哺乳期女性:每日100個μg(每日4,000個IU)。
雖然喺美國成年人嘅UL設定喺每日4,000個IU,不過市面上就有5,000、10,000甚至係50,000個IU嘅非處方維他命D產品(最後嗰種產品建議每個禮拜食1次)。每日攝取超過4,000個IU嘅美國人口比例自1999年以嚟就有增加[53]。
治療
[編輯]特殊情況
[編輯]容許嘅健康聲明
[編輯]政府監管機構為食物同膳食補充劑行業規定咗某啲容許嘅健康聲明,例如係包裝上面嘅說明:
- 美國嘅美國食品藥品監督管理局(FDA):
- 「充足嘅鈣同埋維他命D作為均衡飲食嘅一部分,再加上運動鍛煉,可能降低骨質疏鬆症嘅風險[81]」;
- 日本:具有營養功能聲稱嘅食品(FNFC):
- 「維他命D係1種可以促進腸道吸收鈣嘅營養素,亦都喺骨骼嘅發育幫到手[83]。」
健康影響
[編輯]補充維他命D係預防或者去醫佝僂病嘅可靠方法。另一方面,而家仲係未清楚維他命D嘅補充對非骨骼健康嘅影響[84][85]。有1項評論發現,除咗老人家死亡率可能有暫時性嘅跌咗之外,補充維他命D對非骨骼疾病嘅發病率係冇其他影響[86]。維他命D補充劑唔會改變到心肌梗塞、中風或腦血管病、癌症、骨折或者膝骨關節炎嘅結果[87][88][89]。
美國醫學研究所(IOM)嘅1份報告話:「同癌症、心血管病、高血壓同埋糖尿仲有代謝綜合症有關嘅結果,跌倒同身體機能,免疫功能同自體免疫疾病、感染、神經心理功能,同埋子癇前期有關嘅結果,而呢啲結果並唔可以同鈣質或者維他命D嘅攝入量可靠噉聯繫起上嚟,而且結果通常互相矛盾[7]:5。每種病嘅狀態都詳細提供咗支持同反對嘅證據[7]:124–299。有研究人員話,IOM嘅建議太過明確,而且喺計算同骨骼健康相關嘅維他命D血液水平嗰陣犯咗個數學上嘅錯誤[90]。IOM專家小組成員就堅持認為,佢哋係用咗「膳食建議嘅標準程序」,而嗰份報告係基於可靠嘅數據得出嚟嘅[90]。
骨骼健康
[編輯]
佝僂病係1種小朋友嘅病,特徵係生長受阻同遲緩,長骨柔軟、脆弱同畸形,喺小朋友開始識路識走嗰陣時,長骨會因為佢哋自己身體嘅重量而彎曲同變形。媽咪嘅維他命D缺乏會搞到胎兒喺出世之前出現骨骼缺陷,同埋出世之後骨質受損[91][92]。佝僂病通常喺3-18個月大之間出現[93]。呢個情況可能係由缺乏維他命D、鈣質或者磷質引起[94]。維他命D缺乏症仍然係大部分國家嘅嬰幼兒佝僂病嘅主要原因,因為母乳含有嘅維他命D低啲,而膚色深啲、社會習俗同氣候條件都可能令人曬唔夠太陽[未記出處或冇根據]。嬰幼兒喺斷奶之後嘅西方雜食性飲食,特點係高攝入肉類、魚類、蛋類同維他命D強化奶類係有保護作用,而呢啲食物嘅低攝入量,同埋穀物/穀類攝入量高就會增加有病嘅風險[95][96][97]。對於患咗佝僂病嘅年幼小朋友嚟講,補充維他命D加鈣質對骨骼癒合方面係優勝過單獨噉去用維他命[98][99]。
軟骨病同骨質疏鬆症
[編輯]
骨質疏鬆症嘅特徵係骨骼軟化,搞到脊椎彎曲、骨骼脆弱,同埋增加骨折嘅風險[1]。當25-羥基維他命D嘅水平每毫升低過10個ng嗰陣時,通常就會出現軟骨病[100]。軟骨病會發展去到骨質疏鬆症,呢種病會降低骨礦物質密度降低,同埋骨脆弱性同骨折風險都會增加嘅病。骨質疏鬆症可能係缺乏鈣同維他命D嘅長期後果,後者係透過減少鈣吸收而導致[2]。喺冇確診維他命D缺乏嘅情況下,冇證據顯示話補充維他命D而唔同時補充埋鈣)可以減慢或者阻止軟骨病發展做骨質疏鬆症[101]。對於骨質疏鬆嘅老人家嚟講,維他命D同鈣一齊食可能幫到手去預防髖關節骨折,但係亦都會輕微噉增加胃同腎臟問題嘅風險[102][103]。骨折風險降低嘅風險並未出現喺健康狀況好啲同住喺社區嘅老人家身上[87][104][105]。低血清維他命D水平同仆親有關[106],但係食多啲維他命D似乎唔會減低呢個風險[107]。
缺乏維他命D嘅運動員有高啲嘅疲勞性骨折同埋/或者係重大嘅斷裂風險,特別係參與接觸性運動嘅運動員。隨住血清25(OH)D嘅濃度升高,風險就會逐漸降低,當濃度去到每毫升50個ng嗰陣時會去到平台期,超過呢個濃度就唔會再帶嚟額外嘅好處[108]。
癌症
[編輯]雖然觀察研究顯示,血清25-羥基維他命D水平低嘅狀態同癌症風險高啲有關[109][110][111],雖然有啲證據顯示癌症死亡率會降低[109][112],不過總體結論係,冇足夠證據顯示補充維他命D對癌症風險有影響[2][113][114]。
心血管疾病
[編輯]補充維他命D同降低中風、腦血管病、心肌梗塞同冠心病嘅風險係冇關係嘅[87][115][116]。補充劑並唔能夠降低一般人嘅血壓[117][118][119]。1項綜合分析發現,當鈣同維他命D補充劑一齊食嗰陣,中風嘅風險會輕輕有些少增加[120]。
免疫系統
[編輯]維他命D受體喺參與免疫嘅細胞類型裡面發現。呢個功能仲係未明確。有啲自身免疫疾病同傳染病都係同缺乏維他命D有關,不過一係就話目前仲未有證據顯示維他命D補充係有益定冇益,一係就話或者對於某啲人嚟講,有證據顯示話並冇好處[121][122][123][124]。
自身免疫疾病
[編輯]有報告話,自身免疫性甲狀腺疾病[125]、全身性紅斑狼瘡[126]、重症肌無力[127]、類風濕性關節炎[128],同埋多發性硬化症病人嘅血漿維他命D濃度會低啲[129]。對於多發性硬化症同類風濕性關節炎,用維他命D補充劑嘅干預試驗並未顯示出治療效果[122][130]。
傳染病
[編輯]2021年嘅1項論述分析發現「維他命D補充係安全嘅,而且整體上可以降低急性呼吸道感染(ARI)嘅風險...雖然風險降低嘅幅度係細啲」[131]。一般嚟講,維他命D嘅功能夠去活化先天免疫系統同抑制特異性免疫系統,有抗菌、抗病毒同抗發炎嘅作用[132][133]。低血清維他命D濃度似乎係肺癆嘅危險因素[134]。不過,補充劑嘅試驗顯示冇任何好處[123][124]。
發炎性腸道疾病
[編輯]維他命D缺乏症同發炎性腸道疾病(IBD)嘅嚴重程度有關[135]。不過,維他命D缺乏症係咪引起IBD嘅病因,定係呢個病嘅後果仲係未清楚[136]。維他命D補充劑可以改善發炎性腸道疾病嘅臨床活動度評分同埋生化指標[136][137],仲減少IBD症狀嘅復發[136]。
哮喘
[編輯]COVID-19
[編輯]2020年7月,美國國家衛生院(NIH)話:「而家仲係冇足夠嘅證據去建議或者反對用維他命D補充劑嚟預防或者去醫COVID-19[139]。」同年,英國國家健康與卓越護理研究所(NICE)嘅立場係,唔建議單純為咗預防或者去醫COVID-19而向人提供維他命D補充劑[140]。2022年,NICE更新咗佢哋嘅立場,即係「除非係做臨床試驗嘅一部分,如果唔係就唔好用維他命D嚟去醫COVID-19[141]。」呢兩個機構都建議,因為其他原因(例如係骨骼同肌肉健康),應該視乎情況而決定係咪繼續沿用之前制訂嘅維他命D補充劑建議。兩個組織都話,因為疫情嗰陣曬太陽嘅量少咗,可能有更加多嘅人需要補充維他命D[139][140]。
維他命D缺乏症仲有不足都同COVID-19嘅副作用有關[142][143][144][145][146]。入院嗰陣時大多數係單一高劑量嘅口服補充劑試驗,據報話跟住之後轉送去重症加護同埋全因死亡率都會低啲[147][148][149]。
註
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - 1 2 3 Freedman BI, Register TC (June 2012). "Effect of race and genetics on vitamin D metabolism, bone and vascular health". Nature Reviews. Nephrology. 8 (8): 459–466. doi:10.1038/nrneph.2012.112. PMC 10032380. PMID 22688752. S2CID 29026212.
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<ref>標籤;無文字提供畀叫做"Mallard2016"嘅參照 - ↑ 引用錯誤 無效嘅
<ref>標籤;無文字提供畀叫做"Chen2024"嘅參照 - ↑ Saternus R, Vogt T, Reichrath J (2020). "Update: Solar UV Radiation, Vitamin D, and Skin Cancer Surveillance in Organ Transplant Recipients (OTRs)". Sunlight, Vitamin D and Skin Cancer. Adv Exp Med Biol.第1268卷. pp. 335–53. doi:10.1007/978-3-030-46227-7_17. ISBN 978-3-030-46226-0. PMID 32918227.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Kim YJ (May 2013). "Comparison of the serum vitamin D level between breastfed and formula-fed infants: several factors which can affect serum vitamin D concentration". Korean Journal of Pediatrics. 56 (5): 202–204. doi:10.3345/kjp.2013.56.5.202. PMC 3668200. PMID 23741233.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Autier P, Boniol M, Pizot C, Mullie P (January 2014). "Vitamin D status and ill health: a systematic review". The Lancet. Diabetes & Endocrinology. 2 (1): 76–89. doi:10.1016/S2213-8587(13)70165-7. PMID 24622671.
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- ↑ Massé O, Mercurio CM, Dupuis S, Al Sahwi M, Arruda A, Dallaire G, Desforges K, Dugré N, Williamson D (20 May 2026). "Calcium, vitamin D, or combined supplementation to prevent fractures and falls: systematic review and meta-analysis". BMJ. 393. doi:10.1136/bmj-2025-088050. ISSN 1756-1833. 喺21 May 2026搵到.
{{cite journal}}: Unknown parameter|article-number=ignored (help) - 1 2 Maxmen A (July 2011). "Nutrition advice: the vitamin D-lemma" (PDF). Nature. 475 (7354): 23–25. doi:10.1038/475023a. PMID 21734684. 原先內容歸檔 (PDF)喺3 August 2020. 喺17 November 2011搵到.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Clements MR (1989). "The problem of rickets in UK Asians". Journal of Human Nutrition and Dietetics. 2 (2): 105–16. doi:10.1111/j.1365-277X.1989.tb00015.x.
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- ↑ Dupuis EM (1 February 2002). Nature's Perfect Food: How Milk Became America's Drink. NYU Press. ISBN 978-0-8147-1938-1. 原先內容歸檔喺19 March 2023. 喺9 April 2017搵到.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Munns CF, Shaw N, Kiely M, Specker BL, Thacher TD, Ozono K, Michigami T, Tiosano D, Mughal MZ, Mäkitie O, Ramos-Abad L, Ward L, DiMeglio LA, Atapattu N, Cassinelli H, Braegger C, Pettifor JM, Seth A, Idris HW, Bhatia V, Fu J, Goldberg G, Sävendahl L, Khadgawat R, Pludowski P, Maddock J, Hyppönen E, Oduwole A, Frew E, Aguiar M, Tulchinsky T, Butler G, Högler W (February 2016). "Global Consensus Recommendations on Prevention and Management of Nutritional Rickets". The Journal of Clinical Endocrinology and Metabolism. 101 (2): 394–415. doi:10.1210/jc.2015-2175. PMC 4880117. PMID 26745253.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Bischoff-Ferrari HA, Willett WC, Orav EJ, Lips P, Meunier PJ, Lyons RA, Flicker L, Wark J, Jackson RD, Cauley JA, Meyer HE, Pfeifer M, Sanders KM, Stähelin HB, Theiler R, Dawson-Hughes B (July 2012). "A pooled analysis of vitamin D dose requirements for fracture prevention" (PDF). The New England Journal of Medicine. 367 (1): 40–49. doi:10.1056/NEJMoa1109617. hdl:1871/48765. PMID 22762317. S2CID 24338997. 原先內容歸檔 (PDF)喺15 December 2020. 喺17 July 2019搵到.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Zhao Y, Chen C, Pan W, Gao M, He W, Mao R, Lin T, Huang J (May 2016). "Comparative efficacy of vitamin D status in reducing the risk of bladder cancer: A systematic review and network meta-analysis". Nutrition. 32 (5): 515–523. doi:10.1016/j.nut.2015.10.023. PMID 26822497.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Beveridge LA, Struthers AD, Khan F, Jorde R, Scragg R, Macdonald HM, Alvarez JA, Boxer RS, Dalbeni A, Gepner AD, Isbel NM, Larsen T, Nagpal J, Petchey WG, Stricker H, Strobel F, Tangpricha V, Toxqui L, Vaquero MP, Wamberg L, Zittermann A, Witham MD (May 2015). "Effect of Vitamin D Supplementation on Blood Pressure: A Systematic Review and Meta-analysis Incorporating Individual Patient Data". JAMA Internal Medicine. 175 (5): 745–754. doi:10.1001/jamainternmed.2015.0237. PMC 5966296. PMID 25775274.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Abboud M, Al Anouti F, Papandreou D, Rizk R, Mahboub N, Haidar S (February 2021). "Vitamin D status and blood pressure in children and adolescents: a systematic review of observational studies". Systematic Reviews. 10 (1). doi:10.1186/s13643-021-01584-x. PMC 7898425. PMID 33618764.
{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Khan SU, Khan MU, Riaz H, Valavoor S, Zhao D, Vaughan L, Okunrintemi V, Riaz IB, Khan MS, Kaluski E, Murad MH, Blaha MJ, Guallar E, Michos ED (August 2019). "Effects of Nutritional Supplements and Dietary Interventions on Cardiovascular Outcomes: An Umbrella Review and Evidence Map". Annals of Internal Medicine. 171 (3): 190–198. doi:10.7326/m19-0341. PMC 7261374. PMID 31284304.
- ↑ Al-Saoodi H, Kolahdooz F, Andersen JR, Jalili M (April 2024). "Effect of vitamin D on inflammatory and clinical outcomes in patients with rheumatoid arthritis: a systematic review and dose-response meta-analysis of randomized controlled trials". Nutrition Reviews. 82 (5): 600–11. doi:10.1093/nutrit/nuad083. PMID 37437898.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - 1 2 Cao Y, Wang X, Liu P, Su Y, Yu H, Du J (January 2022). "Vitamin D and the risk of latent tuberculosis infection: a systematic review and meta-analysis". BMC Pulmonary Medicine. 22 (1). doi:10.1186/s12890-022-01830-5. PMC 8772077. PMID 35045861.
{{cite journal}}: Unknown parameter|article-number=ignored (help) - 1 2 Goyal JP, Singh S, Bishnoi R, Bhardwaj P, Kaur RJ, Dhingra S, Yadav D, Dutta S, Charan J (July 2022). "Efficacy and safety of vitamin D in tuberculosis patients: a systematic review and meta-analysis". Expert Review of Anti-Infective Therapy. 20 (7): 1049–1059. doi:10.1080/14787210.2022.2071702. PMID 35477334.
- ↑ Taheriniya S, Arab A, Hadi A, Fadel A, Askari G (August 2021). "Vitamin D and thyroid disorders: a systematic review and meta-analysis of observational studies". BMC Endocrine Disorders. 21 (1). doi:10.1186/s12902-021-00831-5. PMC 8381493. PMID 34425794.
{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Islam MA, Khandker SS, Alam SS, Kotyla P, Hassan R (November 2019). "Vitamin D status in patients with systemic lupus erythematosus (SLE): A systematic review and meta-analysis". Autoimmunity Reviews. 18 (11). doi:10.1016/j.autrev.2019.102392. PMID 31520805.
{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Bonaccorso G (2023). "Myasthenia gravis and vitamin D serum levels: A systematic review and meta-analysis". CNS & Neurological Disorders Drug Targets. 22 (5): 752–60. doi:10.2174/1871527321666220707111344. PMID 35796450.
- ↑ Lee YH, Bae SC (September 2016). "Vitamin D level in rheumatoid arthritis and its correlation with the disease activity: a meta-analysis". Clinical and Experimental Rheumatology. 34 (5): 827–33. PMID 27049238.
- ↑ Balasooriya NN, Elliott TM, Neale RE, Vasquez P, Comans T, Gordon LG (October 2024). "The association between vitamin D deficiency and multiple sclerosis: an updated systematic review and meta-analysis". Multiple Sclerosis and Related Disorders. 90. doi:10.1016/j.msard.2024.105804. PMID 39180838.
{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Clasen JL, Cole R, Aune D, Sellon E, Heath AK (March 2023). "Vitamin D status and risk of rheumatoid arthritis: systematic review and meta-analysis". BMC Rheumatology. 7 (1). doi:10.1186/s41927-023-00325-y. PMC 10015722. PMID 36918989.
{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Jolliffe DA, Camargo CA, Sluyter JD, Aglipay M, Aloia JF, Ganmaa D, 等 (May 2021). "Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials". Lancet Diabetes Endocrinol. 9 (5): 276–92. doi:10.1016/S2213-8587(21)00051-6. PMC 7709175. PMID 33798465.
- ↑ Hewison M (2011). "Vitamin D and innate and adaptive immunity". Vitamins and the Immune System. Vitamins & Hormones.第86卷. Academic Press. pp. 23–62. doi:10.1016/B978-0-12-386960-9.00002-2. ISBN 978-0-12-386960-9. PMID 21419266.
- ↑ Bishop EL, Ismailova A, Dimeloe S, Hewison M, White JH (January 2021). "Vitamin D and immune regulation: Antibacterial, antiviral, anti-Inflammatory". Journal of Bone and Mineral Research Plus. 5 (1). doi:10.1002/jbm4.10405. PMC 7461279. PMID 32904944.
{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Nnoaham KE, Clarke A (February 2008). "Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis". International Journal of Epidemiology. 37 (1): 113–119. CiteSeerX 10.1.1.513.3969. doi:10.1093/ije/dym247. PMID 18245055.
- ↑ Del Pinto R, Pietropaoli D, Chandar AK, Ferri C, Cominelli F (November 2015). "Association Between Inflammatory Bowel Disease and Vitamin D Deficiency: A Systematic Review and Meta-analysis". Inflammatory Bowel Diseases. 21 (11): 2708–2717. doi:10.1097/MIB.0000000000000546. PMC 4615394. PMID 26348447.
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{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Guzman-Prado Y, Samson O, Segal JP, Limdi JK, Hayee B (November 2020). "Vitamin D Therapy in Adults With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis". Inflammatory Bowel Diseases. 26 (12): 1819–1830. doi:10.1093/ibd/izaa087. PMID 32385487.
- ↑ Williamson A, Martineau AR, Sheikh A, Jolliffe D, Griffiths CJ (February 2023). "Vitamin D for the management of asthma". The Cochrane Database of Systematic Reviews. 2023 (2). doi:10.1002/14651858.CD011511.pub3. PMC 9899558. PMID 36744416.
{{cite journal}}: Unknown parameter|article-number=ignored (help) - 1 2 "Vitamin D". Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health (NIH). 17 July 2020. 原著喺21 February 2021歸檔. 喺22 February 2021搵到.
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- ↑ Liu N, Sun J, Wang X, Zhang T, Zhao M, Li H (March 2021). "Low vitamin D status is associated with coronavirus disease 2019 outcomes: a systematic review and meta-analysis". International Journal of Infectious Diseases. 104: 58–64. doi:10.1016/j.ijid.2020.12.077. PMC 7833186. PMID 33401034.
- ↑ Kazemi A, Mohammadi V, Aghababaee SK, Golzarand M, Clark CC, Babajafari S (October 2021). "Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis". Advances in Nutrition. 12 (5): 1636–1658. doi:10.1093/advances/nmab012. PMC 7989595. PMID 33751020.
- ↑ Petrelli F, Luciani A, Perego G, Dognini G, Colombelli PL, Ghidini A (July 2021). "Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies". The Journal of Steroid Biochemistry and Molecular Biology. 211. doi:10.1016/j.jsbmb.2021.105883. PMC 7997262. PMID 33775818.
{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Bassatne A, Basbous M, Chakhtoura M, El Zein O, Rahme M, El-Hajj Fuleihan G (June 2021). "The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis". Metabolism (Systematic review). 119. doi:10.1016/j.metabol.2021.154753. PMC 7989070. PMID 33774074.
{{cite journal}}: Unknown parameter|article-number=ignored (help) - ↑ Dissanayake HA, de Silva NL, Sumanatilleke M, de Silva SD, Gamage KK, Dematapitiya C, Kuruppu DC, Ranasinghe P, Pathmanathan S, Katulanda P (April 2022). "Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-analysis". The Journal of Clinical Endocrinology and Metabolism. 107 (5): 1484–1502. doi:10.1210/clinem/dgab892. PMC 8689831. PMID 34894254.
- ↑ Sartini M, Del Puente F, Carbone A, Schinca E, Ottria G, Dupont C, Piccinini C, Oliva M, Cristina ML (November 2024). "The Effect of Vitamin D Supplementation Post COVID-19 Infection and Related Outcomes: A Systematic Review and Meta-Analysis". Nutrients. 16 (22): 3794. doi:10.3390/nu16223794. PMC 11597733. PMID 39599582.
- ↑ Kow CS, Ramachandram DS, Hasan SS, Wong Z, Thiruchelvam K (October 2024). "The impact of vitamin D administration on mortality in COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials". Inflammopharmacology. 32 (5): 3205–12. doi:10.1007/s10787-024-01564-2. PMID 39225947.
- ↑ Sobczak M, Pawliczak R (May 2024). "Effect of Vitamin D3 Supplementation on Severe COVID-19: A Meta-Analysis of Randomized Clinical Trials". Nutrients. 16 (10): 1402. doi:10.3390/nu16101402. PMC 11124475. PMID 38794642.