原創 RingoKuma 時光派 來自專輯前沿追新
@果熊
關注皮膚衰老與面部年輕化
活著就是當旬期
編者按
在眾多研究和商家的推動下，NAD+家族已經被神化成了「長生不老藥」。而作為NAD+的直接前體，NMN是其中的佼佼者，最近更是借著股市的威勢乘風破浪。距離NAD+同樣一步之遙的NADH，帶了「氫」，還原型NAD+的加持，效果似乎更勝一籌。一些商家甚至稱，NADH直接轉化NAD+強力延壽，效果上更是四倍於NMN。
真的如此麼？
01
NAD+與NADH：有聯繫，但區別更大
煙醯胺腺嘌呤二核苷酸（NAD+）是生物體內許多脫氫酶（/氧化酶）的輔酶，有傳遞氫和電子的功能，在接收別的物質被氧化後脫下來的氫和電子之後，NAD+就變為了還原型煙醯胺腺嘌呤二核苷酸（NADH）[1]。
圖註：NAD+的加氫和NADH的脫氫反應相互轉化
NAD+和NADH在細胞內各種基礎生化反應中相互轉化。但一般來說，細胞質內的NAD+/NADH比值約為60-700，線粒體內的NAD+/NADH比值保持在7-8[2,3]。這種NAD+明顯多於NADH的數量關係才能維持正常的線粒體膜電位，保證正常的線粒體功能和細胞能量代謝[4-6]。
圖註：NAD+/NADH參與糖代謝和生物氧化（@TRENDS in Endocrinology & Metabolism, 時光派編譯）
NAD+/NADH的生物學作用，就同「綠巨人浩克」與變身前「班納」一樣，之間有聯繫，可區別也很大：至少，NAD+通過激活長壽蛋白Sirtuins來延緩衰老的功能，NADH就是沒有的。
圖註：NAD+與NADH的生物學作用（WEIHAI YANG, et al.）
其中還值得拿出來一講的是NADH會引發「還原性應激」，很多人看到NADH名字裡的「還原型」三個字，會想當然地把它認定為還原劑。但是研究已經證明了，過量的NADH會加速ROS生成，加重氧化[10,11]，「還原型」反倒成了NADH的原罪。
圖註：NAD+/NADH與氧化還原和衰老過程的關係（WEIHAI YANG, et al.）
02
NADH還可能讓你的「長壽藥」白吃
目前針對NAD+的研究已經證實了：隨著年齡增長，某些組織內NAD+不斷減少；很多人不知道的是，NADH在這個過程中也在不斷增加，與老化相關[18]。
圖註：人類腦細胞中總NAD、NAD+和NADH水平隨年齡變化[18]
NAD+和NADH之間還有著一種「此消彼長」的關係：一項研究讓受試者補充NADH，在用藥8周後測定血液單核細胞內NAD+和NADH含量，結果發現細胞內NAD+水平下降，NADH水平上升，NAD+/NADH比值下降[19]。
點擊查看大圖，圖註：補充NADH 8周後血單核細胞內NAD+、NADH水平和NAD+/NADH變化[19]
熱量限制（CR）是目前公認最有效的「續命」方式，它就是通過調節Sir2降低NADH水平、升高NAD+/NADH比值來起到延壽的作用[20]。
圖註：NAD+/NADH ——「天平的兩端」
綜上所述，我們認為：以目前的研究來看，外源性補充NADH會提升細胞內NADH水平，降低NAD+水平，可能不利於延長壽命。如果和NMN、NR這類NAD+補充劑「長壽藥」同服，最終的結果是花了雙份錢卻 「吃了個寂寞」。
把NADH包裝成「長壽藥」的商人，其實更應該多吃吃自家產品——「救智、補腦」。
03
NADH真正的跑道：可能是神經 「萬靈藥」，卻並非「聰明藥」
NADH真正「跑起來」，是學者們發現了NADH能間接地為酪氨酸羥化酶催化的多巴胺合成限速步驟提供還原當量，促進內源性左旋多巴（多巴胺前體物質）的合成[21]；同時也有證據表明，NADH能夠增加血漿左旋多巴的生物利用度[22]。NADH還有著調節線粒體能量代謝、調節鈣穩態、調節大腦基因表達、抗凋亡等多種作用，讓它成為有望成為攀越神經系統疾病治療這座高峰的「種子選手」。
上世紀90年代以來，用NADH治療各種神經系統疾病有效的研究報導一時間如雨後春筍般出現：
改善帕金森病（PD）[23,24]、阿爾茨海默症（AD,「老年痴呆」） [22]、 「時差病」[25]和慢性疲勞症候群（CFS）[26,27]；甚至有望將其用於治療亨廷頓舞蹈病（HD）、腦外傷後/腦梗死後腦損傷、多發性硬化症（MS）和腦瘤等「絕症」 [28-36]
多巴胺與學習和記憶有著千絲萬縷的聯繫[37,38]，成就了今天NADH在保健品領域「考生必備『聰明藥』」的地位，很多人試圖服用它來集中注意力、提升工作學習效率。
圖註：某寶上的NADH「聰明藥」廣告
但是，目前的研究只證實了服用NADH可能改善病理狀態下（AD、CFS和時差調整狀態）患者的認知功能，在正常人身上的有效性和安全性的研究尚缺。因此，我們也不主張正常人「拿到半截就開跑」，將NADH作為提高記憶和學習能力的補劑來服用。
時光派點評
對人體自身奧秘的探索過程，和那些試圖解秘森羅萬象的所有科學研究過程都一樣——就像拼圖遊戲，是用碎片去構擬還原出一個全景，這個過程中難免會拼錯那麼一塊兩塊，需要不斷地去修正；我們現在所能看到的是現有拼圖的模樣，可能只是成品的冰山一角。
所以，我們只能告訴你，在結合現有研究證據分析之後，我們認為：NADH有潛力成為一款治療許多神經系統疾病的好藥，但未必利於延壽，不建議未患影響認知功能的疾病的正常人把NADH當作補劑去服用。希望NADH早日「青春歸位」，不會再被用來騙人，回到屬於自己的領域去發光發熱！
每次與NAD+代謝流上的相關物質接觸，筆者總能聞到一股難以名狀的「怪味兒」：NAD+利益相關者把NADH貶得一錢不值，NADH把NAD+妖化成洪水猛獸，NAD+各類補充劑再明爭暗鬥……
我想，負責任的科普應該是羅列事實而臧否兩論。我們不反對靠科普來變現，所以我們也開起了自己的小店；但是以撈錢為目的而扭曲事實去科普，說實話，真的有點臭。
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