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编者按
在众多研究和商家的推动下，NAD+家族已经被神化成了“长生不老药”。而作为NAD+的直接前体，NMN是其中的佼佼者，2020年更是取得爆发式增长。距离NAD+同样一步之遥的NADH，带了“氢”，还原型NAD+的加持，效果似乎更胜一筹。一些商家甚至称，NADH直接转化NAD+强力延寿，效果上更是四倍于NMN。
真的如此么？
01
NAD+与NADH：有联系，但区别更大
烟酰胺腺嘌呤二核苷酸（NAD+）是生物体内许多脱氢酶（/氧化酶）的辅酶，有传递氢和电子的功能，在接收别的物质被氧化后脱下来的氢和电子之后，NAD+就变为了还原型烟酰胺腺嘌呤二核苷酸（NADH）[1]。
图注：NAD+的加氢和NADH的脱氢反应相互转化
NAD+和NADH在细胞内各种基础生化反应中相互转化。但一般来说，细胞质内的NAD+/NADH比值约为60-700，线粒体内的NAD+/NADH比值保持在7-8[2,3]。这种NAD+明显多于NADH的数量关系才能维持正常的线粒体膜电位，保证正常的线粒体功能和细胞能量代谢[4-6]。
图注：NAD+/NADH参与糖代谢和生物氧化（@TRENDS in Endocrinology & Metabolism, 时光派编译）
NAD+/NADH的生物学作用，就同“绿巨人浩克”与变身前“班纳”一样，之间有联系，可区别也很大：至少，NAD+通过激活长寿蛋白Sirtuins来延缓衰老的功能，NADH就是没有的。
图注：NAD+与NADH的生物学作用（WEIHAI YANG, et al.）
其中还值得拿出来一讲的是NADH会引发“还原性应激”，很多人看到NADH名字里的“还原型”三个字，会想当然地把它认定为还原剂。但是研究已经证明了，过量的NADH会加速ROS生成，加重氧化[10,11]，“还原型”反倒成了NADH的原罪。
图注：NAD+/NADH与氧化还原和衰老过程的关系（WEIHAI YANG, et al.）
02
NADH还可能让你的“长寿药”白吃
目前针对NAD+的研究已经证实了：随着年龄增长，某些组织内NAD+不断减少；很多人不知道的是，NADH在这个过程中也在不断增加，与老化相关[18]。
图注：人类脑细胞中总NAD、NAD+和NADH水平随年龄变化[18]
NAD+和NADH之间还有着一种“此消彼长”的关系：一项研究让受试者补充NADH，在用药8周后测定血液单核细胞内NAD+和NADH含量，结果发现细胞内NAD+水平下降，NADH水平上升，NAD+/NADH比值下降[19]。
图注：补充NADH 8周后血单核细胞内NAD+、NADH水平和NAD+/NADH变化[19]
热量限制（CR）是目前公认最有效的“续命”方式，它就是通过调节Sir2降低NADH水平、升高NAD+/NADH比值来起到延寿的作用[20]。
图注：NAD+/NADH ——“天平的两端”
综上所述，我们认为：以目前的研究来看，外源性补充NADH会提升细胞内NADH水平，降低NAD+水平，可能不利于延长寿命。如果和NMN、NR这类NAD+补充剂“长寿药”同服，最终的结果是花了双份钱却 “吃了个寂寞”。
把NADH包装成“长寿药”的商人，其实更应该多吃吃自家产品——“救智、补脑”。
03
NADH真正的跑道：可能是神经 “万灵药”，却并非“聪明药”
NADH真正“跑起来”，是学者们发现了NADH能间接地为酪氨酸羟化酶催化的多巴胺合成限速步骤提供还原当量，促进内源性左旋多巴（多巴胺前体物质）的合成[21]；同时也有证据表明，NADH能够增加血浆左旋多巴的生物利用度[22]。NADH还有着调节线粒体能量代谢、调节钙稳态、调节大脑基因表达、抗凋亡等多种作用，让它成为有望成为攀越神经系统疾病治疗这座高峰的“种子选手”。
上世纪90年代以来，用NADH治疗各种神经系统疾病有效的研究报道一时间如雨后春笋般出现：
多巴胺与学习和记忆有着千丝万缕的联系[37,38]，成就了今天NADH在保健品领域“考生必备‘聪明药’”的地位，很多人试图服用它来集中注意力、提升工作学习效率。
图注：某宝上的NADH“聪明药”广告
但是，目前的研究只证实了服用NADH可能改善病理状态下（AD、CFS和时差调整状态）患者的认知功能，在正常人身上的有效性和安全性的研究尚缺。因此，我们也不主张正常人“拿到半截就开跑”，将NADH作为提高记忆和学习能力的补剂来服用。
时光派点评
对人体自身奥秘的探索过程，和那些试图解秘森罗万象的所有科学研究过程都一样——就像拼图游戏，是用碎片去构拟还原出一个全景，这个过程中难免会拼错那么一块两块，需要不断地去修正；我们现在所能看到的是现有拼图的模样，可能只是成品的冰山一角。
所以，我们只能告诉你，在结合现有研究证据分析之后，我们认为：NADH有潜力成为一款治疗许多神经系统疾病的好药，但未必利于延寿，不建议未患影响认知功能的疾病的正常人把NADH当作补剂去服用。希望NADH早日“青春归位”，不会再被用来骗人，回到属于自己的领域去发光发热！
每次与NAD+代谢流上的相关物质接触，笔者总能闻到一股难以名状的“怪味儿”：NAD+利益相关者把NADH贬得一钱不值，NADH把NAD+妖化成洪水猛兽，NAD+各类补充剂再明争暗斗……
我想，负责任的科普应该是罗列事实而臧否两论。我们不反对靠科普来变现，所以我们也开起了自己的小店；但是以捞钱为目的而扭曲事实去科普，说实话，真的有点臭。
原文阅读：https://mp.weixin.qq.com/s/6d5iL7KOubwVSBijUuQdeg
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