岁月派抗衰争论院撰稿
NAD+家族的NMN以及NR借着股市的威势乘风破浪，它的“一奶同胞”伯仲NADH也正在蠢蠢欲动，打着“1片顶4片NMN的第三代NAD+”、“恢复型NAD+抗氧化”、“直接转化NAD+强力延寿”的灯号猖狂碰瓷，妄想正在富翁续命墟市分上一杯羹……
正文：
NAD+与NADH：有关连，但区分更大
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，有传播氢以及电子的功能，正在领受其余物质被氧化后脱下来的氢以及电子之后，NAD+就变成了恢复型烟酰胺腺嘌呤二核苷酸（NADH）[1]。
图注：NAD+的加氢以及NADH的脱氢反应彼此转化
NAD+以及NADH正在细胞内各类根底生化反应中彼此转化。但普通来讲，细胞质内的NAD+/NADH比值约为60-700，线粒体内的NAD+/NADH比值维持正在7-8[2,3]。这种NAD+分明多于NADH的数目联系才华维持一般的线粒体膜电位，保险一般的线粒体功能以及细胞能量代谢[4-6]。
图注：NAD+/NADH到场糖代谢以及生物氧化（@TRENDS in Endocrinology & Metabolism, 岁月派编译）
NAD+/NADH的生物学影响，就同“绿伟人浩克”与变身前“班纳”一律，之间有关连，可区分也很大：至多，NAD+经过激活短命蛋白Sirtuins来延迟脆弱的功能，NADH便是没有的。
图注：NAD+与NADH的生物学影响（WEIHAI YANG, et al.）
个中还值得拿进去一讲的是NADH会引发“恢复性应激”，良多人看到NADH名字里的“恢复型”三个字，会想固然地把它认定为恢复剂。不过争论一经证实了，适量的NADH会加快ROS天生，加剧氧化[10,11]，“恢复型”反倒成了NADH的原罪。
图注：NAD+/NADH与氧化恢复以及脆弱历程的联系（WEIHAI YANG, et al.）
NADH还大概让你的“短命药”白吃
今朝针对于NAD+的争论一经阐明了：随着春秋增添，某些构造内NAD+不停削减；良多人没有分解的是，NADH正在这个历程中也正在不停推广，与老化相干[18]。
图注：人类脑细胞中总NAD、NAD+以及NADH水平随春秋改变[18]
NAD+以及NADH之间还有着一种“此消彼长”的联系：一项争论让受试者弥补NADH，正在用药8周后测定血液单核细胞内NAD+以及NADH含量，了局发明细胞内NAD+水平下降，NADH水平升高，NAD+/NADH比值下降[19]。
图注：弥补NADH 8周后血单核细胞内NAD+、NADH水和蔼NAD+/NADH改变[19]
热量限制（CR）是今朝公认最无效的“续命”办法，它便是经过调治Sir2升高NADH水平、上升NAD+/NADH比值来起到延寿的影响[20]。
图注：NAD+/NADH ——“天平的两端”
综上所述，咱们以为：以今朝的争论来看，外源性弥补NADH会选拔细胞内NADH水平，升高NAD+水平，大概没有利于缩短寿命。假设以及NMN、NR这类NAD+弥补剂“短命药”同服，最终的了局是花了双份钱却 “吃了个热闹”。
把NADH包装成“短命药”的商人，本来更应该多吃吃自家当品——“救智、补脑”。
NADH真正的跑道：大概是神经 “万妙药”，却并非“聪慧药”
NADH真正“跑起来”，是学者们发明了NADH能间接地为酪氨酸羟化酶催化的多巴胺分解限速方法供给恢复当量，匆匆进内源性左旋多巴（多巴胺前体物质）的分解[21]；同时也有证明说明，NADH恐怕推广血浆左旋多巴的生物运用度[22]。NADH还有着调治线粒体能量代谢、调治钙稳态、调治大脑基因表达、抗凋亡等多种影响，让它成为有望成为攀越神经系统疾病调节这座顶峰的“种子选手”。
上世纪90年代以后，用NADH调节各类神经系统疾病无效的争论报道临时间如雨后春笋般呈现——改善帕金森病（PD）[23,24]、阿尔茨海默症（AD,“末年痴呆”）[22]、“时差病”[25]以及耐性委靡分析征（CFS）[26,27]；以至有望将其用于调节亨廷整理舞蹈病（HD）、脑外伤后/脑梗去世后脑损害、多发性软化症（MS）以及脑瘤等“绝症” [28-36]。
多巴胺与练习以及记忆有着千丝万缕的关连[37,38]，创建了此日NADH正在保健品范畴“考生必备‘聪慧药’”的职位，良多人试图服用它来分散留神力、选拔处事练习效用。
图注：某宝上的NADH“聪慧药”广告
不过，今朝的争论只阐明了服用NADH大概改善病理状态下（AD、CFS以及时差保养状态）患者的认知功能，正在一般人身上的无效性以及安全性的争论尚缺。所以，咱们也没有主张一般人“拿到半截就开跑”，将NADH算作进步记忆以及练习才略的补剂来服用。
岁月派点评
对于人体自身神秘的研究历程，以及那些试图解秘森罗万象的一切迷信争论历程都一律——就像拼图玩耍，是用碎片去构拟恢复出一个全景，这个历程中不免会拼错那么一块两块，须要不停地去批改；咱们而今所能看到的是现有拼图的样子，大概仅仅制品的冰山一角。
因而，咱们只可告知你，正在贯串现有争论证明分解之后，咱们以为：NADH有潜力成为一款调节许多神经系统疾病的好药，但不常利于延寿，没有提议未患作用认知功能的疾病的一般人把NADH看成补剂去服用。指望NADH早日“青春归位”，没有会再被用来骗人，回到属于自身的范畴去发光发热！
每次与NAD+代谢流上的相干物质战斗，笔者总能闻到一股难以名状的“怪味儿”：NAD+好处相干者把NADH贬得一钱没有值，NADH把NAD+妖化成洪水猛兽，NAD+各种弥补剂再明争冷战……
我想，担任任的科普应该是枚举真相而臧否两论。咱们没有拦阻靠科普来变现，因而咱们也开起了自身的小店；不过以捞钱为想法而扭曲真相去科普，说瞎话，真的有点臭。
参照文献：
[1] Mitchell P: Keilin’s respiratory chain concept and its chemiosmotic consequences. Science 1979; 206:1148.
[2] Veech, R.L. et al. (1972) The time-course of the effects of ethanol on the redox and phosphorylation states of rat liver. Biochem. J. 127, 387–397.
[3] Williamson, D.H. et al. (1967) The redox state of free nicotinamide- ad今天1早上enine dinucleotide in the cytoplasm and mitochondria of rat liver. Biochem. J. 103, 514–527.
[4] Ying,W.(2008)NAD+/NADH and NADP+/NADPH incellular functions and cell death: regulation and biological consequences. Antioxid. Redox Signal. 10, 179–206.
[5] Cheng, Z. et al. (2010) Insulin signaling meets mitochondria in metabolism. Trends Endocrinol. Metab. 21, 589–598.
[6] Houtkooper,R.H.etal.(2010)The secret life of NAD+:an old metabolite controlling new metabolic signaling pathways. Endocr. Rev. 31, 194–223.
[7] Kirsch M and De Groot H. NAD(P)H, a directly operating antioxidant? F ASEB J 15: 1569–1574, 2001.
[8] McGuinness ET and Butler JR. NAD+ kinase—-a review. Int J Biochem 17: 1–11, 1985.
[9] Olek RA, Ziolkowski W, Kaczor JJ, Greci L, Popinigis J, and Antosiewicz J. Antioxidant activity of NADH and its analogue—an in vitro study. J Biochem Mol Biol 37: 416–421, 2004.
[10] Jaeschke H, Kleinwaechter C, and Wendel A. NADH-dependent reductive stress and ferritin-bound iron in allyl alcohol-induced lipid peroxidation in vivo: the protective effect of vitamin E. Chem Biol Interact 81: 57–68, 1992.
[11] Zhang Z, Blake DR, Stevens CR, Kanczler JM, Winyard PG, Symons MC, Benboubetra M, and Harrison R. A reappraisal of xanthine dehydrogenase and oxidase in hypoxic reperfusion injury: the role of NADH as an electron donor. Free Radic Res 28: 151–164, 1998.
[12] Kaplin AI, Snyder SH, and Linden DJ. Reduced nicotinamide adenine dinucleotide-selective stimulation of inositol 1,4,5-trisphosphate receptors mediates hypoxic mobilization of calcium. J Neurosci 16: 2002–2011, 1996.
[13] Zima AV, Copello JA, and Blatter LA. Differential modulation of cardiac and skeletal muscle ryanodine receptors by NADH. FEBS Lett 547: 32–36, 2003.
[14] Zhang Q, Piston DW, and Goodman RH. Regulation of corepressor function by nuclear NADH. Science 295: 1895–1897, 2002.
[15] Rutter J, Reick M, Wu LC, and McKnight SL. Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors. Science 293: 510–514, 2001.
[16] Nadlinger K, Birkmayer J, Gebauer F, and Kunze R. Influence of reduced nicotinamide adenine dinucleotide on the production of interleukin-6 by peripheral human blood leukocytes. Neuroim-munomodulation 9: 203–208, 2001.
[17] Zhu K, Swanson RA, and Ying W. NADH can enter into astrocytes and block poly (ADP-ribose) polymerase-1-mediated astrocyte death. Neuroreport 16: 1209–1212, 2005.
[18] Zhu, X.-H., Lu, M., Lee, B.-Y., Ugurbil, K., & Chen, W. (2015). In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proceedings of the National Academy of Sciences, 112(9), 2876–2881.
[19] Castro-Marrero, J., Cordero, M. D., Segundo, M. J., Sáez-Francàs, N., Calvo, N., Román-Malo, L., … Alegre, J. (2015). Does Oral Coenzyme Q10 Plus NADH Supplementation Improve Fatigue and Biochemical Parameters in Chronic Fatigue Syndrome? Antioxidants & Redox Signaling, 22(8), 679–685.
[20] Lin, S. J., E. Ford, M. Haigis, G. Liszt & L. Guarente: Calorie restriction extends yeast life span by lowering the level of NADH. Genes Dev, 18, 12-6(2004).
[21] Swerdlow, R. H.: Is NADH effective in the treatment of Parkinson'后天3晚上s disease? Drugs Aging, 13, 263-8(1998).
[22] Demarin V, Podobnik SS, Storga Tomic D, and Kay G. Treatment of Alzheimer’s disease with stabilized oral nicotinamide adenine dinucleotide: a randomi明天2下午zed, double-blind study. Drugs Exp Clin Res 30: 27–33, 2004.
[23] Kuhn W, Muller T, Winkel R, Danielczik S, Gerstner A, Hacker R, Mattern C, and Przuntek H. Parenteral application of NADH in Parkinson’s disease: clinical improvement partially due to stimulation of endogenous levodopa biosynthesis. J Neural Transm 103: 1187–1193, 1996.
[24] Birkmayer, J. G., C. Vrecko, D. Volc & W. Birkmayer: Nicotinamide adenine dinucleotide (NADH)——a new therapeutic approach to Parkinson's disease. Comparison of oral and parenteral application. Acta Neurol Scand Suppl, 146, 32-5(1993).
[25] NASA: Stabilized NADH as a Countermeasure for Jet Lag. Report/Patent Number JSC-CN-6528.
[26] Forsyth, L. M., Preuss, H. G., MacDowell, A. L., Chiazze, L., Birkmayer, G. D., & Bellanti, J. A. (1999). Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Annals of Allergy, Asthma & Immunology, 82(2), 185–191.
[27] Alegre, J., Rosés, J. M., Javierre, C., Ruiz-Baqués, A., Segundo, M. J., & Fernández de Sevilla, T. (2010). Nicotinamida adenina dinucleótido (NADH) en pacientes con síndrome de fatiga crónica. Revista Clínica Española, 210(6), 284–288.
[28] Vis, J. C., E. Schipper, R. T. de Boer-van Huizen, M. M. Verbeek, R. M. de Waal, P. Wesseling, H. J. ten Donkelaar & B. Kremer: Expression pattern of apoptosis-related markers in Huntington's disease. Acta Neuropathol (Berl), 109, 321-8(2005).
[29] Virag, L. & C. Szabo: The therapeutic potential of poly (ADP-ribose) polymerase inhibitors. Pharmacol Rev, 54, 375-429(2002).
[30] Satchell, M. A., X. Zhang, P. M. Kochanek, C. E. Dixon, L. W. Jenkins, J. Melick, C. Szabo & R. S. Clark: A dual role for poly-ADP-ribosylation in spatial memory acquisition after traumatic brain injury in mice involving NAD+ depletion and ribosylation of 14-3-3gamma. J Neurochem, 85, 697-708(2003).
[31] LaPlaca, M. C., J. Zhang, R. Raghupathi, J. H. Li, F. Smith, F. M. Bareyre, S. H. Snyder, D. I. Graham & T. K. McIntosh: Pharmacologic inhibition of poly (ADP-ribose) polymerase is neuroprotective following traumatic brain injury in rats. J Neurotrauma, 18, 369-76(2001).
[32] Kofler, J., T. Otsuka, Z. Zhang, R. Noppens, M. R. Grafe, D. W. Koh, V. L. Dawson, J. M. de Murcia, P. D. Hurn & R. J. Traystman: Differential effect of PARP-2 deletion on brain injury after focal and global cerebral ischemia. J Cereb Blood Flow Metab, 26, 135-41(2006).
[33] Gilgun-Sherki, Y., E. Melamed & D. Offen: The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol, 251, 261-8(2004).
[34] Kauppinen, T. M., S. W. Suh, C. P. Genain & R. A. Swanson: Poly (ADP-ribose) polymerase-1 activation in a primate model of multiple sclerosis. J Neurosci Res, 81, 190-8(2005).
[35] Tentori, L., I. Portarena, F. Torino, M. Scerrati, P. Navarra & G. Graziani: Poly (ADP-ribose) polymerase inhibitor increases growth inhibition and reduces G(2)/M cell accumulation induced by temozolomide in malignant glioma cells. Glia, 40, 44-54(2002).
[36] Tentori, L., C. Leonetti, M. Scarsella, G. D'Amati, M. Vergati, I. Portarena, W. Xu, V. Kalish, G. Zupi, J. Zhang & G. Graziani: Systemic administration of GPI 15427, a novel poly(ADP-ribose) polymerase-1 inhibitor, increases the antitumor activity of temozolomide against intracranial melanoma, glioma, lymphoma. Clin Cancer Res, 9, 5370-9(2003).
[37] Liang, L., Wang, R., & Zhang, Z. (2012). The Effect of Dopamine on Working Memory. Neural Processing Letters, 35(3), 257–263.
[38] Roffman, J. L., Tanner, A. S., Eryilmaz, H., Rodriguez-Thompson, A., Silverstein, N. J., Ho, N. F., … Catana, C. (2016). Dopamine D1 signaling organizes network dynamics underlying working memory. Science Advances, 2(6), e1501672–e1501672.