Nicotinamide riboside

LOS ANGELES--(BUSINESS WIRE)--Niagen Bioscience, Inc. (NASDAQ: NAGE) (formerly ChromaDex Corp.), the global authority on NAD+ (nicotinamide adenine dinucleotide) with a focus on the science of healthy aging, today announced it has entered into a worldwide exclusive commercial license agreement with the Haukeland University Hospital, Bergen, Norway. The agreement secures exclusive rights to a body of proprietary intellectual property, know-how, and data. These data are expected to support future regulatory filings for Conditional Marketing Authorization (CMA), Accelerated Approval (AA), and Marketing Authorization (MA) in the EU under European Medicines Agency (EMA) guidelines for the potential treatment of Parkinson`s Disease (PD) using the Company’s patented nicotinamide riboside (Niagen®) molecule. Niagen Bioscience Secures Exclusive License to Develop and Commercialize its NAD+ Precursor, Patented Nicotinamide Riboside (Niagen), as a Potential Parkinson’s Disease Therapy in Agreement with Haukeland University Hospital in Bergen, Norway With this license, Niagen Bioscience is the only company with the right to seek regulatory approval for a pharmaceutical NR therapy for PD patients. The company retains the right to either commercialize the drug candidate as a potential therapeutic on its own and/or sublicense the program to a strategic pharmaceutical partner to support regulatory advancement and commercialization. “This milestone underscores our long-term commitment to translating scientific innovation into meaningful therapeutic solutions,” said Rob Fried, CEO of Niagen Bioscience. “Through our partnership with Haukeland and its world-renowned researchers, we are taking bold steps into bringing NAD+-boosting therapies to address clinical unmet needs.” Central to this agreement is access to a robust body of scientific data, including findings from the NOPARK trial, the largest and most comprehensive clinical investigation of NAD+ augmentation in persons with early PD to date. The study was recently completed in June 2025 and is expected to be published by the end of 2025. NOPARK is a randomized, double-blind, placebo-controlled phase III clinical trial featuring 400 individuals with early-stage PD across 12 sites in Norway. Randomized to receive either 500 mg of nicotinamide riboside (Niagen) twice daily or placebo for 52 weeks, participants had follow-up assessments at five time points in a one-year period. The primary endpoint is the MDS-UPDRS total score, a gold standard measure of PD progression. “This is an important milestone in our efforts to bring a potentially disease-modifying treatment for PD closer to patients,” says Professor Charalampos Tzoulis, who leads the NOPARK study and the Neuro-SysMed center, a Norwegian Center of Excellence for Clinical Treatment Research in Neurology at Haukeland University Hospital and the University of Bergen, Norway. “We are fully committed to advancing knowledge and developing treatments that can truly benefit patients with PD and other neurodegenerative disorders. This agreement represents a significant step in that direction, and we are confident that Niagen Bioscience is well positioned to carry this important science forward - ultimately, for the benefit of patients globally.” This agreement builds on a longstanding collaboration between Haukeland University Hospital’s Dr. Charalampos Tzoulis and Niagen Bioscience’s external research program, CERP. The first of several material transfer agreements (MTAs) dates to March 2018. Since then, independent research supported by CERP has helped catalyze over 300 research collaborations and more than 35 peer-reviewed clinical studies, including four landmark trials assessing the therapeutic potential of Niagen NR for PD: the phase I/IIa NADPARK study, published in Cell Metabolism, the phase I NR-SAFE study published in Nature Communications, the phase IIa N-DOSE (not yet published), and the phase III NOPARK study (not yet published). In connection with this license agreement, the Company also established a wholly owned subsidiary, which represents a pivotal step in Niagen Bioscience’s evolution from supplement science to regulated drug development in pursuit of therapeutics for neurodegenerative diseases with high unmet needs. For additional information on Niagen Bioscience visit www.niagenbioscience.com. About Niagen Bioscience: Niagen Bioscience, Inc. (NASDAQ: NAGE), formerly ChromaDex Corp., is the global leader in NAD+ (nicotinamide adenine dinucleotide) science and healthy-aging research. As a trusted pioneer of NAD+ discoveries, Niagen Bioscience™ is dedicated to advancing healthspan through precision science and innovative NAD+-boosting solutions. The Niagen Bioscience team, composed of world-renowned scientists, works with independent investigators from esteemed universities and research institutions around the globe to uncover the full potential of NAD+. A vital coenzyme found in every cell of the human body, NAD+ declines with age and exposure to everyday lifestyle stressors. NAD+ depletion is a key contributor to age-related changes in health and vitality. Distinguished by state-of-the-art laboratories, rigorous scientific and quality protocols, and collaborations with leading research institutions worldwide, Niagen Bioscience sets the gold standard for research, quality, and innovation. There’s a better way to age. Niagen Bioscience’s robust patent portfolio protects NR and other NAD+ precursors. Niagen Bioscience maintains a website at www.niagenbioscience.com, where copies of press releases, news, and financial information are regularly published. Forward Looking Statements: This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including but not limited to statements regarding the development, regulatory pathway, potential approval, and commercialization of nicotinamide riboside as a treatment for Parkinson’s disease; the formation and strategic objectives of NAD Pharmaceuticals, Inc.; the scope and exclusivity of licensing agreements; the potential outcomes and implications of the NOPARK clinical trial; and Niagen Bioscience’s broader pharmaceutical ambitions. Forward-looking statements reflect current expectations and projections about future events and involve known and unknown risks, uncertainties, and other factors that may cause actual results, performance, or achievements to differ materially from those expressed or implied by such statements. These risks and uncertainties include, but are not limited to: the outcomes and interpretation of the NOPARK study and other clinical trials; the ability to obtain regulatory approvals; the timing and success of preclinical and clinical development efforts; market acceptance of new therapies; intellectual property protection and defense; dependence on third parties; supply chain risks; the Company’s financial condition and need for additional capital; and general market, economic, and geopolitical conditions. In some cases, forward-looking statements can be identified by terms such as “anticipates,” “believes,” “could,” “estimates,” “expects,” “intends,” “may,” “plans,” “seeks,” “should,” “will,” and similar expressions, as well as the negative of these terms. These statements speak only as of the date made and are based on current beliefs, assumptions, and information available to management. Niagen Bioscience undertakes no obligation to publicly update or revise any forward-looking statements to reflect events or circumstances after the date of this release, except as required by law. Readers are cautioned not to place undue reliance on such forward-looking statements.

近年来，维生素补剂正以“保健圣品”的姿态，悄悄占领了无数家庭的药箱和健身党的日常补给清单。各类“明星维生素”更是层出不穷：维生素E主打“抗氧化、延缓衰老”，维生素B族则号称“补能神器、代谢加速器”，仿佛吞下一粒，就能满血复活。加上各种“功效种草”视频和健康达人的安利，不少人开始养成“每日一粒”的习惯，甚至觉得多补点也无妨，反正是“有益健康”的嘛。但维生素B和维生素E真的是多多益善吗？最近几项研究给这股维生素B和维生素E补剂热潮泼了盆冷水。谁是脂蛋白里的“抗铁王牌”？维生素E登场来自美国得克萨斯大学西南医学中心的研究团队发表在Nature上的一项研究[1]发现，看似对抗自由基、保护细胞的维生素E，竟然能帮癌细胞逃脱铁死亡的命运。在癌细胞眼中，脂肪可不仅仅是“储能大户”，更是一根关键时刻能救命的“稻草”。越来越多研究发现，脂蛋白作为血液中脂质运输的主力军，似乎也在展露出它的“反派”属性——不仅为癌细胞源源不断输送“口粮”，还能在危急时刻助它们躲过铁死亡的“命运”。铁死亡，是一种不同于凋亡的细胞死亡方式，关键特征是细胞膜上脂质过氧化物的异常堆积。这一过程依赖铁的参与，在肿瘤微环境中尤其容易发生，因为癌细胞常常暴露于持续的氧化应激中。为了在这样的压力下继续生存和增殖，癌细胞必须设法对抗铁死亡。这个号称“铁死亡终结者”的酶，负责清除细胞内的脂质过氧化物，是细胞抵御铁死亡的最后一道防线。而一旦有脂蛋白加入，GPX4的重要性却显著下降。也就是说，在脂蛋白的参与下，癌细胞似乎可以摆脱对GPX4的依赖——这让人不禁好奇：脂蛋白是否隐藏着某种“神秘力量”，能在关键时刻“接管”GPX4的抗铁死亡任务？这一发现明确指出：脂蛋白真正的抗铁死亡能力，来自其原生脂质“核心”。由此可以推断，HDL和LDL对抗铁死亡的能力，很可能主要归功于α-toc的加持。与此同时，这些小鼠的总体健康状况并未受到明显影响，说明α-toc缺乏主要影响的是肿瘤的生长，而非整体机能。GAGs是癌细胞脂蛋白“进货通道”由此看来，维生素E不仅是一种典型的脂溶性抗氧化剂，也是癌细胞抵御铁死亡的“护身符”。不过，这类分子并不会孤身进入细胞，而是喜欢“搭车”——借助LDL、HDL等脂蛋白作为运输工具，被源源不断地送入组织，包括肿瘤。那么，能不能从“交通线”下手，切断这条抗氧化剂的供应链？当然，直接减少维生素E摄入在临床上不太现实。于是，研究者换了个角度：与其拦截维生素E，不如从源头阻断癌细胞对脂蛋白的摄取通路，把它们的“防护罩”摘下来。为了找出癌细胞是靠什么“吃掉”脂蛋白的，研究团队进行了大规模CRISPR筛选。他们挑选了Karpas299等脂蛋白摄取活跃的癌细胞系，并用两个策略展开筛查：一是识别抗铁死亡所必需的基因，二是筛查哪些基因与脂蛋白摄取密切相关。结果一比对，惊喜出现了：既能抵御铁死亡、又能促进脂蛋白摄取的“重合基因”们，竟然都来自一条此前少有人关注的代谢路径——硫酸化糖胺聚糖（GAGs）合成通路。GAGs是什么？可以把它们想象成细胞表面铺设的一层“糖链地毯”，由一串带负电的长链多糖组成，既能与蛋白结合，也能吸附金属离子和脂蛋白。它们的合成过程复杂，关键酶之一就是UGDH，负责制造其中的重要组成——葡萄糖醛酸（GlcUA）。为验证这一机制，研究者进一步敲除了多种癌细胞中的UGDH，结果一目了然：GAGs水平大幅下降，LDL和HDL摄取能力明显减弱，细胞也变得更加容易发生铁死亡。也就是说，癌细胞通过合成硫酸化GAGs来增强脂蛋白摄取，从而获取更多的抗氧化物质（如维生素E），抵御铁死亡。而一旦阻断GAGs合成通路，癌细胞就会暴露在氧化攻击下，防护能力骤降，最终陷入铁死亡命运。总的来说，这项研究提示，癌细胞为了抵御脂质过氧化带来的铁死亡，会通过脂蛋白大量摄取维生素E的主要形式——α-toc，借此增强抗氧化能力，从而助推自身生长。并且，这一过程离不开GAGs的参与，它们帮助肿瘤细胞更高效地“截获”维生素E。这一发现也为未来靶向维生素E摄取通路、突破铁死亡抵抗提供了新思路。抗氧化不一定护体！维生素E“撑腰”肿瘤血管生成说到肿瘤的快速生长，很多人第一反应是“扩散快”“长得猛”。但事实上，“血管新生”才是支撑肿瘤发展的关键因素之一。为了“吃得上、喝得足”，肿瘤细胞必须不断诱导新血管的生成，把氧气和营养“输送”到肿瘤核心区域。一直以来，学界普遍认为这一过程主要由低氧诱导因子（HIFs）主导，在缺氧状态下启动血管生成程序。然而，卡罗林斯卡研究团队发表在 Journal of Clinical Investigation的一项研究[2]打破了这一认知——另一个对氧气和氧化还原状态极其敏感的转录因子BACH1，在肿瘤血管生成中同样扮演着重要角色。更令人意外的是，BACH1还得到了抗氧化剂的强力支持。维生素E和N-乙酰半胱氨酸（NAC）这类经典抗氧化剂，竟能通过稳定BACH1的方式，促进肿瘤新血管的形成，给肿瘤的“供氧通道”开了绿灯。换句话说，抗氧化剂通过“稳住”BACH1，间接促进了肿瘤血管网络的扩张。不过，BACH1并不是孤军奋战。既往已有研究提示，在肿瘤缺氧条件下，HIF1α的稳定会驱动血管生成和糖酵解通路的激活，从而有助于肿瘤在恶劣环境中“自我进化”。而且，BACH1本身也是HIF1α的下游转录靶标之一，这就引出了一个关键问题：BACH1到底是HIF1α的“工具人”，还是也能自己“做主”？为解答这个问题，研究者进一步在HIF1A敲除细胞中展开实验。结果显示：即使在没有HIF1α的情况下，BACH1依然可以独立上调血管生成相关基因。这表明，BACH1的“执行能力”并不完全依赖于HIF。不过，两者之间的关系也并非完全割裂。总结来说，BACH1与HIF1α的关系可用六个字概括：“可依赖，可独立”。换言之，BACH1既可以在HIF1α的引导下参与血管生成，也有能力在HIF缺位时独立“发号施令”，维持甚至扩大血管生成程序。进一步地，研究者还在小鼠体内观察了抗氧化剂对肿瘤血管的影响。他们发现：无论是维生素E还是NAC，均能显著提升肿瘤组织中的血管密度；但这个“增血管”效果依然需要BACH1的支持。综上，这项研究揭示：BACH1是一个同时对氧气状态和氧化还原环境高度敏感的血管生成转录因子。它能在HIF1α缺位时接过“指挥棒”，独立启动肿瘤血管生成程序。与此同时，它还受到维生素E和NAC等抗氧化剂的“扶持”，使得这些原本“保护身体”的分子在某些情境下反而成了肿瘤的“帮凶”。对于像肺癌这种高度依赖血管供应的恶性肿瘤，BACH1不仅是潜在的治疗靶点，也可能是评估治疗敏感性的关键预测因子。维生素B3补充不当或过度或致癌症发生率和脑转移风险增加说到这里，维生素E在某些肿瘤中的“帮凶”身份已经逐渐浮出水面。但让人意想不到的是，并不只有它如此“反常”。在我们的日常营养补充清单中，另一位看似“安全可靠”的成员——维生素B族，也被多项研究指出在某些情境下可能会“倒戈”相向。来自瑞士联邦理工学院的研究团队曾发表一项引发广泛关注的研究[3]，将目光聚焦在维生素B3的一种存在形式——烟酰胺核苷（NR）。这种物质近年来作为“抗衰新宠”频频出现在各种营养补剂中，但研究却提示：一旦补充不当或剂量过高，反而可能增加严重疾病的发生风险，包括癌症的发生和转移。总的来看，这项研究发出了一个明确的信号：补充烟酰胺核苷（NR）不仅与肿瘤发生率的升高密切相关，更显著增加了癌细胞向大脑转移的风险。研究人员进一步推测，NR的过度补充可能提升了癌细胞的“转移潜能”，一方面为肿瘤提供了更强的代谢支持，另一方面则可能削弱了血脑屏障的完整性，从而使得癌细胞更容易“突破防线”，侵入中枢神经系统。晚年阶段减少叶酸摄入改善代谢，利于长寿而每每提到B族维生素，另一个经常被提及、同样不容忽视的成员就是维生素B9（叶酸）。这是一种水溶性维生素，在细胞分裂、DNA合成以及胎儿神经系统发育中，扮演着不可或缺的角色。那么，叶酸是不是补得越多越好？然而，发表于Life Science Alliance的一项研究[4]给出了颠覆性的发现：在老年阶段减少叶酸的摄入，不仅不会带来明显副作用，反而可能改善代谢、延缓衰老、延长健康寿命。首先看一些关键“安全指标”。不少人担心减少叶酸可能出现贫血、体重下降、甚至寿命缩短的问题。但研究结果显示：限制叶酸摄入的小鼠并未出现贫血、生存率下降或体重异常减轻等负面表现，这无疑打消了“少补即有害”的疑虑。更有趣的是，研究团队还观察到了一些“意料之外的好处”。例如，在小鼠85周龄时，限制叶酸摄入的雄性小鼠出现毛发变灰的比例明显更低，而对照组则“白发早生”，提示少补叶酸或许在某种程度上延缓了衰老进程。此外，在叶酸摄入受限的组别中，无论雌性还是雄性小鼠都表现出更强的代谢灵活性。那么，为什么减少叶酸摄入在老年反而可能成为“加分项”？研究人员提出了两个可能的解释机制。其一，与“对抗性多效性理论”有关。简单来说，这个理论认为：某些对年轻人有益的生理机制，到了老年反而可能变成“负担”。比如，叶酸代谢相关通路、以及雷帕霉素靶点（TOR）通路，年轻时有助于细胞生长和修复，但老年时期细胞生长过快却可能增加癌症等健康风险。此时，“适度踩刹车”反而利大于弊。其二，则是涉及IGF-1（胰岛素样生长因子-1）信号通路。已有研究表明，IGF-1活性降低与延长寿命密切相关。而在这项实验中，研究人员也观察到：叶酸摄入减少的雌性小鼠，其IGF-1水平显著降低，这与健康长寿的趋势保持一致。在追求健康的路上，我们常常被各种“神补剂”的光环所吸引，仿佛只要多补补，就能轻松拿捏健康密码。可如今看来，维生素补剂的世界，远没有我们想象的那么简单。它们不是越多越好的“营养堆砌”。有时候，过量的补充可能成为健康之路的“绊脚石”。与其盲目追逐那些被吹得天花乱坠的“高大上”补剂，不如停下匆忙的脚步，回归生活的本真，用自然的方式去呵护身健康。仍需指出的是，这几项研究主要基于动物模型，在人类中的普适性仍需进一步验证。参考资料：[1]Calhoon D, Sang L, Ji F, Bezwada D, Hsu SC, Cai F, Kim N, Basu A, Wu R, Pimentel A, Brooks B, La K, Paulina Serrano A, Cassidy DL, Cai L, Toffessi-Tcheuyap V, Moussa ME, Uritboonthai W, Hoang LT, Kolli M, Jackson B, Margulis V, Siuzdak G, Brugarolas J, Corbin I, Pratt DA, Weiss RJ, DeBerardinis RJ, Birsoy K, Garcia-Bermudez J. Glycosaminoglycan-driven lipoprotein uptake protects tumours from ferroptosis. Nature. 2025 Jun 11. doi: 10.1038/s41586-025-09162-0. Epub ahead of print. PMID: 40500442.[2] Wang T, Dong Y, Huang Z, Zhang G, Zhao Y, Yao H, Hu J, Tüksammel E, Cai H, Liang N, Xu X, Yang X, Schmidt S, Qiao X, Schlisio S, Strömblad S, Qian H, Jiang C, Treuter E, Bergo MO. Antioxidants stimulate BACH1-dependent tumor angiogenesis. J Clin Invest. 2023 Oct 16;133(20):e169671. doi: 10.1172/JCI169671. PMID: 37651203; PMCID: PMC10575724.[3]Maric T, Bazhin A, Khodakivskyi P, Mikhaylov G, Solodnikova E, Yevtodiyenko A, Giordano Attianese GMP, Coukos G, Irving M, Joffraud M, Cantó C, Goun E. A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD+ metabolism. Biosens Bioelectron. 2022 Oct 29;220:114826. doi: 10.1016/j.bios.2022.114826. Epub ahead of print. PMID: 36371959.[4] Blank HM, Hammer SE, Boatright L, Roberts C, Heyden KE, Nagarajan A, Tsuchiya M, Brun M, Johnson CD, Stover PJ, Sitcheran R, Kennedy BK, Adams LG, Kaeberlein M, Field MS, Threadgill DW, Andrews-Polymenis HL, Polymenis M. Late-life dietary folate restriction reduces biosynthesis without compromising healthspan in mice. Life Sci Alliance. 2024 Jul 23;7(10):e202402868. doi: 10.26508/lsa.202402868. PMID: 39043420; PMCID: PMC11266815.撰文 | 木白编辑 | 木白●热议！6岁儿童被马蜂蛰伤，辗转5家医院才给治疗，家长质疑：大三甲都不能治吗？网友：受海南毒蛇咬伤事件影响，一些医生治毒虫伤很谨慎●教训！食管和气管分不清？全麻下气管插管致病人死亡，麻醉科主任被免职！卫健委最新回应！年轻医生临床基本功薄弱，不懂装懂，要引起重视● 4:3轻断食减重更有效！最新研究：远超热量限制60%，暴食改善显著；还能将平均寿命延长18%版权说明：梅斯医学（MedSci）是国内领先的医学科研与学术服务平台，致力于医疗质量的改进，为临床实践提供智慧、精准的决策支持，让医生与患者受益。欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。点击下方「阅读原文」 立刻下载梅斯医学APP！