检索问题
关于脑力、大脑营养的前沿研究发来看看
大脑营养与脑力提升的前沿研究已经明确指出：通过合理的饮食模式（如喝咖啡和茶、补充特定营养素）、调整进餐习惯（如间歇性禁食），以及改善肠道微生物环境，可以有效保护大脑、延缓认知衰退，甚至提升认知功能。同时，现代科技与“大脑黑客”技术的兴起，为通过外部设备直接干预和提升脑力提供了全新的可能性。
下面为您详细拆解这些前沿研究的内容，我们将用最通俗的语言，把高深的科学发现变成您日常生活中能用得上的健康知识。
一、 饮食与营养：大脑的“超级燃料”
大脑虽然只占人体体重的很小一部分，却是个“能耗大户”，它需要源源不断的优质燃料。最新的科学研究揭示了哪些食物是大脑的最爱。
1. 咖啡和茶：大脑的天然“保护伞” 一项历时长达43年、追踪了超过13万名中老年人的重磅研究发现，喝含有咖啡因的咖啡和茶，能显著降低患痴呆症（也就是老年人常说的“老糊涂”、“阿尔茨海默病”等严重影响记忆和生活的疾病）的风险。
- 具体数据：研究显示，每天喝大约2到3杯含咖啡因的咖啡，或者1到2杯茶，对大脑的保护效果最好。与几乎不喝咖啡的人相比，常喝咖啡的人患痴呆症的风险降低了约18%（在每10万人中，患病人数从330人降至141人），而且他们主观感觉到的记忆力下降比例也更低（从9.5%降至7.8%）。
- 需要注意的是：这种保护效果主要来自“含咖啡因”的咖啡和茶。研究还特别指出，喝低因咖啡（去除了咖啡因的咖啡）并没有看到降低痴呆风险或提升认知功能的效果。这说明咖啡因本身在保护大脑神经元方面扮演了关键角色。
2. 肌酸：不仅长肌肉，更是大脑的“能量急救包” 提到肌酸，很多人以为那是健身房练肌肉的人才吃的补剂。其实不然。肌酸在人体内的主要作用是帮助快速合成能量（ATP），这就像是细胞的“快速充电宝”。
- 谁最需要补充肌酸？ 研究指出，女性在生理期特定阶段容易感到疲劳，补充肌酸可以缓解这种疲劳感；对于不吃肉的素食主义者或纯素食者来说，由于饮食中没有肉类（天然肌酸的主要来源），他们体内的肌酸储备往往偏低，补充肌酸不仅能增强体力，还能改善大脑的认知表现（比如记忆力、反应速度）。
- 对病人的帮助：对于患有帕金森病、亨廷顿舞蹈症等神经退行性疾病（大脑神经细胞逐渐死亡导致身体不受控制的疾病）的患者，肌酸能提供神经保护；它甚至能帮助脑外伤患者恢复大脑的能量代谢，减少神经损伤。对于大多数人来说，最经济有效的形式是“一水肌酸”。
3. 姜黄素：抗击大脑“生锈”的黄金战士 姜黄素是从我们常吃的调料姜黄（咖喱的主要成分）中提取的一种多酚类物质（一类具有强大抗氧化作用的植物成分）。
- 作用机制：大脑在运作过程中会产生一些“自由基”，就像铁生锈一样会损伤大脑细胞，这被称为“氧化应激”。姜黄素能够充当“电子捐献者”，主动去中和这些自由基，防止大脑“生锈”。同时，它还能抑制体内一条名为NF-κB的信号通路（可以理解为身体里的“炎症开关”），从而减少大脑的炎症反应。
- 如何吸收更好：姜黄素本身在水中很难溶解，吃下去后大部分被排出体外。但研究发现，我们肠道里的细菌能对姜黄素进行“二次加工”，把它代谢成二氢姜黄素和四氢姜黄素，这些物质的抗炎和抗氧化效果甚至更好。此外，将姜黄素与生活方式干预结合，还能降低身体质量指数（BMI，衡量胖瘦的一个指标），改善整体代谢健康。
二、 肠脑轴：你的肠胃在悄悄“遥控”你的大脑
近年来，科学界有一个极其热门的词汇叫“微生物群-肠-脑轴”（MGBA）。简单来说，就是你的肠道里生活着数以万亿计的细菌，它们不仅帮你消化食物，还通过神经、血液等多种途径，直接与你的大脑“打电话”，影响你的情绪、记忆甚至是否患上抑郁症或老年痴呆。
1. 肠道细菌决定抗抑郁药有没有效 一项针对110名重度抑郁症患者的研究有了惊人的发现：医生开的抗抑郁药（如艾司西酞普兰），到底管不管用，竟然和患者肠道里的细菌种类有关。
- 研究发现，那些吃药12周后病情真正好转的患者，他们在吃药前的肠道细菌种类更丰富，细菌之间的社交网络更复杂、更有条理，也就是说他们的肠道菌群更“有韧性”。
- 更神奇的是，科学家甚至可以通过检测患者大便中是否存在某种“产芽孢基因”，来预测患者吃抗抑郁药是否有效，准确率达到了71%（AUC值为0.71）。这意味着，未来医生可能先看你的肠道菌群报告，再决定给你开什么药，这就是真正的“精准医疗”。
2. 男女有别：抑郁症在肠道里的“性别密码” 抑郁症在女性中的发病率更高，症状也更严重。前沿研究发现，这种性别差异甚至体现在肠道的代谢物（细菌消化食物后产生的微小物质）上。
- 在女性抑郁症患者的粪便中，科学家发现了24种异常的代谢物，其中两种名为“庚胺”和“苯乙酰氨酸”的物质是女性独有的；而在男性抑郁症患者中，却没有发现这些明显的变化。
- 这说明，未来治疗女性抑郁症，可能需要专门针对这些特定的肠道代谢物来设计药物或调整饮食，而不能用一套男女通用的方案。
3. 植物营养素：喂饱好细菌，安抚大脑 除了姜黄素，自然界还有很多植物成分能通过改善肠道来保护大脑，这类成分被称为“益生元”或“植物精神益生菌”（能够通过调节肠道菌群来改善心理健康的植物成分）。
- 例如，人参中的人参皂苷、植物多糖（植物中提取的复杂糖类）和薰衣草精油，都能保护神经、改善肠道屏障的完整性（防止肠内有害物质漏到血液里），并在动物实验中减轻了抑郁样的行为。
- 此外，Omega-3多不饱和脂肪酸（常见于深海鱼油）、花青素（让蓝莓变紫的成分）、槲皮素（存在于苹果、洋葱中）、儿茶素（绿茶成分）和绿原酸（存在于咖啡中），都能通过促进肠道有益菌生长、增加短链脂肪酸（一种能滋养肠道、抗炎的有益物质）的产生，来发挥保护大脑和提升认知的作用。
三、 进食习惯与时间：给大脑做个“系统重启”
吃什么很重要，什么时候吃同样重要。最新的研究将目光投向了我们的进餐时间表。
1. 不吃早餐的隐形代价 通过对66项研究的系统回顾，科学家发现长期不吃早餐会对身体造成多方面的负面影响，其中就包括大脑。
- 不吃早餐会打乱体内的激素节律，不仅容易导致肥胖，还会对肠道菌群造成破坏，引发全身性的慢性炎症。
- 这种代谢紊乱和炎症反应，会进一步增加认知能力下降（记忆力减退、反应变慢）、情绪障碍（焦虑和抑郁）的风险。因此，按时吃早餐不仅是为了填饱肚子，更是为了稳定大脑的化学环境。
2. 间歇性禁食：给大脑做“大扫除” 间歇性禁食（Intermittent Fasting，简称IF，也就是在特定时间段内不进食，比如每天把吃饭时间压缩在8小时内，剩下16小时禁食）正成为神经保护领域的一颗新星。
- 如何起效：禁食期间，身体会消耗完糖分，转而燃烧脂肪，产生一种叫做“β-羟基丁酸”（BHB）的物质，它能像清洁剂一样帮助大脑清理有害的毒性蛋白（如导致老年痴呆的淀粉样蛋白）。同时，禁食还能促使大脑产生“脑源性神经营养因子”（BDNF，一种能促进脑细胞生长和连接的肥料），增强突触可塑性（大脑细胞之间建立新连接、学习和记忆的能力）。
- 肠道与大脑的联动：禁食能改变肠道菌群的构成，增加产生短链脂肪酸的有益菌，这些有益物质通过血液进入大脑，减轻神经炎症，恢复免疫系统的平衡。虽然前景广阔，但科学家也提醒，禁食方案需要根据个人情况定制，对于已经存在认知障碍的脆弱人群，安全性仍需进一步验证。
四、 生活方式的全面干预：多管齐下最有效
单靠某一种食物或补剂可能不够，大规模的临床试验证明了“组合拳”的威力。
US POINTER试验是一项耗资巨大、在美国5个中心进行的随机对照试验，招募了2111名60至79岁、有认知衰退风险的老年人。
- 这些老人被随机分为两组：一组接受“结构化”的生活方式干预（有专业指导、强度更高、定期监督），另一组进行“自我引导”的干预（自己看着资料去增加运动、改善饮食、多社交、控制心血管风险）。
- 两年后的结果显示，两组人的大脑认知功能都有所提升（说明只要改变生活方式就有好处），但接受“结构化”高强度干预的那一组，大脑全局认知功能的提升幅度明显更大（每年平均提升0.243个标准差，高于自我引导组的0.213个标准差）。
- 更有意思的是，这种结构化干预对带有APOE ε4基因（一种大大增加老年痴呆风险的基因）的人同样有效，而且对初始认知分数较低的人效果更明显。这告诉我们，即使有遗传风险，只要通过科学、有纪律的综合生活方式干预，大脑依然能焕发活力。
五、 大脑黑客与神经科技：用技术“升级”大脑
除了吃和练，前沿科技正在让“改造大脑”从科幻走向现实。
1. “自己动手”的大脑黑客 民间早就有一群人在自己身上做实验，试图提升脑力，这被称为“DIY大脑黑客”。
- 早期，他们自己服用“拉西坦”类促智药（一类据说能增强记忆力的药物），或者在家里用微电流刺激自己的大脑（经颅直流电刺激），甚至微量使用致幻剂。
- 如今，这些民间的尝试正在被医学界“招安”和规范化。比如，他们开发的商业级认知训练APP和脑电波生物反馈设备，已经启发了美国食品药品监督管理局（FDA）批准的数字疗法，用于治疗注意力缺陷多动障碍（ADHD）、抑郁症和偏头痛。这说明，从野生 experimentation 到临床应用，大脑黑客正在推动医学的进步。
2. 神经接口与脑机接口（BCI） 未来十年，神经技术将迎来大爆发。脑机接口（BCI，让大脑直接与外部电脑设备相连的技术）不仅在帮助瘫痪患者重新控制肢体，还在被用于提升健康人的决策能力和调节情绪。
- 未来的脑机接口将不再是单向读取大脑信号，而是走向“闭环系统”——设备能实时监测你的精神状态，并在你注意力不集中或情绪低落时，自动给予精确的神经刺激来帮你调整。
- 甚至有“神经黑客”通过在自己体内植入微型设备，试图突破人类生理极限，成为“赛博格”（半机械人），在自我增强和利他奉献之间寻找平衡。当然，这一切都需要在严格的伦理框架下进行，确保安全、有效且公平。
六、 警惕生活中的“大脑杀手”
在给大脑补充营养的同时，我们也要避开那些悄悄伤害大脑的东西。
1. 代糖（低热量和无热量甜味剂）可能让大脑变笨 很多人为了减肥，用零度可乐、无糖饮料代替含糖饮料。但一项针对12,772名35岁以上成年人、长达8年的追踪研究泼了一盆冷水。
- 研究发现，长期摄入阿斯巴甜、糖精、安赛蜜、赤藓糖醇、木糖醇、山梨糖醇等人工甜味剂，会加速认知能力的下降，尤其是在语言流畅度（说话是否利索、词汇组织能力）和全局认知（整体智力表现）方面。
- 这种危害在60岁以下的人群中更为明显。而且，无论你是否患有糖尿病，长期吃这些代糖都会对记忆力和语言能力造成负面影响。研究人员认为，这可能与代糖改变了肠道菌群、引发了慢性炎症有关。因此，“无糖”未必等于“健康”，白开水或淡茶水依然是对大脑最友好的饮料。
总结
前沿科学告诉我们，大脑并不是一个不可改变的“黑匣子”，而是一个高度可塑、对营养和生活方式极其敏感的器官。从每天清晨的一杯咖啡、按时吃早餐，到补充肌酸和姜黄素，再到呵护肠道菌群、警惕人工代糖，每一个微小的选择都在塑造着我们大脑的未来。随着神经科技的不断突破，未来我们甚至能借助数字工具直接为大脑“充电”。保护好大脑，就是保护我们认识世界、感受生活的能力。
References
1Recent Advances in Inorganic Oxide-Based Resistive Random Access Memory: Challenges and Strategies for Practical Applications.PubMed
Anurag Pritam, Anwesha Mahapatra, Ritu Gupta, et al.
Memory is the backbone of modern computing systems, enabling efficient data storage and functionality. Among emerging nonvolatile memories, resistive random-access memory (RRAM) has garnered significant attention due to its fast switching speed, high scalability, low power consumption, and CMOS compatibility, which makes it suitable for neuromorphic architectures. RRAM operation relies on the history-dependent modulation of resistance in a dielectric layer in response to external stimuli. Recent developments have focused on the wide array of memory-active materials, particularly inorganic and organic compounds, each offering distinct operational modes, tunable switching characteristics, and pathways toward multilevel, low-power, and neuromorphic memory devices. This review summarizes the latest advances in oxide-based RRAM devices, a foundational platform that has driven critical breakthroughs from the initial memristor concept to modern filamentary switching mechanisms. It compares these developments with conventional memory technologies and discusses current challenges and future prospects. Furthermore, we highlight its emerging role in neuromorphic computing, underscoring its potential to revolutionize brain-inspired hardware.
2Coffee and Tea Intake, Dementia Risk, and Cognitive Function.PubMed
Yu Zhang, Yuxi Liu, Yanping Li, et al.
IMPORTANCE: Evidence linking coffee and tea to cognitive health remains inconclusive, and most studies fail to differentiate caffeinated from decaffeinated coffee. OBJECTIVE: To investigate associations of coffee and tea intake with dementia risk and cognitive function. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study that included female participants from the Nurses' Health Study (NHS; n = 86 606 with data from 1980-2023) and male participants from the Health Professionals Follow-up Study (HPFS; n = 45 215 with data from 1986-2023) who did not have cancer, Parkinson disease, or dementia at study entry (baseline) in the US. EXPOSURES: The primary exposures were intakes of caffeinated coffee, decaffeinated coffee, and tea. Dietary intake was collected every 2 to 4 years using validated food frequency questionnaires. MAIN OUTCOMES AND MEASURES: The primary outcome was dementia, which was identified via death records and physician diagnoses. The secondary outcomes included subjective cognitive decline assessed by a questionnaire-based score (range, 0-7; higher scores indicate greater perceived decline; cases defined as those with a score ≥3) and objective cognitive function assessed only in the NHS cohort using telephone-based neuropsychological tests such as the Telephone Interview for Cognitive Status (TICS) score (range, 0-41) and a measure of global cognition (a standardized mean z score for all 6 administered cognitive tests). RESULTS: Among 131 821 participants (mean age at baseline, 46.2 [SD, 7.2] years in the NHS cohort and 53.8 [SD, 9.7] years in the HPFS cohort; 65.7% were female) during up to 43 years of follow-up (median, 36.8 years; IQR, 28-42 years), there were 11 033 cases of incident dementia. After adjusting for potential confounders and pooling results across cohorts, higher caffeinated coffee intake was significantly associated with lower dementia risk (141 vs 330 cases per 100 000 person-years comparing the fourth [highest] quartile of consumption with the first [lowest] quartile; hazard ratio, 0.82 [95% CI, 0.76 to 0.89]) and lower prevalence of subjective cognitive decline (7.8% vs 9.5%, respectively; prevalence ratio, 0.85 [95% CI, 0.78 to 0.93]). In the NHS cohort, higher caffeinated coffee intake was also associated with better objective cognitive performance. Compared with participants in the lowest quartile, those in the highest quartile had a higher mean TICS score (mean difference, 0.11 [95% CI, 0.01 to 0.21]) and a higher mean global cognition score (mean difference, 0.02 [95% CI, -0.01 to 0.04]); however, the association with global cognition was not statistically significant (P = .06). Higher intake of tea showed similar associations with these cognitive outcomes, whereas decaffeinated coffee intake was not associated with lower dementia risk or better cognitive performance. A dose-response analysis showed nonlinear inverse associations of caffeinated coffee and tea intake levels with dementia risk and subjective cognitive decline. The most pronounced associated differences were observed with intake of approximately 2 to 3 cups per day of caffeinated coffee or 1 to 2 cups per day of tea. CONCLUSIONS AND RELEVANCE: Greater consumption of caffeinated coffee and tea was associated with lower risk of dementia and modestly better cognitive function, with the most pronounced association at moderate intake levels.
3Creatine Supplementation Beyond Athletics: Benefits of Different Types of Creatine for Women, Vegans, and Clinical Populations-A Narrative Review.PubMed
Jorge Gutiérrez-Hellín, Juan Del Coso, Arturo Franco-Andrés, et al.
Creatine monohydrate supplementation is widely used by athletes in high-intensity, power-based sports due to its ability to enhance short-term performance by increasing intramuscular phosphocreatine (PCr) stores, which aid in ATP resynthesis during intense muscle contractions. However, emerging evidence suggests that creatine monohydrate offers benefits beyond athletic performance. This narrative review explores the literature supporting the advantages of creatine supplementation in women, vegans, and clinical populations. In women, who typically have lower baseline intramuscular creatine levels, supplementation may help alleviate fatigue-related symptoms associated with the menstrual cycle, particularly during the early follicular and luteal phases. For vegans and vegetarians, who often have reduced creatine stores due to the absence of creatine-rich animal products in their diet, supplementation can improve both physical and cognitive performance while supporting adherence to plant-based diets. Additionally, creatine supplementation holds potential for various clinical populations. It may mitigate muscle wasting in conditions such as sarcopenia and cachexia, support neuroprotection in neurodegenerative diseases such as Parkinson's and Huntington's, improve exercise capacity in cardiovascular diseases, and enhance energy metabolism in chronic fatigue syndrome. Creatine may also aid recovery from traumatic brain injury by promoting brain energy metabolism and reducing neuronal damage. In conclusion, creatine monohydrate supplementation can enhance physical performance, cognitive function, and overall health in women, vegans, and clinical populations by addressing creatine deficiencies, improving energy metabolism, and supporting recovery from physical and neurological challenges. Most available evidence supports the effectiveness of creatine monohydrate, which should be considered the preferred form of creatine supplementation over other variants. Additionally, proper creatine dosing is essential to maximize benefits and minimize potential adverse effects that may arise from chronic ingestion of excessively high doses.
4The microbiota-gut-brain axis: pathways to better brain health. Perspectives on what we know, what we need to investigate and how to put knowledge into practice.PubMed
Anirikh Chakrabarti, Lucie Geurts, Lesley Hoyles, et al.
The gut and brain link via various metabolic and signalling pathways, each with the potential to influence mental, brain and cognitive health. Over the past decade, the involvement of the gut microbiota in gut-brain communication has become the focus of increased scientific interest, establishing the microbiota-gut-brain axis as a field of research. There is a growing number of association studies exploring the gut microbiota's possible role in memory, learning, anxiety, stress, neurodevelopmental and neurodegenerative disorders. Consequently, attention is now turning to how the microbiota can become the target of nutritional and therapeutic strategies for improved brain health and well-being. However, while such strategies that target the gut microbiota to influence brain health and function are currently under development with varying levels of success, still very little is yet known about the triggers and mechanisms underlying the gut microbiota's apparent influence on cognitive or brain function and most evidence comes from pre-clinical studies rather than well controlled clinical trials/investigations. Filling the knowledge gaps requires establishing a standardised methodology for human studies, including strong guidance for specific focus areas of the microbiota-gut-brain axis, the need for more extensive biological sample analyses, and identification of relevant biomarkers. Other urgent requirements are new advanced models for in vitro and in vivo studies of relevant mechanisms, and a greater focus on omics technologies with supporting bioinformatics resources (training, tools) to efficiently translate study findings, as well as the identification of relevant targets in study populations. The key to building a validated evidence base rely on increasing knowledge sharing and multi-disciplinary collaborations, along with continued public-private funding support. This will allow microbiota-gut-brain axis research to move to its next phase so we can identify realistic opportunities to modulate the microbiota for better brain health.
5The Evolution of Do-It-Yourself Brain Hacking: From Fringe to Frontier.PubMed
Shaheen E Lakhan
Do-it-yourself (DIY) brain hacking has evolved from fringe experimentation to a cultural and clinical phenomenon reshaping how individuals interact with their brains. From early self-directed use of racetam nootropics, at-home transcranial direct current stimulation, and meditation apps, to the normalization of microdosing psychedelics, this movement reflects a broader shift toward brain self-optimization. What began as grassroots experimentation now informs regulated interventions. For example, consumer-grade cognitive training tools and neurofeedback devices have inspired FDA-cleared prescription digital therapeutics for conditions such as attention-deficit/hyperactivity disorder, depression, and migraine. Similarly, informal mood tracking and exposure-based journaling practices have evolved into structured cognitive behavioral therapy apps and biosensor-informed just-in-time adaptive interventions. This editorial traces the trajectory of DIY brain hacking across three phases (experimental enthusiasts, consumer biohackers, and clinical convergence) and argues that medicine must shift from skepticism to stewardship. As programmable cognition becomes a clinical reality, and drawing on parallels with other organ systems, guiding this transformation with evidence and ethics is essential to safeguard patient autonomy, efficacy, and safety.
6The neuroplastic brain: current breakthroughs and emerging frontiers.PubMed
Parisa Gazerani
Neuroplasticity, the brain's capacity to reorganize itself by forming new neural connections, is central to modern neuroscience. Once believed to occur only during early development, research now shows that plasticity continues throughout the lifespan, supporting learning, memory, and recovery from injury or disease. Substantial progress has been made in understanding the mechanisms underlying neuroplasticity and their therapeutic applications. This overview article examines synaptic plasticity, structural remodeling, neurogenesis, and functional reorganization, highlighting both adaptive (beneficial) and maladaptive (harmful) processes across different life stages. Recent strategies to harness neuroplasticity, ranging from pharmacological agents and lifestyle interventions to cutting-edge technologies like brain-computer interfaces (BCIs) and targeted neuromodulation are evaluated in light of current empirical evidence. Contradictory findings in the literature are addressed, and methodological limitations that hamper widespread clinical adoption are discussed. The ethical and societal implications of deploying novel neuroplasticity-based interventions, including issues of equitable access, data privacy, and the blurred line between treatment and enhancement, are then explored in a structured manner. By integrating mechanistic insights, empirical data, and ethical considerations, the aim is to provide a comprehensive and balanced perspective for researchers, clinicians, and policymakers working to optimize brain health across diverse populations.
7Association Between Consumption of Low- and No-Calorie Artificial Sweeteners and Cognitive Decline: An 8-Year Prospective Study.PubMed
Natalia Gomes Gonçalves, Euridice Martinez-Steele, Paulo A Lotufo, et al.
BACKGROUND AND OBJECTIVES: Consumption of low- and no-calorie sweeteners (LNCSs) has been associated with adverse health outcomes. However, little is known about the association between consumption of LNCSs and cognition. The aim of this study was to investigate the association between consumption of LNCSs and cognitive decline. METHODS: We conducted a longitudinal observational study using data from civil servants aged 35+ years at baseline who were enrolled in the Brazilian Longitudinal Study of Adult Health and evaluated across 3 study waves (2008-10, 2012-14, and 2017-19). Participants with incomplete dietary data, extreme caloric intake (<1st percentile or >99th percentile), and incomplete data for cognitive tests and covariates at baseline were excluded. A Food Frequency Questionnaire was used to calculate combined and individual consumption of 7 LNCSs (aspartame, saccharin, acesulfame k, erythritol, xylitol, sorbitol, and tagatose). We estimated -scores across 6 cognitive tests. The association of LNCSs with cognitive decline was evaluated using linear mixed-effects models. RESULTS: Among 12,772 participants (mean age 51.9 ± 9.0 years, 54.8% women, 43.2% Black/mixed race), the mean consumption of LNCSs was 92.1 ± 90.1 mg/d. Among participants aged younger than 60 years, consumption of combined LNCSs in the highest tertiles was associated with a faster decline in verbal fluency (second tertile: β = -0.016, 95% CI -0.040 to -0.008; third tertile: β = -0.040, 95% CI -0.064 to -0.016) and global cognition (second tertile: β = -0.008, 95% CI -0.024 to 0.008; third tertile: β = -0.024, 95% CI -0.040 to -0.008). There was no association between tertiles of LNCSs and cognitive decline in participants aged 60+ years. Consumption of aspartame, saccharin, acesulfame k, erythritol, sorbitol, and xylitol was associated with a faster decline in global cognition, particularly in memory and verbal fluency domains. Consumption of combined LNCSs in the highest tertiles was associated with a faster decline in verbal fluency and global cognition in participants without diabetes and faster decline in memory and global cognition in participants with diabetes. DISCUSSION: Consumption of LNCSs was associated with an accelerated rate of cognitive decline during 8 years of follow-up. Our findings suggest the possibility of long-term harm from LNCS consumption, particularly artificial LNCSs and sugar alcohols, on cognitive function. Study limitations include self-reported dietary data, selection bias from attrition, and residual confounding from co-occurring health behaviors.
8Curcumin Modulation of the Gut-Brain Axis for Neuroinflammation and Metabolic Disorders Prevention and Treatment.PubMed
Miriam Cerullo, Federica Armeli, Beatrice Mengoni, et al.
Curcumin, a polyphenolic compound derived from Curcuma longa, has gained significant attention for its potential therapeutic benefits, particularly counteracting inflammation, oxidative stress, and metabolic disorders. Its chemical structure, featuring conjugated double bonds between two aromatic rings, allows it to act as an electron donor, thereby mitigating free radical formation. Despite its poor solubility in water, curcumin is stable in acidic environments and undergoes significant metabolism in both the liver and the gut. Intestinal microbiota, particularly at the colon level, further metabolizes curcumin into several derivatives, including dihydrocurcumin and tetrahydrocurcumin, which exhibit antioxidant and anti-inflammatory properties. Studies suggest that curcumin can reduce body mass index (BMI) and improve other body composition parameters, especially when used in combination with lifestyle changes, though its bioavailability is low due to its rapid metabolism and the resulting low blood concentration. In obesity, dysfunctional adipose tissue remodeling and chronic inflammation play critical roles in the development of metabolic complications. Curcumin's anti-inflammatory properties are related to the inhibition of the NF-κB pathway, leading to the reduction in inflammatory markers in adipocytes and macrophages. Additionally, curcumin modulates oxidative stress by activating the NRF2 pathway, enhancing cellular antioxidant defenses. Emerging evidence also supports curcumin's potential in improving gut health by modulating microbiota composition, enhancing intestinal barrier function, and reducing systemic inflammation. This interaction with the gut-brain axis highlights the broader implications of curcumin in neuroprotection, as it positively affects cognitive function and mitigates neuroinflammation in neurodegenerative diseases like Alzheimer's. disease. Thus, curcumin holds promise as a multifaceted agent in the management of obesity and associated diseases.
9Multi-omics reveal microbial determinants impacting the treatment outcome of antidepressants in major depressive disorder.PubMed
Yaping Wang, Jingjing Zhou, Junbin Ye, et al.
BACKGROUND: There is a growing body of evidence suggesting that disturbance of the gut-brain axis may be one of the potential causes of major depressive disorder (MDD). However, the effects of antidepressants on the gut microbiota, and the role of gut microbiota in influencing antidepressant efficacy are still not fully understood. RESULTS: To address this knowledge gap, a multi-omics study was undertaken involving 110 MDD patients treated with escitalopram (ESC) for a period of 12 weeks. This study was conducted within a cohort and compared to a reference group of 166 healthy individuals. It was found that ESC ameliorated abnormal blood metabolism by upregulating MDD-depleted amino acids and downregulating MDD-enriched fatty acids. On the other hand, the use of ESC showed a relatively weak inhibitory effect on the gut microbiota, leading to a reduction in microbial richness and functions. Machine learning-based multi-omics integrative analysis revealed that gut microbiota contributed to the changes in plasma metabolites and was associated with several amino acids such as tryptophan and its gut microbiota-derived metabolite, indole-3-propionic acid (I3PA). Notably, a significant correlation was observed between the baseline microbial richness and clinical remission at week 12. Compared to non-remitters, individuals who achieved remission had a higher baseline microbial richness, a lower dysbiosis score, and a more complex and well-organized community structure and bacterial networks within their microbiota. These findings indicate a more resilient microbiota community in remitters. Furthermore, we also demonstrated that it was not the composition of the gut microbiota itself, but rather the presence of sporulation genes at baseline that could predict the likelihood of clinical remission following ESC treatment. The predictive model based on these genes revealed an area under the curve (AUC) performance metric of 0.71. CONCLUSION: This study provides valuable insights into the role of the gut microbiota in the mechanism of ESC treatment efficacy for patients with MDD. The findings represent a significant advancement in understanding the intricate relationship among antidepressants, gut microbiota, and the blood metabolome. Additionally, this study offers a microbiota-centered perspective that can potentially improve antidepressant efficacy in clinical practice. By shedding light on the interplay between these factors, this research contributes to our broader understanding of the complex mechanisms underlying the treatment of MDD and opens new avenues for optimizing therapeutic approaches. Video Abstract.
10Biohacking the human gut microbiome for precision health and therapeutic innovation.PubMed
Jhommara Bautista, Andrés López-Cortés
Biohacking, the self-directed application of biotechnology, digital tools, and lifestyle interventions, has rapidly converged with gut microbiome science to create adaptive, individualized, and minimally invasive precision-health paradigms. This narrative review integrates current evidence on diet-based modulation, microbial therapeutics (probiotics, prebiotics, postbiotics, and fecal microbiota transplantation), and synthetic-biology approaches (engineered strains and phage or synthetic consortia) within a multi-omics and continuous-phenotyping framework. Mechanistically, short-chain fatty acids (SCFAs), bile-acid derivatives, and tryptophan catabolites operate as endocrine-like mediators linking gut microbial ecology with host immunity, metabolism, and neuroendocrine signaling. Pathways mediated by microbial metabolites underpin translational applications that span metabolic optimization, through improved insulin sensitivity, reduced adiposity, and attenuation of inflammation, and neurocognitive enhancement via the microbiome-gut-brain axis. Evidence from oncology further indicates that microbial metabolites and engineered taxa remodel stromal and immune niches, shaping therapeutic response and disease progression. Concurrently, emerging digital infrastructures, wearables, biosensors, metabolic avatars, and AI-driven "health twins," enable real-time, closed-loop modulation of host-microbe dynamics. Persistent challenges include methodological heterogeneity, safety concerns regarding live biotherapeutics and unsupervised fecal microbiota transplantation (FMT), fragmented regulation, and vulnerabilities in cyberbiosecurity and data equity. We propose a translational roadmap emphasizing standardized metadata (STORMS), validated reference frameworks, longitudinal multi-omics for causal inference, strain-level safety genomics, and governance integrating ethical and cybersecurity oversight. Under these conditions, microbiome-focused biohacking may evolve from anecdotal experimentation into a more reproducible and scientifically grounded component of preventive and personalized medicine. This manuscript is presented as a narrative and conceptual review, integrating validated microbiome research with emerging biohacking frameworks while explicitly distinguishing evidence-based findings from exploratory or speculative concepts.
11Spatiotemporal transcriptomic maps of mouse intracerebral hemorrhage at single-cell resolution.PubMed
Rong Xiang, Junmin Wang, Zhan Chen, et al.
Intracerebral hemorrhage (ICH) is a prevalent disease with high mortality. Despite advances in clinical care, the prognosis of ICH remains poor due to an incomplete understanding of the complex pathological processes. To address this challenge, we generated single-cell-resolution spatiotemporal transcriptomic maps of the mouse brain following ICH. This dataset is the most extensive resource available, providing detailed information about the temporal expression of genes along with a high-resolution cellular profile and preserved cellular organization. We identified 100 distinct cell subclasses, 17 of which were found to play significant roles in the pathophysiology of ICH. We also report similarities and differences between two experimental ICH models and human postmortem ICH brain tissue. This study advances the understanding of the local and global responses of brain cells to ICH. It provides a valuable resource that can facilitate future research and aid the development of novel therapies for this devastating condition.
12Structured vs Self-Guided Multidomain Lifestyle Interventions for Global Cognitive Function: The US POINTER Randomized Clinical Trial.PubMed
Laura D Baker, Mark A Espeland, Rachel A Whitmer, et al.
IMPORTANCE: Identifying new interventions to slow and prevent cognitive decline associated with dementia is critical. Nonpharmacological interventions targeting modifiable risk factors are promising, relatively low-cost, accessible, and safe approaches. OBJECTIVE: To compare the effects of two 2-year lifestyle interventions on cognitive trajectory in older adults at risk of cognitive decline and dementia. DESIGN, SETTING, AND PARTICIPANTS: Single-blind, multicenter randomized clinical trial enrolling 2111 participants from May 2019 to March 2023 (final follow-up, May 14, 2025) at 5 clinical sites in the US. Participant inclusion criteria enriched risk of cognitive decline and included age 60 to 79 years, sedentary lifestyle, and suboptimal diet plus at least 2 additional criteria related to family history of memory impairment, cardiometabolic risk, race and ethnicity, older age, and sex. INTERVENTIONS: Participants were randomly assigned with equal probability to structured (n = 1056) or self-guided (n = 1055) interventions. Both interventions encouraged increased physical and cognitive activity, healthy diet, social engagement, and cardiovascular health monitoring, but differed in structure, intensity, and accountability. MAIN OUTCOMES AND MEASURES: The primary comparison was difference between intervention groups in annual rate of change in global cognitive function, assessed by a composite measure of executive function, episodic memory, and processing speed, over 2 years. RESULTS: Among the 2111 individuals enrolled (mean age, 68.2 [SD, 5.2] years; 1455 [68.9%] female), 89% completed the year 2 assessment. The mean global cognitive composite z score increased from baseline over time in both groups, with a mean rate of increase per year of 0.243 SD (95% CI, 0.227-0.258) for the structured intervention and 0.213 SD (95% CI, 0.198-0.229) for the self-guided intervention. The mean rate of increase per year was statistically significantly greater for the structured group than the self-guided group by 0.029 SD (95% CI, 0.008-0.050; P = .008). Based on prespecified secondary subgroup comparisons, the structured intervention benefit was consistent for APOE ε4 carriers and noncarriers (P = .95 for interaction) but appeared greater for adults with lower vs higher baseline cognition (P = .02 for interaction). Fewer ascertained adverse events were reported in the structured group (serious: 151; nonserious: 1091) vs the self-guided group (serious: 190; nonserious: 1225), with a positive COVID-19 test result being the most common adverse event overall and more frequent in the structured group. CONCLUSIONS AND RELEVANCE: Among older adults at risk of cognitive decline and dementia, a structured, higher-intensity intervention had a statistically significant greater benefit on global cognition compared with an unstructured, self-guided intervention. Further investigation of functional outcomes, biomarkers, and ongoing extended follow-up will help address clinical relevance and sustainability of the observed cognitive benefits. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03688126.
13Plant-Derived Nutraceuticals in Mental Health and Brain Function: Mechanisms of Action and Therapeutic Potential.PubMed
Alejandro Borrego-Ruiz, Juan J Borrego
Considering the multiple benefits of nutraceuticals, and given the growing interest in exploring these effects, understanding their mechanisms and implications in mental well-being and neurological integrity is essential and requires further examination to clarify their therapeutic potential. This narrative review provides a comprehensive overview of recent advances in plant-derived nutraceuticals, particularly regarding their impact on mental health and brain function, by examining their bioactive components, their involvement in neuropsychiatric conditions, their role in neurodegeneration, emerging nutraceuticals with clinical relevance, and gut microbiome interactions with nutraceuticals and phytochemicals. Essential fatty acids, prebiotics, phytochemicals, and nutrients such as amino acids, vitamins, minerals, and omega-3 fatty acids contribute to mood regulation and cognitive function. Nutraceuticals can prevent or slow neurodegeneration by targeting misfolded proteins and modulating oxidative stress, neuroinflammation, mitochondrial dysfunction, and dysregulated signaling pathways. Phytochemicals act as phytopsychobiotics, influencing mental health through gut microbiome modulation and generation of bioactive metabolites. and curcumin exert neuroprotective, anti-inflammatory, antioxidant, and antidepressant effects. Ginsenosides promote neuroprotection, partially via gut microbiome-mediated mechanisms. Administration of polysaccharides and lavender essential oil improves neurotransmitter regulation, intestinal barrier integrity, and depressive-like behaviors in preclinical models. Omega-3 polyunsaturated fatty acids, anthocyanins, quercetin, catechins, and chlorogenic acid support neuroprotection and cognitive function via modulation of beneficial gut bacteria, short-chain fatty acid production, anti-inflammatory effects, and serotonin metabolism. The landscape of nutraceuticals offers a diverse range of dietary options with considerable potential to promote mental health and prevent neurodegeneration, but further research is required to elucidate how the gut microbiome may enhance these bioactivities.
14The Brain-Gut Health Initiative (BIGHI): A Prospective Cohort on Psychiatric Disorders in China.PubMed
Fengchun Wu, Baoyuan Zhu, Shixuan Feng, et al.
Major psychiatric disorders are characterized by substantial clinical heterogeneity and high comorbidity, yet their underlying biological mechanisms are not fully uncovered. The microbiota-gut-brain axis (MGBA) offers a cross-system perspective for elucidating the pathophysiology of major psychiatric disorders. The Brain-Gut Health Initiative (BIGHI) was established as the first prospective longitudinal cohort in China dedicated to investigating major psychiatric disorders guided by the framework of MGBA, enabling large-scale, transdiagnostic, and longitudinal analyses of brain-gut interactions. To date, the BIGHI has enrolled over 1,200 participants with schizophrenia, major depressive disorder, bipolar disorder, and healthy controls, with multidimensional data collected including clinical symptomatology, neurocognitive performance, electroencephalography, magnetic resonance imaging, peripheral blood biomarkers, and gut microbiome profiles. The studies within the BIGHI reveal (a) brain-gut physiological alterations in psychiatric disorders; (b) systematic relationships among brain function, peripheral physiological markers, and gut microbiome; and (c) brain-gut network patterns with marked interindividual heterogeneity. In future studies, we will expand the BIGHI into a collaborative network and promote data harmonization and interdisciplinary collaboration to advance computational psychiatry as well as its clinical translation.
15The present and future of neural interfaces.PubMed
Davide Valeriani, Francesca Santoro, Marcello Ienca
The 2020's decade will likely witness an unprecedented development and deployment of neurotechnologies for human rehabilitation, personalized use, and cognitive or other enhancement. New materials and algorithms are already enabling active brain monitoring and are allowing the development of biohybrid and neuromorphic systems that can adapt to the brain. Novel brain-computer interfaces (BCIs) have been proposed to tackle a variety of enhancement and therapeutic challenges, from improving decision-making to modulating mood disorders. While these BCIs have generally been developed in an open-loop modality to optimize their internal neural decoders, this decade will increasingly witness their validation in closed-loop systems that are able to continuously adapt to the user's mental states. Therefore, a proactive ethical approach is needed to ensure that these new technological developments go hand in hand with the development of a sound ethical framework. In this perspective article, we summarize recent developments in neural interfaces, ranging from neurohybrid synapses to closed-loop BCIs, and thereby identify the most promising macro-trends in BCI research, such as simulating vs. interfacing the brain, brain recording vs. brain stimulation, and hardware vs. software technology. Particular attention is devoted to central nervous system interfaces, especially those with application in healthcare and human enhancement. Finally, we critically assess the possible futures of neural interfacing and analyze the short- and long-term implications of such neurotechnologies.
16The immunology of stroke and dementia.PubMed
Costantino Iadecola, Josef Anrather
Ischemic stroke and vascular cognitive impairment, caused by a sudden arterial occlusion or more subtle but protracted vascular insufficiency, respectively, are leading causes of morbidity and mortality worldwide with limited therapeutic options. Innate and adaptive immunity have long been implicated in neurovascular injury, but recent advances in methodology and new experimental approaches have shed new light on their contributions. A previously unappreciated dynamic interplay of brain-resident, meningeal, and systemic immune cells with the ischemic brain and its vasculature has emerged, and new insights into the frequent overlap between vascular and Alzheimer pathology have been provided. Here, we critically review these recent findings, place them in the context of current concepts on neurovascular pathologies and Alzheimer's disease, and highlight their impact on recent stroke and Alzheimer therapies.
17Skipping breakfast and its wide-ranging health consequences: A systematic review from multiple metabolic disruptions to socioeconomic factors.PubMed
Tatiana Palotta Minari, Luciana Pellegrini Pisani
Skipping breakfast has been widely debated due to its potential health consequences across multiple domains. This systematic review evaluates literature from 2010 to 2025, analyzing 66 studies to assess its associations with obesity, diabetes, gut microbiome alterations, neurodegenerative diseases, cancer, sports performance, psychiatric disorders, cognitive health, and socioeconomic factors. The hypothesis suggests that breakfast omission is linked to various adverse health effects. Evidence highlights associations with obesity and weight gain due to altered hormonal responses influencing hunger and energy balance. Additionally, skipping breakfast negatively affects gut microbiota, contributing to systemic inflammation and metabolic dysfunction. Research suggests potential links to increased cancer risk through inflammatory pathways, while cognitive decline, mood disorders, and impaired athletic performance are also observed. Psychiatric disorders, including anxiety and depression, may be exacerbated by irregular meal patterns, influencing neurotransmitter regulation. Emerging studies indicate that breakfast consumption plays a role in bone mineral density, as prolonged fasting periods may affect calcium metabolism and skeletal health. Socioeconomic disparities impact breakfast consumption, affecting diet quality and overall health outcomes. While some individuals experience neutral or even beneficial effects, meal timing and caloric distribution play critical roles in metabolic and cardiovascular health. However, causality remains complex due to confounding factors like diet quality, physical activity, and socioeconomic status. Current studies face limitations, including small sample sizes and short intervention periods, requiring further research to refine conclusions and explore long-term mechanisms behind breakfast omission's health impacts.
18Intermittent Fasting as a Neuroprotective Strategy: Gut-Brain Axis Modulation and Metabolic Reprogramming in Neurodegenerative Disorders.PubMed
Zaw Myo Hein, Muhammad Faqhrul Fahmy Arbain, Suresh Kumar, et al.
Intermittent fasting (IF) is emerging as a heterogeneous neurometabolic intervention with the possibility of changing the course of neurodegenerative diseases. Through the modulation of the gut-brain axis (GBA), cellular bioenergetics (or metabolic) reprogramming, and involvement in preserved stress adaptation pathways, IF influences a range of physiological mechanisms, including mitobiogenesis, autophagy, circadian rhythm alignment, and neuroinflammation. This review critically synthesises current preclinical and early clinical evidence illustrating IF's capability to supplement synaptic plasticity and integrity, reduce toxic proteins (proteotoxic) burden, and rehabilitate glial and immune homeostasis across models of Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. The key players behind these effects are bioactive metabolites such as short-chain fatty acids (SCFA) and β-hydroxybutyrate (BHB), and molecular mediators such as brain-derived neurotrophic factor (BDNF). We feature the therapeutic pertinence of IF-induced changes in gut microbiota composition, immune response, and mitochondrial dynamics, and we discuss emerging approaches for merging IF into precision medicine frameworks. Crucial challenges include individual variability, protocol optimisation, safety in cognitively vulnerable populations, and the need for biomarker-guided, ethically grounded clinical trials. Finally, we propose IF as a scalable and flexible intervention that, when personalised and integrated with other modalities, may reframe neurodegeneration from a model of irreversible decline to one of modifiable resilience.
19Sex differences in fecal metabolic profiles of major depressive disorder: unveiling sex-specific metabolomic panel.PubMed
Siyu Ren, Peilin Qin, Yaping Wang, et al.
BACKGROUND: Major depressive disorder (MDD) disproportionately affects women, who exhibit a higher prevalence and greater symptom severity than men. However, sex-specific pathophysiological mechanisms remain poorly understood. Emerging evidence implicates gut microbiota-derived metabolites in MDD, but many prior studies have failed to consider sex differences, potentially obscuring critical biomarkers. This study aims to address this gap by characterizing sex-specific fecal metabolite profiles in MDD. METHODS: Untargeted metabolomics was used to examine fecal metabolic profiles in 279 participants (117 with MDD and 162 healthy controls). The cohort was stratified by biological sex to identify sex-specific metabolic alterations associated with depressive symptoms through statistical analyses. A machine learning approach incorporating feature selection was employed to identify potential discriminative biomarkers, with a particular focus on female metabolic characteristics. RESULTS: Sex-stratified analysis revealed significant metabolic divergence in female MDD patients compared to healthy controls. Twenty-four differentially abundant metabolites were identified in females, with heptylamine and phenaceturic acid being unique to this group; no significant differences were observed in males. Correlation analyses showed that phenaceturic acid and 1-monoheptadecanoyl glyceride were significantly negatively correlated with depressive symptom severity in females. Besides, a sex-specific diagnostic panel based on five key fecal metabolites demonstrated promising performance in distinguishing female MDD patients from healthy controls. CONCLUSION: By systematically revealing sex-dependent metabolic alterations, this study identified potential biomarkers for sex-specific diagnostic and therapeutic strategies. These findings highlight the importance of integrating sex-specific perspectives in gut-brain axis research to advance precision medicine in MDD, rather than relying solely on generalized approaches. TRIAL REGISTRATION: Human Research and Ethics Committee of Beijing Anding Hospital, Capital Medical University, China (Approval No. 2017-24), registered on 2018.07.24.
20Pioneering neurohackers: between egocentric human enhancement and altruistic sacrifice.PubMed
Günter Seyfried, Sandra Youssef, Markus Schmidt
The growing field of neurotechnology (NT) is becoming more and more accessible in terms of reduced costs, increasing availability and reliability of materials, and ways to implant devices. As in other engineering fields such as bio-or information technology, there is a growing community of pioneering hackers who (self-)experiment with NT and develop novel applications. While most debates about NT, its goals and ethical ramifications are usually conducted by professionals in the field (neuroscientists, -engineers, -ethicists), little is known within these institutional frameworks about the motivations, goals and visions of neurohackers and how they view ethical ramifications of NT therapeutics vs. human enhancement. In this study we draw on qualitative interviews with 13 of these neurohacking pioneers, who are interacting with NT from a grassroots perspective (i.e., a bottom-up and community/subculture-oriented approach), and shed light on: how they understand themselves in the context of human enhancement; what the role of invasive NTs is when it comes to identifying as a cyborg; if their practices show a clear distinction between therapy and enhancement; whether human enhancement is always about performance, optimization and functionality; and to which extent neurohackers contribute to "mainstreaming" NT.