 根据世界卫生组织(World Health Organization, WHO)的最新定义，大脑健康(Brain health)是指适当的认知，感觉，社会情感，行为和运动功能的状态，允许一个人在整个时间内充分发挥他的潜力，无论是否存在障碍[1]。在优化大脑健康的背景下，一些研究人员[2,3]呼吁关注神经科学的新兴领域-营养认知神经科学(Nutritional cognitive neuroscience)。这个科学分支旨在研究营养如何影响大脑的发育，整体健康和衰老过程[4,5]。神经营养学(Neuronutrition)是一个跨学科领域，研究营养的各个方面对大脑健康的影响，神经疾病的预防和治疗。大脑需要特定的营养物质来维持其结构完整性，支持认知过程，并防止神经退行性疾病[6]。客观地评估大脑健康是神经科学中的一个关键挑战，特别是在检测和诊断早期神经认知变化方面，包括由营养缺乏引起的变化[7]。精准神经营养(Precision neuronutrition)旨在确定个性化的营养需求，以优化大脑健康结果并预防神经系统疾病[8,9]。
指示脑健康状态的生物标志物主要包括神经炎症、氧化应激、肠-脑轴紊乱和营养缺乏。 (1) 神经炎症：神经炎症(Neuroinflammation)的主要生物标志物是C-反应蛋白(C-reactive protein)、白细胞介素-6(Interleukin-6)和肿瘤坏死因子-α(Tumor necrosis factor-α)。这些生物标志物的水平在许多神经系统疾病中发生改变，包括阿尔茨海默病(Alzheimer’s disease, AD)、帕金森病(Parkinson’s disease, PD)、癫痫(Epilepsy)和其他疾病[10-12]。然而，由于该过程的复杂生物学特性以及收集和分析相关数据的新策略的需求，评估神经炎症的程度尚存在许多困难[13,14]。 (2) 氧化应激：氧化应激(Oxidative Stress)已被证明在许多神经退行性疾病(包括AD、PD、肌萎缩侧索硬化和亨廷顿病)的发病机制中起关键作用[15-17]。大脑特别容易受到氧化损伤，活性氧(ROS)的过度形成可导致神经元细胞死亡[18]。过氧化氢酶(Catalase)、谷胱甘肽过氧化物酶-1(Glutathione peroxidase-1)已在血浆中定量，作为氧化应激的指标[19]。许多与氧化应激相关的生物标志物可以使用标准测定法在生物样品中测量[20]。 (3) 肠-脑轴紊乱：肠道菌群及其代谢产物已被证明通过肠-脑轴(Gut-brain axis)调节在许多神经系统疾病的发病机制和进展中发挥作用[21]。短链脂肪酸是可能影响脑功能的代谢物，与一些神经系统疾病有关。吲哚参与各种神经功能，并与几种神经系统疾病有关[22]。二级胆汁酸可以作为大脑中胆汁酸受体的激活剂，它们对单个受体的亲和力不同[23]。血清素、多巴胺、5-氨基戊酸和牛磺酸是由肠道细菌产生的神经递质，它们调节大脑和肠道本身的神经传递[24]。 (4) 营养缺乏：营养缺乏可导致神经炎症、氧化应激和广泛的神经系统问题的表现，包括脑病、认知障碍和精神疾病[25-27]。例如维生素B12缺乏与认知障碍、多发性神经病和精神病表现有关[28]。硫胺素缺乏可导致Wernicke-Korsakoff综合征[29]。维生素D缺乏可导致神经系统表现，如抑郁症，认知障碍和多发性硬化症[30]。镁缺乏与许多神经系统疾病相关，如AD、中风、偏头痛、抑郁症和小脑综合征[31-33]。辅酶Q10可能对神经系统疾病具有神经保护作用，包括AD、PD、亨廷顿氏病、肌萎缩侧索硬化和中风[34,35]。肉毒碱缺乏的神经系统表现包括低血压、烧灼痛、耐力下降、感觉障碍、发育迟缓、僵硬和肌病[36,37]。这些生物标志物可以为营养干预的有效性提供实时反馈。
多酚具有通过同时调节肠-脑轴来解决脑老化的巨大潜力。益生菌可以通过减少氧化应激和降低神经退行性疾病(如AD、中风、多发性硬化、PD等)的风险，对神经系统疾病患者产生有益影响[38]。非消化性低聚糖通过调节肠-脑轴具有神经保护作用[39]。 下图中显示了ω-3多不饱和脂肪酸、α-生育酚、镁和叶酸这4大营养素对对大脑及心理健康的主要生理作用总结。
图 ω-3多不饱和脂肪酸、α-生育酚、镁和叶酸对大脑及心理健康的主要生理作用[40]。 (↓)表示下调；(↑)表示上调。PUFA: 多不饱和脂肪酸；SPM: 专门的促消退介质。 摄入ω-3多不饱和脂肪酸(ω-3 Polyunsaturated fatty acids, ω-3 PUFAs)已被证明可以改善学习，记忆，认知健康和大脑中的血液流动[41]。ω-3 PUFAs还可以靶向神经炎症[42]、氧化应激[43]和肠-脑紊乱[44]。EPA和DHA是主要的ω-3 PUFAs，具有抗炎特性并发挥各种生物活性，主要作为专门促消退介质(SPM)生物合成的底物和细胞受体的激动剂[45]。DHA高度集中在中枢神经系统(CNS)中，在最佳发育和后期认知功能中起着关键作用[46]，DHA在衰老过程中在大脑中减少[47]。令人感兴趣的是，EPA和DHA可以转化为它们各自的内源性大麻素衍生物，二十碳五烯酰乙醇胺(EPEA)和二十二碳六烯酰乙醇胺(DHEA)，具有潜在的抗抑郁作用[48]。 α-生育酚是维生素E的八种异构体之一，主要位于细胞膜中，它增加了脂质包装的规律性。α-生育酚发挥一种保护性抗氧化剂和抗炎活性，有效防止脂质过氧化。维生素E缺乏可发生在慢性脂肪吸收不良或脂蛋白缺乏的情况α-生育酚缺乏会损害先天性和适应性免疫功能[49]，可增加妊娠期间的不良事件，并导致神经异常或疾病[50]。 叶酸是水溶性维生素B9的合成形式，在体内需要代谢成生物利用度更高的L-甲基叶酸，以发挥其多种作用。L-甲基叶酸能够穿过包括B9在内的几种B族维生素也是同型半胱氨酸代谢的辅助因子，能够减少高水平这种氨基酸引起的炎症[51]。叶酸缺乏症主要是由饮食摄入不足引起的，可导致成人神经系统症状和胎儿神经管缺陷[52]。 镁是人体内第二丰富的细胞内阳离子，作为钙拮抗剂，具有广泛的生物学作用，包括细胞能量代谢、神经传导、膜稳定性和突触传递。镁还具有通过减少促炎分子的表达和释放介导的抗炎特性[53]。 [1] World Health Organization. Optimizing Brain Health across the Life Course: WHO Position Paper; World Health Organization: Geneva, Switzerland, 2022. 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