BACKGROUND Caloric restriction (CR) without micronutrient deficiency has been shown to increase both lifespan and healthspan. In animals, CR has been demonstrated to increase glutathione (GSH), a neuroprotective antioxidant, in the brain and preserve brain mitochondrial function by altering neuroenergetics. In humans it has been associated with improvements in mood states and cognitive function. However, most CR studies have employed a 30-60% reduction in calories which is likely too stringent for most people to adhere to long-term. Thus, there is an unmet need for nutritional supplements which can mimic the biological effects of CR, without the need for calorie limitations. AIM The purpose of the present randomized, placebo-controlled clinical trial was to use Proton (1H) Magnetic Resonance Spectroscopic (MRS) measurements to determine non-invasively whether a blend of micronutrients, a putative CR mimetic, positively modulates metabolites related to neuroprotection and neuroenergetics in the brain. METHODS Healthy middle-aged men and women (N = 63 [33 women]; age: 40-60 years) were randomized in a double-blind manner to 6 weeks supplementation with either the putative CR mimetic or placebo. At baseline and 6 weeks, subjects underwent MRS at 3 T to investigate changes in brain chemistry, including the neurometabolites: GSH, Glutamate (Glu), Glutamine (Gln) and N-Acetylaspartate (NAA). RESULTS GSH, a marker of antioxidant and cellular redox status, increased in the brain of participants in the supplement group. The supplement group also showed an increase in the Glu/Gln ratio, a marker of excitatory neurotransmission and bioenergetics. A trend for an increase in NAA/H2O, a marker of neuronal integrity, was observed in females in the supplement group. CONCLUSIONS The present study reveals that 6-weeks daily supplementation with a micronutrient blend elicits positive changes in brain neurochemistry. This is the first study to demonstrate that a putative CR mimetic increases brain GSH concentrations and improves neuroprotection and neuroenergetics in the brain of healthy humans. This study was registered at www.clinicaltrials.gov as NCT02439983.

中文翻译：

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补充假定的限制卡路里的模拟微量营养素混合物可以增加健康的中年男女大脑中的谷胱甘肽浓度并改善其神经能。

背景技术已经显示出无微量营养素缺乏的热量限制（CR）可以增加寿命和健康寿命。在动物中，CR已被证明可通过改变神经能量来增加脑中的谷胱甘肽（GSH）（一种神经保护性抗氧化剂）并保持脑线粒体功能。在人类中，它与情绪状态和认知功能的改善有关。但是，大多数CR研究都采用了减少30-60％的卡路里的做法，这对于大多数人来说可能太严格而不能长期坚持。因此，对营养补充剂的需求未得到满足，其可以模拟CR的生物学作用，而无需限制卡路里。目的本随机目的，安慰剂对照的临床试验是使用质子（1H）磁共振波谱（MRS）测量来无创地确定微量营养素（一种假定的CR模拟物）的混合物是否正调节与大脑神经保护和神经能量相关的代谢产物。方法将健康的中年男女（N = 63 [33名妇女]；年龄：40-60岁）以双盲方式随机分为6周，补充既定的CR模拟药物或安慰剂。在基线和第6周时，受试者在3 T时接受MRS，以研究脑化学物质的变化，包括神经代谢物：谷胱甘肽，谷氨酸盐（Glu），谷氨酰胺（Gln）和N-乙酰乙酰天冬氨酸（NAA）。结果GSH是抗氧化剂和细胞氧化还原状态的标志物，在补充剂组参与者的大脑中升高。补充剂组还显示出Glu / Gln比增加，这是兴奋性神经传递和生物能的标志。在补充剂组的女性中观察到NAA / H2O（神经元完整性的标志物）增加的趋势。结论本研究表明，每天补充微量营养素6周可引起脑神经化学的积极变化。这是第一个证明假定的CR模拟物可增加健康人的大脑GSH浓度并改善其神经保护和神经能量的研究。该研究已在www.clinicaltrials.gov上注册为NCT02439983。结论本研究表明，每天补充微量营养素6周可引起脑神经化学的积极变化。这是第一个证明假定的CR模拟物可增加健康人的大脑GSH浓度并改善其神经保护和神经能量的研究。该研究已在www.clinicaltrials.gov上注册为NCT02439983。结论本研究表明，每天补充微量营养素6周可引起脑神经化学的积极变化。这是第一个证明假定的CR模拟物增加大脑GSH浓度并改善健康人的大脑中神经保护和神经能量的研究。该研究已在www.clinicaltrials.gov上注册为NCT02439983。