PMID- 32335159 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20210618 IS - 1873-4596 (Electronic) IS - 0891-5849 (Linking) VI - 153 DP - 2020 Jun TI - Supplementation with a putative calorie restriction mimetic micronutrient blend increases glutathione concentrations and improves neuroenergetics in brain of healthy middle-aged men and women. PG - 112-121 LID - S0891-5849(20)30283-5 [pii] LID - 10.1016/j.freeradbiomed.2020.04.017 [doi] AB - 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 ((1)H) 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/H(2)O, 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. CI - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Mastaloudis, Angela AU - Mastaloudis A AD - Pharmanex Research, NSE Products, Inc., Provo, UT, USA. FAU - Sheth, Chandni AU - Sheth C AD - Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA; Diagnostic Neuroimaging, University of Utah, Salt Lake City, UT, USA. Electronic address: chandni.sheth@utah.edu. FAU - Hester, Shelly N AU - Hester SN AD - Pharmanex Research, NSE Products, Inc., Provo, UT, USA. FAU - Wood, Steven M AU - Wood SM AD - Pharmanex Research, NSE Products, Inc., Provo, UT, USA. FAU - Prescot, Andrew AU - Prescot A AD - Department of Radiology, University of Utah School of Medicine, Salt Lake City, UT, USA. FAU - McGlade, Erin AU - McGlade E AD - Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA; Diagnostic Neuroimaging, University of Utah, Salt Lake City, UT, USA; George E. Wahlen Department of Veterans Affairs Medical Center, VA VISN 19 Mental Illness Research, Education and Clinical Center (MIRREC), Salt Lake City, UT, USA. FAU - Renshaw, Perry F AU - Renshaw PF AD - Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA; Diagnostic Neuroimaging, University of Utah, Salt Lake City, UT, USA; George E. Wahlen Department of Veterans Affairs Medical Center, VA VISN 19 Mental Illness Research, Education and Clinical Center (MIRREC), Salt Lake City, UT, USA. FAU - Yurgelun-Todd, Deborah A AU - Yurgelun-Todd DA AD - Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA; Diagnostic Neuroimaging, University of Utah, Salt Lake City, UT, USA; George E. Wahlen Department of Veterans Affairs Medical Center, VA VISN 19 Mental Illness Research, Education and Clinical Center (MIRREC), Salt Lake City, UT, USA. LA - eng SI - ClinicalTrials.gov/NCT02439983 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200423 PL - United States TA - Free Radic Biol Med JT - Free radical biology & medicine JID - 8709159 RN - 0 (Micronutrients) RN - GAN16C9B8O (Glutathione) SB - IM MH - Adult MH - Animals MH - Brain/diagnostic imaging MH - *Caloric Restriction MH - Dietary Supplements MH - Female MH - *Glutathione MH - Humans MH - Male MH - Micronutrients MH - Middle Aged EDAT- 2020/04/27 06:00 MHDA- 2021/06/22 06:00 CRDT- 2020/04/27 06:00 PHST- 2020/01/21 00:00 [received] PHST- 2020/04/17 00:00 [revised] PHST- 2020/04/19 00:00 [accepted] PHST- 2020/04/27 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/04/27 06:00 [entrez] AID - S0891-5849(20)30283-5 [pii] AID - 10.1016/j.freeradbiomed.2020.04.017 [doi] PST - ppublish SO - Free Radic Biol Med. 2020 Jun;153:112-121. doi: 10.1016/j.freeradbiomed.2020.04.017. Epub 2020 Apr 23.