PMID- 38014126
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231211
DP  - 2023 Nov 17
TI  - High-Protein Supplementation and Neuromuscular Electric Stimulation after 
      Aneurysmal Subarachnoid Hemorrhage Increases Systemic Amino Acid and Oxidative 
      Metabolism: A Plasma Metabolomics Approach.
LID - rs.3.rs-3600439 [pii]
LID - 10.21203/rs.3.rs-3600439/v1 [doi]
AB  - BACKGROUND: The INSPIRE randomized clinical trial demonstrated that a high 
      protein diet (HPRO) combined with neuromuscular electrical stimulation (NMES) 
      attenuates muscle atrophy and may improve functional outcomes after aSAH. Using 
      an untargeted metabolomics approach, we sought to identify specific metabolites 
      mediating these effects. METHODS: Blood samples were collected from subjects on 
      admission prior to randomization to either standard of care (SOC; N=12) or 
      HPRO+NMES (N=12) and at 7 days as part of the INSPIRE protocol. Untargeted 
      metabolomics were performed for each plasma sample. Paired fold changes were 
      calculated for each metabolite among subjects in the HPRO+NMES group at baseline 
      and 7 days after intervention. Changes in metabolites from baseline to 7 days 
      were compared for the HPRO+NMES and SOC groups. Sparse partial least squared 
      discriminant analysis (sPLS-DA) identified metabolites discriminating each group. 
      Pearson's correlation coefficients were calculated between each metabolite and 
      total protein per day, nitrogen balance, and muscle volume Multivariable models 
      were developed to determine associations between each metabolite and muscle 
      volume. RESULTS: A total of 18 unique metabolites were identified including pre 
      and post treatment and differentiating SOC vs HPRO+NMES. Of these, 9 had 
      significant positive correlations with protein intake: N-acetylserine (rho=0.61, 
      P=1.56x10(-3)), N-acetylleucine (rho=0.58, P=2.97x10(-3)), 
      beta-hydroxyisovaleroylcarnitine (rho=0.53, P=8.35x10(-3)), tiglyl carnitine (rho=0.48, 
      P=0.0168), N-acetylisoleucine (rho=0.48, P=0.0183), N-acetylthreonine (rho=0.47, 
      P=0.0218), N-acetylkynurenine (rho=0.45, P=0.0263), N-acetylvaline (rho=0.44, 
      P=0.0306), and urea (rho=0.43, P=0.0381). In multivariable regression models, 
      N-acetylleucine was significantly associated with preserved temporalis [OR 1.08 
      (95%CI 1.01, 1.16)] and quadricep [OR 1.08 (95%CI 1.02, 1.15)] muscle volume. 
      Quinolinate was also significantly associated with preserved temporalis [OR 1.05 
      (95%CI 1.01, 1.09)] and quadricep [OR 1.04 (95%CI 1.00, 1.07)] muscle volume. 
      N-acetylserine, N-acetylcitrulline, and b-hydroxyisovaleroylcarnitine were also 
      associated with preserved temporalis or quadricep volume. CONCLUSIONS: 
      Metabolites defining the HPRO+NMES intervention mainly consisted of amino acid 
      derivatives. These metabolites had strong correlations with protein intake and 
      were associated with preserved muscle volume.
FAU - Gusdon, Aaron M
AU  - Gusdon AM
AUID- ORCID: 0000-0002-3350-6601
AD  - University of Texas John P and Katherine G McGovern Medical School.
FAU - Savarraj, Jude Pj
AU  - Savarraj JP
AD  - University of Texas John P and Katherine G McGovern Medical School: The 
      University of Texas Health Science Center at Houston John P and Katherine G 
      McGovern Medical School.
FAU - Feng, Dians
AU  - Feng D
AD  - University of Texas John P and Katherine G McGovern Medical School: The 
      University of Texas Health Science Center at Houston John P and Katherine G 
      McGovern Medical School.
FAU - Starkman, Adam
AU  - Starkman A
AD  - University of Maryland Hospital: University of Maryland Medical Center.
FAU - Li, Guoyan
AU  - Li G
AD  - University of Maryland Hospital: University of Maryland Medical Center.
FAU - Bodanapally, Uttam
AU  - Bodanapally U
AD  - University of Maryland Hospital: University of Maryland Medical Center.
FAU - Zimmerman, William Denny
AU  - Zimmerman WD
AD  - University of Maryland Hospital: University of Maryland Medical Center.
FAU - Ryan, Alice S
AU  - Ryan AS
AD  - University of Maryland Hospital: University of Maryland Medical Center.
FAU - Choi, Huimahn A
AU  - Choi HA
AD  - University of Texas John P and Katherine G McGovern Medical School: The 
      University of Texas Health Science Center at Houston John P and Katherine G 
      McGovern Medical School.
FAU - Badjatia, Neeraj
AU  - Badjatia N
AUID- ORCID: 0000-0003-1509-9034
AD  - University of Maryland Hospital: University of Maryland Medical Center.
LA  - eng
GR  - K23 NS121628/NS/NINDS NIH HHS/United States
PT  - Preprint
DEP - 20231117
PL  - United States
TA  - Res Sq
JT  - Research square
JID - 101768035
PMC - PMC10680941
OTO - NOTNLM
OT  - Aneurysmal subarachnoid hemorrhage
OT  - N-acetylleucine
OT  - high protein diet
OT  - metabolomics
OT  - neuromuscular electrical stimulation
OT  - quinolinate
EDAT- 2023/11/28 06:42
MHDA- 2023/11/28 06:43
PMCR- 2023/11/27
CRDT- 2023/11/28 04:02
PHST- 2023/11/28 06:42 [pubmed]
PHST- 2023/11/28 06:43 [medline]
PHST- 2023/11/28 04:02 [entrez]
PHST- 2023/11/27 00:00 [pmc-release]
AID - rs.3.rs-3600439 [pii]
AID - 10.21203/rs.3.rs-3600439/v1 [doi]
PST - epublish
SO  - Res Sq [Preprint]. 2023 Nov 17:rs.3.rs-3600439. doi: 10.21203/rs.3.rs-3600439/v1.