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Branched-Chain Amino Acids Can Predict Mortality in ICU Sepsis Patients.

ABSTRACT: Sepsis biomarkers and potential therapeutic targets are urgently needed. With proton nuclear magnetic resonance (¹H NMR) spectroscopy, several metabolites can be assessed simultaneously. Fifty-three adult medical ICU sepsis patients and 25 ICU controls without sepsis were prospectively enrolled. ¹H NMR differences between groups and associations with 28-day and ICU mortality were investigated. In multivariate metabolomic analyses, we found separate clustering of ICU controls and sepsis patients, as well as septic shock survivors and non-survivors. Lipoproteins were significantly different between sepsis and control patients. Levels of the branched-chain amino acids (BCAA) valine (median 43.3 [29.0-53.7] vs. 64.3 [47.7-72.3] normalized signal intensity units; p = 0.005), leucine (57.0 [38.4-71.0] vs. 73.0 [54.3-86.3]; p = 0.034) and isoleucine (15.2 [10.9-21.6] vs. 17.9 [16.1-24.4]; p = 0.048) were lower in patients with septic shock compared to those without. Similarly, BCAA were lower in ICU non-survivors compared to survivors, and BCAA were good discriminators for ICU and 28-day mortality. In uni- and multivariable logistic regression analyses, higher BCAA levels were associated with decreased ICU- and 28-day mortality. In conclusion, metabolomics using ¹H NMR spectroscopy showed encouraging potential for personalized medicine in sepsis. BCAA was significantly lower in sepsis non-survivors and may be used as early biomarkers for outcome prediction.

SUBMITTER: Reisinger AC

PROVIDER: S-EPMC8469152 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCirculating branched-chain amino acid (BCAA) levels reflect metabolic health and dietary intake. However, associations with breast cancer are unclear.MethodsWe evaluated circulating BCAA levels and breast cancer risk within the Nurses' Health Study (NHS) and NHSII (1997 cases and 1997 controls). A total of 592 NHS women donated 2 blood samples 10 years apart. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer risk in multivariable logistic regression models. We conducted an external validation in 1765 cases in the Women's Health Study (WHS). All statistical tests were 2-sided.ResultsAmong NHSII participants (predominantly premenopausal at blood collection), elevated circulating BCAA levels were associated with lower breast cancer risk (eg, isoleucine highest vs lowest quartile, multivariable OR = 0.86, 95% CI = 0.65 to 1.13, P trend = .20), with statistically significant linear trends among fasting samples (eg, isoleucine OR = 0.74, 95% CI = 0.53 to 1.05, P trend = .05). In contrast, among postmenopausal women, proximate measures (<10 years from blood draw) were associated with increased breast cancer risk (eg, isoleucine OR = 1.63, 95% CI = 1.12 to 2.39, P trend = .01), with stronger associations among fasting samples (OR = 1.73, 95% CI = 1.15 to 2.61, P trend = .01). Distant measures (10-20 years since blood draw) were not associated with risk. In the WHS, a positive association was observed for distant measures of leucine among postmenopausal women (OR = 1.23, 95% CI = 0.96 to 1.58, P trend = .04).ConclusionsNo statistically significant associations between BCAA levels and breast cancer risk were consistent across NHS and WHS or NHSII and WHS. Elevated circulating BCAA levels were associated with lower breast cancer risk among predominantly premenopausal NHSII women and higher risk among postmenopausal women in NHS but not in the WHS. Additional studies are needed to understand this complex relationship.

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Branched-Chain Amino Acids Can Predict Mortality in ICU Sepsis Patients.

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