Impact of MnSOD and GPx1 Genotype at Different Levels of Enteral Nutrition Exposure on Oxidative Stress and Mortality: A Post hoc Analysis From the FeDOx Trial.

BACKGROUND

Converting nutrition support to energy results in mitochondrial free radical production, possibly increasing oxidative stress. Highly prevalent single nucleotide variants (SNV) exist for the genes encoding antioxidant enzymes responsible for the detoxification of reactive oxygen species. Our objective was to explore the interaction between nutrition support and genetic SNV's for two anti-oxidant proteins (rs4880 SNV for manganese superoxide dismutase and rs1050450 SNV for glutathione peroxidase 1) on oxidative stress and secondarily on intensive care unit (ICU) mortality.

METHODS

We performed a post-hoc analysis on 34 mechanically ventilated sepsis patients from a randomized control feeding trial. Participants were dichotomized into those who carried both the rs4880 and the rs1050450 at-risk alleles (Risk Group) versus all others (Nonrisk Group). We explored the interaction between genotype and percent time spent in the upper median of energy exposure on oxidative stress and ICU mortality.

RESULTS

Adjusting for confounders, the slope of log F2-isoprostane levels across percentage of days spent in the upper median of daily kilocalories per kilogram (kcal/kg) was 0.01 higher in the Risk Group compared to the Non-Risk Group (p=0.01). Every 1 percent increase in days spent in the upper median of daily kcal/kg was associated with an adjusted 10.3 percent increased odds of ICU mortality amongst participants in the Risk Group (odds ratio [OR]=1.103, p=0.06) but was highly insignificant in the Nonrisk group (OR=0.991, P=0.79).

CONCLUSION

Nutrition support may lead to increased oxidative stress and worse clinical outcomes in a large percent of ICU patients with an at-risk genotype.

© 2020 American Society for Parenteral and Enteral Nutrition.