Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes

Abstract

BackgroundVitamin C is an essential water-soluble nutrient which cannot be synthesised or stored by humans. It is a potent antioxidant with anti-inflammatory and immune-supportive roles. Previous research has indicated that vitamin C levels are depleted in critically ill patients. In this study we have assessed plasma vitamin C concentrations in critically ill patients relative to infection status (septic shock or non-septic) and level of inflammation (C-reactive protein concentrations). Vitamin C status was also assessed relative to daily enteral and parenteral intakes to determine if standard intensive care unit (ICU) nutritional support is adequate to meet the vitamin C needs of critically ill patients.MethodsForty-four critically ill patients (24 with septic shock, 17 non-septic, 3 uncategorised) were recruited from the Christchurch Hospital Intensive Care Unit. We measured concentrations of plasma vitamin C and a pro-inflammatory biomarker (C-reactive protein) daily over 4 days and calculated patients’ daily vitamin C intake from the enteral or total parenteral nutrition they received. We compared plasma vitamin C and C-reactive protein concentrations between septic shock and non-septic patients over 4 days using a mixed effects statistical model, and we compared the vitamin C status of the critically ill patients with known vitamin C bioavailability data using a four-parameter log-logistic response model.ResultsOverall, the critically ill patients exhibited hypovitaminosis C (i.e., < 23 μmol/L), with a mean plasma vitamin C concentration of 17.8 ± 8.7 μmol/L; of these, one-third had vitamin C deficiency (i.e., < 11 μmol/L). Patients with hypovitaminosis C had elevated inflammation (C-reactive protein levels; P < 0.05). The patients with septic shock had lower vitamin C concentrations and higher C-reactive protein concentrations than the non-septic patients (P < 0.05). Nearly 40% of the septic shock patients were deficient in vitamin C, compared with 25% of the non-septic patients. These low vitamin C levels were apparent despite receiving recommended intakes via enteral and/or parenteral nutritional therapy (mean 125 mg/d).ConclusionsCritically ill patients have low vitamin C concentrations despite receiving standard ICU nutrition. Septic shock patients have significantly depleted vitamin C levels compared with non-septic patients, likely resulting from increased metabolism due to the enhanced inflammatory response observed in septic shock.

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“…Most importantly in the setting of sepsis, vitamin C is an antioxidant and neutralizes reactive oxygen and nitrogen radicals, inhibits activation of pro-inflammatory cytokines, increases endogenous vasopressor synthesis, and inhibits bacterial replication [422][423][424]. Adults with sepsis frequently have very low levels of vitamin C. In one study, 88% of adults with septic shock had hypovitaminosis C [425]. Small studies in adults suggest that treatment of septic patients with vitamin C may improve organ dysfunction [426] and reduce mortality [427].…”

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“…There is accelerated catabolism of skeletal muscle and perhaps smooth muscle as well [209]. In addition, micronutrient (e.g., vitamins, trace metals) effects are also impaired, reflecting either deficiency or altered activity [210,211]. In addition, abnormalities are noted in the level and/or effectiveness of most hormones in sepsis [192].…”

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“…Vitamin C plays an important role in the physiological pathways by acting as an electron donor, protecting biomolecules (proteins, lipids and DNA) through its anti‐oxidant properties, and thus helps preserve essential tissue structure and function . Vitamin C has a role in energy generation as it promotes the transport of long‐chain fatty acids across mitochondrial cell membrane and is also involved in the synthesis of several hormones as it acts as a cofactor for several biosynthetic enzymes . Recent research indicates that vitamin C has an important role in the regulation of gene transcription .…”