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

Abstract

Background: Vitamin 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.

Methods: Forty-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.

Results: Overall, 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).

Conclusions: Critically 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.

Keywords: C-reactive protein; Critical illness; Enteral nutrition; Hypovitaminosis C; Intensive care; Parenteral nutrition; Sepsis; Septic shock; Vitamin C.

Fig. 1

Plasma vitamin C concentrations in critically ill patients. a Septic shock patients had significantly lower vitamin C concentrations than non-septic patients (P < 0.03 using linear mixed effects model). Box plots show median with 25th and 75th percentiles as boundaries, and whiskers are the range. b Time course of plasma vitamin C concentrations in the non-septic group (filled circles) and the septic shock group (filled triangles). Data represent mean and SD. Dotted lines indicate the hypovitaminosis C cutoff (23 μmol/L) and vitamin C deficiency cutoff (11 μmol/L)

Fig. 2

Plasma C-reactive protein concentrations in critically ill patients. a Time course of C-reactive protein concentrations in the non-septic group (filled circles) and the septic shock group (filled triangles). Data represent mean and SD. Significant differences between the two groups are indicated (*P < 0.01 using linear mixed effects model). b C-reactive protein concentrations relative to vitamin C concentrations. Baseline (time 0 h) C-reactive protein concentrations were divided around the hypovitaminosis C value of 23 μmol/L. Box plots show medians with 25th and 75th percentiles as boundaries and whiskers as the range. The C-reactive protein concentration was significantly different between the hypovitaminosis C group and > 23 μmol/L group (P < 0.05)

Fig. 3

Predicted compared with measured vitamin C concentrations in critically ill patients. Vitamin C concentrations predicted from enteral and/or parenteral administration (filled circles) were compared with measured plasma vitamin C concentrations (filled triangles). Predicted levels were obtained by fitting a four-parameter log-logistic response model to the pharmacokinetic data reported elsewhere [23]. Data represent mean and SD. All measured values were significantly lower than predicted values (P < 0.0001). Dotted lines indicate inadequate vitamin C cutoff (50 μmol/L), hypovitaminosis C cutoff (23 μmol/L) and vitamin C deficiency cutoff (11 μmol/L)

Fig. 4

Rapid loss of vitamin C in a critically ill patient. a The patient’s vitamin C concentrations (black circles) were compared with the critically ill cohort (grey circles) over the 4-day study period. Data for the critically ill cohort represents mean and SD (n = 43). b Increasing C-reactive protein (CRP) concentrations (filled diamonds) relative to decreasing vitamin C concentrations (grey circles). Dotted lines indicate inadequate vitamin C cutoff (50 μmol/L), hypovitaminosis C cutoff (23 μmol/L) and vitamin C deficiency cutoff (11 μmol/L); dashed line indicates infectious disease cutoff for CRP (100 mg/L)