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.

Conflict of interest statement

Authors’ information

Not applicable.

Ethics approval and consent to participate

All procedures involving human participants were approved by the Southern Health and Disability Ethics Committee (15/STH/36). Proxy consent was obtained from the treating physician in consultation with family members when patient consent was not possible. Consent from patients was sought as soon as they had sufficiently recovered.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

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)