Elsevier

Nutrition

Volume 26, Issues 11–12, November–December 2010, Pages 1070-1074
Nutrition

Applied nutritional investigation
Metabolic origin of hypovitaminosis C in acutely hospitalized patients

https://doi.org/10.1016/j.nut.2009.08.015Get rights and content

Abstract

Objective

Recent studies have indicated a high prevalence of hypovitaminosis C in acutely hospitalized patients. It is unclear whether hypovitaminosis C in this setting represents deficiency or tissue redistribution of the vitamin as part of the acute-phase response.

Methods

We administered vitamin C for 1 wk to acutely hospitalized, but not critically ill patients with hypovitaminosis C, on the assumption that a large increase in plasma and mononuclear leukocyte vitamin C concentrations, a decrease in metabolic markers of oxidative stress, or an improvement in psychologic mood state would implicate the initial condition as nutritional deficiency rather than tissue redistribution.

Results

Vitamin C administration increased plasma and mononuclear leukocyte vitamin C concentrations from subnormal (16.3 ± 12.4 μmol/L and 6.5 ± 5.5 mmol/L, respectively) to normal (71.0 ± 30.9 μmol/L, P < 0.0001, and 8.2 ± 6.8 mmol/L, P < 0.015); the mood disturbance score improved by 33% (P < 0.008). There was no increase in plasma glutathione concentrations or a reduction in plasma or mononuclear leukocyte malondialdehyde concentrations. An inverse relation was observed between plasma C-reactive protein and plasma vitamin C concentrations (P = 0.006).

Conclusion

Although associated with systemic inflammation, the metabolic features of hypovitaminosis C in acutely hospitalized, non-critically ill patients are more consistent with deficiency than with tissue redistribution.

Introduction

Vitamin C deficiency is considered rare in the United States and Canada, where this vitamin is readily available in the diet and half of Americans use nutritional supplements that typically contain vitamin C [1], [2]. The most recent survey of the vitamin C status of patients in American hospitals, published in 1993, indicated no evidence of deficiency [3]. It is understandable, therefore, why plasma vitamin C concentrations are rarely measured and vitamin C supplements rarely prescribed to patients in American and Canadian hospitals.

In contrast, a high prevalence of hypovitaminosis C has recently been reported in acutely hospitalized patients in Brazil [4], France [5], and England [6]. A population-based survey of the biochemical vitamin C status of patients admitted to a Montreal teaching hospital performed in 2006 disclosed hypovitaminosis C in 60% of the patients but in only 16% of people attending the same hospital's outpatient test center [7].

Hypovitaminosis C usually implies vitamin C deficiency, but it could also occur as part of the acute-phase response. The acute-phase response lowers circulating concentrations of nutrients such as iron, zinc, and retinol through tissue sequestration and lowered plasma binding protein concentrations [8], [9], [10] and has been speculated to similarly affect vitamin C [8], [10]. Consistent with this possibility, intravenous interleukin-2 therapy drastically lowers plasma vitamin C concentrations [11], and the plasma vitamin C concentrations of critically ill patients in intensive care units are often extremely low [12], [13], [14]. A recent expert consultation has suggested that, when associated with infection or trauma, hypovitaminosis C can be attributed to uptake of the vitamin by circulating leukocytes and, hence, is not indicative of deficiency [15]. In the European studies of non-critically ill patients cited earlier, circulating vitamin C and C-reactive protein (CRP) concentrations were inversely related, suggesting that the acute-phase response could indeed account for the hypovitaminosis C observed in this setting [5], [6].

When the acute-phase response lowers the plasma concentration of a nutrient, little or no increase typically results if the nutrient is administered. In contrast, in true deficiency states, administration of the missing nutrient promptly increases its concentration toward normal. We used this paradigm to investigate the metabolic origin of hypovitaminosis C in acutely, but not critically ill patients by measuring their plasma and leukocyte vitamin C response to vitamin C administration.

Subclinical vitamin C deficiency is associated with altered mood [16], [17], lowered plasma glutathione concentrations, and oxidative stress [18]. Plasma concentrations of malondialdehyde (MDA), a byproduct of lipid peroxidation [19], [20], are inversely related to plasma vitamin C concentrations in ambulatory [21] and acutely hospitalized [22] patients. An additional aim was therefore to determine whether the administration of vitamin C to acutely hospitalized patients with hypovitaminosis C increases their plasma glutathione concentrations, lowers plasma and leukocyte MDA concentrations, or improves their mood. Improvement in some or all of these indicators would suggest that the condition before treatment is a deficiency disease that merits prevention and treatment.

Section snippets

Study design

Over a 6-wk period all patients on two medical and three surgical teaching units of a university teaching hospital were eligible for enrollment if they were mentally competent, fluent in French or English, and not currently prescribed a vitamin supplement. The focus of interest of this study was patients with hypovitaminosis C, and because our recent survey [7] indicated that patients with reduced food intake or weight loss were more likely to have hypovitaminosis C, we approached patients for

Results

Of the 80 patients considered for inclusion, 54 were mentally competent, fluent in French or English, understood the nature of the research, signed the informed consent document, and began the study. These patients constituted the initial study group. Fourteen participants were discharged from hospital before completing the 7-d treatment, three withdrew consent during the study, one had all oral intake stopped, and one was transferred to the intensive care unit. One person's data were excluded

Discussion

This is the first study to investigate the metabolic origin of hypovitaminosis C in acutely hospitalized patients by measuring the short-term effects of adequate vitamin C administration on plasma and intracellular vitamin C concentrations, metabolic indicators of oxidative stress, and mood.

In a previous population-based survey in the same hospital, we found that 60% of patients on the active medical units had subnormal plasma vitamin C concentrations (<28.4 μmol/L) and 19% had deficient

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    This work was supported by the Lotte and John Hecht Memorial Foundation, the Canadian Institutes of Health Research, and a medical student research bursary to R. Evans-Olders from the Faculty of Medicine, McGill University.

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