Abstract

In order to study the effects of vitamin C supplementation on gene expression and compare its action between physiological and inflammatory conditions, a pilot study was set up utilizing microarray and qPCR technologies. Five healthy volunteers were supplemented with 1 g vitamin C (Redoxon®) per day for five consecutive days. Peripheral blood mononuclear cells (PBMNC) were isolated before and just after the last supplementation, and RNA was isolated for the Affymetrix gene 1.0 ST chip analysis. PBMNC were also, ex vivo, treated with LPS, and gene expression was quantified by means of a “Human NFkB Signaling” qPCR array. Only a very moderate effect on the baseline gene expression modulation was associated with vitamin C supplementation. However, in spite of the limited number of subjects analyzed, vitamin C supplementation resulted in a markedly different modulation of gene expression upon the inflammatory stimulus, specifically at the level of the MyD88-dependent pathway and of the anti-inflammatory cytokine IL-10 synthesis. This study suggests that vitamin C supplementation in healthy subjects, not selected according to a specific genetic profile, consuming an adequate amount of vitamin C, and having a satisfactory vitamin C plasma concentration at the baseline, does not result in a significant modification of gene expression profile. Under this satisfactory micronutrient status, supplementation of vitamin C is “buffered” within a homeostatic physiological equilibrium. Differently, following a second “hit” constituted of an inflammatory stimulus such as LPS, able to trigger a critical burst to the normal physiological state, the higher availability of ascorbic acid emerges, and results in a significant modulation of cell response.

Highlights

  • Vitamin C or ascorbic acid (AA) is essential for life in humans as the capacity to synthesize it has been lost in course of our evolution

  • This study suggests that vitamin C supplementation in healthy subjects, not selected according to a specific genetic profile, consuming an adequate amount of vitamin C, and having a satisfactory vitamin C plasma concentration at the baseline, does not result in a significant modification of gene expression profile

  • It can be reversibly oxidized to DHA. Both forms have been measured in plasma, indicating that the majority of vitamin C was present in the reduced ascorbate form, while DHA was detectable in very small to negligible amounts

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Summary

Introduction

Vitamin C or ascorbic acid (AA) is essential for life in humans as the capacity to synthesize it has been lost in course of our evolution. Several studies have demonstrated that AA status is related to a decreased risk of a wide range of pathologies, such as stroke (Gale et al 1995) or cardiovascular disease (Salonen et al 2003). In this context, AA supplementation has been reported to ameliorate symptoms and to enhance the expression of specific immune response markers in clinical conditions (Wintergerst et al 2006). It is interesting to mention that most of the available studies addressing the effects of AA on human health considered the supplementation of this vitamin together with other nutrients (usually zinc or within a multivitamin–multimineral formula), while a real understanding of its mechanism of action would possibly require the supplementation as single components (Lykkesfeldt and Poulsen 2010)

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