Vitamin C and Benzoic Acid Intake in Patients with Kidney Disease - Is There Risk of Benzene Exposure

Sep 30, 2026

Uploaded by dhado

Vitamin C is a water-soluble molecule cleared by the kidneys, so declining renal function should raise its plasma concentration. Evidence in chronic kidney disease (CKD) and kidney transplant recipients instead shows a positive association between kidney function and vitamin C levels, independent of intake. This review evaluates explanations for the paradox and tests a linked hypothesis involving benzoic acid exposure from food preservatives, which may react with vitamin C to form benzene, a toxic carcinogen, potentially affecting clinical outcomes in patients with impaired kidney function.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

1. Introduction and Methods

2. Vitamin C

Review Vitamin C and Benzoic Acid Intake in Patients with Kidney Disease: Is There Risk of Benzene Exposure? Manuela Yepes-Calderón 1, *, Caecilia S. E. Doorenbos 1, Eva Corpeleijn 2, Casper F. M. Franssen 1, Michel J. Vos 3, Daan J. Touw 4, Christophe Mariat 5, Annelies E. de Weerd 6 and Stephan J. L. Bakker 1 Academic Editor: Katsuhisa Inoue Received: 27 November 2025 Revised: 21 December 2025 Accepted: 26 December 2025 Published: 31 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands; [s.j.l.bakker@umcg.nl](s.j.l.bakker@umcg.nl) (S.J.L.B.) 2 Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands 3 Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands 4 Department of Pharmacology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands 5 Division of Nephrology, Department of Internal Medicine, Hôpital Nord CHU de Sainte-Etienne, 42270 Saint-Etienne, France 6 Division of Nephrology, Department of Internal Medicine, Erasmus Medical Centre, 3015 GD Rotterdam, The Netherlands * [Correspondence: m.yepes.calderon@umcg.nl](Correspondence: m.yepes.calderon@umcg.nl) Abstract Vitamin C is a small water-soluble molecule primarily cleared by the kidneys. Therefore, its plasma concentration would be expected to increase as kidney function declines. However, studies in patients with chronic kidney disease (CKD) and kidney transplant recipients have shown the opposite: a positive correlation between kidney function and plasma vitamin C levels. In this review, we discuss potential explanations for this counterintuitive finding and suggest alternative mechanisms influencing vitamin C bioavailability in this population. We also explore the hypothesis that this phenomenon may be linked to benzoic acid (benzoate) exposure. Benzoic acid is a widely used food preservative that, like vitamin C, is water-soluble and renally excreted. In individuals with impaired kidney function, reduced clearance may lead to elevated circulating benzoic acid levels, which could increase the likelihood of an in vivo chemical reaction between benzoic acid and vitamin C, resulting in the formation of benzene, which is a known toxic and carcinogenic compound. We summarize experimental evidence demonstrating the vitamin C–benzoic acid reaction in vitro, along with preliminary animal studies suggesting it may also occur in vivo. We also discuss the potential clinical consequences of benzene exposure in the context of patients with kidney function impairment. Given the widespread use of benzoic acid asa food preservative and the ongoing discussion around vitamin C supplementation inpatients with kidney disease, this review invites further investigation to evaluate whether this reaction represents a health hazard for this population. Keywords: vitamin C; benzoic acid; benzoate; benzene; chronic kidney disease 1. Introduction and Methods Vitamin C is water-soluble and renally cleared, so levels would be expected to rise as kidney function declines. Yet, in patients with chronic kidney disease (CKD) and kidney transplant recipients (KTR), studies report the opposite: a positive correlation between kidney function and plasma vitamin C independent of intake. This review interrogates that paradox by evaluating alternative mechanisms influencing vitamin C metabolism in these populations and by exploring a linked hypothesis that benzoate exposure, a common food preservative, may interact with vitamin C in vivo to generate benzene, with

FAQs

Why might plasma vitamin C levels behave unexpectedly in chronic kidney disease and transplant recipients?

Although reduced kidney clearance would predict higher vitamin C levels, studies in CKD and kidney transplant recipients show the opposite pattern, with vitamin C levels positively associated with kidney function independent of intake. The review explores alternative mechanisms that could explain this paradox.

What role does benzoic acid (benzoate) play in the hypothesis discussed?

Benzoic acid is a widely used, water-soluble food preservative that is renally excreted. In impaired kidney function, reduced clearance may elevate circulating benzoic acid and increase the likelihood of an in vivo reaction with vitamin C.

How could the vitamin C–benzoic acid interaction lead to a health risk?

The review discusses evidence that vitamin C and benzoic acid can react to form benzene in vitro, with preliminary animal studies suggesting potential in vivo formation. Because benzene is described as toxic and carcinogenic, the review considers possible clinical consequences for patients with kidney function impairment.

Sep 30, 2026

Uploaded by dhado