Tailored strategies for vitamin C, D, iron, and carnitine in critical illness

Abstract

Abstract

Micronutrients are essential cofactors for metabolic, immune, and cellular processes. Low plasma concentrations are frequent in ICU patients but poorly reflect tissue stores. Inflammation drives redistribution and utilisation, while disease, reduced intake, impaired absorption, dilution, and increased losses may contribute to true deficiency. Plasma values, therefore, cannot distinguish redistribution from deficiency, making individualised requirement estimation difficult. This narrative review focuses on four micronutrients of recent high interest, aiming to address some missing links in critical illness. Current guidelines recommend routine provision of basal micronutrient requirements for all ICU patients, with additional monitoring and increased doses reserved for high-risk groups with losses. Plasma measurements, often the only available tool, should be interpreted alongside inflammatory markers, clinical context, and risk factors. Large RCTs of vitamin C have mainly yielded neutral or negative results, which may reflect unguided supplementation across heterogeneous populations without accounting for timing, duration, dosing strategies, and biochemical formulation variability; alternatively, vitamin C may simply be ineffective as an early intervention in critical illness. Available evidence from ICU vitamin D trials indicates signals of outcome benefit, but the evidence is heterogeneous and trial sizes are limited, preventing firm ICU-specific recommendations. Ongoing large trials are expected to clarify effects of high-dose strategies. Iron status spans a narrow therapeutic window: iron deficiency and anaemia are highly prevalent during and after ICU, yet iron overload and ferroptosis-related toxicity also contribute to organ dysfunction. Targeted, hepcidin-guided intravenous (I.V.) iron therapy appears promising to safely correct deficiency. Both carnitine deficiency and high blood levels are associated with worse outcomes in ICU patients. Risk factors for alterations in carnitine concentrations include CRRT, renal and hepatic dysfunction, valproate use, inflammation, and wound losses. Supplementation should be evaluated in a stepwise approach to detect potentially excessive levels in a dose-finding RCT. New biomarkers and analytical approaches are needed to differentiate redistribution from deficiency, capturing dynamic changes over time. Future approaches should move beyond plasma measurements toward cellular and functional biomarkers that better reflect stores and biological activity. Given current limitations, testing should be selective to where results are expected to alter management, include CRP, and timing guided by underlying risk. Research should prioritise precision strategies with better biomarkers and longitudinal sampling to account for dynamic risk, needs, losses, and responses.