This review synthesizes evidence from the preceding 18 months on micronutrient use in adult critically ill patients and outlines the necessary transition from empiric supplementation toward biomarker-guided precision nutrition. Despite strong biological plausibility for benefit, recent clinical data increasingly challenge routine high-dose single-micronutrient strategies and highlight the need to target therapy to true deficiency states or biologically defined high-risk phenotypes.
Multiple recent studies and clinical trials have failed to show patient-centered benefits from pharmacological doses of vitamin C in critical illness. High-dose intravenous vitamin C did not improve outcomes and has been associated with potential harm across several conditions, specifically sepsis, COVID-19, severe burns, and post-cardiac arrest syndrome. These findings argue against routine administration of high-dose vitamin C in unselected critically ill populations and emphasize caution given possible adverse effects observed in randomized and observational data.
In contrast to negative vitamin C data, a 2025 meta-analysis reported that vitamin D supplementation was associated with reduced short-term mortality and shorter ICU length of stay among patients receiving mechanical ventilation. This signal suggests that, in certain clinical contexts or patient subgroups, vitamin D may confer measurable benefit. The review highlights the importance of patient selection and indicates that benefits may be limited to particular phenotypes or to those with baseline deficiency.
Evidence summarized in the review indicates that thiamine administration may shorten the duration of shock in critically ill patients but has not demonstrated an effect on mortality. These results support thiamine replacement when deficiency is suspected or documented, particularly given its low cost and biological rationale, while acknowledging that mortality benefits remain unproven.
Observational studies indicate that carnitine deficiency is frequently encountered during critical illness, and both deficiency and excess of carnitine have been associated with adverse outcomes. For selenium, randomized and observational data continue to show no consistent clinical benefit in sepsis phenotypes and in high-risk surgical populations. Overall, this body of evidence does not support routine supplementation of these trace elements in unselected critically ill patients and underscores the need for better phenotyping and biomarker confirmation prior to replacement.
New mechanistic evidence links trace element disturbances to the pathogenesis of critical illness–acquired weakness. The review cites roles for copper-dependent processes (including cuproptosis), altered zinc homeostasis, and disruptions in iron metabolism in muscle dysfunction. These mechanistic insights identify potential therapeutic targets but require translation through biomarker-driven clinical studies to determine if correcting specific trace element derangements can prevent or mitigate muscle weakness acquired during critical illness.
Significant advances in biomarker development are improving the ability to detect clinically meaningful micronutrient deficiencies. Biomarkers highlighted include hepcidin, soluble transferrin receptor, ferritin, and selenoprotein P. These markers can help distinguish true deficiency from acute-phase–related changes and may enable targeted replacement strategies rather than empiric high-dose therapy. The review promotes the use of validated biomarkers to guide supplementation decisions.
Based on current evidence, the review recommends against routine high-dose single-micronutrient therapy in unselected critically ill patients and specifically warns about potential harm with pharmacological doses of vitamin C. Clinicians are advised to ensure that daily baseline micronutrient requirements are met and to reserve additional supplementation for patients with biomarker-confirmed deficiency or those who fit biologically defined high-risk phenotypes. The emphasis is on replacing deficiencies identified by reliable biomarkers rather than broad pharmacologic dosing.
The authors conclude that future research should prioritize precision nutritional approaches. Key priorities include validating biomarkers for deficiency states, developing individualized metabolic profiling, and conducting studies that target supplementation to patients most likely to benefit. Such biomarker-guided strategies aim to move clinical practice away from empiric high-dose regimens toward personalized interventions informed by biologic phenotype and objective deficiency measures.