Vitamin B1NEW2026

Mitochondrial dysfunction in sepsis: nutritional strategies for restoring bioenergetic homeostasis.

Zheng Lirong, Yin Xuemin, Zhang Ruifen, Su He et al. — Frontiers in cellular and infection microbiology

Summary

Sepsis, a severe infection, can cause organs to fail because cells struggle to produce enough energy. This scientific review suggests that problems with the cell's 'powerhouses' (mitochondria) are central to this energy failure. It explores how specific nutrients, including vitamin B1 (thiamine), carnitine, and coenzyme Q10, might help restore energy production and improve outcomes in sepsis by targeting these mitochondrial issues.

AI-generated summary — read the original

Key points

Sepsis involves a critical failure in cellular energy production, driven by mitochondrial dysfunction.
Specific mitochondrial problems, like impaired energy pathways, are central to organ damage in sepsis.
Vitamin B1 (thiamine) supplementation has shown promise in restoring these energy pathways.
Other nutrients like carnitine and CoQ10 also show potential, but more human studies are needed.

What the study looked at

### What question did the study ask? This review investigated how mitochondrial dysfunction contributes to the severe organ damage seen in sepsis and explored whether specific nutritional supplements, including vitamin B1 (thiamine), could help restore cellular energy balance. ### How was it studied? Researchers conducted a comprehensive review of scientific literature published between 2005 and 2026, systematically identifying studies that examined mitochondrial problems in sepsis and the effects of thiamine, carnitine, and coenzyme Q10 interventions. They analyzed 105 studies from a pool of over 1,300 records. ### What did it find? The review found strong evidence that specific mitochondrial issues, such as impaired energy production pathways often linked to thiamine deficiency, are central to sepsis-related organ failure. Thiamine supplementation was shown to improve these energy pathways. While carnitine and CoQ10 also showed promise in preclinical and small human studies, more large-scale human trials are needed to confirm their benefits in treating sepsis.

Dietary takeaway

While this research focuses on critical illness like sepsis, it highlights vitamin B1's crucial role in cellular energy production. Ensuring adequate vitamin B1 intake through a balanced diet—found in whole grains, pork, and legumes—is important for overall metabolic health. However, it's important to remember that findings from a single review, especially one focused on severe illness, are not definitive for general dietary advice, and more research is always ongoing.

Abstract

BACKGROUND: Sepsis is increasingly recognized as a syndrome of maladaptive bioenergetic failure in which mitochondrial dysfunction-rather than being a secondary epiphenomenon-acts as a central driver of immune paralysis, endothelial incoherence, and multiple organ injury. Three interconnected molecular lesions are particularly consequential: impairment of the pyruvate dehydrogenase complex (PDC), excessive mitochondrial reactive oxygen species (mtROS) generation, and defective mitophagy. These mechanisms disrupt substrate oxidation, amplify oxidative injury, and prevent effective organelle turnover, creating a self-reinforcing bioenergetic collapse that persists despite hemodynamic stabilization. Nutritional molecules that target these specific mitochondrial nodes may offer a rational adjunctive strategy, yet their mechanistic basis and translational evidence have not been systematically integrated. METHODS: This mechanism‑driven review followed a PRISMA‑structured protocol to identify studies elucidating PDC impairment, mtROS excess, and mitophagy dysfunction in sepsis, as well as the therapeutic rationale for thiamine, carnitine, and coenzyme Q10 (CoQ10). We searched PubMed, Scopus, Web of Science, Cochrane Library, and ClinicalTrials.gov for English‑language literature published between January 1, 2005 and February 1, 2026. Eligible studies addressed mitochondrial dysfunction in sepsis, reported on at least one direct mitochondrial parameter (PDC activity, mtROS, mitophagy markers, membrane potential, or ATP), and evaluated the specified nutritional interventions. Of 1,324 initially identified records, 105 studies met inclusion criteria and were qualitatively synthesized. RESULTS: Preclinical evidence establishes that PDC impairment-driven by thiamine pyrophosphate deficiency-reduces pyruvate oxidation and increases lactate diversion, while excessive mtROS activates the NLRP3 inflammasome and amplifies inflammation, and defective mitophagy allows damaged organelles to accumulate, sustaining bioenergetic failure. These lesions propagate across immune, endothelial, parenchymal, and cerebral compartments, manifesting as immune paralysis, microcirculatory dysfunction, cardiac and renal impairment, and sepsis‑associated encephalopathy. Thiamine supplementation restores PDC activity and improves lactate clearance; L‑carnitine facilitates mitochondrial fatty acid trafficking, with post‑hoc analyses suggesting mortality benefit in patients with baseline acetylcarnitine >35 µM; and CoQ10 stabilizes electron transport, with trials reporting reduced vasopressor duration and improved SOFA scores. However, human data remain limited to small trials and subgroup analyses, and no large‑scale randomized controlled trial has definitively established mortality benefit for any of these agents. CONCLUSION: Mitochondrial dysfunction-specifically PDC impairment, mtROS excess, and mitophagy failure-is a core mechanistic axis of sepsis that drives bioenergetic collapse across multiple organ systems. Thiamine, carnitine, and CoQ10 target complementary nodes within this integrated damage network and are mechanistically grounded interventions, but the field is constrained by biological heterogeneity, lack of routine biomarkers, and inconsistent clinical translation. Future progress will require biomarker‑stratified trials that match intervention to dominant mitochondrial lesion, incorporate direct mitochondrial function endpoints, and test these nutrients within defined septic phenotypes, rather than as undifferentiated supplements.Overall, I believe that the inclusion of one or two well-designed original figures would significantly strengthen the manuscript and make it more engaging and accessible to readers.

View on PubMed →DOI: 10.3389/fcimb.2026.1878518