Thiamine

Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study

Study: This two-center RCT (NCT01070810, Donnino et al., 2016) enrolled 88 patients with septic shock (age ≥18, lactate >3 mmol/L, hypotension post-fluid bolus, vasopressor dependence) at Beth Israel Deaconess and Baystate Medical Centers, USA, from 2010–2014. Participants received IV thiamine (200 mg twice daily for 7 days) or placebo. The primary outcome was absolute lactate level at 24 hours. Secondary outcomes included mortality, ICU stay, and lactate in thiamine-deficient subgroups (baseline thiamine diphosphate <70 nmol/L).

Findings: No significant difference in 24-hour lactate levels was found between thiamine and placebo groups (p>0.05). However, in the thiamine group, lactate decreased significantly from baseline to 24 hours (p<0.05). In the deficient subgroup (15% of patients), thiamine reduced 24-hour lactate (p=0.02) and showed a trend toward lower mortality (p=0.06). No adverse events were reported. The study suggests thiamine may benefit septic shock patients with subclinical deficiency, resembling beriberi, but larger trials are needed.

Link: Critical Care Medicine

Effect of Intravenous Thiamine Administration on Critically Ill Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Study: This meta-analysis (Tao et al., 2024) included 35 RCTs (n=3,494) through April 2023, evaluating IV thiamine (100–600 mg/day, alone or with vitamin C/hydrocortisone) in critically ill patients (sepsis, septic shock, heart failure, post-surgical). Outcomes included mortality (primary), shock duration, lactate levels, Sequential Organ Failure Assessment (SOFA) score, ICU stay, and mechanical ventilation duration. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach assessed evidence certainty

Findings: Thiamine had no significant effect on mortality (RR 0.89, 95% CI 0.75–1.06, low CoE) but reduced shock duration (MD -11.43 hours, 95% CI -20.16 to -2.69, low CoE), lactate levels (MD -0.34 mmol/L, 95% CI -0.63 to -0.05, low CoE), and SOFA score (MD -1.29, 95% CI -1.91 to -0.66, low CoE). ICU stay was slightly increased (MD 0.40 days, 95% CI 0.01–0.79, high CoE). No serious adverse events were reported. The study suggests thiamine may improve organ function and shock in critical illness but not mortality, with inconsistent results necessitating further research.

Link: Clinical Nutrition

A Multicenter Randomized Clinical Trial of Pharmacological Vitamin B1 Administration to Critically Ill Patients Who Develop Hypophosphatemia

Study: This multicenter RCT (Collie et al., 2021, ACTRN12619000121167) enrolled 90 critically ill, enterally fed patients with hypophosphatemia (serum phosphate ≤0.65 mmol/L) across five Australian ICUs from 2019–2020. Participants received IV thiamine (200 mg every 12 hours, up to 14 doses, median 2,200 mg total) or usual care. The primary outcome was blood lactate over time. Secondary outcomes included biochemical markers and clinical outcomes (e.g., ICU stay, mortality)

Findings: No significant differences were found in blood lactate (thiamine: 1.2 [1.0–1.6] mmol/L vs. control: 1.0 [0.8–1.3] mmol/L, p>0.05) or clinical outcomes (e.g., mortality, ICU stay). Baseline characteristics were balanced, and no adverse events were reported. The study suggests IV thiamine does not improve lactate or outcomes in hypophosphatemic ICU patients, possibly due to low prevalence of thiamine deficiency or insufficient dose/duration.

Link: Clinical Nutrition

Pharmacological Thiamine Levels as a Therapeutic Approach in Alzheimer’s Disease

Study: This phase 2a, single-site, randomized, double-blind, placebo-controlled pilot trial (Gibson et al., 2020) enrolled 70 patients with early Alzheimer’s disease (AD, amnestic mild cognitive impairment or mild AD, MMSE 21–26, amyloid PET-positive). Participants received oral benfotiamine (600 mg/day) or placebo for 12 months. Primary outcome was Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-11). Secondary outcomes included Clinical Dementia Rating (CDR) and brain glucose uptake (FDG-PET)

Findings: Benfotiamine increased blood thiamine levels 161-fold and was safe, with no serious adverse events. In the intent-to-treat population, ADAS-Cog decline was reduced by 43% (p=0.125) and CDR decline by 79.2% (p=0.0129) compared to placebo. Biomarker analysis showed reversal of AD-related changes in metabolites/lipids (e.g., thiamine, tyrosine, phosphatidylcholines). The study suggests benfotiamine may slow cognitive decline in early AD, supporting larger trials.

Link: PMC

Sustained High-Dose Thiamine Supplementation in High-Risk Cardiac Patients Undergoing Cardiopulmonary Bypass: A Pilot Feasibility Study (The APPLY Trial)

Study: This RCT (Lomivorotov et al., 2020) enrolled 64 high-risk cardiac surgery patients undergoing cardiopulmonary bypass in Russia. Participants received IV thiamine (4 g pre-surgery, 200 mg/day post-surgery for 3 days) or placebo. Outcomes included lactate levels, oxygen delivery (DO2), and clinical outcomes (e.g., mortality, ICU stay)

Findings: Thiamine significantly reduced lactate levels at 6 hours post-surgery (p<0.05) but not at 24 hours. No differences were found in DO2, mortality, or ICU stay. No adverse events were reported. The study suggests high-dose thiamine is feasible and may reduce early post-surgical lactate in high-risk cardiac patients, but clinical benefits require further study.

Link: Journal of Cardiothoracic and Vascular Anesthesia