High-dose oral thiamine versus placebo for chronic fatigue in patients with primary biliary cholangitis: A crossover randomized clinical trial.

BACKGROUND & AIMS: Fatigue has high negative impact on many patients with primary biliary cholangitis (PBC) and treatment options are limited. Recently we showed favorable effects of four weeks of high-dose thiamine treatment on fatigue in patients with inflammatory bowel disease. We aimed to investigate the effect and safety of high-dose (600-1800 mg daily) oral thiamine treatment on chronic fatigue in patients with PBC. METHODS: Randomized, double-blinded, placebo-controlled crossover trial including patients with severe PBC-related fatigue. Participants were allocated 1:1 to either group 1) 4 weeks of high-dose thiamine, 4 weeks of washout, and 4 weeks of placebo; or group 2) 4 weeks of placebo, washout, and high-dose thiamine, respectively. Fatigue severity was quantified using the fatigue subscale of the PBC-40 questionnaire. The primary outcome was a fatigue reduction of ≥ 5 points after 4 weeks of high-dose thiamine treatment. RESULTS: We enrolled 36 patients; 34 completed the study. The overall mean reduction in fatigue was 5.0 points (95% CI: 2.5 to 7.5; p < 0.001) for the combined group 1 and group 2. Crossover analysis showed a mean increase in fatigue of 0.3 points (95% CI: -4.2 to 3.8) after high-dose thiamine treatment compared to a 1.4 points (95% CI: 6.2 to -3.4) mean reduction after placebo (p = 0.55). Only mild and transient adverse events were recorded. CONCLUSION: Four weeks of high-dose oral thiamine treatment in patients with PBC was well tolerated and safe. However, high-dose thiamine was not superior to placebo in reducing PBC-related fatigue. TRIAL REGISTRATION: The trial was registered in the ClinicalTrials.gov (NCT04893993) and EudraCT (2020-004935-26).

Nystagmus in a child with nephrotic syndrome.

We report a child with steroid-dependent nephrotic syndrome presenting with excessive irritability, double vision and inability to walk for 5 days. On examination, the child was irritable with Glasgow coma sccale (GCS of 12/15, had bilateral convergent squint (R>L), vertical nystagmus, ataxia without any focal neurological deficits and normal fundus. MRI brain with venogram showed bilateral symmetric FLAIR hyperintensity in the medial thalamus and periaqueductal grey matter showing diffuse restriction with normal venogram. A possibility of Wernicke encephalopathy (WE) was considered and the child was started on thiamine supplementation, following which he had significant improvement in his symptoms. His irritability reduced with significant improvement in the range of eye movements and vertical nystagmus. At 3-month follow-up, the child is asymptomatic with normal gait. Although WE is uncommon in children with nephrotic syndrome, the possibility has to be kept in mind when a child presents with atypical neurological symptoms.

Atypical Wernicke's encephalopathy without mental status changes following bariatric surgery in an adolescent patient.

Morbid obesity is a systemic disease which can result in chronic complications, including hypertension, diabetes mellitus, depression, osteoarthritis and low self-esteem in the adolescent population.Bariatric surgery can be indicated to treat more severe forms of obesity, but these procedures are not without long-term risks. Therefore, adequate preoperative and postoperative care, which includes preoperative psychosocial evaluation for compliance, ongoing nutrition counselling and vitamin and micronutrient supplementation, is required for all patients, especially adolescent patients, who generally may not comply with medical therapies and/or be able to developmentally fully appreciate or comprehend the health consequences of their behaviours, prior to as well as after bariatric surgery to prevent complications.Thiamine pyrophosphate, an active form of thiamine (also known as vitamin B1, a water-soluble vitamin), which functions as a coenzyme in glucose and energy metabolism, is one such vitamin that requires supplementation postoperatively. It is mandatory for glucose to be administered concomitantly with thiamine, as glucose alone can precipitate Wernicke's encephalopathy (WE) in thiamine-deficient individuals. WE is a medical emergency, with a mortality rate of up to 20%. WE is best understood as a classic triad of mental confusion, gait ataxia and eye movement abnormalities, and atypical WE or Wernicke's syndrome (WS) is seen when the classic triad is not present. Cases that meet some, but do not necessarily meet all three criteria, are referred to as atypical WE or WS which can lead to delayed diagnosis. Atypical WE has an incidence of 19% which can lead to misdiagnosis of a preventable medical emergency with fatal complications.The following case reviews the consequences of post-bariatric thiamine supplementation therapy non-adherence and resulting in a deficiency in an adolescent patient.

Resuscitation With Vitamin C, Hydrocortisone, and Thiamin in Children With Septic Shock: A Multicenter Randomized Pilot Study.

OBJECTIVES: Adjunctive therapy with vitamin C, hydrocortisone, and thiamin has been evaluated in adults, but randomized controlled trial (RCT) data in children are lacking. We aimed to test the feasibility of vitamin C, hydrocortisone, and thiamin in PICU patients with septic shock; and to explore whether the intervention is associated with increased survival free of organ dysfunction. DESIGN: Open-label parallel, pilot RCT multicenter study. The primary endpoint was feasibility. Clinical endpoints included survival free of organ dysfunction censored at 28 days and nine secondary outcomes, shock reversal, and two proxy measures of intervention efficacy. SETTING: Six PICUs in Australia and New Zealand. PATIENTS: Children of age between 28 days and 18 years requiring vasoactive drugs for septic shock between August 2019 and March 2021. INTERVENTIONS: Patients were assigned 1:1 to receive 1 mg/kg hydrocortisone every 6 hours (q6h), 30 mg/kg ascorbic acid q6h, and 4 mg/kg thiamin every 12 hours (n = 27), or standard septic shock management (n = 33). MEASUREMENTS AND MAIN RESULTS: Sixty of 77 (78%) eligible patients consented with 91% of approached parents providing consent. The median time from randomization to intervention was 44 (interquartile range [IQR] 29-120) min. Seventy of seventy-seven (28%) patients had received IV steroids before randomization. Median survival alive and free of organ dysfunction was 20.0 (0.0-26.0) days in the intervention and 21.0 (0.0-25.0) days in the standard care group. Median PICU length of stay was 5.3 (2.5-11.3) days in the intervention group versus 6.9 (3.0-11.5) days in the control group. Shock reversal occurred at a median of 35.2 (14.6-101.2) hours in the intervention group versus 47.3 (22.4-106.8) hours in the standard care group (median difference -12 hr; 95% CI, -56.8 to 32.7 hr). CONCLUSIONS: In children requiring vasopressors for septic shock, a protocol comparing adjunctive treatment with high-dose vitamin C, hydrocortisone, and thiamin versus standard care was feasible. These findings assist in making modifications to the trial protocol to enable a better-designed larger RCT.

Descriptive spectrum of thiamine deficiency in pregnancy: A potentially preventable condition.

OBJECTIVE: Pregnancy, a nutritionally demanding situation in terms of macro- and micronutrient supply owing to heightened maternal, placental, and fetal needs, significantly affects thiamine reserves. Thiamine deficiency during pregnancy and the postpartum period, presenting with varied manifestations and outcomes, is a relatively common condition in our population. The study aimed to understand the various manifestations and outcomes of acute thiamine deficiency in pregnant and postpartum women, emphasizing the significance of early recognition and thiamine therapy to prevent serious complications during pregnancy and after childbirth. METHODS: This prospective study conducted in a tertiary care center in North India enrolled consecutive pregnant and postpartum women presenting with clinical features consistent with thiamine deficiency disorders, such as thiamine deficiency-related neuropathy, high-output heart failure, heart failure with reduced ejection fraction, Wernicke's encephalopathy, gastric beriberi, and thiamine-responsive acute pulmonary hypertension. In addition to capturing medical history including drug intake, dietary consumption, and comorbidities, women underwent brief relevant clinical examinations and laboratory assessments, including whole-blood thiamine levels. Response to intravenous thiamine supplementation was also monitored. RESULTS: Data of 31 women (12 pregnant, 19 postpartum) with a diagnosis of acute thiamine deficiency and a mean age of 28.88 ± 2.69 years were analyzed. The mean thiamine level was 1.28 ± 0.44 µg/dL with mean blood lactate of 3.46 ± 3.33. The most common presentation was gastric beriberi (n = 10), followed by paraparesis (n = 6), high-output heart failure (n = 6), acute pulmonary hypertension, heart failure with reduced ejection fraction (n = 3 each), and an acute confusional state (n = 2). All patients responded to thiamine challenge. CONCLUSION: In the context of borderline thiamine status, particularly in our population with endemic thiamine deficiency and heightened demand for thiamine during pregnancy and the peripartum period, the deficiency can have varied and serious manifestations of dry and wet beriberi. Early recognition of the clinical features and thiamine therapy can be life-saving. There is a need for validated clinical criteria owing to the non-availability of thiamine testing in resource-limited settings.

An Italian case series' description of thiamine responsive megaloblastic anemia syndrome: importance of early diagnosis and treatment.

BACKGROUND: Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune diabetes. Macrocytic anemia and diabetes may be responsive to high-dosage thiamine treatment, in contrast to sensorineural deafness. Little is known about the efficacy of thiamine treatment on ocular manifestations. CASES PRESENTATION: Our objective is to report data from four Italian TRMA patients: in Cases 1, 2 and 3, the diagnosis of TRMA was made at 9, 14 and 27 months. In 3 out of 4 subjects, thiamine therapy allowed both normalization of hyperglycemia, with consequent insulin suspension, and macrocytic anemia. In all Cases, thiamine therapy did not resolve the clinical manifestation of deafness. In Cases 2 and 3, follow-up showed no blindness, unlike Case 4, in which treatment was started for megaloblastic anemia at age 7 but was increased to high doses only at age 25, when the genetic diagnosis of TRMA was performed. CONCLUSIONS: Early institution of high-dose thiamine supplementation seems to prevent the development of retinal changes and optic atrophy in TRMA patients. The spectrum of clinical manifestations is broad, and it is important to describe known Cases to gain a better understanding of this rare disease.

Effect of adjuvant thiamine and ascorbic acid administration on the neurologic outcomes of out-of-hospital cardiac arrest patients: A before-and-after study.

AIM: This study aimed to evaluate the impact of early thiamine and ascorbic acid administration on the neurologic outcome in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM). METHODS: This before-and-after cohort study used data extracted from two hospitals of the Korean Hypothermia Network prospective registry. The treatment group incorporated patients enrolled from December 2019 to May 2021, that received intravenous thiamine (200 mg) and ascorbic acid (3 g) at 12-hour intervals for a total of six doses. The control group incorporated those enrolled from May 2018 to November 2019. The one-month good neurologic outcome, defined as a Cerebral Performance Category score ≤ 2, between the groups was evaluated using inverse probability of treatment weighting (IPTW). RESULTS: Among the 234 OHCA survivors with TTM, 102 were included in the treatment group and 132 were included in the control group. The one-month (31.4 % vs. 29.5 %, respectively; P = 0.76) good neurologic outcome rates did not differ between the treatment and control groups. After adjusting using the IPTW, vitamin supplementation was not associated with good neurologic outcome (odds ratio [OR], 1.134; 95 % confidence interval [CI], 0.644-1.999; P = 0.66). In subgroup analysis, vitamin administration was significantly associated with a good neurologic outcome in older (≥65 years) patients (adjusted OR, 5.53; 95 % CI, 1.21-25.23; P = 0.03). CONCLUSION: Adjuvant thiamine and ascorbic acid administration in OHCA survivors with TTM did not improve their neurologic outcome after one month. Further clinical trials are warranted.

Ameliorative effects of thiamin on learning behavior and memory dysfunction in a rat model of hypothyroidism: implication of oxidative stress and acetylcholinesterase.

Hypothyroidism causes learning and memory impairment. Considering the neuroprotective properties of thiamine (Vitamin B1), this study was conducted to investigate the effects of thiamine on acetylcholinesterase (AChE) activity, oxidative damage, and memory deficits in hypothyroid rats.In this study, 50 rats (21 days old) were randomly divided into 5 groups and treated with propylthiouracil (0.05% in drinking water) and thiamine (50, 100, and 200 mg/kg, oral) for 7 weeks. Following that, Morris water maze (MWM) and passive avoidance (PA) tests were performed. Finally, oxidative stress indicators and AChE activity were measured in brain tissue.Treatment of hypothyroid rats with thiamine, especially at 100 and 200 mg/kg, alleviated the ability to remember the location of the platform as reflected by less time spent and distance to reach the platform, during the MWM test (P < 0.05 to P < 0.001). In the PA test, the latency to enter the dark chamber and light stay time were increased in rats who received thiamine compared to the hypothyroid group (P < 0.05 to P < 0.001). In addition, thiamine increased the levels of total thiol groups and superoxide dismutase while decreasing the levels of malondialdehyde and AChE.Our results suggest that thiamine supplementation could effectively improve memory loss in a rat model of hypothyroidism. The positive effects of thiamin on the learning and memory of hypothyroid rats may be due to amelioration of redox hemostasis and cholinergic disturbance.

B-vitamins, related vitamers, and metabolites in patients with quiescent inflammatory bowel disease and chronic fatigue treated with high dose oral thiamine.

BACKGROUND: High doses of oral thiamine improve clinical fatigue scores in patients with quiescent inflammatory bowel disease (IBD) and chronic fatigue. In this study we analysed plasma samples obtained in a randomised clinical trial and aimed compare levels of vitamins B1, B2, B3 and B6, and their related vitamers and metabolites in patients with IBD, with or without chronic fatigue and with or without effect of high dose oral thiamine for chronic fatigue. METHODS: Blood samples from patients with fatigue were drawn prior and after thiamine exposure and only once for patients without fatigue. A wide panel of analysis were done at Bevital AS Lab. RESULTS: Concentration of flavin mononucleotide (FMN) was lower in patients with chronic fatigue compared to patients without fatigue (p = 0.02). Patients with chronic fatigue who reported a positive effect on fatigue after 4 weeks of high dose thiamine treatment had a statistically significantly lower level of riboflavin after thiamine treatment (p = 0.01). CONCLUSION: FMN and Riboflavin were associated with chronic fatigue in patients with quiescent IBD. Levels of other B vitamins and metabolites were not significantly different between the investigated groups or related to effect of the thiamine intervention. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov study identifier NCT036347359. Registered 15 August 2018, https://clinicaltrials.gov/study/NCT03634735?cond=Inflammatory%20Bowel%20Diseases&intr=Thiamine&rank=1.

Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: A multicenter retrospective study.

BACKGROUND: Despite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability. AIMS: Given the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome. METHODS: This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed. RESULTS: We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality. CONCLUSIONS: Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE.

Diplopia after Sleeve Gastrectomy: The Canary in the Coal Mine.

Wernicke's encephalopathy (WE) is a neurologic emergency requiring timely intravenous thiamine supplementation to prevent permanent neurologic deficits. Historically, the WE diagnosis was limited to individuals with alcohol use disorder. However, it is now widely recognized to occur in patients who are chronically malnourished, post-bariatric surgery, pregnant with hyperemesis gravidarum, and with severe anorexia nervosa. Here we present a young woman who developed WE after undergoing a recent sleeve gastrectomy followed by protracted emesis for several days. This case underscores the importance of performing a thorough neurological review of systems and physical exam in high-risk patients and having a low clinical threshold to initiate appropriate thiamine treatment.

Severe Pulmonary Arterial Hypertension in Healthy Young Infants: Single Center Experience.

OBJECTIVE: We studied the clinical presentation and management of acute pulmonary arterial hypertension (PAH) in healthy young infants, and the effect of thiamine therapy. METHODS: Review of hospital records was conducted for 56 healthy infants (aged below 6 month) who developed sudden onset of pulmonary arterial hypertension as diagnosed on 2D echocardiography, and were admitted at our institution. RESULTS: All patients received supportive care and pulmonary vasodilator therapy, whereas those admitted after Sep-tember, 2019 (n=28) received thiamine in addition, as per the institute's protocol. Overall, complete recovery was seen in 80% (n=45). Infants who died had significantly lower mean pH (7.05 vs 7.27; P=0.001) and serum bicarbonate (9.1 vs 14.9; P=0.007), higher arterial lactate (72.7 vs 61.5; P=0.92), ventricular dysfunction (16 vs 10; P=0.01) and shock (7 vs 9; P=0.008) when compared to those who survived. Baseline characteristics, severity of acidosis and pulmonary hypertension, time taken to recover from PAH, presence of ventricular dysfunction were comparable among those who received thiamine and those who did not receive it. Similarly, recovery (89% vs 71%; P=0.17) and mortality (11% vs 29%) were also comparable between the two groups. CONCLUSIONS: A significant proportion of infants with PAH improve with supportive treatment and pulmonary vasodilator therapy. Thiamine supplementation may not give any additional benefit in these patients.

Thiamine for Renal Protection in Septic Shock (TRPSS): A Randomized, Placebo-controlled, Clinical Trial.

Rationale: Kidney injury is common and associated with worse outcomes in patients with septic shock. Mitochondrial resuscitation with thiamine (vitamin B1) may attenuate septic kidney injury. Objectives: To assess whether thiamine supplementation attenuates kidney injury in septic shock. Methods: The TRPSS (Thiamine for Renal Protection in Septic Shock) trial was a multicenter, randomized, placebo-controlled trial of thiamine versus placebo in septic shock. The primary outcome was change in serum creatinine between enrollment and 72 hours after enrollment. Measurements and Main Results: Eighty-eight patients were enrolled (42 patients received the intervention, and 46 received placebo). There was no significant between-groups difference in creatinine at 72 hours (mean difference, -0.57 mg/dl; 95% confidence interval, -1.18, 0.04; P = 0.07). There was no difference in receipt of kidney replacement therapy (14.3% vs. 21.7%, P = 0.34), acute kidney injury (as defined by stage 3 of the Kidney Disease: Improving Global Outcomes acute kidney injury scale; 54.7% vs. 73.9%, P = 0.07), or mortality (35.7% vs. 54.3%, P = 0.14) between the thiamine and placebo groups. Patients who received thiamine had more ICU-free days (median [interquartile range]: 22.5 [0.0-25.0] vs. 0.0 [0.0-23.0], P < 0.01). In the thiamine-deficient cohort (27.4% of patients), there was no difference in rates of kidney failure (57.1% thiamine vs. 81.5% placebo) or in-hospital mortality (28.6% vs. 68.8%) between groups. Conclusions: In the TRPSS trial, there was no statistically significant difference in the primary outcome of change in creatinine over time. Patients who received thiamine had more ICU-free days, but there was no difference in other secondary outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT03550794).

A Case of Wernicke's Encephalopathy After Sleeve Gastrectomy.

BACKGROUND: Wernicke's encephalopathy, resulting from thiamine deficiency, is a rare but serious neurological complication of bariatric procedures. A clinical and radiologic diagnosis is often difficult, and thiamine blood tests are not broadly available. Only a few cases of Wernicke's encephalopathy after sleeve gastrectomy have been reported in the literature, nonetheless, subjects can be underdiagnosed, and their cases can be underreported. CASE PRESENTATION: We present the case of a 20-year-old female patient who developed Wernicke's encephalopathy after sleeve gastrectomy for grade II obesity with metabolic complications. She was presented to the Emergency Department showing confusion, gait ataxia and horizontal nystagmus two months after surgery. Persistent vomiting and lack of compliance with vitamin intake were reported. Cerebral MRI showed acute bilateral lesions in the periaqueductal and periventricular regions. Parenteral thiamine supplementation was administered, obtaining a progressive resolution of altered mental status, motor ataxia, and nystagmus. She was discharged on oral thiamine supplementation and underwent a multidisciplinary rehabilitation program, since anterograde, retrograde, and working memory impairment persisted. After a 2-year follow-up, she was compliant with a balanced fractionated diet and vitamin supplementation. A new cerebral MRI showed regression of the neuroradiological findings, but minimal memory impairment remained. CONCLUSION: Wernicke's encephalopathy is a concrete possibility after sleeve gastrectomy and should always be suspected in patients with recurrent vomiting, poor nutritional intake, and non-compliance to vitamin supplementation. Immediate and aggressive thiamine supplementation is mandatory to prevent patients from irreversible neurological impairment, even though full recovery is not always achieved.

Does thiamine supplementation affect heart failure? A systematic review and meta-analysis of randomized control trials.

BACKGROUND: Heart failure is a pathophysiological condition where decreased cardiac output is observed subsequent to any structural deformity or cessation of normal function. Thiamine deficiency is one of the risk factors responsible for causing HF; other risk factors include hypertension, smoking, and obesity. OBJECTIVE: We conducted a systemic review and meta-analysis of RCTs to scrutinize whether the heart failure patients would benefit from thiamine supplementation or not when compared to placebo. METHODS: We selected only those double-arm randomized controlled trials (RCTs) which included participants presenting with symptomatic heart failure. We excluded all the articles published in languages other than English Language. Furthermore, all the studies other than RCTs were also omitted. Articles yielded from the electronic search were exported to EndNote Reference Library software to remove any duplicates. Analyses were done using the Review manager 5.4 tool. Mean values and standard deviations were retrieved for the continuous outcomes given as raw data. RESULTS: The 6 RCTs selected for the statistical analysis consisted of 298 participants (158 in the intervention group, 140 in the placebo group). The outcomes resulted to be non-significant with LVEF p-value= 0.08, NT-pro BNP p-value= 0.94, LVEDV p-value= 0.53, 6MWT p-value=0.59, mortality p-value= 0.61, hospitalization p-value= 0.53 and dyspnea p-value= 0.77. Heart rate is the only significant outcome with a p-value=0.04. CONCLUSION: To conclude, except for heart rate, thiamine supplementation had no effect on the outcomes of heart failure patients.

Pulmonary artery catheter usage in diagnosis of Shoshin beriberi presented with unexplained lactic acidosis.

Wet beriberi is a rare but fatal disease in modern society. The nonspecific clinical manifestations, including symptoms of heart failure and recalcitrant lactic acidosis, can prevent timely diagnosis. The use of a pulmonary artery catheter can promptly confirm a high cardiac output state and plays a crucial role in rapidly deteriorating cases. Appropriate treatment with intravenous administration of thiamine leads to dramatic recovery within hours. We present two cases of Shoshin beriberi, a fulminant variant of wet beriberi, diagnosed in 2016 and 2022 at our institute. The patients experienced haemodynamic collapse and refractory lactic acidosis, which were successfully diagnosed with the use of a pulmonary artery catheter and reversed by thiamine supplementation. We also reviewed 19 cases of wet beriberi reported between 2010 and 2022.

Further evidence of relationship between thiamine blood level and cognition in chronic alcohol-dependent adults: Prospective Pilot Study of an inpatient detoxification with oral supplementation protocol.

BACKGROUND: The relationship between thiamine blood level (TBL) and cognition remains uncertain, including among alcohol-dependent persons (ADP). AIM: To evaluate this relationship during protocol-driven inpatient alcohol detoxification treatment including thiamine supplementation (AD + Th). METHODS: Prospective 3-week study with 100 consecutively admitted detoxification-seeking ADP (47.7 ± 11 years old, 21% females) without superseding comorbidities requiring treatment. TBL and Montreal Cognitive Assessment (MoCA) were measured at admission (t1, pre-AD + Th) and discharge (t3, post-AD + Th). Frontal Assessment Battery (FAB) was performed at t1. AD + Th included abstinence, pharmacological alcohol withdrawal syndrome treatment, and oral thiamine supplementation (200 mg/day for 14 days). Regression and mediation analyses assessed TBL-cognition relationships. RESULTS: We found no cases of Wernicke Encephalopathy (WE) and only one case of thiamine deficiency. Both MoCA and TBL significantly improved across AD + Th (with medium-to-large effect sizes). At t1, TBL significantly predicted MoCA and FAB sum scores (medium effect sizes; extreme and very strong evidence, respectively). The clear TBL-MoCA association disappeared at t3. In multivariate regression and mediation analyses exploring key influential factors of cognition (identified by LASSO regression), the TBL-MoCA interactions did not relevantly change at t1 and t3. Age, serum transaminases, vitamin D levels, drinking-years, and depression score weakly modified the relationship. CONCLUSION: TBL was a robust predictor of pre-detoxification cognitive impairment, and both TBL and cognition improved significantly during AD + Th (including abstinence) in our ADP population, supporting routine thiamine supplementation for ADP, even those at low WE-risk. The TBL-cognition relationship was minimally confounded by age, alcohol-toxicity proxies, mood, and vitamin D levels.

Thiamine pharmaconutrition in sepsis: Monotherapy, combined therapy, or neither? Current evidence on safety and efficacy.

Sepsis is a life-threatening condition characterized by multiorgan dysfunction due to an exaggerated host response to infection associated with a homeostatic failure. In sepsis, different interventions, aimed at improving clinical outcomes, have been tested over the past decades. Among these most recent strategies, intravenous high-dose micronutrients (vitamins and/or trace elements) have been investigated. According to current knowledge, sepsis is characterized by low thiamine levels, which are associated with illness severity, hyperlactatemia, and poor clinical outcomes. However, caution is needed about the clinical interpretation of thiamine blood concentration in critically ill patients, and the inflammatory status, based on C-reactive protein levels, should always be measured. In sepsis, parenteral thiamine has been administered as monotherapy or in combination with vitamin C and corticosteroids. Nevertheless, most of those trials failed to report clinical benefits with high-dose thiamine. The purpose of this review is to summarize the biological properties of thiamine and to examine current knowledge regarding the safety and efficacy of high-dose thiamine as pharmaconutrition strategy when administering singly or in combination with other micronutrients in critically ill adult patients with sepsis or septic shock. Our examination of the most up-to-date evidence concludes that Recommended Daily Allowance supplementation is relatively safe for thiamine-deficient patients. However, current evidence does not support pharmaconutrition with high-dose thiamine as a single therapy or as combination therapy aimed at improving clinical outcomes in critically ill septic patients. The best nutrient combination still needs to be determined, based on the antioxidant micronutrient network and the multiple interactions among different vitamins and trace elements. In addition, a better understanding of the pharmacokinetic and pharmacodynamic profiles of intravenous thiamine is needed. Future well-designed and powered clinical trials are urgently warranted before any specific recommendations can be made regarding supplementation in the critical care setting.

Thiamine for the Treatment of Cardiac Arrest-Induced Neurological Injury: A Randomized, Blinded, Placebo-Controlled Experimental Study.

Background Thiamine supplementation has demonstrated protective effects in a mouse model of cardiac arrest. The aim of this study was to investigate the neuroprotective effects of thiamine in a clinically relevant large animal cardiac arrest model. The hypothesis was that thiamine reduces neurological injury evaluated by neuron-specific enolase levels. Methods and Results Pigs underwent myocardial infarction and subsequently 9 minutes of untreated cardiac arrest. Twenty minutes after successful resuscitation, the pigs were randomized to treatment with either thiamine or placebo. All pigs underwent 40 hours of intensive care and were awakened for assessment of functional neurological outcome up until 9 days after cardiac arrest. Nine pigs were included in both groups, with 8 in each group surviving the entire intensive care phase. Mean area under the curve for neuron-specific enolase was similar between groups, with 81.5 µg/L per hour (SD, 20.4) in the thiamine group and 80.5 µg/L per hour (SD, 18.3) in the placebo group, with an absolute difference of 1.0 (95% CI, -57.8 to 59.8; P=0.97). Likewise, there were no absolute difference in neurological deficit score at the end of the protocol (2 [95% CI, -38 to 42]; P=0.93). There was no absolute mean group difference in lactate during the intensive care period (1.1 mmol/L [95% CI, -0.5 to 2.7]; P=0.16). Conclusions In this randomized, blinded, placebo-controlled trial using a pig cardiac arrest model with myocardial infarction and long intensive care and observation for 9 days, thiamine showed no effect in changes to functional neurological outcome or serum levels of neuron-specific enolase. Thiamine treatment had no effect on lactate levels after successful resuscitation.