Is there any data supporting the use of banana bags (IV fluids + IV thiamine + IV folic acid + IV multivitamin) for patients with alcohol abuse? Specifically for the combination of medications in a banana bag vs IV thiamine alone (or any of the individual agents alone)?

Comment by InpharmD Researcher

Available literature does not support routine use of the traditional “banana bag” (intravenous fluids combined with thiamine, folic acid, and multivitamins) for patients with alcohol use disorder, particularly in critically ill settings. Evidence consistently identifies thiamine as the most clinically important deficiency to assess and replace, while standard banana bag formulations may not deliver adequate thiamine to the central nervous system and lack evidence of benefit from multivitamin inclusion. Although folate and magnesium supplementation may be reasonable in selected patients, the supporting data are weaker and largely indirect. Importantly, there is a lack of direct comparative data comparing banana bags with thiamine alone or with targeted supplementation strategies, limiting definitive conclusions; nonetheless, expert consensus favors a thiamine-centered, targeted approach due to the difficulty of diagnosing Wernicke encephalopathy and the severe consequences of delayed treatment.

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Background

According to the 2020 American Society of Addiction Medicine (ASAM) Clinical Practice Guideline on Alcohol Withdrawal Management, alcohol withdrawal can cause significant morbidity in patients, particularly those in the critical care setting, and intensive care unit (ICU) admission may warrant prophylactic interventions to reduce the risk of developing withdrawal-related complications. Patients in the ICU should be closely monitored for worsening signs and symptoms, as well as for the development of Wernicke encephalopathy (WE), a potentially severe consequence of thiamine (vitamin B1) deficiency. Traditionally, multivitamin infusions, often referred to as “banana bags,” have been administered to ICU patients to prevent WE. However, studies examining the effectiveness of the standard ICU protocol have suggested that the banana bag approach may not adequately address the risk, particularly when signs and symptoms are masked or mimicked by other illnesses. These findings have led to recommendations to abandon routine banana bag administration in favor of targeted therapy, specifically providing patients with 200-500 mg of intravenous (IV) thiamine every eight hours, magnesium sulfate at 64 mg/kg, and IV folate at 400-1,000 mcg for those exhibiting signs or symptoms suggestive of WE. Importantly, when patients also receive glucose, thiamine can be administered before, after, or concurrently with glucose to prevent precipitating or worsening deficiency. [1]

A 2016 review article evaluated vitamin and electrolyte deficiencies in critically ill patients with chronic alcohol use disorder (AUD) and identified thiamine as the most critical nutrient to assess and replace promptly. Based on pharmacokinetic data, standard banana bags are unlikely to optimize thiamine delivery to the central nervous system. Folic acid and magnesium may warrant supplementation, but evidence supporting their routine use is weaker, and there is no evidence for multivitamin administration. For patients admitted to the ICU with symptoms that may mimic or mask WE, the authors recommended abandoning the banana bag in favor of targeted therapy: 200-500 mg IV thiamine every eight hours, magnesium sulfate 64 mg/kg (4-5 g for most adults), and IV folate 400-1,000 mcg during the first day of admission. When alcoholic ketoacidosis (AKA) is suspected, dextrose-containing fluids are preferred over normal saline. The review also emphasized that critically ill patients with chronic AUD are often deficient in thiamine, folate, and magnesium, and typical banana bag formulations do not adequately address the neurological risks associated with these deficiencies. While evidence for nutrients other than thiamine is limited, empiric therapy is often justified due to the difficulty of diagnosing WE or Korsakoff syndrome and the severe consequences of delayed treatment. Ultimately, clinicians should weigh the potential benefits, risks, and costs of supplementation for each patient using the available literature as guidance. For an overview of recommendations for supplementation in critically ill patients with AUD, please refer to Table 1. [2]

A 2020 article highlighted that thiamine supplementation was not included in the 2019 Canadian Family Physician guidance on office management of alcohol withdrawal, despite the well-established risk of nutritional deficiencies in individuals with alcohol use disorder. The authors emphasized that thiamine supplementation reduces the risk of Wernicke syndrome, Korsakoff syndrome, and beriberi, and that clinicians should maintain a high index of suspicion for Wernicke syndrome, particularly in patients presenting with ophthalmoplegia, ataxia, or confusion. While optimal dosing, duration, and route of administration remain uncertain, there is increasing consensus that patients with confirmed or high-risk Wernicke syndrome should receive parenteral thiamine. Oral thiamine may also play a role in preventing or improving thiamine-deficient states; although gastrointestinal absorption is lower than with intramuscular administration, the potential preventive benefit and low risk support its use. Consistent with this, the 2017 update of the National Institute for Health and Clinical Excellence guidelines recommends prophylactic oral thiamine for individuals with alcohol dependence, and the British Association for Psychopharmacology similarly advises oral thiamine in those with poor nutritional intake. Additional outpatient guidance has recommended routine thiamine 100 mg daily with folic acid 1 mg daily. Overall, the article supports routine consideration of thiamine supplementation in the office-based management of alcohol use disorders and alcohol withdrawal, given the serious consequences of unrecognized thiamine deficiency and the potential benefit of prevention. Of note, the use of banana bag formulations was not described within the article. [3]

Lastly, a 2020 review delves into the efficacy of vitamin supplementation for addressing alcoholism and alcohol-related health complications. This comprehensive examination highlights research findings derived from both clinical and basic studies that elucidate the impact of vitamin deficiencies on physiological systems, primarily focusing on the liver and brain. Animal models, particularly rodents, were frequently employed to investigate the effects of vitamin depletion, utilizing behavioral experiments that simulate cognitive, learning, memory, and motivational parameters. These foundational studies offer support for existing hypotheses concerning the detrimental impact of vitamin deficiencies in individuals with alcohol use disorder. Although clinical studies remain scarce, those available generally assess the outcomes of vitamin supplementation within structured treatment programs. The review underscores the significance of deficiencies in specific vitamins, such as retinoids (vitamin A), thiamine (B1), and niacin (B3), which are recurrently explored in the context of alcoholism. Despite promising findings regarding individual vitamins and their combinations, the review stresses the necessity for more extensive clinical research to validate these results and calls for more standardized supplementation and treatment protocols. This exploration affirms the potential of vitamin supplementation in enhancing the understanding and treatment of alcoholism, although it acknowledges the current predominance of basic research over clinical applications. [4]

References: [1] The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management. J Addict Med. 2020;14(3S Suppl 1):1-72. doi:10.1097/ADM.0000000000000668
[2] Flannery AH, Adkins DA, Cook AM. Unpeeling the Evidence for the Banana Bag: Evidence-Based Recommendations for the Management of Alcohol-Associated Vitamin and Electrolyte Deficiencies in the ICU. Crit Care Med. 2016;44(8):1545-1552. doi:10.1097/CCM.0000000000001659
[3] Shakory S. Thiamine in the management of alcohol use disorders. Can Fam Physician. 2020;66(3):165-166.
[4] Lewis MJ. Alcoholism and nutrition: a review of vitamin supplementation and treatment. Curr Opin Clin Nutr Metab Care. 2020;23(2):138-144. doi:10.1097/MCO.0000000000000622
Literature Review

A search of the published medical literature revealed 4 studies investigating the researchable question:

Is there any data supporting the use of banana bags (IV fluids + IV thiamine + IV folic acid + IV multivitamin) for patients with alcohol abuse? Specifically for the combination of medications in a banana bag vs IV thiamine alone (or any of the individual agents alone)?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Tables 1-4 for your response.


 

 

Recommendations for Supplementation in Critically Ill Patients With Alcohol Use Disorders
Supplement Signs/Symptoms of Deficiency in Alcohol Withdrawal Recommended Dose Evidence for Routine Supplementation
Thiamine Altered mental status; Wernicke’s encephalopathy; Korsakoff syndrome; metabolic dysfunction 200-500 mg IV every 8 hours Adequate evidence
Folate Megaloblastic anemia; confusion; sleep disturbances; depression; psychosis; seizures 400-1,000 mcg IV daily Reasonable evidence
Magnesium QT prolongation/torsades de pointes; altered mental status; seizures; tremors; hyperreflexia 64 mg/kg IV on day 1, followed by 32 mg/kg IV on days 2-4 (magnesium sulfate) Reasonable evidence
Multivitamin Various Not recommended No evidence
Phosphorus Respiratory insufficiency; altered mental status; seizures; muscle weakness Not recommended No evidence
Potassium Cardiac arrhythmia; prolonged QT interval; altered mental status; muscle weakness Not recommended No evidence
Riboflavin Possible seizures Not recommended No evidence
Selenium Not well defined Not recommended No evidence
Vitamin A Not well defined Not recommended No evidence
Vitamin C Not well defined Not recommended No evidence
Zinc Not well defined Not recommended No evidence
References:
[1] Adapted from: Flannery AH, Adkins DA, Cook AM. Unpeeling the Evidence for the Banana Bag: Evidence-Based Recommendations for the Management of Alcohol-Associated Vitamin and Electrolyte Deficiencies in the ICU. Crit Care Med. 2016;44(8):1545-1552. doi:10.1097/CCM.0000000000001659
Adding an orange to the banana bag: vitamin C deficiency is common in alcohol use disorders
Design

Retrospective, observational study

N= 69

Objective To determine the incidence of vitamin C deficiency in patients with alcohol use disorders (AUDs) admitted to an intensive care unit and to evaluate the effectiveness of vitamin C supplementation
Study Groups All patients (n= 69)
Inclusion Criteria Patients admitted to the MICU with an AUD and an admission vitamin C level measured, defined by DSM-5 criteria
Exclusion Criteria Patients who were septic on admission, patients less than 18 years or over 90 years of age
Methods Vitamin C levels were measured on admission and repeated on day 2 and day 3. Various vitamin C replacement dosing strategies were used, including a 1.5-g loading dose followed by 500-mg by mouth every 6 hours. 
Duration January 2018 to December 2018
Outcome Measures

Primary: Incidence of hypovitaminosis C

Secondary: Effectiveness of vitamin C supplementation in restoring normal levels

Baseline Characteristics   All patients (n= 69)
Age, years 53 ± 14
Male 52 (75%)
Severe alcohol withdrawal syndrome 32 (46%)
Cirrhosis 18 (26%)
Drug + alcohol intoxication 9 (13%)
COPD/CHF 5 (7%)
BMI, kg/m2 25.2 ± 5.2
BUN, mg/dl 14.6 ± 9.7
Magnesium, mg/dl 1.8 ± 0.4
AST, IU/l 84 ± 84
Albumin, g/dl 3.3 ± 0.8
MCV, fl 89 ± 14
Lactate, mmol/l 2.9 ± 3.1
Results   All patients (n= 69)
< 40 μmol/l (subnormal) 61 (88%)
< 23 μmol/l (hypovitaminosis C) 52 (75%)
< 11 μmol/l (severe deficiency) 29 (42%)
Undetectable 18 (26%)
Adverse Events Not specifically reported
Study Author Conclusions In this retrospective, observational study which included patients with an AUD who were admitted to an ICU for both alcohol- and non-alcohol-related medical conditions, 75% had hypovitaminosis C. Previous research has demonstrated that vitamin C increases ethanol clearance and may reduce alcohol-induced hepatotoxicity. These data suggest that critically ill patients admitted to the ICU with chronic alcoholism should be treated with vitamin C. Additional studies are required to confirm the findings of this small observational study. Furthermore, the optimal dosing strategy and both the shortand long-term benefits of vitamin C supplementation in this patient population remain to be determined.
Critique The study highlights an important nutritional deficiency in a vulnerable population, but its retrospective design and small sample size limit the ability to generalize the findings. The study also lacks a control group and does not explore the clinical outcomes associated with vitamin C supplementation. 
References:
[1] Marik PE, Liggett A. Adding an orange to the banana bag: vitamin C deficiency is common in alcohol use disorders. Crit Care. 2019;23(1):165. Published 2019 May 10. doi:10.1186/s13054-019-2435-4

Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores
Design

Randomized controlled trial

N= 127

Objective To compare the efficacy of thiamine and/or magnesium treatment in patients with alcohol withdrawal syndrome on erythrocyte transketolase activity, lactate concentrations, and alcohol withdrawal scores
Study Groups

Thiamine (n= 38)

Thiamine and Magnesium (n= 37)

Magnesium (n= 40)

Inclusion Criteria Patients presenting to the Emergency Department with symptoms or signs of alcohol withdrawal syndrome, aged ≥18 years, capable of giving informed consent
Exclusion Criteria Patients with a history of chronic renal or hepatic failure, hepatic encephalopathy, known hypersensitivity or previous allergy to trial medications, or severe concurrent medical conditions
Methods Patients were randomized to receive thiamine 250 mg, thiamine plus MgSO4 2 g, or MgSO4 2 g. Blood samples were taken pre- and 2-h post-treatment. Erythrocyte transketolase activity and plasma lactate concentrations were measured
Duration January 2017 to June 2018
Outcome Measures

Primary: 15% change in erythrocyte transketolase activity (ETKA) in group 3

Secondary: Change in plasma lactate concentrations, time to Glasgow Modified Alcohol Withdrawal Score (GMAWS) = 0

Baseline Characteristics   Thiamine (n= 38) Thiamine and Magnesium (n= 37) Magnesium (n= 40)
Age < 50 years 27 19 27
Male 26 30 32
Recent weight loss 23 30 25
Gait disturbance 32 33 30
GMAWS at presentation 4 (2–4) 4 (3–5) 4 (3–4)
Results   Thiamine (n= 38) Thiamine and Magnesium (n= 37) Magnesium (n= 40) p-value
Time to GMAWS = 0, hours 10 5.5 6 <0.001
Plasma lactate normalization, % 20 46 25 <0.001
Adverse Events No significant adverse events reported
Study Author Conclusions Co-administration of thiamine and magnesium resulted in more consistent normalization of plasma lactate concentrations and reduced duration to achieve initial resolution of AWS symptoms.
Critique The study provides valuable insights into the biochemical effects of thiamine and magnesium in AWS patients. However, the lack of significant change in ETKA and the potential confounding effects of other micronutrients like riboflavin were not fully addressed. The study's findings may not be generalizable due to the specific patient population and setting.
References:
[1] Maguire D, Burns A, Talwar D, et al. Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores. Sci Rep. 2022;12(1):6941. Published 2022 Apr 28. doi:10.1038/s41598-022-10970-x

 

Vitamin deficiencies in acutely intoxicated patients in the ED
Design

Prospective, cross-sectional, observational study

N= 77

Objective To determine the prevalences of vitamin deficiencies in patients presenting to the ED with alcohol intoxication
Study Groups All patients (N= 77)
Inclusion Criteria Patients presenting to the ED with acute alcohol intoxication and had blood tests drawn as part of routine care
Exclusion Criteria Repeat visits during the study period
Methods Patients were enrolled during clinical shifts of clinicians. Patients were tested for B12, folate, and thiamine levels as add-ons to their blood samples. B12 levels of 200 to 730 ng/L, folate levels of 2.8 to 13.5 μg/L, and thiamine levels of 87 to 280 nmol/L were considered normal. 
Duration June to November 2006
Outcome Measures Primary: Prevalences of vitamin deficiencies (B12, folate, thiamine)
Baseline Characteristics   All patients (n= 77)
Mean age, years 46
Female 19%
Mean blood alcohol level, mg/dL 280
Results   Deficiency Prevalence 95% CI
B12 0% 0-0.05
Folate 0% 0-0.05
Thiamine, n (%) 6 (15%) 0.06-0.31
Adverse Events None of the patients with low thiamine levels exhibited symptoms or signs of thiamine deficiency
Study Author Conclusions In our ED, patients with acute ethanol intoxication do not have B12 or folate deficiencies. A significant minority (15%) of patients have thiamine deficiency; its clinical significance is unclear. Widespread administration of multivitamins is unwarranted by these findings, but thiamine may be considered.
Critique The study was limited by the inability to complete thiamine levels for all patients due to technical issues. The sample may not be generalizable to other settings as it was conducted in an urban municipal hospital with a specific patient demographic. Additionally, the study did not assess the chronicity of alcohol use or potential prior vitamin supplementation from other sources. 
References:
[1] Li SF, Jacob J, Feng J, Kulkarni M. Vitamin deficiencies in acutely intoxicated patients in the ED. Am J Emerg Med. 2008;26(7):792-795. doi:10.1016/j.ajem.2007.10.003