Audrey Abelleira, PharmD, BCPP. Clinical pharmacist practitioner, Pain Management and Opioid Safety Program Coordinator, VA Connecticut Healthcare System. Clinical instructor, Yale School of Medicine. New Haven, CT.
Dr. Abelleira has no financial relationships with companies related to this material.
Before diving into the topic of thiamine deficiency and how it’s related to alcohol, let’s review what thiamine is and why we need it. Also known as vitamin B1, thiamine is an essential vitamin, meaning that it cannot be synthesized by the body and must be supplied through a person’s diet (Whitfield KC et al, Ann NY Acad Sci 2018;1430(1):3–43). Thiamine is a vital component of many biochemical processes, including energy metabolism and nervous system function. Most people get enough thiamine through dietary sources (more on these below), and many foods are artificially fortified with thiamine.
Thiamine is water soluble, so there is no known adverse effect associated with high intake and no upper limit to how much can be safely consumed. On the other hand, its water solubility means that it has a short half-life, and thiamine must be consumed on a regular basis because there are no long-term stores in the body. Without consistent thiamine intake, the body can become thiamine deficient, resulting in severe and potentially permanent neurologic and cardiovascular damage.
Alcohol use disorder and thiamine deficiency
You may be wondering why thiamine is so susceptible to depletion in patients with alcohol use disorder (AUD). The answer is two-fold. First, ethanol can impede thiamine absorption and utilization, increase thiamine requirements, and decrease the body’s already limited storage capacity. The result is an even greater dependence upon a steady intake of dietary thiamine. This leads to the second contributor to thiamine deficiency: People with AUD tend to have diets that are low in thiamine-rich foods (Leevy CM, Ann NY Acad Sci 1982;378:316–326). This one-two punch explains the high correlation between thiamine deficiency and AUD. In fact, it’s estimated that as many as 80% of patients with AUD are thiamine deficient to some degree (Markowitz JS et al, Ann Clin Psychiatry 2000;12(3):153–158).
Consequences of thiamine deficiency
Symptoms of thiamine deficiency can overlap with other disorders, making it difficult to diagnose based on interview and physical exam alone (Smith TJ et al, Ann NY Acad Sci 2021;1498(1):9–28). The neurologic and cardiovascular symptoms of thiamine deficiency are the most concerning. The most prominent early neurologic symptom of thiamine deficiency is peripheral neuropathy, often characterized by pain. Vitamin B12 deficiency, in contrast, is usually characterized not by pain, but by upper and lower motor neuron dysfunction manifesting in weakness and decreased reflexes (Staff NP and Windebank AJ, Continuum 2014;20(5):1293–1306). If left untreated, thiamine deficiency can progress to encephalopathy, pulmonary hypertension, and right-sided heart failure.
Dietary thiamine deficiency syndromes are sometimes referred to as “beriberi,” meaning “I cannot, I cannot” in Sinhalese. While unconfirmed, some attribute the origin of the term to the response given by those in Sri Lanka afflicted with neurologic symptoms of thiamine deficiency when asked to move. Beriberi has been subsequently characterized as “wet” (heart failure with edema) or “dry” (neurologic symptoms).
Thiamine deficiency may progress to Wernicke-Korsakoff syndrome (WKS). It is estimated that about 13% of patients with AUD will develop some degree of WKS (Smith et al, 2021). Wernicke encephalopathy (WE) and Korsakoff syndrome (KS) comprise the two distinct phases of the same disease (Chandrakumar A et al, J Basic Clin Physiol Pharmacol 2018;30(2):153–162). WE, which develops after four to six weeks of thiamine deficiency, is characterized by the classic triad of oculomotor dysfunction (nystagmus, ophthalmoplegia), cerebellar dysfunction (ataxia), and delirium. However, only about 20% of patients present with the full triad; most present with delirium alone. The Caine criteria can be used to increase the sensitivity and specificity of a WE diagnosis. A patient screens positive for WE if they meet two or more of the following four criteria: oculomotor abnormalities, cerebellar signs, mild memory impairment or confusion, or signs of malnutrition (Isenberg-Grzeda E et al, Psychosomatics 2012;53(6):507–516).
High-dose, parenteral thiamine repletion can reverse the symptoms of WE, usually with oculomotor symptoms resolving first. But if WE is not promptly recognized and thiamine deficiency is not corrected, it may progress to KS. People with AUD are particularly susceptible to progression to KS when compared to thiamine deficiency from other causes. KS is characterized by anterograde and retrograde amnesia, confabulation, and apathy, typically accompanied by a profound lack of insight. Unlike WE, KS is typically not reversible and represents the end stage of alcohol-induced thiamine deficiency.
When it comes to supplementing thiamine, we recommend following the expert consensus issued by the American Society of Addiction Medicine’s (ASAM) Clinical Practice Guideline on Alcohol Withdrawal Management (ASAM, J Addict Med 2020;14(3S Suppl 1):1–72). There are several recommendations based on different clinical situations.
Patients presenting with alcohol withdrawal
All patients in withdrawal should receive thiamine supplementation, regardless of whether they have any symptoms of deficiency. This is done both to prevent WE from developing and to reverse it if it is present.
Inpatient alcohol withdrawal
Parenteral administration (intravenous or intramuscular) is preferred since alcohol can reduce oral absorption (ASAM, 2020). Dosing recommendations are as follows:
Outpatient alcohol withdrawal
Oral supplementation may be used for outpatients if signs of WE are not present. If WE is suspected, the patient should be hospitalized for parenteral supplementation. Contrary to prior recommendations stating that thiamine must be administered prior to glucose, thiamine can in fact be administered before, concomitant with, or after glucose. For outpatients in mild to moderate withdrawal, 100 mg PO thiamine daily for three to five days is recommended (Altman J and Ryan MF, Case Reports in Clinical Medicine 2019;8:245–249).
Daily supplementation for patients with AUD
It’s not clear whether daily oral thiamine supplements are helpful for patients with AUD. Dietary sources are better absorbed, so instead of ongoing thiamine supplementation, recommend thiamine-rich foods to your patients, such as fortified cereals, pork, fish, beans, peas, yogurt, and nuts. In the case of poor diet, daily oral supplementation may help and probably won’t hurt.
Supplementation of other vitamins and minerals
Heavy alcohol use is associated with other nutritional deficiencies as well. Magnesium, a necessary co-factor in thiamine utilization, should be supplemented in patients with low magnesium levels, cardiac arrhythmia, or a history of withdrawal seizures. Severe phosphate deficiency (<1 mg/dL) requires phosphate supplementation. Finally, consider supplementing folate for critically ill patients.
Thiamine deficiency is common among people with AUD and is associated with potentially devastating neurological consequences. Nonetheless, many patients do not receive proper supplementation (for more on thiamine supplementation practices, see the research updates in this issue). All patients being treated for alcohol withdrawal should receive thiamine supplementation, with
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