Thiamin deficiency post RNY

On January 9, 2010, in Vitamins, Water Solubles, by Andrea

Two CMEs off Medscape cause I was working on the Thiamin post and I found them.  Only referenced one cause I had only read it when I wrote up the stuff.  Maybe should have read the other, too, eh?

Thiamine Deficiency May Complicate Gastric Bypass

News Author: Laurie Barclay, MD
CME Author: Charles Vega, MD, FAAFP

Dec. 30, 2005 — Thiamine deficiency with a nonclassic presentation may follow gastric bypass for obesity, according to a case report in the December 27 issue of Neurology.

“The neurological complications following gastric bypass surgery are diverse,” coauthor Raul N. Mandler, MD, from George Washington University in Washington, DC, said in a news release. “Vitamin B1 deficiency and Wernicke encephalopathy should be carefully considered in surgically treated obese patients.”

The authors describe a 35-year-old woman who developed many symptoms following bariatric gastric bypass, including nausea, anorexia, fatigue, apathy, hearing loss, psychomotor slowing, forgetfulness, ataxia, and bilateral hand paresthesias. By the twelfth postoperative week, she had lost 40 lb and had lethargy, confusion, and difficulty walking, which necessitated hospitalization.

Examination showed inattention, fluent speech with decreased comprehension, decreased hearing, strength 3/5 in the lower extremities, vibratory sense decreased in the feet, deep tendon reflexes absent, and wide-based gait. Laboratory abnormalities were a slight elevation in liver enzymes, high serum glucose level (163 mg/dL), and low serum potassium level (2.6 MEq/L). Her mental status continued to decline despite treatment for dehydration.

When hospitalized, her heart rate was 125 beats per minute; she opened her eyes to nail bed pressure but followed no commands and was nonverbal. Pupils were round and fixed at 3 mm; oculocephalic and deep tendon reflexes were absent; and general muscle tone was flaccid without spontaneous movements or withdrawal to painful stimuli. Cerebral spine fluid protein level was 90 mg/dL, and there was diffuse slowing on electroencephalogram.

Brain magnetic resonance imaging (MRI) revealed bilateral symmetric hyperintense signal on T2-weighted and fluid attenuated inversion recovery images at the floor of the fourth ventricle, periaqueductal gray matter, the medial portions of both thalami, and the premotor and motor cortices, with contrast enhancement in all T2 hyperintense regions.

When she was given intravenous (IV) vitamin B 1, 100 mg every 8 hours, her oculocephalic reflexes gradually returned to normal, and she eventually became responsive. Follow-up brain MRI 11 days after thiamine repletion showed interval improvement, with less contrast enhancement, but with increased signal on precontrast T1-weighted images in the premotor and motor cortices, likely representing petechial hemorrhages.

“Wernicke encephalopathy is a well-defined syndrome, but difficult to identify in the absence of the classic triad of oculomotor abnormalities, ataxia, and confusion,” the authors write. “When a patient presents with unusual symptoms (in our case with progressive hearing loss, most likely secondary to thalamic involvement), then blood work (red blood cell transketolase levels) and MRI become helpful tools in making the diagnosis.”

The authors have disclosed no relevant financial relationships.

“This case highlights the variability of Wernicke encephalopathy where the classic trio of eye movement abnormalities, confusion, and ataxia are seen in less than 20% of patients,” says Heidi Schwarz, MD, who wrote a related commentary. “It is unusual because the patient also had hearing loss.”

Dr. Schwarz notes that bariatric surgery may have other complications, including anemia, vitamin D deficiency and bone resorption, rhabdomyolysis, vitamin A deficiency, and hypocalcemia. Neurologic complications are common, especially when there is intractable vomiting causing myelopathy and ataxia due to deficiencies in vitamin B 12, copper, or vitamin E; or peripheral neuropathy, plexopathies, and mononeuropathies due to vitamin or micronutrient deficiencies or as yet unknown causes.

“Although thiamine deficiency was not documented serologically [in this case report], the course, MRI findings, and response to thiamine establish the diagnosis,” Dr. Schwarz writes. “Patients who have had bariatric surgery require a high index of suspicion for Wernicke encephalopathy so that prompt treatment can be given to prevent devastating and often permanent disability.”

Neurology. 2005;65:1847, 1987

Wernicke Encephalopathy After Bariatric Surgery: A Systematic Review

Erlend Tuseth Aasheim, MD


Objective: To review the clinical essentials of Wernicke encephalopathy (WE) after bariatric surgery.
Summary Background Data: An estimated 205,000 bariatric surgical procedures were performed in the United States in 2007. Such procedures may potentially lead to severe nutritional complications.
Methods: Literature searches were performed in Medline, Embase, and abstract collections. Inclusion criteria were WE after bariatric surgery, diagnosed by the presence of two or more of the following signs: mental status changes, eye movement abnormalities, cerebellar dysfunction, and dietary deficiency.
Results: Of 104 reported cases of WE after bariatric surgery, 84 cases were included. Gastric bypass or a restrictive procedure had been performed in 80 cases (95%). Admission to hospital for WE occurred within 6 months of surgery in 79 cases (94%). Frequent vomiting was a risk factor in 76 cases (90%) and had lasted for a median of 21 days at admission. Intravenous glucose administration without thiamine was a risk factor in 15 cases (18%). Brain magnetic resonance imaging identified lesions characteristic of WE in 14 of 30 cases (47%). Incomplete recovery was observed in 41 cases (49%); memory deficits and gait difficulties were frequent sequela. The recent increase in the use of bariatric surgery in the United States was associated with an increase in reported WE cases.
Conclusions: The number of WE cases after bariatric surgery is substantially higher than previously reported. Surgeons, allied health providers, and patients need to be aware of the predisposing factors and symptoms to prevent and optimize the management of this condition.


Nearly 7% of adult U.S. women presently have a body mass index above 40 kg/m2.[1] Bariatric surgery is presently the only treatment likely to yield substantial and durable weight loss, and has beneficial effects on medical conditions associated with severe obesity.[2] As a result, more than 100,000 weight-loss procedures are performed annually in the United States alone, and numbers are rising.[3] The sheer volume suggests that any physician involved in clinical medicine will meet patients who have been treated with obesity surgery. Practitioners will therefore need to familiarize themselves with the potential adverse effects linked with this therapy.

Anastomotic leakage and pulmonary embolism are feared complications of bariatric surgery procedures. However, acute nutritional disturbances may also occur in the early postoperative period. The numerous reports of severe thiamine (vitamin B1) deficiency after obesity surgery have led to the expression bariatric beriberi.[4] Beriberi is derived from the Singhalese word beri meaning weakness and refers to the clinical spectrum of deficiency in thiamine, including affection of the peripheral and central nervous system.[5] The most frequent central neurologic complication of thiamine deficiency is Wernicke encephalopathy (WE), a condition which needs immediate treatment to prevent death or permanent neurologic sequela. The classic presentation is that of mental confusion, eye movement abnormalities, and gait instability. Autopsy series indicate that WE is underdiagnosed.[6] The general epidemiology, pathophysiology, and treatment of this condition was recently reviewed.[6]

Patients have a limited capacity for food intake during the initial weeks after a bariatric procedure. The body’s reserves of thiamine can be depleted after only 20 days of inadequate supply.[6] Patients treated with bariatric surgery may thus still be frankly obese when presenting with symptoms caused by nutritional derangement. Such patients are a diagnostic challenge to physicians not familiar with WE as a potential complication of weight-loss operations. The aim of this paper is to review the clinical essentials of WE after bariatric surgery, with emphasis on presentation, findings on supplementary tests, and patient outcomes.


Search Strategy

Systematic literature searches were performed by one investigator in Medline and Embase (from their inceptions to May 2008), with no language restrictions, for reports of Wernicke encephalopathy after bariatric surgery. The core search consisted of the MeSH terms Wernicke encephalopathy, bariatric surgery, morbid obesity, malnutrition, and polyneuropathies. These terms were also substituted with related terms (eg, bariatric surgery was substituted with obesity surgery, gastric bypass, gastroplasty, gastric banding, and biliopancreatic diversion). Further searches were done in abstract collections published in Obesity Surgery (1991-May 2008) and Surgery for Obesity and Related Diseases (2005-May 2008). Daily e-mails enlisting new articles identifiable in PubMed by using the term obesity were perused throughout February 2005 to May 2008. Nonsystematic literature searches were done using PubMed’s related articles feature, Google Scholar’s cited by feature, Wikipedia (the English version at, and UpToDate ( Bibliographies of original reports and reviews were scanned for additional references. A citing author kindly provided 2 otherwise unattainable abstracts.[7,8] Additional information was sought from the authors of 3 reports.[9-11]

Selection Criteria

Identified publications dealing with bariatric surgery were scrutinized for WE cases. WE was diagnosed in the presence of 2 or more of the following signs[12]: mental status changes (confusion, memory deficits, or impaired consciousness), eye movement abnormalities (nystagmus or palsy of ocular muscles), cerebellar dysfunction (gait incoordination or ataxia), and dietary deficiency (assumed in all cases).

Eleven cases were likely to appear in multiple reports and were only counted once.[8,9,13-22] Patients with encephalopathy after jejunoileal bypass were not included as their presentations were atypical and investigators noted that WE was unlikely.[23-28] Cases were excluded if too limited information was available to confirm a diagnosis of WE.

Data Extraction

One physician extracted data from the included reports. Data were recorded on designated forms. All data were cross-checked and entered in a database including more than 100 items on demographics, clinical symptoms, results of diagnostic tests, and patient outcome. Outcome was recorded at the latest reported follow-up and categorized as complete recovery (including improved when no information of residual deficits was given) or incomplete recovery (any sequela observed clinically).

Data Management

Reported data are number of cases (percentage) or median (range), as appropriate. Software packages used for the management of references, statistics, and graphics included Reference Manager 11 (Thomson ResearchSoft, Carlsbad, CA), SPSS 14 (SPSS Inc., Chicago, IL), and SigmaPlot 10 (Systat Software Inc., San Jose, CA).

Included Studies

Literature searches identified a total of 104 cases of WE reported after bariatric surgery. 20 cases were excluded: 19 described in too limited detail to confirm the WE diagnosis[10,19,29-31] and 1 diagnosed 13 years after bariatric surgery in a setting of excessive alcohol intake.[32] Thus, 84 cases were included in the systematic review. These cases were described in 58 reports published 1977-2008 (Figure 1).[11,13-15,17,21,33-84]

Figure 1. (click image to zoom) Case selection.

Patient Characteristics

The type of bariatric surgical operation performed in the 84 WE cases was gastric bypass in 43 (51%), diverse restrictive procedures in 37 (44%), and the malabsorptive procedure biliopancreatic diversion in 4 (5%). Median patient age was 32 years (range 14-55) and 69 were women (82%).

Duration from surgery until admission to hospital for WE was less than 6 months in 79 cases (94%), and ranged from 3 weeks to 18 months (Figure 2). Median weight loss from surgery to admission was 35 kg (12-129) and weight loss rate was 0.44 kg/d (0.11-1.6) (data on weight loss were reported in 54 patients).

Figure 2. (click image to zoom) Onset of Wernicke encephalopathy (n = 81). Three additional cases were admitted within 6 to 20 weeks (precise week not reported).[39,40] One patient was diagnosed 5 weeks after a reoperation (14 months after the primary procedure)[35] and was considered to be admitted at 5 weeks. One patient diagnosed at 78 weeks used a self-controlled device to infuse a morphine and 5% dextrose solution in water, after a panniculectomy.[54]

Symptoms and Signs

The clinical features are summarized in Figure 3. Recurrent vomiting was reported in 76 cases (90%), and had lasted for a median duration of 21 days (4-90) when patients were admitted to hospital (duration of vomiting was reported in 26 cases). When vomiting was not reported, patients had rapid weight loss, loss of appetite or eating avoidance, or did not take vitamin supplements.[11,15,34,35,46,52,55] Intravenous glucose had been administered without thiamine in 15 patients (18%).[11,17,21,47,54,59-61,63,67,74,75,80,83]

Figure 3. (click image to zoom) Clinical features reported in Wernicke encephalopathy cases (n = 84). Eye movement signs include nystagmus and gaze palsy; mental status changes include confusion, memory deficits, and impaired consciousness; gait ataxia includes incoordination of gait and posture.

The classic WE triad of eye movement abnormalities, mental status changes, and ataxia was present in 32 patients (38%); 2 signs were present in 36 patients (43%); and 1 sign was present in 16 patients (19%). Less common features included visual hallucinations,[17,37,51,67,71] behavioral disturbances,[51,62,76,85] and depression.[52,53,64,76] Also reported were dysarthria,[38,42,52,60,66,76,80] hearing loss,[15,37,38,40,45,52] and dysphagia.[46,49,80] Blurred vision or impaired visual acuity was noted in 17 patients.[14,37,38,40,48,54,56,60,64,70,76,81] Fundoscopy confirmed papilledema in 4 patients and 3 of these had peripapillary or retinal hemorrhages.[14,34,48] A few patients had myoclonus[36,44] or chorea,[41,76] and some eventually became comatose.[34,70,74,86]

Peripheral polyneuropathy occurred in 64 patients (76%). Motor and sensory neuropathy was reported with similar rates (56 versus 55 patients). Neuropathy was more frequent in the lower limbs than in the upper limbs (61 versus 30 patients).


Upper endoscopy or gastrointestinal series demonstrated stomal obstruction in 18 of 41 cases. Specific findings included anastomotic and bandelet stenoses (after gastric bypass),[35,36,51,54,57,58] pouch inlet, and outlet stenoses (vertical banded gastroplasty),[64,71] partition obstruction (gastric partitioning),[73,75] pouch outlet obstruction (adjustable gastric banding),[81] and gastric wall edema (sleeve gastrectomy).[83] Anastomotic leaks and jejunal erosions were also observed (gastric bypass).[46,54]

Results of thiamine assays, lumbar puncture, neuroimaging, and electrodiagnostic studies are shown in Table 1. Notably, brain computed tomography (CT) imaging did not reveal pathology in any of 39 examined cases, whereas brain magnetic resonance (MR) imaging identified lesions characteristic of WE in 14 of 30 cases (47%).[40,43-45,47,48,57,58,66-70] Brainstem evoked potential was delayed in 2 of 4 cases.[60,61,76,79] Autopsy in 2 patients revealed brain changes in the periaqueductal gray matter,[86] mammillary bodies, and about the third ventricle, with capillary proliferations and relative sparing of neurons; consistent with WE.[34,86]

Clinical Outcomes

The clinical outcome was reported in 83 of 84 patients, after a median follow-up of 5 months (0-20). Outcomes ranged from complete recovery to death. Complete recovery was observed in 42 cases (51%), whereas 41 cases (49%) were considered to have had an incomplete recovery. Frequent sequelae were cognitive impairments (n = 16), gait difficulties (n = 13), and nystagmus (n = 7). Brain MR imaging repeated 3 to 28 days after thiamine treatment was initiated showed improvement in 5 of 5 cases.[44,45,47,69,70]

Incidence Trends

Of 84 WE cases undergoing systematic review, 45 (54%) were reported from the United States. The number of WE cases reported from this country increased during the years 2001 to 2007, when the annual number of bariatric surgical procedures increased steeply (Figure 4).

Figure 4. (click image to zoom) Reported cases of Wernicke encephalopathy after bariatric surgery (shown as dots, n = 45) and the number of bariatric procedures (solid line) in the United States. Procedure number estimates data were not available prior to 1992. Courtesy of American Society for Metabolic and Bariatric Surgery, Gainesville, FL.

Among the large bariatric surgery series identified, none reported the incidence of WE after gastric bypass or restrictive bariatric operations. However, 2 series from Southern Europe reported a combined total of 6 WE cases among 3241 patients undergoing biliopancreatic diversion,[18,30] corresponding to an estimated incidence of 19 WE cases per 10,000 procedures (95% confidence interval, 7-40). In one of these series, 3 WE cases were observed after 791 operations, but after starting administration of large doses of thiamine to patients reporting small food intakes during the early postoperative weeks, no WE cases were observed after the next 1450 operations[18] (P = 0.044, Fisher exact test).


This systematic review identified more than 100 reported patients with WE after elective bariatric surgical procedures. Most cases were complications of gastric bypass, the procedure most widely performed at present. The increasing use of bariatric surgery to induce weight loss is linked with an increasing number of patients at risk for WE and its associated potentially lasting neurologic impairments. WE is a medical emergency, yet it is readily preventable.

Predisposing Factors

Severe deficiency in thiamine is the cause of WE, which is most commonly associated with alcoholism.[87] Persistent vomiting leads to inadequate dietary intake of thiamine and is the dominating risk factor after obesity surgery. Pregnant women with hyperemesis may also develop WE.[6] Vomiting after any gastrointestinal surgical procedure might be caused by intestinal obstruction. In spite of this, results of upper endoscopy or gastrointestinal series were reported in less than half of patients in the present review. Glucose loading in patients with thiamine deficiency precipitates a focal lactic acidosis in the medial thalamus and thereby contributes to neuronal damage.[88] Parenteral feeding may have aggravated symptoms in as many as 18% of cases. The high proportion of women (82%) among the reported WE cases may simply mirror the proportion of women among patients undergoing bariatric surgery.[89]

Investigations and Treatment

Supplementary testing should never delay thiamine administration in patients with possible WE. Investigations may help to confirm WE and exclude other diseases, but cannot replace the clinical diagnosis. Although brain MR imaging is useful in verifying WE with a specificity of 93%, the low sensitivity of about 50% means that the diagnosis cannot be excluded based on a normal finding.[90] CT imaging is not useful in patients with suspected WE. Transketolase activity assays have some utility, but specific analysis of thiamine esters in blood might prove more useful: complete discrimination of WE patients and controls was reported for thiamine monophosphate, a dephosphorylation product of the coenzyme thiamine pyrophosphate.[91] However, evidence is sparse and thiamine assays have limited availability and usually do not allow for an immediate diagnosis.

WE may emerge with a variety of symptoms (Figure 3) and patients may thus initially present to physicians in a range of medical specialties. The challenge of making the diagnosis is underscored by the diagnostic delays observed in some patients.[39,51,73] A worse outcome may be expected in late-stage WE, which is associated with elevated spinal fluid protein levels and diffuse slowing of postsynaptic potentials on electroencephalography.[6] Only 2[47,54] of 16 patients with such findings had a complete recovery.[14,34,36,47,50,54,62,67,76,79]

There is insufficient evidence from controlled trials to guide clinicians in the dose, frequency, route, or duration of thiamine treatment in patients with suspected WE.[92] Recently suggested regimens include 500 mg thiamine intravenously 3 times daily for 3 days.[6,93] If the patient does not respond, treatment may be discontinued. In responders, parenteral thiamine should be given once daily for at least 5 more days. Oral supplementation may then be indicated, depending on the cause for thiamine deficiency.

Comparison With Previous Studies

Previous reports proposed that most cases of WE occurred between 4 and 12 weeks after bariatric surgery.[39,42,44,46,66,73] This systematic review demonstrates that a substantial proportion of cases occurred after this period (Figure 2). The present findings contrast those of a former review[94] in showing that about half of patients with WE after bariatric surgery may have lasting neurologic impairments. Furthermore, this review includes more than twice the number of cases that have previously been summarized.[94] Still, because only cases that were actually reported are included, the size of the problem is likely to be underestimated.[4] About 19% of patients may not present with the classic WE symptoms[6] and such potential cases[95,96] were not included. Also not included were patients with symptoms only from peripheral nerves,[97] which may be caused by moderate and prolonged nutrient deficiencies.[6] Damage to peripheral nerves may cause an incoordination of gait that clinically is difficult to discriminate from cerebellar ataxia. It is therefore notable that all cases with gait instability also had either eye movement abnormalities or mental status changes, indicating that each included case had encephalopathy.

The included patients’ succinct clinical features were largely consistent with the findings in 245 WE cases reported by Victor et al[87] In their series, horizontal nystagmus and ataxia were permanent in a majority of patients, and recovery from polyneuropathy was a slow process often lasting a year or longer. Deficits in memory and learning that remained after the acute confusion had cleared (Korsakoff syndrome) rarely resolved completely. Patients with such sequelae may need permanent institutional care. Formal neuropsychiatric assessment is sometimes useful in rehabilitation planning.

A system for reporting of cases has been suggested to estimate the incidence of WE in patients undergoing bariatric surgery.[94] The present findings indicate an incidence of about 1 in 500 patients after malabsorptive bariatric operations. This estimate may not be transferable to other bariatric operations and should be interpreted carefully because of the limited data set. The main limitation of this study is the nonsystematic data available from case reports, including a likely preferential reporting of positive findings. Also, WE had been diagnosed retrospectively in a few cases,[55,82] and because of the short follow-up in some of the reports, it is possible that additional patients eventually had a full recovery.


Printen and Mason observed in 1977 that, Even though surgery for obesity is well established we have not yet arrived at a point where we are aware of all the metabolic consequences (…) only meticulous postoperative observation will ensure that we recognize and treat these complications before irreversible damage has been done.[33] This remark holds true 30 years later. WE is caused by severe thiamine deficiency but there are few studies of thiamine status in bariatric surgery patients. One study identified a significant decrease in thiamine concentrations 6 weeks after gastric partitioning,[75] consistent with when WE typically presents (Figure 2). Further research is needed to determine appropriate supplementation and monitoring of thiamine status in patients undergoing current bariatric surgical operations.

The best treatment of WE is prophylaxis.[59] Patients must be instructed in proper eating patterns[33] and warned of nutritional risk factors such as repeated vomiting. Clinicians need to keep in mind that rapid weight loss may lead to nutritional deficiencies also in obese individuals and that behavioral disturbances or uncooperativeness could potentially be features of WE.[76] In particular, bariatric surgery training programs should include education on the possible nutritional complications of weight-loss operations. Thiamine administration is advisable in all patients readmitted or reporting frequent vomiting after a bariatric procedure as a simple, safe, inexpensive, and efficient preventive measure.


Wernicke encephalopathy is a medical emergency that may occur after any weight-loss operation, often leading to lasting disability. Nearly all reported cases presented after a few weeks of recurrent vomiting and within 6 months of surgery. Surgeons, allied health providers, and patients need to be aware of the predisposing factors and the clinical presentation to prevent and optimize the management of this condition.


The author has received lecture fees from Johnson & Johnson, but all honoraria were donated directly to charity so that he received neither income nor a tax deduction.

The author thanks Chantal Tallaksen, MD, PhD, Heidi Eggesbø, MD, PhD, and Thomas Bøhmer, MD, PhD, for their insightful comments on the manuscript; Karianne Hasledalen and Gyri Hval Straumann at Aker University Hospital Library for their excellent assistance in retrieving literature; and colleagues who supplied additional information regarding their reported cases or assisted in the translation of non-English reports.

Funding Information

Supported by a research fellowship grant from Eastern Norway Regional Health Authority.

Reprint Address

Erlend Tuseth Aasheim, Hormone Laboratory, Department of Endocrinology, Aker University Hospital, Trondheimsveien 235, 0514 Oslo, Norway;