Nutrition in Clinical Practice
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2012 27: 41 originally published online 4 January 2012Nutr Clin Pract
Krishnan Sriram, William Manzanares and Kimberly Joseph
Thiamine in Nutrition Therapy
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Nutrition in Clinical Practice
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Nutrition in Clinical Practice
Volume 27 Number 1
February 2012 41-50
© 2012 American Society
for Parenteral and Enteral Nutrition
Clinicians have traditionally concentrated on macronutrients
in nutrition therapy. For example, there is wide debate on the
actual caloric requirement of a critically ill patient or the
carbohydrate-to-fat ratios. The importance of micronutrients
is often neglected. The attitude that “one size fits all” is not
applicable to vitamin and trace element supplementation. The
practical use of micronutrient supplementation in nutrition
therapy in general has been recently reviewed.1 The present
review focuses on the specific role of thiamine (vitamin B1) in
nutrition therapy and in certain disease states, with a focus on
practical aspects of clinical management. Early suspicion and
recognition of thiamine deficiency are needed so that therapy
can be immediately initiated, as thiamine reserves are depleted
as early as 20 days of inadequate oral intake.2,3 A simple inex-
pensive treatment modality may make the difference between
life and death, thus avoiding unnecessary, invasive, and costly
investigations to determine the cause of the various hemody-
namic, neurologic, and metabolic manifestations of thiamine
deficiency. Preventive measures and treatment are both
The term beriberi is often associated with thiamine deficiency,
although the origin of the word is not clear. It has been sug-
gested that it might come from Sinhalese meaning “I cannot”
or from Arabic (“sailor’s asthma”). Carl Wernicke described the
eponymous syndrome—Wernicke encephalopathy (WE)—in
1881. However, it took many more decades to establish a rela-
tionship between consumption of milled or polished rice and
the development of beriberi due to thiamine deficiency in
humans.4 It was only after the 1950s that enrichment of rice and
other grains became common practice.
After the advent of nutrition therapy in the mid- to late 1970s,
thiamine deficiency was no longer a historic curiosity, especially
in developed countries. It began to be recognized during or after
nutrition therapy, both enteral and parenteral, even in patients
who were seemingly well nourished or overnourished and not
necessarily in the expected patient population—for example,
alcoholics.5 This was especially true when a high carbohydrate
intake is provided, as in parenteral nutrition with a high glucose
content.6 We now also speak of gastrointestinal beriberi and
bariatric beriberi, to be discussed later.
Thiamine in Nutrition Therapy
Krishnan Sriram, MBBS, FACS, FRCS(C)1; William Manzanares, MD, PhD2;
and Kimberly Joseph, MD, FACS, FCCM3
Clinicians involved with nutrition therapy traditionally concentrated on macronutrients and have generally neglected the importance of
micronutrients, both vitamins and trace elements. Micronutrients, which work in unison, are important for fundamental biological pro-
cesses and enzymatic reactions, and deficiencies may lead to disastrous consequences. This review concentrates on vitamin B1, or thia-
mine. Alcoholism is not the only risk factor for thiamine deficiency, and thiamine deficiency is often not suspected in seemingly
well-nourished or even overnourished patients. Deficiency of thiamine has historically been described as beriberi but may often be seen in
current-day practice, manifesting as neurologic abnormalities, mental changes, congestive heart failure, unexplained metabolic acidosis,
and so on. This review explains the importance of thiamine in nutrition therapy and offers practical tips on prevention and management
of deficiency states. (Nutr Clin Pract. 2012;27:41-50)
thiamine; vitamin B1; beriberi; metabolic acidosis; critical illness; micronutrients; enteral nutrition; parenteral nutrition; refeeding
syndrome; congestive heart failure
From 1Division of Surgical Critical Care, Department of Surgery, Stroger
Hospital of Cook County, Chicago, Illinois, 2Department of Critical
Care, Hospital de Clinicas (University Hospital), Faculty of Medicine,
Universidad de la Republica, Montevideo, Uruguay, 3Department of
Trauma, Stroger Hospital of Cook County, Chicago, Illinois
Financial disclosure: none declared.
Received for publication September 5, 2011; accepted for publication
September 16, 2011.
Corresponding Author: K. Sriram, Department of Surgery, Room 3350,
Stroger Hospital, 1901 West Harrison St, Chicago, IL 60612; e-mail:
42 Nutrition in Clinical Practice 27(1)
Absorption of Thiamine
Thiamine is rapidly absorbed in the jejunum and ileum by an
active, carrier-mediated, and rate-limited process, but at higher
concentrations, the uptake is by passive diffusion. However, the
clinical relevance of passive diffusion remains questionable.
The intestine is exposed to 2 sources of thiamine: a dietary
source and a bacterial source in which the vitamin is generated
by the normal intestinal microbiota.7,8 After hydrolysis of the
phosphorylated forms of thiamine in the intestinal lumen, free
thiamine enters the absorptive cells via a specialized sodium-
independent, pH-dependent, and amiloride-sensitive carrier-
mediated mechanism. Two thiamine intestinal transporters
have been indentified: the human thiamine transporter–1
(hTHTR-1; the product of SLC19A2 transporters) and the
hTHTR-2 (the product of SLC19A3). Both hTHTR-1 and
hTHTR-2 are expressed in the small and large intestines.7,9
However, hTHTR-1 shows its maximal expression in the liver,
followed in order by stomach, duodenum, jejunum, colon, and
The intestinal thiamine uptake process appears to be under
the regulation of an intracellular calcium/calmodulin mediated
pathway.7,8 Also, thiamine absorption is adaptively regulated
by the extracellular thiamine level. In fact, thiamine deficiency
was found to lead to an induction in intestinal carrier-mediated
uptake. This effect was associated with a significant induction
in the level of expression of THTR-2 (but not THTR-1).7
Furthermore, chronic alcohol use leads to thiamine defi-
ciency, and inhibition in intestinal thiamine absorption plays a
role in causing this deficiency. This inhibition was associated
with a marked decrease in the level of expression of THTR-1
(but not THTR-2). In addition, a similar mechanism of inhibi-
tion in thiamine uptake was demonstrated in kidneys. Thus,
chronic alcoholism is characterized by inhibition in the intesti-
nal absorption and in the reabsorption by the kidneys, which
determine a negative impact on the thiamine balance in the
In summary, current knowledge indicates that active
absorption of thiamine is the most important and significant.
Thiamine transport seems to be at different capacities along the
gastrointestinal tract: duodenum and jejunum > colon >
Following absorption, thiamine is initially phosphorylated to
thiamine diphosphate, also known as thiamine pyrophosphate
(TPP), by a specific enzyme: thiamine pyro(di)phosphokinase.
TPP is the active form involved in several enzyme functions
associated with metabolism of carbohydrates, lipids, and
branched chain amino acids. TPP is a cofactor for multiple steps
in the glycolysis and oxidative decarboxylation of carbohy-
drates.12,13 TPP is required as a coenzyme for the mitochondrial
enzyme complexes α-ketoglutarate dehydrogenase and pyru-
vate dehydrogenase. Therefore, TPP is required for the conver-
sion of pyruvate to acetyl CoA and entry to Krebs cycle, as well
as the conversion of α-ketoglutarate to succinyl CoA (Figure 1).
Both enzymes decrease its activity during thiamine deficiency
states, but in general α-ketoglutarate dehydrogenase is more
severely affected than the pyruvate dehydrogenase complex14
and is one of the earliest biochemical changes observed in thia-
mine deficiency.15 It is well known that TPP activates decarbox-
ylation of pyruvate dehydrogenase complex. This complex is a
group of enzymes and cofactors that form acetyl CoA, which
then condenses with oxaloacetate to form citrate, the first com-
ponent of the Krebs cycle.12 Thiamine’s important role in tricar-
boxylic acid cycle is explained in Figure 1.
Basically, thiamine is important for the conversion of
lactate to pyruvate; in its absence, lactic acid accumulates.
The acidosis is manifested both systemically and locally. An
example of focal damage due to lactic acidosis is its effect on
vulnerable brain structures (mamillary bodies and posterome-
dial thalamus) detectable by magnetic resonance imaging
scanning. Apoptotic cell death due to N-methyl-D-aspartate
toxicity is responsible for neurologic symptoms in thiamine
Another important enzyme requiring TPP is erythrocyte
transketolase, an enzyme of the pentose phosphate pathways.
The functions of this pathway are to provide pentose phos-
phate for nucleotide synthesis and to supply reduced nicotin-
amide adenine dinucleotide phosphate for various synthetic
Thiamine deficiency occurs due to poor oral intake, inadequate
provision of thiamine in enteral or parenteral nutrition therapy,
reduced gastrointestinal absorption due to disease or surgery,
or increased metabolic requirements. Increased gastrointesti-
nal or renal losses should also be considered. Often, multiple
factors exist, predisposing the patient to thiamine deficiency,
in addition to deficiencies of other micronutrients. Patients
with a history of alcoholism, AIDS, and malignancies form a
substantial group of patients in whom thiamine deficiency
should be suspected. Although thiamine deficiency is often
associated with alcohol abuse, it is being increasingly recog-
nized that it can occur in patients without this history. Preg-
nancy and lactation, hyperthyroidism, renal failure especially
on hemodialysis, systemic infections, advanced age, diabetes
mellitus, and any critical illness are other major risk factors.4
Obese patients, candidates for bariatric surgery, and postbariat-
ric surgery patients are not exempt from developing thiamine
deficiency even if routine multivitamin supplements are being
taken. Because of its short half-life and poor stores, a continu-
ous supply of thiamine is needed for optimal metabolism.
Thiamine in Nutrition Therapy / Sriram et al 43
Some of these specific conditions are discussed in further
detail in this review.
Serum thiamine level represents only a small portion of the
total body thiamine and is not a reliable indicator of thiamine
status.4 However, in clinical practice, serum and red blood cell
thiamine levels are the only tests that can be ordered and
obtained easily. A normal level does not exclude the diagnosis
of thiamine deficiency. Erythrocyte transketolase activation
assay, a functional test, is also mentioned in the literature.
However, the current preferred test is measurement of thia-
mine diphosphate in erythrocyte (ie, red blood cell) hemoly-
sates using high-performance liquid chromatography. It is
more reproducible than the other tests and suitable for research
and clinical purposes.17
Considering the expense of these sophisticated tests and the
delay in obtaining the results from a reference laboratory, the
clinician should depend on clinical judgment and initiate treat-
ment without waiting for a laboratory confirmation.
Additionally, serum tests normalize rapidly after thiamine
administration and must be obtained prior to treatment. We do
not recommend routine testing. A high index of suspicion
Figure 1. The glycolytic pathway and Krebs cycle pathways. TPP, thiamine pyrophosphate. Modified from Klooster A et al, Medical
Hypothesis 2007; 69:873-878, and used with permission from Elsevier Ltd, Oxford, UK.
44 Nutrition in Clinical Practice 27(1)
should result in immediate administration of thiamine—for
example, unexplained situations such as lactic acidosis (or
anion-gap metabolic acidosis) with or without compensatory
respiratory alkalosis,18 changes in sensorium, and congestive
heart failure (CHF).
Clinical Features of Thiamine Deficiency
Central and Peripheral Nervous System
The neurologic manifestations of thiamine deficiency have
recently been extensively reviewed by Kumar.4 Clinical mani-
festations are highly variable and involve the central and
peripheral nervous systems (Table 1). Some symptoms may be
permanent and not reversible even with thiamine administra-
tion. Although WE and Korsakoff psychosis have certain dis-
tinct clinical features, the term Wernicke-Korsakoff syndrome
is often used in clinical practice. Korsakoff psychosis may
sometimes be the initial presentation in some patients, or it
may be a sequel to WE.
The classic triad of WE includes ocular abnormalities (nys-
tagmus, partial or complete ophthalmoplegia, papillary abnor-
malities, fundoscopic changes, optic neuropathy), ataxic gait,
and mental status changes. These may occur occurring acutely
or subacutely.2 All components of the triad may not be seen.
Gait and trunk ataxia are due to vestibular and cerebellar
involvement. Various manifestations of peripheral neuropathy
occur. Rarer neurologic manifestations include seizures, myoc-
lonus and hypertonia, chorea, quadriparesis, and dyspha-
gia.19-22 Tinnitus and hearing loss have also been reported.23
Changes in mental status and sensorium are very often and
constantly seen in WE and include apathy, inability to concen-
trate, spatial disorientation, confusion, and even frank delir-
ium, psychosis, or coma.4,24 Thiamine deficiency must be
suspected in any patient, especially one in the intensive care
unit (ICU), with unexplained changes in sensorium or frank
About 80% of patients who initially survive WE end up with
psychosis. Wernicke-Korsakoff syndrome is an amnestic confab-
ulatory syndrome with severe amnesia and loss of recent and
working memory, while remote or reference memory is preserved.
The patient may appear to be alert and attentive with decent social
behavior and the ability to learn new skills. Some degree of
euphoria is seen. Kumar has described these features in detail in
his excellent review.4
The association between CHF and thiamine deficiency
is being recognized with increasing frequency even in present-
day practice, although wet beriberi was described decades
ago.25,26 Thiamine deficiency must be suspected and treated in
all cases of unexplained CHF. Thiamine deficiency is highly
prevalent among hospitalized patients with CHF and ranges
from 13%–93%.27-29 Several potential factors have been asso-
ciated with thiamine deficiency in CHF patients; among these,
alcoholism, loop diuretic use, malnutrition, advanced age, and
heart failure severity have been described.30 Among these
patients, those with New York Heart Association functional
class III/IV have a more severe deficiency than do class I/II
patients, and furosemide treatment has been shown to exacer-
bate this deficiency, increasing urinary excretion.31 Diuretics
are able to prevent reabsorption of thiamine and increase its
urinary excretion. Zenuk et al found a 98% prevalence of thia-
mine deficiency with furosemide therapy at doses > 80 mg/d.32
However, thiamine deficiency may occur with smaller dosages
of diuretics with long-term use.33 In 100 patients admitted to
the hospital with diagnosis of CHF, Hanninen et al showed that
thiamine deficiency was present in 33% of patients, compared
with 12% of controls (P = .007).31 In this study, thiamine defi-
ciency was associated with urine loss, nonuse of thiamine-
containing supplements, preadmission spironolactone use, and
preserved renal function. Nonetheless, according to multiple
logistic regression analysis, increased urinary thiamine loss
was the most important predictor of thiamine status among
CHF patients. According to these data, thiamine supplementa-
tion should be considered a routine practice in the treatment of
hospitalized CHF patients. In a study by Shimon et al, 30
patients with CHF who were receiving furosemide were given
either thiamine in a daily dose of 200 mg or placebo. The
authors observed a significantly improvement in left ventricu-
lar function, with an increase of 22% in excretion fraction.34
Furthermore, more research is warranted defining the safety
and efficacy of thiamine supplementation in the CHF popula-
tion. These studies should be capable of defining the effect of
thiamine supplementation on illness severity in CHF patients.
Table 1. Clinical Manifestations of Thiamine Deficiency
Organ SystemSigns and Symptoms
MucocutaneousMucosal and skin changes, glossitis,
Congestive heart failure
Unexplained metabolic acidosis
Sensorium Confusion, confabulation, spatial
disorientation, inability to concentrate,
psychosis, frank delirium, coma
Nystagmus, ophthalmoplegia, pupillary
abnormalities, optic neuropathy
Ataxia (extremities and truncal), other
Tinnitus, hearing loss
Myoclonus, hypertonia, chorea,
quadriparesis, dysphasia, seizures
Thiamine in Nutrition Therapy / Sriram et al 45
Cardiac surgery provides another example of systemic inflam-
matory response syndrome. It was recently shown that coronary
artery bypass graft surgery, a surrogate for critical illness and the
stressed states, depletes plasma thiamine levels.35 In this small
study, Donnino et al showed in 15 patients that plasma thiamine
levels significantly decrease from preoperative period to 24 hours
after surgery (mean difference, 10.14 mmol/L, P = .0004). These
results suggest that postoperative patients may require thiamine
supplementation. However, more studies are warranted to define
the need for routine thiamine supplementation after cardiac
Thiamine deficiency must always be considered in cases of
unexplained lactic acidosis.26,36,37 Thiamine deficiency is a rare
cause of lactic acidosis, but it should be considered in alcohol-
ism, patients receiving diuretics, total parenteral nutrition, or
chemotherapy.38,39 Lactic acidosis and the inability to utilize
the Krebs cycle are the major causes of dry beriberi and wet
beriberi, both manifestations of thiamine deficiency. Addition-
ally, an acute fulminant form of cardiac or wet beriberi known
as shoshin is characterized by cardiogenic shock, leading to
death in a short time.40 Also, lactic acidosis due to thiamine
deficiency is often associated with nausea, emesis, and severe
abdominal pain mimicking acute intestinal ischemia and may
result in unnecessary surgery. This syndrome is referred to as
Thiamine Deficiency in Specific Conditions
Thiamine in Pregnancy
Thiamine requirement in pregnancy is increased. Hyperemesis
gravidarum is especially a situation where thiamine deficiency
can rapidly occur. Diagnosis can be difficult as presentation
may be atypical. An elevation of transaminase levels suggest-
ing liver function abnormality may also be seen.42,43 A high
index of suspicion and prompt treatment even without confir-
matory tests results in resolution of symptoms.44 Pregnancy
after weight reduction following bariatric surgery is not
uncommon and is reported to be associated with a reduced
incidence of gestational diabetes.45 This is an additional reason
why surgical options are offered to the obese patient planning
to get pregnant. Thiamine deficiency should always be consid-
ered in the postbariatric surgery patient.
Thiamine in Critical Illness
More than 2 decades ago, Cruickshank et al showed, in a retro-
spective study on 158 patients admitted to the ICU, that thia-
mine deficiency was present in 20% of these patients. In
addition, among patients with thiamine deficiency, mortality
rate was significantly higher (72%) versus 50% of global
mortality.46 In 1999, Jamieson et al concluded that thiamine
deficiency at admission to the emergency room was present in
21% of patients.47 In a very interesting cohort study of 129
patients, Corcoran et al were unable to demonstrate any asso-
ciation between thiamine concentration and other vitamins
based on the APACHE II (Acute Physiology and Chronic
Health Evaluation II) score or the SOFA (Sequential Organ
Failure Assessment) score after admission to the ICU.48 More
recently, thiamine deficiency was recognized in critically ill
patients with severe sepsis, and low thiamine levels have been
associated with higher lactic acid levels in these patients even
in the absence of hepatic dysfunction.49 In critically ill chil-
dren, the incidence of low blood thiamine levels upon admis-
sion to ICU has been recently reported. In a Brazilian study,
Lima et al found that 28.2% of patients upon admission to
pediatric ICU had thiamine deficiency. In addition, low thia-
mine levels were not associated with malnutrition. However,
the authors found a C-reactive protein concentration greater
than 20 mg/dL as an independent risk factor for deficiency
(P = .02).50 These findings show that the magnitude of sys-
temic inflammation is a risk factor for thiamine deficiency
among critically ill children admitted to the ICU.
In burn patients, thiamine balance may be affected through
reduced intestinal absorption, increased losses, tissue redistri-
bution, and increased requirements.51 However, optimal nutri-
tion requirements for burn patients are still unknown. Falder et
al observed that thiamine supplementation is able to increase
serum thiamine levels and concomitantly decrease pyruvate
and lactate levels due to an increased utilization of pyruvate by
pyruvate dehydrogenase activity. Likewise, thiamine supple-
mentation showed a maximum benefit when its serum levels
reach a concentration of 40 ng/mL.51
Current guidelines suggest that thiamine supplementation at
daily dose of 100–300 mg should be provided during the first 3
days in the ICU in patients with possible thiamine deficiency
and especially when alcohol abuse is suspected (grade B).52
Thiamine in Refeeding Syndrome
Refeeding syndrome is a potentially life-threatening complica-
tion of refeeding in severely starved individuals. This syndrome
includes electrolyte abnormalities such as hypophosphatemia,
hypokalemia and hypomagnesaemia, heart failure, respiratory
failure, neurologic and musculoskeletal abnormalities, hemato-
logical and hepatic dysfunction, vitamins deficiency, and
death.53-55 Thiamine deficiency is often a component of refeed-
ing syndrome.56 Upon the introduction of carbohydrates, there
is a shift of metabolism from lipids to carbohydrates. In this
context, acute thiamine deficiency may be precipitated due to
increasing carbohydrate metabolism and consumption of thia-
mine during glycolysis, especially among patients suffering
from chronic alcoholism who usually have chronic thiamine
46 Nutrition in Clinical Practice 27(1)
deficiency.57 Prior to initiating nutrition therapy cautiously,
thiamine must be administered intravenously. It is likely that
thiamine may be one of the contributing factors leading to sud-
den death in refeeding syndrome. Current guidelines for pre-
vention of the refeeding syndrome suggest that adult patients at
high risk should receive thiamine 300 mg intravenously at least
30 minutes before starting nutrition therapy and then 200–300
mg daily intravenously or orally until day 3. Nonetheless, other
authors recommend continuing with a daily dose of 100 mg by
enteral route. In the pediatric population, thiamine should also
be replaced giving a daily dose of 10–25 mg during the first few
days and, thereafter, 5–10 mg/d for 1 month.58
Thiamine in Acute Renal Failure and Renal
Acute renal failure, or the preferred term, acute kidney injury,
and its treatment by continuous renal replacement therapy
(CRRT) are able to affect micronutrients status, including
water-soluble vitamins.59 Furthermore, adult patients with
chronic kidney disease requiring dialysis have shown poor
intake and negative balance of thiamine.60 Nevertheless,
Coveney et al compared serum levels of water-soluble vita-
mins in a group of extended- and conventional-hours hemodi-
alysis adult patients. The authors showed that thiamine levels
were lower in the extended group, although no cases of thia-
mine deficiency were reported.61 CRRT results in significant
losses and negative balance of thiamine and other micronutri-
ents, which contribute to thiamine deficiency. A prospective
study from Switzerland evaluated 19 sessions in 11 critically
ill patients and showed that the 24-hour balances were nega-
tive for thiamine (–4.12 mg, equivalent to 1.5 times the recom-
mended intake).62 These data suggest that usual thiamine
supplementation is not enough to substitute losses; hence, to
optimize carbohydrate metabolism in critically ill patients who
require CRRT, additional thiamine is needed. Current recom-
mendations suggest a daily dose of 100 mg for patients treated
Thiamine in Obese Patients and
Surgery for obesity is being performed with increasing fre-
quency, not only for weight loss, but also as a treatment option
for obese diabetic patients.65 Clinical and laboratory manifes-
tations of diabetes are resolved or improved and maintained
for more than 2 years.66 Many obese patients have deficiencies
of micronutrients, including thiamine, even prior to surgery.67
Thiamine deficiency after bariatric surgery is actually substan-
tially higher than previously recognized.68 This may occur as
early as 4 weeks after surgery, and a new term has been coined:
bariatric beriberi.69 Cerebral dysfunction due to thiamine defi-
ciency after gastric restrictive and/or malabsorptive weight
loss surgery occurs in 73.8% of cases.70
Micronutrient deficiencies in general after bariatric surgery
are more common after bypass procedures (eg, biliary-pancre-
atic diversion and Roux-en-Y gastrointestinal bypass) than
restrictive procedures (eg, gastric banding and sleeve gastrec-
tomy).71 This is true for thiamine deficiency too; thiamine lev-
els decrease more rapidly after bypass procedures than
Thiamine Deficiency in Parenteral Nutrition
Inadvertent nonadministration of thiamine during parenteral
nutrition is a serious and preventable situation. Several case
reports are available to emphasize that this is not an uncom-
mon occurrence, even with so many decades of experience in
parenteral nutrition.73,74 The importance of a nutrition support
team in the delivery of safe parenteral nutrition is emphasized.
The multivitamin admixture used must contain adequate
amounts of thiamine.
Thiamine Deficiency in Trauma
Little exists in the literature regarding the effects of thiamine
deficiency with respect to major trauma specifically. In 1988,
McConachie and Haskew looked at 5 previously healthy
patients who sustained significant trauma with Injury Severity
Score ≥ 12 requiring admission to the ICU.75 Each patient had
daily measurements of erythrocyte transketolase activity per-
formed as marker for thiamine status. In each patient, there
was a statistically significant biochemical deficiency noted but
no obvious clinical sequelae or attributable acidosis; wound
healing was not specifically commented on. All patients made
a full recovery from their illness. There is some suggestion that
thiamine administration may play a role in recovery from
trauma. A prospective, randomized, double-blinded, placebo-
controlled trial conducted by Berger et al included 102 patients
who were given supplemental selenium, zinc, vitamin C, and
thiamine, with double doses of the supplements on days 1 and
2.76 Although there was no difference in early organ dysfunc-
tion as measured by the acute kidney injury score, there was a
significant decrease in the inflammatory response noted in
both trauma and cardiac surgery patients. Also, in contrast to
the other studied groups, length of stay was noted to be shorter
in the surviving trauma patients who received supplementation
compared with controls. Supplemented trauma patients also
appeared to have better perceived health status based on SF-36
health survey data collected at 3-month follow-up. This study did
not separate out the effects of each supplement; thiamine,
although not an antioxidant per se, was believed to be an
important part of the supplement package due to its role as the
coenzyme of all carbohydrate decarboxylation reactions. How-
ever, an earlier study done with supplementing only vitamin C,
vitamin E, and selenium showed similar results with similar
limitations.77 It remains unclear how important a role thiamine
itself plays in recovery from major trauma; however, its
Thiamine in Nutrition Therapy / Sriram et al 47
requirement for transketolase activity in the pentose phosphate
pathway suggests that it likely has at least an indirect influence
on oxidative stress.
Thiamine, along with riboflavin and pyridoxine, contribute
to wound healing by functioning in antibody and leukocyte
cell formation and collagen synthesis. Alvarez and Gilbreath
demonstrated differences in lysyl oxidase activity and wound
breaking strength between rats fed a normal versus thiamine-
deficient diet in unwounded and wounded tissue.78 Thus,
maintaining thiamine levels is important for patients with trau-
matic and other surgical wounds.
Thiamine in Alcohol Withdrawal States
Thiamine replacement has long been a mainstay of therapy for
patients with suspected alcohol-related disease and for those
who are at risk for or are undergoing alcohol withdrawal.
Although a causal role of thiamine deficiency in delirium tre-
mens has largely been excluded,79 a number of neuropsychiat-
ric conditions common in alcoholic patients are directly
attributable to thiamine deficiency, including Wernicke-Korsa-
koff syndrome and peripheral neuropathy.80 Torvik et al looked
at postmortem findings in more than 500 alcoholic patients and
found that 12.5% had WE and 3.9% died as a direct result of
complications of the same.81
As noted, daily administration of thiamine is standard in
the care of patients with alcohol withdrawal syndrome; the
purpose of this is not to address the autonomic hyperactivity
often seen with the syndrome but rather to avoid the above-
mentioned complications of thiamine deficiency. The stan-
dard replacement dose is 50–100 mg, but there can be
significant variations in the amount required to treat active
WE.80 This may be due to the existence of different forms of
the apoenzyme of transketolase in different patients. As
implied elsewhere in this review, the problem may become
even more complex if critical illness, infection, and/or the
need for renal replacement therapy is superimposed on the
situation of a patient with alcohol-related comorbidity. In such
cases, the standard replacement doses of thiamine may be
inadequate to counter the deficits. Other metabolic concerns
may manifest as well. In a study that looked at glucose regula-
tion in infected rats,82the authors found that thiamine-deficient
animals exposed to endotoxin not only had decreased dietary
intake but also had increased hyperlacticacidemia and a
decrease in the expected rise of serum glucose expected with
infection. Although they could not say why with certainty,
they suspected that this might be due to the inability of pyru-
vate and lactate to enter gluconeogenesis. This impaired glu-
cose response may have implications for chronically
malnourished alcoholic patients who develop gram-negative
A recent review by Zahr et al discusses in detail the clinical
and alcohol-related damage to the brain.83
Table 2 summarizes our dosage recommendations based on
several sources and clinical experience. There are wide varia-
tions in the dosages suggested; however, thiamine is safe to
administer. The recommended daily allowance for thiamine is
only 1.1–1.2 mg.84 This, however, is for oral or enteral admin-
istration. Parenteral multivitamin products usually contain
3.0–3.5 mg. Enteral formulas contain 2.2–2.9 mg per 1500
kcal/d of feed. The European Community directive for enteral
nutrition suggests a thiamine minimum daily dose of 1.2 mg
and a maximum dose of 10 mg.85 The exact requirement of
thiamine in critical illness is not known, a fact that is true for
most micronutrients. However, it is generally believed that
thiamine requirements increase in critical illness.86
In the prevention or treatment of WE, thiamine hydrochlo-
ride is formally indicated and supported by guidelines.87 Current
guidelines suggest that thiamine is indicated for the treatment of
suspected or manifest WE (level C). However, there is no evi-
dence to recommend the best dosage, route of administration,
and treatment time. Although it has been the practice to admin-
ister thiamine parenterally in dosages of 100 mg 3 times a day,
more recent guidelines recommend that thiamine should be
given intravenously 200 mg 3 times daily (level C).87 In all cases
of WE, thiamine should be given before feeding, and standard
diet should be started only after thiamine supplementation. After
clinical improvement, the oral route is used with varying dosage
recommendations, usually 50–100 mg per day.
The safety of thiamine is very good, regardless of route of
administration (level B). In a retrospective analysis on adverse
events due to thiamine supplementation, Wren et al have
not identified serious side effects in more than 300,000
Table 2. Thiamine Dosage Recommendations
Usual enteral formula
Suggested range for enteral
At risk for deficiency
High suspicion or proven
Maintenance dose in proven
2.2–2.9 mg per 1500 kcal/d
100 mg, 3 times a day, parenteral
200 mg, 3 times a day, parenteral
50–100 mg by mouth daily
300 mg intravenously before
initiating nutrition therapy,
200–300 mg intravenously daily
for at least 3 more days
100 mg daily Renal replacement
48 Nutrition in Clinical Practice 27(1)
treatments.88 Anaphylactoid reactions may occur with doses >
400 mg given parenterally. Other symptoms and signs of
overdosage include nausea, lethargy, ataxia, and diminution of
We have highlighted the various clinical scenarios where thia-
mine deficiency should be suspected. Treatment should be ini-
tiated before laboratory confirmation, which is not always
needed. Workup for other causes of the various manifestations
of thiamine deficiency can be avoided in most cases. Early sus-
picion, recognition, and treatment are very important as some
neurologic manifestations may become permanent. Wherever
possible, such as in postbariatric surgery patients, preventive
measures must be taken. Clinicians are encouraged to not only
evaluate the macronutrient requirement of patients but also be
aware of the crucial role that micronutrients play in enteral and
parenteral nutritional therapy.
Based on clinical experience and practice, we recom-
mend that thiamine be administered under the following
• Mucocutaneous changes suggestive of thiamine or
other vitamin deficiencies
• History of excessive alcohol intake
• At risk of refeeding syndrome (cachexia, malignan-
cies, chronic malnutrition)
• Sensorium changes or delirium, especially in ICUs
• Unexplained CHF
• Unexplained metabolic acidosis
• Renal replacement therapy
The services of Shyam K. Sriram, MA, for proofing and copy
editing is gratefully acknowledged.
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