Nutrition in Clinical Practice
Volume 00 Number 0
xxxx 2019 1–7
C2019 American Society for
Parenteral and Enteral Nutrition
Role of Thiamin in Health and Disease
Bertha F. Polegato, MD, PhD ; Amanda G. Pereira, MS; Paula S. Azevedo, MD,
PhD; Nara A. Costa, PhD; Leonardo A. M. Zornoff, MD, PhD;
Sergio A. R. Paiva, MD, PhD; and Marcos F. Minicucci, MD, PhD
Thiamin is a hydrosoluble vitamin that plays a role in several biological processes, mainly in glucose metabolism. There are several
risk factors for developing thiamin deciency, such as malnutrition, refeeding syndrome, gastrointestinal surgery, and alcoholism.
Recently, the role of thiamin in critically ill patients has gained prominence, and the prevalence of thiamin deciency was found to
be increased in patients with severe burns, major surgery, septic shock, end-stage renal disease, and heart failure. In adults, thiamin
deciency presents as encephalopathy, dry beriberi (with neurological signs and symptoms), or wet beriberi (with cardiovascular
signs and symptoms). Thiamin deciency can be diagnosed clinically, and all clinicians should be aware of this disease, especially
in patients with risk factors for thiamin deciency. Thiamin supplementation should be started as early as possible in patients
suspected to have thiamin deciency. Treatment is safe, inexpensive, simple, and life-saving. Diagnosis is conrmed on a positive
response to treatment. (Nutr Clin Pract. 2019;00:1–7)
beriberi; Korsakoff syndrome; thiamin; thiamin deciency; Wernicke encephalopathy
Thiamin: Function and Sources
Thiamin, also called vitamin B1, plays a role in several
biological processes and is therefore an important vitamin
for the body. The deciency of this vitamin is a critical
issue because it is still underdiagnosed and is associated
with high morbidity and mortality. Mortality rates close
to 20% have been observed in untreated or inadequately
treated patients, and up to 85% of survivors can develop
an irreversible neurological condition.1,2 Although access
to food is easier nowadays, micronutrient deciency is
widespread in industrialized and developing nations.
One of thiamin’s primary functions is acting as a
cofactor of enzymes involved in generating energy and
in the metabolism of glucose, such as the pyruvate de-
hydrogenase complex, transketolase, and α-ketoglutarate
dehydrogenase.3,4 Consequently, thiamin deciency leads
to decreased activity of these enzymes, reduction of pyru-
vate oxidation, and lactate accumulation in the brain and
blood. All of these features are accompanied by decreased
production of adenosine triphosphate. Lactate accumula-
tion leads to lactic acidosis, and the decrease in pH of
the brain can contribute to the onset of the neurological
manifestations that accompany thiamin deciency.5,6 In
addition, a reduction in enzyme activity leads to a decrease
in the synthesis of neurotransmitters, such as acetylcholine
and γ-aminobutyric acid, which may further worsen brain
function (Figure 1).5,7,8
Because our bodies do not synthesize thiamin, our
thiamin needs must be met through diet. There are several
dietary sources of thiamin: meat (especially lean cuts of
pork), yeasts, grains, cereals, and other products of plant
origin.9,10 Thiamin is present in plant products, almost in
its entirety, in phosphorylated form as thiamin diphosphate
ester (also called thiamin pyrophosphate), which is the
active form of the vitamin.11,12 Among vegetables, the main
sources of thiamin are legumes, including peas, lentils, and
potatoes. Despite this, the prolonged cooking of vegetables,
mainly in water, can considerably diminish the availability
of thiamin because it is thermosensitive and hydrosoluble.7
Diets based on polished rice are a risk factor for thiamin
deciency because it is a poor source of thiamin.13
Some factors interfere signicantly with thiamin absorp-
tion, such as the type of food processing, alcohol intake,
From the Internal Medicine Department, Medical School, S˜
State University (Unesp), Botucatu, S˜
ao Paulo, Brazil.
Financial disclosure: None declared.
Conicts of interest: None declared.
This article originally appeared online on xxxx 0, 2018.
Bertha F. Polegato, Internal Medicine Department, Botucatu Medical
ao Paulo State University (Unesp), Av. Prof. M´
aes Montenegro, s/n, UNESP – Campus de Botucatu, S ˜
Paulo 18618687, Brazil.
2Nutrition in Clinical Practice 00(0)
Figure 1. (A) Thiamin functions. Thiamin serves as a cofactor for enzymatic activity of transketolase, α-ketoglutarate
dehydrogenase, and pyruvate dehydrogenase complex. Thiamin participates in glucose metabolism, energy generation, and
synthesis of nucleic acids. In thiamin deciency status (B), activity of these enzymes is decreased. Consequently, there is a
reduction of pyruvate oxidation and lactate accumulation and a decrease in pH and acidosis (in the brain and blood). Decreased
pyruvate dehydrogenase complex and α-ketoglutarate dehydrogenase activity interfere with Krebs cycle and impair ATP
generation. Additionally, myelin sheaths are damaged, leading to neurological decits. ATP, adenosine triphosphate; acetyl CoA,
acetyl coenzyme A; I, complex I of mitochondrial respiratory chain; II, complex II of mitochondrial respiratory chain; III,
complex III of mitochondrial respiratory chain; IV, complex IV of mitochondrial respiratory chain; V, ATP synthase.
protein and folate nutrition level, and the presence of
antithiaminic factors in the diet.14-17 Intake of raw foods
with high thiaminase content (such as crustaceans, sprouts,
microorganisms, and some sh) can contribute or even
be the direct cause of thiamin deciency.16,18 Thiaminase
is also thermolabile, and the act of cooking these foods
considerably reduces the risk of thiamin deciency.9,15 In
addition, ingestion of beverages such as coffee, tea, and
other beverages rich in tannins also contributes to thiamin
deciency.9,19 On the other hand, ingestion of juices from
citrus fruits increases the bioavailability of thiamin because
of their citric acid and ascorbic acid content.20,21
Thiamin absorption from the diet occurs throughout the
small intestine, especially in the jejunum, depending on the
pH of the medium.11,22 The absorption is severely decreased
in the presence of alkaline pH, and it occurs in passive
and active forms. Passive absorption occurs when there are
large amounts of thiamin in the intestinal lumen, whereas
Polegato et al 3
active absorption occurs when thiamin is present in small
amounts.5,7 Alcoholism is one of the most important factors
leading to decreased absorption of thiamin because alcohol
inhibits the active transport of the vitamin by up to 50%,
even in patients with good nutrition status.7,23
The daily needs of thiamin vary according to sex and age
group; for adults, the recommendation is about 1.1–1.2 mg
per day and 1.4 mg per day for pregnant women.7,22 For
comparison, 100 g of pork provides about 1 mg of thiamin,
1 cup of cereals provides around 2 mg, and 1 cup of cooked
peas provides about 0.8 mg of thiamin.9Ingesting quantities
much larger than these recommended ones, whether from
dietary sources or oral supplementation, usually does not
cause any side effects.11
Risk Factors for Thiamin Deciency
All patients with malnutrition or nutrition risk are potential
candidates for thiamin deciency, regardless of the etiology
of malnutrition. In addition, malnourished patients or
patients in prolonged fasting who will be articially fed
may develop refeeding syndrome.24,25 During refeeding, the
increased supply of glucose leads to increased secretion
of insulin and decreased secretion of glucagon, thereby
stimulating the synthesis of glycogen, fats, and proteins,
with a consequent inux of phosphate, potassium, and mag-
nesium into the intracellular medium, whereas serum con-
centrations are markedly diminished.26,27 In addition, with
glucose now available because of refeeding, the metabolism
increases with consequent depletion of thiamin, which
serves as a cofactor of enzymatic reactions.28,29
Causes of thiamin deciency include the use of the
diuretic furosemide, the presence of chronic kidney disease
on hemodialysis, diabetes mellitus with increased urinary
excretion of thiamin, malignant neoplasms, acquired im-
munodeciency syndrome, hyperemesis gravidarum, and
diseases and surgeries of the gastrointestinal tract, including
bariatric surgery.1,7,9,30 Bariatric surgeries increase the risk
of thiamin deciency through several mechanisms, includ-
ing lower vitamin intake, higher prevalence of postoperative
vomiting, and impaired absorption, mainly in patients who
have undergone Roux-en-Y gastric bypass surgery. In these
patients, the bypass of the small intestine, the preferred
location for thiamin absorption, and bacterial overgrowth
are important causes of thiamin deciency.31-33 In addition,
obesity alone can increase risk of thiamin deciency. In
general, these patients consume a diet poor in vegetables
and rich in simple sugars and processed foods, which is a
low source of thiamin.9,19
The main and most important risk factor for thiamin
deciency is alcoholism.19,22 There are several mechanisms
associated with alcohol intake and thiamin deciency. One
is the decrease in thiamin absorption in the small intestine,
which is already mentioned above. Another reason is that
alcohol intake causes decreased caloric intake from sources
other than alcohol and thus reduces the supply of thiamin
from the diet.34,35 In addition, liver cirrhosis, a complication
of chronic alcoholism, also leads to a decreased supply
of thiamin to the liver.7Postmortem studies have shown
that the prevalence of Wernicke’s encephalopathy, one of
the clinical features of thiamin deciency, among patients
with alcoholism varies from 12.5% to 35%, whereas the
prevalence of this encephalopathy in the general population
Recently, the role of thiamin in critically ill patients has
gained much attention. It is known that patients with septic
shock, severe burns, recent cardiac surgery, and renal failure
present with lower serum thiamin levels.40,41 In addition,
thiamin deciency in patients with septic shock admitted to
the intensive care unit can reach up to 70%.42 It is not known
exactly when, how, or if thiamin should be replaced for
critically ill patients in the absence of clinical deciency, but
new evidence is emerging. In patients with septic shock, the
administration of thiamin in the subgroup of patients with
a deciency of the vitamin led to a reduction in mortality.43
However, thiamin replacement in patients who underwent
myocardial revascularization surgery did not change clinical
outcomes such as postoperative serum lactate concentration
or the number of hospitalization days.44 Box 1 summarizes
the risk factors for thiamin deciency.
Box 1. Risk Factors for Thiamin Deciency
Other gastrointestinal tract surgery
Chronic kidney disease on hemodialysis
Polished rice-based diet
Acquired immunodeciency syndrome
The 2 classical clinical forms of thiamin deciency are
Wernicke-Korsakoff syndrome45 and beriberi; the latter can
be classied as wet beriberi, dry beriberi,46 and infantile
beriberi. This article does not include discussion on infantile
beriberi. Box 2 shows the main clinical manifestations of
4Nutrition in Clinical Practice 00(0)
Box 2. Clinical Manifestation of Thiamin
Ocular signs such as nystagmus and ophthalmoplegia1
Loss of short-term memory2
Weakness of the lower limbs
Peripheral symmetric sensory-motor polyneuropathy
Tac hy cardi a
Increased cardiac chambers
Heart failure plus:
Decreased cardiac output
Increased lactate levels
1Classical triad of Wernicke encephalopathy.
2Korsakoff syndrome symptoms.
Wernicke-Korsakoff syndrome presents 2 clinical foci:
Wernicke’s encephalopathy and Korsakoff’s syndrome, of-
ten referred to in conjunction as Wernicke-Korsakoff
syndrome.47 Wernicke’s encephalopathy manifests as ataxia,
mental confusion, and abnormal ocular signs such as
nystagmus and ophthalmoplegia.48,49 However, this triad
is present in only a small portion of patients, which can
hinder the diagnosis.1,50 The presence of only 1 of the
events described in the classic triad and of at least 1 risk
factor for deciency should raise diagnostic suspicion.2
Together with the classical clinical condition, the presence
of other neurological symptoms such as irritability, seizures,
paresthesias, papilledema, and even coma is not rare.1
Because thiamin deciency is a disease whose diagnosis is
based solely on clinical ndings, in almost all cases, it is
essential to rule out other diagnoses. Imaging studies are
therefore crucial in such cases. Computed tomography scans
of the brain are usually normal, but magnetic resonance
imaging, although not very sensitive, provides very specic
ndings of the disease, such as bilateral and symmetrical T2
signal increase in the thalamus, hypothalamus, oor of the
fourth ventricle, mamillary bodies, and the midline of the
Wernicke’s encephalopathy occurs or is even accompa-
nied by Korsakoff’s syndrome in 80% of patients, mainly
when thiamin deciency is not treated properly.1Although
rare, Korsakoff’s syndrome might not be accompanied by
Wernicke’s encephalopathy. It is characterized by chronic,
persistent, and severe loss of short-term memory, and
confabulation may be present, especially at the beginning
of the clinical picture. Temporospatial disorientation and
mood changes can also be present.51 In general, the motor
functions are preserved.
Korsakoff’s syndrome is a differential diagnosis of
patients with dementia. However, the diagnosis of this
syndrome is often neglected, leading to treatment delay and
permanent decits. Despite the lack of uniform response,
the early identication and treatment of Korsakoff’s
syndrome can change the outcomes of these patients.1
Regarding beriberi, the dry form is characterized by
peripheral polyneuropathy, which is predominantly distal,
related to sensory-motor, and symmetrical.10,33 The onset
of the condition is usually not acute, and patients typically
mention weakness of the lower limbs. Some cases may
have a quicker onset and mimic other paresthesias, such as
e syndrome.52,53 Most patients show a good
response to thiamin replacement.54
Wet beriberi presents as congestive high-output heart
failure.55 The exact mechanisms by which thiamin deciency
leads to heart failure are not yet completely understood, but
it is believed that the energy decit in the myocardium that is
due to the decreased enzyme activity may play an important
role.56,57 In addition, thiamin deciency causes peripheral
vasodilation, decreased organ perfusion, and subsequent
retention of sodium and water, which may generate a
hypervolemic state and a consequent increase in peripheral
venous pressure and edema.55
The diagnosis of wet beriberi is made for patients who
meet all of the following criteria: 1) increased cardiac
chambers in echocardiography study, 2) edema, 3) high
central venous pressure, 4) peripheral polyneuropathy, 5)
absence of another cause of heart failure, 6) history of con-
sumption of a thiamin-decient diet for at least 3 months,
and 7) improved symptoms and decreased cardiac chambers
in response to thiamin supplementation. In addition, pa-
tients may show tachycardia, increased serum troponin, and
acidosis.58-60 In some cases, heart failure may be followed
by decreased cardiac output and shock. Hemodynamic
deterioration is accompanied by markedly increased lactate
levels and acidosis.59,61 This form of wet beriberi is the
most severe and is known as Shoshin beriberi (from the
Japa nese sho =acute, shin =heart). These patients need
to be diagnosed quickly because the disease could progress
to death in a short time.62,63 In these patients, atypical
Polegato et al 5
clinical presentations are observed, including pulmonary
hypertension and right ventricular failure.64
The complementary examinations conducted to evaluate
patients with suspected wet beriberi are the same as those
used to investigate other diseases that cause heart failure, in-
cluding blood biochemical analysis, chest x-ray, electrocar-
diogram, and echocardiography.65 These examinations are
useful for the identication of cardiac hypertrophy caused
by beriberi and the exclusion of other causes of heart failure.
The various clinical forms of thiamin deciency can
occur in isolation or in a concomitant way in the same
patient,60 depending on the cause of deciency, age of the
patient, presence of other comorbidities, genetic suscep-
tibility, degree of deciency, and speed of onset. Asians
tend to manifest thiamin deciency most often as wet
beriberi, whereas Europeans tend to develop dry beriberi
and Wernicke’s encephalopathy.1In addition, severe thiamin
deciency with rapid onset usually leads to Wernicke’s
encephalopathy, whereas mild to moderate deciency with
slow and prolonged onset tends to evolve into peripheral
The concentration of thiamin in the blood is not an appro-
priate parameter to evaluate the body supply of thiamin.10
The best approach to determine the thiamin nutrition status
of an individual would be through indirect methods, such
as the evaluation of transketolase activity in erythrocytes
or the determination of concentration of thiamin diphos-
phate ester in erythrocytes through high-performance liquid
chromatography.7,66 However, these methods are expensive
and rarely available in clinical practice, and the diagnosis
is usually made based on the clinical condition of the
patient and satisfactory response to the therapeutic test.2
Therefore, it is very important for the clinicians to keep a
high suspicion and to be aware of the signs and symptoms
of thiamin deciency, especially in patients with risk factors
Misdiagnosis can often occur in the emergency room,
where the patient needs to be cared for quickly and the
clinical history taken, in general, is quite concise. Some
signs and symptoms of thiamin deciency are sometimes
confused with those of the patient’s underlying disease,
where the decits observed can be wrongly attributed, for
example, to alcoholism or to heart failure itself.60
Treatment regimens reported in the literature vary widely
and depend on the cause of thiamin deciency and the
clinical manifestations of the patients. For the treatment of
Wernicke-Korsakoff syndrome in patients with alcoholism,
thiamin deciency should be treated with 500 to 1500 mg
per day, 2 or 3 doses, through intramuscular injection or
intravenous route for 5 days. After this initial period, the
recommendation is an oral dose of 300 mg per day for
1–2 weeks, followed by 100 mg daily for maintenance.2,67
Some authors recommend that thiamin replacement with
high doses intravenously should be maintained for longer
periods of up to 2 months.50 However, most recommen-
dations suggest initial parenteral replacement periods of
up to 1 week or until symptoms improve. After starting
replacement, the ocular manifestations and ataxia usually
regress within hours or days, but mental confusion can take
2 or 3 weeks to improve.1
It is important that the initial thiamin replacement be
parenteral because these patients have a signicant decit of
thiamin absorption. In addition, patients with alcoholism,
even without clinical deciency, should always receive thi-
amin before any replacement of glucose because the supply
of glucose can increase the need for thiamin in a patient who
often has a small reserve of the vitamin and thus precipitates
the emergence of exuberant clinical deciency.67,68
Patients without alcoholism who have a diagnosis of
Wernicke-Korsakoff syndrome require lower doses of thi-
amin than patients with alcoholism, with doses of 100–
300 mg per day being enough to obtain clinical response,
but there is also need for parenteral replacement in the
Treatment of wet beriberi includes thiamin supplemen-
tation accompanied by hemodynamic support. The rec-
ommended dose used for the treatment of wet beriberi is
usually small and may be provided orally. Overall, doses of
100–300 mg per day are enough to improve symptoms.7In
Shoshin beriberi, when patients are severely ill, parenteral
administration may be recommended for initial treatment,
followed by oral administration.61,64 Some authors recom-
mend a high dose of thiamin,69 but most suggest 100–
300 mg per day in these cases. Thiamin replacement should
be maintained for an extended period and until the risk
factor for thiamin deciency is removed.
Thiamin supplementation is also indicated for the pre-
vention and treatment of refeeding syndrome, with the
recommended oral dose of 100–300 mg per day. Thiamin
replacement must be started concomitantly to the refeed-
ing of patients at risk of developing the syndrome and
maintained for 10 days after refeeding begins.7,28
Oral ingestion of quantities larger than those recom-
mended usually does not cause any side effects. However,
the parenteral administration of thiamin for therapeutic
purposes can cause severe complications such as anaphy-
laxis and cardiopulmonary arrest, although the frequency
of these events is rare.1,7 Parenteral thiamin must be diluted
in 100 mL of saline solution and infused over 30 minutes
to decrease the risk of side effects. Ideally, every patient
receiving thiamin intravenously should be monitored by a
healthcare team with access to resuscitation facilities during
the infusion of medication; however, the absence of such
6Nutrition in Clinical Practice 00(0)
a team should not delay the administration of the vitamin
because of the high potential of developing disability in the
case of severe deciency.
Thiamin replacement in other patient groups, such as in
critically ill patients with an absence of diagnosed deciency,
is still controversial. Although some authors recommend
prophylactic supplementation in these situations, scientic
evidence for this practice has not been established.57
The exact prevalence of thiamin deciency is unknown.
However, autopsy studies have reported higher prevalence
of thiamin deciency than clinical studies, which suggests
that the disease is underdiagnosed.1More risk factors
for thiamin deciency have now been recognized, and the
disease has been diagnosed in patients without classical
risk factors, such as in critically ill patients.40 In addition,
patients may have a subclinical thiamin deciency, and most
of these cases are not currently treated.
It is essential to prioritize research on thiamin deciency.
It is also important to identify easier methods to diagnose
thiamin deciency or to improve those already available in
order to simplify their methods, reduce costs, and increase
their availability. Although there are not efcient ways
to make the diagnosis, clinicians must maintain a high
suspicion of the disease and treat patients promptly if a
diagnosis is suspected. The treatment is inexpensive, simple,
Statement of Authorship
L. A. M. Zornoff, S. A. R. Paiva, and M. F. Minicucci
equally contributed to the conception and design of the
research; P. S. Azevedo contributed to the design of the
research; B. F. Polegato, A. G. Pereira, and N. A. Costa
contributed to the acquisition and analysis of the data;
Azevedo contributed to the interpretation of the data; and
B. F. Polegato, A. G. Pereira, and N. A. Costa drafted the
manuscript. All authors critically revised the manuscript,
agree to be fully accountable for ensuring the integrity and
accuracy of the work, and read and approved the nal
1. Sechi G, Serra A. Wernicke’s encephalopathy: new clinical settings
and recent advances in diagnosis and management. Lancet Neurol.
2. Latt N, Dore G. Thiamine in the treatment of Wernicke encephalopa-
thy in patients with alcohol use disorders. Intern Med J. 2014;44(9):
3. Wooley JA. Characteristics of thiamin and its relevance to the manage-
ment of heart failure. Nutr Clin Pract. 2008;23(5):487-493.
4. Sica DA. Loop diuretic therapy, thiamine balance, and heart failure.
Congest Heart Fail. 2007;13(4):244-247.
5. Manzetti S, Zhang J, van der Spoel D. Thiamin function, metabolism,
uptake, and transport. Biochemistry. 2014;53(5):821-835.
6. Abdou E, Hazell AS. Thiamine deciency: an update of pathophysi-
ologic mechanisms and future therapeutic considerations. Neurochem
7. Frank LL. Thiamin in clinical practice. JPEN J Parenter Enteral Nutr.
8. Fernandes LMP, Bezerra FR, Monteiro MC, et al. Thiamine de-
ciency, oxidative metabolic pathways and ethanol-induced neurotox-
icity: how poor nutrition contributes to the alcoholic syndrome, as
Marchiafava-Bignami disease. Eur J Clin Nutr. 2017;71(5):580-586.
9. Kerns JC, Arundel C, Chawla LS. Thiamin deciency in people with
obesity. Adv Nutr. 2015;6(2):147-153.
10. WHO | Thiamine deciency and its prevention and control in ma-
jor emergencies. WHO. Available at: http://www.who.int/nutrition/
publications/emergencies/WHO_NHD_99.13/en/. Accessed April 12,
11. Brown G. Defects of thiamine transport and metabolism. J Inherit
Metab Dis. 2014;37(4):577-585.
12. Amrein K, Oudemans-van Straaten HM, Berger MM. Vitamin therapy
in critically ill patients: focus on thiamine, vitamin C, and vitamin D.
Intensive Care Med. 2018;44(11):1940-1944.
13. Dong W, Thomas N, Ronald PC, Goyer A. Overexpression of thiamin
biosynthesis genes in rice increases leaf and unpolished grain thiamin
content but not resistance to xanthomonas oryzae pv. oryzae. Front
Plant Sci. 2016;7:1-11.
14. Said HM. Intestinal absorption of water-soluble vitamins in health and
disease. Biochem J. 2011;437(3):357-372.
15. Vernau K, Napoli E, Wong S, et al. Thiamine deciency-mediated
brain mitochondrial pathology in Alaskan Huskies with mutation in
SLC19A3.1. Brain Pathol. 2015;25(4):441-453.
16. Croft L, Napoli E, Hung CK, et al. Clinical evaluation and biochemical
analyses of thiamine deciency in Pacic harbor seals (Phoca vitulina)
maintained at a zoological facility. J Am Vet Med Assoc. 2013;243(8):
17. Leevy CM. Thiamin deciency and alcoholism. Ann N Y Acad Sci.
18. Noble S, Saxena V, Ekker M, Devlin R. Expression of thiaminase
in Zebrash (Danio rerio) is lethal and has implications for use as
a biocontainment strategy in aquaculture and invasive species. Mar
19. Nath A, Tran T, Shope TR, Koch TR. Prevalence of clinical thiamine
deciency in individuals with medically complicated obesity. Nutr Res.
20. Tanphaichitr V. Thiamin. In: Shills ME. Olson JA, Shike M, eds.
Modern Nutrition in Health and Disease. 8th ed. Philadelphia, PA: Lea
& Febiger, 1994;359-365.
21. Tanphaichitr V, Wood B. Thiamin. In: Olson RE, Broquist HP,
Chichester CO, et al., eds. Present Knowledge in Nutrition.5thed.
Washington, DC: Nutrition Foundation, 1984;274-284.
22. Crook MA, Sriram K. Thiamine deciency: the importance of recog-
nition and prompt management. Nutrition. 2014;30(7-8):953-954.
23. Sriram K, Manzanares W, Joseph K. Thiamine in nutrition therapy.
Nutr Clin Pract. 2012;27(1):41-50.
24. Koekkoek KWAC, van Zanten ARH. Nutrition in the ICU: new trends
versus old-fashioned standard enteral feeding? Curr Opin Anaesthesiol.
25. Crook MA, Hally V, Panteli JV. The importance of the refeeding
syndrome. Nutrition. 2001;17(2):632-637.
26. Maiorana A, Vergine G, Coletti V, et al. Acute thiamine deciency
and refeeding syndrome: similar ndings but different pathogenesis.
27. Kawamura H, Tanaka S, Uenami Y, et al. Hypophosphatemia occurs
with insulin administration during refeeding by total parenteral nutri-
tion in rats. J Med Invest. 2018;65(1.2):50-55.
Polegato et al 7
28. Mehanna HM, Moledina J, Travis J. Refeeding syndrome: what it is,
and how to prevent and treat it. BMJ. 2008;336(7659):1495-1498.
29. Collie JTB, Greaves RF, Jones OAH, Lam Q, Eastwood GM, Bellomo
R. Vitamin B1 in critically ill patients: needs and challenges. Clin Chem
Lab Med. 2017;55(11):1652-1668.
30. Mallat J, Lemyze M, Thevenin D. Do not forget to give thiamine to
your septic shock patient!. J Thorac Dis. 2016;8(6):1062-1066.
31. Aasheim ET. Wernicke encephalopathy after bariatric surgery: a sys-
tematic review. Ann Surg. 2008;248(5):714-720.
32. Pellitero S, Mart´
ınez E, Puig R, et al. Evaluation of vitamin and trace
element requirements after sleeve gastrectomy at long term. Obes Surg.
33. Stroh C, Meyer F, Manger T. Beriberi, a severe complication after
metabolic surgery – review of the literature. Obes Facts. 2014;7(4):246-
34. Ijaz S, Thorley H, Porter K, et al. Interventions for preventing
or treating malnutrition in homeless problem-drinkers: a systematic
review. Int J Equity Health. 2018;17(1):8.
35. Fama R, Le Berre A-P, Hardcastle C, et al. Neurological, nutri-
tional and alcohol consumption factors underlie cognitive and mo-
tor decits in chronic alcoholism. Addict Biol. 2017. https://doi.org/
10.1111/adb.12584. [Epub ahead of print].
36. Alim U, Bates D, Langevin A, et al. Thiamine prescribing practices
for adult patients admitted to an internal medicine service. Can J Hosp
37. Gerridzen IJ, Hertogh CMPM, Depla MF, Veenhuizen RB, Verschuur
EML, Joling KJ. Neuropsychiatric symptoms in people with Korsakoff
Syndrome and other alcohol-related cognitive disorders living in spe-
cialized long-term care facilities: prevalence, severity, and associated
caregiver distress. J Am Med Dir Assoc. 2018;19(3):240-247.
38. Sanvisens A, Zuluaga P, Fuster D, et al. Long-term mortality of pa-
tients with an alcohol-related Wernicke-Korsakoff syndrome. Alcohol
39. Cook CC, Hallwood PM, Thomson AD. B Vitamin deciency
and neuropsychiatric syndromes in alcohol misuse. Alcohol Alcohol.
40. Manzanares W, Hardy G. Thiamine supplementation in the critically
ill. Curr Opin Clin Nutr Metab Care. 2011;14(6):610-617.
41. McGarvey C, Franconi C, Prentice D, Bynevelt M. Metformin-
induced encephalopathy:the role of thiamine. Intern Med J. 2018;48(2):
42. Costa NA, Gut AL, Dorna MS, et al. Serum thiamine concentration
and oxidative stress as predictors of mortality in patients with septic
shock. JCritCare. 2014;29(2):249-252.
43. Donnino MW, Andersen LW, Chase M, et al. Randomized, double-
blind, placebo-controlled trial of thiamine as a metabolic resuscitator
in septic shock: a pilot study. Crit Care Med. 2016;44(2):360-367.
44. Andersen LW, Holmberg MJ, Berg KM, et al. Thiamine as an adjunc-
tive therapy in cardiac surgery: a randomized, double-blind, placebo-
controlled, phase II trial. Crit Care. 2016;20:92.
45. Kamas¸ak T, Kul S, Tus¸at M, Ozgun N, Cansu A. A case of Wernicke
Encephalopathy developing after ileal bypass surgery. Pediatr Emerg
46. Lei Y, Zheng MH, Huang W, Zhang J, Lu Y. Wet beriberi with
multiple organ failure remarkably reversed by thiamine administration.
Medicine (Baltimore). 2018;97(9):e0010.
47. Nakamura ZM, Tatreau JR, Rosenstein DL, Park EM. Clinical char-
acteristics and outcomes associated with high-dose intravenous thi-
amine administration in patients with encephalopathy. Psychosomatics.
48. Galvin R, Br ˚
athen G, Ivashynka A, Hillbom M, Tanasescu R,
Leone MA. EFNS guidelines for diagnosis, therapy and prevention of
Wernicke encephalopathy. Eur J Neurol. 2010;17(12):1408-1418.
49. Harper CG, Giles M, Finlay-Jones R. Clinical signs in the Wernicke-
Korsakoff complex: a retrospective analysis of 131 cases diagnosed at
necropsy. J Neurol Neurosurg Psychiatry. 1986;49(4):341-345.
50. Infante MT, Fancellu R, Murialdo A, Barletta L, Castellan L, Serrati
C. Challenges in diagnosis and treatment of Wernicke Encephalopathy:
Report of 2 cases. Nutr Clin Pract. 2016;31(2):186-190.
51. Arts NJ, Walvoort SJ, Kessels RP. Korsakoff’s syndrome: a critical
review. Neuropsychiatr Dis Treat. 2017;13:2875-2890.
52. Faigle R, Mohme M, Levy M. Dry beriberi mimicking Guillain-
Barre syndrome as the rst presenting sign of thiamine deciency. Eur
53. Riahi A, Mansour M, Bedoui I, et al. Acute beriberi neuropathy
e syndrome after a strict vegetarian diet. Iran
54. DiNicolantonio JJ, Niazi AK, Lavie CJ, O’Keefe JH, Ventura HO.
Thiamine supplementation for the treatment of heart failure: a review
of the literature. Congest Heart Fail. 2013;19(4):214-222.
55. DiNicolantonio JJ, Liu J, O’Keefe JH. Thiamine and cardiovascular
disease: a literature review. Prog Cardiovasc Dis. 2018; 61(1):27-32.
56. Roman-Campos D, Cruz JS. Current aspects of thiamine deciency on
heart function. Life Sci. 2014;98(1):1-5.
57. Costa NA, Azevedo PS, Polegato BF, Zornoff LAM, Paiva SAR,
Minicucci MF. Thiamine as a metabolic resuscitator in septic shock:
one size does not t all. J Thorac Dis. 2016;8(6):e471-472.
58. Minicucci MF, Zornoff LAM, Matsue M, et al. Generalized edema
and hyperdynamic circulation: a possible case of beriberi. Arq Bras
59. Imamura T, KinugawaK. Shoshin beriberi with low cardiac output and
hemodynamic deterioration treated dramatically by thiamine adminis-
tration. Int Heart J. 2015;56(5):568-570.
60. Chisolm-Straker M, Cherkas D. Altered and unstable: wet beriberi, a
clinical review. JEmergMed. 2013;45(3):341-344.
61. Dabar G, Harmouche C, Habr B, Riachi M, Jaber B. Shoshin beriberi
in critically-ill patients: case series. Nutr J. 2015;14:51.
62. Ward KE, Happel KI. An eating disorder leading to wet beriberi heart
failure in a 30-year-old woman. Am J Emerg Med. 2013;31(2):460.e5-
63. Bhat JI, Rather HA, Ahangar AA, et al. Shoshin beriberi-thiamine
responsive pulmonary hypertension in exclusively breastfed infants: a
study from northern India. Indian Heart J. 2017;69(1):24–27.
64. Coelho LS, Hueb JC, Minicucci MF, Azevedo PS, Paiva SAR, Zornoff
LAM. Thiamin deciency as a cause of reversible cor pulmonale. Arq
Bras Cardiol. 2008;91(1):e7-9.
65. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for
the diagnosis and treatment of acute and chronic heart failure: the
Task Force for the diagnosis and treatment of acute and chronic heart
failure of the European Society of Cardiology (ESC). Developed with
the special contribution of the Heart Failure Association (HFA) of the
ESC. Eur Heart J. 2016;37(27):2129-2200.
66. Leite HP, de Lima LFP, de Taddei JAAC, Paes ˆ
AT. Effect of blood
thiamine concentrations on mortality: inuence of nutritional status.
67. Soyka M, Kranzler HR, Hesselbrock V, Kasper S, Mutschler J, M¨
HJ. Guidelines for biological treatment of substance use and related
disorders, part 1: alcoholism, rst revision. World J Biol Psychiatry.
68. Giacalone M, Martinelli R, Abramo A, et al. Rapid reversal of severe
lactic acidosis after thiamine administration in critically ill adults: a
report of 3 cases. Nutr Clin Pract. 2015;30(1):104-110.
69. Cottini M, Ranucci M, Facciolo C, et al. An unusual case of cardio-
genic shock in which thiamine administration led to reversal of lactic
acidosis and heart function recovery: Shoshin beriberi in an adolescent.
Int J Cardiol. 2016;222:401-403.