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INTRODUCTION — VitaminsNo table of figures entries found. are a number of 

chemically unrelated families of organic substances that cannot be synthesized by humans

but need to be ingested in the diet in small quantities to prevent disorders of metabolism.

They are divided into water-soluble and fat-soluble vitamins (table 1).

Many of the vitamin deficiency diseases, such as rickets (vitamin D), scurvy (vitamin C),

beriberi (thiamine), and pellagra (niacin), have been almost completely eliminated indeveloped countries. Great interest and controversy continues into whether vitamin

supplementation can prevent cancer, heart disease, upper respiratory infections, and other

common diseases. (See "Vitamin supplementation in disease prevention".)

The best dietary sources for most of the water-soluble vitamins are fruits and vegetables;

these also contain many related substances such as flavins and carotenoids which are

generally not recognized as vitamins but may have protective effects against various

diseases. This topic review will focus on the water-soluble vitamins excluding folic acid and

vitamin B12, which are discussed separately. (See "Etiology and clinical manifestations of 

vitamin B12 and folic acid deficiency".)

Minerals and fat-soluble vitamins are also reviewed elsewhere. (See "Overview of vitaminA" and "Overview of vitamin D" and "Overview of vitamin E" and "Overview of vitamin

K" and "Overview of dietary trace minerals".)

DEFINITIONS — Several systems have been used to describe nutritional requirements of a

population. Dietary Reference Intakes (DRIs) were developed by the Food and Nutrition

Board of the Institute of Medicine to guide nutrient intake in a variety of settings. Under this

system, requirements can be expressed as a Recommended Dietary Allowance (RDA), which

is defined as the dietary intake that is sufficient to meet the daily nutrient requirements of 

97 percent of the individuals in a specific life stage group. If there is insufficient data to

determine an RDA for a given nutrient, requirements can be expressed as an Adequate

Intake (AI), which is an estimation of the nutrient intake necessary to maintain a healthy

state. These terms are described in greater detail in a separate topic review. (See "Dietaryhistory and recommended dietary intake in children".)

VITAMIN B1 (THIAMINE) — Thiamine, first named "the antiberiberi factor" in 1926, has a

historical value due to the very early description of Beriberi in the Chinese medical texts, as

far back as 2697 BC [1]. Formerly known as vitamin B1, thiamine is soluble in water and

partly soluble in alcohol. Thiamine consists of a pyrimidine and a thiazole moiety, both of 

which are essential for its activity (figure 1).

Sources — Thiamine is found in larger quantities in food products such as yeast, legumes,

pork, rice, and cereals. Milk products, fruits, and vegetables are poor sources of thiamine

[1]. The thiamine molecule is denatured at high pH and high temperatures. Hence, cooking,

baking, and canning of some foods as well as pasteurization can destroy thiamine [2].

Metabolism — Thiamine is absorbed in the small intestine via both passive diffusion and

active transport. The maximal absorption of thiamine is in the jejunum and ileum [3].

Thiamine passes through the mucosal cells to enter the blood stream via a sodium and ATP

dependent pump. Bound to albumin, it is carried by the portal circulation to the liver.

Thiamine enters the red blood cells by passive diffusion while its entry into other cells is via

an active energy requiring process [3]. The highest concentrations are found in the skeletal

muscles, the liver, the heart, the kidneys, and the brain. Thiamine's biologic half-life is

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approximately 10 to 20 days; due to limited tissue storage, continuous supplementation is

required [3]. Through a series of metabolic processes, thiamine is incorporated into many

phosphorylated esters, including thiamine pyrophosphate (TPP) and thiamine

monophosphate (TMP). Thiamine and all of its metabolites are excreted in the urine. Biliary

excretion is a minor route of its homeostasis [4].

Actions —

Thiamine is an important cofactor for enzymes involved in amino-acid andcarbohydrate metabolism. Functioning along with many coenzymes such as flavin and NAD,

thiamine serves as a catalyst in the conversion of pyruvate to acetyl CoA, an oxidative

decarboxylation reaction mediated by pyruvate dehydrogenase:

Pyruvate + CoA + NAD → Acetyl CoA + CO2 + NADH + H

Thiamine is also involved in many other cellular metabolic activities such as the

transketolation of the pentose phosphate pathway [3]. Thiamine has a role in the initiation

of nerve impulse propagation that is independent of its coenzyme functions [3].

Deficiency — Thiamine deficiency can be assessed by measuring the blood thiamine

concentration, erythrocyte thiamine transketolase (ETKA), or transketolase urinary thiamine

excretion (with or without a 5 mg thiamine load) [5]. Most laboratories now measure blood

thiamine concentration directly, in preference to the ETKA method [6]. The ETKA method is

a functional test and results are influenced by the hemoglobin concentration.

Thiamine deficiency has been associated with three disorders:

 Beriberi (infantile and adult)

 Wernicke-Korsakoff syndrome

 Leigh's syndrome

Infantile beriberi — Beriberi in infants becomes clinically apparent between the ages of 

two and three months. The clinical features are variable and may include a fulminantcardiac syndrome with cardiomegaly, tachycardia, a loud piercing cry, cyanosis, dyspnea,

and vomiting [7]. A form of aseptic meningitis has also been described in which the affected

infants exhibit vomiting, nystagmus, purposeless movements, and seizure, despite a

"normal" cerebrospinal fluid [8].

In 2003, infantile beriberi was discovered in a series of infants in Israel, due to feeding with

a soy-based formula that was inadvertently deficient in thiamine [9]. Most of the infants

with severe symptoms at the time of diagnosis, which included cardiomyopathy and

seizures, had severe permanent disabilities even after thiamine was replaced. Among

infants with apnea or seizures at presentation, all had moderate or severe intellectual

disability when reevaluated five years later, and most had chronic epilepsy [10]. A few of 

the severely affected infants died. Many other infants were asymptomatic or had nonspecificsymptoms while being fed the thiamine-deficient diet (eg, vomiting, irritability or failure to

thrive). However, follow-up testing revealed delays in language and motor development

[11].

Adult beriberi — Adult beriberi is described as dry or wet. Dry beriberi is the development

of a symmetrical peripheral neuropathy characterized by both sensory and motor

impairments, mostly of the distal extremities. Wet beriberi includes a neuropathy, as well as

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signs of cardiac involvement with cardiomegaly, cardiomyopathy, congestive heart failure,

peripheral edema, and tachycardia [1].

Beriberi has been reported as a complication of weight loss surgery, presenting as a

polyneuropathy with a burning sensation in the extremities, weakness, and falls [12-14].

Several of the case reports have been in adolescents, but whether this nutritional

complication is more common in the adolescent age group as compared to adultsundergoing weight loss surgery has not been established. (See "Surgical management of 

severe obesity in adolescents".)

Thiamine deficiency can occur as a complication of total parenteral nutrition if adequate

thiamine supplements are not provided. As an example, during the late 1990s, there were

multiple reports of symptomatic thiamine deficiency among recipients of parenteral nutrition

during a widespread shortage of parenteral multivitamins in the United States [15].

A number of studies have suggested that patients with heart failure, especially those

treated with loop diuretics, may be thiamine deficient and should be treated with 50 to 200

mg of thiamine per day [16-18]. However, this remains controversial because of questions

involving assay validity and a lack of controlled trials [19]. (See "Causes of dilatedcardiomyopathy".)

Wernicke-Korsakoff syndrome — Wernicke-Korsakoff syndrome is the best known

neurologic complication of thiamine (vitamin B1) deficiency. The term refers to two different

syndromes, each representing a different stage of the disease. Wernicke's encephalopathy

(WE) is an acute syndrome requiring emergent treatment to prevent death and neurologic

morbidity. Korsakoff's syndrome (KS) refers to a chronic neurologic condition that usually

occurs as a consequence of WE. It is characterized by impaired short-term memory and

confabulation with otherwise grossly normal cognition. (See "Overview of the chronic

neurologic complications of alcohol", section on 'Korsakoff's syndrome'.)

WE is a triad of nystagmus, ophthalmoplegia, and ataxia, along with confusion. Thiscombination is almost exclusively described in chronic alcoholics with thiamine deficiency.

The two entities are not separate diseases, but a spectrum of signs and symptoms. There

may be a genetic predisposition for the development of WE since not all thiamine deficient

patients are affected. Impairment in the synthesis of one of the important enzymes of the

pentose phosphate pathway (erythrocyte transketolase) may explain such a predisposition

[20]. (See "Wernicke's encephalopathy".)

WE is treated with thiamine supplementation. A range of replacement doses have been used

successfully, but large doses are typically used because they appear to be safe. It is

common practice to delay giving dextrose to alcoholic patients until thiamine

supplementation has been initiated to avoid precipitating Wernicke's encephalopathy.

(See "Wernicke's encephalopathy", section on 'Treatment'.)

Leigh syndrome — Thiamine deficiency has occasionally been reported in infants

presenting with features of Leigh syndrome, a progressive subacute necrotizing

encephalomyopathy. This is a sporadic mitochondrial disorder with a subacute neurologic

course. It is manifested with ataxia, dysarthria, movement disorders, areflexia, muscle

atrophy, and weakness. (See "Hereditary neuropathies associated with generalized

disorders", section on 'Leigh syndrome'.)

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Toxicity — No real syndrome of excess thiamine exists since the kidneys can rapidly clear

almost all excess thiamine [21]. Its half-life is 9.5 to 18.5 days.

Requirements — The RDA for thiamine in the United States is 1.2 mg daily for adult men

and 1.1 mg daily for adult women (about 0.5 mg/1000 kcal), and 1.4 mg/day during

pregnancy and lactation (table 2) [22].

Thiamine can be administered via intravenous and intramuscular routes. For the treatment

of patients with beriberi, the daily doses range from 50 to 100 mg for 7 to 14 days. Then an

oral dose of 10 mg per day is given until full recovery is achieved [1].