Vitamin B1 (Thiamine)

Thiamine, or vitamin B1, is involved in a number of functions in the body, including nervous system (axonal conduction) and muscular functioning (electrolyte flow in these cells), carbohydrate metabolism, enzymatic processes, and production of hydrochloric acid needed for digestion.[1, 2]

In whole blood, the reference range of vitamin B1 (thiamine) is 2.5-7.5 μg/dL, or 74-222 nmol/L.

A stimulation of over 20%-25% during a red blood cell transketolase measurement using thiamine pyrophosphate (TTP) indicates deficiency.

The exact range depends on the laboratory used.

Low levels of thiamine reflect malabsorption states, poor nutritional status, or inadequate oral intake, while high levels suggest excessive intake or absorption issues. Conditions that increase the risk of vitamin B1 deficiency include the following:[3]

• Alcoholism

• Malnutrition

• Malabsorption (eg, chronic diarrhea)

• Dieting

• Renal dialysis

• Poor nutritional status on parenteral glucose (TPN)

• Bariatric weight-loss surgery

• Long-term diuretic therapy due to urinary losses

• Prolonged hyperemesis gravidarum or anorexia in women

Worldwide, poor oral intake is the most cause of thiamine deficiency, whereas alcoholism or chronic illnesses (eg, cancer) are more common in Western nations.[4]

Blood[5, 6]

Specimen type: Whole blood

Container: Vacutainer, green top (heparin)

Collection method: Venipuncture

Specimen volume: 0.6 mL (minimum) to 5 mL, depending on the laboratory

Other instructions: Fasting specimen

Panels: Vitamin B complex

Stability: Frozen (preferred), 48 hours up to 6 days; refrigerated, 4 hours to 7 days

There is a wide variability in container (lavender and pink have also been suggested), specimen volume, and stability, depending on which laboratory is used.

It is not affected by hemolysis, lipemia, or icterus.

Do not send in glass vial.

Whole blood is the preferred specimen (as opposed to plasma or serum), as 90% of vitamin B1 in whole blood is thiamine diphosphate (the biologically active form) and 80% of thiamine in whole blood is found in red blood cells. Whole blood specimens can be used to measure concentration of thiamine diphosphate (or thiamine pyrophosphate [TTP]). This type of measurement with high-performance liquid chromatography reflects recent intake rather than stores.

A functional enzymatic assay of transketolase activity measured before and after the addition of TTP is a more reliable way to measure thiamine nutritional status. A stimulation exceeding 20%-25% after the addition of TTP indicates severe thiamine deficiency (an activity coefficient of 1.25).[4]

Urine[7, 5]

Specimen type:[8] 24-hour urine collection

Container: Sterile plastic container

Collection method: Discard the first morning void. Begin the time of the collection for the next 24 hours, including the void at the end of the 24th hour, and record the last voiding time. An exact 24-hour count ensures accurate results. If an indwelling catheter is in place, keep the drainage bag on ice and empty the urine into the urine container periodically during the 24-hour period. Keep urine cool during collection. If any urine is lost, discard the entire specimen and begin collection again the next day.

Reference range: 100-200 µg/24 hours

Description

Thiamine, or vitamin B1, is a water-soluble vitamin that was first characterized in the 1920s; it was one of the first compounds to be described as a vitamin. It is involved in numerous functions in the body, including nervous system (axonal conduction) and muscular functioning (electrolyte flow in these cells), carbohydrate metabolism, enzymatic processes, and production of hydrochloric acid needed for digestion.[1]

It is absorbed in the jejunum by two processes. When the thiamine level in the small intestines is low, an active transport mechanism is responsible for absorption. When the thiamine concentration is high, a passive mucosal process takes place. Since very little thiamine is actually stored in the body (approximately 25-30 mg), depletion can take place in 14 days to one month.[1, 3]

Foods that are rich in thiamine include the following:[3]

• Whole-grain foods

• Meat, fish, poultry, eggs

• Milk and milk products

• Vegetables (eg, green, leafy vegetables; beets; potatoes)

• Legumes (eg, lentils, soybeans, nuts, seeds)

• Orange and tomato juices

Thiamine combines with adenosine triphosphate (ATP) in the liver, kidneys, and leukocytes to form thiamine diphosphate (also known as thiamine pyrophosphate). This biologically active form is a coenzyme in multiple metabolic pathways, including carbohydrate metabolism (through decarboxylation of pyruvic and alpha ketoacids), as well as transketolations in the pentose monophosphate pathway.

Deficiency leads to decreased transketolase activity in red blood cells (erythrocytes) and increases pyruvic acid in the blood, which, in turn, is not converted to acetyl-CoA and is unable to enter the Krebs cycle (for aerobic oxidative metabolism). Thus, there is a buildup of pyruvic acid, which is metabolized anaerobically to lactic acid.[3, 9]

The prevalence of thiamine deficiency, also known as beriberi, is much higher in East Asian countries because of the consumption of milled rice. Thiamine is contained in the outer coat of rice, and polishing destroys it. Raw fish, shellfish, tea, and coffee (regular and decaffeinated) contain thiaminases, which make the vitamin inactive. Thus, drinking large amounts of tea or coffee can theoretically lower body stores.

Table 1. Thiamine Nutritional Needs ^[3] (Open Table in a new window)

Indications/Applications

Assessing the serum thiamine level is indicated for diagnosing thiamine deficiency. Initial manifestations include anorexia and nonspecific symptoms such as irritability, fatigue, indigestion, sleep disturbances, and paresthesias. Prolonged deficiency is termed beriberi and is classically divided into wet and dry forms, although there is considerable overlap and most cases have a mixture of these types.

The division of wet and dry beriberi refers to the amount of fluid accumulation in the body. Beriberi means "I can't, I can't" in Singhalese, the language of natives of what was once part of the Dutch East Indies (now Sri Lanka).[10] Dry beriberi primarily involves the central nervous system, whereas wet beriberi classically has cardiovascular symptoms. Either type can result in pain and paresthesias.

Symptoms of dry beriberi include the following:

• Decreased vibratory position sense

• A peripheral neuropathy consisting of bilateral symmetric lower-extremity paresthesias

• Absent knee jerk and other deep-tendon reflexes

• Progressive weakness and muscle atrophy

Sensory disturbances occur first, followed by motor disturbances.[8, 3]

Another manifestation of CNS involvement is Wernicke-Korsakoff syndrome, which is most classically seen in individuals with chronic alcoholism. Wernicke encephalopathy is characterized by a triad of confusion, ataxia, and ocular abnormalities (nystagmus or palsies). Severe Wernicke disease can result in irreversible amnestic dementia and a confabulatory state known as Korsakoff syndrome.

Theoretically, glucose administration before thiamine in a thiamine-deficient person could precipitate this syndrome, as the glucose would be metabolized via anaerobic pathways, which would lead to more acidosis. However, this has not been proven in the medical literature.

Wet beriberi manifests as cardiovascular involvement. Individuals with this disease report palpitations due to tachycardia, weakness, and shortness of breath. Physical examination findings may include wide pulse pressure, hypotension, edema, and high-output cardiac failure (pulmonary congestion, pleural fluid).[8, 3]

A study by Mifsud et al described the characteristics of 56 cases of thiamine deficiency that were seen at a French tertiary hospital. A history of alcohol abuse was found in 45 patients (80%), and while neurologic symptoms were the basis for diagnosis in the majority of individuals, there were frequent instances of nonspecific and digestive symptoms. Moreover, the criteria for malnutrition were fulfilled in 34% of patients. Of the 54% of patients in whom brain magnetic resonance imaging (MRI) scans were performed, abnormal scans were found in 63% of cases.[11]

Infantile beriberi occurs in breastfed babies of thiamine-deficient mothers and has a very high fatality rate due to the rapidity of symptoms.

Considerations

For practical reasons, replacing thiamine as an initial test may be most feasible. If the patient responds to treatment, it is safe to assume that a measure of thiamine deficiency was responsible for the condition. Renal excretion of thiamine adjusts to dietary levels; thus, ingestion of large doses does not result in real toxicity, meaning that this route carries little risk. In addition, time is saved in treating the patient and money is saved in testing.

Thiamine is also used as a component of treatment in metabolic disorders (eg, subacute necrotizing encephalopathy, maple syrup urine disease, pyruvate carboxylase deficiency, hyperalaninemia).[1]

Other studies to consider include the following:

• Blood pyruvate

• Blood alpha-ketoglutarate

• Plasma lactate

• Glycosylate

• Urinary thiamine and metabolites (thiazole or pyrimidine)

• Urinary methylglyoxal