Vitamin B₁, Whole Blood

Whole blood, frozen

1 mL

0.5 mL

Lavender-top (EDTA) tube

Blood samples should be collected before breakfast in the morning and prior to any medication.

For the assessment of thiamine deficiency

The biologically active form of the vitamin, thiamine pyrophosphate (TPP), is best measured in whole blood and is not found in measurable concentration in plasma. Plasma thiamine concentration reflects recent intake rather than body stores; therefore, whole blood is the preferred specimen for thiamine assessment.

This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.

Liquid chromatography/tandem mass spectrometry (LC/MS-MS)

66.5−200.0 nmol/L

Vitamin B₁ refers to a group of compounds that include thiamin and its phosphate esters: thiamine monophosphate (TMP), thiamine pyrophosphate (TPP), and thiamine triphosphate.^1-5 All living organisms require thiamine, but it is only synthesized by bacteria, fungi, and plants. Thus, thiamine is an essential nutrient for animals that must obtain it from their diets. The principal biologically active form of thiamine is the pyrophosphate, TPP, which serves as a coenzyme for essential decarboxylation reactions by which carbohydrates, fats, and alcohol are metabolized to produce energy. Thiamine serves a role in the biosynthesis of acetylcholine and gamma-aminobutyric acid (GABA). TPP also facilitates the production of reducing substances involved in oxidant stress defenses, as well as for the synthesis of nucleic acid precursors.⁵ Thiamine triphosphate serves an important role in the regulation of ion channels of the nervous system.²

Primary thiamine deficiency is most common in underdeveloped countries due to poor oral intake or diets consisting of non-enriched grains.^1,5-8 The most common causes of thiamine deficiency in more affluent countries are alcoholism or malnutrition in nonalcoholic patients.⁵ Secondary thiamine deficiency can occur due to impaired gastrointestinal absorption related to disease or bariatric surgery. Consumption of anti-thiamin enzymes found in raw fish, ferns and betel nuts can reduce the absorption of thiamin.⁶ A relative thiamine deficiency can also occur in patients receiving enteral or parenteral nutrition therapy, in prolonged diarrheas, and in impaired utilization conditions such as in severe liver disease.⁵ Conditions that increase metabolic requirements for thiamine such as hyperthyroidism, pregnancy, lactation, and systemic infections with or without fever have been associated with thiamin deficiency. Increased gastrointestinal or renal losses, especially for patients on hemodialysis, can be a risk factor as well as advanced age, diabetes mellitus, AIDS, malignancies and any critical illness.^5,7

The earliest symptoms of thiamine deficiency are nonspecific and include fatigue, irritation, poor memory, sleep disturbances, anorexia, abdominal discomfort, and constipation.⁵ Severe thiamin deficiency is rare and can present as congestive heart failure (wet beriberi), peripheral neuropathy (dry beriberi), Wernicke encephalopathy (WE) and/or Korsakoff syndrome.^3-5

Dry beriberi is characterized by central and peripheral neuropathy that can be permanent even following thiamin repletion.^3,4 Clinical signs of dry beriberi are bilateral and symmetric, predominantly involving the lower extremities and have been well described in the literature.⁵ The neurological side effects of thiamin deficiency can progress to Wernicke encephalopathy (WE) and Korsakoff psychosis.^3,5,7,9 This diagnosis denotes the acute cerebral manifestation of severe thiamine deficiency that can lead to irreversible memory loss and dementia.^5,7,9 Patients with WE present with nystagmus, ophthalmoplegia, mental-status changes, and unsteadiness of stance and gait.^9,10 Korsakoff psychosis, an irreversible amnestic confabulatory state, can be the initial presentation in some patients, or it may be a sequel to WE.⁷ These patients present with clinical manifestations that are highly variable that can include oculomotor abnormalities, gait disturbance, and global confusion with retrograde amnesia, cognitive impairment, and confabulation.³

Wet beriberi refers to a thiamine deficiency condition where impaired cardiac performance leads to systemic symptoms.^4,5 In the initial stages of wet beriberi, high cardiac output produces peripheral vasodilation with warm extremities and excessive sweating.⁵ As the heart starts to fail further symptoms including tachycardia, a wide pulse pressure and lactic acidosis develop, leading to salt and water retention in the kidneys.⁵ The resulting fluid overload leads to edema of the dependent extremities.⁵ A more rapidly progressing form of wet beriberi has been referred to as acute fulminant cardiovascular beriberi or Shoshin beriberi, in which vasodilation continues, resulting in shock in a patient with heart failure.⁵

The signs and symptoms of wet beriberi and similar to those associated with heart failure from other causes. Several studies have shown that the prevalence of thiamine deficiency is increased in heart failure patients relative to the general population.^4,7,11-15 It has been postulated that thiamin deficiency may actually exacerbate underlying heart failure symptoms.^3,6 Research has shown that correction of thiamin deficiency can improve left ventricular ejection fraction, an indicator of long term prognosis in heart failure patients.^3,16-18 Malnutrition, advanced age, frequent hospitalization, and use of diuretic medications have all been shown to increase the risk of thiamin deficiency in patients with HF.^4,7

The levels of TPP in plasma or serum are very low relative to the erythrocyte. Plasma contains mainly thiamine and TMP, whereas TPP predominates in erythrocytes.²⁰ TPP accounts for 90% of the thiamine content in whole blood.² The TPP concentration in erythrocytes correlates with that in whole blood, a characteristic that allows the use of whole blood, rather than washed erythrocytes, for thiamine assessment.^2,19,20 Thus, whole blood is the preferred sample type for analysis of thiamine concentration.