Vitamin B1 (Thiamine)

Article Author:
Julianna Martel
Article Editor:
David Franklin
Updated:
10/27/2018 12:31:55 PM
PubMed Link:
Vitamin B1 (Thiamine)

Indications

Vitamin B1 is one of the eight B vitamins. It has acquired several names since discovery including Aneurin and, as of the year 2000, thiamin (thiamine). Because thiamin can only be stored in the body for a short time before it is readily excreted, a regular dietary intake of thiamin is necessary to maintain proper blood levels. Moderate amounts of thiamin can be found in most foods, yet the food sources richest in thiamin include whole-grains, brown rice, pork, poultry, soybeans, nuts, dried beans, peas, and fortified or enriched grain products such as cereals. The recommended daily intake (RDI) for adults over age eighteen is 1.2 mg/day for men and 1.1 mg/day for women. For children, adequate intake levels are lower, with RDI levels at 0.2 mg/day during early infancy that steadily increase with age. Women of any age who are pregnant or should increase their daily intake of thiamin to 1.4 mg/day.

Vitamin B1 deficiencies may occur if the RDI is not maintained. This can be seen with alcohol abuse, poor nutrition, fasting, restricted access to food, persistent vomiting, and in cases where the absorption of thiamin is hindered. Additionally, individuals with excessive carbohydrate consumption may fail to compensate by increasing their level of thiamin intake, resulting in a thiamin deficiency since thiamin is used in carbohydrate metabolism.

Decreased thiamin levels can result in reduced enzymatic activity, altered mitochondrial activity, impaired oxidative metabolism, and decreased energy production. Many cells and organ systems can be affected, and cell death can occur. Neurons have high energy requirements and therefore are especially vulnerable to a thiamin deficit.

Wernicke-Korsakoff syndrome (WKS) and Beriberi are the two most common complications that may arise from a thiamin deficiency, though these two syndromes rarely occur simultaneously in an individual. WKS affects the central nervous system, which involves the brain and spinal cord. It is most commonly caused by alcohol abuse seen alongside poor nutrition but can be seen in individuals who are at risk for thiamin deficiency. Technically, WKS consists of two different syndromes that can often present together. Wernicke encephalopathy occurs early in the disease course and is characterized by non-inflammatory brain lesions. It can present with ataxia, ophthalmoplegia, punctate hemorrhages in the brain, altered mental status, and balance abnormalities. If left untreated, Wernicke encephalopathy can eventually evolve to include Korsakoff psychosis. Individuals will now present with delirium and permanent memory loss. Treatment should ensue emergently to prevent disease progression and irreversible brain damage. Empirically, WKS is treated with at least 500 mg thiamine hydrochloride per 100mL of normal saline given over 30 minutes. This should be repeated 3 times a day, for 2 to 3 days. Thiamine therapy should be given before or alongside glucose.

Beriberi is another disorder caused by a thiamin deficiency. It is most frequently seen in people who abuse alcohol but also can be due to other etiologies resulting in thiamin deficiency. Early on, symptoms of beriberi are nonspecific and include constipation, appetite suppression, nausea, mental depression, fatigue, peripheral neuropathy, anorexia, and weight loss. With progression, chronic symptoms can begin to manifest as either wet beriberi or dry beriberi. Wet beriberi presents with edema, an enlarged heart, cardiac failure, warm extremities, pleural effusions, and pulmonary edema. Meanwhile, complications of dry beriberi are predominantly neurological with peripheral nervous system involvement. Individuals with dry beriberi may have paresthesia, foot drop, muscle wasting, numbness, and absent ankle reflexes.

Mechanism of Action

Like all B vitamins, Vitamin B1 is water soluble and gets absorbed directly into the blood from the gastrointestinal tract. Once absorbed into the circulatory system, thiamin can circulate freely without carrier molecules in plasma and red blood cells until it is eventually excreted in the urine. While in the body, it can be stored in the liver, but only for a maximum of eighteen days. It has the ability to cross the blood-brain barrier.

Once absorbed into the blood, the thiamin diphosphotransferase enzyme converts thiamin from its provitamin form into its active form, thiamin pyrophosphate (TPP). This reaction requires magnesium as a cofactor. TPP is a coenzyme that now can be used for energy metabolism. It is an essential component of the following three reactions:

  1. TPP is a cofactor in the E1 subunit of the pyruvate dehydrogenase (PDH) complex. The E1 subunit specifically converts pyruvate to hydroxyethyl-TPP and carbon dioxide. Meanwhile, the PDH complex as a whole decarboxylates pyruvate to convert it to acetyl-CoA while also generating nicotinamide adenine dinucleotide (NADH) in the process. NADH can later be converted to ATP, a source of energy for cells. Ultimately, the acetyl-CoA produced can then proceed to enter the Citric Acid Cycle to generate additional ATP. Thus, the PDH complex, which requires thiamin as a cofactor, has a significant role in deriving energy from carbohydrate metabolism. Additionally, PDH complex function is important in the production of acetylcholine (a neurotransmitter) and myelin.
  2. TPP is also used in the Citric Acid Cycle as a cofactor in the alpha-ketoglutarate dehydrogenase reaction where alpha-ketoglutarate is decarboxylated to form succinyl-CoA. This reaction is essential in propagating the Citric Acid Cycle, in which energy can be derived. Also, this reaction has a role in maintaining glutamate, aspartate, and gamma-aminobutyric acid (GABA) levels. GABA is an inhibitory neurotransmitter in the brain that prevents the over-excitation of neurons, thus preventing delirium.
  3. TPP is required as a cofactor in the Pentose Phosphate Pathway (PPP), specifically in the transketolase reaction. The PPP occurs within the cytosol of cells as an alternate pathway in carbohydrate catabolism, and its purpose is to provide nicotinamide adenine dinucleotide phosphate (NADPH) and ribose-5-phosphate. NADPH can then be used in several biochemical pathways such as in steroid, fatty acid, amino acid, neurotransmitter, and glutathione synthesis. Glutathione synthesis is particularly important because glutathione can reduce oxidative stress and free radical damage to cells. Meanwhile, ribose-5-phosphate is an essential building block in nucleic acids. However, if nucleic acids are not needed in a cell, then ribose-5-phosphate can enter the non-oxidative phase of the PPP where transketolase and TPP are needed to help transform ribose-5-phosphate back into glycolysis intermediates (such as glucose-6-phosphate). In this reaction, TPP is required as a cofactor to stabilize a 2 carbon carbanion intermediate.

Based on its role in these reactions, it is apparent that thiamin, in the form of TPP, is essential for energy production, cell viability, and proper neuronal functioning.

Administration

Individuals at risk of acquiring a thiamin deficiency or individuals who have a non-emergent thiamin deficiency can be instructed to take 50 mg of thiamin by mouth daily or can be given an injection of 50 to 100 mg of thiamin three to four times daily. Oral thiamin supplements may be taken with or without food since the absorption of Vitamin B1 is not influenced by food intake. Thiamin supplementation is nontoxic, even in excess.

Adverse Effects

In individuals receiving Vitamin B1 supplementation, the most commonly reported adverse effects include sensations of warmth, urticaria, pruritus, angioedema, diaphoresis, cyanosis, and anaphylaxis.

Contraindications

Allergic individuals should avoid taking Vitamin B1 supplements to avoid a hypersensitivity reaction. Also, pregnant individuals should use thiamin with caution as the RDI of thiamin increases during pregnancy and lactation. Finally, some thiamin products that are administered parenterally may contain aluminum. Therefore, these products should be used with caution in individuals with renal impairments, particularly in premature infants, to avoid the accumulation of aluminum and subsequent aluminum toxicity.

Monitoring

The best way to measure thiamin levels in patients is with erythrocyte transketolase activity. Thiamin levels also can be obtained from blood and urine; however, these values fail to include the amount of stored thiamin that may be present in the liver. It is important to note that thiamin is easily destroyed by heat.