Thiamin (B1) and Its Application in Patients with Critical Condition

*Bastian Lubis, Putri Amelia, Aznan Lelo, Muhammad Akil and Vincent Viandy*

#### **Abstract**

Thiamin is an essential water-soluble nutrient that is naturally available in some foods and available as a supplement. This nutrient plays a vital role in metabolism, cell growth and development. The recommended daily intake of thiamin for adults is around 1.1–1.2 mg/day. Several studies have described that thiamin deficiency is commonly seen in critically ill patients, mainly sepsis. Thiamin deficiency reduces pyruvate access to the Krebs cycle, therefore, increases the production of lactate. The administration of thiamin in critically ill patients has been linked to better outcomes and depletion of mortality rate.

**Keywords:** thiamin, vitamin B1, sepsis, septic shock

#### **1. Introduction**

Thiamin is the first vitamin B discovered; thus, it is known as vitamin B1. This micronutrient is also known as aneurine. Thiamin is an essential micronutrient that is water-soluble and involved in aerobic metabolism. Humans' daily requirement of thiamin is highly dependent on food intake due to their inability to synthesise it endogenously. Some bacteria in the human intestine can produce thiamin. However, the amount is limited [1].

The chemical name for B1 is 3-[(4-amino-2-methyl-5-pyrimidine)methyl]- (2-hydroxy ethyl)-4-methylthiazolium. Thiamin originated from pyrimidine and thiazole ring substitution, combined with the methylene bridge (**Figure 1**) [2].

**Figure 1.** *Thiamin structure [2].*

#### **2. Pharmacokinetics and pharmacodynamics of thiamin**

Thiamin works as a cofactor in citric acid cycles. Vitamin B1 reacts with adenosine triphosphate (ATP) to form an active form called thiamin pyrophosphate.

Thiamin is an essential cofactor for enzymes pyruvate dehydrogenase, alphaketoglutarate dehydrogenase, and transketolase. Pyruvate dehydrogenase enzymes are the main entrance to the Krebs cycle, catalysing oxidative decarboxylation of pyruvate to form acetyl-coenzyme A (acetyl-CoA). Without this enzyme, pyruvate would be converted to lactate. Alpha-ketoglutarate dehydrogenase catalyses the oxidative decarboxylation of alpha-ketoglutarate to succinyl-CoA to complete the Krebs cycle. Transketolase is an enzyme necessary for the pentose phosphate pathway and the production of nicotinamide adenine dinucleotide phosphate (NADPH). Thiamin is required in each of these three steps (**Figure 2**) [3, 4].

The mechanism of thiamin absorption in the body is still controversial. Some researchers argue that it is only absorbed from active transport mechanisms in the proximal small intestine. However, recent studies show that thiamin is also absorbed by passive diffusion [5]. Thiamin absorption by the intestine is mediated by a transport system and absorbed by cells in the liver, heart, and other various tissues from the blood, except neural fibres. In the nervous system, thiamin is transported from circulation blood towards cerebrospinal fluid across the blood– brain barrier [2, 6]. Vitamin B1 is rapidly absorbed and transformed through a

**Figure 2.** *Pathogenesis of cell death in deficiency thiamin [2, 16].*

#### **Figure 3.**

*Oral Thiamin concentration in blood [5].*

phosphorylation process into an active coenzyme, thiamin pyrophosphate. Vitamin B1 is absorbed in the jejunum at low concentrations, involving the phosphorylation process through an active transport system. At high concentrations, absorption of vitamin B1 occurs by passive diffusion. The relative bioavailability of vitamin B1 is about 5.3%. A study by Smithline et al. (2012) shows oral thiamin concentration reaching the peak at 4 hours after consumption (**Figure 3**) [5].

Thiamin is widely distributed to almost all body tissues, including breast milk. Thiamin is not stored in the body. Thiamin transport occurs through the blood, both in erythrocytes and plasma. About 90–94% of vitamin B1 is bounded to protein [2].

Thiamin metabolism occurs in the liver and produces active metabolites, thiamin pyrophosphate, thiamin monophosphate, and thiamin triphosphate. Thiamin diphosphate is the primary active metabolite, which acts as a coenzyme in carbohydrate metabolism through transketolase reaction [2, 7].

Thiamin half-life ranges from 9 to 18 days on daily consumption, and the elimination or dephosphorylation process occurs in kidneys. This half-life appears to be variable and highly dose-dependent. One study showed that the half-life of thiamin is only about 6 hours at high doses (500-1500 mg). For intravenous administration, peak levels reached within 2–6 hours depending on doses [5]. If there is an excess of free-form vitamin B1, it will be excreted in the urine. In regular doses, it is secreted in the urine in unchanged form [2].

#### **3. Sources**

Thiamin cannot be produced indigenously in the human body. Therefore, we rely on dietary intake [8]. The sources of thiamin include fortified flours, whole grain cereals, meat (pork, beef or poultry), eggs, dried beans, soybeans and nuts. Nevertheless, polished rice, fats, processed flours, dairy products and vegetables are not reliable sources to satisfy the daily requirements of thiamin [9]. Significant losses of thiamin happen when the food is cooked or undergone other heating processes. Polyphenolic compounds in tea and coffee may inactivate thiamin;

therefore, their consumption must be in moderation. Similarly, uncooked fish and shellfish contain thiaminases that inactivate and break down thiamin [9, 10].
