How does thiamine (Vitamin B1) deficiency cause metabolic acidosis?

From the Guidelines

Thiamine deficiency causes acidosis primarily by impairing the function of key metabolic enzymes that require thiamine as a cofactor, leading to lactic acidosis. When thiamine levels are inadequate, pyruvate dehydrogenase complex activity decreases, preventing the conversion of pyruvate to acetyl-CoA, as noted in the context of thiamine disorders, including beriberi and refeeding syndrome 1. This leads to pyruvate accumulation, which is then converted to lactate, resulting in lactic acidosis. Additionally, thiamine deficiency impairs the function of alpha-ketoglutarate dehydrogenase in the Krebs cycle, further compromising aerobic metabolism and energy production. The body's cells are forced to rely more heavily on anaerobic glycolysis for energy, producing excess lactic acid. This metabolic shift is particularly problematic in tissues with high energy demands like the heart and brain.

Key points to consider in the management of thiamine deficiency include:

• Early suspicion and recognition of thiamine deficiency are crucial to enable immediate initiation of therapy, as thiamine reserves are depleted as early as 20 days of inadequate oral intake 1.
• Thiamine supplementation is essential, with typical initial doses of 100mg IV or IM, followed by 50-100mg daily until symptoms resolve.
• Addressing the underlying cause of thiamine deficiency, such as malnutrition or alcoholism, is also critical in managing the condition.
• Supportive care for managing acidosis is necessary, particularly in severe cases or in vulnerable populations like preterm infants, where parenteral thiamine intake recommendations vary 1.

In clinical practice, it is essential to prioritize the prevention and early treatment of thiamine deficiency to avoid severe complications, including lactic acidosis, which can be life-threatening if not addressed promptly.

From the FDA Drug Label

CLINICAL PHARMACOLOGY: ... Its role in carbohydrate metabolism is the decarboxylation of pyruvic acid in the blood and α-ketoacids to acetaldehyde and carbon dioxide. Increased levels of pyruvic acid in the blood indicate vitamin B 1 deficiency. The deficiency of thiamine leads to impaired decarboxylation of pyruvic acid, resulting in elevated levels of pyruvic acid in the blood. This can contribute to the development of acidosis.

• Key points:
  • Thiamine plays a crucial role in carbohydrate metabolism
  • Thiamine deficiency impairs the decarboxylation of pyruvic acid
  • Elevated pyruvic acid levels can lead to acidosis 2

From the Research

Thiamine Deficiency and Acidosis

• Thiamine deficiency can cause acidosis, particularly lactic acidosis, due to its essential role as a cofactor in energy production and glucose metabolism 3, 4, 5, 6, 7.
• The deficiency can lead to impaired glucose metabolism, resulting in the accumulation of lactate and subsequent development of lactic acidosis 4, 5, 6.
• Thiamine deficiency can be caused by inadequate nutrition, alcohol use disorders, increased urinary excretion, and acute metabolic stress, making certain populations more susceptible to this condition 3, 7.
• The clinical presentation of thiamine deficiency can include congestive heart failure, peripheral neuropathy, Wernicke's encephalopathy, Korsakoff's syndrome, and gastrointestinal beriberi, in addition to lactic acidosis 3.
• Treatment with thiamine can rapidly improve lactic acidosis, cardiac function, and other symptoms associated with thiamine deficiency 3, 4, 5, 6, 7.

Mechanism of Thiamine Deficiency-Induced Acidosis

• Thiamine plays a crucial role in the pyruvate dehydrogenase complex, which is necessary for the conversion of pyruvate to acetyl-CoA 4, 6.
• In the absence of thiamine, pyruvate is converted to lactate, leading to the accumulation of lactate and the development of lactic acidosis 4, 5, 6.
• Thiamine deficiency can also impair the function of other enzymes involved in energy production, contributing to the development of acidosis 3, 6.

Diagnosis and Treatment

• Thiamine deficiency should be considered in the differential diagnosis of lactic acidosis, particularly in high-risk populations such as malnourished patients, alcoholics, and those with increased urinary excretion or acute metabolic stress 3, 4, 7.
• Empiric treatment with thiamine should be initiated immediately in patients suspected of having thiamine deficiency, as delaying treatment can lead to severe life-threatening metabolic acidosis 7.
• Thiamine supplementation can rapidly improve lactic acidosis, cardiac function, and other symptoms associated with thiamine deficiency, making it a critical component of treatment 3, 4, 5, 6, 7.