Why does thiamine deficiency occur in refeeding syndrome?

January 9, 2026 •

3 min read

During refeeding, a rapid metabolic shift from fat to carbohydrate utilization places a high demand on key micronutrients. This is why thiamine deficiency occurs in refeeding syndrome, as the body's limited vitamin B1 stores are rapidly overwhelmed by the increased need for metabolic cofactors.

Quick Summary

Thiamine deficiency in refeeding syndrome stems from the body's abrupt metabolic transition from fat to glucose usage, rapidly depleting inadequate vitamin B1 stores.

Key Points

Metabolic Shift: Refeeding triggers a switch from fat-based catabolism to glucose-based anabolism, creating a high demand for energy metabolism cofactors like thiamine.
Depleted Stores: In starved individuals, thiamine stores are already low, and can be completely exhausted within 7-10 days without replenishment.
Insulin Surge: The reintroduction of carbohydrates causes an insulin spike, driving glucose into cells and massively accelerating thiamine-dependent metabolic pathways.
Wernicke-Korsakoff: The resulting acute thiamine deficiency can precipitate serious neurological conditions, including Wernicke's encephalopathy and Korsakoff's syndrome.
Preventive Strategy: Prophylactic thiamine supplementation must begin before or at the start of refeeding to prevent severe complications, especially in high-risk patients.

Understanding Refeeding Syndrome

Refeeding syndrome (RFS) is a potentially fatal condition characterized by severe electrolyte and fluid shifts, and metabolic/hormonal changes, occurring during aggressive nutritional support for severely malnourished individuals. It results from physiological adaptations to prolonged starvation and the sudden metabolic reversal during re-feeding.

Starvation-Induced Metabolic Changes

During starvation, the body conserves energy by shifting from glycogen to fat and protein for fuel. This involves decreased insulin and increased counter-regulatory hormones. Intracellular minerals, including thiamine, are depleted, though serum levels may not reflect this due to reduced intracellular volume.

The Sudden Shift of Refeeding

Reintroducing nutrients, particularly carbohydrates, causes a rapid insulin increase. Insulin promotes cellular uptake of glucose and electrolytes. The metabolic system, adapted to starvation, is overwhelmed by the glucose load, creating a high demand for already low micronutrient reserves.

The Critical Role of Thiamine

Thiamine (vitamin B1) is vital for carbohydrate metabolism, acting as thiamine pyrophosphate (TPP), a cofactor for key enzymes. These include:

Pyruvate Dehydrogenase Complex: Converts pyruvate to acetyl-CoA for the Krebs cycle.
Alpha-Ketoglutarate Dehydrogenase: Another TPP-dependent enzyme in the Krebs cycle.
Transketolase: Involved in the pentose phosphate pathway.

Insufficient thiamine impairs these pathways, hindering energy production from carbohydrates.

Why Thiamine Stores are Depleted

Thiamine stores are limited, lasting only a few weeks without intake. Patients at risk of refeeding syndrome, such as those with anorexia nervosa or chronic alcohol abuse, likely have severely depleted thiamine levels.

The Glucose Metabolism Thiamine Trap

Refeeding causes an insulin surge, driving glucose into cells and rapidly increasing carbohydrate metabolism. This demands significant thiamine as a cofactor. With low reserves, the increased demand quickly causes acute deficiency. Pyruvate may then be converted to lactate, potentially leading to lactic acidosis.

The Insulin Surge

Carbohydrate reintroduction triggers the insulin surge. While normal physiologically, in a malnourished state, this can lead to rapid intracellular electrolyte shifts and increased thiamine use, worsening deficiency.

Clinical Consequences of Thiamine Depletion

Acute thiamine deficiency in refeeding syndrome can cause severe complications.

Neurological Manifestations: Wernicke's encephalopathy (ocular issues, ataxia, confusion) is a key complication. It can progress to irreversible Korsakoff's syndrome (memory loss).
Cardiovascular Manifestations: Wet beriberi can cause heart failure and edema.
Metabolic Complications: Impaired pyruvate metabolism can result in lactic acidosis.

Prevention and Management

Preventing refeeding syndrome involves cautious refeeding and preemptive vitamin/electrolyte supplementation. Guidelines advise identifying at-risk patients and giving thiamine before or with the start of nutrition.

Prophylactic Thiamine Supplementation

Guidelines for high-risk patients often recommend:

High Doses: Intravenous thiamine for several days for rapid delivery.
Timing: Supplementation before or concurrently with refeeding, especially with IV glucose.
Electrolytes: Monitoring and replacing other electrolytes (phosphate, potassium, magnesium) alongside thiamine.

Comparison of Starvation and Refeeding Metabolism


Feature	Starvation Phase (Baseline)	Refeeding Phase
Primary Fuel Source	Fatty acids and ketones	Carbohydrates (glucose)
Hormonal Profile	Low insulin, high glucagon	High insulin, low glucagon
Thiamine Stores	Depleted due to low intake	Rapidly consumed
Metabolic State	Catabolism (breakdown of tissue)	Anabolism (synthesis of tissue)
Electrolyte Movement	Intracellular minerals low, serum levels may appear normal	Insulin drives electrolytes and water into cells
Risk of Complications	Low (relative to refeeding)	High, due to sudden metabolic and fluid shifts

Conclusion

Thiamine deficiency in refeeding syndrome results from a rapid metabolic shift following starvation. The reintroduction of carbohydrates triggers an insulin surge, increasing glucose metabolism and creating a significant demand for thiamine, rapidly depleting already low stores. This can lead to serious neurological and cardiovascular issues like Wernicke's encephalopathy and beriberi. Prophylactic thiamine supplementation and electrolyte monitoring are crucial for prevention. A slow, controlled refeeding process is essential for at-risk patients.

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Frequently Asked Questions

Refeeding syndrome is a potentially fatal condition caused by the severe metabolic shifts that occur when nutrition is reintroduced to a malnourished person. It involves abrupt changes in fluid and electrolytes, as well as vitamin deficiencies.

Individuals at high risk include those who are severely malnourished, have had little to no nutritional intake for over 5-10 days, have a history of chronic alcoholism, or have anorexia nervosa.

The surge of insulin caused by carbohydrate intake drives glucose into the cells, stimulating metabolic pathways that require thiamine as a cofactor. This high demand rapidly depletes the body's already low vitamin B1 stores.

Thiamine deficiency can cause Wernicke's encephalopathy, characterized by eye movement abnormalities, loss of coordination (ataxia), and confusion. In some cases, this can lead to Korsakoff's psychosis, a form of amnesia.

Yes. Severe thiamine deficiency can lead to 'wet beriberi,' which affects the cardiovascular system. It can cause heart failure, rapid heart rate, and edema (fluid buildup).

Prevention involves giving thiamine supplements, often intravenously, to at-risk patients before or at the time refeeding starts. This ensures that the vitamin is available to support the sudden increase in glucose metabolism.

Intravenous (IV) thiamine is often preferred in acute, high-risk cases because it ensures rapid and complete delivery of the vitamin, bypassing potential absorption issues common in malnourished patients.