A ketogenic diet lowers the activity of enzymes that convert thyroxine (T4) into triiodothyronine (T3) in tissues like muscle and liver, resulting in reduced levels of active thyroid hormone.
Mechanism
Synthesis from 1 study
When carbs are very low, insulin drops and turns off the enzyme that makes the active thyroid hormone in muscles and liver. This causes less active hormone to be available, while more inactive hormone is made instead. Other factors like stress hormones or gut bacteria changes may play a small role,...
Most probable mechanism
When carbohydrate intake is very low, insulin levels drop, which turns off the enzyme that converts inactive thyroid hormone into its active form in muscles and liver. This causes less active thyroid hormone to be available, while the body makes more of an inactive version instead.
Carbohydrate restriction reduces glucose availability and suppresses insulin secretion
Low insulin fails to relieve transcriptional repression of the DIO2 gene in skeletal muscle, liver, and brown adipose tissue
DIO2 enzyme expression and activity decline in peripheral tissues
Reduced DIO2 activity decreases conversion of thyroxine (T4) to triiodothyronine (T3)
DIO3 activity increases, converting T4 to reverse T3 (rT3), which competes with T3 for receptor binding
Tissue-level T3 deficiency occurs despite normal serum T4, resulting in reduced thyroid hormone signaling
Less supported by current evidence, but not ruled out
In the first few days of a ketogenic diet, stress hormone levels rise and temporarily reduce signals that tell the thyroid to produce more hormone, lowering T3 production.
Carbohydrate restriction activates the hypothalamic-pituitary-adrenal axis, increasing cortisol secretion
Elevated cortisol inhibits thyrotropin-releasing hormone (TRH) synthesis in the hypothalamus
Reduced TRH decreases thyroid-stimulating hormone (TSH) release from the pituitary
Cortisol suppresses DIO1 and DIO2 enzyme activity and promotes DIO3-mediated conversion of T4 to reverse T3
Weight loss from the diet reduces fat tissue, which lowers a hormone that signals the brain to stimulate thyroid hormone production, leading to less T3.
Fat mass decreases due to sustained energy deficit from the diet
Leptin secretion from adipose tissue declines
Reduced leptin signaling suppresses thyrotropin-releasing hormone (TRH) expression in the hypothalamus
Lower TRH reduces thyroid-stimulating hormone (TSH) secretion, decreasing thyroid hormone synthesis
The diet removes fiber, which starves gut bacteria that produce a compound needed to activate the enzyme that converts thyroid hormone in the gut, reducing overall T3 levels.
Dietary fiber intake is severely restricted
Butyrate-producing gut bacteria decline, reducing short-chain fatty acid production
Reduced butyrate decreases DIO2 expression in enterocytes and glial cells
Local T4-to-T3 conversion in gut-associated tissues is impaired
Evidence from Studies
Supporting (1)
Community contributions welcome
Ketogenic Diet and Thyroid Function: A Delicate Metabolic Balancing Act
Contradicting (0)
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