A ketogenic diet lowers free triiodothyronine levels without raising thyroid-stimulating hormone in healthy adults and people with epilepsy, indicating a metabolic adjustment to low carbohydrate...
Mechanism
Synthesis from 1 study
When the body switches from burning carbs to burning fat, insulin drops and this turns down the enzyme that makes the active thyroid hormone, while turning up the enzyme that breaks it down into an inactive form. The brain notices the lower hormone levels but doesn't respond by making more TSH...
Most probable mechanism
When the body runs on fat instead of carbs, insulin drops, which turns down the enzyme that makes the active thyroid hormone from its inactive form. At the same time, another enzyme is turned up that breaks down the active hormone into an inactive version. This lowers the amount of active thyroid hormone in the blood without triggering the brain to make more, because the brain recognizes this as a normal energy-saving change.
Carbohydrate restriction reduces glucose availability and suppresses insulin secretion
Low insulin signaling reduces transcriptional activation of deiodinase type 2 (DIO2) in liver, muscle, and brain tissue
Decreased DIO2 activity reduces conversion of thyroxine (T4) to biologically active triiodothyronine (T3)
Ketosis increases activity of deiodinase type 3 (DIO3), which converts T4 into inactive reverse T3 (rT3)
Elevated reverse T3 competes with T3 for nuclear receptor binding, reducing thyroid hormone signaling in target tissues
Reduced adipose tissue mass lowers leptin secretion, which suppresses thyrotropin-releasing hormone (TRH) expression in the hypothalamus
Lower TRH reduces stimulation of the pituitary gland, maintaining stable thyroid-stimulating hormone (TSH) secretion despite low T3
Less supported by current evidence, but not ruled out
The main ketone body directly blocks inflammatory pathways in immune cells and activates antioxidant systems in thyroid tissue, reducing damage that could otherwise trigger abnormal hormone production.
Beta-hydroxybutyrate inhibits the NLRP3 inflammasome in macrophages, reducing release of interleukin-1 beta and interleukin-18
Reduced inflammatory cytokines decrease lymphocytic infiltration and thyrocyte damage in the thyroid gland
Beta-hydroxybutyrate activates the Nrf2 pathway, increasing production of superoxide dismutase and glutathione peroxidase in thyrocytes
Enhanced antioxidant defense reduces oxidative damage and prevents ROS-driven autoimmune activation in thyroid tissue
The main ketone body changes gene activity in immune cells to increase regulatory T cells and reduce inflammatory T cells, which may stabilize thyroid function by preventing autoimmune attack.
Beta-hydroxybutyrate enters immune cells and inhibits histone deacetylases
Histone deacetylase inhibition increases acetylation at the FoxP3 gene promoter, enhancing regulatory T cell differentiation
Increased regulatory T cell activity suppresses autoreactive T helper 17 cells that promote thyroid inflammation
In the first few days of the diet, stress hormones rise and temporarily reduce the brain's signal to the thyroid, lowering hormone production and increasing inactive hormone forms.
Carbohydrate restriction activates the hypothalamic-pituitary-adrenal axis, increasing cortisol secretion
Elevated cortisol suppresses thyrotropin-releasing hormone expression in the hypothalamus
Cortisol reduces thyroid-stimulating hormone release from the pituitary gland
Cortisol inhibits deiodinase type 1 and type 2 activity while promoting conversion of T4 to reverse T3
Evidence from Studies
Supporting (1)
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Ketogenic Diet and Thyroid Function: A Delicate Metabolic Balancing Act
Contradicting (0)
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