The ketogenic diet raises reverse T3 levels in some people, and this increase interferes with active T3 binding to thyroid receptors, resulting in hypothyroid symptoms despite normal TSH and T4...
Mechanism
Synthesis from 1 study
Eating very few carbs lowers insulin, which stops the body from making the active thyroid hormone and starts making an inactive version instead. The inactive version blocks the active one from working in cells, so even if thyroid tests look normal, the body cannot use thyroid hormone properly and...
Most probable mechanism
When someone eats a very low-carb diet, their insulin levels drop, which turns off an enzyme that makes the active thyroid hormone and turns on an enzyme that makes an inactive version. The inactive version blocks the active one from working in cells, so even though the thyroid gland makes normal amounts of hormone, the body cannot use it properly and symptoms like fatigue and cold intolerance appear.
Carbohydrate restriction reduces glucose availability and suppresses insulin secretion
Low insulin signaling downregulates deiodinase type 2 (DIO2) expression and activity in liver, muscle, and brain
Reduced DIO2 activity decreases conversion of thyroxine (T4) to biologically active triiodothyronine (T3)
Low insulin and metabolic stress increase deiodinase type 3 (DIO3) activity, enhancing conversion of T4 to reverse T3 (rT3)
Elevated reverse T3 competes with triiodothyronine for binding to nuclear thyroid hormone receptors
Reverse T3 binding blocks triiodothyronine from activating gene transcription in target tissues
Less supported by current evidence, but not ruled out
Weight loss from the diet lowers leptin, which signals the brain to reduce thyroid hormone production. Early in the diet, stress hormones rise and further suppress thyroid hormone synthesis and activation.
Reduced adipose tissue mass lowers leptin secretion from fat cells
Low leptin signaling decreases thyrotropin-releasing hormone (TRH) production in the hypothalamus
Reduced TRH lowers thyroid-stimulating hormone (TSH) release from the pituitary
Acute carbohydrate restriction increases cortisol, which inhibits TRH synthesis and DIO2 activity
The diet removes fiber, which kills off gut bacteria that produce short-chain fatty acids. These fatty acids normally help convert thyroid hormone into its active form in the gut and brain, so their loss reduces active hormone levels.
Elimination of dietary fiber reduces populations of butyrate-producing gut bacteria
Depletion of short-chain fatty acids, especially butyrate, reduces DIO2 expression in enterocytes and glial cells
Reduced local DIO2 activity in gut and brain tissues decreases conversion of T4 to T3
Evidence from Studies
Supporting (1)
Community contributions welcome
Ketogenic Diet and Thyroid Function: A Delicate Metabolic Balancing Act
Contradicting (0)
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