Changes of thyroid hormonal status in patients receiving ketogenic diet due to intractable epilepsy

J Pediatr Endocrinol Metab. 2017 Apr 1;30(4):411-416. doi: 10.1515/jpem-2016-0281.


Background: Ketogenic diet (KD), which is high in fat and low in carbohydrates, mimics the metabolic state of starvation and is used therapeutically for pharmacoresistant epilepsy. It is known that generation of triiodothyronine (T3) from thyroxine (T4) decreases during fasting periods. The aim of this study was to evaluate the thyroid function of children receiving KD for at least 1 year due to drug-resistant epilepsy.

Methods: A total of 120 patients [63 males, 52.5%; mean age 7.3±4.3 years, median interquartile range (IQR): 7.0 (4-10 years)] treated with KD for at least 1 year were enrolled. Seizure control, side effects, and compliance with the diet were recorded, and free T3, free T4, and thyroid-stimulating hormone (TSH) levels were measured at baseline and at post-treatment months 1, 3, 6, and 12. The Mann-Whitney U-test, repeated measures analysis of variance (ANOVA) with post-hoc Bonferroni correction, and logistic regression analysis were used for data analysis.

Results: Hypothyroidism was diagnosed and L-thyroxine medication was initiated for eight, seven and five patients (20 patients in total, 16.7%) at 1, 3, and 6 months of KD therapy, respectively. Logistic regression analysis showed that baseline TSH elevation [odds ratio (OR): 26.91, 95% confidence interval (CI) 6.48-111.76, p<0.001] and female gender (OR: 3.69, 95% CI 1.05-12.97, p=0.042) were independent risk factors for development of hypothyroidism during KD treatment in epileptic children.

Conclusions: KD causes thyroid malfunction and L-thyroxine treatment may be required. This is the first report documenting the effect of KD treatment on thyroid function. Thyroid function should be monitored regularly in epileptic patients treated with KD.

Keywords: children; epilepsy; hypothyroidism; ketogenic diet; thyroid hormones.

MeSH terms

  • Adolescent
  • Biomarkers / blood*
  • Child
  • Child, Preschool
  • Diet, Ketogenic / adverse effects*
  • Drug Resistant Epilepsy / diet therapy*
  • Female
  • Follow-Up Studies
  • Humans
  • Hypothyroidism / blood*
  • Hypothyroidism / diagnosis
  • Hypothyroidism / etiology
  • Infant
  • Male
  • Prognosis
  • Thyrotropin / blood*
  • Thyroxine / blood*
  • Triiodothyronine / blood*


  • Biomarkers
  • Triiodothyronine
  • Thyrotropin
  • Thyroxine