Stress biomarkers in adult patients with drug‐resistant epilepsy on a modified Atkins diet: A prospective study

OBJECTIVE: Ketogenic diets like the modified Atkins diet (MAD) are increasingly used in patients with refractory epilepsy. For epilepsy patients, stress is a well‐known seizure‐precipitating factor. New possibilities for measuring biomarkers of stress are now available. The purpose of this study was to investigate the impact of MAD on endocrine stress biomarkers. METHODS: Forty‐nine patients with drug‐resistant epilepsy were investigated at baseline and after 12 weeks on MAD. Cortisol and cortisol‐binding globulin (CBG) were measured and free cortisol index (FCI) calculated. We also measured metanephrine, normetanephrine, and methoxytyramine, all markers of epinephrine, norepinephrine, and dopamine, respectively. Changes were analyzed according to sex and antiseizure medications. The different markers at baseline and after 12 weeks of MAD treatment were correlated with seizure frequency and weight loss, respectively. RESULTS: The change in total cortisol was modest after 12 weeks on the diet (from 432.9 nmol/L (403.1–462.7)) to 422.6 nmol/L (384.6–461.0), P = 0.6). FCI was reduced (from 0.39 (0.36–0.42) to 0.34 (0.31–0.36), P = 0.001). CBG increased during the study (from 1126.4 nmol/L (1074.5–1178.3) to 1272.5 nmol/L (1206.3–1338.7), P < 0.001). There were no changes in the metanephrines after 12 weeks on the diet. The decrease in FCI was significant only in women, and only observed in patients using nonenzyme‐inducing ASMs. We did not find any correlation between cortisol, CBG, or FCI levels and seizure frequency. SIGNIFICANCE: After being on MAD for 12 weeks, FCI decreased significantly. The reduction in FCI may reflect reduced stress, but it may also be an effect of increased CBG. The reasons behind these alterations are unknown. Possibly, the changes may be a result of a reduction in insulin resistance and thyroid hormone levels. Treatment with MAD does not seem to influence “fight or flight” hormones.