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

Ellen Molteberg; Per M Thorsby; Magnhild Kverneland; Per Ole Iversen; Kaja K Selmer; Dag Hofoss; Karl O Nakken; Erik Taubøll

doi:10.1002/epi4.12808

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

Epilepsia Open. 2023 Dec;8(4):1331-1339. doi: 10.1002/epi4.12808. Epub 2023 Sep 13.

Authors

Ellen Molteberg^{1

2}, Per M Thorsby^{2

3}, Magnhild Kverneland¹, Per Ole Iversen^{4

5}, Kaja K Selmer^{1

6}, Dag Hofoss¹, Karl O Nakken¹, Erik Taubøll^{2

7}

Affiliations

¹ National Centre for Epilepsy, Oslo University Hospital, Oslo, Norway.
² Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ Hormone Laboratory, Dep of Medical Biochemistry and Biochemical endocrinology and metabolism research group, Oslo University Hospital, Oslo, Norway.
⁴ Department of Nutrition, University of Oslo, Oslo, Norway.
⁵ Department of Haematology, Oslo University Hospital, Oslo, Norway.
⁶ Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital and the University of Oslo, Oslo, Norway.
⁷ Department of Neurology, Oslo University Hospital, Oslo, Norway.

Abstract

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.

Keywords: adrenal hormones; cortisol; cortisol binding globulin; free cortisol index; metanephrines.

MeSH terms

Adult
Diet, High-Protein Low-Carbohydrate*
Drug Resistant Epilepsy*
Female
Humans
Hydrocortisone
Prospective Studies
Seizures

Substances

Hydrocortisone