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Anyone can get epilepsy.

A serious neurological disorder, epilepsy can manifest in dangerous seizures and sometimes death. Though it is more common amongst younger children or the elderly, the disorder can delevop in people of all ages and backgrounds. Surgeries have been developed to treat epilepsy, but not all epileptic patients are viable for those necessary to keep them safe, and so for decades, scientists have been searching for other possible treatment plans. In recent decades, the ketogenic diet (KD), a high fat, low carbohydrate diet, has encountered a resurgence in popularity as an epilepsy treatment plan, though it remains unclear exactly why the KD is as efficient as it is. In a recent clinical trial, researchers examined the effects of the KD on leptin and ghrelin regulation in patients with GLUT1-Deficiency Syndrome and Drug Resistant Epilepsy, hoping it would shed light on the factors that play into the efficacy of the KD (De Amisis et al. 2019). This study was one of the first conducted to measure the long-term effects of the diet and appears to disprove the theory that leptin and ghrelin regulation plays into the anti-convulsant mechanisms of the KD.

Since the 1910s, dieting has been used to treat epilepsy (Meira et al. 2019). Diets like the KD mimic a state of starvation, which changes the metabolic process enough to kickstart an anti-convulsant mechanism while still providing the body with enough nutrients to sustain itself (Wheless 2007). Despite the KD’s widespread success as a treatment, there remains uncertainty over what exactly causes this mechanism. Several research groups have theorized that the KD might impact the body’s regulation of leptin and ghrelin, a peptide and hormone respectively, which could reduce the convulsant tendencies in epileptics.

Previous studies have been conducted on the regulation of leptin and ghrelin in patients with GLUT1-DS or DRE post-dieting, however many of these previous tests have taken place over a short series of months, with the most frequent test length being three months (De Amisis et al. 2019). While most of these studies showed some change in leptin and ghrelin regulation over the short term, little was known about the KD’s long-term effects in these chemical levels.

To further investigate this hypothesis, Ramona De Amicis and several other researchers conducted a long-term study out of the Department of Child Neurology and Psychiatry at Fondazione IRCCS Istituto Neurologico C.Mondino and the Pediatric Neurology Unit at “V. Buzzi” Hospital, measuring the leptin and ghrelin levels in patients with GLUT1-Deficiency Syndrome and Drug Resistant Epilepsy while on the KD. Thirty patients were enrolled in 2018, twenty-five of whom were children and adolescents. Prior to the experiment, all patients met the requirements for a GLUT1-DS diagnosis. They each had their regular dietary schedule evaluated by a dietitian over the course of a week. Due to the restrictive nature of the KD, patients then received counseling to fully understand the requirements and process of partaking in the KD.

Over the next twelve months, patients were gradually introduced to the diet with set caloric and dietary prescriptions based on age, weight, etc. Patients were instructed to document their ketonemia daily for the first month, and then once every two weeks. A neurological evaluation was performed on patients thrice during the twelve months, and a number of anthropomorphic measurements were conducted at set intervals by the original dietician. Final measurements were taken, recorded, and compared at the conclusion of the designated twelve-month experimentation period.

After a year, the researchers examined their results and found no change in leptin and ghrelin regulation that could be traced back solely to the KD. Their findings were published in MDPI in 2019. According to the author’s knowledge, this study is the first to not show any clear difference in leptin and ghrelin regulation before and after the introduction of the ketogenic diet (De Amicis et al. 2019). This suggests that leptin and ghrelin regulation may not play as large a role in the anti-convulsant effects of the KD as previously believed.

For such a conclusion to be holistically agreed upon, further studies on the subject must be done. This study is easily replicable, but future tests may want to consider the use of a control group, particularly in contrast with the adolescent patients undergoing rapid growth and development. This would allow for a clearer delegation of what results were due to the KD. A larger sample size with a patient pool from more than two hospitals could also be beneficial, as it would increase variation and potentially remove confounding variables which could impede the investigation.

Future studies must also consider the ethics of KD testing. Though it has proven to be effective as an epilepsy treatment plan, many patients have opted to discontinue their use of it, as the diet’s requirements are so strict as to make it difficult to sustain for extended periods of time (Meira et al. 2019). With this in mind, researchers must take great care to ensure that future studies are endurable and ethical for subjects, especially those who are children and require the proper nutrients to healthily develop.

Should these findings be replicated, this study could be key in narrowing down the possible explanations for the efficacy of the KD in epileptics. Ruling out leptin and ghrelin as a factor opens up new avenues for exploration, which could eventually lead to a more in-depth understanding of the KD. With epilepsy as wide-spread and dangerous as it is, reliable non-surgical treatments are necessary to improve the safety of those living with it, and the KD has the potential lead in this field.







De Amicis R, Leone A, Lessa C, Foppiani A, Ravella S, Ravasenghi S, Trentani C, Ferraris C, Veggiotti P, De Giorgis V, et al. 2019. Long term effects of a classic ketogenic diet on ghrelin and leptin concentration: A 12-Month prospective study in a cohort of Italian children and adults with GLUT1-deficiency syndrome and drug resistant epilepsy. MDPI. [accessed 2020 Aug 31];11(8). doi:


Meira ID, Romão TT, Pires do Prado HJ, Krüger LT, Pires MEP, da Conceição PO. 2019. Ketogenic diet and epilepsy: What we know so far. Guedes RC, editor. Frontiers in Neuroscience. [accessed 2020 Aug 25];13(5):1–8.


Wheless, J. W. 2008. History of the ketogenic diet. Epilepsia 49, 3–5. doi: 10.1111/j.1528-1167.2008.01821.x


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