Unfortunately, the KD is associated with various adverse effects (AEs), which are listed in Table 3.1,2 Not surprising, gastrointestinal complications such as constipation, diarrhea, abdominal pain, and nausea/vomiting are of the most common AEs. Although the majority of AEs associated with the KD are mild and do not cause an interruption in the diet, some AEs can be considered severe. One AE that has been quite worrisome in the past is the effect of the KD on cardiac function.3 In several past studies, it has been reported that the KD has the ability to cause cardiac conduction abnormalities as well as vascular and myocardial dysfunction. A recent prospective study by Ozdemir et al, however, found that the KD did not produce negative effects on ventricular function in children treated with the KD over 12 months.

Drug interactions are also an important aspect for clinicians to consider when a patient is receiving the KD. Fortunately, no antiepileptic drugs need to be discontinued while a patient is receiving the KD.6 Research has found, however, that there is an increased risk of acidosis and kidney stones in KD patients who are taking topiramate or zonisamide as well. There is also conflicting evidence regarding the co-administration of the KD and valproate. Some evidence suggests that this combination can lead to an increased risk of valproate toxicity as well as carnitine deficiency. A recent retrospective study, however, found that only 2 of 75 patients receiving the KD and valproate concurrently experienced mild to moderate AEs, suggesting co-administration is relatively safe.5  

The KD has proven to be an effective treatment option for pediatric patients with refractory epilepsy. Recent studies published have verified the effectiveness of the KD in various patient populations and have demonstrated its safety as well. Appropriate patient selection, diet initiation and administration, and patient monitoring are important aspects in the management of the KD. 


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References

    1.      Alberti MJ, Agustinho A, Argumedo L et al. Recommendations for the clinical management of children with refractory epilepsy receiving the ketogenic diet. Arch Argent Pediatr. 2016; 114(1): 56-63.

    2.      Van der Louw E, van den Hurk D, Neal E, et al. Ketogenic diet guidelines for infants with refractory epilepsy. Eur J Paediatr Neurol. 2016 Jul 17; DOI: 10.1016/j.ejpn.2016.07.009.

    3.      Ozdemir R, Kucuk M, Guzel O, Karadeniz C, Yilmaz U, Mese T. Does ketogenic diet have any negatives effect on cardiac systolic and diastolic functions in children with intractable epilepsy?: One-year follow-up results. Brain Dev. 2016 Apr 5. DOI: 10.1016/j.braindev.2016.03.009.

    4.      Appavu B, Vanatta L, Condie J, Kerrigan JF, Jarrar R. Ketogenic diet treatment for pediatric super-refractory status epilepticus. Seizure. 2016; DOI: http://dx.doi.org/10.1016/j.seizure.2016.07.006.

    5.      Spilioti M, Pavlou E, Gogou M et al. Valproate effect on ketosis in children under ketogenic diet. Eur J Paediatr Neurol. 2016 Jul;20(4):555-559.

    6.      Ketogenic diet. Epilepsy Foundation Web site. http://www.epilepsy.com/learn/treating-seizures-and-epilepsy/dietary-therapies/ketogenic-diet. Published August 2013. Reviewed March 2014. Accessed September 1, 2016.

Table 1 — Indications for the KD1

• Failure to control seizures after addition of a second medication

• Refractory epilepsy

• Epileptic syndromes

          o Myoclonic astatic epilepsy

          o Seizures caused by tuberous sclerosis complex

          o West syndrome refractory to vigabatrin or adrenocorticotropic hormone

          o Dravet syndrome

• Symptomatic epilepsies

          o Lafora body disease

          o Seizures caused by Rett syndrome

          o Landau-Kleffner syndrome

          o Sub acute sclerosing panencephalitis

          o Febrile infection-related epilepsy syndrome (FIRES)

          o Refractory status epilepticus

• Other conditions

          o Glucose transporter type 1 (GLUT-1) deficiency

          o Pyruvate dehydrogenase complex (PDHC) deficiency

          o Phosphofructokinase deficiency

          o Glycogen storage disease type V

          o Mitochondrial respiratory chain complex disorders

Table 2 — Essential Baseline Laboratory Monitoring1,2

• Complete blood count

• Renal profile (sodium, potassium, urea, creatinine, bicarbonate, albumin)

• Liver profile

• Calcium, phosphate, magnesium

• Glucose

• Vitamin D

• Lipid profile

• Free and acylcarnitine profile

• Urinalysis: calcium: creatinine ratio, hematuria, organic acids

Table 3 — Adverse Effects of the KD2,3

Implementation Phase

Maintenance Phase

Common Adverse Effects

• Metabolic acidosis

• Gastrointestinal complications (abdominal pain, nausea/vomiting, diarrhea)

• Dehydration

• Hypoglycemia

Dyslipidemia

• Gastrointestinal alterations (constipation, nausea, acid-reflux)

• Metabolic alterations (acidosis, hypokalemia, hypomagnesemia, carnitine deficiency, anemia, element deficiency)

• Osteopenia

Rare Adverse Effects

• Eating disorders (decreased appetite, food/ fluid rejection, self-induced vomiting)

• Kidney stones

• Pancreatitis

• Gallstones

• QT prolongation

• Cardiac conduction abnormalities

• Vascular and myocardial dysfunction

• Impaired growth in children

• Increased infection risk

• Bruising

• Increased serum uric acid

• Fractures

• Lipid-aspiration pneumonia