Ketogenic Diet: Which Patients Benefit?

John Watson; Reviewed by: Anya Romanowski, MS, RD

Disclosures

March 20, 2018

In This Article

Latest Clinical Data for Various Diseases and Conditions

Epilepsy: An Old Treatment's New Benefits and Risks

KD may be attracting new attention, but its medical roots are nearly a century old. It was first designed as a treatment for epilepsy in 1921,[4] meant to mimic fasting and its known seizure-suppression benefits. The treatment fell out of favor with the advent of antiseizure medications like phenytoin a little over a decade later, but it returned in earnest when anecdotal accounts of children with treatment-resistant epilepsy becoming seizure free after adopting it were confirmed in a seminal 2008 randomized trial.[5]

KD is now widely in use for patients who have failed two mainline drugs,[6] with systematic reviews finding seizure-reduction rates as high as 85% after treatment.[7] Last year, Medscape reported on data that this intervention is just as effective as corpus callosotomy and vagal nerve stimulation in reducing seizures and improving other outcomes in children not responsive to drugs.

The reasons why it is so effective, however, are decidedly less clear. According to Jong M. Rho, MD, section chief of pediatric neurology at Alberta Children's Hospital in Canada, there are key unresolved questions around the direct effects of fatty acids on excitability, restricting glycolysis, and antioxidant activity and a possible role for the gut microbiome. His own recent work suggests that no single mechanism, but instead an array, drives the effects of this diet, including the antiseizure action of ketone bodies.[8]

"The notion that altered or abnormal metabolism is a root cause of epilepsy is growing," said Rho. He added that, in turn, this has increased research into novel targets that work as a "ketogenic diet in a pill," an idea that Rho and a colleague first outlined 10 years ago[9] and which remains elusive.

Despite its resounding success, KD is not without risks. In 2008, researchers reported two cases of sudden cardiac arrest in children on the diet for a period of 3 years.[10] Impaired myocardia function and QT prolongation (as documented on ECG) are complications associated with selenium deficiency from following KD.

Type 2 Diabetes/Obesity: Breaking a Cycle

The historical shift toward promoting low-fat diets, often in the form of high-carbohydrate foods with an increased glycemic burden, is viewed as a major contributor to the current obesity epidemic.[11]

Now researchers are investigating whether KD can help put the genie back in the bottle. The results have been promising, as separate meta-analyses show that KD leads to greater weight loss than its low-fat counterparts[12] while simultaneously suppressing appetite.[13]

In related efforts, KD has become a focal point for researchers targeting type 2 diabetes.

"By definition, type 2 diabetes is a state of carbohydrate intolerance," said Ludwig. "So it conceptually makes sense that reducing or eliminating carbohydrates would at least improve control (eg, reduce medication requirements) and perhaps help reverse the underlying metabolic problem."

KD's ability to reduce the necessity for antidiabetic drugs by improving glycemic control, weight loss, and other key outcomes has been observed in multiple studies in the past 20-plus years, both alone and in comparison with other dietary interventions.[14,15,16,17,18,19] It was also recently reported that ketogenic drink supplements may improve glycemia and insulin sensitivity, a sign of the continued desire to provide KD's benefits without the burden of making patients commit to it in full.[20]

Despite these gains, Ludwig reminds clinicians that "no existing trial is of sufficient quality to establish long-term safety and efficacy."

Because patients with diabetes who are restricting carbohydrates are at risk for hypoglycemia, it is recommended that implementation of this diet be accompanied by modification of dosage of insulin and insulin secretagogues.[21]

Cancer: Targeting Tumors Where They Grow

Cancer is a famously heterogeneous disease, though one throughline that connects multiple types is the Warburg effect, which describes how cancer cells use glucose as their main source of energy.[2] This has made KD an attractive option for supplemental cancer therapy, the theory being that cutting off the tumor's supply of energy will aid in containing its spread.

Fitting for a disease as multifaceted as cancer, the results have been inconsistent.[22] A case series of 78 patients with a variety of tumor types reported a trend toward improved outcomes, including one case of halted progression, among strict adherents to KD in the palliative setting.[23] In patients with glioma, case reports have noted no major side effects to this dietary approach and the achievement of stable disease of up to 6 weeks in certain patients.[24] Recent MR scans have noted the accumulation of ketone bodies in two patients with brain tumors who adhered to this diet.[25]

Building a compelling case for the efficacy of this approach is not currently possible.[22,26] To date, studies have been defined by their inconsistency, and even positive reports suffer from poor designs. Until these anecdotal reports are submitted to the rigors of randomized trials, KD will remain a promising but unfounded intervention for cancer.

Neurologic Disorders: Building Out From Epilepsy

The unquestionable efficacy of KD in epilepsy has given rise to a number of studies looking into its use for several neurologic disorders. The rationale behind this research is that KD can profoundly affect neuronal plasticity to enhance and normalize function.[27,28]

"The basic premise for using the ketogenic diet is that this therapy may provide neuroprotective effects in a very broad manner," explained Rho .

Results are early and often anecdotal but are impressive in their sheer range of applications. Migraines, thought to be caused in part by an energy deficiency disorder, responded favorably to ketone supplements in a preliminary study. Patients with mild to moderate Alzheimer disease exhibited improved scores on cognitive testing following 3 months of a variation of KD, and those with Parkinson disease also experienced improved function following exposure to this dietary intervention.[27] Behavioral improvements have also been noted in children with autism spectrum disorder who were receiving KD.[28]

Animal data also suggest a role for KD in the treatment of traumatic brain injuries, in that it may mitigate the metabolic changes in the brain caused by such injuries. The same may be true in amyotrophic lateral sclerosis, for which mitochondrial dysfunction is thought to possibly have a contributory role.[27]

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