As we explained in an earlier blog post, ketogenic diets were originally developed in the 1920s as a treatment for pediatric epilepsy. They fell out of favor after the development of anticonvulsant drugs, but were still used by people with intractable or refractory epilepsy that didn’t respond to these medications. The past few years have seen a major resurgence in interest in this very low-carb, high-fat diet for applications far beyond epilepsy. With exploding epidemics of obesity, type 2 diabetes, and metabolic syndrome, low-carb and ketogenic diets are garnering an increased share of research effort due to their powerful effects on lowering blood glucose and insulin, but these carbohydrate-restricted ways of eating are also being explored for other purposes, such as athletic performance and managing neurodegenerative disease.

Proven Therapeutic Applications of the Ketogenic Diet

Some of the physiology of ketosis mimics that seen in fasting, but the upside is, people don’t have to fast to experience these effects. Chief among what is typically observed are reductions in blood glucose and insulin levels, usually both fasting levels and post-prandial or area under the curve. In fact, reduction in dietary carbohydrate is so powerful for these purposes that some researchers have said it should be the first approach in diabetes management and the default treatment for type 2 diabetes and metabolic syndrome. (It should be noted, however, that not all patients require a strict KD to accomplish these ends. Some will experience metabolic improvements with a reduced carb intake above the threshold for ketosis.) Very low carbohydrate diets also reliably reduce triglycerides and raise HDL. Blood sugar improves so rapidly and so dramatically that some patients taking insulin and/or other hypoglycemic medications may need to have these doses adjusted as soon as the first day of adopting the diet.

Other effects noted on ketogenic diets include rapid and dramatic reductions in liver fat and improvement of cardiometabolic risk factors in obese patients with non-alcoholic fatty liver disease (NAFLD), significant reductions in body weight and insulin levels and improvements in hormonal profiles in women with PCOS, and exceptional glycemic control and reduction in hypoglycemic events in individuals with type 1 diabetes. (Type 1 diabetes is not a contraindication for a ketogenic or carbohydrate-restricted diet.)  

New Research Frontiers for the KD and Exogenous Ketones

Ketogenic diets and other ways of inducing ketosis are being explored for several applications beyond health concerns related to diabetes, obesity, and metabolic syndrome or insulin resistance. Obviously, KDs and variations thereof have a robust, proven track record for childhood and adult epilepsy. The use of KDs and exogenous ketones are also being studied for Alzheimer’s and Parkinson’s diseases, as well as amyotrophic lateral sclerosis (ALS) and traumatic brain injury. Mechanisms behind these include improved mitochondrial function and neuronal energy generation, increased GABA and decreased reactive oxygen species, increased glutathione levels, and more. Research is preliminary, and much of it so far has been done in animals, but the human data are promising, especially considering there are few to no effective interventions, pharmaceutical or otherwise, for these issues.

Ketogenic diets happen to be an effective nutritional therapy for a range of medical concerns, but that doesn’t mean that’s their only application. A perhaps surprising audience for interest in KDs is people who are already perfectly healthy but who are looking to boost athletic performance. Endurance athletes are finding there’s less frequency of “bonking” or “hitting the wall” when they’re fueled primarily by fat and ketones rather than carbohydrates. Research in this area is relatively new, and findings are mixed. Overall, it appears that those engaged in endurance activities may reap the most benefit, while those who prefer short bursts of high intensity activity may see a performance decline.  

Keto is Not a One-Size-Fits-All

Something to keep in mind with the growing popularity of KDs is that there is a high degree of individual variability. Not all individuals need to restrict carbohydrate to the same degree in order to experience the benefits of the shift from a glucose-centric to a fat-centric metabolism. Some people can be “in ketosis” (that is, showing elevated ketones in the blood, breath, or urine) while consuming more carbohydrate than others, and even those not displaying elevated ketones may still be “fat-adapted” as long as carbohydrate intake is sufficiently low. Plus, a high ketone level may not be required to induce some of the beneficial effects. In a study of the KD for type 2 diabetes, within just 10 weeks, many patients were able to discontinue insulin injections and several other medications even though the mean serum βOHB level was just 0.6 mmol/L. Even for epilepsy, seizure control has not been shown to be correlated with the ketone level; for some individuals it appears to be more closely related to fluctuations in blood glucose or insulin.

When the KD was originally developed for epilepsy, it was an extremely strict, difficult, and some would say unpalatable regimen. Over the years, increased research and a deeper understanding of some of the mechanisms at work has allowed the diet to be liberalized, allowing a greater carbohydrate intake while still being effective. Variations that have been proven effective, at least for epilepsy, include the modified Atkins, low glycemic, and MCT diets. This was welcome research, because depending on individual carbohydrate tolerance, ketogenic diets now can include an array of vegetables and low-sugar berries, and many individuals do not need to restrict their protein intake in order to experience the benefits of nutritional ketosis.