The ketogenic diet originated as medical therapy in the 1920s as standard of care for epilepsy. With the advent of anti-seizure drugs in the 1940s, the diet fell out of favor with clinicians and its use became relegated to a small number of children’s hospitals for use in pediatric epilepsy cases. In recent years, interest has been reignited in the diet due to its array of potential therapeutic applications.
Keto Defined The ketogenic diet consists of modifying macronutrient composition to a high-fat, low/moderate-protein, and very-low carbohydrate intake. The aim is to achieve nutritional ketosis—a metabolic state where the body shifts from utilization of glucose from carbohydrate intake to that of ketone metabolism from fatty acids. These ketone bodies can be derived exogenously from consumption of dietary fats, as well as endogenously from fatty acids liberated from adipose tissue. Ketones are considered to be an efficient fuel source for cellular energy production, and generate fewer metabolic byproducts such as reactive oxygen species. In addition, ketones possess anti-inflammatory and cell signaling properties, which impart additional physiological benefits alongside the metabolic, mitochondrial advantages (1). As a result of these various effects, the ketogenic diet is being researched and applied clinically across a range of chronic, pathological conditions.
Related: The Keto Diet
Neurological/Neurodegenerative Disease As mentioned previously, the ketogenic diet provides significant therapeutic benefits to epileptic patients. The glucose stabilizing effects of keto prevent dramatic shifts in blood sugars, which can induce neuronal firing in epileptic patients more sensitive to such swings in energy substrate. Greater glucose regulation and reduction in overall blood glucose can also help decrease the formation of advanced glycation end-products—metabolic byproducts identified as contributing factors in neurodegenerative disease such as Alzheimer’s and Parkinson’s disease (2). Growing evidence suggests that variations of the ketogenic diet provide a host of benefits in neurodegenerative patients including improvements to memory and cognitive performance (1, 3).
Related: Keto May Improve Memory
Diabetes Echoing the same enhancements to blood glucose homeostasis noted above, ketogenic diets appear to positively influence diabetic patients. Therapeutically, the reduction in carbohydrate intake reduces blood glucose load, resulting in improvements to insulin receptor sensitivity and insulin response. Research demonstrates the ketogenic diet improves glycemic control in diabetics and is associated with significant weight loss, which attenuates dysglycemia and improves related metabolic dysfunction (4, 5).
Cancer The often-devastating diagnosis of cancer leaves many oncology patients searching for any and every means to improve their chances for resolution, remission, and recovery. While diet alone is not enough to resolve tumor, dietary interventions can play a crucial role in as adjunct therapies in cancer treatment. The mechanisms that underpin keto’s effects in the body—anti-inflammatory activity, reduction in glycolysis/glycolytic flux, decreased oxidative stress, cell signaling, etc.—provide benefit against many of the hallmarks of cancer (6). Morphological and functional characteristics of the malignant cell vary; therefore, keto may not impact carcinogenesis across various cancer types in the same fashion. The greatest evidence for keto’s therapeutic benefits in cancer thus far is in relation to brain cancer or glioma (7, 8, 9). A substantial amount of preclinical literature and a growing body of clinical data suggests that ketogenic diet therapy possesses a good safety profile and serves as an efficacious adjunct to conventional antineoplastic treatment (7, 8, 9). In addition to its influence on cancer biology, keto has been shown to potentiate the anti-tumor effect of chemotherapies and radiation treatment, while simultaneously reducing toxicity (8, 10, 11).
Future Perspectives and Feasibility As new evidence emerges, clinicians will need to address the challenges of implementation and maintenance of the diet in patients. One of the greatest barriers may be long-term adherence to the dietary intake, as many patients report difficulty in consuming adequate dietary fat on a daily basis (upwards of 75-80% daily caloric intake should be derived from fats). One solution to overcome food-based limitations of fat consumption would be to supplement with a high-quality, high-fat formulation that mimics keto macronutrient balance.
Consuming a shake/smoothie with ingredients that provide adequate fat, while limiting protein and restricting carbohydrates, can serve as a complement to food intake. In addition, medium chain triglycerides (MCTs) can be used to augment the diet, in order to achieve daily targets of fat consumption. Caprylic acid is a medium chain triglyceride with 8 carbon atoms, hence its chemical shorthand, C8. C8 may have unique effects that other MCFAs lack. For example, research shows that capric acid (C10) is oxidized in human neurons at only 20% the rate of C8 (12). An oil that is purely C8 may have a larger therapeutic impact than one containing both C8 and C10, as many commercial products do. MCTs have unique properties that distinguish them from other fatty acids and which give them utility for adding to ketogenic diets as well as for incorporating into other dietary approaches for therapeutic reasons.
Clinical evaluation into the therapeutic benefits of keto continues, with conditions such as non-alcoholic fatty liver disease (NAFLD) (13), obesity (14), and migraine (15) being examined as potential targets for the metabolic dietary therapy.
Note: The views and opinions expressed here are those of the author(s) and contributor(s) and do not necessarily reflect those of the publisher and editors of WholeFoods Magazine.
- Anti-Oxidant and Anti-Inflammatory Activity of Ketogenic Diet: New Perspectives for Neuroprotection in Alzheimer’s Disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981249/
- The role of advanced glycation end products in various types of neurodegenerative disease: a therapeutic approach https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275793/
- The Expanding Role of Ketogenic Diets in Adult Neurological Disorders https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119973/
- Ketogenic diet in endocrine disorders: Current perspectives https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664869/
Ketogene Diät: evidenzbasierte therapeutische Anwendung bei endokrinologischen Erkrankungen
Hallmarks of Cancer: The Next Generation
Critical Reviews in Oncology/Hematology
The ketogenic diet for the treatment of malignant glioma http://www.jlr.org/content/56/1/5.long
Metabolic therapy: A new paradigm for managing malignant brain cancer
Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5110522/
Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism
Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium‐chain triglyceride ketogenic diet
Post hoc analyses of surrogate markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in patients with type 2 diabetes in a digitally supported continuous care intervention: an open-label, non-randomised controlled study
Ketogenic Diet for Obesity: Friend or Foe?
Potential Protective Mechanisms of Ketone Bodies in Migraine Prevention