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Getting to Know the Ketogenic Diet and Its Clinical Applications

The ketogenic diet proves to be a powerful treatment plan to reach and stay at a healthy weight

by Christopher Keroack, MD, IFMCP

Excess adiposity remains one of the leading healthcare concerns in America. Two-thirds of our nation is overweight and one-third is obese.1 As a healthcare force, we recognize that lifestyle factors like nutrition and physical activity are major contributors to this epidemic. Because of this, novel approaches to nutrition have come about in the last decade to address this epidemic…some helpful, others not so much. Along with Hippocrates, the father of healthcare who said, “There are in fact two things, science and opinion; the former begets knowledge, the latter ignorance,” I also look at these advancements through the lens of science over opinion.

Recent approaches to the epidemic of obesity involve the return to a low-carbohydrate approach to nutrition.2 This has brought about two major styles of dieting currently: The ketogenic diet and the Paleolithic diet. These diets are unique and not interchangeable. The Paleolithic diet is difficult to define, with many interpretations based on opinion. At its core, the Paleolithic diet describes a modern diet plan requiring the consumption of foods presumed to have been the only foods available to or consumed by humans during the Paleolithic era. The Paleolithic diet typically includes vegetables, fruits, nuts, roots, and meat, while usually excluding foods such as dairy products, grains, sugar, legumes, processed oils, salt, alcohol, and coffee.3-4 The diet not only abstains from processed foods, but also avoids the foods that humans began eating after the Neolithic Revolution when humans transitioned from hunter-gatherer lifestyles to settled agriculture.3-4

The ketogenic diet is very different from the “Paleo” way of eating. The ketogenic diet originates from its use in the 1920s as a treatment for epilepsy. It was reintroduced as a weight loss method in the 1960s. The key to the ketogenic plan is the macronutrient content of fats, proteins, and carbohydrates rather than the mere removal of processed foods along with the inclusion of wild or hunter/gatherer foods. In this way, changes in physiology and metabolic processes occur within the body based on the strategic breakdown of macronutrients (i.e., high-fat, moderate-protein, low-carbohydrate) and therefore, primary fuel source utilized by the body (i.e., ketones from fat metabolism).2,5

It is this shift in macronutrient composition that makes the ketogenic plan so powerful in the treatment of overweight and obesity.2 The macronutrient constitution leads to greater satiety, even with lower calorie content. In addition, there are metabolic effects- gluconeogenesis from amino acids and triglyceride-derived glycerol- which lead to greater calorie utilization in the ketogenic diet. These factors make the ketogenic diet well-suited for the patient struggling with obesity. However, the ketogenic diet is able to do far more than induce weight loss.

The high-fat/low-carbohydrate nutritional approach of the ketogenic diet produces two major effects: lowering of insulin and the production of ketone bodies. And it is these two metabolic shifts that generate the health benefits associated with the ketogenic diet.6 First, the insulin reduction from the low-carbohydrate input leads to specific health improvements influenced by obesity, for example: elevated cholesterol, type 2 diabetes, polycystic ovarian syndrome (PCOS), metabolic syndrome, and several types of cancer.2

In addition, the production of ketones from the elevated dietary fat resources becomes an alternative fuel source for the brain, heart, and muscle cells.2 Ketones are more efficient and less oxidative than carbohydrate fuel sources. In addition, ketones influence many physiological and neurological pathways. For example, ketones are believed to increase mitochondrial genesis and decrease neuronal membrane excitability; both of these mechanisms are beneficial to the brain and heart health.2 In addition, ketones influence mechanistic target of rapamycin (mTOR) receptors, which play a large role in the regulation of cell growth, proliferation, motility, and survival, as well as protein synthesis, autophagy, and transcription.2

It is this macronutrient composition and subsequent insulin suppression and utilization of ketones for fuel that set the ketogenic diet apart from other dietary approaches. It is critical to understand the science behind any diet plan that we choose for our patients, so we can partner with them using personalized, targeted nutrition therapies. The ketogenic diet should be considered a useful, evidence-based tool for weight management. In fact, several studies suggest that the ketogenic pattern may be more effective at weight loss and related comorbid improvements than low-fat diets or Mediterranean diets.2 Furthermore, the body of evidence is growing for the broader use of the ketogenic diet in many healthcare issues that your patients face, particularly those with underlying metabolic dysfunction such as hyperlipidemia, diabetes, PCOS, metabolic syndrome, and cancers, as well as cardiovascular and neurological diseases.2


  1. USDHHS. CDC. NCHS. Health, United States, 2016: With Chartbook on Long-term Trends in Health. Accessed July 17, 2018.
  2. Paoli A et al. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr. 2013;67(8):789–796.
  3.  Zuk M. Paleofantasy: What Evolution Really Tells Us about Sex, Diet, and How We Live. W.W. Norton & Co. 2013.
  4.  Environmental Nutrition. The modern take on the Paleo diet: is it grounded in science? Accessed July 17, 2018.
  5. Atkins RC. Dr Atkins’ Diet Revolution: The High Calorie Way to Stay Thin Forever. D. McKay Co. 1972.
  6. Veech RL. The therapeutic implications of ketone bodies: The effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot Essent Fatty Acids. 2004;70(3):309–319.

Christopher Keroack, MD, IFMCP

Dr. Christopher Keroack is the chief executive officer at New England Center for Functional Medicine. Dr. Keroack guides patients through foundational and practical approaches to health that focus on dietary guidelines, activity regimens, stress management, and sleep management that are personally designed for each patient. Dr. Keroack authored “Changing Directions: Navigating the Path to Optimal Health and Balanced Living,” a pioneering work that blends traditional and alternative medicine into a balance of healing that is Dr. Keroack’s signature approach to healthcare. Dr. Keroack is board certified in Internal Medicine and Functional Medicine. He received his formal education from Amherst College (BA), Springfield College (MS), and Tufts University School of Medicine (MD).

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