The ketogenic diet has become increasing popular in recent years. With 25.4 million unique searches, the keto diet was the most Googled diet in the United States in 2020.1 With increased consumer interest, the “keto” food industry has grown rapidly, and as a result, the global ketogenic diet market was valued at $9.57 billion in 2019.2 The ketogenic diet has been discussed in popular culture by celebrities, health magazines, and documentaries. The popularity of this diet, and diets in general may be explained by the obesity epidemic in the United States and Missouri.
As of 2018, the prevalence of obesity in this country is 42%.3 In Missouri, two-thirds of the adult population is overweight or obese.4 Patients trying to lose weight often turn to popular diets, and in the past few years, the ketogenic diet has been a trendy option. With the increased interest in this diet, researchers are working to understand the impact of this pattern of eating on patients’ health. There is evidence of benefit, especially regarding weight loss, but there are also risks and concerns. The goal of this review is to offer clarity to physicians counseling patients on the ketogenic diet with the latest literature about benefits and risks.
In 1911, the first modern use of starvation for the treatment of epilepsy was noted. Two physicians in Paris reported that seizures were less severe in period of starvation.5 While this was the origin for the ketogenic diet, it wasn’t until 1921 that any physician tried to generate ketosis. Dr. Rollin Woodyatt noted that under conditions of starvation, acetone, and beta-hydroxybutyric acid appear.5 Woodyatt also uncovered that acetone and beta-hydroxybutyric acid were observed if patients ate a low carbohydrate diet. Around the same time, Dr. Russell Wilder theorized that ketonemia could be produced for therapeutic benefit, but with a low carb diet rather than starvation.5 He developed the term “ketogenic diet.” The ketogenic diet become very popular in the treatment of childhood epilepsy.5 As better epilepsy medications were developed throughout the twentieth century, the ketogenic diet lost prominence as an epilepsy treatment.
In the 1970s, nutritional ketosis was introduced as an idea for weight loss by Dr. Robert Atkins. In his book published in 1972, he describes how reducing carbohydrates “creates a unique chemical situation in the body…ketones are excreted, and hunger disappears.”6 Although the Atkins diet was one of the first, many other low carb diets have been popularized since the 1970s, from the South Beach Diet to variations of the Paleo and Mediterranean diets. While the details of low-carbohydrate diets may have changed, they have remained a mainstream option for weight loss. Over the past few decades, many studies have sought to quantify the efficacy of low carb diets in terms of weight loss as well as evaluate the potential for amelioration of chronic disease. As research has investigated the mechanisms behind ketosis and weight loss, the ketogenic diet has become the de facto low carb diet of choice in the media and public dialogue.
The mainstay of the ketogenic diet is that dietary carbohydrates are kept very low, with varying levels of protein and fat. The classic ketogenic diet is defined as a diet with one gram protein per kilogram of body weight, 10–15g carbohydrates per day, and the remaining calories from fat.7 The goal of the diet is to induce ketosis. Ketosis is thought to alter metabolic pathways to induce weight loss and potentially improve other health outcomes, such as a reduction of hyperglycemia and improvement in lipid profiles.
Under ordinary circumstances, the body primarily relies on carbohydrates for energy production. Insulin functions to extract and store energy derived from glucose. When the body has reduced carbohydrates available, insulin secretion is reduced. Initially, stored glucose in the form of glycogen is available for fuel, but after three to four days, this is depleted. Stored fat then becomes the most readily available fuel, and its breakdown into free fatty acids provides the raw materials for ketone production in the liver. Ketone production is primarily seen in times of starvation and prolonged exercise, but is also a function of adherence to a very-low carbohydrate diet. Importantly, in physiological ketosis, there is no change in blood pH versus pathological ketosis where there is a lowering of blood pH.
There is evidence that the ketogenic diet is an effective weight loss therapy. However, the exact mechanisms behind this weight loss remain unclear. For example, in a review of thermodynamic principles of weight loss, Feinman and Fine explain that low-carbohydrate diets have decreased insulin fluxes causing an increased rate of lipolysis.8 In other words, insulin inhibits lipolysis, and decreased insulin in low-carb diets causes increased fat breakdown.8 This theory is demonstrated in a study that follows 15 subjects for 12 weeks. The first six weeks they ate a low-carbohydrate diet and the next six weeks a low-fat diet. Blood results after the low-carbohydrate diet displayed decreased circulating triacylglycerol levels versus the low-fat diet.9 This reiterates the idea that low-carb diets increase fat breakdown.9
Another proposed weight loss mechanism is with decreased carbohydrate intake, the body will have to undergo increased amounts of gluconeogenesis to provide glucose to the brain.10 Gluconeogenesis is an expensive metabolic process.10 Theoretically, restricting carbohydrates depletes glucose stores, and increases gluconeogenesis.10 Another mechanism of weight loss is theorized to be direct appetite suppression. In a study with 17 men, subjects were given a high protein diet with two weeks of high-carb and two weeks of moderate-carb intake. During the low-carb, ketogenic diet phase, the participants reported significantly decreased hunger, leading the authors to hypothesize that ketosis itself may suppress hunger.11 While these mechanisms provide insight into how the ketogenic diet promotes decreased appetite and fat loss, it is important to note that evidence shows weight loss from the ketogenic diet can be partially attributed to water loss. In another study, 20 obese subjects were followed for four months on a ketogenic diet. Utilizing body composition assessments, investigators noted a substantial reduction in weight due to free water loss early in the study.12 It is important to look at length of duration in ketogenic diet studies as early, dramatic weight loss may be due to diuresis.
With these mechanisms in mind, numerous studies have evaluated the keto diet’s weight loss efficacy. There are many examples of randomized controlled trials where significant weight loss is achieved. For example, a meta-analysis by Mansoor et al. looked at mean weight loss in 11 randomized controlled trials for six months with a total of 1,369 participants. In the trials analyzed, participants were randomized into low carbohydrate versus low-fat diet plans. This study found that compared to low-fat diets, low-carbohydrate diets participants lost 2.17 kg more than the low-fat diets (95% CI −3.36, −0.99).13 However, the duration of some included studies was only six months. When looking at studies with a longer duration, the weight loss is less superior. For example, in a meta-analysis by Bueno et al., they analyzed 13 randomized controlled trials with a total of 1,415 subjects that were followed for at least 12 months. Again, the very-low-carbohydrate ketogenic diet was compared to a low-fat diet. After twelve months, subjects adhering to the ketogenic diet had lost 0.91 kg compared to the low-fat diet arm (95% CI −1.65, −0.17).14 While this was a significant result, the weight loss is less than what is seen in the shorter trials.
An interesting perspective is seen in a retrospective analysis of 89 subjects who were followed for 12 months. Subjects followed a diet plan which cycled between shorter periods of a ketogenic Mediterranean diet followed by longer periods of a traditional Mediterranean diet. For a majority (88.25%) of subjects there was substantial weight loss 100.7 ± 16.54 to 84.59 ± 9.71 kg.15 This study gives a good example of a weight loss regimen that patients may find more feasible. It combines benefits of the ketogenic diet’s short-term effects, with a maintenance diet that is less restrictive.
