Nutrition & Health Info Sheets provide current information about nutrition, health, and food for both consumers and professionals. This article synthesizes available data to provide a detailed overview of the ketogenic diet, also known as the "keto" diet.
Introduction to the Ketogenic Diet
The ketogenic diet is a strict eating pattern characterized by high fat, moderate protein, and very low carbohydrate intake. Following this diet can induce a metabolic state called ketosis, where the body shifts from using glucose to using fat as its primary energy source. The ketogenic diet has gained popularity as a method for weight loss and potential health benefits.
Historical and Current Uses
The ketogenic diet was first used in the 1920s as a treatment for pediatric drug-resistant epilepsy to reduce seizure activity. It is still prescribed for seizures in the United States when medications are ineffective and other treatments are not viable.
The Science Behind Ketosis
The primary focus of the ketogenic diet is not calorie or portion restriction, but rather the careful restriction of certain foods, which causes the body to switch from glucose metabolism to fat metabolism to meet energy needs. Clinical trials and popular versions of this diet generally restrict daily carbohydrate consumption to below 50 grams, mainly from non-starchy vegetables, while emphasizing protein and fat consumption.
The general premise of the ketogenic diet is the induction of physiological ketosis, also known as nutritional ketosis. Reducing carbohydrate intake below 20 grams per day results in insufficient body glucose reserves for supplying the central nervous system with enough energy solely through glucose. Glucose serves as the human brain’s primary source of energy as fatty acids are unable to pass the blood-brain barrier.
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Due to carbohydrate restrictions, the liver uses body fat stores to create ketone bodies for energy metabolism. These ketone bodies can cross the blood-brain barrier, allowing the brain to use these compounds for fuel. During ketosis, the brain adapts to lower levels of available glucose by changing its fuel source to rely on ketone bodies for energy. It is important to note that amino acids in protein food sources can be converted to glucose, and therefore halt physiological ketosis.
Food Choices on a Ketogenic Diet
Individuals following the ketogenic diet primarily consume animal products, such as meat, poultry, fish, processed meat, shellfish, and eggs; salad vegetables, such as leafy greens, cucumber, and celery; and low-carbohydrate/non-starchy vegetables, such as cauliflower, broccoli, asparagus, and squash.
Potential Health Benefits
There has been interest in low-carbohydrate and ketogenic diets for various health reasons, including:
Weight Loss
Research suggests that a ketogenic diet can be effective for weight loss. One randomized, controlled trial compared a very-low-carbohydrate diet (VLCD) to a calorie-restricted low-fat diet (LFD). Results showed that participants on both diets reduced calorie consumption by comparable amounts at 3 to 6 months, but those on a VLCD lost more weight and more body fat than those following a LFD. Researchers concluded that VLCD diets are more effective than LFD diets in the short term for weight loss and, after 6 months, are not associated with increased risk that would impair cardiovascular health. An uncontrolled 12-week intervention with obese adults on the ketogenic diet resulted in significant weight loss in the subjects (-18 +/- 9 kg in men and -11 +/- 3 kg in women). In a meta-analysis of 13 studies, individuals assigned to a very-low-carbohydrate ketogenic diet (VLCKD) achieved greater weight loss than those assigned to a LFD in the long term, which was defined as 12 months or more post-intervention.
Glycemic Control in Type 2 Diabetes
Other research has investigated the impact of the ketogenic diet on insulin sensitivity and glycemic control for diabetes management. In one study, researchers compared the effectiveness of a VLCKD in improving glycemic control and weight loss in adults with type 2 diabetes to an energy-restricted diet with 45 - 60% of calories from carbohydrates. The percent of participants with hemoglobin A1c (HbA1c) levels above 7% decreased from 46.7% to 12.8% in the ketogenic diet group, which was not significantly different from the energy-restricted group.
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Cancer Treatment
The Warburg effect describes the tendency of cancer cells to rely on glycolysis to generate energy, which requires glucose for fuel. In contrast, healthy cells are able to adapt to alternative fuel sources, such as ketone bodies acetoacetate and beta-hydroxybutyrate; therefore, researchers have hypothesized that consuming a ketogenic diet deprives cancer cells of energy creating an anti-tumor effect. This hypothesis has been tested in many animal studies and a limited number of human clinical trials. However, lack of compliance with the diet and the effect of weight loss on reducing risk makes it difficult to draw conclusions about the effect of a ketogenic diet on cancer survival. Other research suggests that different types of cancer respond to a ketogenic diet with an anti-tumor effect, while others respond with no or even a pro-tumor effect.
Other Potential Treatments
The ketogenic diet is being investigated as a treatment for Parkinson’s disease, Alzheimer’s disease, hypercholesterolemia, autism, and depression. It is also being investigated as a way to promote healthy aging; many animal trials support beta-hydroxybutyrate's effect of reducing aspects of cell aging. However, to date, there are too few reported studies to enable conclusions regarding efficacy in humans.
Risks and Side Effects
It is strongly advised and encouraged to receive supervision and consultation by experienced physicians and dietitians while on this diet, especially for those taking insulin or oral hypoglycemic medications for diabetes, due to a risk of serious hypoglycemia. This dietary pattern is not recommended for individuals with pancreatic disease, liver conditions, thyroid problems, eating disorders or a history of eating disorders, and gallbladder disease or those who have had their gallbladders removed.
Early-onset adverse effects associated with the ketogenic diet are sometimes referred to as the “keto flu” and include acidosis (low blood pH), hypoglycemia (low blood sugar), constipation, dehydration, dizziness, and fatigue. Long-term harmful effects from the ketogenic diet may include dyslipidemia (abnormal amount of lipids in the blood), kidney stones, and decreased bone density. There is also concern that highly restrictive diets, such as the ketogenic diet, may be low in certain key nutrients. For example, one intervention study observed that a ketogenic diet resulted in an average fiber intake of 6.4 grams per day, well below the recommended 28 grams per day for a 2,000 calorie diet.
Dyslipidemia
Limited research suggests blood levels of cholesterol and lipids can be adversely affected when on the ketogenic diet. One study of dyslipidemia on the ketogenic diet, observed 141 children over the course of 2 years, and found an increase in very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) and a decrease in high-density lipoprotein cholesterol (HDL). Total cholesterol increased by an average of 33% in the participants of the study, resulting in 61% of participants with total cholesterol classified as “high” and another 17% who were “borderline high.” Over a 2-year follow-up period, average total cholesterol decreased, but remained above the high total cholesterol cutoff values.
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Kidney Stones
Kidney stones have been observed to occur more frequently in children on the ketogenic diet. Kidney stones are thought to be a secondary factor associated with acidosis, urine acidification, hypercalciuria (high calcium in the urine), and hypocitraturia (low citrate in the urine) when on the ketogenic diet.
Bone Density
Bone density may decrease while on the ketogenic diet. There have been reports in scientific literature of a higher risk of skeletal fractures in children on the ketogenic diet.
Comparison to Dietary Guidelines
The ketogenic diet differs from the 2015 - 2020 Dietary Guidelines for Americans (DGA) and National Academy of Medicine (NAM) recommendations for dietary proportions of protein, fat, and carbohydrates. Both the DGA and NAM recommend 20 - 35% of calories from fat per day, while the example ketogenic diet has 70-80% fat from total daily calories. The ketogenic diet tends to be higher in protein and fat, and lower in carbohydrates and dietary fiber than recommended by the DGA due to limited amounts of grains, refined sugars, legumes, and certain vegetables and fruits.
Ketosis Explained
Ketosis is a process that occurs when your body uses fat as its main fuel source. Normally, your body uses blood sugar (glucose) as its key energy source. You typically get glucose in your diet by eating carbohydrates (carbs) such as starches and sugars. Your body breaks the carbohydrates down into glucose and then uses the glucose as fuel. Your liver stores the rest and releases it as needed.
When your carb intake is very low, these glucose stores drain down. Since your body doesn’t have enough carbs to burn for energy, it burns fat instead. As your body breaks down fat, it produces a compound called ketones. The ketones, or ketone bodies, become your body and brain’s main source of energy.
The fat your body uses to create ketones may come from your diet (nutritional ketosis), or it may come from your body’s fat stores. Your liver produces a small amount of ketones on its own. But when your glucose level decreases, your insulin level decreases. This causes your liver to ramp up the production of ketones to ensure it can provide enough energy for your brain. Therefore, your blood has high levels of ketones during ketosis.
Entering Ketosis
To enter and stay in ketosis, you’ll need to stay under 50 grams of carbohydrates per day. That’s about three slices of bread, two bananas, or 1 cup of pasta. If you eat between 20 and 50 grams of carbohydrates each day, it will usually take you two to four days to enter ketosis. However, the time it takes to enter this state varies based on several factors. It may take you a week or longer to get into ketosis. Factors that may influence how long it takes you to achieve this state include your:
- Age
- Carbohydrate, fat, and protein intake
- Physical activity level
- Metabolism
- Sleep health
- Stress level
If you eat a high-carb diet before starting a keto diet, it may take you longer to reach ketosis than someone who consumes a low-carb diet because your body needs to exhaust its glucose stores first. You may be able to get into ketosis faster with intermittent fasting. The most common method of intermittent fasting involves eating all of your food within eight hours. Then, you fast for the remaining 16 hours of a 24-hour period.
Benefits of Ketosis
Research has shown that ketosis may have several health benefits. One of the biggest benefits of ketosis may be weight loss. The process can help you feel less hungry, which may lead to eating less food. It can help you lose belly fat (visceral fat) while maintaining a lean mass. Other possible benefits of ketosis include treating and managing diseases such as:
- Epilepsy: Healthcare providers often put children with epilepsy on the keto diet to reduce or even prevent seizures by altering the “excitability” part of their brain.
- Other Neurologic Conditions: Research has shown the keto diet may help improve neurological conditions such as Alzheimer’s disease, autism, and brain cancers such as glioblastoma.
- Type 2 Diabetes: The keto diet can help people with Type 2 diabetes lose weight and manage their blood sugar levels.
- Heart Disease: The keto diet may lower your risk of developing cardiovascular disease by lowering your blood pressure, improving your HDL (“good”) cholesterol levels, and lowering your triglycerides.
- Metabolic Syndrome: The keto diet may reduce your risk of developing metabolic syndrome, which is associated with your risk of heart disease.
Ketosis has also been shown to increase your focus and energy. The keto diet delivers your body’s energy needs in a way that reduces inflammation. Research suggests your brain works more efficiently on ketones than on glucose.
Side Effects of Ketosis
The keto diet has many benefits, but it may come with some side effects. One of the signs of ketosis may include “keto flu,” which includes symptoms such as upset stomach, headache, and fatigue.
Clinical Significance of Ketogenic Diet
Recent epidemiological studies have challenged the popular belief that high-fat diets directly cause obesity and diseases like coronary heart disease, diabetes, and cancer. These studies have not observed a conclusive causal relationship between dietary fat intake and these conditions. Additionally, research on animals fed high-fat diets has not demonstrated a direct link to obesity. Regarding overall caloric intake, carbohydrates comprise around 55% of the typical American diet, ranging from 200 to 350 grams daily. Until recently, the significant potential of refined carbohydrates to cause detrimental effects was largely overlooked.
A comprehensive study conducted in 2012 examining cardiometabolic deaths in the United States revealed that approximately 45.4% of these deaths, including those attributed to heart disease, stroke, and type 2 diabetes, were associated with suboptimal intakes of 10 specific dietary factors. Among the nutritional factors examined, the study found that the highest estimated mortality was associated with high sodium intake, accounting for 9.5% of cardiometabolic deaths. This was followed by nuts and seeds (8.5%), high intake of processed meats (8.2%), low intake of omega-3 fats (7.8%), low intake of vegetables 7.6%), low intake of fruits (7.5%), and high intake of artificially sweetened beverages (7.4%). The lowest estimated mortality was associated with consuming low polyunsaturated fats (2.3%) and unprocessed red meats (0.4%). In addition to the direct harm caused by excessive consumption of low-quality carbohydrates, another concern is that such consumption can crowd out healthier food options from the diet.
Diabetes
A recently published randomized crossover trial comparing the effects of ketogenic and Mediterranean diets revealed that patients who adhered to a well-formulated ketogenic diet experienced improved glucose control and reduced body weight. Although the blood sugar levels were reduced, the decrease in HbA1c levels was modest, with a reduction of less than 20%. Additionally, study participants had difficulty adhering to the strict dietary regimen. These findings have led to debates, as some argue that any restriction on carbohydrate intake would inevitably lead to a reduction in blood sugar and HbA1c levels.
Heart Disease
Research suggests that a ketogenic diet can reduce the risk of heart disease. A systematic review published in the American Journal of Clinical Nutrition in 2019 found that a ketogenic diet can lower markers of inflammation, which is associated with a decreased risk of heart disease. Furthermore, a study published in Circulation in 2020 demonstrated that a low-carbohydrate, high-fat ketogenic diet could reduce low-density lipoprotein (LDL) cholesterol levels, a significant risk factor for heart disease. These findings indicate that a ketogenic diet may effectively reduce the risk of heart disease.
Obesity
Over the past century, the prevalence of obesity has increased, leading to the emergence of various diet programs. Among them, the ketogenic diet has shown significant benefits compared to other diets. A meta-analysis of 11 studies found that the low-carbohydrate diet group experienced considerable weight reductions compared to the low-fat diet group. Individuals assigned to a very low-carbohydrate ketogenic diet (VLCKD) experienced decreases in body weight, triglycerides, and diastolic blood pressure, as well as increases in HDL-C and LDL-C. Moreover, the VLCKD resulted in more significant long-term weight loss compared to a low-fat diet, suggesting it is a potential alternative option for obesity management. Similarly, a meta-analysis of randomized controlled trials (RCTs) revealed that the ketogenic diet is particularly effective in improving metabolic parameters related to glycemic control, weight management, and lipid control in obese individuals, particularly those with preexisting diabetes. Compared to low-fat diets, the ketogenic diet demonstrated superior outcomes in terms of glycemic control, weight loss, and lipid markers. The ketogenic diet also showed positive effects on insulin resistance and lipid markers, suggesting it can improve metabolic markers independent of weight loss.
Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease characterized by hepatic adiposity, which can lead to liver damage, fibrosis, and inflammation. Weight loss is recommended as part of the general clinical management of NAFLD. The ketogenic diet induces a shift in the gut microbiome, resulting in increased folate production and reduced inflammation and oxidative stress. Furthermore, the ketogenic diet promotes a sense of satiety and induces epigenetic modifications that play a role in the pathogenesis of NAFLD and allows the expression of antiinflammatory markers at the genetic level.
Polycystic Ovarian Syndrome (PCOS)
PCOS is related to increased insulin resistance, hyperinsulinemia, T2DM, dyslipidemia, and hyperandrogenism. The mechanism by which a ketogenic diet helps PCOS is unclear. However, many theories postulate lowering insulin resistance helps with improving androgen levels. A crossover study compared the effects of a standard diet and a low-carbohydrate diet on PCOS and showed that the low-carbohydrate diet decreased glycemia, fasting serum insulin, and testosterone and increased insulin sensitivity.
Neurodegenerative Disorders
- Alzheimer Disease: A ketogenic diet regulates brain metabolism, mitochondrial homeostasis, and inflammation in Alzheimer disease by increasing mitochondrial function and reducing oxidative stress.
- Parkinson Disease: A pilot RCT compared the effect of a low-fat diet versus the ketogenic diet in Parkinson's disease. The study had 47 patients, and both groups showed a decrease in the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS). However, the group on the ketogenic diet showed a more significant reduction than the low-fat diet group. Also, the ketogenic group showed more significant improvements in nonmotor symptoms.
- Epilepsy: The ketogenic diet, described initially as a successful treatment for epilepsy, has regained attention through numerous studies showcasing its effectiveness in patients with drug-resistant epilepsy and certain pediatric epilepsy syndromes.
Cancer
The therapeutic impact of the ketogenic diet on tumors, such as neuroblastoma, acute myeloid leukemia, and glioblastoma, is attributed to its ability to downregulate GPR109A expression, activate mTORC1, and reduce glucose uptake at the tumor site. This results in suppressed tumor growth, improved survival rates, and enhanced efficacy of chemotherapy.
Variations of the Ketogenic Diet
There are several variations of the ketogenic diet therapy:
- Classic Ketogenic Diet: This is the strictest form of diet therapy, where 70 to 90 percent of your child’s calories being provided by fat (compared to the 25 to 40 percent that is usually recommended for children). The amount of fat is determined by the ketogenic ratio, which is the ratio of grams of fat to grams of carbohydrate plus protein. It is the strongest and most precise but also the least flexible of diet therapies. All foods must be carefully prepared and weighed on a gram scale using recipes created by a ketogenic dietitian. It consists of a ratio in grams of fat to non-fat nutrients (protein and carbohydrates combined). Ratios range from 4:1 to 1:1.
- Modified Atkins Diet (MAD): This is a more flexible version of the classic ketogenic diet that is popular amongst adolescents and adults as it allows patients more freedom in food choice, meal timing, and portion sizes. The diet therapy team educates patients during an outpatient teaching session, which includes individualized meal planning and how to use household measures (e.g. measuring cups and spoons) to prepare meals. The primary source of calories (~80-90% of diet) is fat: vegetable oils, butter, mayonnaise and heavy cream. Carbohydrates are very limited on the diet; carbohydrate sources include non-starchy vegetables and small amounts of fruit. Grains are eliminated, and small amounts of dairy may be incorporated depending on the individual’s diet prescription.
- Low Glycemic Index Treatment (LGIT): This is an alternative dietary treatment, which is less commonly used and not intended to promote ketosis. On LGIT, patients limit carbohydrate intake to ~40-60 grams daily with an emphasis on complex carbohydrates.
Long-Term Considerations
Following a very high-fat diet may be challenging to maintain. Some negative side effects of a long-term ketogenic diet have been suggested, including increased risk of kidney stones and osteoporosis, and increased blood levels of uric acid (a risk factor for gout). Possible nutrient deficiencies may arise if a variety of recommended foods on the ketogenic diet are not included. It is important to not solely focus on eating high-fat foods, but to include a daily variety of the allowed meats, fish, vegetables, fruits, nuts, and seeds to ensure adequate intakes of fiber, B vitamins, and minerals (iron, magnesium, zinc)-nutrients typically found in foods like whole grains that are restricted from the diet.