Obesity remains a significant global health concern, contributing to millions of deaths annually and increasing the risk of chronic diseases. Implementing tailored dietary regimens, such as the ketogenic diet, can help mitigate this epidemic. The ketogenic diet, characterized by high-fat and very low-carbohydrate intake, has shown efficacy in rapid weight loss and potential benefits for various health conditions.
Introduction to the Ketogenic Diet
Despite continuous advances in the medical world, obesity remains a major worldwide health hazard, contributing to adult mortality as high as 2.8 million per year. This pervasive issue is closely linked to the development of chronic diseases, including diabetes, hypertension, and heart disease, all predominantly associated with an unhealthy lifestyle and poor dietary habits. However, implementing appropriately tailored diet regimens for weight reduction can potentially mitigate the obesity epidemic to some extent. Among these regimens, the very low-carbohydrate and high-fat ketogenic diet has emerged as a highly effective approach for rapid weight loss.
The ketogenic diet is a dietary approach characterized by high-fat and low-carbohydrate intake, aiming to facilitate weight loss, enhance mental clarity, and boost energy levels. By significantly reducing carbohydrate consumption and increasing fat and protein intake, this diet induces a metabolic state called ketosis, where the body utilizes fat as its primary fuel source instead of carbohydrates. The primary goal of the ketogenic diet is to decrease overall body fat and improve metabolic health. Recent research indicates potential benefits in reducing the risk of certain diseases, including type 2 diabetes, hyperlipidemia, heart disease, and cancer.
How the Ketogenic Diet Works
A ketogenic diet primarily consists of high fat intake, moderate protein consumption, and low carbohydrate intake. The macronutrient distribution typically ranges from approximately 70-80% fat, 10-20% protein, and 5-10% carbohydrates. Russell Wilder first used the ketogenic diet to treat epilepsy in 1921. He also coined the term "ketogenic diet." Through his observations, Wilder noticed the diet reduced the frequency and intensity of seizures in a subset of his patients who followed this dietary approach. Carbohydrates typically serve as the main source of energy production in the body's tissues. However, when carbohydrate intake is restricted to less than 50 grams daily, insulin secretion decreases significantly, leading the body into a catabolic state. As a result, glycogen stores are depleted, triggering a series of metabolic changes. Two prominent metabolic processes come into play when carbohydrates are limited in body tissues: gluconeogenesis and ketogenesis.
Gluconeogenesis
Gluconeogenesis is the process by which the body produces glucose internally, primarily in the liver, using substrates such as pyruvate, lactic acid, glycerol, and specific amino acids classified as glucogenic. When glucose availability drops, the endogenous breakdown of glucose cannot provide sufficient energy, ie, adenosine triphosphate (ATP). The metabolic pathway switches to ketogenesis to provide an alternate energy source in the form of ketone bodies. Ketone bodies replace glucose as a primary source of energy.
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Ketogenesis and Nutritional Ketosis
During ketogenesis, insulin secretion is low due to feedback from blood glucose levels, leading to a decrease in the stimulation of fat and glucose storage. Other hormonal changes may contribute to the increased fat breakdown resulting in fatty acids. Fatty acids are metabolized to acetoacetate, later converted to beta-hydroxybutyrate and acetone. These primary ketone bodies (ie, acetoacetate, beta-hydroxybutyrate, and acetone) accumulate in the body as the ketogenic diet is sustained and serve as an alternative energy source for the body. This metabolic state is referred to as "nutritional ketosis." As long as the body is deprived of carbohydrates, the metabolism remains ketotic. Nutritional ketosis is generally considered safe since it involves the production of ketone bodies in moderate concentrations without significantly impacting blood pH. Nutritional ketosis differs from ketoacidosis, a severe and life-threatening condition characterized by excessively high levels of ketone bodies, leading to acidosis in the blood.
Ketone bodies synthesized within the body can be effectively utilized as an energy source by vital organs such as the heart, muscle tissue, and kidneys. Ketone bodies can also cross the blood-brain barrier to provide an alternative energy source for the brain. RBCs and the liver do not utilize ketones due to a lack of mitochondria and enzyme diaphorase.
Ketone body production depends on several factors, such as resting basal metabolic rate (BMR), body mass index (BMI), and body fat percentage. Ketone bodies, often referred to as a "super fuel," produce a greater amount of ATP than glucose. When comparing energy production, 100 grams of acetoacetate generates 9,400 grams of ATP, 100 grams of beta-hydroxybutyrate yields 10,500 grams of ATP, while 100 grams of glucose produces only 8,700 grams of ATP. Ketone bodies enable the body to maintain efficient fuel production even when experiencing a caloric deficit. Four types of ketogenic diets are categorized based on the percentage of macronutrients they contain, allowing for increased compliance with the regimens. The ketogenic diet's short-term effects (up to 2 years) are well-reported and established. However, the long-term health implications are unknown due to limited literature.
Types of Ketogenic Diets
Several versions of the ketogenic diet exist, each with varying macronutrient ratios and approaches:
- Standard Ketogenic Diet (SKD): A very low-carb, moderate-protein, and high-fat diet, typically consisting of 70% fat, 20% protein, and 10% carbs.
- Cyclical Ketogenic Diet (CKD): Involves periods of higher carb refeeds, such as 5 ketogenic days followed by 2 high-carb days.
- Targeted Ketogenic Diet (TKD): Allows the addition of carbs around workouts.
- High-Protein Ketogenic Diet: Similar to SKD, but includes more protein, with a ratio of 60% fat, 35% protein, and 5% carbs.
The standard and high-protein ketogenic diets are the most extensively studied. Cyclical and targeted ketogenic diets are more advanced methods primarily used by bodybuilders or athletes.
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Clinical Significance and Health Benefits
Recent epidemiological studies have challenged the 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.
Diabetes Management
A randomized crossover trial comparing ketogenic and Mediterranean diets revealed that patients who adhered to a well-formulated ketogenic diet experienced improved glucose control and reduced body weight. Although blood sugar levels were reduced, the decrease in HbA1c levels was modest. A small study in women with type 2 diabetes also found that following a ketogenic diet for 90 days significantly reduced levels of hemoglobin A1C, which is a measure of long-term blood sugar management. Another study in 349 people with type 2 diabetes found that those who followed a ketogenic diet lost an average of 26.2 pounds (11.9 kg) over a 2-year period. This is an important benefit when considering the link between weight and type 2 diabetes. What’s more, they also experienced improved blood sugar management, and the use of certain blood sugar medications decreased among participants throughout the course of the study.
The ketogenic diet can boost insulin sensitivity and cause fat loss, leading to significant health benefits for people with type 2 diabetes or prediabetes.
Heart Disease Risk Reduction
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.
Obesity Management
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.
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A ketogenic diet can help you lose slightly more weight than a low fat diet. This often happens with less hunger.
Nonalcoholic Fatty Liver Disease (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)
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. The ketogenic diet can help reduce insulin levels, which may play a key role in polycystic ovary syndrome.
Neurodegenerative Disorders
- Alzheimer's Disease: A ketogenic diet regulates brain metabolism, mitochondrial homeostasis, and inflammation in Alzheimer's disease by increasing mitochondrial function and reducing oxidative stress.
- Parkinson's Disease: A pilot RCT compared the effect of a low-fat diet versus the ketogenic diet in Parkinson's disease. 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. Research has shown that the ketogenic diet can cause significant reductions in seizures in epileptic children
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.
Foods to Eat and Avoid on a Ketogenic Diet
The key to keto is knowing what's in your food. A typical keto diet will consist of foods high in protein and healthy fats, including red meat and poultry, fatty fish, non-starchy vegetables, dark, leafy greens, avocado, coconut oil, keto-style coffee, bone broths and of course plenty of water.
Foods to Avoid
- Sugary foods: soda, fruit juice, smoothies, cake, ice cream, candy, etc.
- Grains or starches: wheat-based products, rice, pasta, cereal, etc.
- Fruit: all fruit, except small portions of berries or strawberries
- Beans or legumes: peas, kidney beans, lentils, chickpeas, etc.
- Root vegetables and tubers: potatoes, sweet potatoes, carrots, parsnips, etc.
- Low fat or diet products: low fat mayonnaise, salad dressings, and condiments
- Some condiments or sauces: barbecue sauce, honey mustard, teriyaki sauce, ketchup, etc.
- Unhealthy fats: processed vegetable oils, mayonnaise, etc.
- Alcohol: beer, wine, liquor, mixed drinks
- Sugar-free diet foods: sugar-free candies, syrups, puddings, sweeteners, desserts, etc.
Avoid carb-based foods like grains, sugars, legumes, rice, potatoes, candy, juice, and even most fruits.
Foods to Eat
- Meat: red meat, steak, ham, sausage, bacon, chicken, and turkey
- Fatty fish: salmon, trout, tuna, and mackerel
- Eggs: pastured or omega-3 whole eggs
- Butter and cream: grass-fed butter and heavy cream
- Cheese: unprocessed cheeses like cheddar, goat, cream, blue, or mozzarella
- Nuts and seeds: almonds, walnuts, flaxseeds, pumpkin seeds, chia seeds, etc.
- Healthy oils: extra virgin olive oil, and avocado oil
- Avocados: whole avocados or freshly made guacamole
- Low carb veggies: green veggies, tomatoes, onions, peppers, etc.
- Condiments: salt, pepper, herbs, and spices
Base the majority of your diet on foods such as meat, fish, eggs, butter, nuts, healthy oils, avocados, and plenty of low carb veggies. It’s best to base your diet mostly on whole, single-ingredient foods.
Sample Ketogenic Meal Plan
Here is a sample five-day ketogenic meal plan:
- Monday
- Breakfast: Veggie and egg muffins with tomatoes
- Lunch: Chicken salad with olive oil, feta cheese, olives, and a side salad
- Dinner: Salmon with asparagus cooked in butter
- Tuesday
- Breakfast: Egg, tomato, basil, and spinach omelet
- Lunch: Almond milk, peanut butter, spinach, cocoa powder, and stevia milkshake with a side of sliced strawberries
- Dinner: Cheese-shell tacos with salsa
- Wednesday
- Breakfast: Nut milk chia pudding topped with coconut and blackberries
- Lunch: Avocado shrimp salad
- Dinner: Pork chops with Parmesan cheese, broccoli, and salad
- Thursday
- Breakfast: Omelet with avocado, salsa, peppers, onion, and spices
- Lunch: A handful of nuts and celery sticks with guacamole and salsa
- Dinner: Chicken stuffed with pesto and cream cheese, and a side of grilled zucchini
- Friday
- Breakfast: Sugar-free Greek, whole milk yogurt with peanut butter, cocoa powder, and berries
- Lunch: Ground beef lettuce wrap tacos with sliced bell peppers
- Dinner: Loaded cauliflower and mixed veggies
Always try to rotate the vegetables and meat over the long term, as each type provides different nutrients and health benefits. Order this and replace any high carb food with extra vegetables.Egg-based meals are also a great option, such as an omelet or eggs and bacon.Another favorite is bun-less burgers. You could also swap the fries for vegetables instead. Add extra avocado, cheese, bacon, or eggs.At Mexican restaurants, you can enjoy any type of meat with extra cheese, guacamole, salsa, and sour cream.For dessert, ask for a mixed cheese board or berries with cream.
Potential Side Effects and How to Manage Them
The ketogenic diet may present some common and generally mild short-term adverse effects, known as the "keto flu." These symptoms can include nausea, vomiting, headache, fatigue, dizziness, insomnia, reduced exercise tolerance, and constipation. These symptoms resolve in a few days to weeks. Ensuring adequate fluid and electrolyte intake can help counter some of these symptoms.
Keto Flu
One of the most common side effects of the ketogenic diet is "keto flu." Some people may experience headaches, fatigue, dizziness, sleep problems, heart palpitations, cramps, and diarrhea as the body adjusts to a low-carbohydrate diet. During keto flu, the body's stored glucose begins depleting, and it starts adapting to producing and utilizing ketones as energy. According to Harvard Health Publishing, these side effects usually diminish and resolve in a week or so. To lessen these effects, consider gradually lowering your carbohydrate intake and increasing your dietary fat intake. Make sure you are not too low on electrolytes - sip on broth or take a salt tablet to get needed sodium. Remember that this transition might last about three to five weeks, and the benefits can certainly outweigh the immediate side effects.
Digestive Issues
Gastrointestinal side effects like keto constipation and diarrhea aren't uncommon. "If not done properly - with most of your carbohydrates coming from fiber-rich vegetables - you may not be getting enough fiber, which can lead to constipation," says Dr. Mohr.
Nutrient Deficiencies
Eliminating food groups can be problematic. "Ketogenic diets are often low in calcium, vitamin D, magnesium, and folic acid, which over time can lead to nutrient deficiencies if the diet is not planned carefully," adds Marie Spano, RD, a sports performance nutritionist in Atlanta.
Heart Health Concerns
Research shows that a diet rich in animal fats and proteins may negatively impact heart health. "This diet is not for anyone who is at risk of developing cardiovascular disease or who has already been diagnosed with it," Spano cautions. This means that if you have risk factors for heart disease - such as elevated cholesterol, high blood pressure (hypertension), or a strong family history of the disease - you should speak with a healthcare provider before starting this diet. The diet's heavy reliance on fat, especially saturated fat, can raise cholesterol levels, further increasing your chances of developing heart disease in the future.
Low Blood Sugar with Diabetes
For any individual with diabetes, discussing dietary changes - especially those as dramatic as the ones the ketogenic diet requires - with your healthcare team is essential. Because carbohydrates are broken down into glucose in the blood, cutting carbohydrates from your diet could cause levels to crash rapidly depending on your current medication regimen. Such a change may require significant adjustments to medication and insulin to prevent dangerous side effects such as low blood sugar, called hypoglycemia.
Weight Cycling
One of the biggest concerns of the ketogenic diet may be long-term adherence. "It's a very difficult diet to stick to and maintain. Compliance is a challenge because it is so restrictive," explains Mohr. Following a strict diet for weight loss and then quickly reverting to old habits when the dietary changes are too restrictive can lead to what is known as weight cycling, or yo-yo dieting.
Contraindications
Patients with diabetes taking insulin or oral hypoglycemic agents may experience severe hypoglycemia if their medications are not appropriately adjusted before initiating a ketogenic diet. The ketogenic diet is contraindicated in individuals with pancreatitis, liver failure, disorders of fat metabolism, primary carnitine deficiency, carnitine palmitoyltransferase deficiency, carnitine translocase deficiency, porphyrias, or pyruvate kinase deficiency. Additionally, individuals following a ketogenic diet may rarely experience a false positive breath alcohol test due to the conversion of acetone to isopropanol by hepatic alcohol dehydrogenase, resulting in an inaccurate reading.
Supplementation on a Ketogenic Diet
Although no supplements are required, some can be useful.
- MCT oil: Added to drinks or yogurt, MCT oil provides energy and helps increase ketone levels.
- Minerals: Added salt and other minerals can be important when starting out due to shifts in water and mineral balance.
- Caffeine: Caffeine can have benefits for energy, fat loss, and performance.
- Exogenous ketones: This supplement may help raise the body’s ketone levels.
- Creatine: Creatine provides numerous benefits for health and performance. This can help if you are combining a ketogenic diet with exercise.
- Whey: Use half a scoop of whey protein in shakes or yogurt to increase your daily protein intake.
Long-Term Considerations
While the keto diet has its benefits, staying on it in the long term may have some negative effects, including risks of the following:
- Low protein in the blood
- Extra fat in the liver
- Kidney stones
- Micronutrient deficiencies
A type of medication called sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes can increase the risk for diabetic ketoacidosis, a dangerous condition that increases blood acidity. Anyone taking this medication should avoid the keto diet.
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