Obesity remains a significant worldwide health hazard, contributing to adult mortality rates 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, often resulting from an unhealthy lifestyle and poor dietary habits. The implementation of 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. But is it a sustainable solution or just another fleeting trend?
What is the Keto Diet?
The ketogenic or keto 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 Keto 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 55% to 60% fat, 30% to 35% protein, and 5% to 10% carbohydrates. 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 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.
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.
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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.
Types of Ketogenic Diets
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.
Clinical Significance and Potential Benefits
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. However, emerging research has highlighted the negative impact of consuming excessive amounts of sugar-laden foods. Studies have shown that a higher intake of sugar-laden foods is associated with a 44% increased prevalence of metabolic syndrome and obesity and a 26% higher risk of developing diabetes.
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. When individuals consume an excess of low-quality carbohydrates, there may be limited space in their diet for more nutritious foods like nuts, unprocessed grains, fruits, and vegetables.
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Specific Health Conditions
The ketogenic diet has shown promise in managing several health conditions:
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. A ketogenic diet also has been shown to improve blood sugar control for patients with type 2 diabetes, at least in the short term.
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 (NAFLD): 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. However, it has been reported that low-carbohydrate diets, particularly those high in fat, may exacerbate hepatic steatosis due to their impact on cholesterol levels and liver function. 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.
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Polycystic Ovary 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. We have solid evidence showing that a ketogenic diet reduces seizures in children, sometimes as effectively as medication.
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.
Is it sustainable?
A recent systemic review and meta-analysis of RCTs comparing the long-term effects (more than 1 year) of dietary interventions on weight loss revealed a lack of substantial evidence supporting the recommendation of low-fat diets. Low-carbohydrate diets were found to be more effective in achieving significant weight loss compared to low-fat interventions. Additionally, a carbohydrate-restricted diet was found to maintain better an individual's basal metabolic rate (BMR), suggesting that the quality of calories consumed can impact the number of calories burned at rest.
Potential Risks and Side Effects
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. 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.
Negative Health Effects
It may also be too restrictive to follow long-term and may have negative health effects, including:lower bone mineral density and increased risk of fracturesincreased risk of kidney stones hypercalcemia (too much calcium in the blood)low parathyroid hormone, vitamin D, and alkaline phosphate (ALP) levelsrisk of impaired renal function
Keto vs. Other Low-Carb Diets
In the world of weight-loss diets, low-carbohydrate, high-protein eating plans often grab attention. The Paleo, South Beach, and Atkins diets all fit into that category. They are sometimes referred to as ketogenic or "keto" diets. But a true ketogenic diet is different. Unlike other low-carb diets, which focus on protein, a keto plan centers on fat, which supplies as much as 90% of daily calories.
Atkins Diet
The Atkins diet is another low carb diet with some research behind it. Created by cardiologist Robert Atkins in the early 1970s, the Atkins diet claims to produce rapid weight loss without hunger.It consists of four stages during which you can consume unlimited amounts of protein and fat:
- Phase 1 (Induction): During the initial phase, proponents recommend you consume 20 to 25 grams (g) of net carbs per day until you are 15 pounds (lb) or 7 kilograms (kg) from your goal weight. During this phase, your body begins converting fat into ketones and uses them as its main source of energy.
- Phase 2: You can eat 25 to 50 g of net carbs daily until you are 10 lb (5 kg) from your goal weight.
- Phase 3: This phase raises your net carb allowance to 50 to 80 g per day until you have met your goal weight and maintained it for 1 month.
- Phase 4: During the final phase, you can consume 80 to 100 g of net carbs daily to maintain your weight.
For stages 2 through 4, the Atkins diet asks followers to gradually add back their carbs in 5-gram increments to determine their âcritical carbohydrate levelsâ for losing weight and maintaining it.While most of the research on the Atkins diet is older, research on low carb diets in general suggests that they are effective for weight loss for the first 6 to 12 months. They may also benefit insulin and blood glucose levels and risk factors for cardiovascular disease.
Negative health effects of the Atkins Diet include:
- risk of metabolic acidosis (when your body contains too much acid)
- risk of other metabolic side effects
- potential for urinary stone formation due to decreased urine pH and calcium balance
- risk of chronic kidney disease
South Beach Diet
Like Dr. Atkins, Dr. Arthur Agatston was a cardiologist interested in helping his patients lose weight sustainably without feeling hungry.He liked certain aspects of the Atkins diet, but was concerned that unrestricted use of saturated fat might increase the risk of heart disease.Therefore, in the mid-1990s, he created a lower-carb, lower-fat, high protein diet called the South Beach Diet, named for the area in South Florida where he practiced medicine.Although Stage 1 of the diet is low in carbs and very low in fat, the diet becomes less restrictive in Phases 2 and 3, which allow limited quantities of all types of unprocessed foods while keeping protein intake high. The diet encourages a high protein intake, because protein may burn more calories during digestion than carbs or fat. Protein stimulates the release of hormones that suppress hunger and help you feel full longer.Although the diet is nutritious overall, it recommends a significant restriction of saturated fat that may not be warranted. It also requires specific planning and may be too restrictive for some people.
Negative health effects of the South Beach Diet can include:
- increased risk of ketoacidosis
- hypocalcemia (calcium deficiency)
- fiber deficiency
Is the Keto Diet a Fad?
Whether the keto diet is a "fad" depends on how the term is defined. If a fad diet is characterized by rapid weight loss promises, restrictiveness, and unsustainability, then the keto diet certainly exhibits some of these traits. However, unlike many fad diets that lack scientific backing, the keto diet has a growing body of research supporting its potential benefits for specific conditions like epilepsy, type 2 diabetes, and obesity. A 2023 review of research suggests that the ketogenic diet may be an effective treatment for:epilepsyimproving blood lipids in people with type 2 diabetesThe researchers note that though some research suggests it may benefit weight loss in people who are overweight or have obesity, the evidence isnât strong enough to draw conclusions. More research is also needed to determine its long-term safety.
What Makes the Keto Diet Unsustainable?
- Restrictiveness: The keto diet requires significant dietary changes and restricts many common foods, making it challenging to adhere to long-term.
- Nutrient Deficiencies: Without careful planning, the keto diet can lead to deficiencies in essential vitamins, minerals, and fiber.
- Side Effects: The "keto flu" and other potential side effects can be unpleasant and discourage long-term adherence.
- Social Limitations: The diet's restrictions can make social eating and dining out difficult.
The Importance of Sustainable Lifestyle Changes
Instead of engaging in the next popular diet that would last only a few weeks to months (for most people that includes a ketogenic diet), try to embrace change that is sustainable over the long term. Ultimately, itâs up to you to decide what approach to nutrition is right for you.