The Ketogenic Diet: Common Questions Answered
Authors: Sarah M. Rice, Douglas B. Reynolds
The Ketogenic Diet: Benefits
Many studies have investigated the effectiveness and safety of a low-carbohydrate, high-fat diet, and evidence consistently reports metabolic, hormonal, and neurological benefits. The ketogenic diet amplifies those benefits where a state of nutritional ketosis occurs.
Improves glycemic response and insulin sensitivity
A significant number (40%) of U.S. adults have some degree of insulin resistance, which is characterized by worsening blood glucose control, contributing to high inflammation and the development of chronic diseases including mental health and neurological conditions.122,123
Because chronic carbohydrate consumption is a significant driver of insulin resistance, a ketogenic diet offers an effective and simple strategy to reverse insulin resistance and restore metabolic balance. Restricting carbohydrates reduces the need for insulin, a critical metabolic hormone that governs blood sugar regulation. Stable, low insulin levels can gradually improve insulin sensitivity and enhance cellular glucose uptake.124
Regulates appetite
As discussed in Section 3.10, a higher fat content in the diet triggers changes in appetite regulation and satiety control and helps curb cravings, especially cravings for sugar and carbohydrates. A high carbohydrate diet that elevates blood glucose and insulin results in a roller coaster of blood sugar levels throughout the day. This dysregulates hormones like ghrelin and leptin, triggering cravings and leaving people feeling ‘hangry’. Reducing insulin improves leptin sensitivity which allows the brain to receive the signals that we are full. In the context of a reduced carbohydrate diet, a higher fat intake has been found to be more satisfying due to its action on brain reward centers.71
A ketogenic diet keeps blood sugar levels stable, reduces insulin, and allows for the regulation of hunger hormones, thereby reducing cravings and regulating appetite.71,72
Promotes healthy weight loss
The use of carbohydrate restriction for weight loss can be found in the literature as far back as the 1800s when it was the standard treatment for obesity.125,126 Over time, the development of the ketogenic diet for epilepsy has been explored for other applications and there is strong evidence for its efficacy in the treatment of obesity.80 This evidence is supported by the experiences of millions of people worldwide who have used a ketogenic diet to achieve and maintain a healthy body weight.
Generally, there is no calorie restriction associated with the diet. This is because a ketogenic diet regulates hunger signaling and allows the body to access its own fat stores for fuel, naturally reducing hunger and food intake. A properly formulated ketogenic diet is complete in the essential nutrients it provides, so weight loss and improved health are achieved at the same time.127,128 Ensuring sufficient protein intake helps with feeling full and supports body composition (protects muscle). Suggested protein intake for a reduced carbohydrate approach is around 1.2 to 2.0 g/kg goal weight.2 Key features of a ketogenic diet include the following—none of which are controversial in and of themselves:
- eating nutritious whole foods
- including sufficient, high-quality protein sources
- eating healthy fats
- limiting carbohydrates
- avoiding sugars
While the ketogenic diet is a powerful tool in weight management, other factors that can affect success include physical activity, good quality sleep, and stress reduction.
Lipedema and Lymphoedema Lipedema is a condition that may be confused with obesity, where fat tissue accumulates primarily in the lower half of the body (from the waist down to the ankle). This type of fat tissue is resistant to traditional diet and exercise approaches, which may be due to the disease process that includes tissue fibrosis and water retention.129,130 Due to these complications, lipedema is a painful condition which negatively impacts quality of life in a number of ways, including its resistance to treatment and risk of misdiagnosis. Studies have shown a ketogenic diet to be a promising intervention for this condition by promoting weight loss, reducing pain, reducing inflammation, and improving lymph vessel function.130,131
Lymphedema, which has previously been associated with cancer treatments, trauma, or infection, is now recognized as a feature of obesity, where lymphatic function is compromised and limb swelling occurs.132,133 Early studies have shown reduced weight and limb swelling using a ketogenic approach, with ketone body metabolism thought to be an important component of success via its ability to improve lymphatic function.132,134
Improves type 2 diabetes control
Almost 30 million U.S. adults have been diagnosed with diabetes, and just over 97 million have prediabetes.135 Until recently, many guidelines stated that type 2 diabetes was chronic and progressive, and there was no mention of the success of a low carbohydrate approach. Sadly, many doctors and diabetes educators are unaware that guidelines now state that a low-carbohydrate dietary approach can effectively improve blood sugar control and put type 2 diabetes into remission136,137. Unfortunately, a treatment protocol of a high carbohydrate diet, dosing with insulin, and other blood sugar controlling drugs like metformin may not give the best outcomes. The consequences of poorly controlled diabetes include the following:
- Cardiovascular disease
- Kidney dysfunction
- Vision loss
- Neuropathy
- Lower limb amputations
- Multiple medications
- Reduced life expectancy
The American Diabetes Association (ADA) recommends measuring your response to carbohydrates in your diet to guide management.138 This is helpful, but unfortunately not everyone has access to measuring technology, and with the ADA ‘Diabetes Plate Method’ suggesting 1/4 of the plate should consist of starchy carbohydrates, the intake of carbohydrates can quickly add up.139 At the same time, one of their most recent statements says: “Reducing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia and may be applied to a variety of eating patterns that meet individual needs and preferences.”137 These mixed messages add to confusion and detract from the data showing that individuals who have a disorder of carbohydrate metabolism tend to do better when they reduce their intake of carbohydrates.
The evidence is clear that therapeutic carbohydrate reduction lowers blood glucose and insulin, leading to reduced inflammation, improved insulin sensitivity, and reduced HbA1c levels.140 Gradually, the titration and elimination of type 2 diabetes medications may occur, and remission from the disease could be achieved.110
The ketogenic diet may be more effective in lowering blood glucose and, consequently, insulin levels due to the very low level of carbohydrate consumed. This approach is often recommended, with many research studies reporting significant therapeutic results when restricting carbohydrates to no more than 20 to 50 grams per day1,22 and many practitioners have adopted the ketogenic diet to prevent, manage, and even reverse diabetes.109,141
Improves type 1 diabetes control
Despite improvements in technology and healthcare, trends in glycaemic control seem to be worsening for type 1 diabetes.142 Before insulin was available, a reduced-carbohydrate diet was the only beneficial treatment option for type 1 diabetes.143 With the arrival of insulin as a treatment option (initially used in conjunction with the low carbohydrate approach) the amount of carbohydrate in the diet began to trend upwards and now the challenge of insulin resistance in type 1 diabetes has become a new concern.144 This has created a sub-type of diabetes known as “double diabetes” who are more at risk of micro- and macrovascular disease. Studies indicate that irrespective of glycemic control, the rate of complications is higher in this subgroup, suggesting that poor glycemic control is not the only reason for worse outcomes in type 1 diabetes and that double diabetes is an important and independent risk factor for developing complications.144,145 Maintaining insulin sensitivity may be a significant factor in improving outcomes for type 1 diabetes, especially given the inconsistencies in outcomes relating to glycemic control alone.146,147
Historical evidence points to the benefit of therapeutic carbohydrate reduction in type 1 diabetes and renewed interest has seen a recent increase in publications exploring low-carbohydrate and ketogenic diets for this population. Type 1 diabetes is an autoimmune disease where the insulin producing beta-cells in the pancreas are destroyed. In the early stages, a “honeymoon” phase is reported where beta-cells remain functional, producing enough insulin to contribute to blood glucose control. This leads to reduced insulin dosing. Several case studies have reported an extended honeymoon period following the implementation of a low-carbohydrate or ketogenic approach148–150 with one patient showing preserved function for more than 5 years.150 In general, the use of this approach for type 1 diabetes has demonstrated lower HbA1c values,151–153 lower glycemic variability and more time in range,154,155 less frequent and less severe hypoglycemic episodes,152–154 a reduction in insulin requirements (reported as much as 70%),156151,152 and reduced cardiovascular disease risk markers.153 Overall studies reflect that this approach is safe, feasible, and can be adhered to in the long-term.152,153,157
A reduced carbohydrate approach has been less studied in younger populations but available data suggest blood glucose control (and other metrics) improve and is in a similar range to the adult population.158–160 In one study, glycemic control was quoted as being “exceptional” (mean HbA1c of 5.67% ± 0.66%)158 and qualitative data reflect the following experiences159: “I think his last A1C was 6.3 before we went low carb and then that went to 5.3 as soon as we went low carb.” “The first [low-carbohydrate] meal we did was breakfast … that just changed our day. Like, you know as soon as you start off with fabulous flat numbers, you can just carry on… ” “I feel so much better doing it, like I feel I’ve got so much more energy…”
Finally, the state of nutritional ketosis has been examined with respect to type 1 diabetes and endurance exercise, with positive results.161–163
With the prevalence of double diabetes on the rise,164 it makes sense to address the dual concerns of blood glucose control and insulin resistance by applying a reduced carbohydrate approach. To this effect, the SMHP have published a peer-reviewed consensus statement outlining their position and the benefits of reduced-carbohydrate approaches for type 1 diabetes.165
Protects against metabolic syndrome
Metabolic syndrome is a group of conditions that, taken together, raise your risk of coronary heart disease, diabetes, stroke, and other serious health problems. Insulin resistance is the primary driver of metabolic syndrome.166 The criteria for metabolic syndrome are met with three or more of the following conditions:
- A large waistline (abdominal obesity)
- Elevated blood pressure
- High triglycerides
- Low HDL cholesterol
- High fasting blood sugars
Metabolic syndrome can have serious health consequences, and following a ketogenic diet is a safe and highly effective strategy to improve or normalize all these conditions.124 Reducing obesity and improving blood glucose control have been reviewed in previous sections. Other features of metabolic syndrome will be examined in the following sections.
Reduces triglycerides
It’s a common misunderstanding that dietary fats alone are linked to elevated triglyceride levels. In fact,blood triglyceride levels primarily respond to excessive carbohydrate consumption.167
The body has a minimal capacity to store sugars and converts excess blood sugar into triglycerides, which are then carried to the fat cells for storage. The hormone insulin drives this process. With insulin resistance, triglyceride production is increased, thereby raising the level in circulation. Overfull fat cells leak triglycerides back into circulation, further contributing to rising blood triglyceride levels.
In a ketogenic diet, a reduced carbohydrate load decreases triglyceride production in the liver, reducing circulating triglycerides. As insulin levels fall, fat cell storage and release mechanisms normalize, whereby stored fat can be accessed and oxidized to produce ketones. Subsequently, triglyceride levels fall. A ketogenic diet has been shown to consistently reduce triglycerides with a reduction of 50% found in one study in patients with metabolic syndrome.140,168
Improves HDL cholesterol
HDL plays an important role in the regulation of cholesterol metabolism by removing excess cholesterol from cells. Low levels signify impaired cholesterol metabolism and this is associated with insulin resistance and an increased risk of cardiovascular disease.169 The ketogenic diet consistently improves insulin sensitivity and cholesterol metabolism, resulting in increased HDL concentrations.140
As mentioned in Section 3.4, the triglyceride / HDL ratio and the count of small, dense LDL particles are much more useful predictors of potential cardiac risk than total cholesterol. These metrics are consistently improved on a ketogenic diet.33
Supports healthy blood pressure
Nearly half of all U.S. adults have elevated blood pressure, also known as hypertension, leaving a large proportion of the population at risk of cardiovascular disease, stroke, kidney dysfunction, and vision problems.170
Insulin and blood glucose concentrations influence blood pressure through their action on the kidneys and blood vessels. Insulin resistance causes the kidneys to retain sodium and impairs the relaxation (dilation) of blood vessels.171 Other features of metabolic syndrome, like abdominal obesity, leptin resistance, and inflammation also contribute to increased blood pressure through various signaling pathways.172
The ketogenic diet has been found to offer a simple and effective strategy to promote healthy, normal blood pressure.173,174 If someone is taking medication for hypertension, it is critical that they consult a doctor who is familiar with the effects of the ketogenic diet on blood pressure. A reduction in blood pressure may occur rapidly and proper adjustment of medication is essential.175,174 See Section 6: Resources, for information on guiding medication adjustments.
Improves fatty liver disease
Metabolic-associated fatty liver disease (MAFLD), also known as nonalcoholic fatty liver disease or NAFLD, occurs when the liver is overwhelmed by the fatty acids in circulation and not able to dispose of them efficiently. The liver’s production of fat in response to an excessive intake of carbohydrates exacerbates this.176
The ketogenic diet promotes fat burning, increasing the body’s capacity to utilize fats as its primary fuel source. This enables the liver to readily access stored fatty acids within liver cells, which can lower liver fat accumulation and may help reverse a fatty liver. This process is enhanced during fasting, when dietary fats are unavailable, which explains why combining a ketogenic diet with intermittent fasting is an excellent strategy to improve fatty liver disease.177
There are now many studies investigating the effects of a ketogenic diet for treating nonalcoholic fatty liver disease.178,179 One in particular found that participants following a ketogenic diet for only six days showed markedly reduced liver fat and improved insulin resistance, a primary cause of fatty liver disease.179
May protect or improve kidney function
Concerns about kidney function in the context of a ketogenic diet have been briefly addressed in Section 3.14. Recently, a new expression has emerged in the metabolic health space, cardiovascular-kidney-metabolic syndrome,180 reflecting the interconnected disease processes contributing to these disorders. This comes as no surprise if we consider the underlying role of insulin resistance in these conditions—clearly reflected in the staging definitions of this newly defined syndrome.181 This collection of diseases affected more than 25% of American adults between 2015 and 2020180 and a recent review states the “mechanisms of hyperglycemia-induced damage to the cardio-renal system are well validated.”182 In light of this, it is hardly controversial to suggest that a diet proven to address the pathophysiology (the dysregulated physiological pathways associated with the development of a disease) of the cardiovascular-kidney-metabolic syndrome could be helpful where kidney disease is present. A recent paper (The case for a ketogenic diet in the management of kidney disease)16 answers many of the questions commonly raised and emphasizes that a well-formulated ketogenic diet is moderate in protein, while being low in carbohydrates, and that a state of nutritional ketosis offers additional benefits in support of kidney function. These beneficial effects may include the provision of an efficient fuel source, reduced oxidative stress, improved mitochondrial function, reduced inflammation, and antifibrotic effects.
A number of papers support the consideration of a reduced carbohydrate or ketogenic diet for mild kidney disease in type 2 diabetes, reflecting improved estimated glomerular filtration rate (eGFR) tracking with ketone levels and adherence (dose dependent),99 improvements in three measures of renal function (serum creatinine, eGFR and albumin-to-creatinine ratio),183 the possibility of regression from chronic kidney disease (CKD) stage 3 to 2,184 and reversal of diabetic nephropathy (6 year duration) in a case study.185 In general, the intervention has shown to be safe and effective in this population.186,187
In patients with obesity, but without kidney disease, a meta-analysis found the improvement in kidney function was greater using a reduced carbohydrate approach compared with the control diet,188 and in patients with impaired kidney function, a ketogenic diet demonstrated weight loss and improved metabolic markers without change in kidney function.100
Autosomal-dominant polycystic kidney disease (ADPKD) is a genetic kidney disease involving the progressive development of cysts and declining kidney function, eventually leading to kidney failure.101,189 Ketogenic interventions are showing promise in slowing disease progression in the presence of elevated ketones (higher ketones associated with less decline),189 and a recent feasibility trial demonstrated improved kidney function in patients with ADPKD using this approach.101
Lastly, metabolic syndrome appears to predict decreased renal function in a middle aged and elderly population190 and an increased risk of CKD in general.191,192 Implementing therapeutic carbohydrate reduction, proven to be successful in reversing metabolic syndrome,141 would appear to be a beneficial strategy in helping to prevent the development of CKD.
Improves reproductive health
Reproductive health is closely linked to metabolic health, and with approximately 1 in 6 adults experiencing infertility, it is a significant health concern.193 Insulin plays a critical role in the reproductive health of men and women via its effects on the hypothalamus-pituitary-gonadal (HPG) axis and hormone production and regulation. Adipose (fat) tissue acts as an endocrine organ (hormone producing) and can also influence hormone levels and increase inflammation, contributing to reproductive dysfunction. In women, conditions like polycystic ovarian syndrome (PCOS), recurrent pregnancy loss, egg quality, and complications in pregnancy are associated with insulin resistance and obesity.194 In men, insulin resistance and obesity are associated with reduced testosterone levels, reduced sperm quality, erectile dysfunction, and inflammation of the prostate gland.194,195
In PCOS, elevated insulin and insulin resistance appear to drive hormonal imbalances (especially an elevation in testosterone outside of the normal range), which lead to symptoms such as polycystic ovaries, menstrual irregularities, infertility, increased body weight (variable), acne, and facial hair.196 Lowering insulin levels through the adoption of a ketogenic diet is an effective non-pharmaceutical strategy to restore hormone balance and alleviate PCOS symptoms.197,198 Even against the Mediterranean diet, which is commonly thought to be very healthy, a ketogenic diet has been found to be superior.199 Therapeutic carbohydrate reduction may also benefit conditions like abnormal uterine bleeding,200 gestational diabetes,201 and weight gain in menopause.202 In men, a ketogenic diet has been found to improve testosterone levels,203,204 semen quality,205 erectile function,204 and reduce prostatitis and prostate-specific antigen (PSA) levels.195,203
Improves sleep disorders
Sleep is an essential pillar of health.206 It is critical for proper brain and metabolic function, with disruption causing significant consequences for short- and long-term health.207 Sleep problems are common in both metabolic and neurological conditions.208,209 Nighttime wakefulness (insomnia) and daytime sleepiness are common in both groups, with sleep apnea found more in metabolic conditions and overweight.
Multiple factors influence sleep quality, but therapeutic carbohydrate reduction has been shown to improve sleep quality in a number of settings. One mechanism is suggested to be the reduction of inflammatory markers and, consequently, an increase in melatonin levels.210 In sleep apnea, weight loss is thought to be a significant factor for improved sleep, and in type 2 diabetes, hyperglycemia has been found to be associated with poor sleep.211 A ketogenic diet has demonstrated improved sleep quality and quality of life in patients with obesity,212,213 sleep apnea,214 and type 2 diabetes.211
Sleep disturbances can occur in neurological conditions like epilepsy, migraine, and multiple sclerosis,208,215 and they are the main feature of a rare sleep disorder called narcolepsy. Through its action on various pathways, including neurotransmitter regulation, reduced inflammation, and metabolism effects, the ketogenic diet has been shown to improve various elements of sleep quality. These elements include improved sleep structure (normalized REM sleep and improved slow-wave sleep)216,217 and regulation of the sleep-wake cycle.216,218 Specifically, studies have been shown to benefit sleep parameters in people with epilepsy,219 migraine,220 narcolepsy,221 and multiple sclerosis.215,222
At the intersection of metabolic health and neurology lies mental health. Disordered sleep and sleep-wake cycles often occur along with psychiatric disorders.223 A recent study demonstrated a 19% improvement in sleep quality compared to initial scores when a ketogenic diet was given to individuals experiencing serious mental illness. There was also an improvement in the severity of mental illness scores.224
Reduces inflammation
While short-term inflammation forms part of the healing process, a state of chronic inflammation is associated with a variety of chronic diseases such as obesity, type 2 diabetes, the development of atherosclerosis, and Alzheimer’s disease. The NLRP3 inflammasome pathway is thought to be a principal driver of inflammation via multiple effects (it also controls the release of inflammatory cytokines) and is activated via immune signaling.225
Fasting and ketogenic therapies suppress the activity of the NLRP3 inflammasome and related (multiple) pathways to reduce inflammation. This has been demonstrated in individuals with obesity,226,227 type 2 diabetes, and prediabetes.184,228 While weight loss can improve inflammation markers, in a study where healthy individuals were placed on a short-term ketogenic diet, inflammation markers decreased even without weight loss, showing that nutritional ketosis appears to have unique anti-inflammatory benefits.229
Other inflammatory conditions that have been shown to improve with carbohydrate reduction include fibromyalgia,230 osteoarthritis,231 psoriatic arthritis,232 and chronic pain.233 Improvements in skin conditions like psoriasis,234 acne,235 and hidradenitis suppurativa (acne inversa)236 have also been observed. Inflammatory gastrointestinal conditions will be covered in Section 4.14.
Inflammation is closely connected to metabolic syndrome and insulin resistance, and is implicated in most chronic disease states. This includes cardiovascular disease, type 2 diabetes, neurodegenerative disease, and cancer. The ketogenic diet is able to regulate multiple pathways and reduce inflammation, making it a good choice for maintaining metabolic health.237
Supports gastrointestinal health
The gut plays a key role in mediating immune and inflammatory pathways due to its barrier function—it is the connection between our bodies and the outside world. The balance of different types of bacteria and other organisms (the microbiome), the food we eat, and environmental exposures (medication, geography, age, and exercise) all contribute to our gut health. Because the gut acts as a barrier between our internal physiology and the outside world, it is acutely sensitive to metabolites and irritants, which can trigger inflammation and immune responses and increase gut permeability. Food processing changes the properties of fresh foods, altering the food matrix and often includes the addition of preservatives and other manufactured ingredients. These have the potential to irritate and upset the gut, triggering inflammatory and immune pathways.67
Returning to a more ancestral diet, moving away from processed foods, can support gut healing and reduce inflammation.65,238 Therapeutic carbohydrate reduction includes the removal of processed foods, grains, and legumes, which are potential irritants.12,60,61
A ketogenic diet has been shown to induce favorable changes in the microbiome and promote gut healing.7,68,239 The presence of ketone bodies, which can be used to fuel the cells of the gut lining,65 is one mechanism of healing. As mentioned in Sections 4.13 and 4.15, the ketogenic diet also reduces inflammation and supports immune function.
Inflammatory bowel disease has been reported to respond to carbohydrate reduction, including a ketogenic diet,7,240,241 and similar success has been observed in irritable bowel syndrome patients.242–244 In small intestine bacterial overgrowth (SIBO) a complete removal of carbohydrates (zero carbohydrate, animal based foods only) from the diet has been shown to promote recovery and normalization of the bacterial overgrowth.9
Gastroesophageal reflux disease (GERD) is associated with insulin resistance and higher carbohydrate consumption245,246 and has been successfully resolved by carbohydrate reduction.247,248
Supports immune function
As mentioned in Section 4.13, the ketogenic diet is able to suppress the activity of the NLRP3 inflammasome pathway, which is a significant component of the immune response.249 Preclinical (laboratory) studies have investigated the effects of ketone bodies on immune function demonstrating improved T-cell function and nitric oxide (NO) production (NO can regulate T-cell responses) and these are now being reproduced in human trials.250–252 Immune function and metabolic health are closely connected, and this has come to the fore in recent years with an increased interest in respiratory viral diseases and their management. Ketone bodies and metabolic health status appear to have an important role in the management of respiratory disease.253–255 Therapeutic carbohydrate reduction has been found to benefit a range of respiratory conditions such as chronic obstructive pulmonary disease (COPD),256,257 chronic lung disease in infants,258 and intubated patients with acute respiratory failure.259
Immune function also drives allergic and autoimmune diseases through various pathways which include the interplay between the innate and adaptive immune systems. In asthma, both immune and inflammatory pathways contribute to the condition, and insulin resistance tends to make things worse.260 The ketogenic diet has shown promise in improving airway inflammation and immune signaling in preclinical261 and clinical settings.262
A key regulator of these immune and inflammatory pathways is the microbiome and gastrointestinal system which is driven by its function as a barrier. Irritants and exposures to foreign substances can trigger inappropriate immune and inflammatory responses that contribute to the development of autoimmune disease.263 Therapeutic carbohydrate reduction has demonstrated the ability to improve the microbiome and has shown promise in improving a variety of autoimmune conditions such as multiple sclerosis,264 autoimmune thyroiditis,265 ankylosing spondylitis,266 and others12 (see Sections 4.13 and 4.14).
Improves neurological conditions
Neurological disorders encompass a wide range of conditions which include neurodevelopmental and neurodegenerative disorders, as well as traumatic neurological injuries and migraine. There is overlap between the conditions through various pathways that include brain energy metabolism, neurotransmitter regulation, inflammation, metabolic, and the gut-brain axis. Neurological disorders may be particularly responsive to the ketogenic diet where nutritional ketosis is achieved and maintained at more therapeutic levels, between 3–5 mmol/L (17–29 mg/dL).23
The ketogenic diet has been used for around 100 years for treating epilepsy, where it was observed that fasting resulted in a reduction of seizures. In order to maintain the therapeutic effect without causing starvation, the ketogenic diet was developed to maintain the physiological benefit whilst providing adequate nutrition.23 Around one third of people experience treatment resistant epilepsy (to medication), and the ketogenic diet offers the possibility of improvement. Though there is variation on an individual level, in general, the ketogenic diet improves seizure control in around 50% of individuals (may be up to 90%) and complete control may be seen in approximately 25% of those that respond. This approach can be successful for both adults and children.23
Epilepsy medication is also used in the treatment of migraine, giving us a clue that a ketogenic diet may benefit this condition. Common to other conditions involving the brain, the regulation of neuronal excitability and brain energy supply appear to play a major role in the onset of migraines.267 The migraine brain appears to be more sensitive to metabolic disturbances, particularly in glucose metabolism (reactive hypoglycemia),267,268 and the regulation of cell membrane ion channels (electrolyte imbalance).12,269,270 The ketogenic diet provides a steady energy supply via ketone bodies, stabilizing blood glucose and targeting multiple pathways involved in migraine attacks.271,272 Improvements in migraine frequency have been demonstrated using a ketogenic diet.268,272,273 Ketone bodies are also being explored in the context of traumatic brain injury due to their ability to effect neuroprotection, decrease inflammation, mitigate seizure activity, and increase neurotrophic factors.274 A range of evidence from animal to human studies suggests a ketogenic diet could improve recovery.275 At present, human studies show that a ketogenic approach is safe and feasible,276,277 improves the microbiome and metabolic health in spinal cord injury,278,279 and increases some components of memory in a small study on post-concussion syndrome.280
Helpful in neurodegenerative conditions
Nutritional ketosis results in a metabolic shift that improves brain energy metabolism (via the use of ketone bodies and increased mitochondrial function), decreases inflammation, regulates neurotransmitters, and removes old and damaged cells (autophagy). It can restore and protect the myelin sheath (the insulation around nerves) via its action on specialized cells that perform maintenance functions. This is in addition to the beneficial effects of the ketogenic diet on metabolic health which helps protect against the development of many neurological conditions.281,282 A recent case study demonstrated that a ketogenic diet significantly improved metabolic markers in a person with metabolic syndrome and Parkinson’s disease. Improvement in the non-motor symptoms of Parkinson’s disease were also reported.283
Neurodegenerative diseases where the ketogenic diet has shown benefit include Alzheimer’s disease,281,284 Parkinson’s disease,12,285 Huntington’s disease,286 and amyotrophic lateral sclerosis (ALS).287 Other conditions which have an autoimmune component and have responded to a ketogenic intervention include inclusion body myositis288 and multiple sclerosis.222,281
Supportive in neurodevelopmental disorders
Neurodevelopmental disorders are a broad spectrum of conditions (that frequently coexist) such as autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), and can include movement (Tourette syndrome), speech, and language disorders.
Interest in the ketogenic diet for supporting ASD is being driven by its frequent coexistence with epilepsy, and early studies have shown promise.289–291 In fact, there are common overlaps across many neurodevelopmental disorders, another example being Tourette syndrome (TS) and ADHD or obsessive compulsive disorder (OCD).292 The use of epilepsy medications in treating the symptoms of these neurodevelopmental disorders highlights the overlap in features. There are many contributing factors that result in neurodevelopmental conditions but common themes have emerged such as mitochondrial and metabolic dysfunction, brain energy metabolism, genetics, and the microbiome, all of which can respond to a ketogenic intervention.
At present, the ketogenic diet has not been specifically studied in other conditions like ADHD, but because of the overlap in neuroprocessing and neuroregulation difficulties (dysfunction of the dopamine system is common in ASD, ADHD, and TS) one may expect that a diet that is nutrient dense (avoiding deficiencies) and low in processed foods and sugars (irritating to the gut and brain), would be supportive of brain function.12 Children with ADHD appear more at risk of other psychiatric conditions in adulthood. In a recent paper,293 three adults with anxiety, depression, and comorbid ADHD experienced improvements in all scores related to anxiety and depression (changes in ADHD not recorded) with remission status achieved. This promising result should drive more research into the effects of a ketogenic diet on ADHD symptoms.
Allergies, food sensitivities, and fussy eating appear common in neurodevelopmental disorders and gluten-free/casein-free approaches have been used with some success.291,294,295 A new study looking at the microbiome and inflammation markers in ASD found the implementation of a ketogenic diet led to improvements in these areas which may drive improvements in behavior and sociability.289,296 A ketogenic diet was found to outperform a gluten-free diet in some areas in individuals with ASD,291 and a gluten-free diet (followed for one year) led to a marked reduction in tics and OCD in both adults and children with TS.297 Considering the various evidence streams, it seems clear that it is worth considering therapeutic carbohydrate reduction as a supportive approach in these conditions.
Promotes mood stability and cognitive function
Mood and cognition are inherently related to neurological function and, once again, we see the use of epilepsy medications for the treatment of mental illness giving us clues as to the potential role of the ketogenic diet in supporting mental health. Metabolic health and mental health are also intrinsically connected as metabolic dysfunction drives brain energy deficiency, network instability, and neurotransmitter imbalances.298,299 This connection, and possible metabolic therapies, are being explored in a field named “metabolic psychiatry” where several recent papers have shown the ketogenic diet to be successful in improving the condition of patients with severe mental illness.300–302
The use of ketogenic metabolic therapy for mental health is an area where higher levels of ketone bodies (and adherence) may influence the therapeutic effect and therefore one should seek medical oversight for implementation (especially if medication is in use).293,301,302 Ketogenic therapy in this setting is a powerful intervention that can require medication adjustments and oversight in order to safely transition into this supportive approach.303 As an adjunct therapy, the ketogenic diet is able to improve mental health via its effects on improving brain energy metabolism, neurotransmitter regulation, network stability, and insulin resistance.298 Over time, medication reduction may be possible and remission of symptoms can be achieved for some people.301,303,304 See Section 6: Resources, for more information and links to help you find an experienced provider to support you if you have a mental health condition.
Many people notice an improvement in mood stability and cognitive function as a benefit of the ketogenic diet, even if the primary application was to address metabolic health.304,305 Even in young healthy individuals, a ketogenic diet has been shown to improve network stability, an important marker of brain aging. In a study that examined the effect of diet on network stability, glucose destabilized and ketones stabilized brain networks.299 Overall, a diet that promotes metabolic flexibility, insulin sensitivity, and a steady energy supply is associated with improved cognitive function across the lifespan—a ketogenic (or a low-carbohydrate) diet is one way to achieve this.306
Metabolic syndrome has been associated with impaired network efficiency and cognitive impairment,307 and Alzheimer’s disease is being referred to as type 3 diabetes due to its connection to disorders of glucose metabolism.308 Using a reduced carbohydrate approach to manage metabolic syndrome and type 2 diabetes could protect against the development of Alzheimer’s disease, the most common neurodegenerative disorder.308,309
Supports healthy aging
The leading causes of death globally are cardiovascular disease (CVD) and cancer—together, they account for around 50% of deaths globally.310 These are non-communicable diseases where insulin resistance appears to be a significant driving factor for disease development.123,311,312 In support of this, the data also suggest that insulin sensitivity and, by extension, metabolic syndrome, may predict healthy aging.313,314 We have previously discussed the role of insulin in CVD development (see Section 3.6 and related). In contributing to cancer risk, elevated levels of insulin can cause inflammation and drive pathways that may result in inappropriate growth and division of cells, and a reduced ability to clear old and poorly functioning cells.111 Taken together, this dysfunctional metabolic state can increase the risk of cancer and CVD.111,311,312
A state of nutritional ketosis has been associated with increased longevity in animal models through mechanisms that include decreased inflammation and insulin signaling, increased autophagy (removal of old and poorly functioning cells), and improved mitochondrial function. While many of the models use caloric restriction or fasting to obtain the benefits of ketosis, a ketogenic diet can mimic the positive effects of ketosis with nutritional sufficiency—an important feature of healthy aging. A study looking at long-term adherence to a ketogenic diet found no adverse findings and excellent metabolic flexibility—a hallmark of good metabolic health.111
A loss of muscle mass (sarcopenia) is a concern of aging and is associated with insulin resistance and the development of frailty.12,315,316 Ketogenic diets improve mitochondrial function, an important feature of muscle function, and have shown promising results in rodent studies for aging and motor function.317,318 In humans a ketogenic diet can improve grip strength, body composition, metabolic status, and weight319; preserve muscle mass during weight loss320,321 —even in older adults (60–75 years)322; and has been shown to increase circulating levels of myokines which play a role in the regulation of muscle metabolism.323 Myokines are released during resistance training (an important component of healthy aging) and are thought to contribute to the restoration of metabolic health via various pathways.324 Studies support the importance of protein and nutrient dense foods for protection against frailty which are key components of a reduced carbohydrate approach.12,54,325
Could play a role in the prevention and treatment of cancer
Cancer is the second ranked (at nearly 20%) cause of death globally.326 There are multiple factors that can contribute to the development of cancer including age, chronic inflammation, viral infections, environmental exposures (toxins, radiation exposure, chemical exposures), and rare inherited mutations.85 The metabolic disturbances associated with insulin resistance, metabolic syndrome, diabetes, and obesity (even where obesity is classified as metabolically healthy)327 likely contribute to these being known risk factors for the development of cancer.312,328,329 Therapeutic carbohydrate reduction, as an established treatment for these risk factors, indicates a role in prevention and lends itself to considered application in the presence of a cancer diagnosis.12,87
A key feature of the development of cancer is altered energy metabolism resulting in abnormal cell growth. This dysfunctional metabolism is known as the Warburg effect where energy deficiency within the cancer cell drives increased dependence on glucose and glutamine as fermentable fuels.12,85 A ketogenic diet is showing promise as an adjunct metabolic therapy due to its ability to reduce glucose, suppress insulin signaling, and elevate ketone bodies—all of which can support cancer treatment. These metabolic changes weaken tumor cells (normal cells are unaffected) and make them more vulnerable to the treatment modalities applied.330–333 While a metabolic approach to cancer management shows promise, there is still some way to go in standardizing the approach and stratifying for all cancer cell (metabolic) subtypes,334 so a considered and sensitive approach to discussions around this strategy is most appropriate. Currently, the ketogenic diet in this setting should be seen as a supportive addition to standard of care protocols (see Section 6: Resources, for more information).
Insulin resistance and obesity are associated with worse outcomes in cancer patients which implies that any metabolic therapy that improves these features could have a clinical benefit.335–337 A ketogenic diet has been found to be safe and effective at addressing these elements in patients undergoing cancer treatment and can be considered to have a supportive role in this context.337–340
May improve sports performance
The question of sports performance is a complex topic due to significant variations in individual physiology, goals, and exercise response. During exercise, both carbohydrate and fat metabolism can contribute to energy supply. Energy required by the muscle can be derived from the oxidation of free fatty acids or from sources of carbohydrates, which include blood glucose, muscle glycogen, and liver glycogen.341 Metabolic health, metabolic flexibility, and dietary choices all play a role in how the body responds to exercise stress. Studies show that switching to a low-carbohydrate or ketogenic approach improves the ability of the body to burn fat for fuel, reduces reliance on carbohydrates for fuel, and can improve metabolic health.342 Reducing reliance on carbohydrates for fuel has many benefits, especially in endurance sports, where gastrointestinal distress can be exacerbated by the consumption of multiple glucose delivery options (gels or liquids).
The best fueling strategy for prolonged exercise has been a matter for debate and inconsistencies in the data do not support the paradigm that muscle glycogen depletion is the sole limitation determining prolonged exercise performance.343 An alternative theory to the carbohydrate dependent (muscle glycogen) model is that an enhanced ability to oxidize fat at a sustained rate during prolonged exercise would benefit the endurance athlete and help mitigate hypoglycaemic drift by delaying exhaustion of liver (and brain) glycogen.343 Pre-adapting to a low-carbohydrate, high-fat (LCHF) diet in this context shows promise. Increasing efficiency for fat burning can occur quite rapidly though a longer adaptation period may be necessary for optimum results—suggested to be around 4 weeks (though there may be individual variation).12,343 Response to carbohydrate input is individual and appears to be a feature of brain metabolic flexibility and how adapted for fat oxidation and ketone use they are. Very little carbohydrate may be required to protect performance (around 37-74 g), though some may be required.344,345
For short duration and strength performance, a study on elite artistic gymnasts demonstrated no differences in strength after 30 days on a ketogenic diet, and a significant improvement in body composition (decreased weight and fat mass, non-significant increase in muscle mass).346 Similarly, a study examining the effect of a very low-carbohydrate high-fat diet (ketones detected) on high-intensity interval training (HIIT) found no evidence of performance compromise during final stages of the graded exercise test or HIIT sessions.347
Evaluation of studies that conclude negative effects of LCHF diet shows individual variation12,345,348 and the totality of evidence essentially reflects performance equivalence (despite different demands), though there is some variation of effect amongst individuals.343 In consideration of best performance, being of a healthy weight for the sport in question and being metabolically flexible are likely to support performance.12 An individualized approach on the low-carbohydrate to ketogenic spectrum, considering performance goals (professional or amateur) and underlying health markers (e.g., insulin resistance), would seem to offer the most promise.
Conclusion
A carbohydrate reduced or ketogenic diet that is well formulated and focused on whole foods is a way of eating rooted in ancestral patterns that have demonstrated resilience to disease. Our modern food environment has been shown to be detrimental to our health which, in conjunction with other changes in lifestyle, has led to an epidemic of poor metabolic health and chronic disease. A whole foods, carbohydrate reduced approach is a simple way to address metabolic dysregulation that acts on multiple pathways. A ketogenic diet amplifies the effect and may be especially useful for severe metabolic diseases, neurological diseases, and improving mental health. The ketogenic diet addresses the root causes of many of the conditions discussed above, which include insulin resistance, obesity, and type 2 diabetes—major risk factors for heart disease and cancer.
Misconceptions around the ketogenic diet abound, but evidence suggests the concerns are largely unfounded when examined critically, with the majority of individuals being able to improve their health status using this approach. However, it would be a misconception to consider that any one variation of the ketogenic diet is right for everyone—it is an approach that should be tailored to individual health goals and metrics.
As with any lifestyle change, individual responses vary, and appropriate medical monitoring is advised, especially where medication is in use (see Section 6: Resources, for Clinical Guidelines). There is now a growing body of clinicians who recognize the importance of metabolic health and the role of lifestyle interventions in the treatment of chronic disease. Clinicians from a broad range of specialties are now embracing this approach as a powerful tool in helping patients improve their health (see Section 6: Resources, for Practitioner listing).
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