Ketogenic Diet

Wajeed Masood; Pavan Annamaraju; Kalyan R. Uppaluri.

Author Information and Affiliations

Last Update: June 11, 2022.

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Continuing Education Activity

Despite continuous advances in the medical world, obesity continues to remain a major worldwide health
hazard with adult mortality as high as 2.8 million per year. The majority of chronic diseases like diabetes,
hypertension, and heart disease are largely related to obesity which is usually a product of an unhealthy lifestyle
and poor dietary habits. Appropriately tailored diet regimens for weight reduction can help manage the obesity
epidemic to some extent. One diet regimen that has proven to be very effective for rapid weight loss is a very-
low-carbohydrate and high-fat ketogenic diet. This activity reviews the evaluation and considerations for
the ketogenic diet and discusses the role of the interprofessional team in educating patients on the risks and
benefits of this diet.
Objectives:
• Describe the significance of obesity as a health hazard worldwide.
• Identify the major diseases associated with obesity.
• Outline the use of the ketogenic diet in treating obesity.
• Review the evaluation and considerations for the ketogenic diet and outline the role of the
interprofessional team in educating patients on the risks and benefits of this diet.
Access free multiple choice questions on this topic.
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Introduction
Despite continuous advances in the medical world, obesity continues to remain a major worldwide health
hazard with adult mortality as high as 2.8 million per year. The majority of chronic diseases like diabetes,
hypertension, and heart disease are largely related to obesity which is usually a product of an unhealthy lifestyle
and poor dietary habits. Appropriately tailored diet regimens for weight reduction can help manage the obesity
epidemic to some extent. One diet regimen that has proven to be very effective for rapid weight loss is a very-
low-carbohydrate and high-fat ketogenic diet.[1][2][3]
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Function
A ketogenic diet primarily consists of high fats, moderate proteins, and very low carbohydrates. The dietary
macronutrients are divided into approximately 55% to 60% fat, 30% to 35% protein, and 5% to 10%
carbohydrates. Specifically, in a 2000 kcal per day diet, carbohydrates amount up to 20 to 50 g per day.
History and Origin
Russel Wilder first used the ketogenic diet to treat epilepsy in 1921. He also coined the term "ketogenic diet."
For almost a decade, the ketogenic diet enjoyed a place in the medical world as a therapeutic diet for pediatric
epilepsy and was widely used until its popularity ceased with the introduction of antiepileptic agents. The
resurgence of the ketogenic diet as a rapid weight loss formula is a relatively new concept the has shown to be
quite effective, at least in the short run.
Physiology and Biochemistry
Basically, carbohydrates are the primary source of energy production in body tissues. When the body is
deprived of carbohydrates due to reducing intake to less than 50g per day, insulin secretion is significantly
reduced and the body enters a catabolic state. Glycogen stores deplete, forcing the body to go through certain
metabolic changes. Two metabolic processes come into action when there is low carbohydrate availability in
body tissues: gluconeogenesis and ketogenesis.[4][5]
Gluconeogenesis is the endogenous production of glucose in the body, especially in the liver primarily from
lactic acid, glycerol, and the amino acids alanine and glutamine. When glucose availability drops further, the
endogenous production of glucose is not able to keep up with the needs of the body and ketogenesis begins in
order to provide an alternate source of energy in the form of ketone bodies. Ketone bodies replace glucose as a
primary source of energy. During ketogenesis due to low blood glucose feedback, the stimulus for insulin
secretion is also low, which sharply reduces the stimulus for fat and glucose storage. Other hormonal changes
may contribute to the increased breakdown of fats that result in fatty acids. Fatty acids are metabolized to
acetoacetate which is later converted to beta-hydroxybutyrate and acetone. These are the basic ketone bodies
that accumulate in the body as a ketogenic diet is sustained. This metabolic state is referred to as "nutritional
ketosis." As long as the body is deprived of carbohydrates, the metabolism remains in the ketotic state. The
nutritional ketosis state is considered quite safe, as ketone bodies are produced in small concentrations without
any alterations in blood pH. It greatly differs from ketoacidosis, a life-threatening condition where ketone
bodies are produced in extremely larger concentrations, altering blood ph to an acidotic state.
Ketone bodies synthesized in the body can be easily utilized for energy production by the heart, muscle tissue,
and kidneys. Ketone bodies also can cross the blood-brain barrier to provide an alternative source of energy to
the brain. RBCs and the liver do not utilize ketones due to lack of mitochondria and enzyme diaphorase
respectively. Ketone body production depends on several factors such as resting basal metabolic rate (BMR),
body mass index (BMI), and body fat percentage. Ketone bodies produce more adenosine triphosphate in
comparison to glucose, sometimes aptly called a "super fuel." One hundred grams of acetoacetate generates
9400 grams of ATP, and 100 g of beta-hydroxybutyrate yields 10,500 grams of ATP; whereas, 100 grams of
glucose produces only 8,700 grams of ATP. This allows the body to maintain efficient fuel production even
during a caloric deficit. Ketone bodies also decrease free radical damage and enhance antioxidant capacity.
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Issues of Concern
Adverse Effects
The short-term effects (up to 2 years) of the ketogenic diet are well reported and established. However, the
long-term health implications are not well known due to limited literature.[6][7][8]
The most common and relatively minor short-term side effects of the ketogenic diet include a collection of
symptoms like nausea, vomiting, headache, fatigue, dizziness, insomnia, difficulty in exercise tolerance, and
constipation, sometimes referred to as keto flu. These symptoms resolve in a few days to few weeks. Ensuring
adequate fluid and electrolyte intake can help counter some of these symptoms. Long-term adverse effects
include hepatic steatosis, hypoproteinemia, kidney stones, and vitamin and mineral deficiencies.
Cautions and Contraindications
People suffering from diabetes and taking insulin or oral hypoglycemic agents suffer severe hypoglycemia if the
medications are not appropriately adjusted before initiating this diet. The ketogenic diet is contraindicated in
patients with pancreatitis, liver failure, disorders of fat metabolism, primary carnitine deficiency, carnitine
palmitoyltransferase deficiency, carnitine translocase deficiency, porphyrias, or pyruvate kinase
deficiency. People on a ketogenic diet rarely can have a false positive breath alcohol test. Due to ketonemia,
acetone in the body can sometimes be reduced to isopropanol by hepatic alcohol dehydrogenase which can give
a false positive alcohol breath test result.
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Clinical Significance
The popular belief that high-fat diets cause obesity and several other diseases such as coronary heart disease,
diabetes, and cancer has not been observed in recent epidemiological studies. Studies carried out in animals that
were fed high-fat diets did not show a specific causal relationship between dietary fat and obesity. On the
contrary, very-low-carbohydrate and high-fat diets such as the ketogenic diet have shown to beneficial to
weight loss.
Evidence Behind The Ketogenic Diet
In relation to overall caloric intake, carbohydrates comprise around 55% of the typical American diet, ranging
from 200 to 350 g/day. The vast potential of refined carbohydrates to cause harmful effects were relatively
neglected until recently. A greater intake of sugar-laden food is associated with a 44% increased prevalence of
metabolic syndrome and obesity and a 26% increase in the risk of developing diabetes mellitus. In a 2012
study of all cardiometabolic deaths (heart disease, stroke, and type 2 diabetes) in the United States, an estimated
45.4% were associated with suboptimal intakes of 10 dietary factors. The largest estimated mortality was
associated with high sodium intake (9.5%), followed by low intake of 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 low polyunsaturated fats (2.3%) and unprocessed red meats (0.4%). In addition to this direct
harm, excess consumption of low-quality carbohydrates may displace and leave no room in the diet for
healthier foods like nuts, unprocessed grains, fruits, and vegetables.
A recent systemic review and meta-analysis of randomized controlled trials comparing the long-term effects
(greater than 1 year) of dietary interventions on weight loss showed no sound evidence for recommending low-
fat diets. In fact, low-carbohydrate diets led to significantly greater weight loss compared to low-fat
interventions. It was observed that a carbohydrate-restricted diet is better than a low-fat diet for retaining an
individual’s BMR. In other words, the quality of calories consumed may affect the number of calories burned.
BMR dropped by more than 400 kcal/day on a low-fat diet when compared to a very low-carb diet.
A well-formulated ketogenic diet, besides limiting carbohydrates, also limits protein intake moderately to less
than 1g/lb body weight, unless individuals are performing heavy exercise involving weight training when the
protein intake can be increased to 1.5g/lb body weight. This is to prevent the endogenous production of glucose
in the body via gluconeogenesis. However, it does not restrict fat or overall daily calories. People on
a ketogenic diet initially experience rapid weight loss up to 10 lbs in 2 weeks or less. This diet has a diuretic
effect, and some early weight loss is due to water weight loss followed by a fat loss. Interestingly with
this diet plan, lean body muscle is largely spared. As a nutritional ketosis state sustains, hunger pangs subside,
and an overall reduction in caloric intake helps to further weight loss.
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Other Issues
Long-term compliance is low and can be a big issue with a ketogenic diet, but this is the case with any lifestyle
change. Even though the ketogenic diet is significantly superior in the induction of weight loss in otherwise
healthy patients with obesity and the induced weight loss is rapid, intense, and sustained until at least 2 years,
the understanding of the clinical impacts, safety, tolerability, efficacy, duration of treatment, and prognosis after
discontinuation of the diet is challenging and requires further studies to understand the disease-specific
mechanisms.
A ketogenic diet may be followed for a minimum of 2 to 3 weeks up to 6 to 12 months. Close monitoring of
renal functions while on a ketogenic diet is imperative, and the transition from a ketogenic diet to a
standard diet should be gradual and well-controlled.
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Enhancing Healthcare Team Outcomes

To counter the obesity epidemic, some healthcare workers do recommend the ketogenic diet. However, the
primary care provider, nurse practitioner, dietitian, and internist need to be aware of a few facts.
Overweight individuals with metabolic syndrome, insulin resistance, and type 2 diabetes are likely to see
improvements in the clinical markers of disease risk with a well-formulated very-low-carbohydrate diet.
Glucose control improves due to less glucose introduction and improved insulin sensitivity. In addition to
reducing weight, especially truncal obesity and insulin resistance, low-carb diets also may help improve blood
pressure, blood glucose regulation, triglycerides, and HDL cholesterol levels. However, LDL cholesterol may
increase on this diet.
Also, in various studies, the ketogenic diet has shown promising results in a variety of neurological disorders,
like epilepsy, dementia, ALS, traumatic brain injury, acne, cancers, and metabolic disorders.
Due to the complexity of the mechanism and lack of long-term studies, a general recommendation of
the ketogenic diet for prevention of type 2 diabetes mellitus or cardiovascular disease may seem premature but
is, however, not farfetched for primary weight loss.
While in the short term the ketogenic diet may help one lose weight, this is not sustained over the long run. In
addition, countless studies show that the diet is associated with many complications that often lead to
emergency room visits and admissions for dehydration, electrolyte disturbances, and hypoglycemia. [9][10][11]
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