KETOGENIC DEIT

ABSTRACT
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.

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.

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.
 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.

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.
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. 

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.

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.

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.