KETOGENIC DIET – MAKING A

COMEBACK

Dr. S. Lavanya,
II year PG Resident,
Department of Medicine.
 INTRODUCTION

• In recent years, there is a rapid growth in the prevalence

of chronic non-communicable diseases (CNCDs).
• The effects of diet compounds on metabolic pathways
related to diabetes mellitus, cardiovascular diseases, and
other CNCD is currently under investigation and it is
leading the traditional nutritional counseling to a more
complex approach.
 INTRODUCTION
• The primary determinant of weight loss is energy deficit.
• Many strategies have been proposed for reducing energy
intake (diets, drugs, and bariatric surgery) and for increasing
energy output (exercise and non-exercise movement), but
even though there may exist a general agreement about the
fundamental conceptual basis—changing energy intake and
physical activity levels— how to achieve these goals is less
clear.
 INTRODUCTION
• The most commonly used diet therapy is based on
relatively high levels of carbohydrates and low in fat.
• However, these diets often result in modest weight
loss, and adherence to diet is quite low in the long
term, because obese individuals tend to have
preference for foods with a high fat content.
 INTRODUCTION
• Furthermore, as a result questionable effectiveness
for weight loss of these types of diet, there was a
growing interest in low-carbohydrate ketogenic diets
(LCDs), very low-calorie ketogenic diets (VLCKDs,
<800 kcal day-1), or simply ketogenic diets (KDs).
 HISTORY OF KETOGENIC DIET
• The first modern use of starvation as a treatment for
epilepsy was recorded by a pair of Parisian physicians,
Gulep and Marie, in 1911.
• They treated 20 children and adults with epilepsy and
reported that seizures were less severe during
treatment, but no specific details were given.
• The United States contemporary accounts of fasting
were also recorded early in the 20th century: the first
was a report on a patient of an osteopathic physician,
Dr. Hugh W. Conklin, of Battle Creek, Michigan.
 HISTORY OF KETOGENIC DIET
• The second concerned was Bernarr
Macfadden who was a physical fitness
guru/cultist and publishing genius of the early
part of the 20th century.
• The success of Dr. Conklin’s results with fasting
quickly spread and by 1941 it had achieved
prominence in the textbook of Penfield and
Erickson on epilepsy from the Montreal
Neurologic Institute.
 HISTORY OF KETOGENIC DIET
• In 1921, two pivotal observations were made.
• Woodyatt noted that acetone and beta-
hydroxybutyric acid appear in a normal subject by
starvation or a diet containing too low a
proportion of carbohydrate and too high a
proportion of fat.
• Concurrently, Dr. Wilder at the Mayo Clinic
proposed that the benefits of fasting could be
obtained if ketonemia was produced by other
means.
 HISTORY OF KETOGENIC DIET
• Wilder proposed that a ketogenicdiet(KD) be
tried in a series of patients with epilepsy.
• He suggested that the diet should be as
effective as fasting and could be maintained
for a much longer period of time.
• Wilder subsequently reported on patients
treated with the ketoneproducing diet at the
Mayo Clinic and coined the term “ketogenic
diet.”
 WHAT IS KETOGENIC DIET?
• The ketogenic diet (KD) is described as high-fat, adequate-
protein, and low-carbohydrate diet.
• It consists of around 80% fat, 15% protein, and 5%
carbohydrates.
• Traditional KD involves the use of lipid : non-lipid ratios
measured in grams.
• Today, the KD’s goal lipid : non-lipid ratio ranges from 4:1 to
2:1, with the higher ratio being more effective.
KETOGENIC DIET - COMPOSITION
CARBOHYDRATES
PROTEIN
FAT
5%
15%

80%
 WHAT IS KETOGENIC DIET?

• With the inadequate availability of carbohydrates, the

body burns fats rather than carbohydrates to provide
energy.

• The liver converts fat into fatty acids and produces

ketone bodies (KB), which replace glucose as a
primary energy source.

• This dietary accumulation of ketones in blood is also

known as nutritional ketosis (NK).
 TYPES OF KETOGENIC DIET
• Standard ketogenic diet (SKD): This is a very low-
carbohydrate with moderate-protein and high-fat diet. It
typically contains 70 per cent fat, 20 per cent protein and
only 10 per cent carbohydrates.

1. Classic ketogenic diet - provides 60–80% of

dietary energy through long-chain fats, which have 16–20
carbon atoms.

Indian J Med Res. 2018 Sep; 148(3): 251–253.

 TYPES OF KETOGENIC DIET
2. Medium-chain triglyceride (MCT) ketogenic diet - fats
are provided through triglycerides comprising about 60%
octanoic acid (an eight-carbon fatty acid) and about 40%
decanoic acid (a ten-carbon fatty acid).
• Cyclical ketogenic diet (CKD): This diet involves periods of
higher-carbohydrates in between the ketogenic diet cycles,
for example, five ketogenic days followed by two high-
carbohydrate days as a cycle.
 TYPES OF KETOGENIC DIET

• Targeted ketogenic diet (TKD): This diet permits

adding additional carbohydrates around the periods of
the intensive physical workout.

• High-protein ketogenic diet (HPKD): This diet includes

more protein and the ratio around 60 per cent fat, 35 per
cent protein and five per cent carbohydrates but as can
be seen, it is still a very high fat diet.

Indian J Med Res. 2018 Sep; 148(3): 251–253.

KETONE BODY GENERATION AND
UTILIZATION
BIOCHEMISTRY BEHIND THE KD
 BIOCHEMISTRY BEHIND THE KD

• Ketone build-up in a particular individual depends on several

physiological parameters such as body fat percentage, body
mass index (BMI), and resting metabolic rate.

• The KD should ideally be administered under controlled

environment.

• KD is quite safe as the concentration of ketones in persons

on KD is far lower than the concentration seen in diabetic
ketoacidosis and is not associated with any changes in blood
pH.
BIOCHEMISTRY BEHIND THE KD
• It is proposed that such diet may favor more fat loss
with preservation of lean body mass.
• This effect is partly mediated by reduced plasma
insulin levels.
• Risk of lean body mass loss and sarcopenia can
prevented with judicious supplementation of amino
acids and whey protein.
BIOCHEMISTRY BEHIND THE KD
• Studies have shown induction of fibroblast growth
factor-1 (FGF-1) gene by KD.
• FGF-1 acts as a metabolic regulator of lipolysis,
serum phosphate, active Vitamin D level, and
triglyceride clearance in the liver.
 BENEFICIAL IMPACTS
Benefits in Neurologic Diseases :
• The KD first achieved scientific validity in the treatment of
epilepsy.
• Clinical trials and systematic reviews have shown its efficacy
in reducing seizure frequency in children with refractory
epilepsy.
• Additionally, children treated with the KD were able to remain
seizure-free after halting the KD.
 BENEFICIAL IMPACTS

• A variety of hypotheses have been proposed.

• It is likely that interplay between many metabolic
systems and the downstream effects of KBs, taken
together, provide protection from seizures.
• One hypothesis is that the KBs’ beta-hydroxybutyrate
and acetoacetate protect against oxidative stress in
neuronal cells.
 BENEFICIAL IMPACTS
• Other hypotheses suggest that KBs act as
anticonvulsants or that metabolic systems that
modulate other physiological functions are triggered
with the KD.
• Leptin, the satiety hormone, is increased during the
KD.
• Leptin also has a role in modulating and suppressing
seizure activity.
 BENEFICIAL IMPACTS
• Given the hypothesized neuroprotective effects,
researchers have used the KD for neurological
disorders besides epilepsy.
• A common theme in all neurological conditions is
cellular energy and metabolic dysregulation, which
contribute to pathogenesis.
• The ketogenic diet also seems to have some utility in
Alzheimer's disease, Parkinson's disease, and
glaucoma.
 BENEFICIAL IMPACTS

Benefits in diabetes mellitus :

• KD are significantly beneficial in improving glycemic
control (glycated hemoglobin), eliminate/reduce
diabetic medications, increase high-density
lipoprotein-cholesterol (HDL-C), and cause weight loss
in overweight and obese individuals with type 2
diabetes over a 24-week period compared to low
glycemic index diet.
 BENEFICIAL IMPACTS
Benefits in obesity :
• In obese patients, KD treatment had shown greater weight loss as
compared to other balanced diets.

• This comparative greater weight loss makes it an alternative tool

against obesity.

• The possible mechanisms for higher weight loss may be controlled

hunger due to higher satiety effect of proteins, direct appetite
suppressant action of KB, and changes in circulating the level of
several hormones such as ghrelin and leptin which controls appetite.
 BENEFICIAL IMPACTS

• Other mechanisms proposed are reduced lipogenesis,

increased lipolysis, reduction in resting respiratory
quotient, increased metabolic costs of
gluconeogenesis, and the thermic effect of proteins.
 BENEFICIAL IMPACTS
Benefits in Metabolic syndrome :
• Insulin resistance in peripheral tissues manifests as
hyperglycemia, hyperinsulinemia, abnormal fatty acid
metabolism and atherogenic dyslipidemia in MetS, and
cardiovascular diseases.

• Dietary carbohydrate modulates lipolysis, assembly, and

processing of lipoprotein.
 BENEFICIAL IMPACTS
• KD in long term (12 months or more) results in
decreased body weight, triglycerides, and diastolic
blood pressure whereas it causes increased HDL-C
and low-density lipoprotein-C as compared to low fat
diet.
 BENEFICIAL IMPACTS

Benefits in polycystic ovarian diseases:

• Polycystic ovary syndrome (PCOS) is associated with obesity,
hyperinsulinemia, insulin resistance, reproductive and
metabolic implications.

• The metabolic and endocrine effects of low carbohydrate KD

are evidenced by improvements in body weight, free
testosterone percentage, luteinizing hormone/follicle-
stimulating hormone ratio, and fasting insulin levels.
 BENEFICIAL IMPACTS
• It leads to decrease in androgen secretion and increase in
sex-hormone binding globulin, improves insulin sensitivity and
thereby renormalizes endocrine functions.
• Such dietary intervention and lifestyle management has
beneficial effects in the treatment of PCOS patients affected
with obesity and type 2 diabetes.
• It has also been shown to improve depressive symptoms,
psychological disturbances, and health-related quality of life in
these patients.
 KETOGENIC DIETS AS ANTICANCER
APPROACHES
• Brian tumor cells are less able than healthy
brain tissue to use ketones as an energy
source.
• May restrict glucose required to produce
components critical to proliferative cell
growth in tumor cells.
• Provide additional energy substrate to normal
healthy tissues at risk of cell death.
CLINICAL TRIALS USING KD IN CANCER
TREATMENT
KETOGENIC DIET IN OBESITY- FRIEND
OR FOE
 BURDEN OF OBESITY
• Obesity is reaching epidemic proportions and is a
strong risk factor for a number of cardiovascular and
metabolic disorders such as hypertension, type 2
diabetes, dyslipidemia, atherosclerosis, and also
certain types of cancers.
• Despite the constant recommendations of health care
organizations regarding the importance of weight
control, this goal often fails.
• Genetic predisposition in combination with inactive
lifestyles and high caloric intake leads to excessive
weight gain.
 BURDEN OF OBESITY
• Obesity is a rapidly growing epidemic
worldwide that has nearly doubled since
1980.
• In 2008, over 200 million men and nearly 300
million women aged 20 and over were obese,
and 65% of the world’s population live in
countries where overweight and obesity kills
more people than underweight.
 BURDEN OF OBESITY
• For physicians, obesity is one of the most
challenging problems confronted in daily
practice and despite the efforts of both
patients and physicians, this disorder is
increasing in prevalence.
 BURDEN OF OBESITY
• There has been a resurgence of interest in low-
carbohydrate diets for treatment of obesity and
type 2 diabetes, partly as a backlash against prior
decades of low-fat diet advice that failed to
prevent these twin epidemics.
• Proponents of low-carbohydrate diets have
advertised the potential benefits of improved
glycemic control and concomitant lowering of
cardiometabolic risk factors.
 WEIGHT LOSS
• Very low carbohydrate diets result in a
substantial‘metabolic advantage’ due to
increased energy expenditure amounting to as
much as a 400–600 kcal/day.
• Indeed, a recent low-carbohydrate diet book
promised an increase in energy expenditure
equivalent to about an hour of moderate
vigorous physical activity.
 WEIGHT LOSS
• Furthermore, low-carbohydrate diets have
been purported to result in preferential body
fat loss in comparison with isocaloric, higher
carbohydrate diets due to decreased insulin
secretion resulting in increased adipose
lipolysis, increased fat oxidation, and less fat
synthesis
 WEIGHT LOSS
• An alternative mechanism whereby low-
carbohydrate diets may lead to increased
weight loss regards their ability to
spontaneously decrease calorie intake.
• For example, very low-carbohydrate diets may
reduce appetite by promoting an increase in
circulating ketones.
 WEIGHT LOSS
• Also, low-carbohydrate diets often result in
higher protein intake which may also increase
satiety, decrease overall energy intake, and
result in preferential body fat loss.
 GLYCEMIC CONTROL
• Most dietary carbohydrates are absorbed in
the circulation as glucose which stimulates
insulin secretion as part of a negative
endocrine feedback circuit to control glucose
levels.
• Type 2 diabetes is clinically defined by
hyperglycemia and arises because insulin
responsive tissues like the liver, adipose, and
muscle become resistant to its effects.
 GLYCEMIC CONTROL
• The pancreatic beta cells produce insufficient
insulin to maintain normal glucose
concentrations.
• Therefore, it makes sense for people with type
2 diabetes to eat a diet that does not require
the body to produce copious quantities of
insulin to maintain normal glucose levels.
 GLYCEMIC CONTROL
• Very low-carbohydrate diets substantially
decrease endogenous insulin requirements
and result in markedly reduced postprandial
glucose excursions .
• Fasting glucose levels also decrease because
endogenous glucose production is reduce
primarily due to decreased rates of
glycogenolysis with an incomplete
compensatory increase in gluconeogenesis.
 GLYCEMIC CONTROL
• Thus, there is a strong physiological rationale
for using low-carbohydrate diets for the
treatment of hyperglycemia.
 INSULIN SECRETION
• The effect of low-carbohydrate diets on insulin
secretion may be two-fold.
• As mentioned above, low carbohydrate diets
decrease circulating glucose concentrations
resulting in a rapid reversal of the ‘glucotoxicity’
to pancreatic beta cells.
• However, lower insulin concentrations with low-
carbohydrate diets also results in increased
lipolysis and higher concentrations of circulating
nonesterified fatty acids(NEFA).
 INSULIN SECRETION
• With chronic exposure to elevated NEFA, there
is impairment in glucose-stimulated insulin
secretion which could worsen glucose
tolerance, especially in individuals with
impaired glucose tolerance or a family history
of diabetes.
 INSULIN SECRETION
• This ‘lipotoxicity’ of increased lipid delivery to
beta cells, and impairment of insulin
secretion, may depend on accumulation of
pancreatic triglycerides, and is less likely to
occur if the low-carbohydrate diet also leads
to weight loss.
 INSULIN RESISTANCE
• If hyperinsulinemia is the primary driver of
insulin resistance, consuming a low-
carbohydrate diet should improve insulin
sensitivity, because it lowers circulating insulin
concentrations.
• Furthermore, low-carbohydrate diets should
also increase insulin sensitivity in people with
diabetes because ‘glucotoxicity’ due to
hyperglycemia also impairs insulin action.
 INSULIN RESISTANCE
• Indeed, some studies have demonstrated that
low-carbohydrate diets increase insulin
sensitivity as measured by the gold-standard
glucose-insulin clamp method.
 LIPID METABOLISM
• Low-carbohydrate diets generally increase
blood HDL cholesterol and decrease
triglycerides in the overnight-fasted state
which is encouraging given their potential
causal role in coronary heart disease.
• There is no doubt that there is strong
supportive evidence that the use of ketogenic
diets in weight-loss therapy is effective.
• The first law of thermodynamics, also known
as the law of conservation of energy, has in
effect controlled the concepts for the basis of
weight loss for over a century—resulting in a
difficulty in accepting other ways of thinking.
• Adhering to these traditional concepts the US
Department of Agriculture has concluded that
diets, which reduce calories, will result in
effective weight loss independent of the
macronutrient composition, which is
considered less important, even irrelevant.
• In contrast with these views, the majority of ad-
libitum studies demonstrate that subjects who
follow a low carbohydrate diet lose more weight
during the first 3–6 months compared with those
who follow balanced diets.
• One hypothesis is that the use of energy from
proteins in VLCKD is an ‘expensive’ process for
the body and so can lead to a ‘waste of calories’,
and therefore increased weight loss compared
with other ‘less-expensive’ diets.