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Exp Clin Cardiol Vol 9 No 3 2004200
Long-term effects of a ketogenic diet in obese patients
Hussein M Dashti MD PhD FICS FACS1, Thazhumpal C Mathew MSc PhD FRCPath4, Talib Hussein MB ChB5,
Sami K Asfar MB ChB MD FRCSEd FACS1, Abdulla Behbahani MB ChB FRCS FACSI PhD FICS FACS1,
Mousa A Khoursheed MB ChB FRCS FICS1, Hilal M Al-Sayer MD PhD FICS FACS1,
Yousef Y Bo-Abbas MD FRCPC2, Naji S Al-Zaid BSc PhD3
Departments of 1Surgery, 2Medicine and 3Physiology, Faculty of Medicine, and 4Faculty of Allied Health Sciences, Kuwait University, Safat;
5Ministry of Health, Safat, Kuwait
Correspondence: Dr Naji Al-Zaid, Department of Physiology, Faculty of Medicine, PO Box 24923, 13110, Safat, Kuwait.
Telephone 965-531-9593, fax 965-531-9597, e-mail alzaidnajeee@hotmail.com
HM Dashti, TC Mathew, T Hussein, et al. Long-term effects
of a ketogenic diet in obese patients. Exp Clin Cardiol
2004;9(3):200-205.
BACKGROUND: Although various studies have examined the
short-term effects of a ketogenic diet in reducing weight in obese
patients, its long-term effects on various physical and biochemical
parameters are not known.
OBJECTIVE: To determine the effects of a 24-week ketogenic diet
(consisting of 30 g carbohydrate, 1 g/kg body weight protein,
20% saturated fat, and 80% polyunsaturated and monounsaturated
fat) in obese patients.
PATIENTS AND METHODS: In the present study, 83 obese
patients (39 men and 44 women) with a body mass index greater than
35 kg/m2, and high glucose and cholesterol levels were selected. The
body weight, body mass index, total cholesterol, low density lipopro-
tein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol,
triglycerides, fasting blood sugar, urea and creatinine levels were
determined before and after the administration of the ketogenic diet.
Changes in these parameters were monitored after eight, 16 and
24 weeks of treatment.
RESULTS: The weight and body mass index of the patients decreased
significantly (P<0.0001). The level of total cholesterol decreased from
week 1 to week 24. HDL cholesterol levels significantly increased,
whereas LDL cholesterol levels significantly decreased after treatment.
The level of triglycerides decreased significantly following 24 weeks of
treatment. The level of blood glucose significantly decreased. The
changes in the level of urea and creatinine were not statistically signif-
icant.
CONCLUSIONS: The present study shows the beneficial effects of a
long-term ketogenic diet. It significantly reduced the body weight and
body mass index of the patients. Furthermore, it decreased the level of
triglycerides, LDL cholesterol and blood glucose, and increased the
level of HDL cholesterol. Administering a ketogenic diet for a relatively
longer period of time did not produce any significant side effects in the
patients. Therefore, the present study confirms that it is safe to use a
ketogenic diet for a longer period of time than previously demonstrated.
Key Words: Diet; Ketosis; Obesity
Obesity has become a serious chronic disease in both devel-
oping and developed countries. Furthermore, it is associated
with a variety of chronic diseases (1-4). It is estimated that in the
United States alone approximately 300,000 people die each year
from obesity-related diseases (5,6). Different methods for reduc-
ing weight using reduced calorie and fat intake combined with
exercise have failed to show sustained long-term effects (7-9).
Recent studies from various laboratories (10,11), including our
own (12), have shown that a high fat diet rich in polyunsatu-
rated fatty acids (ketogenic diet) is quite effective in reducing
body weight and the risk factors for various chronic diseases.
The ketogenic diet was originally introduced in 1920 (13). In
this diet, the fat to carbohydrate ratio is 5:1. While there was a
significant decrease in the weight of obese patients who were on
a ketogenic diet (12), the reverse occurred when the diet
changed to one high in carbohydrates (14).
It should be noted that the concept that fat can be eaten
ad libitum and still induce weight loss in obese subjects is not
a recent one (13-33). Ketosis occurs as a result of the change
in the body’s fuel from carbohydrate to fat. Incomplete oxida-
tion of fatty acids by the liver results in the accumulation of
ketone bodies in the body. A ketogenic diet maintains the
body in a state of ketosis, which is characterized by an eleva-
tion of D-b-hydroxybutyrate and acetoacetate.
Mild ketosis is a natural phenomenon that occurs in
humans during fasting and lactation (19,20). Postexercise
ketosis is a well-known phenomenon in mammals. Although
most of the changes in the physiological parameters induced
following exercise revert back to their normal values rapidly,
the level of circulating ketone bodies increases for a few hours
after muscular activity ceases (21). It has been found that in
trained individuals, a low blood ketone level protects against
the development of hypoglycemia during prolonged intermit-
tent exercise (22). In addition, ketosis has a significant influ-
ence on suppressing hunger. Thus, a ketogenic diet is a good
regulator of the body’s calorie intake and mimics the effect of
starvation in the body.
It is generally believed that high fat diets may lead to the
development of obesity and several other diseases such as coro-
nary artery disease, diabetes and cancer. This view, however, is
based on studies carried out in animals that were given a high fat
diet rich in polyunsaturated fatty acids. In contrast, our labora-
tory has recently shown that a ketogenic diet modified the risk
factors for heart disease in obese patients (12).
Although various short-term studies examining the effect of
a ketogenic diet in reducing the weight of obese patients have
been carried out (10), its long-term effects in obese subjects are
not known (15). Therefore, the purpose of the present study
©2004 Pulsus Group Inc. All rights reserved
CLINICAL CARDIOLOGY
Dashti.qxd 21/10/2004 11:45 AM Page 200
was to investigate the long-term effects of a ketogenic diet on
obesity and obesity-associated risk factors in a large population
of obese patients.
PATIENTS AND METHODS
Patients and biochemical analysis
The prospective study was carried out at the Academic
Department of Surgery, Consultation and Training Centre,
Faculty of Medicine, Kuwait University (Jabriya, Kuwait) in
83 obese subjects (39 men and 44 women). The body mass index
(BMI) of men and women was 35.9±1.2 kg/m2and
39.4±1.0 kg/m2, respectively. The mean age was 42.6±1.7 years
and 40.6±1.6 years for men and women, respectively. The mean
age, initial height, weight and BMI for all patients are given in
Table 1. Fasting blood tests were carried out for all of the subjects.
Initially, all patients were subjected to liver and renal function
tests, and glucose and lipid profiles, using fasting blood samples,
and a complete blood count. Thereafter, fasting blood samples were
tested for total cholesterol, high density lipoprotein (HDL) choles-
terol, low density lipoprotein (LDL) cholesterol, triglycerides,
blood sugar, urea and creatinine levels at the eighth, 16th and
24th week. In addition, weight and height measurements, and
blood pressure were monitored at each visit.
Protocol for ketogenic diet-induced body weight reduction
All 83 subjects received the ketogenic diet consisting of 20 g to 30 g
of carbohydrate in the form of green vegetables and salad, and 80 g
to 100 g of protein in the form of meat, fish, fowl, eggs, shellfish and
cheese. Polyunsaturated and monounsaturated fats were also
included in the diet. Twelve weeks later, an additional 20 g of car-
bohydrate were added to the meal of the patients to total 40 g to
50 g of carbohydrate. Micronutrients (vitamins and minerals) were
given to each subject in the form of one capsule per day (Table 2).
Statistical analysis
Statistical differences between body weight, total cholesterol,
HDL cholesterol, LDL cholesterol, triglycerides, level of fasting
blood sugar, and urea and creatinine levels before and after the
administration of the ketogenic diet were analyzed using a paired
Student’s ttest using the Stat-view version 4.02 (Abacus Concepts
Inc, USA). Weight, BMI and all biochemical parameters are
expressed as mean ± SEM.
RESULTS
The mean initial weight of the subjects was 101.03±2.33 kg. The
weight decreased significantly during all stages of the treatment
period. The body weights at the eighth, 16th and 24th week
were 91.10±2.76 kg, 89.39±3.4 kg and 86.67±3.70 kg, respec-
tively (Figure 1). Similar to the loss in body weight, a significant
decrease was observed in the BMI of the patients following the
administration of the ketogenic diet. The initial BMI, and the
BMI after the eighth, 16th and 24th week were
37.77±0.79 kg/m2, 33.90±0.83 kg/m2, 33.24±1.00 kg/m2and
32.06±1.13 kg/m2, respectively (Figure 2).
The level of total cholesterol showed a significant decrease
from week 1 to week 24 (Figure 3). The level of HDL choles-
terol significantly increased (Figure 4), whereas LDL choles-
terol levels significantly decreased with treatment (Figure 5).
Ketogenic diet and obesity
Exp Clin Cardiol Vol 9 No 3 2004 201
TABLE 1
Patient data at baseline before treatment with the
ketogenic diet
Age Height Weight Body mass index
n (years) (m) (kg) (kg/m2)
Men 39 42.6±1.7 1.7±0.01 102.4±3.7 35.9±1.2
Women 44 40.6±1.6 1.6±0.01 99.8±2.9 39.4±1.0
All data are mean ± SEM
TABLE 2
Composition of the capsule*
Para-aminobenzoic acid (PH) 30 mg
Vitamin B1(thiamin mononitrate) (BP) 15 mg
Vitamin B2(riboflavin) (BP) 3 mg
Vitamin B5(nicotinamide) (BP) 25 mg
Vitamin B3(calcium pantothenate) (PH) 3 mg
Vitamin B6(pyridoxine HCI) (BP) 5 mg
Vitamin B12 (cyanocobalamin) (BP) 10 µg
Biotin (PH) 5 µg
Folic acid (BP) 100 µg
Vitamin C (ascorbic acid ) BP 60 mg
Vitamin A (retinol) (USP; 2000 IU) 0.6 mg
Vitamin D (calciferol) (INN; 200 IU) 5 µg
Vitamin E (tocopherol acetate) (USNF) 10 mg
Lecithin (PH) 40 mg
Wheat germ oil 100 mg
Lysine (FP) 40 mg
Methionine (DAB) 60 mg
Rutin (DAB) (rutoside) (INN) 10 mg
Iron (as fumarate; BP) 12 mg
Calcium (as dicalcium phosphate) (BP) 52 mg
Phosphorus (as dicalcium phosphate) (BP) 40 mg
Potassium (as KCl) (BP) 2 mg
Zinc (as ZnSO4) (BP) 8 mg
Copper (as CuSO4) (BP) 1 mg
Manganese (as MnSO4) (BP) 2 mg
Iodine (as potassium iodide) (BP) trace
Ginseng (Siberian) (5:1 concentrated extract) 4 mg
*Net weight 45 g. BP British Pharmacopoeia; DAB German Pharmacopoeia;
FP French Pharmacopoeia; INN International nonpropietary names;
IU International units; PH Swiss Pharmacopoeia; USNF United States
National Formulary; USP United States Pharmacopoeia
Figure 1) Reduction in body weight at eight, 16 and 24 weeks follow-
ing the administration of the ketogenic diet in obese patients. The
weights are expressed as mean ± SEM
82.5
85
87.5
90
92.5
95
97.5
100
102.5
105
1 8 16 24
Weeks
)gK( thgiew ydoB
Dashti.qxd 21/10/2004 11:45 AM Page 201
Dashti et al
Exp Clin Cardiol Vol 9 No 3 2004202
The level of triglycerides decreased significantly after 24 weeks
of treatment. The initial level of triglycerides was
2.75±0.23 mmol/L, whereas at week 24, the level decreased to
1.09±0.08 mmol/L (Figure 6). The level of blood glucose signif-
icantly decreased at week 24. The initial blood glucose level
and its level at the eighth, 16th and 24th week were
7.26±0.38 mmol/L, 5.86±0.27 mmol/L, 5.56±0.19 mmol/L and
5.62±0.18 mmol/L, respectively (Figure 7). The changes in the
levels of urea (Figure 8) and creatinine (Figure 9) were not sta-
tistically significant.
DISCUSSION
Until recently, ketosis was viewed with apprehension in the
medical world; however, current advances in nutritional
research have discounted this apprehension and increased pub-
lic awareness about its favourable effects. In humans, ketone
bodies are the only additional source of brain energy after glu-
cose (23,24). Thus, the use of ketone bodies by the brain could
be a significant evolutionary development that occurred in
parallel with brain development in humans. Hepatic genera-
tion of ketone bodies during fasting is essential to provide an
alternate fuel to glucose. This is necessary to spare the destruc-
tion of muscle from glucose synthesis.
A ketogenic diet is clinically and experimentally effective
in antiepileptic and antiobesity treatments; however, the
molecular mechanisms of its action remain to be elucidated. In
some cases, a ketogenic diet is far better than modern anticon-
vulsants (25). Recently, it has been shown that a ketogenic
diet is a safe potential alternative to other existing therapies
for infantile spasms (27). It was further shown that a ketogenic
diet could act as a mood stabilizer in bipolar illness (28).
Beneficial changes in the brain energy profile have been
observed in subjects who are on a ketogenic diet (28). This is a
significant observation because cerebral hypometabolism is a
characteristic feature of those who suffer from depression or
mania (28). It has also been found that a ketogenic diet affects
signal transduction in neurons by inducing changes in the
basal status of protein phosphorylation (29). In another study
(30), it was shown that a ketogenic diet induced gene expres-
sion in the brain. These studies provide evidence to explain
the actions of a ketogenic diet in the brain.
One of the mechanisms of a ketogenic diet in epilepsy may
be related to increased availability of beta-hydroxybutyrate, a
ketone body readily transported through the blood-brain barrier.
In support of this hypothesis, it was found that a ketogenic diet
was the treatment of choice for glucose transporter protein
30
31
32
33
34
35
36
37
38
39
1 8 16 24
Weeks
m
/gK
(
x
ednI ss
a
M
yd
o
B
2
)
Figure 2) Decrease in body mass index at eight, 16 and 24 weeks dur-
ing the administration of a ketogenic diet in obese patients. The values
are expressed as mean ± SEM
1.05
1.1
1.15
1.2
1.25
1.3
1.35
1.4
1.45
1.5
1
816 24
)L/lo
mm( L
D
H
fo
leveL
Weeks
Figure 4) Changes in the level of high density lipoprotein (HDL) cho-
lesterol in obese patients during treatment with a ketogenic diet for a
period of 24 weeks. Data are expressed as mean ± SEM
116824
4.5
4.6
4.7
4.8
4.9
5
5.1
5.2
5.3
5.4
5.5
5.6
Weeks
)L/lomm( loretselohC fo leveL
Figure 3) Decreased levels of total cholesterol (expressed as mean ± SEM)
in obese patients at eight, 16 and 24 weeks during the administration of a
ketogenic diet
3
3.2
3.4
3.6
3.8
4
4.2
4.4
1 8 16 24
)L/lomm( LDL fo leveL
Weeks
Figure 5) Changes in the level of low density lipoprotein (LDL) cho-
lesterol during treatment with a ketogenic diet in obese patients at eight,
16 and 24 weeks. The values are expressed as mean ± SEM
Dashti.qxd 21/10/2004 11:45 AM Page 202
Ketogenic diet and obesity
Exp Clin Cardiol Vol 9 No 3 2004 203
syndrome and pyruvate dehydrogenase deficiency, which are
both associated with cerebral energy failure and seizures (26).
One argument against the consumption of a high fat diet is
that it causes obesity. The major concern in this regard is
whether a high percentage of dietary fat promotes weight gain
more than a low percentage of fat intake. Because fat has a
higher caloric density than carbohydrate, it is thought that the
consumption of a high fat diet will be accompanied by a higher
energy intake (31). On the contrary, recent studies from our
laboratory (12) and many other laboratories (24,32-34) have
observed that a ketogenic diet can be used as a therapy for
weight reduction in obese patients.
It has been found that a sugary diet is the root cause of var-
ious chronic diseases of the body. A recent study (35) showed
that sugar can accelerate aging. Several recent studies (36,37)
have pointed to the fact that a diet with a high glycemic load
is independently associated with the development of cardio-
vascular diseases, type II diabetes and certain forms of cancer.
Glycemic load refers to a diet of different foods that have a
high glycemic index. Glycemic index is a measure of the ele-
vation of glucose levels following the ingestion of a carbohy-
drate. The classification of a carbohydrate based on its
glycemic index provided a better predictor of risk for coronary
artery diseases than the traditional method of classification of
carbohydrate into simple or complex forms (38). In other stud-
ies (38-46), it was shown that the risk of dietary glycemic load
from refined carbohydrates was independent of other known
risk factors for coronary diseases.
It is now evident that high carbohydrate diets increase fast-
ing plasma triglyceride concentrations (47-51) and decrease
HDL cholesterol concentrations (52-55). These changes are
associated with enhanced atherogenesis (55). However, it has
been shown that short-term ketogenic diets improve the lipid
disorders that are characteristic of atherogenic dyslipidemia
(56). It has also been found that sugary drinks decreased blood
levels of vitamin E, thus reducing the amount of antioxidants
in the body. It has been proven, beyond a doubt, that disrupt-
ing the oxidant-antioxidant status of the cell will lead to vari-
ous diseases of the body (57).
The relation between a high fat diet and cancer is not con-
clusive. Recent epidemiological studies (17,58-60) could not
explain a specific causal relationship between dietary fat and
cancer. It has been found that altered energy metabolism and
substrate requirements of tumour cells provide a target for
.75
1
1.25
1.5
1.75
2
2.25
2.5
2.75
3
3.25
1
816 24
)
L
/lom
m
( sed
i
r
e
cyl
g
irT fo le
v
eL
Weeks
Figure 6) Changes in the level of triglycerides in obese patients during
treatment with a ketogenic diet over a period of 24 weeks. The values
are expressed as mean ± SEM
)L
/l
o
mµ(
a
e
r
U
fo l
e
ve
L
4.4
4.6
4.8
5
5.2
5.4
5.6
5.8
6
6.2
6.4
6.6
1 8 16 24
Weeks
Figure 8) Changes in the level of urea in obese patients during a 24-week
ketogenic diet. The level of urea is expressed as mean ± SEM
1 8 16 24
5.25
5.5
5.75
6
6.25
6.5
6.75
7
7.25
7.5
7.75
)L/lomm( esoculG fo leveL
Weeks
Figure 7) Decreased levels of blood glucose (expressed as mean ± SEM)
in obese patients at eight, 16 and 24 weeks during the administration of
a ketogenic diet
)L/lomm(eninitaerC fo leveL
64
66
68
70
72
74
76
78
80
82
84
86
1 8 16 24
Weeks
Figure 9) Changes in the level of creatinine in obese patients during a
24-week ketogenic diet. Values are expressed as mean ± SEM
Dashti.qxd 21/10/2004 11:45 AM Page 203
Dashti et al
Exp Clin Cardiol Vol 9 No 3 2004204
selective antineoplastic therapy. The supply of substrates for
tumour energy metabolism can be reduced by dietary manipula-
tion (eg, ketogenic diet) or by pharmacological means at the
cellular level (eg, inhibitors of glycolysis or oxidative phospho-
rylation). Both of these techniques are nontoxic methods for
controlling tumour growth in vivo (61). Sugar consumption is
positively associated with cancer in humans and test animals
(58-61). This observation is quite logical because tumours are
known to be enormous sugar absorbers. It has also been found
that the risk of breast cancer decreases with increases in total
fat intake (16). Further studies on the role of a ketogenic diet in
antineoplastic therapy are in progress in our laboratory.
A link between low fat diets and osteoporosis has been sug-
gested. Very low fat diets are considered to be low in calcium
content. Women on low fat diets excrete most of the calcium
they consume; therefore, they are more prone to osteoporosis.
However, a high fat diet can rectify this situation (62).
In the present study, a control population on a low fat diet
was not included due to the difficulties in recruiting subjects
for a control group. However, several studies (63,64) with
appropriate control groups that compared the effect of a low fat
diet with a low carbohydrate ketogenic diet have recently been
published. In this regard, these two recent studies are compara-
ble with the present study. Brehm et al (23) showed that obese
women on a low carbohydrate ketogenic diet lost 8.5 kg over
six months compared with 4.2 kg lost by those in the low fat diet
group (P<0.001). Twenty-two subjects from the low carbohy-
drate ketogenic diet and 20 subjects from the low fat diet com-
pleted the study, with both groups reducing their energy
intake by approximately 450 kcal from the baseline level. In
another study performed in 132 severely obese subjects for six
months (24), there was greater weight loss in the low carbohy-
drate ketogenic diet group than in the low fat diet group (5.8 kg
versus 1.9 kg, P=0.002). Both of these studies support the find-
ings presented in the present paper.
CONCLUSIONS
The data presented in the present study showed that a keto-
genic diet acted as a natural therapy for weight reduction in
obese patients. This is a unique study monitoring the effect of
a ketogenic diet for 24 weeks. There was a significant decrease
in the level of triglycerides, total cholesterol, LDL cholesterol
and glucose, and a significant increase in the level of HDL
cholesterol in the patients. The side effects of drugs commonly
used for the reduction of body weight in such patients were not
observed in patients who were on the ketogenic diet.
Therefore, these results indicate that the administration of a
ketogenic diet for a relatively long period of time is safe.
Further studies elucidating the molecular mechanisms of a
ketogenic diet are in progress in our laboratory. These studies
will open new avenues into the potential therapeutic uses of a
ketogenic diet and ketone bodies.
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