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Long Term Effects of Ketogenic Diet in Obese Subjects with High Cholesterol Level

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Various studies have convincingly shown the beneficial effect of ketogenic diet (in which the daily consumption of carbohydrate is less than 20 grams, regardless of fat, protein and caloric intake) in reducing weight in obese subjects. However, its long term effect on obese subjects with high total cholesterol (as compared to obese subjects with normal cholesterol level is lacking. It is believed that ketogenic diet may have adverse effect on the lipid profile. Therefore, in this study the effect of ketogenic diet in obese subjects with high cholesterol level above 6 mmol/L is compared to those with normocholesterolemia for a period of 56 weeks. In this study, 66 healthy obese subjects with body mass index (BMI) greater than 30, having high cholesterol level (Group I; n = 35) and those subjects with normal cholesterol level (Group II; n = 31) were selected. The body weight, body mass index, total cholesterol, LDL-cholesterol, HDL-cholesterol, urea, creatinine, glucose and triglycerides were determined before and after the administration of the ketogenic diet. Changes in these parameters were monitored at 8, 16, 24, 32, 40, 48 and 56 weeks of the treatment. The body weight and body mass index of both groups decreased significantly (P < 0.0001). The level of total cholesterol, LDL cholesterol, triglycerides and blood glucose level decreased significantly (P < 0.0001), whereas HDL cholesterol increased significantly (P < 0.0001) after the treatment in both groups. This study shows the beneficial effects of ketogenic diet following its long term administration in obese subjects with a high level of total cholesterol. Moreover, this study demonstrates that low carbohydrate diet is safe to use for a longer period of time in obese subjects with a high total cholesterol level and those with normocholesterolemia.
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Molecular and Cellular Biochemistry 286: 1–9, 2006.
DOI: 10.1007/s11010-005-9001-x c
gSpringer 2006
Long term effects of ketogenic diet in obese
subjects with high cholesterol level
Hussein M. Dashti,1Naji S. Al-Zaid,2Thazhumpal C. Mathew,3
Mahdi Al-Mousawi,4Hussain Talib,4Sami K. Asfar1
and Abdulla I. Behbahani1
1Department of Surgery, Kuwait University, Kuwait; 2Department of Physiology, Kuwait University, Kuwait; 3Faculty of
Medicine and Faculty of Allied Health Sciences, Kuwait University, Kuwait; 4Primary Health Care Salmeiah and Shaab Clinic
Received 8 May 2005; accepted 8 September 2005
Abstract
Objective: Various studies have convincingly shown the beneficial effect of ketogenic diet (in which the daily consumption of
carbohydrate is less than 20 grams, regardless of fat, protein and caloric intake) in reducing weight in obese subjects. However,
its long term effect on obese subjects with high total cholesterol (as compared to obese subjects with normal cholesterol level)
is lacking. It is believed that ketogenic diet may have adverse effect on the lipid profile. Therefore, in this study the effect of
ketogenic diet in obese subjects with high cholesterol level above 6 mmol/L is compared to those with normocholesterolemia
for a period of 56 weeks.
Materials and methods: In this study, 66 healthy obese subjects with body mass index (BMI) greater than 30, having high
cholesterol level (Group I; n=35) and those subjects with normal cholesterol level (Group II; n=31) were selected. The body
weight, body mass index, total cholesterol, LDL-cholesterol, HDL-cholesterol, urea, creatinine, glucose and triglycerides were
determined before and after the administration of the ketogenic diet. Changes in these parameters were monitored at 8, 16, 24,
32, 40, 48 and 56 weeks of the treatment.
Results: The body weight and body mass index of both groups decreased significantly (P<0.0001). The level of total
cholesterol, LDL cholesterol, triglycerides and blood glucose level decreased significantly (P<0.0001), whereas HDL
cholesterol increased significantly (P<0.0001) after the treatment in both groups.
Conclusion: This study shows the beneficial effects of ketogenic diet following its long term administration in obese subjects
with a high level of total cholesterol. Moreover, this study demonstrates that low carbohydrate diet is safe to use for a longer
period of time in obese subjects with a high total cholesterol level and those with normocholesterolemia. (Mol Cell Biochem
286: 1–9, 2006)
Key words: blood glucose, cholesterol, HDL, ketogenic diet, LDL, low carbohydrate diet, obesity, triglycerides
Introduction
Ketogenic diet has been around in the medical literature
for well over 70 years [1]. It has been known that fasting
has beneficial effects on seizure control. For many years,
it was used as an anti-convulsant for controlling seizures.
Address for offprints: H.M. Dashti, Department of Surgery, Faculty of Medicine, P.O. Box 24923, 13110, Safat, Kuwait (E-Mail: info@drdashti.com)
In some cases it is actually better than the modern anti-
convulsants at controlling seizures. Mild ketosis is a natu-
ral phenomenon that occurs in man during fasting and lac-
tation. Post-exercise ketosis is a well known phenomenon
in mammals, the diet mimics the effects of starvation
[1–3].
2
In this study a low carbohydrate diet (Ketogenic diet) in
which the daily consumption of carbohydrate is less than 20 g,
regardless of fat, protein and caloric intake is used. In sub-
jects with ketogenic diet, the metabolic energy requirements
are obtained from the adipose tissue and/or from dietary fat
consumed by the subject. The ketone bodies, acetoacetic
acid, β-hydroxybutyrate and acetone produced during the
fat metabolism substitute for glucose in subjects with keto-
genic diet. Furthermore, 1 g of protein can give away 0.5 g
of glucose whenever patient is on ketogenic diet [4], thus it
sustains positive nitrogen balance and ultimately preserves
the lean body mass [5].
Currently, there is a wide popularity about ketogenic diet,
prompting concerns regarding the use of ketogenic diet in
weight reductions programs. However, very few studies eval-
uated their effect in cardiac risk factors [6, 7]. These studies
indicated that application of ketogenic diet results in sig-
nificant decrease in serum triglycerides, small increase in
total and LDL cholesterol and moderate increase in HDL
cholesterol in subjects with normal lipid profile. In another
study it is shown that for every kilogram of weight loss,
HDL cholesterol increases 0.009 and triglycerides decrease
0.015 mmol/L [8]. Elevated fasting triglyceride is found to
be an independent risk factor for cardiovascular diseases [9].
On the other hand, numerous studies suggest that a high
carbohydrate diet raise triglyceride levels and reduce HDL
cholesterol along with insulin resistance [10, 11]. Interest-
ingly, these changes in triglyceride and HDL levels were
reversed by replacing saturated fat instead of carbohydrate
[12, 13].
Considering the complications caused by high cholesterol
level in the blood, the usual tendency is to modify the diet
so as to eliminate cholesterol and unsaturated fat. In this re-
gard, it is reasonable to believe that the best alternative in
such a situation is to enable the cells to use excess lipids
to produce energy, which also reduces obesity. The cells
can be primed to this type of metabolism by using a high
fat diet and by not providing carbohydrate, which is the
usual source of fuel for the energy requirements in the body.
Various studies have convincingly shown the beneficial ef-
fects of ketogenic diet in reducing weight in obese subjects
as compared to other diet programs [14–20], its long term
effect on the lipid profile of obese subjects with high to-
tal cholesterol as compared to obese subjects with normal
cholesterol level is lacking. Therefore, the present study was
carried out to demonstrate the changes in body weight, lipid
profile, glucose, urea and creatinine that might occur after
the administration of ketogenic diet throughout the period
of study (56 weeks), in healthy obese subjects with hyper-
cholesterolemia as compared to those obese subjects with
normocholesterolemia.
Materials and methods
Obese subjects (BMI greater than 30) who attended the
Consultation and training office in the Faculty of Medicine,
Kuwait University, were included in the study. Medical his-
tory and clinical examination were carried out on all the sub-
jects during each visit. Among the 997 obese subjects who
attended the Consultation and training office, only 66 sub-
jects (34 males and 32 females) were included in this study.
119 subjects refused to participate in this study, whereas 812
subjects who were suffering from other health related prob-
lems such as heart diseases, hepatic diseases, serum creatinine
above 120 μmol/L and with history of weight loss medica-
tion were excluded from the study. All the subjects who were
included in this study were Kuwaitis. The subjects were di-
vided into two groups: Group I (21 males and 14 females),
subjects with high cholesterol level above 6mmol/L (normal
3.4–6.00 mmol/L); and Group II (13 males and 18 females),
subjects with normal cholesterol level less than 6mmol/L.
Among the 66 subjects included in the study, 35 subjects
belonged to Group I and 31 to Group II.
All 66 subjects received a ketogenic diet consisting of less
than 20 g of carbohydrates in the form of green vegetables
and salad and 80–100 g of proteins in the form of meat, fish,
fowl, eggs, shellfish and cheese. Polyunsaturated and mo-
nounsaturated fats (5 tablespoons olive oil) were included
in the diet. Gradually, the amount of carbohydrate is raised
from the original 20 to 40 g in order to supply sufficient glu-
cose to sustain the cells with few or no mitochondria such as
erythrocytes, cornea, lens, renal medulla and leukocytes [4].
A list of recommended and restricted food in ketogenic
diet is given in Table 1. In addition, micronutrients (vitamins
and mineral; Centrum Select, Canada) in the form of 1 cap-
sule/day were given to each subjects (Table 2). Twelve weeks
later an additional 20 g of carbohydrate was given. During
each visit, participants were asked regarding the adherence
to the diet and adverse effects. All participants were asked to
perform exercise in the form of 45min walking daily.
Fasting blood tests were carried out in all the subjects. The
subjects were subjected to liver and renal function tests, com-
plete blood count, total cholesterol, high density lipoprotein
(HDL), low density lipoprotein (LDL; directly measured),
triglycerides (TG), urea and creatinine in the beginning after
8, 16, 24, 32, 40, 48 and 56 weeks. Biochemical analysis of
lipid, liver, renal profiles and electrolytes were performed by
Beckman CX 5 C E and complete blood count was carried
out by Coulter MD II. The body mass index (the weight in
kilograms divided by square of the height) was determined
initially and after 8, 16, 24, 32, 40, 48 and 56 weeks. We stan-
dardized our results with daily internal and external quality
control program with “Lab quality Finland”. During each
3
Table 1. Recommended and restricted food in ketogenic diet
Recommended food Fully restricted food
Proteins Vegetables/Fruits Oil Carbohydrates Fruits/drinks
Fish: Tuna, Sardine Prawns,
Shrimps. Lobster
Spinach, Watercress, Eggplant,
Parsley, Mulberry, Coriander,
Mint, Artichoke, Okra, Cabbage,
Mushroom, Avocado, Leek,
Carrot, Radish, Celery,
Cauliflower, Green pepper,
Lettuce, Cucumber, Tomato,
10–15 olives/day, Lemon
Olive oil (5
tablespoon, added to
the salad
Flour, Potato, Macaroni Spaghetti,
Noodles, Bread, Rice, Sugar,
Sweets, Honey, Cakes
All fruit juices
Meat: Kababs, Sausages, Minced Strawberry-6/day, Avocado Flax seed oil All soft drinks
Poultry: Chicken, Eggs Berries-10/day
Cheese: Full fat cheese
Table 2. Composition of the capsule containing micronutrients
Vit. A 1000 IU
Beta-Carotene 3000 IU
Vit E 75 IU
Vit C 90 mg
Folic Acid 0.6 mg
Vit. B1 2.25 mg
Vit. B2 3.2 mg
Niacinamide 15 mg
Vit. B6 8 mg
Vit. B12 25 mg
Vit D 400 IU
BIOTIN 45 mcg
Pantathenic acid 10 mg
Minerals
Calcium 200 mg
Phosphorus 125 mg
Iodine 0.15 mg
Iron 4 mg
Magnesium 50 mg
Copper 2 mg
Manganese 5 mg
Pottassium 80 mg
Chlorine 72 mg
Chromium 100 mcg
Malybdenum 25 mcg
Selenium 25 mcg
Zinc 15 mg
Nickel 5 mcg
Tin 0.010 mg
Vanadium 10 mcg
Silicon 0.010 mg
Other Ingredients
Lutein 250 mg
Source: Centrum Select, Canada.
visit, enquiries were made regarding their adherence to the
diet, exercise habits and any side effects or uncomfortable
feelings they felt.
Statistical differences between parameters before and af-
ter the administration of ketogenic diet were analyzed by
ANOVA and student- ttest using a package (Stat view 4.02).
Age, body mass index and all biochemical parameters were
expressed as mean ±standard error.
Results
Among the 66 subjects who were included in this study, 35
subjects belonged to group I and 31 to group II. Their age
ranged from 17 to 67. Only 49 subjects (74%) completed 56
weeks successfully. At 56 weeks, there were 26 subjects in
group I (with high cholesterol level) and 23 in group II (with
normal cholesterol level). Among the 49 subjects who com-
pleted the study, 25 were male and 24 were female subjects
(Table 3).
The average age, weight, BMI and the baseline values
of other biochemical parameters examined in this study are
given in Table 4. There was a significant reduction ( P<
0.0001) in the body weight (Fig. 1) and the BMI of males
Table 3. Number of patients at different stages of the study
Group I (High Group II (Normal Total
Cholesterol) N(%) Cholesterol) N(%) N(%)
Week-1 35 (100) 31 (100) 66 (100)
Week-24 34 (97.1) 28 (90.3) 62 (93.9)
Week-32 32 (91.4) 27 (87.1) 59 (89.4)
Week-40 30 (85.7) 26 (83.9) 56 (84.8)
Week-56 26 (74.3) 23 (74.2) 49 (74.2)
4
Table 4. Baseline values of different physical and biochemical parameters
monitored in persons subjected to low carbohydrate diet (ketogenic diet)
Group I Group II
Total (n=35) (n=31) p-value
Age (years) 42.9 ±10.8 45.5 ±9.2 39.9 ±11.8 0.0731
Weight (Kg) 106.9 ±18.3 112.3 ±19.3 100.7 ±15.3 0.0168
BMI (Kg/m2) 39.1 ±6.1 40.1 ±6.1 38.0 ±6.1 0.1385
Tot.Chol. (mmol/l) 6.1 ±1.4 7.0 ±0.9 5.0 ±0.8 <0.0001
HDL (mmol/l) 1.1 ±0.3 1.1 ±0.3 1.2 ±0.3 0.0076
LDL (mmol/l) 4.6 ±1.2 5.4 ±0.8 3.6 ±0.7 <0.0001
TG (mmol/l) 3.2 ±2.3 4.3 ±2.6 2.0 ±1.1 <0.0001
Glucose (mmol/l) 7.7 ±3.4 9.4 ±3.7 5.7 ±1.5 <0.0001
HDL: High density lipoprotein; LDL: Low density lipoprotein; TG: Triglyc-
eride BMI: Body mass index; Tot.Chol.: Total cholesterol.
Data is expressed as mean ±standard deviation.
Fig. 1. Reduction in body weight at 8, 16, 24, 32, 40, 48 and 56 weeks
following the administration of ketogenic diet in obese subjects with hy-
percholesterolemia as compared to those with normocholesterolemia. The
weights are expressed as mean ±SEM. LOCF; Last observation carried
forward. pValue <0.0001 compared with week 1.
and females in both Group I (high cholesterol) and Group II
(normal cholesterol) throughout the program (Fig. 2).
There was a significant change (P<0.0001) in the lipid
profile of the subjects during the entire study period. The
level of total cholesterol decreased significantly after week 1
until the end of the study (Fig. 3). HDL-cholesterol increased
significantly (Fig. 4), whereas LDL-cholesterol decreased
significantly (Fig. 5). The level of triglycerides significantly
decreased from the start till the end of the study (Fig. 6).
The blood glucose level of males and females decreased sig-
nificantly (P<0.0001) from the start until the 56th week
(Fig. 7).The percentage changes in the various parameters
observed at the end of the study and the statistical signifi-
cance between week one and week 56 observations in total,
group I and group II subjects are given in Tables 5 and 6 re-
Fig. 2. Reduction in body mass index (BMI) at 8, 16, 24, 32, 40, 48 and
56 weeks following the administration of ketogenic diet in obese subjects
with hypercholesterolemia as compared to those with normocholesterolemia.
The BMI are expressed as mean ±SEM. LOCF; Last observation carried
forward. pValue <0.0001 compared with week 1.
Fig. 3. Decreased levels of total cholesterol expressed as mean ±SEM, in
obese subjects with hypercholesterolemia as compared to those with nor-
mocholesterolemia at 8, 16, 24, 32, 40, 48 and 56 weeks following the
administration of ketogenic diet. LOCF; Last observation carried forward.
pValue <0.0001 compared with week 1.
spectively. The changes in the level of urea and creatinine at
week 1 and week 56 are given in Figs. 8 and 9 respectively.
The changes in the levels of urea were statistically significant
while changes in the levels of creatinine were not significant.
The ratio of triglyceride/HDL, LDL/HDL and total choles-
terol/HDL at week 1 and week 56 are given in Figs. 10, 11
and 12 respectively.
Discussion
Obesity has become a serious chronic disease in both de-
veloping and developed countries [21–24]. Furthermore, it
5
Table 5. Percentage changes in the various parameters observed at week 56 in persons subjected to ketogenic diet
Total Group I (N=35; Group II (N=31;
(N=66) High cholesterol) Normal cholesterol) p-value
Weight (Kg) 25.9 ±6.3 25.8 ±6.7 26.0 ±5.8 0.9065
Tot.Chol. (mmol/l) 19.3 ±17.0 29.2 ±9.4 6.2 ±16.2 0.0005
HDL (mmol/l) 52.3 ±43.8 63.7 ±52.7 37.1 ±20.6 0.1778
LDL (mmol/l) 28.2 ±20.1 33.5 ±19.5 21.3 ±19.1 0.1331
TG (mmol/l) 59.0 ±32.1 69.8 ±32.6 44.7 ±25.7 0.0537
Glucose (mmol/l) 31.0 ±25.0 44.0 ±22.6 12.8 ±15.1 0.0004
HDL: High density lipoprotein; LDL: Low density lipoprotein; TG: Triglyceride BMI: Body mass index; Tot.Chol.: Total cholesterol.
Data is expressed as mean ±standard deviation. Statistical significance between Group I and Group II are given.
Fig. 4. Changes in the level of HDL-cholesterol expressed as mean ±SEM,
following treatment with ketogenic diet in obese subjects with hypercholes-
terolemia as compared to those with normocholesterolemia for a period of
56 weeks. LOCF; Last observation carried forward. pValue <0.0001 com-
pared with week 1.
Fig. 5. Changes in the level of LDL-cholesterol following treatment with
ketogenic diet at 8, 16, 24, 32, 40, 48 and 56 weeks in obese subjects with high
level of cholesterol as compared to those with normal level of cholesterol.
The levels of LDL-cholesterol are expressed as mean ±SEM. LOCF; Last
observation carried forward. pValue <0.0001 compared with week 1.
Fig. 6. Changes in the level of triglycerides in obese subjects with hyperc-
holesterolemia as compared to those with normocholesterolemia following
treatment with ketogenic diet in obese subjects at 8, 16, 24, 32, 40, 48 and
56 weeks. The levels of triglycerides are expressed as mean ±SEM. LOCF;
Last observation carried forward. pValue <0.0001 compared with week 1.
Fig. 7. Decreased levels of glucose expressed as mean ±SEM following the
administration of ketogenic diet in obese subjects with hypercholesterolemia
as compared to those with normocholesterolemia at 8, 16, 24, 40, 48 and
56 weeks. LOCF; Last observation carried forward. pValue <0.0001 com-
pared with week 1.
6
Table 6. Statistical significance between week 1 and week 56 observation
of various parameters studied in total, group I and group II subjects
Group I (n=35; Group II (n=31;
Total High cholesterol) Normal cholesterol)
Weight (Kg) <0.0001 <0.0001 <0.0001
BMI (Kg/m2)<0.0001 <0.0001 <0.0001
Tot.Chol. (mmol/l) <0.0001 <0.0001 0.0170
HDL (mmol/l) <0.0001 <0.0001 <0.0001
LDL (mmol/l) <0.0001 <0.0001 <0.0001
TG (mmol/l) <0.0001 <0.0001 0.0002
Glucose (mmol/l) <0.0001 <0.0001 0.0034
Fig. 8. Changes in the level of urea in obese subjects with hypercholes-
terolemia as compared to those with normocholesterolemia following treat-
ment with ketogenic diet in obese subjects at 8, 16, 24, 40, 48 and 56 weeks.
The levels of triglycerides are expressed as mean ±SEM. LOCF; Last
observation carried forward. pValue <0.0001 compared with week 1 in
hypercholesterolemic subjects. ∗∗pValue 0.0131 compared with week 1 in
normocholesterolemic subjects.
Fig. 9. Changes in the level of creatinine in obese subjects with hyperc-
holesterolemia as compared to those with normocholesterolemia following
treatment with ketogenic diet in obese subjects at 8, 16, 24, 40, 48 and 56
weeks. The levels of triglycerides are expressed as mean ±SEM. LOCF;
Last observation carried forward.
Fig. 10. Triglyceride/HDL ratio in obese subjects with hypercholes-
terolemia as compared to those with normocholesterolemia following treat-
ment with ketogenic diet in obese subjects at 8, 16, 24, 40, 48 and 56 weeks.
The levels of triglycerides are expressed as mean ±SEM. LOCF; Last
observation carried forward. pValue <0.0001 compared with week 1 in
hypercholesterolemic subjects. ∗∗pValue 0.0001 compared with week 1 in
normocholesterolemic subjects.
Fig. 11. LDL/HDL ratio in obese subjects with hypercholesterolemia as
compared to those with normocholesterolemia following treatment with ke-
togenic diet in obese subjects at 8, 16, 24, 32, 40, 48 and 56 weeks. The
levels of triglycerides are expressed as mean ±SEM. LOCF; Last observa-
tion carried forward. pValue <0.0001 compared with week 1.
is associated with a variety of chronic diseases. It is es-
timated that in United States alone about 300,000 people
die each year from obesity related diseases. There is a grad-
ual increase in the number of obese people in United States
[21–24]. A similar trend is observed in Kuwait and other
Middle East countries. The different attempts for reducing
weight by reduced calorie and fat intake combined with ex-
ercise have failed to show a sustained long term effect. Re-
cent studies from various laboratories, including ours have
shown that a high fat diet rich in polyunsaturated fatty acids
(ketogenic diet) is quite effective in reducing body weight
7
Fig. 12. Total cholesterol/ HDL ratio in obese subjects with hypercholes-
terolemia as compared to those with normocholesterolemia following treat-
ment with ketogenic diet in obese subjects at 8, 16, 24, 32, 40, 48 and 56
weeks. The levels of triglycerides are expressed as mean ±SEM. LOCF;
Last observation carried forward. pValue <0.0001 compared with week 1.
and risk factors associated with various chronic diseases
[1, 25–29].
These studies show the beneficial effects of ketogenic diet
following its long term administration. It significantly re-
duces the body weight and body mass index. Furthermore,
it decreases the level of triglycerides, and LDL-cholesterol
[26–29].
The data presented in this study shows that both high and
normal cholesterol groups showed reduction of LDL, how-
ever, there was no significant alteration between genders. The
level of triglycerides significantly reduced after 8 weeks and
showed a further gradual decrease in both groups till the end
of the year. Similar changes occurred in males and females.
Glucose level decreased significantly in both groups in males
and females. As there were no significant differences in male
and female subjects in all the parameters examined, the data
of males and females in each group are pooled and presented
together.
Majority of the subjects who attended the Consultation and
training office in the Faculty of Medicine, Kuwait University,
suffered from metabolic syndrome (visceral obesity, athero-
genic dyslipedemia (i.e low level of high density lipoprotein
and elevation of total cholesterol and triglyceride) and eleva-
tion of blood sugar. Various investigators have convincingly
shown that triglyceride-rich lipoprotein plays a major role
in atherogenesis [30–34] and fasting triglyceride is directly
related to cardiovascular disease [35, 36], myocardial infarc-
tion, hypertension and diabetes mellitus [37, 38].
Ratio of total cholesterol/HDL and LDL/HDL are used as
predictors of cardiac disease. Recent studies have shown that
an increase in one unit in the LDL/HDL ratio and an increase
in total cholesterol /HDL ratio is associated with a 53% [39,
40] and 49% [27], increase in the risk of myocardial infarc-
tion, respectively. In another study it is found that an increase
in the ratio of LDL to HDL by one unit may even contribute
to a 75% increase in the risk of myocardial infarction [38].
Unfortunately, one of the limitations of this study was that
we were unable to estimate the fasting insulin level in these
subjects. However, there was obvious improvement in their
blood sugar level. In a similar study with low carbohydrate
diet, Noakes et al. [41] have shown a 33% decrease in fasting
insulin level along with improvement of fasting glucose level,
blood pressure and reduction in body weight.
Other investigators have also shown that low carbohydrate
diet had an influence in decreasing fasting triglyceride as well
as the ratio of triglyceride to high density lipoprotein and im-
provement in blood sugar along with reduction in body weight
[42–44]. Although, these studies did not compare the effects
of ketogenic diet in subjects with hypercholesterolemia to
those with normocholesterolemia, these studies collectively
indicate that a low carbohydrate diet had more favourable
outcomes with regard to weight and lipid profile than those
who were on a conventional diet.
Regarding exercise most of the subjects as advised by their
General Practitioners were following at least a daily walk of
45 min before participating in this program. However, they
have not experienced any reduction in body weight. Thus, we
have not introduced a new pattern of exercise together with
this diet. On the other hand we just allowed them to con-
tinue with their routines. It should be noted that we have
included about 5 tablespoons olive oil in the diet recom-
mended to the participants in this programme. Historically,
olive oil is one of the most characteristic components of
Mediterranean diet [45]. It has a protective role in cardio-
vascular diseases, and various cancers, as well as to diminish
the age-related cognitive decline [45–47]. Olive oil is rich
in monounsaturated fatty acids and antioxidant substances.
The health benefits of olive oil are attributed to these factors.
Furthermore, it is shown that olive oil may have protective
role for the dynamic blood cholesterol levels in a healthy
population [47]. It should be noted that in our previous study
[1], we have not included olive oil in the diet and the de-
crease in weight in obese subjects was similar in both the
studies.
Administering ketogenic diet for a relatively longer period
did not produce any significant side effects in subjects with
high level of total cholesterol. Therefore, this study suggests
that it is safe to use ketogenic diet for a longer period of time
regardless of the total cholesterol level of the subjects.
Acknowledgments
We would like to thank Dr. J. Longnecker, Department of
Community Medicine, Faculty of Medicine, Kuwait Univer-
sity for expert statistical consultation.
8
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... The KD has increasingly garnered research attention in the past decade, due to emerging evidence of the therapeutic potential for various diseases, in addition to epilepsy, from obesity to malignancies. Several reports proposed that the KD has probable beneficial results Citation: Flores 36 in combating multiple neurological disorders, e.g., epilepsy, dementia, ALS, traumatic brain injury, acne, cancers, and metabolic disorders [5,7,9,10]. ...
... Most animal studies used KDs rich in saturated fats, which may have detrimental effects on the lipid profile compared to a KD rich in unsaturated fats. Moreover, the KD has been associated with significant reductions in total cholesterol, triglycerides, and LDL and increases in HDL cholesterol levels [36]. ...
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The ketogenic diet (KD) is a high-fat, adequate-protein, and very low-carbohydrate diet that stimulates the creation of ketones by mimicking the metabolism of the fasting state. A high level of blood ketone caused by a KD induces the state of ketosis, which has several physiological and therapeutic advantages. The KD first gained popularity as an epilepsy treatment in the 1920s and 1930s. It has rapidly attracted research interest in the last 20 years due to mounting evidence of the KD's possible therapeutic potential for other diseases besides epilepsy, including obesity, neurodegenerative diseases, and malignancies. The KD alters multiple cellular signaling cascades, receptors, and biomarker levels in various medical situations. KD therapy differs from the typical Western diet in that it focuses on nutritional supplements, electrolytes, and hydration in addition to the diet. If the KD is followed closely, significant dietary changes can positively affect the dieting individual. However, several treatable short-and long-term adverse effects are linked to the KD. It may be challenging to follow the KD long-term if some of the most enjoyable meals are not allowed. Numerous physicians are considering including KD programs in the therapeutic regimen in light of the importance of lifestyle modification in managing diseases. However, before this can be advised, doctors must ensure its efficacy and safety, and further human research is necessary. Numerous economic opportunities will soon arise as a result of the potential medical benefits of the KD. These safeguards and limitations can therefore be used to develop distinctive and personalized interventional procedures replicating the effects of a KD or as potential drug development targets.
... Taking, however, into account the literature, the results differ significantly, and on their basis, no unequivocal conclusions can be drawn. In a 56-week study in individuals using a ketogenic diet, reductions in total cholesterol, triglyceride, and LDL concentrations were noted, with a simultaneous increase in HDL lipoprotein concentration [56]. More and more frequently, potential benefits related to the diet are reported, such as improvement of the lipid profile, i.e., reduction in LDL and triglyceride concentrations and increase in HDL level [57]. ...
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The combination of ketogenic diet (KD) with intermittent fasting (IF) has, for years, aroused a great interest in the scientific world and among healthy lifestyle enthusiasts. Its importance is even greater when the study subjects are physically active individuals. The aim of the study was a determination of the effect of strict calculated ketogenic menu combined with IF and with caloric deficit on the selected biochemical markers and body composition in a 23-year-old man performing strength training. At the same time, we decided to conduct the first so-deeply investigated and controlled case study in this respect. The study protocol included a 13-week-long ketogenic diet with intermittent fasting (of delayed time-restricted eating 16:8 type) and caloric deficit. A detailed menu was designed and was used by the man throughout the whole study duration. A number of blood tests were performed before and after the implemented dietary intervention. Additionally, body composition was determined weekly and the concentrations of glucose and ketone bodies, as well as pulse rate and arterial pressure, were measured daily. The most important changes noted included a significant increase in testosterone and vitamin D concentrations and significant reduction in the HOMA-IR index and concentrations of hepatic enzymes, insulin, glucose, iron, urea, and free triiodothyronine (FT3). Moreover, a significant improvement of body composition occurred (the ratio of total body mass to the adipose and muscular tissue and water mass improved). Favourable changes were also noted in heart rate and arterial pressure values. In view of that, the KD with IF and caloric deficit exerted favourable effects on most biochemical parameters and on body composition and caused an almost twofold increase in serum testosterone concentration.
... [7][8][9][10] It has been suggested that IF improves cardiovascular risk factors through three possible mechanisms: decreasing oxidative stress, synchronization with the circadian system, and increasing ketogenesis. [11][12][13] Also, a decrease in systolic/ diastolic blood pressure was reported with IF, 14 but there is no consensus yet on how IF reduces blood pressure. One of the possible mechanisms could be a decrease in cardiovascular sympathetic tone and an increase in parasympathetic tone, which significantly corrects the autonomic imbalance observed in most hypertensive patients. ...
... Total cholesterol, LDL cholesterol, triacylglycerol, and blood glucose levels all decreased significantly (P > 0.0001) after the treatment, but HDL cholesterol increased significantly (P > 0.0001). In this study, Dashti et al. (2006) demonstrated that patients with high total cholesterol and obese subjects that follow low carbohydrate diets can continue to do so for longer periods of time. There was evidence that vegan diets were associated with a lower BMI, a lower total cholesterol level, a lower glucose level, a lower level of inflammation, and a lower blood pressure level in studies that looked at vegan diets (Kaiser et al., 2021). ...
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Nutritional therapy and disease causes have been studied sparingly. It is one of the main objectives of this study to look for a nutritional diet that promotes cardiovascular health. Various electronic databases and scientifically published articles were searched for relevant information for this review. In addition to these parameters, diabetes, blood pressure, smoking, lifestyle, and inactivity also play a significant role in these diseases. Various scientific studies have shown that consuming the right kind of food, following healthy eating habits, and leading a healthy lifestyle can reduce the risk of heart disease and stroke. The gut microbiome and cardiovascular risk have been shown to be significantly affected by vegetarian and Mediterranean diets. As an adjunct to traditional drug treatment, a healthy lifestyle and a proper diet are essential to improving cardiac patients' lipid profiles. It is essential to understand CVD's molecular and cellular mechanisms and develop targeted therapies.
... For example, the ketogenic diet has been widely praised for its rapid results across social media platforms, news media and print media. Despite its widespread popularity and positive media portrayal, long-term adherence is linked to negative health consequences (Dafoe & Gyenes, 2020; Dashti et al., 2006), similar to other fad-type diets. Despite the overall lack of positive empirical findings, fad-type diets proliferate the media we consume. ...
... [7][8][9][10] It has been suggested that IF improves cardiovascular risk factors through three possible mechanisms: decreasing oxidative stress, synchronization with the circadian system, and increasing ketogenesis. [11][12][13] Also, a decrease in systolic/ diastolic blood pressure was reported with IF, 14 but there is no consensus yet on how IF reduces blood pressure. One of the possible mechanisms could be a decrease in cardiovascular sympathetic tone and an increase in parasympathetic tone, which significantly corrects the autonomic imbalance observed in most hypertensive patients. ...
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Resumo Fundamento Embora tenha sido relatado que a dieta de jejum intermitente (JI) tem efeitos positivos na saúde do coração e na melhora da pressão arterial, ainda não foi suficientemente esclarecido como poderia ter esses efeitos positivos.Objetivo: Nosso objetivo foi avaliar os efeitos do JI no sistema nervoso autônomo (SNA) e no sistema renina-angiotensina (SRA), que estão intimamente relacionados à pressão arterial. Métodos Setenta e dois pacientes hipertensos foram incluídos no estudo, e os dados de 58 pacientes foram usados. Todos os participantes jejuaram por cerca de 15-16 horas por 30 dias. Os participantes foram avaliados com monitorização ambulatorial da pressão arterial de 24 horas e eletrocardiograma Holter antes e após o JI; também, amostras de sangue venoso de 5 ml foram coletadas para avaliação dos níveis séricos de angiotensina I (Ang-I) e angiotensina II (Ang-II) e da atividade da enzima conversora de angiotensina (ECA). Para análise dos dados, o valor de p < 0,05 foi aceito como significativo. Resultados Comparado ao pré-JI, observou-se queda significativa nas pressões arteriais dos pacientes no pós-JI. Um aumento na potência de alta frequência (AF) e na raiz quadrada média da soma dos quadrados das diferenças entre intervalos NN adjacentes (RMSSD) foram observados após o protocolo JI (p=0,039, p=0,043). A Ang-II e a atividade da ECA foram menores em pacientes após JI (p=0,034, p=0,004), e níveis decrescentes de Ang-II foram determinados como fatores preditivos para melhora da pressão arterial, como o aumento da potência de AF e RMSSD. Conclusão Os presentes achados de nosso estudo demonstraram uma melhora na pressão arterial e a relação da pressão arterial com resultados positivos, incluindo VFC, atividade da ECA e níveis de Ang-II após o protocolo JI.
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Background: Oxidative stress and tissue damage (OSD) play a pivotal role as an early-stage process in chronic disease pathogenesis. However, there has been little research to better understand the temporal (χρόνος[chronos]) dimensions of OSD process associated with environmental (non-genetic, including behaviors/lifestyle) and/or occupational stressors, like night shift work. OSD processes have recently attracted attention in relation to time-resolved external stressor trajectories in personalized medicine (prevention) initiatives, as they seem to interact with circadian clock systems towards the improved delineation of the early stages of (chronic) disease process. Objectives: This work critically reviewed human studies targeting the temporal dynamics of OSD and circadian clock system's activity in response to environmental/occupational stressors; the case of night shift work was examined. Methods: Being a key stressor influencing OSD processes and circadian rhythm, night shift work was evaluated as part of a scoping review of research in OSD, including inflammatory and metabolic processes to determine the extent of OSD research undertaken in human populations, methodologies, tools and biomarkers used and the extent that the temporal dimensions of exposure and biological effect(s) were accounted for. Online databases were searched for papers published from 2000 onwards, resulting in the selection of 53 original publications. Results and discussion: The majority of studies (n = 41) took place in occupational settings, while the rest were conducted in the general population or patient groups. Most occupational studies targeted outcomes of oxidative stress/damage (n = 19), followed by the combination of OSD with inflammatory response (n = 10), and studies focused on metabolic outcomes (n = 12). Only a minor fraction of the studies measured biomarkers related to circadian rhythm, such as, melatonin, its metabolite, or cortisol. Night shift work was associated with select biomarkers of OSD and inflammation, albeit with mixed results. Although much progress in delineating the biological mechanisms of OSD process has been made, an equally thorough investigation on the temporal trajectory of OSD processes as triggered by environmental/occupational stressors in human studies has yet to fully evolve.
Chapter
Advancing age is allied to neuromorphological and neurochemical changes in several brain regions, which manifests as generalized reduction in the performance of aged individuals. Besides, some regions like the basal ganglia (BG), cortex, hippocampus, etc., are predisposed to degeneration, due to exaggerated functional deterioration with age. The gradual increase in elderly populace worldwide fosters the need to scrutinize age-associated protective factors. It is further prudent to examine links between normal aging and neurodegenerative alterations in specific brain regions, for example, substantia nigra pars compacta (SNpc) and Parkinson’s disease (PD). Dysfunction of biological clocks precede neurodegenerative disease states. Reduction in telomere length in aged individuals who experience delayed sleep phase syndrome signals deterioration of cellular health. In PD, the rapid eye movement behavioral disorder precedes the onset of motor symptoms by years, often by decades. Yoga, exercise, and social enrichment show positive dispositions during aging and in PD. It is, therefore, imperative to study the mechanisms employed by these lifestyle strategies. More importantly, the mechanisms and consequences need to be studied during middle age, which is a stage of complex neurobiological changes in the BG. The present chapter reviews early and contemporary studies on normal age effects in BG as well as the most common disorder of this region, PD.
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The role of high density lipoprotein (HDL) and of triglyceride in coronary heart disease (CHD) prevention has been extensively debated over the past few years. To address these issues the National Institute of Health convened a Consensus Development Conference on Triglyceride, High Density Lipoprotein, and Coronary Heart Disease. This paper provides an overview of the Consensus Conference and presents its conclusions and recommendations. Major issues addressed by the conference included: 1. casuality of the relationships of HDL, triglyceride and CHD, 2. role of HDL and triglyceride in CHD risk assessment, and 3. treatment recommendations. The panel concluded that the information on HDL and CHD provides considerable support for a causal relationship; for triglyceride, the evidence is still incomplete. The panel recommended adding HDL-cholesterol measurement to total cholesterol measurement when evaluating CHD risk in healthy individuals while triglyceride assessment was recommended only for individuals with increased risk of CHD. With regards to treatment the panel recommended that hygienic measures should always be employed when triglycerides are elevated or HDL cholesterol is low regardless of total cholesterol. Drugs, however, should be used sparingly under these circumstances in the absence of an elevation of LDL cholesterol in individuals without known CHD.
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Background: A previous paper reported the 6-month comparison of weight loss and metabolic changes in obese adults randomly assigned to either a low-carbohydrate diet or a conventional weight loss diet. Objective: To review the 1-year outcomes between these diets. Design: Randomized trial. Setting: Philadelphia Veterans Affairs Medical Center. Participants: 132 obese adults with a body mass index of 35 kg/m 2 or greater; 83% had diabetes or the metabolic syndrome. Intervention: Participants received counseling to either restrict carbohydrate intake to <30 g per day (low-carbohydrate diet) or to restrict caloric intake by 500 calories per day with <30% of calories from fat (conventional diet). Measurements: Changes in weight, lipid levels, glycemic control, and insulin sensitivity. Results: By 1 year, mean (±SD) weight change for persons on the low-carbohydrate diet was -5.1 ± 8.7 kg compared with -3.1 ± 8.4 kg for persons on the conventional diet. Differences between groups were not significant (-1.9 kg [95% Cl, -4.9 to 1.0 kg]; P = 0.20). For persons on the low-carbohydrate diet, triglyceride levels decreased more (P = 0.044) and high-density lipoprotein cholesterol levels decreased less (P = 0.025). As seen in the small group of persons with diabetes (n = 54) and after adjustment for covariates, hemoglobin A 1c levels improved more for persons on the low-carbohydrate diet These more favorable metabolic responses to a low-carbohydrate diet remained significant after adjustment for weight loss differences. Changes in other lipids or insulin sensitivity did not differ between groups. Limitations: These findings are limited by a high dropout rate (34%) and by suboptimal dietary adherence of the enrolled persons. Conclusion: Participants on a low-carbohydrate diet had more favorable overall outcomes at 1 year than did those on a conventional diet. Weight loss was similar between groups, but effects on atherogenic dyslipidemia and glycemic control were still more favorable with a low-carbohydrate diet after adjustment for differences in weight loss.
Article
Background: Low-carbohydrate diets remain popular despite a paucity of scientific evidence on their effectiveness. Objective: To compare the effects of a low-carbohydrate, ketogenic diet program with those of a low-fat, low-cholesterol, reduced-calorie diet. Design: Randomized, controlled trial. Setting: Outpatient research clinic. Participants: 120 overweight, hyperlipidemic volunteers from the community. Intervention: Low-carbohydrate diet (initially, <20 g of carbohydrate daily) plus nutritional supplementation, exercise recommendation, and group meetings, or low-fat diet (<30% energy from fat, <300 mg of cholesterol daily, and deficit of 500 to 1000 kcal/d) plus exercise recommendation and group meetings. Measurements: Body weight, body composition, fasting serum lipid levels, and tolerability. Results: A greater proportion of the low-carbohydrate diet group than the low-fat diet group completed the study (76% vs. 57%; P = 0.02). At 24 weeks, weight loss was greater in the low-carbohydrate diet group than in the low-fat diet group (mean change, -12.9% vs. -6.7%; P < 0.001). Patients in both groups lost substantially more fat mass (change, -9.4 kg with the low-carbohydrate diet vs. -4.8 kg with the low-fat diet) than fat-free mass (change, -3.3 kg vs. -2.4 kg, respectively). Compared with recipients of the low-fat diet, recipients of the low-carbohydrate diet had greater decreases in serum triglyceride levels (change, -0.84 mmol/L vs. -0.31 mmol/L [-74.2 mg/dL vs. -27.9 mg/dL]; P = 0.004) and greater increases in high-density lipoprotein cholesterol levels (0.14 mmol/L vs. -0.04 mmol/L [5.5 mg/dL vs. -1.6 mg/dL]; P < 0.001). Changes in low-density lipoprotein cholesterol level did not differ statistically (0.04 mmol/L [1.6 mg/dL] with the low-carbohydrate diet and -0.19 mmol/L [-7.4 mg/dL] with the low-fat diet; P = 0.2). Minor adverse effects were more frequent in the low-carbohydrate diet group. Limitations: We could not definitively distinguish effects of the low-carbohydrate diet and those of the nutritional supplements provided only to that group. In addition, participants were healthy and were followed for only 24 weeks. These factors limit the generalizability of the study results. Conclusions: Compared with a low-fat diet, a low-carbohydrate diet program had better participant retention and greater weight loss. During active weight loss, serum triglyceride levels decreased more and high-density lipoprotein cholesterol level increased more with the low-carbohydrate diet than with the low-fat diet.
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GREAT progress has been made over the past 30 years in identifying cardiovascular risk factors and in developing and implementing measures to correct them. The Adult Treatment Panel of the National Cholesterol Education Program developed guidelines in 1988 that identified low-density lipoprotein (LDL) as the major atherogenic lipoprotein and high levels of LDL cholesterol (LDL-C) as the primary target for cholesterol-lowering therapy. Since these guidelines were developed, the scientific database has significantly expanded. Genetic investigations into familial dyslipidemias, advances in molecular biology, animal experiments, human observational studies, lipid metabolic studies, epidemiologic data, and the results of interventional clinical trials looking at mortality, cardiovascular end points, and angiographic changes in atheromatous lesions have created interest in further examination of the role of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) in the pathogenesis of coronary artery disease. To address these questions, the National Heart, Lung, and Blood Institute and the Office of
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To determine the relation between plasma triglyceride levels and the risk of incident cardiovascular disease, the semiquantitative techniques of meta-analysis were applied to 17 population-based prospective studies of triglyceride and cardiovascular disease. Sixteen of these studies represented 2,445 events among 46,413 Caucasian men followed for an average period of 8.4 years, and 5 studies represented 439 events among 10,864 Caucasian women followed for an average period of 11.4 years. Univariate relative risk (RR) estimates for incident cardiovascular disease associated with a 1-mmol/L increase in triglyceride was 1.07-1.98 in men, with a summary RR of 1.32 (95% confidence interval [CI]: 1.26-1.39), indicating a 32% increase in disease risk associated with increased triglyceride. In the studies involving women, individual RR estimates for triglyceride were 1.69-2.05, with a summary RR of 1.76 (95% CI: 1.50-2.07), indicating a 76% increase in disease risk associated with increased triglyceride. After adjustment for high-density lipoprotein cholesterol and other risk factors, these risks were decreased to 14% in men and 37% in women but remained statistically significant. Three recent prospective epidemiologic studies have also shown that plasma triglyceride and low-density lipoprotein particle size predict subsequent coronary artery disease in Caucasian populations. Taken together, these studies demonstrate the importance of triglyceride levels as a risk factor for cardiovascular disease.