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Long-Term Ketogenic Diet Induces Metabolic Acidosis, Anemia, and Oxidative Stress in Healthy Wistar Rats

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Journal of Nutrition and Metabolism
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Background: Ketogenic diet has been used as supportive therapy in a range of conditions including epilepsy, diabetes mellitus, and cancer. Objective: This study aimed to investigate the effects of long-term consumption of ketogenic diet on blood gas, hematological profiles, organ functions, and superoxide dismutase level in a rat model. Materials and methods: Fifteen male Wistar rats were divided into control (n = 8) and ketogenic (n = 7) groups. Controls received standard diet contained 52.20% of carbohydrates, 7.00% fat, and 15.25% protein; meanwhile, the ketogenic group received a high-fat-low-carbohydrate diet which contained 5.66% of carbohydrate, 86.19% fat, and 8.15% protein. All rats were caged individually and received 30g of either standard or high-fat-low-carbohydrate pellets. The experiment was carried out for 60 days before the blood samples were taken and analyzed to obtain blood gas, cell counts, organ biomarkers, and plasma antioxidant superoxide dismutase (SOD) levels. Results: The rats subjected to ketogenic diet experienced a marked decrease in body weight, blood sugar, and increased blood ketones (p < 0.05). The average blood pH was 7.36 ± 0.02 and base excess was -5.57 ± 2.39 mOsm/L, which were significantly lower than controls (p < 0.05). Hematological analysis showed significantly lower erythrocyte, hemoglobin, and hematocrit levels. No significant changes were found in alanine aminotransferase, aspartate aminotransferase, urea, and creatinine levels, indicating normal liver and kidney functions. Nevertheless, plasma SOD level significantly reduced with ketogenic diet. Conclusion: Long-term ketogenic diet induces metabolic acidosis, anemia, and reduced antioxidant enzyme level in rats following 60 days of consuming high-fat-low-carbohydrate diet.
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Research Article
Long-Term Ketogenic Diet Induces Metabolic Acidosis, Anemia,
and Oxidative Stress in Healthy Wistar Rats
Aryadi Arsyad ,
1
Irfan Idris,
1
Andi A. Rasyid,
2
Rezky A. Usman,
2
Kiki R. Faradillah,
2
Wa Ode U. Latif,
2
Zidni I. Lubis,
3
Aminuddin Aminuddin,
4
Ika Yustisia,
5
and Yulia Y. Djabir
6
1
Department of Physiology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
2
Biomedical Science Study Program, Postgraduate School, Hasanuddin University, Makassar, Indonesia
3
Department of Physiotherapy, Faculty of Health Science, University of Muhammadiyah Malang, Malang, Indonesia
4
Department of Nutrition, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
5
Department of Biochemistry, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
6
Laboratory of Clinical Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar, Indonesia
Correspondence should be addressed to Aryadi Arsyad; aryadi.arsyad@gmail.com
Received 13 December 2019; Revised 19 April 2020; Accepted 21 May 2020; Published 29 June 2020
Academic Editor: Phillip B. Hylemon
Copyright ©2020 Aryadi Arsyad et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background. Ketogenic diet has been used as supportive therapy in a range of conditions including epilepsy, diabetes mellitus, and
cancer. Objective. is study aimed to investigate the effects of long-term consumption of ketogenic diet on blood gas, he-
matological profiles, organ functions, and superoxide dismutase level in a rat model. Materials and Methods. Fifteen male Wistar
rats were divided into control (n8) and ketogenic (n7) groups. Controls received standard diet contained 52.20% of car-
bohydrates, 7.00% fat, and 15.25% protein; meanwhile, the ketogenic group received a high-fat-low-carbohydrate diet which
contained 5.66% of carbohydrate, 86.19% fat, and 8.15% protein. All rats were caged individually and received 30g of either
standard or high-fat-low-carbohydrate pellets. e experiment was carried out for 60 days before the blood samples were taken
and analyzed to obtain blood gas, cell counts, organ biomarkers, and plasma antioxidant superoxide dismutase (SOD) levels.
Results. e rats subjected to ketogenic diet experienced a marked decrease in body weight, blood sugar, and increased blood
ketones (p<0.05). e average blood pH was 7.36 ±0.02 and base excess was 5.57 ±2.39 mOsm/L, which were significantly
lower than controls (p<0.05). Hematological analysis showed significantly lower erythrocyte, hemoglobin, and hematocrit levels.
No significant changes were found in alanine aminotransferase, aspartate aminotransferase, urea, and creatinine levels, indicating
normal liver and kidney functions. Nevertheless, plasma SOD level significantly reduced with ketogenic diet. Conclusion. Long-
term ketogenic diet induces metabolic acidosis, anemia, and reduced antioxidant enzyme level in rats following 60 days of
consuming high-fat-low-carbohydrate diet.
1. Introduction
e ketogenic diet is a food regimen which consists of a high
concentration of fat, with moderate/low protein and very
low carbohydrate content. is type of diet triggers high
production of ketone bodies derived from the breakdown of
fat to produce energy [1]. Some studies show that the ke-
togenic diet has therapeutic benefits in a range of illnesses. It
has been recommended as a supplementary therapy for
polycystic ovary syndrome, acne, cancer, and respiratory
distress [2]. It is also beneficial as anticonvulsant therapy to
reduce the frequency of seizures in people with epilepsy
[3, 4]. Ketogenic diet may also help to reduce HbA1C levels
in people with type 2 diabetes, maintaining mood stability
for people with bipolar disorder, and reducing cholesterol
levels in obese patients [5].
A clinical study has demonstrated that a short-term
ketogenic diet for 14 days might increase the concentration
Hindawi
Journal of Nutrition and Metabolism
Volume 2020, Article ID 3642035, 7 pages
https://doi.org/10.1155/2020/3642035
of ketone bodies in the blood, but it also improved the
antioxidant capacity of the blood that contributes to reduced
oxidative stress [6]. Another clinical trial has shown that
consuming ketogenic diet for 20 days significantly reduced
carbon dioxide deposits in the body, which may find clinical
benefit in patients with increased PaCO
2
due to respiratory
failure [2].
Despite its popular use, some concerns arise on how
ketogenic diet will affect the whole-body system. Since ke-
togenic diet replaces glucose with fat as the main source of
energy, the body is forced to activate a series of fat metabolic
processes to acquire energy [7]. Fat metabolic processes
form acetyl coenzyme A (acetyl-CoA) as the main product,
which then enters the citric acid cycle and is oxidized to
produce ATP [8]. Acetyl-CoA that exceeds the availability of
oxaloacetate and/or the activity of the citric acid cycle leads
to an increase in ketone bodies (acetoacetate, β-hydrox-
ybutyrate, and acetone). is process is called ketogenesis
[9]. e ketone bodies formed from ketogenic diets are
acidic; therefore, excessive excretion of these acids through
kidneys may cause a decrease in alkaline reserves or bi-
carbonate ions (HCO
3-
) [10]. As a result, the implication of
ketogenic diet reduced blood pH, leading to ketoacidosis
[11].
Several animal models have been used to learn about the
effect of a high-fat diet on the function of vital organs, such
as the kidneys and liver [12, 13]. High-fat diet is more likely
to trigger a reduction in mitochondrial quinone pool and is
associated with increased mitochondrial reactive oxygen
species (ROS) formation in the rat liver [14]. A high-fat diet
has been shown to induce alteration in renal lipid meta-
bolism in mice, especially the balance between lipogenesis
and lipolysis, leading to the accumulation of lipid in the
kidneys and, consequently, renal dysfunction [15].
To obtain more comprehensive data on how ketogenic
diet may affect the whole-body system, this present study
aimed to investigate the effects of long-term consumption of
ketogenic diet on blood gas profiles, hematological pa-
rameters, organ functions, and antioxidant level in a rat
model.
2. Materials and Methods
2.1. Preparation of Standard and Ketogenic Diet.
Standard food was obtained from a manufacturer as stan-
dard pellets for rodents (AD2®, Indonesia), while the ke-
togenic food was prepared in our laboratory by involving a
nutritionist. e ketogenic pellets contain 30% of nonpure
fat mixed with 70% of goat fat (Table 1), which is formulated
based on NutriSurvey®software to calculate the calorie
intake and the percentage of macro and micronutrients per
gram pellet. All ingredients were liquefied and mixed using a
hand mixer and then frozen for 24 hours with the tem-
perature of 20°C. e solidified material was then pul-
verized and molded into pellets. e standard and ketogenic
pellets were then examined for their fat, protein, and car-
bohydrate contents at the Laboratory of Animal Food
Chemistry, Faculty of Animal Science, Universitas
Hasanuddin.
2.2. Experimental Protocols. Male Wistar rats weighing
200330 g age 34 months (n15) were acclimated for 7 days
in the laboratory before starting the experiment. At this stage, all
rats received standard pellets and water ad libitum. Rats were
cared for according to the standard for laboratory animal care,
and all animal protocols have been approved by the Animal
Ethics Committee of the Faculty of Medicine, Universitas
Hasanuddin. Rats were divided into two groups. e first group
(n8) received a standard diet, while the second group received
the ketogenic diet for 60 days. is 60-day period of adult rat life
is equivalent to 4 years of human life [17]. Each rat was caged
individually and offered 30 g of food per day ad libitum and not
subjected to calorie restriction.e remaining food was weighed
every morning to record the calorie intake of each rat. e blood
samples were withdrawn following 60 days of treatments and
prepared for further analysis.
2.3. Analysis of Blood Gas, Hematological Parameters, Organ
Biomarkers, and Superoxide Dismutase Level. e blood gas
analysis was performed on rat whole blood immediately
following blood sampling with the use of the i-Stat®analyzer
(Abbott®). For hematological analysis, blood samples were
collected using a BD®vacutainer with EDTA, centrifuged
for 20 min with the rate of 3000 rpm before analyzed using a
hematology analyzer (ermo Scientific®). e organ bio-
markers, such as alanine aminotransferase (ALT), aspartate
aminotransferase (AST), creatinine, and urea were measured
using Humalyzer 3500 (Human Global Diagnostic®)
according to the instruction on the reagent kits (Human®).
To measure plasma superoxide dismutase (SOD) level, the
plasma was prepared based on instruction in Rat SOD for
ELISA kit (Abbexa®) and analyzed with the enzyme-linked
immunosorbent assay (ELISA) reader (ermo Scientific®).
2.4. Analysis of Lipid Peroxidation Activity in Liver and Renal
Tissues. At the end of the experiment, rats were anes-
thetized, euthanized, and laparotomy was performed. e
Table 1: Composition of standard and ketogenic diet.
Composition Percentage
Standard diet
a
Water 12
Protein 15
Palm oil 7
Fiber 6
Calcium 7
Phosphor 0.7
Enzyme 0.1
Corns 52.2
Ketogenic diet
b
Water —
Avocado 5.69
Chicken egg yolk 19.45
Roasted peanuts 4.86
Goat fat 70
a
Formula is obtained from the commercial rodent chow label.
b
Formula is
prepared based on ketogenic diet for rats, with the ratio of 8.6 : 1 portion of
fat:(carbohydrate + protein) [16].
2Journal of Nutrition and Metabolism
liver and the kidneys of the rats were removed and im-
mediately immersed in liquid nitrogen. Organs were
weighed 400 mg and homogenized before adding 2mL of
phosphate buffer solution pH 7.4. e mixture is centrifuged
at 3000 rpm for 20 minutes. e supernatant (0.5 mL) was
mixed with 1 mL of 1% thiobarbituric acid and 1 mL of 1%
trichloroacetic acid and heated to 100°C for 20 minutes. e
mixture was then centrifuged at 3000 rpm for 10 minutes to
separate the residue. Organ lipid peroxidation was measured
as malondialdehyde (MDA) level (λ530 nm) using a UV-
VIS spectrophotometer (Agilent®).
2.5. Statistical Analysis. e data obtained were analyzed
using the SPSS IBM 23 software. Data distribution was
examined using Kolmogorov–Smirnov to determine
whether the data were normally distributed or not. e data
that were normally distributed were subsequently analyzed
using an independent t-test, while data that were not nor-
mally distributed were analyzed using the Mann–Whitney U
test. A significant difference was achieved if p<0.05 or very
significant difference if p<0.01. All data were presented in
mean ±SEM.
3. Results
3.1. Long-Term Ketogenic Diet on Rats Causes Significant
Weight Loss, Reduced Blood Glucose, and Increased Blood
Ketone Levels. e food composition of the ketogenic pellet
has far less carbohydrate (5.66% vs 52.20%) and much higher
fat content (86.19% vs 7.00%) compared to the standard diet
(Table 2). e calorie of the standard chow is 5.85 kCal/g,
while that of the ketogenic pellet is 8.29 kCal/g. e average
of daily calorie intake per rat in each week is depicted in
Table 3. It is found that the standard group consumed more
amount of food than the ketogenic group; hence, the calorie
intakes of both groups are quite similar despite the difference
in calories per gram food.
e difference in the diet composition was found to
significantly affect the body weight, blood glucose, and blood
ketone levels in the male rats after 60-day intake. Table 4
shows the impact of ketogenic diet on rat body weight after
60 days. While all rats fed with standard diet gained weight
after 2 months (on average 25% increase from baseline
weight), the ketogenic-fed rats experienced a weight loss by
around 100 g from their baseline body weight (40% loss).
Apart from weight loss, the blood glucose level of ke-
togenic-fed rats was significantly lower compared to the
standard diet group (Figure 1). At this stage, the value of
blood glucose was 57 ±5.69 mg/dl, suggesting a hypogly-
cemic condition of the ketogenic diet group. Meanwhile, the
level of blood ketone markedly elevated in the ketogenic
group, about 8 times higher than the standard rats
(7.97 ±0.15 vs 0.34 ±0.02 mmol/L).
3.2. Long-Term Ketogenic Diet Significantly Lowered Blood pH
and Reduced Base Excess Level. e analysis of blood gas
values demonstrates that the administration of the ketogenic
diet for 60 days causes a significant alteration in blood gas
homeostasis (Table 5). It was found there was a very sig-
nificant decrease in blood pH of rats following 2 months of
having a ketogenic diet compared to those fed with a
standard diet (p<0.01). e decrease in blood pH was not
accompanied by significant changes in carbon dioxide
pressure (pCO
2
), oxygen pressure (pO
2
), total carbon di-
oxide (TCO
2
), and hemoglobin oxygen saturation (SO
2
).
Although the blood bicarbonate (HCO
3) level of the ke-
togenic group insignificantly decreased (19.74 ±2.54 vs
22.75 ±0.79 mmol/L), it was found that the group’s base
excess level was significantly lower compared to the standard
group (p<0.05).
3.3. Long-Term Ketogenic Diet Induces Anemia in Male Rats.
e result of hematological analysis after receiving standard
and ketogenic diets for 60 days is presented in Table 6. e
ketogenic group appears to have slightly lower red blood cell
(RBC) counts, significantly lower hemoglobin, and hemat-
ocrit, as well as significantly smaller mean corpuscular
volume (MCV) and mean corpuscular hemoglobin (MCH)
indices. ese hematological abnormalities indicate that rats
fed with the ketogenic diet were anemic.
3.4. Long-Term Ketogenic Diet Does Not Significantly Alter the
Functions of Liver and Kidney. is study also measured the
effect of a long-term ketogenic diet in rats on liver and renal
functions. e result is presented in Figure 2. From the data,
it is revealed that the levels of liver biomarkers, the alanine
aminotransferase (ALT) and aspartate aminotransferase
(AST), were not significantly different between the standard
and ketogenic groups. However, when comparing the renal
function test, a slight increase in plasma creatinine and urea
levels was found in the ketogenic group compared to
standard, although the difference was not statistically
significant.
3.5. Long-Term Ketogenic Diet Increases Lipid Peroxidation
and Reduces the Antioxidant Level. e level of lipid per-
oxidation and antioxidant activity could be a good indi-
cator to reveal oxidative stress level in the system. In this
study, it was found that the ketogenic diet in rats for 60 days
may induce an increase in malondialdehyde (MDA) level in
the liver and kidney (Figure 3). e increase of MDA level
in both vital organs was very significant in the ketogenic
group compared to standard (p<0.01). e increase of
MDA level in the ketogenic group was accompanied by a
reduced level of antioxidant superoxide dismutase (SOD),
which was 80% lower compared to that of standard
(p<0.01).
Table 2: e comparison of carbohydrate, fat, and protein contents
of standard and ketogenic diets obtained from food analysis.
Type of diet Carbohydrate (%) Fat (%) Protein (%)
Standard 52.20 7.00 15.25
Ketogenic 5.66 86.19 8.15
Journal of Nutrition and Metabolism 3
4. Discussion
e ketogenic diet has gained public attention since it is first
introduced as an alternative therapy for pharmacoresistant
epilepsy [18]. Nowadays, the use of ketogenic diet has ex-
panded beyond epileptic therapy; indeed, its use in healthy
individuals has become more popular, especially to those
who wish to lose weight. Unfortunately, the benefits of
ketogenic diet may come with side effects. is study ex-
amined the long-term effects of ketogenic diet in a healthy
male rat model to obtain more information about the po-
tential complications of this type of diet.
Standard food with its high carbohydrate content allows
the body to use glucose as the main source of energy. When
carbohydrate intake is more than sufficient to meet the needs
of ATP, the body will physiologically convert glucose into
glycogen as energy stores in tissues. Consumption of a diet
rich in carbohydrates will also cause an increase in the
Table 3: e average of daily calorie intake per rat each week in standard and ketogenic diet groups.
Diet e calorie intake (kCal/day)
Week I Week II Week III Week IV Week V Week VI Week VII Week VIII
Standard 83.11 81.24 81.13 82.83 80.62 78.29 76.19 75.57
Ketogenic 88.77 84.78 82.86 83.45 86.70 84.78 88.77 98.24
Table 4: Changes in rat body weight after receiving standard and ketogenic diets for 60 days.
Type of diet NBody weight Mean ±SEM (g) pvalue
Standard 8 Baseline 252 ±20.61 0.001
Posttreatment 319 ±19.35
Ketogenic 7 Baseline 260 ±12.60 0.01
Posttreatment 157 ±06.40
0
20
40
60
80
100
120
140
160
Standard Ketogenic
Blood glucose (mg/dl)
∗∗
(a)
0.00
2.00
4.00
6.00
8.00
10.00
Standard Ketogenic
Blood ketone (mmol/L)
∗∗
(b)
Figure 1: e level of blood glucose and blood ketone of rats consuming standard and ketogenic diet for 60 days. e symbol ∗∗ implies a
very significant difference (p<0.01) between groups.
Table 5: e comparison of blood gas profiles of rats receiving
standard and ketogenic diets for 60 days.
Blood gas NDiet Mean ±SEM pvalue
pH 8 Standard 7.52 ±0.01 0.001
7 Ketogenic 7.36 ±0.02
pCO
2
(mmHg) 8 Standard 27.63 ±1.34 1.00
7 Ketogenic 35.72 ±5.96
pO
2
(mmHg) 8 Standard 107.75 ±2.93 0.32
7 Ketogenic 88.14 ±12.14
HCO
3-
(mmol/l) 8 Standard 22.75 ±0.79 0.48
7 Ketogenic 19.74 ±2.54
Base excess (mmol/l) 8 Standard 1.08 ±0.43 0.04
7 Ketogenic 0.32 ±0.11
TCO
2
(mmol/l) 8 Standard 23.63 ±0.84 0.56
7 Ketogenic 20.86 ±2.77
SO
2
(%) 8 Standard 98.63 ±0.18 0.20
7 Ketogenic 90.29 ±6.18
Table 6: e comparison of hematology profiles of rats receiving
standard and ketogenic diets for 60 days.
Hematology parameters NDiet Mean ±SEM pvalue
RBC (10
6
/μL) 8 Standard 8.04 ±0.24 0.33
7 Ketogenic 7.65 ±0.29
Hemoglobin (g/dl) 8 Standard 13.76 ±0.33 0.02
7 Ketogenic 11.98 ±0.54
Hematocrit (%) 8 Standard 39.90 ±0.97 0.001
7 Ketogenic 32.77 ±1.69
MCV (fL) 8 Standard 49.78 ±1.40 0.001∗∗
7 Ketogenic 42.67 ±0.89
MCH (pg) 8 Standard 17.15 ±0.37 0.01
7 Ketogenic 15.62 ±0.19
4Journal of Nutrition and Metabolism
amount of fat deposited in adipose tissue under the skin or in
the abdominal cavity. is is the main reason for the increase
in body weight of rats fed with a standard diet.
On the other hand, rats treated with the ketogenic diet
had a significant weight loss as a result of induced ketosis.
Ketogenic diet with high fat, low protein, and low carbo-
hydrate composition renders the body depends on the
process of gluconeogenesis, the formation of non-
carbohydrate glucose, to produce energy [19]. When the
fatty acids (fat content) are mainly used to produce energy, it
will induce the formation of ketone bodies, such as ace-
toacetate, beta-hydroxybutyrate, and acetone. e presence
of ketosis in the ketogenic group was confirmed by a sig-
nificantly higher level of blood ketone (8 mmol/L) and a
significantly low blood sugar level (<60 mg/dl). Apart from
weight loss, the rats also experience a decrease in pH or
acidosis, which occurs as a result of increased blood ketone
level [11]. e ketone bodies are acidic; thus, an increase in
ketone bodies in circulation may induce acidosis [11, 20].
Anemia is not uncommon side effects of high-fat diets.
is study also found reduced hematological indices, such as
RBC, hemoglobin, hematocrit, MCV, and MCH in rats fed
with ketogenic diet for 60 days. Studies on epileptic children
have revealed that ketogenic diet is more likely to cause
anemia, which may occur due to dietary restriction, leading
to copper deficiency [21, 22]. However, this complication of
the ketogenic diet can be managed with copper
supplementation.
In this study, the administration of ketogenic diet in rats
for 60 days did not significantly alter liver and kidney
function. Nevertheless, the plasma creatinine and urea of the
ketogenic-fed rats were somewhat higher than standard-fed
rats, which may suggest a minor effect of the ketogenic diet
on renal function. is effect could be more striking if the
duration of the ketogenic diet administration is prolonged.
It is interesting that although the liver and renal function
were not significantly altered, the lipid peroxidation activity
in both organs significantly increased. is was indicated by
a significantly higher MDA level of liver and renal tissues in
ketogenic-fed rats compared to those with a standard diet.
Increased activity of lipid peroxidation could be triggered by
the elevation of reactive oxygen species (ROS) in the organs
and incapability of the antioxidant enzyme activity to protect
cell membranes from ROS-induced damage. is result
could emerge as a potential threat to both organs should the
diet be sustained longer than the period investigated. In line
with this, the plasma concentration of superoxide dismutase
(SOD) significantly reduced in ketogenic-fed animals
(p<0.01), suggesting the presence of oxidative stress in-
duced by long-term ketogenic diet in rats.
0.00
20.00
40.00
60.00
80.00
100.00
120.00
140.00
160.00
Standard Ketogenic
AST (U/L)
(a)
0.00
10.00
20.00
30.00
40.00
50.00
60.00
70.00
80.00
Standard Ketogenic
ALT (U/L)
(b)
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
Standard Ketogenic
Creatinine (mg/dl)
(c)
0.00
10.00
20.00
30.00
40.00
50.00
60.00
Standard Ketogenic
Urea (mg/dl)
(d)
Figure 2: e level of aspartate aminotransferase (a), alanine aminotransferase (b), plasma creatinine (c), and plasma urea (d) in rats
consuming standard and ketogenic diet for 60 days.
Journal of Nutrition and Metabolism 5
e reason why a ketogenic diet may induce oxidative
stress has been explained in several studies. Ketone bodies
are known to stimulate the mitochondria to produce more
ATP compared to glucose [23–25]. However, fat metabolism
requires more complex processes, such as reduction, oxi-
dation, hydroxylation, and conjugation, which may elevate
the production of reactive oxygen species (ROS) in the liver
cells [26, 27]. If the release of ROS is in balance with the
body’s antioxidant activities, the occurrence of oxidative
stress can be prevented. In contrast, if ROS formation has
exceeded antioxidant levels, the free radicals will attack
macromolecules, such as, proteins, polysaccharides, DNA,
and cell membranes that contain polyunsaturated fatty acids,
leading to cellular damage [28]. is study shows an increase
in liver and renal MDA levels, which is accompanied by a
decrease in plasma SOD after 60-day consumption of ke-
togenic diet. is might implicate a precaution on the long-
term use of the ketogenic diet.
5. Conclusions
Despite the weight loss, low blood sugar, and high blood
ketone, sustainable consumption of keto diet for 60 days in
rats also instigated some concerning effects such as meta-
bolic acidosis, anemia, and decreasing plasma antioxidant
enzyme level. It is interesting that albeit a significant increase
in lipid peroxidation activity on the liver and kidney, both
organ functions were remained intact, at least during the
period investigated.
Data Availability
e data used to support the findings of this study are
available from the corresponding author upon request.
Conflicts of Interest
e authors declare no conflicts of interest.
Acknowledgments
is publication was made possible by a block grant from the
Faculty of Medicine, Hasanuddin University, Indonesia.
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34.00
35.00
36.00
37.00
38.00
39.00
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41.00
Standard Ketogenic
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∗∗
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Standard Ketogenic
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6Journal of Nutrition and Metabolism
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... These results thus obtained by Omozee EB et al (2018) 22 were in concordance with the observations made in our study. Arsyad A et al (2020) 23 divided fifteen male Wistar rats into control (n=8) and Ketogenic (n=7) groups. Controls received standard diet containing 52.20% carbohydrates, 7.00% fat and 15.25% protein; meanwhile, the Ketogenic group received a high fat low carbohydrate diet which contained 5.66% of carbohydrates, 86.19% and 8.15% protein. ...
... Observations thus made showed that the rats subjected to Ketogenic diet experienced a marked decrease in body weight, diet. With regards to the body weight, the results obtained by Arsyad A et al (2020) 23 during their study conducted for a period of sixty days were similar to the results obtained during our study conducted for 24 weeks. ...
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Background: At least 2.8 million adults die from Obesity related causes every year and 65% of the world's population lives in the countries where Obesity causes more deaths than underweight. The rat liver is the most cranial structure on the right side of the abdominal cavity, in the intrathoracic portion, coming in intimate contact with the diaphragm. The liver of the rat is a multilobulated organ. The mass of the rat liver accounts for about 6% of the total body weight. Objectives: To observe the effects of ketogenic diet on body weight and histology of liver of male albino rats. Methods: Twenty four Albino rats weighing on an average 200-300 grams were taken from animal house of Government. Medical College Srinagar for the present study. The animals were divided into two groups after randomization. Group A-served as control. Group B-were fed on isocaloric Ketogenic diet (consisting of 65% calories from fat, 30% from protein, 6% from carbohydrates). The microscopic observations were recorded group wise using light microscope. Appropriate photographs were taken by using a photographic microscope and labelled. Results: The groups were designated as Group A and Group B consisting of six and eighteen rats respectively. Group A animals were fed with normal diet containing rat chow (black gram and pellet) and water and Group B animals were fed with isocaloric Ketogenic diet. Control group consisting of 6 animals were fed with normal diet consisting of pellet and gram. The animals in this group were fed with isocaloric Ketogenic diet consisting of 65% caloric intake from fat, 30% from protein, 6% from carbohydrates. Conclusion: Despite the beneficial role of Ketogenic diet in the weight reduction, Ketogenic diet has deleterious effects on Liver of Albino rats. Its use for weight reduction should be restricted to subjects with normal Liver parameters.
... However, long-term ketogenic dieting has been linked to higher concentrations of LDL cholesterol and a 2-fold higher risk of adverse cardiac events [26]. Healthy rodents on a ketogenic diet chow showed induced senescence, metabolic acidosis, and increased oxidative stress in normal tissues [27,28]. Additionally, MRI spectroscopic markers collected on a cohort of rats on long-term ketogenic diets showed structural and functional changes [29]. ...
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Purpose: Ketone bodies could be useful biomarkers in multiple sclerosis (MS) because the pathophysiological processes underlying MS disease progression induce metabolic stress. The purpose was to assess the relationships of ketone bodies with biomarkers of metabolic, inflammatory, and oxidative stress in MS. Methods: Blood samples and neurological assessments were obtained from 153 healthy controls (HC), 187 relapsing-remitting (RRMS), and 91 progressive MS (PMS) patients. AcAc, BHB, and acetone were measured using proton nuclear magnetic resonance spectroscopy. Indices of inflammatory vulnerability (IVX), metabolic malnutrition (MMX), and metabolic vulnerability (MVX) were computed from the NMR profiles. Cholesterol, apolipoprotein, lipid peroxidation, and antioxidant profiles were obtained. Regression analysis adjusted for age, sex, body mass index, and HC, RRMS, or PMS disease status. Results: AcAc and BHB levels were greater in MS compared to HC. BHB and ketone bodies were positively associated with disability on the MS Severity Scale and ambulation time. BHB was positively associated with IVX, MMX, and MVX. AcAc was positively associated with MMX and negatively associated with IVX and MVX. Total ketone body concentration was positively associated with MMX and MVX. BHB and AcAc levels were negatively associated with the amino acids alanine, valine, and leucine. Conclusions: Ketone bodies are associated with inflammatory vulnerability, metabolic vulnerability, and ambulatory disability measures in MS.
... While our data do not identify the specific binding target of BHB responsible for this anti-inflammatory effect, they do show that an excess of a small anion (BHB anion or chloride anion) and a small pH change (or sufficient anion excess to be reflected in pH) both appear to be required. Physiologically, the endogenous production of ketones induces a metabolic acidosis that is well compensated in blood under normal conditions 86 . However, there may be meaningful changes in pH in specific compartments: KD induces intracerebral acidosis (from pH 7.2 to 6.9), which has anticonvulsant effects in a rat model of infantile spasms 87 , and the acid form of BHB inhibits the growth of Bifidobacterium in vitro by a pH-dependent mechanism 16 . ...
... While feeding an HFD increased liver enzyme activity in KC mice, there were no changes in liver enzymes nor in markers of kidney function with the KD. Consistent with our findings, liver and kidney function tests remained within the normal range in rats fed a KD for 2 months [42]. ...
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Background: High-fat diets (HFDs) have been associated with an increased risk of pancreatic cancer. In contrast, ketogenic diets (KDs) have been shown to display anti-tumor characteristics. The objective of this work was to evaluate the efficacy of a KD on late-stage pancreatic carcinogenesis in a genetically modified mouse model of pancreatic cancer [LSL-KrasG12D/+; Ptf1-Cre (KC) mice], as well as its liver safety, and to compare it to that of an HFD. Methods: Six-month-old female and male KC mice were randomly allocated to either a control diet (CD) (%kcal: 20% fat, 15% protein, 65% carbohydrates), an HFD (%kcal: 40% fat, 15% protein, 45% carbohydrate) or a KD (%kcal: 84% fat, 15% protein, 1% carbohydrate) and fed these diets for 6 months. Results: HFD-fed, but not KD-fed, mice showed a 15% increase in body weight, plus elevated serum insulin (2.4-fold increase) and leptin (2.9-fold increase) levels, compared to CD-fed mice. At the pancreas level, no differences in pancreatic cancer incidence rates were observed among the diet groups. Regarding the liver safety profile, the HFD-fed mice had higher serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), when compared to the CD and KD groups. In addition, upon histologic examination, an HFD, but not a KD, showed a ~2-fold increase in both macro- and microsteatosis, as well as 35% and 32% higher levels of TLR4 and NF-κB activation, respectively, compared to CD-fed mice. Conclusions: In summary, although a KD intervention alone did not prevent pancreatic carcinogenesis, our data suggests that a KD modulates insulin signaling and hepatic lipid metabolism, highlighting its beneficial effects on healthspan and liver function when compared to an HFD.
... A sudden increase in carbohydrate consumption may also lead to a reduction in ketosis 'benefits [56,57]. It is unclear how diet affects growth and development, cardiovascular and bone health over the long term [58]. Few data are available about the potential impact on growth in the pediatric age group. ...
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Background There are conflicting findings regarding the effect of low-carbohydrate diets on obesity-related factors. This study aimed to investigate the effect of a carbohydrate-restricted (CR) diet on changes in anthropometric indicators of adiposity and fat distribution in pediatrics populations. Methods A systematic search was conducted in PubMed/MEDLINE, Web of Science, Scopus, and Embase electronic databases using predefined keywords to identify all randomized controlled trials examining the effects of CR on obesity-related factors. The pooled weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated using a random-effects model. Results Findings from 11 studies demonstrated significant reductions in weight (WMD: -2.31 kg; 95% CI: -4.44, -0.18), BMI (WMD:-1.08 kg/m²; 95% CI: -1.91, -0.26), and fat mass (WMD: -1.43%; 95% CI: -2.43 to -0.43) as well as a significant increase in adiponectin levels (WMD: 0.74 ng/ml; 95% CI: 0.02, 1.47) in the CR diet group compared to the control group. However, no significant effect was observed on BMI z-score (WMD:-0.10; 95% CI: -0.21, 0.01), waist circumference (WMD:-3.03 cm; 95% CI: -6.57, 0.51) or leptin levels (WMD: -0.82 ng/ml; 95% CI: -2.26, 0.61). Stratified analysis rrevealed a greater effect of CR on weight and BMI reduction in interventions ≤ 12 weeks and in very low-carbohydrate diets. Conclusions In conclusion, it appears that CR diet, along with other lifestyle factors, can lead to significant improvements in weight loss on pediatrics with obesity/overweight.
... In both the KD and control groups, a low blood glycemic level was observed, whereas the KD group returned to normal glycemic conditions. By contrast, a decrease in body weight was observed in KD-fed rats due to the induction of ketosis [6]. Analysis of the percentage of body weight loss indicated that more than 10% of the initial body weight was lost by Table 1. ...
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The ketogenic diet (KD) is characterized by minimal carbohydrate, moderate protein, and high fat intake, leading to ketosis. It is recognized for its efficiency in weight loss, metabolic health improvement, and various therapeutic interventions. The KD enhances glucose and lipid metabolism, reducing triglycerides and total cholesterol while increasing high-density lipoprotein levels and alleviating dyslipidemia. It significantly influences adipose tissue hormones, key contributors to systemic metabolism. Brown adipose tissue, essential for thermogenesis and lipid combustion, encounters modified UCP1 levels due to dietary factors, including the KD. UCP1 generates heat by uncoupling electron transport during ATP synthesis. Browning of the white adipose tissue elevates UCP1 levels in both white and brown adipose tissues, a phenomenon encouraged by the KD. Ketone oxidation depletes intermediates in the Krebs cycle, requiring anaplerotic substances, including glucose, glycogen, or amino acids, for metabolic efficiency. Methylation is essential in adipogenesis and the body’s dietary responses, with DNA methylation of several genes linked to weight loss and ketosis. The KD stimulates FGF21, influencing metabolic stability via the UCP1 pathways. The KD induces a reduction in muscle mass, potentially involving anti-lipolytic effects and attenuating proteolysis in skeletal muscles. Additionally, the KD contributes to neuroprotection, possesses anti-inflammatory properties, and alters epigenetics. This review encapsulates the metabolic effects and signaling induced by the KD in adipose tissue and major metabolic organs.
... Effect of dietary phase change from common starter to the common grower diet on plasma sodium and chloride concentrations in growing broiler chickens. of which is CO 2 . The authors are unaware of any published work in poultry demonstrating an association between dietary digestible carbohydrate intake and blood gases but Alessandro et al. (2015) and Arsyad et al. (2020) observed higher blood TCO 2 in humans and rats, respectively, when a diet with a high digestible carbohydrate concentration was contrasted with one with a low carbohydrate load. Thus, transitioning birds from starter to grower, and presumably also from grower to finisher, diets, may be expected to generate both shortterm and longer-term changes in blood metabolite composition, including shifts in osmotic equilibrium, HCO 3 and blood gases. ...
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A total of 720 male Cobb 500 broiler chicks were used in a 5 treatment and 8 replicate experiment to explore dynamic changes in blood metabolites in response to short-term nutrient depletion and repletion. Day old chicks were offered a corn and soybean meal-based common starter diet from d1 to 14 that was formulated to meet all nutrient requirements of the birds. From d15 to 17, the experimental diets were offered, before returning all groups to a common diet from d18 to 20, at which point the experiment was terminated. A total of 5 experimental diets were designed. A standard grower diet served as a control and was offered to 1 of the 5 groups of chicks. The additional 4 experimental groups comprised diets that were low in digestible phosphorus (P), total calcium (Ca), crude protein and digestible amino acids (AA) or apparent metabolizable energy (AME). The common grower diet that was offered from d18-20 was designed to be nutritionally complete and was intended to explore dynamic response to nutrient repletion. Blood was drawn from 8 chicks per treatment at time 0 (immediately prior to introduction of the experimental diets) and then again 3, 6, 12, 24, and 48h after introduction of the nutrient depleted diets. Additionally, blood was drawn 3, 6, 12, 24, and 48h after the introduction of the nutritionally complete common grower diet. Chicks were not sampled more than once. Feed intake, body weight and feed conversion ratio (FCR) were assessed on d14, 17, and 20. Blood metabolites were analyzed using the iSTAT Alinity V handheld blood analyzer, the Vetscan VS2 Chemistry Analyzer and the iCheck Carotene Photometer. Live performance metrics were not affected by the short-term nutrient depletion and all chicks grew normally throughout the experiment. The diet with low digestible P generated a rapid temporary decrease in plasma P and an increase in plasma Ca, that were returned to baseline following the re-introduction of the common grower feed. Introduction of the diet with low total Ca resulted in a significant increase in plasma P, effects which were also mitigated during the nutrient repletion phase. Total plasma protein, albumin and uric acid (UA) were decreased, and plasma glucose increased, in the chicks that received the diet with low crude protein and digestible AA. There was a delayed increase in aspartate amino transaminase (AST) associated with the diets with low digestible P and low AME. These results demonstrate the capacity of blood biochemistry to adapt to quantitative and qualitative changes in nutrient intake. Point-of-care analysis of blood biomarkers offers nutritionists a valuable opportunity to calibrate nutritional matrices for common dietary ingredients, zootechnical feed additives and to optimize diet phase changes. It can be concluded that many blood biomarkers are plastic to changes in diet nutrient density and offer an objective index for optimization of nutritional programs for commercial broiler production.
... In fact, initial administration of KD produces mild oxidative stress, and following 3 weeks of KD administration the oxidative stress was reduced by activating Nrf2 signaling pathway (Milder et al., 2010 Oct 1). Conversely, Arsyad et al., (Arsyad et al., 2020 Jun 29) revealed that long-term (2 months) administration of KD for rats led to anemia, metabolic acidosis, and oxidative stress by reducing the levels of antioxidant enzymes. However, a recent analysis revealed that KD prevents the development of oxidative stress (Alhamzah et al., 2023 Feb 17). ...
... The main problem (excess of 2C supply with respect to energy needs) remains, and is simply 'exported' to peripheral tissues, often not fully designed to use them as main energy substrates. In addition, ketone bodies induce metabolic irritation, causing acidosis [601] and, eventually, serious bidirectional alterations in the control of insulin and glycaemia [602][603][604]. Dietary protein may in part limit these problems by providing hydrocarbon skeletons that partly compensate (see below) the problems elicited by lipid-laden ketogenic diets. ...
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This review focuses on the question of metabolic syndrome (MS) being a complex, but essentially monophyletic, galaxy of associated diseases/disorders, or just a syndrome of related but rather independent pathologies. The human nature of MS (its exceptionality in Nature and its close interdependence with human action and evolution) is presented and discussed. The text also describes the close interdependence of its components, with special emphasis on the description of their interrelations (including their syndromic development and recruitment), as well as their consequences upon energy handling and partition. The main theories on MS’s origin and development are presented in relation to hepatic steatosis, type 2 diabetes, and obesity, but encompass most of the MS components described so far. The differential effects of sex and its biological consequences are considered under the light of human social needs and evolution, which are also directly related to MS epidemiology, severity, and relations with senescence. The triggering and maintenance factors of MS are discussed, with especial emphasis on inflammation, a complex process affecting different levels of organization and which is a critical element for MS development. Inflammation is also related to the operation of connective tissue (including the adipose organ) and the widely studied and acknowledged influence of diet. The role of diet composition, including the transcendence of the anaplerotic maintenance of the Krebs cycle from dietary amino acid supply (and its timing), is developed in the context of testosterone and β-estradiol control of the insulin-glycaemia hepatic core system of carbohydrate-triacylglycerol energy handling. The high probability of MS acting as a unique complex biological control system (essentially monophyletic) is presented, together with additional perspectives/considerations on the treatment of this ‘very’ human disease.
... Arsyad et al. (2020) [27] used a KD on rats for 60 days and observed weight loss and low blood sugar but also high metabolic acidosis and anemia and decreased plasma antioxidant enzyme levels. Therefore, interpreting the facts of the harmful effect may occur due to acidosis as a side effect of this diet type, which could affect salivary gland cells. ...
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Objective This study was carried out in the submandibular salivary glands (SSGs) of rats to demonstrate the effect of a ketogenic diet (KD) in comparison with dietary chitosan supplementation. Method Eighteen albino rats were randomly divided into three equal groups of six animals each. Rats in Group I were fed a balanced diet and considered controls. Meanwhile, those of Groups II and III were fed a KD, a balanced diet with high molecular weight chitosan, respectively. After 45 days, rats were euthanized, and the SSGs were dissected carefully for staining with hematoxylin and eosin (H&E), alpha-smooth muscle actin (α-SMA) immunohistochemical staining, and Congo red special stain. Quantitative data from α-SMA staining and Congo red staining were statistically analyzed using one-way ANOVA followed by Tukey’s multiple comparisons post hoc test. Results Regarding Congo red and α-SMA staining, one-way ANOVA revealed a significant difference between the three groups. For α-SMA staining and Congo red staining, Group II had the highest mean values of 91.41 ± 3.30 and 68.10 ± 5.04, respectively, while Group I had the lowest values of 56.13 ± 3.96 and 16.87 ± 2.19, respectively. Group III had mean values of 60.70 ± 3.55 for α-SMA and 19.50 ± 1.78 for Congo red. Tukey’s multiple comparisons post hoc test revealed significant differences between groups I & II and between groups II & III (P < 0.05). Meanwhile, there was a nonsignificant difference between groups I and III (P > 0.05). Conclusion A KD has a deleterious effect on rats’ SSG whatever the test we used, and dietary chitosan supplementation ameliorates these damaging effects.
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Current fueling tactics for endurance exercise encourage athletes to ingest a high carbohydrate diet. However, athletes are not generally encouraged to use fat, the largest energy reserve in the human body. A low carbohydrate, high fat ketogenic diet (KD) is a nutritional approach ensuring that the body utilizes lipids. Although KD has been associated with weight-loss, enhanced fat utilization in muscle and other beneficial effects, there is currently no clear proof whether it could lead to performance advantage. To evaluate the effects of KD on endurance exercise capacity, we studied the performance of mice subjected to a running model after consuming KD for eight weeks. Weight dropped dramatically in KD-feeding mice, even though they ate more calories. KD-feeding mice showed enhanced running time without aggravated muscle injury. Blood biochemistry and correlation analysis indicated the potential mechanism is likely to be a keto-adaptation enhanced capacity to transport and metabolize fat. KD also showed a potential preventive effect on organ injury caused by acute exercise, although KD failed to exert protection from muscle injury. Ultimately, KD may contribute to prolonged exercise capacity.
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The treatment of obesity and cardiovascular diseases is one of the most difficult and important challenges nowadays. Weight loss is frequently offered as a therapy and is aimed at improving some of the components of the metabolic syndrome. Among various diets, ketogenic diets, which are very low in carbohydrates and usually high in fats and/or proteins, have gained in popularity. Results regarding the impact of such diets on cardiovascular risk factors are controversial, both in animals and humans, but some improvements notably in obesity and type 2 diabetes have been described. Unfortunately, these effects seem to be limited in time. Moreover, these diets are not totally safe and can be associated with some adverse events. Notably, in rodents, development of nonalcoholic fatty liver disease (NAFLD) and insulin resistance have been described. The aim of this review is to discuss the role of ketogenic diets on different cardiovascular risk factors in both animals and humans based on available evidence.
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Ketone body metabolism is a central node in physiological homeostasis. In this review, we discuss how ketones serve discrete fine-tuning metabolic roles that optimize organ and organism performance in varying nutrient states and protect from inflammation and injury in multiple organ systems. Traditionally viewed as metabolic substrates enlisted only in carbohydrate restriction, observations underscore the importance of ketone bodies as vital metabolic and signaling mediators when carbohydrates are abundant. Complementing a repertoire of known therapeutic options for diseases of the nervous system, prospective roles for ketone bodies in cancer have arisen, as have intriguing protective roles in heart and liver, opening therapeutic options in obesity-related and cardiovascular disease. Controversies in ketone metabolism and signaling are discussed to reconcile classical dogma with contemporary observations.
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Although a ketogenic diet (KD) is used to treat various metabolic diseases, the organ-specific metabolic changes that occur in response to a KD remain unclear. Therefore, we tested the hypothesis that duration of KD consumption and regular exercise in addition to KD consumption affect metabolic fuel selection at gene levels in heart and skeletal muscle. Six-week-old male C57BL/6J mice were divided into 2 groups, one fed a standard diet and the other fed a KD, and maintained for either 4 weeks (short term) or 12 weeks (long term). The long-term group was further divided into 2 subgroups, and mice in 1 of the 2 groups had an exercise load 5 days a week. Body weight decreased significantly in the KD groups during the first few weeks only. Plasma ketone levels rose and muscle glycogen levels declined significantly in the KD groups, but these changes were less severe in the KD plus exercise group. KD consumption decreased the expression of genes related to glucose utilization in heart and skeletal muscle; however, this decrease did not occur with KD consumption plus exercise. Long-term but not short-term KD consumption increased the expression of genes related to lipid utilization, regardless of exercise. In the KD groups, the expression of genes related to ketolysis was suppressed, and that of genes related to ketogenesis was increased. These results indicate that KD exposure and pairing a KD with exercise have differential impacts on energy substrate selection at gene expression levels in energy-consuming organs, the heart and skeletal muscle.
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Copper deficiency is an uncommon cause of hematologic abnormalities in children that is often overlooked or misdiagnosed. Although cases have been reported because of malabsorption syndromes or after gastrointestinal surgeries, we report a case of copper deficiency-associated anemia and neutropenia in a child because of dietary restrictions, specifically, transitioning from a formula-based ketogenic diet to a pureed food-based ketogenic diet. On copper supplementation, the patient's anemia and neutropenia resolved. To our knowledge, this report is the first revealing copper deficiency anemia and neutropenia developing because of a ketogenic diet.
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Diets that increase production of ketone bodies to provide alternative fuel for the brain are evolving from the classic ketogenic diet for epilepsy devised nearly a century ago. The classic ketogenic diet and its more recent variants all appear to have similar efficacy with approximately 50% of users showing a greater than 50% seizure reduction. They all require significant medical and dietetic support, and there are tolerability issues. A review suggests that low-grade chronic metabolic acidosis associated with ketosis is likely to be an important contributor to the short term and long term adverse effects of ketogenic diets. Recent studies, particularly with the characterization of the acid sensing ion channels, suggest that chronic metabolic acidosis may increase the propensity for seizures. It is also known that low-grade chronic metabolic acidosis has a broad range of negative health effects and an increased risk of early mortality in the general population. The modified ketogenic dietary treatment we propose is formulated to limit acidosis by measures that include monitoring protein intake and maximizing consumption of alkaline mineral-rich, low carbohydrate green vegetables. We hypothesize that this acidosis-sparing ketogenic diet is expected to be associated with less adverse effects and improved efficacy. A case history of life-long intractable epilepsy shows this diet to be a successful long-term strategy but, clearly, clinical studies are needed.
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Guide to the use of the dictionary Dictionary terms Appendices: Food and nutrition board, National Academy of Sciences - National Research Council Recommended Dietary Allowances, revised 1989 Estimated safe and adequate daily dietary intakes of selected vitamins and minerals recommended dietary standards for adults in selected countries and FAO/WHO The food guide pyramid (USA) Nutrition labelling (USA) US daily values for nutrition labelling Dietary guidelines for all healthy americans over two years old National nutrition objectives for the year 2000 Classification of carbohydrates Classification of proteins Summary of digestive enzymes Summary of selected hormones Utilization of proteins Utilization of fats Interrelationship of carbohydrate, protein, and fat Summary of vitamins Summary of minerals Median weights and heights for children from birth to 18 years Average weights for men and women aged 18-74 years Acceptable weights for men and women 1983 metropolitain height-weight tables Estimation of frame size and stature Reference values for triceps skinfold thickness Reference values for midarm muscle circumference Estimation of energy and protein requirements Interpretations and equations for assessing nutritional status Physical assessment of nutritional status Biochemical assessment of nutritional status Reference values for blood lipids Expected 24-hour urinary creatinine excretion Reference values for normal blood constituents Normal reference values for urine Dietary fibre in selected foods Alcohol and caloric content of alcoholic beverages Cholesterol and fatty acid content of selected foods (per 100g of edible portion) Average caffeine content of selected food (mg0 Salt, salt substitutes, and seasonings: sodium and potassium contents Composition of milk and selected formulas for infant feeding Composition of oral and intravenous electrolyte solutions Proprietary formulas for enteral nutrition Selected amino acid solutions for parenteral nutrition Intravenous fat emulsions Suggested intravenous multivitamin formulation Caloric values and osmolarities of intravenous dextrose solutions Nutrition therapy in inborn errors of metabolism Common prefixes, suffixes, and symbols Common abbreviations in nutrition and the medical records Cultural food practices Religious food practices Public health nutrition programs and surveys (USA) Agencies and organizations with nutrition-related activities Sources of nutrition information.
Article
Background: The carbohydrate-insulin model of obesity posits that habitual consumption of a high-carbohydrate diet sequesters fat within adipose tissue because of hyperinsulinemia and results in adaptive suppression of energy expenditure (EE). Therefore, isocaloric exchange of dietary carbohydrate for fat is predicted to result in increased EE, increased fat oxidation, and loss of body fat. In contrast, a more conventional view that "a calorie is a calorie" predicts that isocaloric variations in dietary carbohydrate and fat will have no physiologically important effects on EE or body fat. Objective: We investigated whether an isocaloric low-carbohydrate ketogenic diet (KD) is associated with changes in EE, respiratory quotient (RQ), and body composition. Design: Seventeen overweight or obese men were admitted to metabolic wards, where they consumed a high-carbohydrate baseline diet (BD) for 4 wk followed by 4 wk of an isocaloric KD with clamped protein. Subjects spent 2 consecutive days each week residing in metabolic chambers to measure changes in EE (EEchamber), sleeping EE (SEE), and RQ. Body composition changes were measured by dual-energy X-ray absorptiometry. Average EE during the final 2 wk of the BD and KD periods was measured by doubly labeled water (EEDLW). Results: Subjects lost weight and body fat throughout the study corresponding to an overall negative energy balance of ∼300 kcal/d. Compared with BD, the KD coincided with increased EEchamber (57 ± 13 kcal/d, P = 0.0004) and SEE (89 ± 14 kcal/d, P < 0.0001) and decreased RQ (-0.111 ± 0.003, P < 0.0001). EEDLW increased by 151 ± 63 kcal/d (P = 0.03). Body fat loss slowed during the KD and coincided with increased protein utilization and loss of fat-free mass. Conclusion: The isocaloric KD was not accompanied by increased body fat loss but was associated with relatively small increases in EE that were near the limits of detection with the use of state-of-the-art technology. This trial was registered at clinicaltrials.gov as NCT01967563.
Article
We investigated the effects different diets on adipose tissue, liver and serum morphology and biomarkers in rats that voluntarily exercised. Male Sprague-Dawley rats (~9-10 weeks of age) exercised with resistance-loaded voluntary running wheels (EX; wheels loaded with 20-60% body mass) or remained sedentary (SED) over 6 weeks. EX and SED rats were provided isocaloric amounts of either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), a Western diet (WD; 15.2%-42.7-42.0%), or standard chow (SC; 24.0%-58.0%-18.0%); n=8-10 in each diet for SED and EX rats. Following the intervention, body mass and feed efficiency was lowest in KD rats independent of exercise (p<0.05). Absolute and relative (body mass-adjusted) omental adipose tissue (OMAT) masses were greatest in WD rats (p<0.05) and OMAT adipocyte diameters were lowest in KD-fed rats (p<0.05). None of the assayed OMAT or subcutaneous (SQ) protein markers were affected by the diets [total acetyl coA carboxylase (ACC), CD36 and CEBPα or phosphorylated NF-κB/p65, AMPKα and hormone-sensitive lipase (HSL)], although EX unexpectedly altered some OMAT markers (i.e., higher ACC and phosphorylated NF-κB/p65, and lower phosphorylated AMPKα and phosphorylated HSL). Liver triglycerides were greatest in WD rats (p<0.05) and liver phosphorylated NF-κB/p65 was lowest in KD rats (p<0.05). Serum insulin, glucose, triglycerides and total cholesterol were greater in WD and/or SC rats compared to KD rats (p<0.05), and serum β-hydroxybutyrate was greater in KD versus SC rats (p<0.05). In conclusion, KD rats presented a healthier metabolic profile, albeit the employed exercise protocol minimally impacts any potentiating effects that KD has on fat loss.