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Effects of Twenty Days of the Ketogenic Diet on Metabolic and Respiratory Parameters in Healthy Subjects

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Purpose: The effects of the ketogenic diet (KD) on weight loss, metabolic, and respiratory parameters were investigated in healthy subjects. Methods: Thirty-two healthy subjects were randomized into two groups. The KD group followed a ketogenic diet for 20 days (KD t 0-t 20), then switched to a low-carbohydrate, no-ketogenic diet for 20 days (KD t 20-t 40), and finally was on a Mediterranean diet (MD) for 2 more months (KD t 40-t 2m). The MD group followed a MD for 20 days (MD t 0-t 20), then followed a MD of 1400 kcal over the next 20 days (MD t 20-t 40), and completed the study with the MD for 2 months (MD t 40-t 2m). Body weight, body fat, respiratory rate, and respiratory gas parameters (including respiratory exchange ratio (RER) and carbon dioxide end-tidal partial pressure (PETCO2), oxygen uptake (VO2), carbon dioxide production (VCO2), and resting energy expenditure (REE)) were measured at each point. Results: A significant decrease (p < 0.05) in RER was observed after 20 and 40 days in the KD group, but not in the MD group. In the KD group, significant reductions were observed for both carbon dioxide output and PETCO2, however, there was no significant change in VO2, VCO2, and REE. While both diets significantly decreased body fat mass, the KD diet overall proved to have a higher percentage of fat loss versus the MD diet. Conclusion: The KD may significantly decrease carbon dioxide body stores, which may theoretically be beneficial for patients with increased carbon dioxide arterial partial pressure due to respiratory insufficiency or failure.
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Effects of Twenty Days of the Ketogenic Diet on Metabolic
and Respiratory Parameters in Healthy Subjects
Rubini Alessandro
1
Bosco Gerardo
1
Lodi Alessandra
1
Cenci Lorenzo
1
Parmagnani Andrea
1
Grimaldi Keith
2
Zhongjin Yang
3
Paoli Antonio
1
Received: 30 June 2015 / Accepted: 21 September 2015
Springer Science+Business Media New York 2015
Abstract
Purpose The effects of the ketogenic diet (KD) on weight
loss, metabolic, and respiratory parameters were investi-
gated in healthy subjects.
Methods Thirty-two healthy subjects were randomized
into two groups. The KD group followed a ketogenic diet
for 20 days (KD t
0
t
20
), then switched to a low-carbohy-
drate, no-ketogenic diet for 20 days (KD t
20
t
40
), and
finally was on a Mediterranean diet (MD) for 2 more
months (KD t
40
t
2m
). The MD group followed a MD for
20 days (MD t
0
t
20
), then followed a MD of 1400 kcal
over the next 20 days (MD t
20
t
40
), and completed the
study with the MD for 2 months (MD t
40
t
2m
). Body
weight, body fat, respiratory rate, and respiratory gas
parameters (including respiratory exchange ratio (RER)
and carbon dioxide end-tidal partial pressure (PETCO
2
),
oxygen uptake (VO
2
), carbon dioxide production (VCO
2
),
and resting energy expenditure (REE)) were measured at
each point.
Results A significant decrease (p\0.05) in RER was
observed after 20 and 40 days in the KD group, but not in
the MD group. In the KD group, significant reductions
were observed for both carbon dioxide output and
PETCO
2
, however, there was no significant change in VO
2
,
VCO
2
, and REE. While both diets significantly decreased
body fat mass, the KD diet overall proved to have a higher
percentage of fat loss versus the MD diet.
Conclusion The KD may significantly decrease carbon
dioxide body stores, which may theoretically be beneficial
for patients with increased carbon dioxide arterial partial
pressure due to respiratory insufficiency or failure.
Keywords Ketogenic diet Respiration parameters
Metabolism Resting energy expenditure
Introduction
The ketogenic diet, which is of a high-fat, adequate-pro-
tein, low-carbohydrate content, is originally designed to
treat refractory epilepsy in children. Though underlying
mechanisms are not fully understood, systemic acidosis,
electrolyte changes, and hypoglycemia induced by the
ketogenic diet have all been suggested to be responsible for
its therapeutic effects [1]. Recent studies have suggested
that the ketogenic diet may be used as an adjunc-
tive therapy in many other pathological conditions such as
diabetes mellitus, polycystic ovary syndrome, acne, neu-
rological diseases, cancer, and the amelioration of respi-
ratory and cardiovascular disease risk factors [2,3].
Moreover, very low-carbohydrate ketogenic diets are more
effective for body weight reduction and fat loss compared
to balanced or low-calorie Mediterranean diets, at least in
the short-medium term [4,5]. Despite the widespread use
of the ketogenic diet, its effect on respiratory parameters is
still not well investigated. One of the metabolic effects of
the ketogenic diet is the higher than usual oxidation of fats,
which reduces the respiratory exchange ratio (RER) values
[6,7]. Measured RER can be used to estimate the respi-
ratory quotient (RQ), an indicator of which fuel
&Zhongjin Yang
Yangz@upstate.edu
1
Department of Biomedical Sciences, University of Padova,
35131 Padua, Italy
2
Biomedical Engineering Laboratory, University of Athene,
15773 Athens, Greece
3
The Institute for Human Performance, SUNY Upstate
Medical University, Syracuse, NY 13210, USA
123
Lung
DOI 10.1007/s00408-015-9806-7
(carbohydrate or fat) is being metabolized to supply the
body with energy. Metabolic carbon dioxide output
(VCO
2
) can be calculated as the product of alveolar ven-
tilation times alveolar fractionalcarbon dioxide content. A
recent study suggests that administering the ketogenic diet
for 6 months in patients with medically refractory epilepsy
increased fat oxidation, and decreased RER and the RQ,
without appreciable changes in resting energy expenditure
(REE) [7]. Theoretically, the ketogenic diet decreases RER
and metabolic carbon dioxide production, therefore, may
lead to a decreased arterial carbon dioxide partial pressure
(PETCO
2
) and decreased pulmonary ventilation. These
effects may be useful as an adjunctive therapy in managing
patients with respiratory failure. However, this respiratory
aspect of the ketogenic diet has not been previously
investigated. In the present report, we studied the effect of
the ketogenic diet on metabolic and respiratory parameters,
including RER, PETCO
2
, and pulmonary ventilation in
healthy subjects, during and after the ketogenic diet period,
and we compared these effects with the results obtained
during and after a Mediterranean diet protocol. The effects
of the ketogenic diet and Mediterranean diet protocol on
body weight and fat mass (FM) have also been
investigated.
Materials and Methods
Subjects
Participants were recruited via advertisement placed in two
pharmacies located in the province of Vicenza (Veneto,
Italy). Primary eligibility criteria included being
18–65 years old, BMI 25 to 30 kg/m
2
, currently on a diet
with normal to high amount of carbohydrate
([55 %)/compatible to a modified ketogenic diet i.e., a
Mediterranean ketogenic diet with phytoextracts (KD) [8
10]. The subjects had normal renal function and no dia-
betes, nor were they pregnant or lactating. Changes of
habits, like starting a new exercise program or taking new
drugs during experimental period, would be excluded from
final analysis. Forty female subjects were initially recruited
in this study; six were excluded for medical reasons, one
was following a low-carbohydrate diet already and 1
refused to participate after the first interview, thus 32
subjects participated in the study and were randomized into
two groups (n=16 for each group): MD (age 44.7 ±13.9,
BMI 27.5 ±2.8, weight 77.2 ±9.8 kg) and KD (age
51.4 ±12.4, BMI 29.3 ±2.8, weight 82 ±12.4 kg). The
study was approved by the Ethical Board of the University
of Padova, Department of Biomedical Sciences, and con-
formed to standards for the use of human subjects in
research as outlined in the current Declaration of Helsinki.
Investigators explained the purpose of the study, the pro-
tocol to be followed, and the experimental procedures to be
used prior to allowing participants to enter the study.
Subjects received no monetary compensation for their
participation and signed a voluntary consent before initi-
ating the diet.
Diet
During a preliminary meeting, diets were explained and
each participant received a detailed menu containing per-
mitted and non-permitted food. The KD subjects were
followed for 20 days on a ketogenic diet (KD t
0
t
20
) with
extremely low carbohydrate (\30 g/day). The diet used
meals that mimic the aspect and the taste of carbohydrate,
but with virtually zero carbohydrate, and added with phy-
toextracts (Tisanoreica
by Gianluca Mech SpA, Asigliano
Veneto, Vicenza, Italy). The permitted food during the
ketogenic diet phase was cooked or raw green vegeta-
bles (200 g/meal); meat, fish, or eggs (1 time/day); and
olive oil 30 g/day. Allowed drinks were water, infusion tea,
Mocha coffee, and specific herbal extracts (Estratti
Decottopia Tisanoreica
by Gianluca Mech SpA, Asi-
gliano Veneto, Vicenza, Italy). The diet was also integrated
with four PATs
per day (PAT is the acronym for Porzione
Alimentare Tisanoreica =Tisanoreica Nutritional Por-
tion), which is composed of high-quality proteins (each
PAT is equivalent to 18 g of protein) and virtually zero
carbohydrates. After the ketogenic diet phase, the subjects
were followed on a low-carbohydrate no-ketogenic diet
over the next 20 days (KD t
20
t
40
). During this period,
complex carbohydrates (50–80 g/day) and cheese
(60 g/day) were introduced and the number of permitted
PATs was reduced to two, while the other indications
remained unchanged. The distribution of nutrients (pro-
teins, carbohydrates, and fats) in terms of percentage of
total caloric intake was 43, 14, and 43 % during the
ketogenic phase, and 27, 34, and 39 % during the next
stage, respectively. Throughout the ketogenic period, all
subjects consumed 30 ml of extract A and 30 ml of extract
B diluted in 1.5 l water, daily. They also consumed 15 ml
of extract C before breakfast and lunch, diluted in one glass
of water. Following 20 days, after dinner, 20 ml of extract
D diluted in one glass of warm water was added. The diet
protocols have been tested in our previous researches [5,9,
10].
The MD group followed a Mediterranean diet, con-
suming 1200 kcal/day for 20 days (MD t
0
t
20
), and it was
then followed with another set of Mediterranean diet con-
sisting of 1400 kcal/day over the next 20 days (MD
t
20
t
40
). The macronutrient percentage during the
Mediterranean diet consisted of 15 % protein, 60 % car-
bohydrate, and 25 % fat for the total daily caloric uptake.
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123
After the initial 40 days, both the KD and MD groups were
followed on a Mediterranean diet with a total daily caloric
uptake of 1400 kcal. The Mediterranean regime consisted
of a balanced diet, in which the use of whole grain pasta,
bread, and rice was permitted, mainly at breakfast and
lunch, but in a smaller quantity at dinner. Raw and cooked
vegetables were prescribed at lunch and dinner; fruits were
permitted as snacks in the morning or in the afternoon; and
proteins (meat/fish/cheese/eggs/bean curd, etc.) were pro-
vided only at dinner. Sweets, pizza, and alcoholic drinks
were allowed once a week and the accepted dressings were
olive oil, salt, spices, and vinegar. Moderate physical
activity and the use of infusions during the daytime were
also suggested.
Detailed composition of the diet is listed in Tables 1,2,
and 3.
Measurements
Subjects were invited to the Laboratory of Physiology,
Department of Biomedical Sciences, University of Padua,
where measurements were performed. REE and RR and
body weight were measured in the morning after overnight
fasting at the start of the study (t
0
), after 20 days (t
20
), at
the end of the diet-period (t
40
), and 2 months after the end
of the study (t
2m
). Subjects were weighed at the same time
of the day at the start (t
0
), at t
20
,t
40
, and t
2m
using the same
weighing scales (Digital Scale Joycare
Jc431). Body
composition analysis was performed using the Akern STA-
BIA instrument, which provided us with the following
information: fat free mass (FFM), FM, total body water
(TBW), and muscular mass. REE was analyzed using
oxygen uptake (VO
2
), carbon dioxide production (VCO
2
),
and RER measurements with a Vmax
Encore 29 System
(Vmax) (Viasys Healthcare, Inc., Yorba Linda, CA). Vmax
used a mixing chamber and generated VO
2
and VCO
2
;
those data were converted to REE expressed in Kcal/d
using appropriate RR values and established tables based
on the Weir equation [10]. The device was calibrated with
reference gases prior to each participant. Oxygen uptake
was measured (ml/min) and also normalized to body
weight (ml/kg/min), and the respiratory RR was deter-
mined. After resting for 15 min, the data were collected for
30 min, and only the last 20 min were used to calculate the
respiratory gas parameters [9].
All tests were performed in the morning before breakfast
(7–8 am), while the subjects were seated. The room was
dimly lit, quiet, and approximately 24 C. Subjects were
requested to abstain from caffeine or alcohol consumption
for 24 h prior to the measurement.
Statistical Analysis
The data were expressed as mean and standard deviation.
Bland–Altman plots and comparison of the test–retest
measurements performed in our laboratory confirmed good
reproducibility of the measurements for RR and VO
2
(ICC
[0.85 and [0.9, respectively, with p\0.05). A one-way
ANOVA for repeated measurements was used (GraphPad
Prism version 4.00 for Windows, GraphPad Software, San
Diego, California USA). Tukey’s post hoc test was used.
p\0.05 was considered significant. Normality of the data
was checked and subsequently confirmed using the Sha-
piro–Wilk test. The present sample size was selected based
on a power analysis. Body weight and body FM data were
analyzed using two-way ANOVA test for repeated mea-
sures, and unpaired t-tests with Welch’s correction were
performed when appropriate.
Results
Respiratory Gas Analysis
As shown in Fig. 1, the KD group showed a significant
decrease (p\0.05) in the mean value of RER after
20 days of ketogenic diet. The RER was maintained at
lower levels even after 40 days (t
40
), when subjects were
no more in ketosis. The reduction in PETCO
2
(Fig. 2) was
observed after both the ketogenic diet and Mediterranean
diet. There were no significant changes in VO
2
(Fig. 3),
VCO
2
(Fig. 4), and VE (Fig. 5).
The MD group did not show any significant difference
(data not shown).
As shown in Fig. 6, a significant body weight loss was
noticed in both groups between t
0
and t
20
(p\0.01), the
body weight loss was more significant in the KD group
than in the MD group. The mean values of body weight in
both groups are as follows:
Table 1 Diet composition in
KD diets (values are expressed
in mean per day)
KD t
0
t
20
KD t
20
t
40
KD t
40
t
2m
Daily energy, Kcal/day 848 938 1400
Protein, g/day (% daily energy) 92 (43.4) 64.4 (27.5) 52.5 (15)
Carbohydrate, g/day (% daily energy) 30 (14.1) 80 (34.1) 210 (60)
Fat, g/day (% daily energy) 42 (42.4) 42 (38.4) 54.4 (35)
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123
Table 2 Plant extracts during the KD group’s diet (from)
Plant extracts ml/day Composition
Extract A 30 Durvillaea Antarctica, Black Radish, Mint, Liquorice, Artichoke, Horsetail, Burdock,
Dandelion, Rhubarb, Gentian, Lemon Balm, Chinaroot, Juniper, Spear Grass, Elder, Focus,
Anise, Parsley, Bearberry, Horehound
Extract B 30 Serenoa, Red Clover, Chervil, Bean, Elder, Dandelion, Uncaria, Equisetum, Horehound,
Rosemary
Extract C (only during the first
ketogenic phase)
30 Eleuthero, Eurycoma Longifolia, Ginseng, Corn, Muira Puama, Grape, Guarana
`, Arabic
Coffee, Ginger
Extract D (only during the second
non-ketogenic phase)
20 Horsetail, Asparagus, Birch, Cypress, Couch Grass, Corn, Dandelion, Grape, Fennel, Elder,
Rosehip, Anise
Table 3 Main active ingredients of phytoextracts and their reported beneficial effects (from)
Extract Main active ingredients Reported beneficial effects
A Mint Indigestion
Black radish Antioxidant
Burdock Choleretic, increases bile secretion helping digestion
B Serenoa Repens (Saw Palmetto) Hormonal regulating effect
White bean Alpha-amylase inhibitory properties have been reported to aid
weight loss and glycemic control
C Ginseng Ameliorate the commonly reported symptoms of weakness and tiredness
during 1st phase of ketosis (1/2 weeks)
Muira puama
Guarana
`
D Equisetum
Dandelion (Taraxacum officinale)
Fig. 1 The effect of ketogenic diet on respiratory exchange ratio
(RER) measured at different time points during the diet period.
Ketogenic diet significantly decreased the respiratory exchange ratio
as measured on day 20. RER continues to decrease as measured on
day 40, and returned to the baseline as measured in 2 months. t
0
day
0, the value as baseline; t
20
as measured on day 20; t
40
as measured on
day 40; t
2m
as measured in 2 months. **p\0.01. Values are shown
as mean and SD
Fig. 2 The changes of carbon dioxide end-tidal partial pressure
(PETCO
2
) measured at different time points during the diet period.
Comparing with the baseline of PETCO
2
at the start of the study (t
0
),
significant decrease (p\0.05) was observed after 20 days (t
20
)of
ketogenic diet, at the end of the diet-period (t
40
), and 2 months after
the end of the weight reduction program (t
2m
). t
0
day 0, the value as
baseline; t
20
as measured on day 20; t
40
as measured on day 40; t
2m
as
measured in 2 months. **p\0.01. Values are shown as mean and
SD
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123
KD: t
0
82.0 ±12.4; t
20
77.8 ±12.0; t
40
74.8 ±11.7;
t
2m
73.5 ±12.6
MD: t
0
77.2 ±9.8; t
20
74.4 ±10.0 t
40
72.5 ±9.6; t
2m
72.1 ±10.7
The average weight loss was 8.4 kg for the KD group
and 5.1 kg for the MD group at t
2m
.
As shown in Fig. 7, both groups showed a good drop in
FM between t
0
and t
20
, although it was more significant for
the KD group (pvalue MD t
20
\0.01; pvalue KD
t
20
\0.001). The average of the FM lost in this group
between t
40
and t
2m
is 1 kg in KD and 0.2 kg in MD group.
All subjects completed the experimental trial.
Discussion
The main findings in the present study are that (1) the
ketogenic diet significantly decreased the value of RER; (2)
the ketogenic diet significantly decreased carbon dioxide
end-tidal partial pressure (PETCO
2
); (3) the ketogenic diet
Fig. 3 The changes in oxygen uptake (VO2) measured at different
time points during the diet period. There was no significant change in
VO2 during the entire diet period. t
0
day 0, the value as baseline; t
20
as measured on day 20; t
40
as measured on day 40; t
2m
as measured in
2 months. Values are shown as mean and SD
Fig. 4 The changes in carbon dioxide production (VCO2) measured
at different time points during the diet period. There were no
significant changes observed during the diet period. t
0
day 0, the value
as baseline; t
20
as measured on day 20; t
40
as measured on day 40; t
2m
as measured in 2 months. Carbon dioxide output relies largely on the
amount of energy your body is using. Values are shown as mean and
SD
Fig. 5 The changes in expired total ventilation (VE) measured at
different time points during the diet period. There were no significant
changes observed during the diet period. t
0
day 0, the value as
baseline; t
20
as measured on day 20; t
40
as measured on day 40; t
2m
as
measured in 2 months. Values are shown as mean and SD
Fig. 6 The effect of ketogenic diet on body weight measured at
different time points during the diet period. Significant body weight
loss was observed in both diet groups. t
0
day 0, the value as baseline;
t
20
as measured on day 20; t
40
as measured on day 40; t
2m
as measured
in 2 months. No significant differences were detected between
treatments. Values are shown as mean and SD
Fig. 7 The effect of ketogenic diet on body fat mass measured at
different time points during the diet period. Significant body fat mass
loss was observed in both diet groups. t
0
day 0, the value as baseline;
t
20
as measured on day 20; t
40
as measured on day 40; t
2m
as measured
in 2 months. At t
2m
, KD group showed significant decrease
(*p\0.05) compared to MD group. Values are shown as mean and
SD
Lung
123
had no significant effect on REE, oxygen consumption
(VO
2
), carbon dioxide production (VCO
2
), or expired total
ventilation (VE); (4) the ketogenic diet significantly
decreased body mass and body FM.
The RER is the ratio between the amount of CO
2
pro-
duced and molecules of O
2
consumed in one breath. A RER
of 0.70 indicates that fat is the predominant fuel source, a
RER of 0.85 suggests a mix of fat and carbohydrates, and a
value of 1.00 or above is indicative of carbohydrates being
the predominant fuel source. Deceased RER seen in the
present study reflects fat as the predominant fuel source
during consumption of the ketogenic diet. This is in agree-
ment with our previous study [6] and others [7].
Oxygen consumption is linearly related to the workload;
consumption of different diets should not significantly
change REE. A recent study showed that administering the
ketogenic diet for 6 months in patients with medically
refractory epilepsy increased fat oxidation without chang-
ing REE [7]. Our data are in agreement with their findings
that KD did not change REE. As pointed out by Tagliabue
et al. the body has a great capacity to adjust substrate
oxidation to substrate intake after approximately 1 week of
carbohydrates and fats. Fat oxidation increased in our study
as an adaptation to the high-fat intake, typical of the KD.
The consequence of an isoenergetic exchange of fat for
carbohydrate is that the results can also be interpreted as
being an adaptation to a low-carbohydrate intake [11,12].
We have previously demonstrated that using KD for
30 days can decrease body weight and body FM without
negative effects on strength performance in high level
athletes [9]. The data from the present study validate the
weight reduction effect of KD. We previously suggested
that KD reduced body weight and FM loss and it may be due
to reduced REE in elite artistic gymnasts caused by glu-
coneogenesis and the thermic effect of proteins [9]. In the
present study, in healthy subjects the reduced body weight
and FM were not associated with reduced REE. The pos-
sible mechanisms may be due to reduction in lipid synthesis
and increased lipolysis mechanisms, reduction in at rest RQ
and, therefore, an increase in fat metabolism for energy use.
High-fat content in the ketogenic diet causes ketosis and
metabolic acidosis, which leads to a reduction in carbon
dioxide metabolic production for a given oxygen con-
sumption. As shown in the present study, REE was not
changed; therefore, the total oxygen consumption was not
altered by the ketogenic diet. The carbon dioxide metabolic
production should decrease as the present study demon-
strated. As a consequence, decreased pulmonary ventila-
tion parameters values should be expected. Expired minute
volume is an important parameter in respiratory medicine
due to its relationship with blood carbon dioxide levels.
Blood carbon dioxide levels generally vary inversely with
minute volume. For example, a person with increased
minute volume should demonstrate a lower blood carbon
dioxide level. The healthy human body will alter minute
volume in an attempt to maintain physiologic homeostasis.
However, our data do not follow this principle; reduced
carbon dioxide metabolic production is not associated with
increased expired total ventilation. This phenomenon sug-
gests that reduced carbon dioxide output may be due to a
decreased carbon dioxide body store. This may be partially
caused by reductions in body mass and FM, and/or, greater
oxygen uptake necessary to obtain the same energy yield as
on a mixed diet due to increased fat oxidation after the
ketogenic diet. According to the definition of carbon
dioxide store, the amount of CO
2
contained in the body as a
gas and in the form of carbonic acid, carbonate, bicar-
bonate, and carbaminohemoglobin, during a steady state of
ventilation and aerobic respiration, the rate at which CO
2
leaves the body equals the rate at which it is produced, and
CO
2
store remains constant. The ketogenic diet decreases
the production of CO
2
, and since the rate of CO
2
leaving
the body does not change (no change in expired volume),
the CO
2
store consequently decreases.
Few studies have described the consequent changes in
pulmonary ventilation and/or arterial carbon dioxide partial
pressure during high fat metabolism. For example, Saba-
pathy et al. examined the relationship between minute
ventilation, CO
2
production, and blood lactate concentra-
tions during incremental exercise performed with reduced
muscle glycogen stores [13]. Peak oxygen uptake was
unchanged with glycogen reduction. Peak blood lactate
decreased significantly. At any percentage of peak oxygen
uptakes, O
2
uptake and minute ventilation were similar for
both treatment conditions, whereas VCO
2
and RER values
were lower during the reduced glycogen trial than under
normal glycogen conditions. Therefore, VE/VCO
2
tends to
be higher and end-tidal CO
2
partial pressure tends to be
lower during exercise performed in the reduced glycogen
state. Minute ventilation was significantly correlated
with CO
2
production under both treatment conditions.
Minute ventilation during exercise was similar under both
treatment conditions. This suggests that factors other than
CO
2
delivery to the lung and metabolic acidosis play an
important role in regulating minute ventilation during
exercise. Similar results were also reported [14]. Cai et al.
evaluated the efficacy of feeding a high-fat, low-carbohy-
drate (CHO) nutritional supplement as opposed to a high-
carbohydrate diet in COPD patients on parameters of pul-
monary function. They found that lung function measure-
ments decreased significantly and forced expiratory
volume increased significantly in the high-fat, low-carbo-
hydrate diet group. Their study demonstrates that pul-
monary function in COPD patients can be significantly
improved with a high-fat, low-CHO oral supplement as
compared with the traditional high-CHO diet. These
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123
findings suggest that factors other than CO
2
delivery to the
lung and metabolic acidosis play an important role in
regulating ventilation during ketogenic diet. The present
study supports their findings that the high-fat diet may
decrease the carbon dioxide store, and therefore, improve
pulmonary ventilation. In this preliminary study we tested
healthy subjects; it is reasonable to suppose that the vari-
ations of blood gases during a ketogenic diet follow the
same trend in normal subjects and in respiratory compro-
mised patients. The ketogenic diet has been described to be
associated with an increased leptin blood concentration
[15], and leptin has been recognized as an effective ven-
tilation stimulant [16,17]. Thus, the ketogenic diet-induced
reduction in carbon dioxide metabolic load is coupled with
a reduced carbon dioxide partial pressure value, with
maintained pulmonary ventilation.
Hypercapnic respiratory failure (type II) is characterized
by an increased carbon dioxide arterial partial pressure
values higher than 50 mm Hg. Through the specific treat-
ment on the etiology of respiratory failure, the ketogenic
diet may provide the potential useful effects because it
lowers carbon dioxide arterial partial pressure values. In
our opinion, it is not possible to definitely state that the
observed changes in PETCO
2
may be clinically relevant in
all conditions. Such a little change may reveal not to be
decisive in some clinical settings, but even such minor
changes may have clinically relevant consequences in
border-line patients with risk of respiratory failure.
One limitation of our study was the relative low number
of subjects and the heterogeneity of sample (even though
the differences of investigated variables at the start of the
study was not statistically significant). Further studies are
needed to verify this working hypothesis. In particular, it
would be of interest to verify that the constancy of pul-
monary ventilation is associated with a lack of any sig-
nificant changes in the mechanical work of breathing. This
would suggest that respiratory failure patients undergo
reduced arterial carbon dioxide partial pressure values
without an incremented risk of respiratory failure on a
mechanical basis because of respiratory muscle fatigue.
Acknowledgments We wish to thank Kim Hare and Marcelyn
Cook for their English editorial assistance.
Compliance with Ethical Standards
Conflict of interest The authors declare that they have no conflict
of interest.
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... On a pathophysiological basis, fat oxidation produces less carbon dioxide (CO 2 ) per amount of oxygen consumed compared to carbohydrates (CHO) (38), resulting in reduced ventilatory requirements. Therefore, ketogenic diet decreases metabolic carbon dioxide production for a given oxygen consumption, and may theoretically lead to a reduction in arterial carbon dioxide partial pressure (PETCO 2 ), pulmonary ventilation, and CO 2 body stores (29,30). ...
... Rubini et al. (29) observed that a ketogenic diet (CHO < 30 g/day) administered for 20 days reduced PETCO 2 in 32 healthy subjects, without modifications in oxygen uptake, carbon dioxide production nor expired total ventilation, which may be related to a reduction in CO 2 body stores. Therefore, it may be beneficial for patients with high carbon dioxide arterial partial pressure due to respiratory insufficiency, because it lowers CO 2 levels without increasing respiratory muscle fatigue, with the consequent risk of respiratory failure on mechanical basis. ...
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Morbid obese people are more likely to contract SARS-CoV-2 infection and its most severe complications, as need for mechanical ventilation. Ketogenic Diet (KD) is able to induce a fast weight loss preserving lean mass and is particularly interesting as a preventive measure in obese patients. Moreover, KD has anti-inflammatory and immune-modulating properties, which may help in preventing the cytokine storm in infected patients. Respiratory failure is actually considered a contraindication for VLCKD, a very-low calorie form of KD, but in the literature there are some data reporting beneficial effects on respiratory parameters from ketogenic and low-carbohydrate high-fat diets. KD may be helpful in reducing ventilatory requirements in respiratory patients, so it should be considered in specifically addressed clinical trials as an adjuvant therapy for obese patients infected with SARS-CoV-2.
... In both developing and developed countries, obesity levels continue to grow with ∼38 and 20% of the world's adult population predicted to be overweight and obese by 2030 (1), respectively. On a global level, obesity is one of the most serious health issues (2,3). Moreover, a recent study by Pi-Sunyer et al. (3) suggested that obesity was a major potential risk factor for chronic diseases, such as cardiovascular disease, diabetes mellitus (DM), cerebrovascular disease, metabolic syndrome, and cancer, thereby increasing social, medical, and economic burdens. ...
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Background: The purpose of this meta-analysis was to explore the effects of low-carbohydrate ketogenic diets on cardiovascular risk factors in overweight or obese patients. However, there are limited literature data about effects of low-carbohydrate ketogenic diets on cardiovascular risk factors in obese or overweight patients. Methods: We systematically searched PubMed, EMBASE, Web of Science, OVID, and Cochrane Library databases (last updated in September 2022) for randomized controlled trials (RCTs) which recruited overweight or obesity patients on ketogenic diets in order to control cardiovascular risk factors (blood glucose, weight, and lipids). The overall effect size for continuous variables was expressed as a weighted standardized mean difference (SMD) with a confidence interval of 95%. Considering type 2 diabetes mellitus (T2DM) status at baseline, subgroup analyses were performed when appropriate, based on T2DM comorbidity among patients. The effect model was selected according to heterogeneity. Results: We finally selected 21 studies. Low carbohydrate ketogenic diets exerted a greater impact on cardiovascular risk factors in obese/ overweight patients with T2DM when compared with those on non-ketogenic diets, with lower fasting plasma glucose (FPG) (SMD, -0.75; P < 0.001) and hemoglobin A1c (HbA1c) (SMD, -0.53; P < 0.001) levels identified. Low-carbohydrate ketogenic diets significantly reduced body mass index (BMI) (SMD, -2.27; P = 0.032), weight (SMD, -6.72; P < 0.001), and waist circumference (SMD, -4.45; P = 0.003) in obese/ overweight patients with T2DM. Also, ketogenic diets improved lipid profiles in these patients; triglyceride (TG) (SMD, -0.32; P = 0.013) levels were lowered and high density lipoprotein (HDL) showed an upward trend with the P-value close to statistically significant level (SMD, -0.32; P = 0.052). In general, irrespective of diabetic status at baseline, ketogenic diets were more effective in reducing TG (SMD, -0.2; P = 0.02) and increasing HDL (SMD, 0.11; P = 0.03) levels when compared with non-ketogenic diets. Conclusions: Low-carbohydrate ketogenic diets effectively improved cardiovascular risk factors (blood glucose, weight, and lipids) in obese/ overweight patients, especially those with T2DM when compared with non-ketogenic diets.
... 325 Regarding food composition, a low-carbohydrate, high-fat KD is discovered to potentially preserve respiratory function through a decrease in the storage of carbon dioxide in the lungs. 326 Meanwhile, KD remodels the metabolic process of γδ T cells and contributes to γδ T-cells expansion, which improves lung barrier functions to resist influenza virus infection. 327 In addition, dietary fibre has a vital effect on lung functions. ...
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Nutriments have been deemed to impact all physiopathologic processes. Recent evidences in molecular medicine and clinical trials have demonstrated that adequate nutrition treatments are the golden criterion for extending healthspan and delaying ageing in various species such as yeast, drosophila, rodent, primate and human. It emerges to develop the precision-nutrition therapeutics to slow age-related biological processes and treat diverse diseases. However, the nutritive advantages frequently diversify among individuals as well as organs and tissues, which brings challenges in this field. In this review, we summarize the different forms of dietary interventions extensively prescribed for healthspan improvement and disease treatment in pre-clinical or clinical. We discuss the nutrient-mediated mechanisms including metabolic regulators, nutritive metabolism pathways, epigenetic mechanisms and circadian clocks. Comparably, we describe diet-responsive effectors by which dietary interventions influence the endocrinic, immunological, microbial and neural states responsible for improving health and preventing multiple diseases in humans. Furthermore, we expatiate diverse patterns of dietotheroapies, including different fasting, calorie-restricted diet, ketogenic diet, high-fibre diet, plants-based diet, protein restriction diet or diet with specific reduction in amino acids or microelements, potentially affecting the health and morbid states. Altogether, we emphasize the profound nutritional therapy, and highlight the crosstalk among explored mechanisms and critical factors to develop individualized therapeutic approaches and predictors.
... They are also second messengers for many pathways, such as food intake stimuli 64 . The ketogenic regimen is also related to the increase of lipid metabolism 65 which in the case of OOS is often associated with the decrease of body fat percentage and weight loss 4,6,49 . Considering that sailors are exposed to harsh environmental conditions and that motion sickness and working rates can influence nutrition habits during a race 4 , it is of utmost importance to maintain an adequate water intake during navigation to prevent renal damage and to keep proper caloric intake to sustain physical performance. ...
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Competitive Offshore Ocean Sailing is a highly demanding activity in which subjects are exposed to psychophysical stressors for a long time. To better define the physiological adaptations, we investigated the stress response of subjects exposed to 3-days long ocean navigation with disruption of circadian rhythms. 6 male subjects were involved in the study and provided urine and saliva samples before setting sail, during a single day of inshore sailing, during 3-days long ocean navigation, and at the arrival, to measure oxidative stress, cortisol, nitric oxide metabolites (NOx) and metabolic response. Motion Sickness questionnaires were also administered during the navigation. The crew suffered a mean weight loss of 1.58 kg. After the long navigation, a significant increase in ROS production and decrease in total antioxidant capacity and uric acid levels were observed. Lipid peroxidation, NO metabolites, ketones, creatinine, and neopterin levels were also increased. Furthermore, a significant increase in cortisol levels was measured. Finally, we found a correlation between motion sickness questionnaires with the increase of NOx, and no correlation with cortisol levels. Physical and psychological stress response derived from offshore sailing resulted in increased oxidative stress, nitric oxide metabolites, and cortisol levels, unbalanced redox status, transient renal function impairment, and ketosis. A direct correlation between motion sickness symptoms evaluated through questionnaires and NOx levels was also found.
... Respiratory system-The respiratory system is also impaired with age, especially in obese individuals (Dixon and Peters, 2018). One study in humans using the ketogenic diet found that individuals had reduced storage of carbon dioxide in the lungs, which was suggested to potentially preserve respiratory function (Rubini et al., 2015). However, chronic low-carbohydrate diets such as the ketogenic diet have also been shown to impair exercise performance in middle-aged individuals who were considered healthy (Pilis et al., 2018) (Figure 3). ...
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Dietary restriction (DR) has long been viewed as the most robust nongenetic means to extend lifespan and healthspan. Many aging-associated mechanisms are nutrient responsive, but despite the ubiquitous functions of these pathways, the benefits of DR often vary among individuals and even among tissues within an individual, challenging the aging research field. Furthermore, it is often assumed that lifespan interventions like DR will also extend healthspan, which is thus often ignored in aging studies. In this review, we provide an overview of DR as an intervention and discuss the mechanisms by which it affects lifespan and various healthspan measures. We also review studies that demonstrate exceptions to the standing paradigm of DR being beneficial, thus raising new questions that future studies must address. We detail critical factors for the proposed field of precision nutrigeroscience, which would utilize individualized treatments and predict outcomes using biomarkers based on genotype, sex, tissue, and age.
... However, the full spectrum of the effects of the KD on respiratory parameters was not reported in this study. To our In humans, one study in adults has shown that a 20-day exposure to the KD resulted in a decrease in 1) patient carbon dioxide end-tidal partial pressure and 2) respiratory exchange ratio, indicating hypoventilation and/or the metabolism of fats as opposed to glucose as an energy source (Rubini et al., 2015). In another study, patients with chronic obstructive pulmonary disease treated with the KD for 3 weeks showed a decreased and consequent indicating KD- ...
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Infantile Spasms syndrome is a catastrophic, epileptic encephalopathy of infancy that is often refractory to current antiepileptic therapies. The ketogenic diet has emerged as an alternative treatment for patients with medically intractable epilepsy, though the prospective validity and mechanism of action for Infantile Spasms remains largely unexplored. We investigated the ketogenic diet’s efficacy as well as its mechanism of action in a rodent model of intractable Infantile Spasms. The spasms were induced using the triple-hit paradigm and the animals were then artificially reared and put on either the ketogenic diet (4:1 fats: carbohydrate + protein) or a control-milk diet (CM; 1.7:1). 31Phosphorus magnetic resonance spectroscopy (MRS) and head-out plethysmography were examined in conjunction with continuous video-EEG behavioural recordings in lesioned animals and sham-operated controls. The ketogenic diet resulted in a peripheral ketosis observed both in the blood and urine. The ketogenic diet led to a robust reduction in the frequency of spasms observed, with approximately a 1.5-fold increase in the rate of survival. Intriguingly, the ketogenic diet resulted in an intracerebral acidosis as measured with 31Phosphorus magnetic resonance spectroscopy. In addition, the respiratory profile of the lesioned rats on the ketogenic diet was significantly altered with slower, deeper, and longer breathing, resulting in decreased levels of expired CO2. Sodium bicarbonate supplementation, acting as a pH buffer, partially reversed the ketogenic diet’s protective effects on spasm frequency. There were no differences in the mitochondrial respiratory profiles in the liver and brain frontal cortex measured between the groups, supporting the notion that the effects of the ketogenic diet on breathing are not entirely due to changes in intermediary metabolism. Together, our results indicate that the ketogenic diet produces its anticonvulsant effects through changes in respiration leading to intracerebral acidosis. These findings provide a novel understanding of the mechanisms underlying the anti-seizure effects of the ketogenic diet in Infantile Spasms. Further research is required to determine whether the effects of the ketogenic diet on breathing and intracerebral acid-base balance are seen in other pediatric models of epilepsy.
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A very low-calorie ketogenic diet (VLCKD) is characterized by low daily caloric intake (less than 800 kcal/day), low carbohydrate intake (<50 g/day) and normoproteic (1–1.5 g of protein/kg of ideal body weight) contents. It induces a significant weight loss and an improvement in lipid parameters, blood pressure, glycaemic indices and insulin sensitivity in patients with obesity and type 2 diabetes mellitus. Cushing’s syndrome (CS) is characterized by an endogenous or exogenous excess of glucocorticoids and shows many comorbidities including cardiovascular disease, obesity, type 2 diabetes mellitus and lipid disorders. The aim of this speculative review is to provide an overview on nutrition in hypercortisolism and analyse the potential use of a VLCKD for the treatment of CS comorbidities, analysing the molecular mechanisms of ketogenesis.
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A dysregulation between energy intake (EI) and energy expenditure (EE), the two components of the energy balance equation, is one of the mechanisms responsible for the development of obesity. Conservation of energy equilibrium is deemed a dynamic process and alterations of one component (energy intake or energy expenditure) lead to biological and/or behavioral compensatory changes in the counterpart. The interplay between energy demand and caloric intake appears designed to guarantee an adequate fuel supply in variable life contexts. In the past decades, researchers focused their attention on finding efficient strategies to fight the obesity pandemic. The ketogenic or “keto” diet (KD) gained substantial consideration as a potential weight-loss strategy, whereby the concentration of blood ketones (acetoacetate, 3-β-hydroxybutyrate, and acetone) increases as a result of increased fatty acid breakdown and the activity of ketogenic enzymes. It has been hypothesized that during the first phase of KDs when glucose utilization is still prevalent, an increase in EE may occur, due to increased hepatic oxygen consumption for gluconeogenesis and for triglyceride-fatty acid recycling. Later, a decrease in 24-h EE may ensue due to the slowing of gluconeogenesis and increase in fatty acid oxidation, with a reduction of the respiratory quotient and possibly the direct action of additional hormonal signals.
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Dietary restriction of carbohydrate has been demonstrated to be beneficial for nervous system dysfunction in animal models and may be beneficial for human chronic pain. The purpose of this review is to assess the impact of a low-carbohydrate/ketogenic diet on the adult nervous system function and inflammatory biomarkers to inform nutritional research for chronic pain. An electronic data base search was carried out in May 2021. Publications were screened for prospective research with dietary carbohydrate intake <130g/day and duration of ≥2 weeks. Studies were categorised into those reporting adult neurological outcomes to be extracted for analysis and those reporting other adult research outcomes Both groups were screened again for reported inflammatory biomarkers. From 1548 studies there were 847 studies included. Sixty-four reported neurological outcomes with 83% showing improvement. Five hundred and twenty-three studies had a different research focus (metabolic n=394, sport/performance n=51, cancer n=33, general n=30, neurological with non-neuro outcomes n=12, or gastrointestinal n=4). The second screen identified 63 studies reporting on inflammatory biomarkers with 71% reporting a reduction in inflammation. The overall results suggest a favourable outcome on the nervous system and inflammatory biomarkers from a reduction in dietary carbohydrates. Both nervous system sensitisation and inflammation occur in chronic pain and the results from this review indicate it may be improved by low-carbohydrate nutritional therapy. More clinical trials within this population are required to build on the few human trials that have been done.
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Ketogenic diets, which are carbohydrate-restricted high-fat diets, may have therapeutic effects on various diseases, including cancer. However, ketogenic diets are often not standardized and, therefore, results are difficult to interpret. We previously investigated the usefulness of ketogenic diets in cancer therapy, where ketogenic formulas (KF) were used as supplements to enhance blood ketone bodies; however, the amount of KF was determined empirically with reference to blood ketone bodies levels. Here, to determine a standardized optimal amount of KF, we investigated temporal changes in blood ketone bodies (acetoacetic acid (AcAc), β-hydroxybutyrate (BHB)) and safety in 20 healthy individuals when KF was taken repeatedly under the conditions of a ketogenic diet (UMIN000034216). The diurnal variation in total ketone bodies, and AcAc and BHB levels significantly increased after lunch and after dinner, on the 4th day of KF administration. There were no significant safety issues related to KF in the context of anthropometric, metabolic, nutritional, urological and gastrointestinal parameters. In addition, ketogenic diets lead to changes in gut microbiota. KF showed a decrease in phylum Firmicutes. Our study provides baseline data of the usefulness of KF in a ketogenic diet.
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Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand.European Journal of Clinical Nutrition advance online publication, 26 June 2013; doi:10.1038/ejcn.2013.116.
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Background The benefits of exercise are well established but one major barrier for many is time. It has been proposed that short period resistance training (RT) could play a role in weight control by increasing resting energy expenditure (REE) but the effects of different kinds of RT has not been widely reported. Methods We tested the acute effects of high-intensity interval resistance training (HIRT) vs. traditional resistance training (TT) on REE and respiratory ratio (RR) at 22 hours post-exercise. In two separate sessions, seventeen trained males carried out HIRT and TT protocols. The HIRT technique consists of: 6 repetitions, 20 seconds rest, 2/3 repetitions, 20 secs rest, 2/3 repetitions with 2′30″ rest between sets, three exercises for a total of 7 sets. TT consisted of eight exercises of 4 sets of 8–12 repetitions with one/two minutes rest with a total amount of 32 sets. We measured basal REE and RR (TT0 and HIRT0) and 22 hours after the training session (TT22 and HIRT22). Results HIRT showed a greater significant increase (p < 0.001) in REE at 22 hours compared to TT (HIRT22 2362 ± 118 Kcal/d vs TT22 1999 ± 88 Kcal/d). RR at HIRT22 was significantly lower (0.798 ± 0.010) compared to both HIRT0 (0.827 ± 0.006) and TT22 (0.822 ± 0.008). Conclusions Our data suggest that shorter HIRT sessions may increase REE after exercise to a greater extent than TT and may reduce RR hence improving fat oxidation. The shorter exercise time commitment may help to reduce one major barrier to exercise.
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Background: Despite the increasing use of very low carbohydrate ketogenic diets (VLCKD) in weight control and management of the metabolic syndrome there is a paucity of research about effects of VLCKD on sport performance. Ketogenic diets may be useful in sports that include weight class divisions and the aim of our study was to investigate the influence of VLCKD on explosive strength performance. Methods: 8 athletes, elite artistic gymnasts (age 20.9 ± 5.5 yrs) were recruited. We analyzed body composition and various performance aspects (hanging straight leg raise, ground push up, parallel bar dips, pull up, squat jump, countermovement jump, 30 sec continuous jumps) before and after 30 days of a modified ketogenic diet. The diet was based on green vegetables, olive oil, fish and meat plus dishes composed of high quality protein and virtually zero carbohydrates, but which mimicked their taste, with the addition of some herbal extracts. During the VLCKD the athletes performed the normal training program. After three months the same protocol, tests were performed before and after 30 days of the athletes' usual diet (a typically western diet, WD). A one-way Anova for repeated measurements was used. Results: No significant differences were detected between VLCKD and WD in all strength tests. Significant differences were found in body weight and body composition: after VLCKD there was a decrease in body weight (from 69.6 ± 7.3 Kg to 68.0 ± 7.5 Kg) and fat mass (from 5.3 ± 1.3 Kg to 3.4 ± 0.8 Kg p < 0.001) with a non-significant increase in muscle mass. Conclusions: Despite concerns of coaches and doctors about the possible detrimental effects of low carbohydrate diets on athletic performance and the well known importance of carbohydrates there are no data about VLCKD and strength performance. The undeniable and sudden effect of VLCKD on fat loss may be useful for those athletes who compete in sports based on weight class. We have demonstrated that using VLCKD for a relatively short time period (i.e. 30 days) can decrease body weight and body fat without negative effects on strength performance in high level athletes.
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We measured the effects of a diet in which D-β-hydroxybutyrate-(R)-1,3 butanediol monoester [ketone ester (KE)] replaced equicaloric amounts of carbohydrate on 8-wk-old male C57BL/6J mice. Diets contained equal amounts of fat, protein, and micronutrients. The KE group was fed ad libitum, whereas the control (Ctrl) mice were pair-fed to the KE group. Blood d-β-hydroxybutyrate levels in the KE group were 3-5 times those reported with high-fat ketogenic diets. Voluntary food intake was reduced dose dependently with the KE diet. Feeding the KE diet for up to 1 mo increased the number of mitochondria and doubled the electron transport chain proteins, uncoupling protein 1, and mitochondrial biogenesis-regulating proteins in the interscapular brown adipose tissue (IBAT). [(18)F]-Fluorodeoxyglucose uptake in IBAT of the KE group was twice that in IBAT of the Ctrl group. Plasma leptin levels of the KE group were more than 2-fold those of the Ctrl group and were associated with increased sympathetic nervous system activity to IBAT. The KE group exhibited 14% greater resting energy expenditure, but the total energy expenditure measured over a 24-h period or body weights was not different. The quantitative insulin-sensitivity check index was 73% higher in the KE group. These results identify KE as a potential antiobesity supplement.
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There has been increased interest in recent years in very low carbohydrate ketogenic diets (VLCKD) that, even though they are much discussed and often opposed, have undoubtedly been shown to be effective, at least in the short to medium term, as a tool to tackle obesity, hyperlipidemia and some cardiovascular risk factors. For this reason the ketogenic diet represents an interesting option but unfortunately suffers from a low compliance. The aim of this pilot study is to ascertain the safety and effects of a modified ketogenic diet that utilizes ingredients which are low in carbohydrates but are formulated to simulate its aspect and taste and also contain phytoextracts to add beneficial effects of important vegetable components. The study group consisted of 106 Rome council employees with a body mass index of ≥ 25, age between 18 and 65 years (19 male and 87 female; mean age 48.49 ± 10.3). We investigated the effects of a modified ketogenic diet based on green vegetables, olive oil, fish and meat plus dishes composed of high quality protein and virtually zero carbohydrate but which mimic their taste, with the addition of some herbal extracts (KEMEPHY ketogenic Mediterranean with phytoextracts). Calories in the diet were unlimited. Measurements were taken before and after 6 weeks of diet. There were no significant changes in BUN, ALT, AST, GGT and blood creatinine. We detected a significant (p < 0.0001) reduction in BMI (31.45 Kg/m2 to 29.01 Kg/m2), body weight (86.15 kg to 79.43 Kg), percentage of fat mass (41.24% to 34.99%), waist circumference (106.56 cm to 97.10 cm), total cholesterol (204 mg/dl to 181 mg/dl), LDLc (150 mg/dl to 136 mg/dl), triglycerides (119 mg/dl to 93 mg/dl) and blood glucose (96 mg/dl to 91 mg/dl). There was a significant (p < 0.0001) increase in HDLc (46 mg/dl to 52 mg/dl). The KEMEPHY diet lead to weight reduction, improvements in cardiovascular risk markers, reduction in waist circumference and showed good compliance.
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Ketogenic diets are an effective healthy way of losing weight since they promote a non-atherogenic lipid profile, lower blood pressure and decrease resistance to insulin with an improvement in blood levels of glucose and insulin. On the other hand, Mediterranean diet is well known to be one of the healthiest diets, being the basic ingredients of such diet the olive oil, red wine and vegetables. In Spain the fish is an important component of such diet. The objective of this study was to determine the dietary effects of a protein ketogenic diet rich in olive oil, salad, fish and red wine. A prospective study was carried out in 31 obese subjects (22 male and 19 female) with the inclusion criteria whose body mass index and age was 36.46 +/- 2.22 and 38.48 +/- 2.27, respectively. This Ketogenic diet was called "Spanish Ketogenic Mediterranean Diet" (SKMD) due to the incorporation of virgin olive oil as the principal source of fat (> or =30 ml/day), moderate red wine intake (200-400 ml/day), green vegetables and salads as the main source of carbohydrates and fish as the main source of proteins. It was an unlimited calorie diet. Statistical differences between the parameters studied before and after the administration of the "Spanish Ketogenic Mediterranean diet" (week 0 and 12) were analyzed by paired Student's t test. There was an extremely significant (p < 0.0001) reduction in body weight (108.62 kg--> 94.48 kg), body mass index (36.46 kg/m(2)-->31.76 kg/m(2), systolic blood pressure (125.71 mmHg-->109.05 mmHg), diastolic blood pressure (84.52 mmHg--> 75.24 mmHg), total cholesterol (208.24 mg/dl-->186.62 mg/dl), triacylglicerols (218.67 mg/dl-->113.90 mg/dl) and glucose (109.81 mg/dl--> 93.33 mg/dl). There was a significant (p = 0.0167) reduction in LDLc (114.52 mg/dl-->105.95 mg/dl) and an extremely significant increase in HDLc (50.10 mg/dl-->54.57 mg/dl). The most affected parameter was the triacylglicerols (47.91% of reduction). The SKMD is safe, an effective way of losing weight, promoting non-atherogenic lipid profiles, lowering blood pressure and improving fasting blood glucose levels. Future research should include a larger sample size, a longer term use and a comparison with other ketogenic diets.
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This 6-month prospective, single-arm observational study was designed to assess the effects of the KD on the nutritional status, resting energy expenditure (REE), and substrate oxidation in patients with drug-resistant epilepsy. Eighteen patients with medically refractory epilepsy underwent assessment of body composition, REE, and substrate oxidation rates before and after 6 months of KD. Compared with baseline, there were no statistically significant differences at 6 months in terms of height, weight, BMI z-scores, and REE. However, the respiratory quotient decreased significantly (from 0.80 ± 0.06 to 0.72 ± 0.05, p < 0.001) whereas fat oxidation was significantly increased (from 50.9 ± 25.2 mg/min to 97.5 ± 25.7 mg/min, p < 0.001). Interestingly, we found that the increase in fat oxidation was the main independent predictor of the reduction in seizure frequency (beta = -0.97, t = -6.3, p < 0.05). Administering a KD for 6 months in patients with medically refractory epilepsy increases fat oxidation and decreases the respiratory quotient, without appreciable changes in REE.
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The ketogenic diet is a therapeutic dietary treatment for epilepsy in children which is resistant to medication. Until recently, evidence for use and resources available has been sparse. This review aims to provide a summary of the evidence supporting its use in children, some guidance towards its implementation and the services currently available in the UK.
Article
Maximal oxygen uptake (VO2 max) and lactate threshold (LT) were measured during graded, incremental exercise in 8 healthy, untrained volunteers (aged 22 +/- 0.9 yrs) following 3 days on a control, mixed diet, or a ketogenic (50% fat, 45% protein and 5% carbohydrates) diet of equal energy content. Before and after exercise tests acid base balance, plasma beta-hydroxybutyrate (beta-HB), free fatty acid (FFA), and some hormone concentrations were determined. In comparison with the normal diet, the ketogenic diet resulted in: an increased VO2 max, decreased respiratory exchange ratio an a shift of LT towards higher exercise loads. Blood LA concentrations were lower before, during and after exercise. Post exercise blood pH, as well as pre-and post exercise base excess and bicarbonates were reduced. Resting beta-HB concentration was elevated to approx. 2.0 mM, and FFA to approx. 1.0 mM. During a 1 h recovery period beta-HB decreased to 0.85 mM (p < 0.01) after the ketogenic diet, while plasma FFA did not change after exercise under either conditions. Both the pre-and post-exercise levels of adrenaline, noradrenaline, and cortisol were enhanced, whilst plasma insulin concentration was decreased on the ketogenic diet. It is concluded that the short-term ketogenic diet does not impair aerobic exercise capacity, as indicated by elevated VO2 max and LT. This may be due to increased utilization of beta-HB and FFA when carbohydrate stores are diminished. Stimulation of the sympatho-adrenal system, and cortisol secretion with reduced plasma insulin concentration seem to be of importance for preservation of working capacity.