ArticlePDF Available

Abstract and Figures

Objectives: To investigate diet-exercise interactions related to bone markers in elite endurance athletes after a 3.5-week ketogenic low-carbohydrate, high-fat (LCHF) diet and subsequent restoration of carbohydrate (CHO) feeding. Methods: World-class race walkers (25 male, 5 female) completed 3.5-weeks of energy-matched (220 kJ·kg·d−1) high CHO (HCHO; 8.6 g·kg·d−1 CHO, 2.1 g·kg·d−1 protein, 1.2 g·kg·d−1 fat) or LCHF (0.5 g·kg·d−1 CHO, 2.1 g·kg·d−1 protein, 75–80% of energy from fat) diet followed by acute CHO restoration. Serum markers of bone breakdown (cross-linked C-terminal telopeptide of type I collagen, CTX), formation (procollagen 1 N-terminal propeptide, P1NP) and metabolism (osteocalcin, OC) were assessed at rest (fasting and 2 h post meal) and after exercise (0 and 3 h) at Baseline, after the 3.5-week intervention (Adaptation) and after acute CHO feeding (Restoration). Results: After Adaptation, LCHF increased fasting CTX concentrations above Baseline (p = 0.007, Cohen's d = 0.69), while P1NP (p < 0.001, d = 0.99) and OC (p < 0.001, d = 1.39) levels decreased. Post-exercise, LCHF increased CTX concentrations above Baseline (p = 0.001, d = 1.67) and above HCHO (p < 0.001, d = 0.62), while P1NP (p < 0.001, d = 0.85) and OC concentrations decreased (p < 0.001, d = 0.99) during exercise. Exercise-related area under curve (AUC) for CTX was increased by LCHF after Adaptation (p = 0.001, d = 1.52), with decreases in P1NP (p < 0.001, d = 1.27) and OC (p < 0.001, d = 2.0). CHO restoration recovered post-exercise CTX and CTX exercise-related AUC, while concentrations and exercise-related AUC for P1NP and OC remained suppressed for LCHF (p = 1.000 compared to Adaptation). Conclusion: Markers of bone modeling/remodeling were impaired after short-term LCHF diet, and only a marker of resorption recovered after acute CHO restoration. Long-term studies of the effects of LCHF on bone health are warranted.
Content may be subject to copyright.
ORIGINAL RESEARCH
published: 21 January 2020
doi: 10.3389/fendo.2019.00880
Frontiers in Endocrinology | www.frontiersin.org 1January 2020 | Volume 10 | Article 880
Edited by:
Gordon L. Klein,
University of Texas Medical Branch at
Galveston, United States
Reviewed by:
Peter Ebeling,
Monash University, Australia
Hasmik Jasmine Samvelyan,
Edinburgh Napier University,
United Kingdom
Craig Sale,
Nottingham Trent University,
United Kingdom
Gustavo A. Nader,
Pennsylvania State University (PSU),
United States
*Correspondence:
Louise M. Burke
louise.burke@ausport.gov.au
These authors have contributed
equally to this work
Specialty section:
This article was submitted to
Bone Research,
a section of the journal
Frontiers in Endocrinology
Received: 04 September 2019
Accepted: 02 December 2019
Published: 21 January 2020
Citation:
Heikura IA, Burke LM, Hawley JA,
Ross ML, Garvican-Lewis L,
Sharma AP, McKay AKA, Leckey JJ,
Welvaert M, McCall L and
Ackerman KE (2020) A Short-Term
Ketogenic Diet Impairs Markers of
Bone Health in Response to Exercise.
Front. Endocrinol. 10:880.
doi: 10.3389/fendo.2019.00880
A Short-Term Ketogenic Diet Impairs
Markers of Bone Health in Response
to Exercise
Ida A. Heikura 1,2† , Louise M. Burke 1,2
*, John A. Hawley 2, Megan L. Ross 1,2 ,
Laura Garvican-Lewis 1,2 , Avish P. Sharma 1, 3, Alannah K. A. McKay 1, 4, Jill J. Leckey 2,
Marijke Welvaert 1,5,6 , Lauren McCall 7and Kathryn E. Ackerman 7,8
1Australian Institute of Sport, Canberra, ACT, Australia, 2Exercise and Nutrition Research Program, Mary MacKillop Institute
for Health Research, Australian Catholic University, Melbourne, VIC, Australia, 3Griffith Sports Physiology and Performance,
School of Allied Health Sciences, Griffith University, Gold Coast, QLD, Australia, 4School of Human Sciences (Exercise and
Sport Science), The University of Western Australia, Crawley, WA, Australia, 5University of Canberra Research Institute for
Sport and Exercise, Canberra, ACT, Australia, 6Statistical Consulting Unit, Australian National University, Canberra, ACT,
Australia, 7Division of Sports Medicine, Boston Children’s Hospital, Boston, MA, United States, 8Neuroendocrine Unit,
Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
Objectives: To investigate diet-exercise interactions related to bone markers in elite
endurance athletes after a 3.5-week ketogenic low-carbohydrate, high-fat (LCHF) diet
and subsequent restoration of carbohydrate (CHO) feeding.
Methods: World-class race walkers (25 male, 5 female) completed 3.5-weeks of
energy-matched (220 kJ·kg·d1) high CHO (HCHO; 8.6 g·kg·d1CHO, 2.1 g·kg·d1
protein, 1.2 g·kg·d1fat) or LCHF (0.5 g·kg·d1CHO, 2.1 g·kg·d1protein, 75–80%
of energy from fat) diet followed by acute CHO restoration. Serum markers of bone
breakdown (cross-linked C-terminal telopeptide of type I collagen, CTX), formation
(procollagen 1 N-terminal propeptide, P1NP) and metabolism (osteocalcin, OC) were
assessed at rest (fasting and 2 h post meal) and after exercise (0 and 3 h) at Baseline,
after the 3.5-week intervention (Adaptation) and after acute CHO feeding (Restoration).
Results: After Adaptation, LCHF increased fasting CTX concentrations above Baseline
(p=0.007, Cohen’s d=0.69), while P1NP (p<0.001, d=0.99) and OC (p<0.001,
d=1.39) levels decreased. Post-exercise, LCHF increased CTX concentrations above
Baseline (p=0.001, d=1.67) and above HCHO (p<0.001, d=0.62), while P1NP
(p<0.001, d=0.85) and OC concentrations decreased (p<0.001, d=0.99) during
exercise. Exercise-related area under curve (AUC) for CTX was increased by LCHF after
Adaptation (p=0.001, d=1.52), with decreases in P1NP (p<0.001, d=1.27)
and OC (p<0.001, d=2.0). CHO restoration recovered post-exercise CTX and CTX
exercise-related AUC, while concentrations and exercise-related AUC for P1NP and OC
remained suppressed for LCHF (p=1.000 compared to Adaptation).
Conclusion: Markers of bone modeling/remodeling were impaired after short-term
LCHF diet, and only a marker of resorption recovered after acute CHO restoration.
Long-term studies of the effects of LCHF on bone health are warranted.
Keywords: ketogenic diet, bone health, exercise, nutrition, endurance athletes
Heikura et al. Ketogenic Diet Impairs Bone Markers
INTRODUCTION
Despite the generally positive effects of exercise in promoting
bone health, bone injuries represent a challenge to consistent
training and competition in high performance sport (1). This, in
part, is due to the interaction of dietary factors (e.g., low energy
availability, poor vitamin D status, inadequate calcium intake)
with unique features of the exercise program [e.g., minimal
or excessive bone loading associated with weight- and non-
weight-bearing sports, poor biomechanics (1,2)]. Low energy
availability (a mismatch between energy intake and the energy
cost of exercise) occurs in both female and male athletes (2)
and impairs bone health via direct (uncoupled bone turnover
with increased resorption rates) and indirect (mediation by
reproductive and metabolic hormones) mechanisms (1). In
addition, carbohydrate (CHO) availability may also play a role
in bone health. Indeed, results from several studies show that
commencing endurance exercise with low compared to normal
or high glycogen availability stimulates the release of the cytokine
interleukin-6 (IL-6) from the exercising muscles (3,4). Among its
range of effects, IL-6 has been hypothesized to lead to enhanced
activity of the receptor activator of the nuclear factor K B-ligand,
which controls bone turnover by increasing osteoclastic activity
(thereby increasing bone breakdown) (5). In support of this
contention, bone resorption is acutely increased when CHO is
restricted before (6), during (7), and after (8) prolonged (1–2 h)
endurance (running) exercise, and may be linked to concomitant
increases in IL-6 concentrations (7). However, a recent study
has reported that acute reductions in CHO availability around
exercise mediated an increase in markers of bone resorption that
are independent of energy availability and circulating IL-6 (9).
Apparent effects on other markers of bone metabolism, such as
osteocalcin (OC) and the bone formation marker procollagen 1
N-terminal propeptide (P1NP) in these models have been small
(69), although a 24 h fast has been reported to reduce blood OC
concentrations in lightweight rowers (10).
Whether these changes in markers of bone metabolism persist
(or are amplified) after chronic exposure to low CHO availability
around exercise remains unknown, but is of relevance in view
of the promotion of a ketogenic low CHO-high fat (LCHF) diet
to athletes and its putative benefits for endurance performance
(11). To date, no studies have examined the effects of longer-
term restriction of CHO at rest or in relation to exercise, although
in animal models and children with intractable epilepsy, chronic
adaptation to a ketogenic LCHF diet is associated with poor bone
health (1216). In view of our recent observations of increased
post-exercise IL-6 concentrations in elite race walkers following
a 3.5-week adaptation to a LCHF diet (17), we investigated
the interaction of this diet and strenuous exercise on markers
of bone modeling/remodeling as secondary outcomes of our
larger study.
METHODS
Participants
Thirty world-class athletes (25 male, 5 female race walkers; ages
27.7 ±3.4 yr, BMI 20.6 ±1.7 kg/m2) were recruited over
three separate training camps during preparation for the 2016
Summer Olympic Games and the 2017 World Championships,
and provided written informed consent in accordance with
the Human Ethics Committee of the Australian Institute of
Sport (ethics approval no. 20150802 and 20161201). Six male
participants undertook two camps, however two of these data
sets were incomplete due to insufficient tissue samples, resulting
in 4 participants who had completed two camps being included
in the final analysis. In addition, two additional (male) data sets
were excluded from the final analysis due to their inability to
complete one of the experimental trials due to injury (unrelated
to bone). Therefore, our final data set provided a total of 32
trials (n=28 participants, 23 males, 5 females) with data for
pre- (Baseline) and post-treatment (Adaptation), of which 18
trials (13 males, 5 females) also contributed to data from acute
restoration to a HCHO diet (Restoration). Participants and elite
coaches contributed to the concept and implementation of the
research camps, helping to prioritize the themes of interest
and contributing to the design of the training program and
test protocols.
Study Overview
Participants completed a 3.5-week block of intensified training
and laboratory and field testing, supported by either a high-
CHO (HCHO) or an isoenergetic LCHF diet (Figure 1,Table 1),
consumed under strict dietary control (18). Upon completion
of the 3.5-week dietary intervention, a subset of participants
(n=18) completed a further testing block under conditions
of acute high CHO availability. Markers of bone metabolism
were measured after an overnight fast, in response to an energy-
matched meal of nutrient composition matching the intervention
diet, and in response to a bout of strenuous exercise (19), at
Baseline, Adaptation, and Restoration (Figure 1).
Dietary Control
Details of dietary control are described briefly here; more details
are described in prior work (18). Participants were allocated
into HCHO and LCHF groups based on preference. Both diets
were isocaloric (Table 1), however dietary CHO and fat intakes
differed between groups during intervention. Study diets were
designed and individualized for each athlete by trained members
of the research team including registered sports dietitians, a
professional chef, and exercise physiologists. All meals were
weighed (food scales accurate to 2 g) and provided for athletes
at set meal times. In addition, a collection of snacks per
individual meal plans were provided to the athletes each day. Any
unconsumed items or changes made to menu plans were weighed
and recorded for final analysis of dietary intakes. Compliance
to the meal plans was assessed daily. Meal plans were designed
and final dietary analysis of actual intakes was conducted using
FoodWorks 8 Professional Program (Xyris Software Australia Pty
Ltd, Australia). Further analysis of intakes was completed using
Microsoft Excel.
Experimental Design
Testing at Baseline, Adaptation, and Restoration involved a
hybrid laboratory/field test of 25 km (males) or 19 km (females)
Frontiers in Endocrinology | www.frontiersin.org 2January 2020 | Volume 10 | Article 880
Heikura et al. Ketogenic Diet Impairs Bone Markers
FIGURE 1 | Study flowchart and overview. Thirty-two data sets were gathered from 30 participants who participated in one or more training camps. After Baseline
testing on a carbohydrate-rich (HCHO) diet, they elected to follow a 3.5-week energy-matched dietary intervention of either HCHO or ketogenic low
carbohydrate-high fat (LCHF) principles. After Adaptation, the participants underwent an acute period of Restoration of high carbohydrate availability. At Baseline and
at the end (Adaptation) of this intervention, as well as after acute carbohydrate reintroduction (Restoration) they undertook a test block including a 25km (2 h) hybrid
laboratory/field race walking protocol at 75% VO2max. Venous blood samples were collected after an overnight fast, 2 h after an energy-matched breakfast based
on their diet (immediately pre-exercise), immediately post exercise and after 3 h of passive recovery during which an intervention-matched recovery shake was
consumed at 30 min. Blood samples were analyzed for serum concentrations of C-terminal telopeptide of type I collagen (CTX), procollagen 1 N-terminal propeptide
(P1NP), and osteocalcin (OC).
Frontiers in Endocrinology | www.frontiersin.org 3January 2020 | Volume 10 | Article 880
Heikura et al. Ketogenic Diet Impairs Bone Markers
TABLE 1 | Dietary intakes in the HCHO and LCHF groups.
Intervention Restoration
HCHO (n=14) LCHF (n=18) HCHO (n=8) LCHF (n=10)
Energy (kJ·d1) 14,518 ±2,142 15,138 ±2,104 13,705 ±1,948 15,706 ±1,774
Energy (kJ·kg·d1) 229 ±13 227 ±23 219 ±16 239 ±27
Protein (g·d1) 133 ±22 143 ±19 132 ±24 151 ±18
Protein (g·kg·d1) 2.1 ±0.2 2.1 ±0.2 2.1 ±0.2 2.3 ±0.2
Fat (g·d1) 74 ±14 318 ±45*** 77 ±14 95 ±12**$$$
Fat (g·kg·d1) 1.2 ±0.1 4.8 ±0.5*** 1.2 ±0.1 1.4 ±0.2**$$$
CHO (g·d1) 549 ±75 35 ±5*** 492 ±60$552 ±62$$$
CHO (g·kg·d1) 8.7 ±0.4 0.5 ±0.1*** 7.9 ±0.6$$ 8.4 ±1.0$$$
HCHO, high carbohydrate diet; LCHF, low carbohydrate high fat diet; CHO, carbohydrate.
**p<0.01, ***p<0.001 significant difference between diets.
$p<0.05, $$p<0.01, $$$ p<0.001 significantly different compared to Intervention.
at around 50 km race pace (75% of maximal oxygen uptake [VO2
max]) (Figure 1). Upon entering the laboratory in an overnight
fasted and rested state between 0600 and 0800 in the morning
(times were kept consistent within-participant), a cannula was
inserted into an antecubital vein for collection of blood samples
at rest (Fasting), immediately before exercise (2 h post-meal),
immediately after exercise (Post-ex) and 3 h post-exercise (3 h
post-ex). Blood was analyzed for concentrations of cross-linked
C-terminal telopeptide of type I collagen (CTX), P1NP and
total OC to determine the effects of dietary interventions and
exercise on bone metabolism. The cannulas were flushed with
3 ml of saline every 30 min throughout the trials. A standardized
breakfast (2 g·kg1CHO for both groups during Baseline
and Restoration, or an isocaloric low CHO option for LCHF
during Adaptation) was consumed 30 min after the first blood
sample, after which the participants rested for 120 min before
beginning the session. During the Baseline and Restoration
exercise test, both groups ingested glucose (60 g·h1) throughout
the test, while during Adaptation, isocaloric high fat snacks
were provided for the LCHF group. Upon completion of the
exercise test, the participants rested in the laboratory for a further
3 h, and received a standardized recovery shake (1.5 g·kg1
CHO for both groups during Baseline and Restoration, or an
isocaloric low CHO option for LCHF during Adaptation; both
shakes included 0.3 g·kg1protein) at 30 min post-exercise to
improve satiety.
Analysis of Serum Bone
Modeling/Remodeling Biomarkers
Blood samples were collected into a 3.5 mL EDTA BD Vacutainer
Plus SST II tube, and allowed to clot by standing at room
temperature for 2 h before centrifuging at 1,000 G for 10 min
for subsequent analysis of serum markers of bone resorption
(CTX), bone formation (P1NP) and overall bone metabolism
(OC). Analysis was undertaken by chemiluminescence on IDS-
iSYS (Immunodiagnostic Systems Limited; Boldon, Tyne and
Wear, UK). Inter-assay coefficient of variation as reported by
the manufacturer was 6.2, 4.6, and 6.1%, respectively. CVs
were determined as follows: OC: 6 serum controls were run,
using 3 reagents lots, in duplicate twice per day for 20 days,
on 2 analyzers; P1NP: 3 serum controls were run, using 3
reagent lots, in quadruplicates once per day for 20 days, on
2 analyzers; CTX: 5 serum controls were run, using 3 reagent
lots, in duplicate twice per day for 20 days, on 3 analyzers. In
addition to these tests, the laboratory ran quality control samples
throughout testing and the results were within the established
acceptable manufacturer ranges. The raw data for the analyses
of serum bone modeling/remodeling markers are provided in the
Supplementary Table to this publication.
Statistical Analyses
Statistical analyses were conducted using SPSS Statistics 22
software (INM, New York, USA) and R (R Core Team, 2018)
with a significance level set at p0.05. Normality of data was
checked with a Shapiro-Wilk test and visual inspection of residual
plots. General Linear Mixed models were fitted using the R
package lme4 (20) and included random intercepts for Subjects
and Camps to account for baseline inter individual heterogeneity
and the partial cross-over design. Because the estimated Camp
effect variance was 0, this random intercept was subsequently
removed to resolve boundary issues in the Restricted Maximum
Likelihood estimation. P-values were obtained using Type II
Wald F tests with Kenward-Roger degrees of freedom. Initial
models included all possible interactions but non-significant
interaction terms were dropped for ease of interpretation. Fasting
values and exercise-related area under curve [AUC; Pre-exercise
to 3 h post-exercise (21)] for all markers were compared with
a two-way mixed analysis of variance (ANOVA), with post-
hoc tests of Student’s t-tests for independent samples (between-
groups) and for paired samples (within-groups); where normality
was violated, Wilcoxon’s test and Mann-Whitney U-test were
used. Where a data point was missing, AUC was not calculated;
this resulted in exclusion of 1 participant in the CTX AUC
calculations, and 2 participants from both P1NP and OC
calculations. Effect sizes were calculated based on the Classical
Cohen’s dwhile accounting for the study design by using the
square root of the sum of all the variance components (specified
random effects and residual error) in the denominator. Data are
presented as means (95% confidence intervals [CI]).
Frontiers in Endocrinology | www.frontiersin.org 4January 2020 | Volume 10 | Article 880
Heikura et al. Ketogenic Diet Impairs Bone Markers
RESULTS
Bone Modeling/Remodeling Biomarkers
During Fasting
Compared to Baseline, fasting concentrations of CTX were
increased after the LCHF diet (+22% [9, 35]: p=0.008, d=0.69),
with a decrease in P1NP (14% [19, 9]; p=0.001, d=0.99)
and OC (25% [35, 14]; p<0.001, d=1.39) levels
(Figure 2). In addition, the change in fasting P1NP (p<0.001,
d=1.64) and OC (p<0.001, d=1.78) after the 3.5-
week intervention was significantly different between the diets
(Figure 2).
Exercise Bone Markers
CTX decreased post-meal independent of dietary intervention
(Figures 3A,4A,p<0.001, d=1.63). At Adaptation, post-
exercise CTX concentrations in LCHF increased above Baseline
(p=0.001, d=1.67) and HCHO (p<0.001, d=0.62)
(Figure 3A). LCHF decreased P1NP (Figure 3B,p<0.001,
d=0.85) and OC across exercise (Figure 3C,p<0.001,
d=0.99) compared to Baseline. At Restoration, post-exercise
CTX returned to Baseline levels for LCHF (Figure 4A,p>0.05,
d=0.20 compared to Baseline), while concentrations of P1NP
(Figure 4B,p<0.001, d=0.23) and OC (Figure 4C,p<0.001,
d=0.21) remained suppressed across exercise.
Bone Marker Exercise Area Under Curve
At Adaptation, LCHF exercise-related AUC for CTX was greater
[+81% (54, 109); p<0.001, d=1.52] than Baseline, and
higher than HCHO (p=0.035, d=0.81) (Figure 3D). Exercise-
related AUC for P1NP decreased at Adaptation for LCHF
[19% (25, 12); p=0.003, d=1.27] compared with
Baseline and was lower than HCHO (p=0.009, d=1.03)
FIGURE 2 | Percentage change in fasting serum C-terminal telopeptide of
type I collagen (CTX), procollagen 1 N-terminal propeptide (P1NP) and
osteocalcin (OC) for high carbohydrate (HCHO; solid bars) and low CHO high
fat (LCHF; striped bars) after the 3.5-week dietary intervention. Data are means
±standard deviations. ***p<0.001 Significant between-group difference;
##p<0.01; ### p<0.001 Significant change from Baseline within-group.
(Figure 3E), with similar outcomes for OC [29% (35, 23);
p<0.001, d=2.0 and p<0.001, d=1.64, Figure 3F]. At
Restoration, LCHF experienced a return of exercise-related AUC
for CTX back to Baseline values [43% (21, 31); p=0.003,
d=1.08 compared to Adaptation and no difference compared
to HCHO; Figure 4D], meanwhile AUC for P1NP [+3% (17,
48), p=1.000 compared to Adaptation and p=0.009, d=1.50
compared to HCHO; Figure 4E], OC [3% (19, 14), p=1.000
compared to Adaptation and p=0.010, d=1.47 compared to
HCHO; Figure 4F] remained suppressed.
DISCUSSION
Our data reveal novel and robust evidence of acute and likely
negative effects on the bone modeling/remodeling process in
elite athletes after a short-term ketogenic LCHF diet, including
increased marker of resorption (at rest and post-exercise) and
decreased formation (at rest and across exercise), with only
partial recovery of these effects following acute restoration of
CHO availability. Long-term effects of such alterations remain
unknown, but may be detrimental to bone mineral density
(BMD) and bone strength, with major consequences to health
and performance. While ketogenic diets are of interest to athletes
due to their ability to induce substantial shifts in substrate
metabolism, increasing the contribution of fat-based fuels during
exercise (11), we have previously reported the downside of a
concomitantly greater oxygen cost and reduced performance of
sustained high-intensity endurance exercise (19). The current
study identifies further complexity in the interaction between
the ketogenic diet and exercise with respect to markers of
bone modeling/remodeling, in which catabolic processes are
augmented and anabolic processes are reduced.
The LCHF diet is also popular within the general community
for its purported health benefits, including rapid weight loss
and improved glycemic control (22). However, data from
animal studies (12,13) demonstrate that chronic LCHF diets
are associated with impaired bone growth, reduced bone
mineral content, compromised mechanical properties, and
slower fracture healing. Furthermore, increased bone loss has
been reported in children with intractable epilepsy placed on
a medically supervised LCHF diet for 6 months (14,15). In
contrast, adults with type 2 diabetes mellitus who self-selected
to consume a LCHF diet for 2 years experienced no changes in
spinal BMD in comparison to a “usual care” group (22). One
explanation for these divergent outcomes involves interactions
of the LCHF diet with the level of habitual contractile activity.
Indeed in mice, a LCHF diet negated the positive benefits of
exercise on BMD in trabecular bone (16), while in children
with epilepsy, the rate of bone loss was greater in the more
active patients (14). Therefore, the hormonal response to exercise
undertaken with low CHO availability was of particular interest
in our study.
Previous studies involving acute strategies of low CHO
availability around exercise have identified effects on bone
resorption, as measured by increased blood CTX concentrations.
For example, males who undertook 60 min of treadmill running
Frontiers in Endocrinology | www.frontiersin.org 5January 2020 | Volume 10 | Article 880
Heikura et al. Ketogenic Diet Impairs Bone Markers
FIGURE 3 | Time course of changes in bone marker concentrations across exercise (left panel) and exercise area under curve (right panel) for serum C-terminal
telopeptide of type I collagen (CTX) (A,D), procollagen 1 N-terminal propeptide (P1NP) (B,E), and osteocalcin (OC) (C,F) after the 3.5-week dietary intervention. Black
bars/symbols represent Baseline, gray bars/symbols represent Adaptation. Squares and circles represent high carbohydrate (HCHO) and low carbohydrate high fat
(LCHF), respectively. Gray bars represent a hybrid laboratory/field 19–25 km walk test at 75% VO2max. Data are means ±standard deviations. ##p<0.01;
###p<0.001 denotes significant differences at time points or tests within diet groups. *p<0.05; **p<0.01; ***p<0.001 denotes significant differences between
diet groups at a specific time point.
at 65% VO2max following a CHO-rich breakfast (1 g·kg1)
showed small variations in CTX responses, but only around the
exercise period, while dietary effects on parathyroid hormone,
OC and P1NP were not detected (6). Meanwhile, a more
strenuous protocol (120 min at 70% VO2max) was associated
with an attenuation of acute (pre-exercise to 2 h post-exercise)
Frontiers in Endocrinology | www.frontiersin.org 6January 2020 | Volume 10 | Article 880
Heikura et al. Ketogenic Diet Impairs Bone Markers
FIGURE 4 | Time course of changes in bone marker concentrations across exercise (left panel) and exercise area under curve (right panel) for serum C-terminal
telopeptide of type I collagen (CTX) (A,D), procollagen 1 N-terminal propeptide (P1NP) (B,E), and osteocalcin (OC) (C,F) after acute reintroduction of carbohydrate
(right panel). Gray bars/symbols represent Adaptation, and white bars/symbols represent Restoration. Squares and circles represent high carbohydrate (HCHO) and
low carbohydrate high fat (LCHF), respectively. Gray bars represent a hybrid laboratory/field 19–25 km walk test at 75% VO2max. Data are means ±standard
deviations. $$p<0.01; $$$ p>0.001 denotes significant within-group difference compared to Restoration. *p<0.05; **p<0.01; ***p<0.001 denotes significant
differences between diet groups at a specific time point.
concentrations of IL-6, CTX, and P1NP when CHO was
consumed (0.7 g·kg·h1) during exercise (7). However, OC was
unchanged by diet and no differences in markers of bone
metabolism were detected over the subsequent three days,
suggesting that these effects are transient and quickly reversed
(7). Short-term effects were also reported when 24 elite male
runners with energy-matched intake over an 8 d period were
divided into a group who consumed CHO before, during, and
Frontiers in Endocrinology | www.frontiersin.org 7January 2020 | Volume 10 | Article 880
Heikura et al. Ketogenic Diet Impairs Bone Markers
immediately after each of their 13 training sessions (additional
total CHO) while the others consumed an artificially sweetened
placebo (23). Here, CTX concentrations were suppressed at
80 min of recovery following an interval training sessions in
the CHO group with no dietary effects on P1NP or OC;
furthermore, fasting concentrations of all markers were similar
at baseline and on the ninth morning (23). Finally, Hammond
and colleagues (9) investigated the independent effects of low
CHO availability and acute energy restriction during the recovery
from one session of high-intensity interval running and the
completion of a subsequent session (3.5 h into recovery). They
reported lower CTX concentrations in the high CHO (control)
diet compared with both of the other conditions across the
various acute responses to exercise-related feeding, while there
were no differences between the energy and CHO restricted trials.
Meanwhile, only energy restriction produced an increase in IL-
6 responses to exercise, and there were no differences in P1NP
concentrations between dietary treatments (9). Furthermore, 5
d of low vs. optimal energy availability, which also resulted in
a 2-fold difference in CHO availability, was shown to result in
a significant difference in the AUC of fasting CTX (+85 vs.
+15%, respectively) and P1NP (60 vs. 25%, respectively)
(24). To date, the only study to report an effect of acute
manipulations of CHO around exercise on bone formation
markers was that of Townsend et al. (8), in which the immediate
consumption of a protein-CHO feeding after a run to exhaustion
at 75% VO2max was associated with a suppression of the post-
exercise rise in CTX levels and a higher concentration of P1NP.
These authors concluded that immediate post-exercise meal
ingestion may benefit bone health compared to delayed feeding,
although the effects on CTX concentrations were reversed at
4 h post-exercise and a similar time course of P1NP changes
was not provided; therefore, it appears that the overall effect
on bone modeling/remodeling processes appears to follow meal
ingestion patterns.
The novelty of the current study was the interrogation of
the effects of prolonged adaptation to CHO restriction on bone
metabolism. Unlike the previous investigations, we identified
clear and consistent effects on bone metabolism at rest and in
response to exercise following 3.5-weeks of a ketogenic LCHF
diet (Figures 24), with increases in a marker of bone resorption
(CTX) and decreases in markers of bone formation (P1NP) and
metabolism (OC). Although some might argue that a complete
adaptation to a LCHF diet requires much longer than the 3.5-
week period utilized in the current study, it should be noted that
adaptations in substrate metabolism and exercise economy have
been reported across this (19,25), and much shorter (26), time
periods. Nevertheless, the current study is reflective of a shorter-
term adaptation to a LCHF diet and our findings warrant further
investigation across longer time periods.
Acute restoration of high CHO availability was only partially
effective in reversing these outcomes. Here, marker of bone
resorption returned to baseline with high CHO pre-exercise meal
and CHO ingestion throughout exercise, while the other markers
of bone metabolism remained suppressed, indicating impaired
overall balance of bone metabolism. This supports the concept
proposed by Hammond et al. (9) that CTX is responsive to acute
intake of CHO, possibly mediated through enteric hormone
secretion. Meanwhile, differences in muscle glycogen content,
which are not addressed by studies of acute feedings, may have a
greater effect on OC and P1NP concentrations. Given the serious
nature of injury risks and long-term outcomes of poor bone
health in later life in endurance athletes, further consideration
of the potential effects of the LCHF diet in exacerbating existing
risk factors for poor bone health is warranted. In particular, we
note that the impairment of bone metabolism around exercise
and recovery would involve a significant portion of the day in
athletes who undertake multiple training sessions, as well as being
superimposed on the changes identified at rest.
The interaction of diet and exercise on bone metabolism is
complex and requires more sophisticated investigation including
replication of the current findings. Furthermore, evolving
knowledge of inter-organ crosstalk suggests that outcomes
of altered bone metabolism may be more far-reaching than
the fate of the structural integrity of bone. Indeed, we note
the recognition of muscle and bone as endocrine organs,
with evidence that IL-6 released from contracting muscle has
autocrine, paracrine and endocrine effects (27). This includes
a purported feed-forward loop in which contraction-induced
stimulation of osteocalcin in myofibers promotes the release of
IL-6 and enhances muscle adaptation to exercise (27). Results
of the current study challenge this synergistic relationship
between osteocalcin signaling and IL-6, and remind us of
the pleiotropic nature of the molecules stimulated by diet-
exercise interactions.
Limitations
The data analysis undertaken in this study was a secondary
outcome of our investigations of the ketogenic LCHF diet;
these were not specifically powered to optimally address the
potential effects on markers of bone modeling/remodeling.
However, the detection of changes in the IL-6 response to
prolonged exercise in our initial study (12) provided motivation
to examine possible downstream effects. Because an identical
protocol was undertaken in two separate studies of the LCHF
diet, we were able to pool data from these investigations to
double the sample size previously known to allow detection of
changes in metabolism and performance. Indeed, changes in
markers of bone metabolism in the response to the interaction
of exercise and the dietary treatments were clearly detected
with the pooled data, but were also identifiable in the case
of the smaller sample size of the carbohydrate restoration
arm of the current dataset. Therefore, we feel confident that
our data are robust and warrant further investigation of
this theme.
CONCLUSIONS
Despite recent interest in the potential benefits of LCHF diets on
endurance performance or metabolic adaptation, the long-term
health effects of this dietary intervention are largely unknown.
We are the first to show that a 3.5-week ketogenic LCHF diet
in elite endurance athletes has negative effects on the markers of
bone modeling/remodeling at rest and during a prolonged high
Frontiers in Endocrinology | www.frontiersin.org 8January 2020 | Volume 10 | Article 880
Heikura et al. Ketogenic Diet Impairs Bone Markers
intensity exercise session. We also show only partial recovery
of these adaptations with acute restoration of CHO availability.
Given the injury risks and long-term outcomes underpinned by
poor bone health in later life, in athletes as well as individuals who
undertake exercise for health benefits, additional investigations
of the ketogenic diet and its role in perturbing bone metabolism
are warranted.
DATA AVAILABILITY STATEMENT
The datasets analyzed for this study were harvested from 2 trials
registered at Australian New Zealand Clinical Trial Registry
(ACTRN12619001015134 and ACTRN12619000794101), found
at: http://www.ANZCTR.org.au/ACTRN12619001015134.aspx
and http://www.ANZCTR.org.au/ACTRN12619000794101.aspx.
ETHICS STATEMENT
The studies involving human participants were reviewed and
approved by Australian Institute of Sport Ethics Committee. The
patients/participants provided their written informed consent to
participate in this study.
AUTHOR CONTRIBUTIONS
Conception and design of the experiments was undertaken
by IH, LB, MR, LG-L, AS, AM, JL, MW, LM, and KA.
Collection, assembly, analysis, and interpretation of data was
undertaken by IH, LB, MR, LG-L, AS, AM, JL, MW, LM,
and KA. Manuscript was prepared by IH, LB, KA, and JH.
All authors approved the final version of the manuscript. IH
and LB had full access to all the data in the study and take
responsibility for the integrity of the data and the accuracy of the
data analysis.
FUNDING
This study was funded by a Program Grant from the
Australian Catholic University Research Funds to Professor LB
(ACURF, 2017000034).
ACKNOWLEDGMENTS
We thank our research colleagues and supporters of the
Supernova research series and acknowledge the commitment of
the elite race-walking community.
SUPPLEMENTARY MATERIAL
The Supplementary Material for this article can be found
online at: https://www.frontiersin.org/articles/10.3389/fendo.
2019.00880/full#supplementary-material
Supplementary Table 1 | Individual data for the serum concentrations of bone
modeling/remodeling markers (CTX, P1NP and Osteocalcin) in response to
strenuous exercise (2 h race walking) and dietary interventions (high carbohydrate
and low carbohydrate high fat diets) in elite race walkers.
REFERENCES
1. Mountjoy M, Sundgot-Borgen J, Burke L, Ackerman KE, Blauwet C,
Constantini N, et al. International Olympic committee (IOC) consensus
statement on relative energy deficiency in sport (RED-S): 2018 update. Int J
Sport Nutr Exerc Metab. (2018) 28:316–31. doi: 10.1123/ijsnem.2018-0136
2. Scofield KL, Hecht S. Bone health in endurance athletes:
runners, cyclists, and swimmers. Curr Sports Med Rep. (2012)
11:328–34. doi: 10.1249/JSR.0b013e3182779193
3. Steensberg A, Febbraio MA, Osada T, Schjerling P, van Hall G, Saltin B, et al.
Interleukin-6 production in contracting human skeletal muscle is influenced
by pre-exercise muscle glycogen content. J Physiol. (2001) 537(Pt 2):633–
9. doi: 10.1111/j.1469-7793.2001.00633.x
4. Keller C, Steensberg A, Pilegaard H, Osada T, Saltin B, Pedersen BK, et al.
Transcriptional activation of the IL-6 gene in human contracting skeletal
muscle: influence of muscle glycogen content. FASEB J. (2001) 15:2748–
50. doi: 10.1096/fj.01-0507fje
5. Lombardi G, Sanchis-Gomar F, Perego S, Sansoni V, Banfi G. Implications
of exercise-induced adipo-myokines in bone metabolism. Endocrine. (2016)
54:284–305. doi: 10.1007/s12020-015-0834-0
6. Scott JP, Sale C, Greeves JP, Casey A, Dutton J, Fraser WD. Effect of fasting
versus feeding on the bone metabolic response to running. Bone. (2012)
51:990–9. doi: 10.1016/j.bone.2012.08.128
7. Sale C, Varley I, Jones TW, James RM, Tang JC, Fraser WD, et al. Effect
of carbohydrate feeding on the bone metabolic response to running. J Appl
Physiol. (2015) 119:824–30. doi: 10.1152/japplphysiol.00241.2015
8. Townsend R, Elliott-Sale KJ, Currell K, Tang J, Fraser WD, Sale C. The effect
of postexercise carbohydrate and protein ingestion on bone metabolism. Med
Sci Sports Exerc. (2017) 49:1209–18. doi: 10.1249/MSS.0000000000001211
9. Hammond KM, Sale C, Fraser W, Tang J, Shepherd SO, Strauss JA, et al. Post-
exercise carbohydrate and energy availability induce independent effects on
skeletal muscle cell signalling and bone turnover: implications for training
adaptation. J Physiol. (2019) 597:4779–96. doi: 10.1113/JP278209
10. Talbott SM, Shapses SA. Fasting and energy intake influence bone
turnover in lightweight male rowers. Int J Sport Nutr. (1998) 8:377–
87. doi: 10.1123/ijsn.8.4.377
11. Volek JS, Noakes T, Phinney SD. Rethinking fat as a fuel for endurance
exercise. Eur J Sport Sci. (2015) 15:13–20. doi: 10.1080/17461391.2014.
959564
12. Bielohuby M, Matsuura M, Herbach N, Kienzle E, Slawik M, Hoeflich A, et al.
Short-term exposure to low-carbohydrate, high-fat diets induces low bone
mineral density and reduces bone formation in rats. J Bone Miner Res. (2010)
25:275–84. doi: 10.1359/jbmr.090813
13. Scheller EL, Khoury B, Moller KL, Wee NK, Khandaker S, Kozloff
KM, et al. Changes in skeletal integrity and marrow adiposity
during high-fat diet and after weight loss. Front Endocrinol. (2016)
7:102. doi: 10.3389/fendo.2016.00102
14. Simm PJ, Bicknell-Royle J, Lawrie J, Nation J, Draffin K, Stewart KG, et al. The
effect of the Ketogenic diet on the developing skeleton. Epilepsy Res. (2017)
136:62–6. doi: 10.1016/j.eplepsyres.2017.07.014
15. Bergqvist AG, Schall JI, Stallings VA, Zemel BS. Progressive bone
mineral content loss in children with intractable epilepsy treated with the
Ketogenic diet. Am J Clin Nutr. (2008) 88:1678–84. doi: 10.3945/ajcn.2008.
26099
16. Scott MC, Fuller SE, Watt JD, Osborn ML, Johannsen N, Irving BA, et al.
Cortical and trabecular bone morpohology in response to exercise and a
Ketogenic diet: 2712 Board #4 May 31 1:00 PM - 3:00 PM. Med Sci Sports
Exerc. (2019) 51:755–6. doi: 10.1249/01.mss.0000562752.04493.10
Frontiers in Endocrinology | www.frontiersin.org 9January 2020 | Volume 10 | Article 880
Heikura et al. Ketogenic Diet Impairs Bone Markers
17. McKay AKA, Peeling P, Pyne DB, Welvaert M, Tee N, Leckey JJ, et al. Chronic
adherence to a ketogenic diet modifies iron metabolism in elite athletes. Med
Sci Sports Exerc. (2019) 51:548–55. doi: 10.1249/MSS.0000000000001816
18. Mirtschin JG, Forbes SF, Cato LE, Heikura IA, Strobel N, Hall R, et al.
Organization of dietary control for nutrition-training intervention
involving periodized carbohydrate availability and ketogenic low-
carbohydrate high-fat diet. Int J Sport Nutr Exerc Metab. (2018)
28:480–9. doi: 10.1123/ijsnem.2017-0249
19. Burke LM, Ross ML, Garvican-Lewis LA, Welvaert M, Heikura IA, Forbes
SG, et al. Low carbohydrate, high fat diet impairs exercise economy and
negates the performance benefit from intensified training in elite race walkers.
J Physiol. (2017) 595:2785–807. doi: 10.1113/JP273230
20. Bates D, Maechler M, Bolker B, Walker S. Fitting linear mixed-effects models
using lme4. J Stat Softw. (2015) 67:1–48. doi: 10.18637/jss.v067.i01
21. Matthews JNS, Altman DG, Campbell MJ, Royston P. Analysis of
serial measurements in medical research. Br Med J. (1990) 300:230–
5. doi: 10.1136/bmj.300.6719.230
22. Athinarayanan SJ, Adams RN, Hallberg SJ, McKenzie AL, Bhanpuri NH,
Campbell WW, et al. Long-term effects of a novel continuous remote care
intervention including nutritional lchfsis for the management of type 2
diabetes: a 2-year non-randomized clinical trial. Front Endocrinol. (2019)
10:348. doi: 10.3389/fendo.2019.00348
23. de Sousa MV, Pereira RM, Fukui R, Caparbo VF, da Silva ME. Carbohydrate
beverages attenuate bone resorption markers in elite runners. Metabolism.
(2014) 63:1536–41. doi: 10.1016/j.metabol.2014.08.011
24. Papageorgiou M, Elliott-Sale K, Parsons A, Tang JCY, Greeves JP, Fraser
WD, et al. Effects of reduced energy availability on bone metabolism
in women and men. Bone. (2017) 115:191–9. doi: 10.1016/j.bone.2017.
08.019
25. Shaw DM, Merien F, Braakhuis A, Maunder ED, Dulson DK. Effect of a
ketogenic diet on submaximal exercise capacity and efficiency in runners. Med
Sci Sports Exerc. (2019) 51:2135–46. doi: 10.1249/MSS.0000000000002008
26. Burke LM, Angus DJ, Cox GR, Cummings NK, Febbraio MA, Gawthorn K,
et al. Effect of fat adaptation and carbohydrate restoration on metabolism
and performance during prolonged cycling. J Appl Physiol. (2000) 89:2413–21.
doi: 10.1152/jappl.2000.89.6.2413
27. Karsenty G, Mera P. Molecular bases of the crosstalk between bone and
muscle. Bone. (2018) 115:43–9. doi: 10.1016/j.bone.2017.04.006
Conflict of Interest: The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could be construed as a
potential conflict of interest.
Copyright © 2020 Heikura, Burke, Hawley, Ross, Garvican-Lewis, Sharma, McKay,
Leckey, Welvaert, McCall and Ackerman. This is an open-access article distributed
under the terms of the Creative Commons Attribution License (CC BY). The use,
distribution or reproduction in other forums is permitted, provided the original
author(s) and the copyright owner(s) are credited and that the original publication
in this journal is cited, in accordance with accepted academic practice. No use,
distribution or reproduction is permitted which does not comply with these terms.
Frontiers in Endocrinology | www.frontiersin.org 10 January 2020 | Volume 10 | Article 880
... This hypothesis has substantial implications for investigating the protective potential of nutritional factors on exercise-induced bone catabolism. Indeed, available research suggests that strategies such as acute calcium supplementation [15,16] and attention to adequate energy and carbohydrate availability [17,18] can attenuate exercise-induced increases in the bone resorption marker CTX-1. These strategies are also considered key to protecting longer-term bone health [4]. ...
... Six additional articles were identified during forward citation screening, bringing the total to 22 articles [15-18, 26, 29-45], comprising 502 participants (337 male and 165 female). Of these, three investigated feeding status or energy availability (outcome 1) (17,35,36), eight macronutrients (outcome 2) [17,18,30,[36][37][38][39][40], eight micronutrients (all calcium-outcome 3) [15,16,26,29,[41][42][43][44] and six investigated other interventions, namely dairy products [33,34] or collagen [30][31][32]45] (outcome 4). Two studies included both a low energy and a low-carbohydrate/high-fat condition [17,36] and were included in both outcome categories 1 (feeding status and energy availability) and 2 (macronutrients). ...
... The supplemental macronutrients were carbohydrate [37][38][39], a protein/ carbohydrate mix [40] or whey protein [30,39]. The other three manipulated dietary carbohydrate and fat composition [17,18,36]. Standardised mean effect sizes are presented in Fig. 3, and further information on the characteristics, design and primary findings from each study are presented in Online Resource 2, Table S2 (see the electronic supplementary material). ...
Article
Full-text available
Background Although nutrition and exercise both influence bone metabolism, little is currently known about their interaction, or whether nutritional intervention can modulate the bone biomarker response to acute exercise. Improved understanding of the relationships between nutrition, exercise and bone metabolism may have substantial potential to inform nutritional interventions to protect the bone health of exercising individuals, and to elucidate mechanisms by which exercise and nutrition influence bone. Objective The aim was to synthesise available evidence related to the influence of nutrition on the response of the bone biomarkers procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX-1) to acute exercise, using a systematic review and meta-analytic approach. Methods Studies evaluating the influence of nutritional status or intervention on the bone biomarker response to an acute exercise bout were included and separated into four categories: (1) feeding status and energy availability, (2) macronutrients, (3) micronutrients and (4) other. Studies conducted on healthy human populations of any age or training status were included. Meta-analysis was conducted when data from at least five studies with independent datasets were available. In the case of insufficient data to warrant meta-analysis, results from individual studies were narratively synthesised and standardised mean effect sizes visually represented. Results Twenty-two articles were included. Of these, three investigated feeding status or energy availability, eight macronutrients, eight micronutrients (all calcium) and six other interventions including dairy products or collagen supplementation. Three studies had more than one intervention and were included in all relevant outcomes. The largest and most commonly reported effects were for the bone resorption marker CTX-1. Meta-analysis indicated that calcium intake, whether provided via supplements, diet or infusion, reduced exercise-induced increases in CTX-1 (effect size − 1.1; 95% credible interval [CrI] − 2.2 to − 0.05), with substantially larger effects observed in studies that delivered calcium via direct infusion versus in supplements or foods. Narrative synthesis suggests that carbohydrate supplementation may support bone during acute exercise, via reducing exercise-induced increases in CTX-1. Conversely, a low-carbohydrate/high-fat diet appears to induce the opposite effect, as evidenced by an increased exercise associated CTX-1 response, and reduced P1NP response. Low energy availability may amplify the CTX-1 response to exercise, but it is unclear whether this is directly attributable to energy availability or to the lack of specific nutrients, such as carbohydrate. Conclusion Nutritional intervention can modulate the acute bone biomarker response to exercise, which primarily manifests as an increase in bone resorption. Ensuring adequate attention to nutritional factors may be important to protect bone health of exercising individuals, with energy, carbohydrate and calcium availability particularly important to consider. Although a wide breadth of data were available for this evidence synthesis, there was substantial heterogeneity in relation to design and intervention characteristics. Direct and indirect replication is required to confirm key findings and to generate better estimates of true effect sizes.
... Esto repercute a su vez en la salud de los huesos ya que hay estudios que muestran como los marcadores serológicos de la salud ósea se ven alterados por el uso de la dieta cetogénica en cortos periodos de tiempo. Este aspecto es de vital importancia principalmente en deportes de resistencia y en aquellos en los que pueda aparecer de forma habitual la triada del deportista (23). Para acabar con esta dieta, mencionar la dificultad que la población suele encontrar en seguir esta dieta tan restrictiva en comparación otras como la dieta mediterránea (24). ...
... Salud ósea: Heikura et al. (23) encuentran que una dieta cetogénica a corto plazo puede afectar negativamente los marcadores de salud ósea. Lo que destaca la importancia de considerar los efectos a largo plazo de este tipo de dieta para la salud de los huesos del deportista. ...
Article
El objetivo de este trabajo es elaborar una guía alimentaria específicamente diseñada para nadadores de velocidad, para ayudarlos a seleccionar una nutrición adecuada que potencie su rendimiento. Revisión bibliográfica de la literatura científica de los últimos cinco años gracias al empleo de los buscadores bibliográficos. Consecuentemente, se encontraron 33 estudios relevantes, los cuales fueron analizados por su relevancia científica hacia el tema. El conjunto de estudios señala que las dietas analizadas (dieta Mediterránea, dieta Cetogénica, dieta alta en hidratos y dieta de ayuno intermitente) por lo general mejoran el rendimiento. Sin embargo, en el caso de la natación de velocidad solo la dieta Mediterránea y la dieta alta en hidratos muestran unos datos favorables, puesto que las otras dos muestran que la mejora en el rendimiento se da a intensidades bajas 65% del consumo máximo de oxígeno (VO2 Máx.) en mujeres y 80% del VO2 Máx. en hombres. Debido a las necesidades metabólicas de los nadadores de velocidad tanto la dieta Mediterránea como la dieta alta en hidratos de carbono son adecuadas para mejorar su rendimiento. No obstante, a largo plazo la dieta alta en hidratos puede ser perjudicial para la salud en comparación con una dieta equilibrada.
... 1 An expert analysis in 2020 by the American College of Cardiology suggested that endurance athletes consuming a diet rich in unsaturated fats and plant-based proteins may consider adopting a ketogenic diet to meet performance goals. 56 However, concerns have also been raised on how ketogenic diets and ketone supplements may impair exercise performance by reducing exercise economy or inducing side effects, 11,27 and a review published in 2015 concluded that there were no clear performance advantages of ketogenic diets. 9 Moreover, athletes playing different types of sports may have different needs to improve performance, and therefore the effects of ketogenic diets and ketone supplements on specific types of sports may be different. ...
Article
Context: Ketogenic diets and ketone supplements have gained popularity among endurance runners given their purported effects: potentially delaying the onset of fatigue by enabling the increased utilization of the body's fat reserve or external ketone bodies during prolonged running. Objective: This systematic review was conducted to evaluate the effects of ketogenic diets (>60% fat and <10% carbohydrates/<50 g carbohydrates per day) or ketone supplements (ketone esters or ketone salts, medium-chain triglycerides or 1,3-butadiol) on the aerobic performance of endurance runners. Data sources: A systematic search was conducted in PubMed, Web of Science, Pro Quest, and Science Direct for publications up to October 2023. Study selection: Human studies on the effects of ketogenic diets or ketone supplements on the aerobic performance of adult endurance runners were included after independent screening by 2 reviewers. Study design: Systematic review. Level of evidence: Level 3. Data extraction: Primary outcomes were markers of aerobic performance (maximal oxygen uptake [VO2max], race time, time to exhaustion and rate of perceived exertion). Results: VO2max was assessed by incremental test to exhaustion. Endurance performance was assessed by time trials, 180-minute running trials, or run-to-exhaustion trials; 5 studies on ketogenic diets and 7 studies on ketone supplements involving a total of 132 endurance runners were included. Despite the heterogeneity in study design and protocol, none reported benefits of ketogenic diets or ketone supplements on selected markers of aerobic performance compared with controls. Reduction in bodyweight and fat while preserving lean mass and improved glycemic control were reported in some included studies on ketogenic diets. Conclusion: This review did not identify any significant advantages or disadvantages of ketogenic diets or ketone supplements for the aerobic performance of endurance runners. Further trials with larger sample sizes, more gender-balanced participants, longer ketogenic diet interventions, and follow-up on metabolic health are warranted.
... It has also been proposed that low carbohydrate availability may play a role in the development of REDs and related outcomes (Stellingwerff et al., 2021). Race walkers achieving adequate EA but subjected to carbohydrate restriction (<50 g carbohydrates per day) for 3.5 weeks were found to have impaired bone remodeling (Heikura et al., 2019) and both adequate EA and carbohydrate intake have been shown to be necessary to support bone formation at rest (Fensham et al., 2022). In recent years, continuous glucose monitors (CGMs) have been used in healthy endurance athletes to assess individualization of fuelling strategies (Podlogar & Wallis, 2022), and this same technology may potentially assist in a greater understanding of the interplay between LEA, low carbohydrate availability, and the development of REDs (Bowler et al., 2023). ...
Article
Full-text available
This study aimed to determine energy availability (EA) and within-day energy balance (WDEB) in female soccer players during preseason and also explored eating disorder risk and athlete food choice. We hypothesized commonly used indicators of low energy availability (LEA) risk would correlate with measured EA and WDEB variables, and that food choice determinants would differ according to EA. Eleven National Premier League female soccer players participated in this observational cross-sectional study over 3 weeks. Assessment of resting metabolic rate and physique traits, including bone mineral density, was conducted during Weeks 1 or 3. During Week 2, dietary intake, energy expenditure, and continuous monitor-derived glucose were measured for 5 days. EA was calculated daily and WDEB calculated hourly with deficits/surpluses carried continuously. Questionnaires were administered throughout the 3 weeks, including the Athlete Food Choice Questionnaire, the Eating Disorders Screen for Athletes, and the Low Energy Availability in Females Questionnaire. Resting metabolic rate ratio, bone mineral density, Low Energy Availability in Females Questionnaire, and Eating Disorders Screen for Athletes scores were used as indicators of LEA risk. EA averaged 30.7 ± 7.5 kcals·kg fat-free mass ⁻¹ ·day ⁻¹ . Approximately one-third (36%) of athletes were at risk of an eating disorder, while approximately half (45%) were identified at risk of the female athlete triad via Low Energy Availability in Females Questionnaire, compared with approximately one-third (36%) of athletes identified with EA < 30 kcal·kg fat-free mass ⁻¹ ·day ⁻¹ . No athlete achieved EA >45 kcal·kg fat-free mass ⁻¹ ·day ⁻¹ , and no indicator of LEA risk was associated with calculated EA or WDEB. However, overnight glycemic variability was positively correlated with measured EA ( r = .722, p = .012).
... While outside the scope of this work, evidence in support for a modulatory role of interleukin-6 (IL-6) in regulation of acute markers of bone metabolism is provided from several studies. For example, when exercising in conditions of CHO restriction (Heikura et al. 2019) or with low muscle glycogen (Keller et al. Fig. 2 Plasma βCTX (A), PINP (C), PTH (E) concentrations before, during and after training. ...
Article
Full-text available
Purpose To test the hypothesis that training with reduced carbohydrate (CHO) availability increases bone resorption in adolescent soccer players. Methods In a randomised crossover design, ten male players (age: 17.4 ± 0.8 years) from an English Premier League academy completed an acute 90-min field-based training session (occurring between 10:30–12:00) in conditions of high (TRAIN HIGH; 1.5 g.kg⁻¹, 60 g, 1.5 g.kg⁻¹ and 1.5 g.kg⁻¹ consumed at 08:00, during training, 12:30 and 13:30, respectively) or low CHO availability (TRAIN LOW; 0 g.kg⁻¹). Participants also completed a non-exercise trial (REST) under identical dietary conditions to TRAIN LOW. Venous blood samples were obtained at 08:30, 10:30, 12:30 and 14:30 for assessment of bone resorption (βCTX), bone formation (PINP) and calcium metabolism (PTH and ACa). Results External training load did not differ (all P > 0.05) between TRAIN HIGH and TRAIN LOW, as evident for total distance (5.6 ± 0.8; 5.5 ± 0.1 km), average speed (81 ± 9; 85 ± 12 m.min⁻¹) and high-speed running (350 ± 239; 270 ± 89 m). Area under the curve for both βCTX and PINP was significantly greater (P < 0.01 and P = 0.03) in TRAIN LOW versus TRAIN HIGH, whilst no differences in PTH or ACa (P = 0.11 and P = 0.89) were observed between all three trials. Conclusion CHO restriction before, during and after an acute soccer training session increased bone (re)modelling markers in academy players. Despite acute anabolic effects of bone formation, the long-term consequence of bone resorption may impair skeletal development and increase injury risk during growth and maturation.
... Previous research has consistently shown the importance of social dynamics within sports teams in shaping athletes' behaviors and perceptions, particularly regarding nutrition. Studies have identified that peer influences, team norms, and social identity processes are key in determining athletes' dietary choices and adherence to nutrition plans [84,85]. ...
Article
Full-text available
(1) Background: This qualitative study explores Division III college student-athletes’ experiences and perceptions of personalized nutrition plans in collegiate sports settings. (2) Methods: Semi-structured interviews were conducted using a general qualitative research design. Using a grounded theory approach, a thematic analysis was utilized to analyze the interview transcripts, allowing for the identification of recurring themes and patterns. (3) Results: A total of 30 Division III college student-athletes, 16 males (53.3%) and 14 females (46.7%), representing a diverse range of sports disciplines, engaged in discussions about personalized nutrition plans. Analysis of the data revealed five main themes: (1) Nutritional Knowledge and Awareness, (2) Perceived Benefits of Personalized Nutrition Plans, (3) Challenges and Barriers to Implementation, (4) Influence of Team Culture and Environment, and (5) Suggestions for Improvement. (4) Conclusion: This study sheds light on the complexities of implementing personalized nutrition plans in collegiate sports settings and emphasizes the need for comprehensive, athlete-centered approaches to optimize performance and well-being.
Chapter
V tretjem in četrtem modulu Adolescentne medicine smo povzeli aktualne vsebine pomembne za zdravnike in druge zdravstvene delavce, ki se pri svojem delu srečujejo z mladostniki in mladimi odraslimi. Uspešno vključevanje in ustrezna uporaba zdravstvenega sistema je med ključnimi dejavniki za zdrav razvoj mladostnikov. Zato je zdravstveno opismenjevanje pomembna naloga zdravstvenih delavcev, zdravstvenega sistema in celotne družbe. Poznavanje etičnih in pravnih vidikov pravic in odgovornosti mladostnikov ter staršev znatno prispeva k varni zdravstveni obravnavi. Iskanje spolne identitete in skrb za spolno zdravje predstavlja mladostnikom poseben izziv. Ozaveščeni zdravstveni delavci lahko z ustreznim preventivnim delovanjem in primernim pristopom znatno razbremenijo mladostnike stisk povezanih s spolnim razvojem in spolnim življenjem. Različne oblike nasilja med mladimi ter kemične in ne kemične zasvojenosti so aktualen družbeni pojav. V učbeniku so predstavljeni mehanizmi, vzroki, posledice in različni pristopi k zdravljenju in zmanjševanju bremena odvisnosti in nasilja med mladostniki. Preventivno zdravstveno varstvo za otroke in mladostnike ima v Sloveniji bogato tradicijo in odlične rezultate. Predstavljeni sta organizacija preventivnega zdravstvenega varstva za šolske otroke in mladostnike ter študente. Bralcem naše publikacije želimo uspešno delo z mladimi.
Article
Full-text available
Bone health encompasses not only bone mineral density but also bone architecture and mechanical properties that can impact bone strength. While specific dietary interventions have been proposed to treat various diseases such as obesity and diabetes, their effects on bone health remain unclear. The aim of this review is to examine literature published in the past decade, summarize the effects of currently popular diets on bone health, elucidate underlying mechanisms, and provide solutions to neutralize the side effects. The diets discussed in this review include a ketogenic diet (KD), a Mediterranean diet (MD), caloric restriction (CR), a high-protein diet (HP), and intermittent fasting (IF). Although detrimental effects on bone health have been noticed in the KD and CR diets, it is still controversial, while the MD and HP diets have shown protective effects, and the effects of IF diets are still uncertain. The mechanism of these effects and the attenuation methods have gained attention and have been discussed in recent years: the KD diet interrupts energy balance and calcium metabolism, which reduces bone quality. Ginsenoside-Rb2, metformin, and simvastatin have been shown to attenuate bone loss during KD. The CR diet influences energy imbalance, glucocorticoid levels, and adipose tissue, causing bone loss. Adequate vitamin D and calcium supplementation and exercise training can attenuate these effects. The olive oil in the MD may be an effective component that protects bone health. HP diets also have components that protect bone health, but their mechanism requires further investigation. In IF, animal studies have shown detrimental effects on bone health, while human studies have not. Therefore, the effects of diets on bone health vary accordingly.
Article
Full-text available
Key points Reduced carbohydrate (CHO) availability before and after exercise may augment endurance training‐induced adaptations of human skeletal muscle, as mediated via modulation of cell signalling pathways. However, it is not known whether such responses are mediated by CHO restriction, energy restriction or a combination of both. In recovery from a twice per day training protocol where muscle glycogen concentration is maintained within 200–350 mmol kg⁻¹ dry weight (dw), we demonstrate that acute post‐exercise CHO and energy restriction (i.e. < 24 h) does not potentiate potent cell signalling pathways that regulate hallmark adaptations associated with endurance training. In contrast, consuming CHO before, during and after an acute training session attenuated markers of bone resorption, effects that are independent of energy availability. Whilst the enhanced muscle adaptations associated with CHO restriction may be regulated by absolute muscle glycogen concentration, the acute within‐day fluctuations in CHO availability inherent to twice per day training may have chronic implications for bone turnover. Abstract We examined the effects of post‐exercise carbohydrate (CHO) and energy availability (EA) on potent skeletal muscle cell signalling pathways (regulating mitochondrial biogenesis and lipid metabolism) and indicators of bone metabolism. In a repeated measures design, nine males completed a morning (AM) and afternoon (PM) high‐intensity interval (HIT) (8 × 5 min at 85% V̇O2 peak ) running protocol (interspersed by 3.5 h) under dietary conditions of (1) high CHO availability (HCHO: CHO ∼12 g kg⁻¹, EA∼ 60 kcal kg⁻¹ fat free mass (FFM)), (2) reduced CHO but high fat availability (LCHF: CHO ∼3 (⁻¹, EA∼ 60 kcal kg⁻¹ FFM) or (3), reduced CHO and reduced energy availability (LCAL: CHO ∼3 g kg⁻¹, EA∼ 20 kcal kg⁻¹ FFM). Muscle glycogen was reduced to ∼200 mmol kg⁻¹ dw in all trials immediately post PM HIT (P < 0.01) and remained lower at 17 h (171, 194 and 316 mmol kg⁻¹ dw) post PM HIT in LCHF and LCAL (P < 0.001) compared to HCHO. Exercise induced comparable p38MAPK phosphorylation (P < 0.05) immediately post PM HIT and similar mRNA expression (all P < 0.05) of PGC‐1α, p53 and CPT1 mRNA in HCHO, LCHF and LCAL. Post‐exercise circulating βCTX was lower in HCHO (P < 0.05) compared to LCHF and LCAL whereas exercise‐induced increases in IL‐6 were larger in LCAL (P < 0.05) compared to LCHF and HCHO. In conditions where glycogen concentration is maintained within 200–350 mmol kg⁻¹ dw, we conclude post‐exercise CHO and energy restriction (i.e. < 24 h) does not potentiate cell signalling pathways that regulate hallmark adaptations associated with endurance training. In contrast, consuming CHO before, during and after HIT running attenuates bone resorption, effects that are independent of energy availability and circulating IL‐6.
Article
Full-text available
Purpose: Studies on long-term sustainability of low-carbohydrate approaches to treat diabetes are limited. We previously reported the effectiveness of a novel digitally-monitored continuous care intervention (CCI) including nutritional ketosis in improving weight, glycemic outcomes, lipid, and liver marker changes at 1 year. Here, we assess the effects of the CCI at 2 years.Materials and methods: An open label, non-randomized, controlled study with 262 and 87 participants with T2D were enrolled in the CCI and usual care (UC) groups, respectively. Primary outcomes were retention, glycemic control, and weight changes at 2 years. Secondary outcomes included changes in body composition, liver, cardiovascular, kidney, thyroid and inflammatory markers, diabetes medication use and disease status.Results: Reductions from baseline to 2 years in the CCI group resulting from intent-to-treat analyses included: HbA1c, fasting glucose, fasting insulin, weight, systolic blood pressure, diastolic blood pressure, triglycerides, and liver alanine transaminase, and HDL-C increased. Spine bone mineral density in the CCI group was unchanged. Use of any glycemic control medication (excluding metformin) among CCI participants declined (from 55.7 to 26.8%) including insulin (-62%) and sulfonylureas (-100%). The UC group had no changes in these parameters (except uric acid and anion gap) or diabetes medication use. There was also resolution of diabetes (reversal, 53.5%; remission, 17.6%) in the CCI group but not in UC. All the reported improvements had p < 0.00012.Conclusion: The CCI group sustained long-term beneficial effects on multiple clinical markers of diabetes and cardiometabolic health at 2 years while utilizing less medication. The intervention was also effective in the resolution of diabetes and visceral obesity with no adverse effect on bone health.Clinical Trial Registration:Clinicaltrials.gov NCT02519309
Article
Full-text available
Purpose: The short-term restriction of carbohydrate (CHO) can potentially influence iron regulation via modification of post-exercise interleukin-6 (IL-6) and hepcidin levels. This study examined the impact of a chronic ketogenic low CHO-high fat (LCHF) diet on iron status and iron-regulatory markers in elite athletes. Methods: International-level race walkers (n=50) were allocated to one of three dietary interventions; i) a high CHO diet (HCHO; n=16), ii) periodized CHO availability (PCHO; n=17) or iii) a LCHF diet (n=17) while completing a periodized training program for 3 weeks. A 19-25 km race walking test protocol was completed at baseline and following adaptation, and changes in serum ferritin, IL-6 and hepcidin concentrations were measured. Results from HCHO and PCHO were combined into one group (CHO; n=33) for analysis. Results: The decrease in serum ferritin across the intervention period was substantially greater in the CHO group (37%) compared to the LCHF (23%) group (p=0.021). After dietary intervention, the post-exercise increase in IL-6 was greater in LCHF (13.6-fold increase; 95% CI 7.1-21.4), than athletes adhering to a CHO-rich diet (7.6-fold increase; 5.5-10.2; p=0.033). While no significant differences occurred between diets, confidence intervals indicate 3 h post-exercise hepcidin concentrations were lower after dietary intervention compared to baseline in CHO (β=-4.3; -6.6, -2.0), with no differences evident in LCHF. Conclusion: Athletes who adhered to a CHO-rich diet experienced favorable changes to the post-exercise IL-6 and hepcidin response, relative to the LCHF group. Lower serum ferritin after 3 weeks of additional dietary CHO might reflect a larger more adaptive hematological response to training.
Article
Purpose: We investigated the effect of a 31-d ketogenic diet (KD) on submaximal exercise capacity and efficiency. Methods: A repeated-measures, crossover study with preintervention and postintervention outcomes was conducted in eight trained male endurance athletes (maximal oxygen uptake (V[Combining Dot Above]O2max), 59.4 ± 5.2 mL⋅kg⋅min). Participants ingested their habitual diet (HD) (43% ± 8% carbohydrate and 38% ± 7% fat) or an isoenergetic KD (4% ± 1% carbohydrate and 78% ± 4% fat) from days 0 to 31 (P < 0.001). On days -2 and 29, participants undertook a fasted graded metabolic test (~25 min), and on days 0 and 31, participants completed a run-to-exhaustion trial at 70% of their V[Combining Dot Above]O2max (~12.9 km⋅h) after the ingestion of a high-carbohydrate meal (2 g⋅kg) or an isoenergetic low-carbohydrate, high-fat meal, with carbohydrate (~55 g⋅h) or isoenergetic fat (coconut oil) supplementation during exercise. Results: Training load did not differ between trials, and there was no effect of diet on V[Combining Dot Above]O2max (all, P > 0.05). The KD impaired exercise efficiency, particularly at >70% V[Combining Dot Above]O2max, as evident by oxygen uptake that could not be explained by shifts in RER and increased energy expenditure (all, P < 0.05). However, exercise efficiency was maintained on a KD when exercising at <60% V[Combining Dot Above]O2max (all, P > 0.05). There was no effect of diet on time-to-exhaustion (237 ± 44 min (pre-HD) vs 231 ± 35 min (post-HD), P = 0.44; 239 ± 27 min (pre-KD) vs 219 ± 53 min (post-KD), P = 0.36). Conclusion: A 31-d KD can preserve submaximal exercise capacity in trained endurance athletes; however, endurance variability increases.
Article
We describe the implementation of a 3-week dietary intervention in elite race walkers at the Australian Institute of Sport, with a focus on the resources and strategies needed to accomplish a complex study of this scale. Interventions involved: traditional guidelines of high carbohydrate (CHO) availability for all training sessions (HCHO); a periodized CHO diet which integrated sessions with low CHO and high CHO availability within the same total CHO intake, and a ketogenic low-CHO high-fat diet (LCHF). 7-day menus and recipes were constructed for a communal eating setting to meet nutritional goals as well as individualized food preferences and special needs. Menus also included nutrition support pre, during and post-exercise. Daily monitoring, via observation and food checklists, showed that energy and macronutrient targets were achieved: diets were matched for energy (~14.8 MJ/d) and protein (~2.1 g.kg/d), and achieved desired differences for fat and CHO: HCHO and PCHO: CHO = 8.5 g/kg/d, 60% energy; fat = 20% of energy; LCHF: 0.5 g/kg/d CHO, fat = 78% energy. There were no differences in micronutrient intakes or density between HCHO and PCHO diets; however, the micronutrient density of LCHF was significantly lower. Daily food costs per athlete were similar for each diet (~AUDS$27 ± 10). Successful implementation and monitoring of dietary interventions in sports nutrition research of the scale of the present study require meticulous planning and the expertise of chefs and sports dietitians. Different approaches to sports nutrition support raise practical challenges around cost, micronutrient density, accommodation of special needs and sustainability.
Article
Background: The short-term effects of low energy availability (EA) on bone metabolism in physically active women and men are currently unknown. Purpose: We evaluated the effects of low EA on bone turnover markers (BTMs) in a cohort of women and a cohort of men, and compared effects between sexes. Methods: These studies were performed using a randomised, counterbalanced, crossover design. Eleven eumenorrheic women and eleven men completed two 5-day protocols of controlled (CON; 45kcal·kgLBM-1·d-1) and restricted (RES; 15kcal·kgLBM-1·d-1) EAs. Participants ran daily on a treadmill at 70% of their peak aerobic capacity (VO2 peak) resulting in an exercise energy expenditure of 15kcal·kgLBM-1·d-1 and consumed diets providing 60 and 30kcal·kgLBM-1·d-1. Blood was analysed for BTMs [β-carboxyl-terminal cross-linked telopeptide of type I collagen (β-CTX) and amino-terminal propeptide of type 1 procollagen (P1NP)], markers of calcium metabolism [parathyroid hormone (PTH), albumin-adjusted calcium (ACa), magnesium (Mg) and phosphate (PO4)] and regulatory hormones [sclerostin, insulin-like growth factor 1 (IGF-1), triiodothyronine (T3), insulin, leptin, glucagon-like-peptide-2 (GLP-2)]. Results: In women, β-CTX AUC was significantly higher (P=0.03) and P1NP AUC was significantly lower (P=0.01) in RES compared to CON. In men, neither β-CTX (P=0.46) nor P1NP (P=0.12) AUCs were significantly different between CON and RES. There were no significant differences between sexes for any BTM AUCs (all P values>0.05). Insulin and leptin AUCs were significantly lower following RES in women only (for both P=0.01). There were no differences in any AUCs of regulatory hormones or markers of calcium metabolism between men and women following RES (all P values>0.05). Conclusions: When comparing within groups, five days of low EA (15kcal·kgLBM-1·d-1) decreased bone formation and increased bone resorption in women, but not in men, and no sex specific differences were detected.
Article
The ketogenic diet (KD) is a medically supervised, high fat, low carbohydrate and restricted protein diet which has been used successfully in patients with refractory epilepsy. Only one published report has explored its effect on the skeleton. We postulated that the KD impairs skeletal health parameters in patients on the KD. Patients commenced on the KD were enrolled in a prospective, longitudinal study, with monitoring of Dual-energy X-ray absorptiometry (DXA) derived bone parameters including bone mineral content and density (BMD). Areal BMD was converted to bone mineral apparent density (BMAD) where possible. Biochemical parameters, including Vitamin D, and bone turnover markers, including osteocalcin, were assessed. Patients were stratified for level of mobility using the gross motor functional classification system (GMFCS). 29 patients were on the KD for a minimum of 6 months (range 0.5-6.5 years, mean 2.1 years). There was a trend towards a reduction in lumbar spine (LS) BMD Z score of 0.1562 (p = 0.071) per year and 20 patients (68%) had a lower BMD Z score at the end of treatment. While less mobile patients had lower baseline Z scores, the rate of bone loss on the diet was greater in the more mobile patients (0.28 SD loss per year, p = 0.026). Height adjustment of DXA data was possible for 13 patients, with a mean reduction in BMAD Z score of 0.19 SD. Only two patients sustained fractures. Mean urinary calcium-creatinine ratios were elevated (0.77), but only 1 patient developed renal calculi. Children on the KD exhibited differences in skeletal development that may be related to the diet. The changes were independent of height but appear to be exaggerated in patients who are ambulant. Clinicians should be aware of potential skeletal side effects and monitor bone health during KD treatment. Longer term follow up is required to determine adult/peak bone mass and fracture risk throughout life.