EAL

NAP: Competition (2007)

Citation:

De Bock K, Richter EA, Russell AP, Eijnde BO, Derave W, Ramaekers M, Koninckx E, Leger B, Verhaeghe J, Hespel P. Exercise in the fasted state facilitates fibre type-specific intramyocellular lipid breakdown and stimulates glycogen resynthesis in humans. J Physiol. 2005 Apr 15; 564 (Pt 2): 649-60.

PubMed ID: 15705646

Study Design:

Randomized crossover trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To investigate whether an endurance exercise bout performed in the fasting state, compared with identical exercise performed in combination with an optimal rate of carbohydrate intake to support performance

Facilitates degradation of IMTGs and
Enhances post-exercise muscle glycogen resynthesis.

Inclusion Criteria:

Healthy, physically active men.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment: Methods not specified
Design: Randomized crossover trial
Blinding used: Not possible; lab tests.

Intervention
Subjects participated in two sessions separated by three weeks
Subjects performed two hours of constant-load bicycle exercise (~75% VO_2max), followed by four hours of controlled recovery
On one occasion, they exercised after an overnight fast and on the other, they received carbohydrates before (~150g) and during (one gram per kg body weight per hour) exercise. In both conditions, subjects ingested five grams CHO per kg body weight during recovery.

Statistical Analysis

Treatment effects were evaluated using repeated-measures ANOVA
Two-way ANOVA was performed to examine interaction between treatment and time. Where ANOVA yielded significant effects, planned contrast analysis was used for post-hoc comparisons.
The strength of association between parameters was analyzed by Pearson product moment correlation analysis.

Data Collection Summary:

Timing of Measurements

Muscle biopsies taken before, immediately after and four hours after exercise
Gas exchange measurements were taken before, halfway through and at end of exercise
Blood was sampled before and after the first and second hour of exercise.

Dependent Variables

Fiber type-specific relative intramyocellular triglyceride content was determined by Oil red O staining in needle biopsies from vastus lateralis
Muscle glycogen, muscle lysate production and glycogen synthase activity also were measured from muscle biopsies
Gas exchange measurements were completed through ergospirometry system
Blood samples were analyzed for glucose, lactate, glycerol, FFA, insulin, adiponectin, leptin, cortisol and plasma catecholamines.

Independent Variables

Overnight fast or carbohydrates before (~150g) and during (one gram per kg body weight per hour) exercise. In both conditions, subjects ingested five grams CHO per kg body weight during recovery.
Subjects received a standardized diet during three days prior to trials
Subjects were instructed to abstain from strenuous physical exercise prior to trials.

Description of Actual Data Sample:

Initial N: Nine men
Attrition (final N): Nine
Age: Mean age, 22.8±0.4 years
Ethnicity: Not mentioned
Location: Belgium.

Summary of Results:

	Pre-Exercise	Post-Exercise	Four Hours' Recovery
Glucose; CHO	6.0±0.3	4.1±0.2, P<0.05	6.3±0.7
Glucose; Fasting	4.8±0.1, P<0.05	3.5±0.1, P<0.05	6.5±0.7, P < 0.05
FFA; CHO	57±9	452±98, P<0.05	34±15
FFA; Fasting	358±113, P<0.05	1680±165, P<0.05	44±18, P<0.05
Glycerol; CHO	58±3	144±23, P<0.05	51±6
Glycerol; Fasting	77±8, P<0.05	522±54, P<0.05	54±7, P<0.05
Insulin; CHO	36.7±9.3	12.1±1.8, P<0.05	26.8±3.0
Insulin; Fasting	4.6±0.9, P<0.05	1.3±0.5, P<0.05	48.0±11.8, P<0.05
Leptin; CHO	2.74±0.3	2.23±0.4, P<0.05	3.06±0.5
Leptin; Fasting	2.39±0.4	1.20±0.2, P<0.05	1.16±0.3, P<0.05
Adrenaline; CHO	0.10±0.01	0.13±0.03	0.09±0.01
Adrenaline; Fasting	0.10±0.01	0.26±0.05, P<0.05	0.09±0.01
Noradrenaline; CHO	0.29±0.03	0.63±0.05, P<0.05	0.39±0.04, P<0.05
Noradrenaline; Fasting	0.24±0.03	0.70±0.08, P<0.05	0.40±0.05, P<0.05
Cortisol; CHO	17.1±1.6	16.1±1.0	15.0±1.6
Cortisol; Fasting	18.3±1.0	20.2±3.0	11.8±1.4, P<0.05

Other Findings

During fasting, but not during CHO supplementation (before and during exercise), the exercise bout decreased intramyocellular triglyceride content in type I fibers from 18±2% to 6±2% (P=0.007) area lipid staining
Conversely, during recovery, intramyocellular triglyceride in type I fibers decreased from 15±2% to 10±2% in CHO supplementation (P=0.03), but did not change in fasting
Neither exercise nor recovery changed intramyocellular triglyceride in type IIa fibres in any experimental condition
Exercise-induced net glycogen breakdown was similar in fasting and CHO supplementation. However, compared with CHO supplementation (11.0±7.8mmol per kg per hour), mean rate of post-exercise muscle glycogen resynthesis was three-fold greater in fasting (32.9±2.7mmol per kg per hour; P=0.02).
Furthermore, oral glucose-loading during recovery increased plasma insulin markedly more in fasting (+46.80microU per ml) than in CHO supplementation (+14.63microU per ml; P=0.02)
RER was consistently lower in fasting than in CHO supplementation (P=0.0001)
In the fasting condition, the calculated fat oxidation rate was higher (P=0.03), while the CHO oxidation rate was lower (P=0.003).

Author Conclusion:

In conclusion, the current study shows that intramyocellular triglyceride breakdown during prolonged submaximal exercise in the fasted state takes place predominantly in type I fibres. Furthermore, we show for the first time that intramyocellular triglyceride breakdown during exercise is completely prevented in the CHO-fed state
In addition, exercise in the fasted state enhances the post-exercise insulin response to glucose ingestion, which in turn is likely to contribute to stimulation of post-exercise muscle glycogen resynthesis
Finally, CHO ingestion, either before, during or after exercise, is a potent inhibitor of UCP3 gene expression in skeletal muscle.

Funding Source:

Government:

Media and Grants Secretariat of the Danish Ministry of Culture, Danish Medical Research Council, European Commission

University/Hospital:

Copenhagen Muscle Research Centre

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Inclusion and exclusion criteria and recruitment methods were not well-defined.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		???
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	No
	2.2.	Were criteria applied equally to all study groups?	???
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	N/A
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes