EAL

NAP: Training (2014)

Citation:

Psilander N, Frank P, Flockhart M, Sahlin K. Exercise with low glycogen increases PGC-1a gene expression in human skeletal muscle. Eur J Appl Physiol. 2013; 113: 951-963.

PubMed ID: 23053125

Study Design:

Randomized Crossover Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

To determine if exercise in a glycogen-depleted state enhances expression PGC-1a and other genes related to mitochondrial biogenesis and CHO metabolism
To investigate the role of oxidative stress and other potential signaling pathways.

Inclusion Criteria:

Male cyclists
Competing at national level or been competing at national elite level during the preceding years in road or mountain biking.

Exclusion Criteria:

Females
Non-elite cyclists.

Description of Study Protocol:

Design

RCT with crossover.

Intervention (if applicable)

High-CHO (NG) diet vs. low-CHO (LG) diet.

Statistical Analysis

Two-way repeated measures ANOVA (time and dietary intervention)
When a significant primary effect or interaction was observed, post-hoc analysis were performed to locate the difference.

Data Collection Summary:

Timing of Measurements

At 15 minutes before and three hours after exercise.

Dependent Variables

Lactate, glucose, free fatty acids (FFA): Blood from antecubital vein
mRNA peroxisome proliferator-activated receptor-ý coactivator-1, cytochrome c oxidase subunit I, pyruvate dehydrogenase kinase isozyme 4 mRNA, phosphorylation of AMP-activated protein kinase, p38 mitogen-activated protein kinases, acetyl-CoA carboxylase, mitochondrial reactive oxygen species production, glutathione oxidative status: Muscle biopsy from middle portion of vastus lateralis muscle.

Independent Variables

NG diet:
- Two high-CHO meals:
  - Dinner (pasta with meat sauce and lemonade): 1.83g CHO, 0.53g protein and 0.14g fat per kg body weight (bw)
  - Breakfast (oatmeal and orange juice): 1.54g CHO, 0.31g protein and 0.12g fat per kg bw]
- High-CHO beverages (50/50% maltodextrin-dextrose powder dissolved in water): 1.0g CHO per kg bw
- A banana was served together with beverage nr. three, five, seven and eight, adding an additional 0.31g CHO, 0.01g protein and 0.01g fat per kg bw.
LG diet (12.6g CHO, 0.9g protein and 0.3g fat per kg bw):
- Two low-CHO meals [dinner and breakfast (egg and bacon)]: less than 0.02g CHO, 0.6g protein and 0.8g fat per kg bw (approximately 19kcal per kg bw, or 1,425kcal).
Energy content of both diets was similar:
- NG provided 88% of total energy intake from CHO, 6% protein and 6% fat
- LG provided less than 1% total energy from CHO, 22% protein and 77% fat.

Control Variables
Two exercise tests separated by 14 h; one to deplete muscle glycogen (depletion exercise) and other to test the influence of low muscle glycogen on the signaling response (test exercise). No exhaustive exercise and alcohol during 2 d prior to tests. Food diary 24-h prior to first experiment that subjects duplicated before the second experiment

Description of Actual Data Sample:

Initial N: 10 males
Attrition (final N): 10 males
Age: 27.8±1.6 years
Anthropometrics: 74.7±2.0kg, 183±2cm, VO_2max 4.9±0.1L per minute
Location: Stockholm, Sweden.

Summary of Results:

Findings

mRNA of peroxisome proliferator-actived receptor-ÿ coactivator-1 was enhanced to a greater extent when exercise was performed with low compared with normal glycogen levels (8.1-fold vs. 2.5-fold increase). Cytochrome c oxidase subunit 1 and pyruvate dehydrogenase kinase isozyme 4 mRNA were increased after LG (1.3-fold and 114-fold increase, respectively), but not after NG. Phosphorylation of AMP-activated protein kinase, p38 mitogen-activated protein kinases and acetyl-CoA carboxylase was not changed three hours post-exercise. Mitochondrial reactive oxygen species production and glutathione oxidate status tended to be reduced three hours post-exercise.

Author Conclusion:

Exercise with low glycogen levels amplifies the expression of the major genetic marker for mitochondrial biogenesis in highly trained cyclists.

Funding Source:

University/Hospital:

Swedish School of Sport and Health Sciences

Not-for-profit

Swedish National centre for Research in Sports, Swedish Reserach Council

Reviewer Comments:

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?	N/A
	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?		Yes
	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?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	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?	Yes
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?		N/A
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	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%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	N/A
	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?		N/A
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	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.)	N/A
	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?	N/A
	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