EAL

NAP: Competition (2007)

Citation:

Claassen A, Lambert EV, Bosch AN, Rodger IM, St. Clair Gibson A, Noakes TD. Variability in exercise capacity and metabolic response during endurance exercise after a low carbohydrate diet. Int J Sport Nutr Exerc Metab. 2005; 15 (2): 97-116.

PubMed ID: 16089270

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 examine the effect of glucose infusion to maintain euglycemia vs. saline (placebo) infusion on endurance exercise capacity in persons whose glycogen stores had been lowered by prior exercise and a low-CHO diet.

Inclusion Criteria:

Endurance-trained male cyclists who were selected based on regular training of over 200km per week, who had completed a 105-kilometer cycling race in under 3.5 hours.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment: Subjects volunteered to participate in the study and were selected based on training and performance
Design: Randomized crossover trial
Blinding used: Single-blind.

Intervention

Low-carbohydrate diet for 48 hours, followed by one trial with glucose infusion during the experimental ride to maintain euglycemia and a second trial with saline (placebo) infusion.

Statistical Analysis

Between-group differences were assessed by two-way ANOVA for repeated measures over time for the first 80 minutes
To determine which means were significantly different, Tukey's honest significance difference post-hoc analysis was used
Subjects fatigued and dropped out at different time points after 80 minutes
Paired T-tests were performed for comparisons between groups of variables at the point of exhaustion
Pearson's correlations were performed between continuous variables. For correlations with endurance time, the Kendall tau technique was used.

Data Collection Summary:

Timing of Measurements

Subjects underwent euglycemic or placebo clamps (separated by a one-week washout period), while performing up to 150 minutes of cycling at 70% VO_2max after 48 hours on a low-carbohydrate diet.

Dependent Variables

Blood samples were analyzed for plasma glucose, 14C-glucose specific activity, lactate, serum FFA, beta-hydroxybutyrate, cortisol and insulin
Muscle glycogen was measured in muscle biopsies from vastus lateralis
Gas exchange measurements taken
Rates of plasma glucose oxidation measured through glucose tracer.

Independent Variables

Low-carbohydrate diet for 48 hours
Glucose or saline placebo infusion: Rate of glucose infusion was to maintain euglycemia.

Description of Actual Data Sample:

Initial N: Nine trained men
Attrition (final N): Nine subjects
Age: Mean age, 29±8 years
Ethnicity: Not mentioned
Other relevant demographics: Mean VO_2max, 63±7ml per kg per minute
Location: South Africa.

Summary of Results:

Muscle Glycogen Concentration (mmol per kg wet weight)	Placebo Infusion	Glucose Infusion
Pre-exercise (N=9)	83±15	74±21
Post-exercise (N=9)	44±15	39±12

Other Findings

The range in improvement in endurance capacity with glucose infusion was large (28±26%, P<0.05)
Time to fatigue in the glucose infusion trial was significantly longer than the placebo trial (137±14 vs. 112±29 minutes, P<0.05)
56% of subjects in euglycemic clamps failed to complete 150 minutes of exercise despite maintenance of euglycemia, while only two subjects in placebo clamps completed 150 minutes of exercise, despite being hypoglycemic
Total CHO oxidation remained similar between trials
Despite longer exercise times in glucose infusion, similar amounts of muscle glycogen were used in placebo infusion.

Author Conclusion:

In summary, our findings provide additional evidence for the ergogenic effect of CHO supplementation during prolonged exercise in subjects with reduced glycogen content, however this effect is highly variable between individuals and independent of changes in the rate of total CHO oxidation
Furthermore, despite euglycemic glucose infusion and an increase in plasma glucose oxidation, the majority of these well-trained endurance subjects still could not complete the prescribed 150 minutes of exercise
This study establishes that some aspect of intra-muscular or intra-hepatic glucose metabolism influences the endurance capacity of subjects who begin exercise with low glycogen content
The exact link between plasma glucose concentration and endurance capacity remains unclear, as subjects whose blood glucose concentrations did not change markedly during placebo infusion demonstrated the greatest benefit from glucose infusion with regard to increased endurance capacity.

Funding Source:

Government:	Medical Research Council of South Africa
University/Hospital:	University of Capetown

Reviewer Comments:

Inclusion and exclusion criteria were not well-defined and subject selection may have led to bias
Data were not analyzed after the 80-minute time point, due to declining subject numbers.

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)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	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?	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.)	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?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	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?		???
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	???
	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?	No
9.	Are conclusions supported by results with biases and limitations taken into consideration?		???
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	???
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