Adult Weight Management

AWM: Low Carbohydrate Diet (2006)


Brehm BJ, Spang SE, Lattin BL, Seeley RJ, Daniels SR, D'Alessio DA.  The role of energy expenditure in the differential weight loss in obese women on low-fat and low-carbohydrate diets.  J Clin Endocrinol Metab 2005; 90: 1475-1482.

PubMed ID: 15598683
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To evaluate the hypothesis that low-carbohydrate diets increase energy expenditure relative to a low-fat diet.
Inclusion Criteria:
Aged at least 18 years, moderate obesity with BMI of 30 - 35, stable weight over preceding 6 months (no weight loss or gain of > 10% body weight).
Exclusion Criteria:
Presence of cardiovascular disease, untreated hypertension, diabetes, hypothyroidism, substance abuse, pregnancy, or lactation.
Description of Study Protocol:


Recruited by advertisement.


Randomized Controlled Trial.  Randomized using computerized randomization program.

Blinding used (if applicable)

DEXA scan readings and biochemical analyses conducted by personnel blinded to the group assignment of subjects.

Intervention (if applicable)

Subjects randomized to 4 months of ad libitum low-carbohydrate diet or energy-restricted, low-fat diet.

Statistical Analysis

Baseline characteristics compared between the 2 groups using t tests.  To assess the effects of the diets, 2-way repeated-measures ANOVA, with time as the repeated factor, was performed.  If the main effect was significant, the Bonferroni multiple comparison was implemented to determine the specific differences.  If the interaction was significant, the Bonferroni adjustment was used.  Differences between the groups are indicated only when there is a significant interaction between diet and time.  Body weight, DEXA measurements, biochemical parameters, REE measurements and pedometer readings were analyzed for the 40 subjects who completed the study.  Comparisons of TEF between the 2 diets were made using paired t tests for 8 subjects.

Data Collection Summary:

Timing of Measurements

REE measured at baseline, 2 months, and 4 months.  Thermic effect of food in response to low-fat and low-carbohydrate breakfasts assessed over 5 hours in subset of 8 subjects.

Dependent Variables

  • REE measured by computerized, open-circuit indirect calorimetry after overnight fast and 30 min relaxation in dark 
  • Physical activity estimated by pedometers
  • Thermic effect of food measured on 2 mornings after overnight fast with postprandial energy expenditure measured for 300 minutes with indirect calorimetry
  • Height
  • Weight on single electronic scale
  • ECG
  • Blood pressure
  • Fasting blood samples analyzed for total, LDL and HDL cholesterol, triglycerides, glucose, insulin, and beta-hydroxybutyrate
  • Body fat measured through DEXA
  • Assessment of urinary ketones through Ketostix

Independent Variables

  • 4 months of ad libitum low-carbohydrate diet (maximum intake of 20 g carbohydrate/day for first 2 weeks, followed by increase to 40 - 60 g) or an enegrgy-restricted, low-fat diet (55% kcals from carbohydrate, 15% from protein, 30% from fat, energy prescriptions based on body size and Harris-Benedict equations).  Subjects required to keep weekly 3-day food records and pedometer records.  2 RDs delivered 2-month intervention including weekly counseling, individualized and group, reviewing food and activity records, with minimal contact after 2 months.

Control Variables


Description of Actual Data Sample:

Initial N: 50 women

Attrition (final N):  40 women (80%) with equal number of dropouts in each group.  Final n=20 in each group.

Age:  Low-fat diet group mean age:  41.4 +/- 3.2 years, low-carbohydrate diet group mean age:  44.8 +/- 2.4 years 

Ethnicity:  10 African-Americans and 40 Caucasian at baseline 

Other relevant demographics:  Low-fat BMI:  33.5 +/- 0.5, Low-carbohydrate BMI: 32.8 +/- 0.5 

Anthropometrics:  There were no significant differences between groups.

Location:  Ohio 


Summary of Results:


Baseline 2 Months 4 Months
Low Carb -  energy 2166 kcal 1288 1531

Low Carb - % protein




Low Carb - % CHO 48 15 24
Low Carb - % Fat 36 57 52
Low Fat - energy 2176 kcal 1339 1422
Low Fat - % protein 14 18 20
Low Fat - % CHO 51 53 48
Low Fat - % Fat




Other Findings

The low-carbohydrate group lost more weight (9.79 +/- 0.71 vs 6.14 +/- 0.91 kg; P < 0.05) and more body fat (6.20 +/- 0.67 vs 3.23 +/- 0.67 kg, P < 0.05) than the low-fat group.

There were no differences in energy intake between the diet groups as reported on 3-day food records at the conclusion of the study (1422 +/- 73 vs 1530 +/- 102 kcal, 5954 +/- 306 vs. 6406 +/- 427 kJ).

Mean REE in the 2 groups was comparable at baseline, decreased with weight loss, and did not differ at 2 or 4 months.

The low-fat meal caused a greater 5-hour increase in TEF than did the low-carbohydrate meal (53 +/- 9 vs 31 +/- 5 kcal, 222 +/- 38 vs 130 +/- 21 kJ, P = 0.017).

Estimates of physical activity were stable in the dieters during the study and did not differ between groups. 

Author Conclusion:

In summary, we have demonstrated that women consuming a low-carbohydrate diet lose more weight than women consuming a low-fat diet over several months.  The more pronounced weight loss in the low-carbohydrate dieters is not explained by increased REE, TEF or physical activity and cannot be accounted for by their reported energy intakes.  However, we believe that the best explanation for the difference in weight loss between groups is a difference in energy intake that was not apparent in their self-reported 3-day food records.  The reason for decreased energy intake in the low-carbohydrate group, even in the face of no restrictions on energy, remains to be explained.  Some have speculated that this self-restriction is a result of the effect of circulating ketones on appetite or other satiating effects of low-carbohydrate diets, but this remains unproven.  The major point is that the principal means of voluntarily shifting energy balance to promote weight loss is restriction of intake and increase in expenditure.

Funding Source:
Government: NIH
University/Hospital: University of Cincinatti, Children's Hospital Medical Center
Foundation associated with industry:
Reviewer Comments:
TEF measured in only 8 subjects.  Dietary compliance measured through RD assessment biweekly.
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? 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? 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? Yes
  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? Yes
  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? 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)? Yes
  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