Adult Weight Management

Macronutrient Proportion and Energy Density - CNPP


Luscombe-Marsh ND, Noakes M, Wittert GA, Keogh JB, Foster P, Clifton PM.  Carbohydrate-restricted diets high in either monounsaturated fat or protein are equally effective at promoting fat loss and improving blood lipids.  Am J Clin Nutr 2005; 81: 762-772.

PubMed ID: 15817850
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 compare the effects of 2 isocaloric, energy-restricted, carbohydrate-matched diets that differed in protein and fat content on weight loss, lipids, appetite regulation, and energy expenditure.
Inclusion Criteria:
Included if between ages 20 - 65 years, nondiabetic, fasting serum insulin concentration > 12 mU/L, BMI between 27- 40.
Exclusion Criteria:
Excluded if they had diabetes mellitus, had microalbuminuria, history of liver, unstable cardiovascular, respiratory or gastrointestinal disease, had malignancy, or were pregnant or lactating.  Subjects taking antihypertensive or lipid-lowering medication were asked to maintain all medications at prestudy doses.
Description of Study Protocol:


Recruited through public advertisement.


Randomized controlled trial, parallel design.

Blinding used (if applicable)

Not used.

Intervention (if applicable)

Subjects received either low-fat, high-protein diet or high-fat, standard-protein diet for 12 weeks of energy restriction and 4 weeks of energy balance.

Statistical Analysis

Baseline measurements assessed using 2-factor ANOVA with diet and sex as fixed factors.  Effect of diet intervention was assessed by using repeated-measures ANOVA, for each dependent variable, the measurements at weeks 0, 4, 8, 12 and 16 are the within-subject factor and diet and sex are the between-subject factors.  Baseline weight, cholesterol, total fat mass, and total lean mass were included as covariates.  Week 0 and 16 response curves after the test meals were compared by using repeated-measures ANOVA with week and blood sampling time as the within-subject factors and diet and sex as the between-subject factors.  When significant interactions of time-by-diet or time-by-diet-by-sex were found, paired t tests were used to find differences.  The study had 80% power to detect differences between dietary groups of 3.6 kg in body weight, 0.9 kg in lean and fat mass, 3 mU/L in fasting insulin, 0.2 mmol/L in LDL cholesterol, and 7% in REE.

Data Collection Summary:

Timing of Measurements

Subjects visited the unit at 2 weekly intervals for dietary counseling and food supplies.  Body weight, blood pressure and venous blood samples taken at weeks 0, 4, 8, 12 and 16.

Dependent Variables

  • Fasting blood samples analyzed for glucose, insulin and lipid concentrations, serum creatinine
  • 24-hour urine sample collected for assessment of ratio of urea to creatinine for dietary compliance
  • Body composition measured using whole-body DEXA
  • Total energy expenditure
  • 3-hour meal tolerance test of experimental meals
  • REE, TEF, RQ and appetite sensations (hunger, satiety, fullness, desire to eat) measured before and after test meal using visual analogue scales
  • Body weight recorded while subjects wearing light clothing without shoes

Independent Variables

  • Low-fat, high-protein diet (prescribed:  30% fat, 40% protein, actual:  29 +/- 1% fat, 34 +/- 0.8% protein) or high-fat, standard-protein diet (prescribed:  50% fat, 20% protein, actual: 45 +/- 0.6% fat, 18 +/- 0.3% protein) during 12 weeks of energy restriction (6 +/- 0.1 MJ/day) and 4 weeks of energy balance (7.4 +/- 0.3 MJ/day).  Carbohydrate was matched at 30% in both diets.  Subjects followed menu plans and foods were supplied.  RD provided counseling and instruction on keeping dietary intake checklists.
  • Most subjects were sedentary at baseline and were asked to continue usual physical activity levels and to refrain from drinking more than 2 glasses of alcohol per week throughout the study

Control Variables


Description of Actual Data Sample:

Initial N: 73 eligible subjects enrolled, low-fat/high-protein n=36, high-fat/standard protein n=37.  5 dropped out before intervention started leaving 34 in each group.

Attrition (final N):  11 more dropped out during study.  27 completed low-fat/high-protein (12 men, 15 women), 30 completed high-fat/standard protein (13 men, 17 women).

Age:  High fat/standard protein men:  50 +/- 3 years, women:  48 +/- 3 years.  Low-fat/high-protein men:  50 +/- 3 years, women:  53 +/- 2 years. 

Ethnicity:  Not mentioned.

Other relevant demographics:  High fat/standard protein men BMI: 34.8 +/- 1.0, women BMI: 34.4 +/- 0.9.  Low fat/high protein men BMI: 32.2 +/- 0.9, women BMI: 34.4 +/- 0.9.   

Anthropometrics:  No significant differences between treatment groups at baseline. 

Location:  Australia


Summary of Results:


HFSP - Energy Restrict HFSP - Energy Balance LFHP - Energy Restrict LFHP - Energy Balance
Energy (kJ/d) 5972 +/- 125 7175 +/- 327 6164 +/- 105 7560 +/- 268
Carbs (%) 35 +/- 0.6 36 +/- 1.0 35 +/- 0.6 36 +/- 1.0
Carbs (g/day) 123 +/- 3.0 149 +/- 7.0 126 +/- 3.0 158 +/- 5.0
Protein (%) 18 +/- 0.3 18 +/- 0.4 34 +/- 0.8 33 +/- 0.5
Protein (g/day) 68 +/- 1.4 80 +/- 3 130 +/- 3.5 156 +/- 5
Fat (%) 45 +/- 0.6

45 +/- 1.0

29 +/- 1.0

29 +/- 1.0

Fat (g/day) 72 +/- 2.0

88 +/- 5.0

49 +/- 1.6

60 +/- 4.0

Other Findings

Weight loss (low-fat/high-protein group:  9.7 +/- 1.1 kg, high-fat/standard protein group: 10.2 +/- 1.4 kg, P = 0.78) and fat loss were not significantly different between diet groups even though the subjects desired less to eat after the low-fat/high-protein meal (P = 0.02).

The decrease in REE was not significantly different between groups (low-fat/high-protein: -342 +/- 185 kJ/day, high-fat/standard protein: -349 +/- 220 kJ/day).

The decrease in the thermic effect of feeding with weight loss was smaller in the low-fat/high-protein group than in the high-fat/standard-protein group (-0.3 +/- 1.0% compared with -3.6 +/- 0.7%, P = 0.014).

Glucose and insulin responses to test meals improved after weight loss (P < 0.001) with no significant diet effect.

Bone turnover, inflammation, and calcium excretion did not change significantly.

Author Conclusion:

In summary, in obese subjects with moderately elevated insulin concentrations, after 12 weeks of energy restriction and 4 weeks of energy balance, the magnitude of weight loss and the improvements in insulin resistance and lipid metabolism that were achieved with carbohydrate-restricted diets that contained either moderately increased amounts of protein or monounsaturated fat were not significantly different.  Nevertheless, the high-protein meals had the advantage of blunting the decrease in TEF observed after weight loss and also reduced the amount of food desired at the next meal.  Whether these mechanisms lead to differential weight loss under ad libitum conditions needs to be explored over the long term.  The implication of these findings is that protein from meat, poultry and dairy foods or fat from food sources rich in monounsaturated fatty acids are both suitable options to replace some dietary carbohydrate, at least in the short term, and the choice of weight-loss diet can be tailored to individual preferences.

Funding Source:
Government: NHMRC, CSIRO (Australia)
University/Hospital: University of Adelaide (Australia)
Reviewer Comments:
Dietary compliance assessed through urinalysis.
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? No
  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.) No
  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? Yes
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