EAL

AWM: Low Carbohydrate Diet (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine body weight, body composition, serum lipid levels and adverse effects over 24 weeks in hyperlipidemic persons, who were randomly assigned to follow a low-carbohydrate ketogenic diet or a low-fat, low-cholesterol, reduced-calorie diet commonly used to induce weight loss and decrease serum lipid levels.

Inclusion Criteria:

Aged 18 to 65 years
BMI 30 to 60
Desire to lose weight
Elevated lipid levels [total cholesterol >5.17 mmol/L (>200 mg/dl)]
LDL cholesterol level >3.36 mmol/L (>130 mg/dl)
Triglyceride level >2.26 mmol/L (>200 mg/dl)
No serious medical condition.

Exclusion Criteria:

Use of any prescription medication in the previous two months (except for oral contraceptives, estrogen therapy and stable thyroid medication)
Pregnancy or breastfeeding
Use of any weight loss diet or diet pills in the previous six months
Baseline ketonuria.

Description of Study Protocol:

Recruitment

Recruited from the community, method not defined.

Design

Randomized controlled trial, randomized using computer-generated simple randomization list.

Blinding used (if applicable)

Not used.

Intervention (if applicable)

Low-carbohydrate diet (<20g carbohydrates per day) plus nutritional supplementation, exercise recommendations and group meetings or low-fat diet (<30% energy from fat, <300mg cholesterol daily and deficit of 500-1,000kcals per day) plus exercise recommendations and group meetings, for 24 weeks.

Statistical Analysis

For categorical outcomes, groups were compared using chi-square test or Fisher exact test, as appropriate. For all primary and secondary continuous outcomes, linear mixed-effects models that included fixed and random effects were used to determine expected mean values at each time point and to test hypotheses of group differences.
In most body weight and body composition models, time and group assignments were included as fixed effects with linear and quadratic time-by-group interaction terms.
In the fat-free mass, total body water and vital sign models, time-by-group interaction was treated as a categorical variable.
In all body weight and body composition models, random effects included intercept and linear slope terms. For the serum outcome measure models, the time-by-group interaction was treated as a categorical variable and an unstructured covariance was used to account for within-patient correlation over time.
All available data, including those from participants who subsequently discontinued the study, were used for the longitudinal analyses. Mixed-effects models assume non-informative dropout, meaning that the probability of dropout may depend on covariates or participants' previous responses, but not on current or future responses.

Data Collection Summary:

Timing of Measurements

Group visits twice a month for three months, then monthly for three months.

Dependent Variables

Body weight on same calibrated scale while wearing lightweight clothing and no shoes
Body composition through biolectrical impedance
Blood pressure and pulse rate measured in non-dominant arm by automated digital cuff
Fasting blood samples analyzed for serum lipid levels and other metabolic parameters
Tolerability and adverse effects measured through questionnaire
Urinalysis for ketonuria through dipstick.

Independent Variables

Low-carbohydrate diet (<20g carbohydrates per day) and nutritional supplements or low-fat diet (<30% kcals from fat, <10% saturated fat, <300mg cholesterol, 500-1,000 kcal restriction based on body weight in lbs x10).
Both groups received group meetings, diet instruction and exercise recommendations.
One-hour group meetings took place twice monthly for three months, then monthly for two months.
Participants selected own menus and prepared or bought own meals.
Dietary adherence measured by self-report, food records and urinary ketones for low-carbohydrate group. Diet composition analyzed for subsample of 20 people, 13 from low-carbohydrate, seven from low-fat.
Encouraged to exercise for 30 minutes three times per week.

Description of Actual Data Sample:

Initial N

1,051 volunteers screened for eligibility.
120 underwent randomization.

Attrition (final N)

79 of 120 subjects completed the study (34% dropout rate)
45 of 59 (76%) low-carbohydrate subjects
34 of 60 (57%) low-fat subjects.

Age

Low-fat: 44.1±8.7
Low-carbohydrate: 45.3±9.5.

Ethnicity

Low fat: 79% white, 18% African-American
Low-carbohydrate: 80% white, 18% African-American.

Other Relevant Demographics

Low fat BMI: 33.9±5.3
Low-carbohydrate BMI: 34.6±5.2.

Anthropometrics

Groups were similar, statistics not reported.

Location

North Carolina, USA.

Summary of Results:

Other Findings

A greater proportion of the low-carbohydrate diet group than the low-fat diet group completed the study (76% vs. 57%, P=0.02).
13 low-carbohydrate subjects consumed 8% kcals from carbohydrates, 26% from protein and 68% from fat. Seven low-fat subjects consumed 52% of kcals from carbohydrates, 19% from protein and 29% from fat. Estimated daily energy intake was 6.14±1.37 MJ (1,461.0±325.7kcal) in the low-carbohydrate group and 6.31±0.68 MJ (1,502.0±162.1kcal) in the low-fat group.
At 24 weeks, weight loss was greater in the low-carbohydrate diet group than in the low-fat diet group (mean change: -12.9% vs. -6.7%, P<0.001).
Patients in both groups lost substantially more fat mass (change: -9.4kg with low-carbohydrate vs. -4.8kg with low-fat diet) than fat-free mass (change: -3.3kg vs. -2.4kg, respectively; P=0.054).
Compared with recipients of the low-fat diet, recipients of the low-carbohydrate diet had greater decreases in serum triglyceride levels [change: -0.84mmol/L vs. -0.31mmol/L (-74.2mg/dl vs. -27.9mg/dl); P=0.004] and greater increases in HDL cholesterol levels [0.14mmol/L vs. -0.04mmol/L (5.5mg/dl vs. -1.6mg/dl); P<0.001].
Changes in LDL cholesterol level did not differ statistically [0.04mmol/L (1.6mg/dl) with the low-carbohydrate diet and -0.19mmol/L (-7.4mg/dl) with the low-fat diet; P=0.2].
Minor adverse effects were more frequent in the low-carbohydrate diet group.

Author Conclusion:

In summary, over 24 weeks, healthy hyperlipidemic persons who followed a low-carbohydrate diet lost more body weight and body fat than did those who followed a low-fat diet. Serum lipid profiles improved in both groups, but monitoring remains important because a small percentage of persons may experience adverse changes. Further research is needed in other groups and for longer periods to determine the safety of this dietary approach.

Funding Source:

University/Hospital:

Robert C. Atkins Foundation

Reviewer Comments:

Large dropout rates, especially in low-fat group. Diet composition only reported for 20 subjects: 13 in the low-carbohydrate group, seven in low-fat.

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?		???
	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?	???
	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?		???
	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%.)	???
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	???
	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?		???
	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?	???
	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?		???
	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?	???
	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