EAL

H/A: Dietary Intake (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate the effect of a dietary intervention plus n-3 fatty acid supplementation on serum triglycerides and markers of insulin sensitivity.

Inclusion Criteria:

Persons with HIV
Aged older than 18 years
BMI between 19 and 30kg/m²
Elevated serum triglycerides (higher than 150mg per dL) and abnormal Quantitative Insulin Sensitivity Check Index (QUICKI) values (less than 0.35 but more than 0.30)
Subjects had to be free of any opportunistic infections, have no active injection drug use and not have taken any n-3 fatty acid supplements for more than three months before the study started
Willing to remain weight stable (±3% change) over the six months of the study.

Exclusion Criteria:

Triglyceride concentration higher than 550mg per dL
Persons taking HMG-CoA reductase inhibitors (statins).

Description of Study Protocol:

Recruitment

Subjects with HIV were recruited between July 2003 and March 2007. Subjects were recruited via the network of groups and sites that were used and maintained during a large observational study in the HIV population in the Boston area.

Design

Randomized controlled trial. Randomization was done by block design to ensure equal numbers in each group for every 10 subjects recruited.

Blinding Used

Implied with laboratory measurements.

Intervention

Subjects were randomly assigned to an intervention or control group
Subjects in the intervention group received supplementation with n-3 fatty acids (3.0g per day) to achieve an intake of 6.0g per day, as well as vitamin E supplements
Total fat, type of fat, fiber and glycemic load were controlled; meals were formulated for the daily intake to be lower in fat (approximately 25% of energy from total fat), be lower in saturated fat (approximately 7% of energy), have a saturated:monounsaturated:polyunsaturated fatty acid ratio of 1:1:1, provide a dietary intake of n-3 fatty acids of 3.0g per day, provide a dietary fiber intake of more than 40g per day and to have a reduced glycemic load.

Statistical Analysis

Non-parametric statistics were used except when looking at normally distributed variables
For comparisons of characteristics between groups, the Wilcoxon's rank-sum test was used for continuous variables, and the chi-square test or Fisher's exact test for categorical variables
Wilcoxon's signed rank test was used to determine the significance of within-group changes between visits
Two-sample T-tests were used to test the significance of the difference in mean changes between groups over time
Results were analyzed with a multiple imputations model since it was an intention-to-treat analysis.

Data Collection Summary:

Timing of Measurements

Measurements were made at baseline, three weeks and 13 weeks.

Dependent Variables

Blood samples were analyzed for serum lipids, glucose, insulin, highly sensitive C-reactive protein and serum phospholipid fatty acids.

Independent Variables

Subjects were randomly assigned to an intervention or control group
Subjects in the intervention group received supplementation with n-3 fatty acids (3.0g per day) to achieve an intake of 6.0g per day, as well as vitamin E supplements
Dietary intake was obtained using a three-day food record or 24-hour dietary recall.

Control Variables

Total fat, type of fat, fiber and glycemic load were controlled. Meals were formulated for the daily intake to be lower in fat (approximately 25% of energy from total fat), be lower in saturated fat (approximately 7% of energy), have a saturated:monounsaturated:polyunsaturated fatty acid ratio of 1:1:1, provide a dietary intake of n-3 fatty acids of 3.0g per day, provide a dietary fiber intake of more than 40g per day and to have a reduced glycemic load.

Description of Actual Data Sample:

Initial N

54 subjects, 80% male.

Attrition (final N)

47 subjects. Seven dropped out before the week 13 visit, all from the intervention group.

Age

Median age, 46.8 years; range 41.5 to 51.3 years.

Ethnicity:

43% African American
50% white
7% other.

Other Relevant Demographics:

87% of subjects were receiving HAART (24% without PI, 63% with PI)
13% were not receiving any HIV medication.

Anthropometrics

There were no significant differences between groups at baseline:

Mean CD4 count = 468 cells per mm³
Log₁₀ viral load = 2.3 copies per ml.

Location

Boston, Massachusetts.

Summary of Results:

Key Findings

Triglycerides in the intervention group decreased from a median of 180mg per dL (interquartile range: 141, 396) to 114mg per dL (interquartile range: 84, 169) from baseline to three weeks, whereas they remained stable in the control group (P=0.003)
Serum phospholipid fatty acids indicated a decrease in de novo lipogenesis and a decrease in arachidonic acid (percent nmol; P<0.001) in the intervention group
Oleic acid was significantly reduced in the intervention group at week 13 (P<0.001) and was significantly lower than in the control group (P<0.001)
Supplementation of the fatty acids EPA and DHA in the intervention group resulted in significant and large increases in these fatty acids in the phospholipid fraction, while the values in the control group remained relatively stable
At three weeks, the insulin area under the curve decreased, but not significantly.

Author Conclusion:

In summary, our HIV study subjects who received HAART and had elevated serum triglycerides and insulin resistance, had high levels of fatty acids formed by the Δ-9, -6, and -5 desaturase enzymes increased de novo lipogenesis and increased levels of AA (20:4n-6), which is characteristic of increased inflammation. All of these effects were ameliorated through the consumption of a healthier diet low in total and saturated fats, that was higher in fiber and n-3 fatty acids, and that had a lower n-6/n-3 ratio.

Funding Source:

Government:	National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
University/Hospital:	General Clinical Research Center of Tufts Medical Center

Reviewer Comments:

Relatively small sample size; all dropouts from the intervention group.

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?	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?	???
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?		???
	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?	No
	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?		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)?	Yes
	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?	No
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