EAL

H/A: Dietary Intake (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To study the nutritional and metabolic effects of a 10-week trial of dietary fish oil (Maximum EPA 18g per day) in men with weight loss due to acquired immune deficiency syndrome (AIDS).

Inclusion Criteria:

Men with documented HIV seropositivity and more than 5% involuntary weight loss, due to AIDS over the past 12 months
Controls were matched for age and weight loss.

Exclusion Criteria:

Presence of opportunistic infections
Other medical diseases (liver, kidney, lung, metabolic disorders)
Severe or watery diarrhea
Inability to give informed consent
Use of medications known to have nutritional or metabolic actions
Inability to reliably complete a seven-day weighed food record at home
If taking n-3 fatty acid supplements.

Description of Study Protocol:

Recruitment

Subjects recruited by advertisement.

Design

Non-randomized clinical trial.

Blinding Used

Not possible, due to fish oil supplementation.

Intervention

Dietary n-3 fatty acid supplementation was for 10 weeks at 18g per day with MaxEPA capsules, containing one gram lipid with 100mg docosahexaenoic acid and 150mg eicosapentaenoic acid.

Statistical Analysis

Effects of fish oil supplementation on measured parameters were compared by ANOVA. The interaction between clinical outcome and DNL was analyzed by two-factor repeated measures ANOVA, with a group factor and a trial (or time) factor, each factor having two levels.

Data Collection Summary:

Timing of Measurements

Food intake, body composition, blood chemistries, serum cytokine concentrations, in vitro production of IL-1 and TNF by PBMC and clinical course were followed.

Dependent Variables

Blood chemistries
Body composition
Clinical evaluation
In vitro production of IL-1beta and TNF-alpha by peripheral blood mononuclear cells (PBMC)
Subset of subjects (N=12) underwent stable isotope infusions to measure de novo hepatic lipogenesis, an in vivo metabolic index that is influenced by cytokine presence and has previously been found to be elevated in AIDS.

Independent Variables

Dietary n-3 fatty acid supplementation was for 10 weeks at 18g per day with MaxEPA capsules, containing one gram lipid with 100mg docosahexaenoic acid and 150mg eicosapentaenoic acid
Every two weeks, subjects were required to return for refills of fish oil capsules and pill counts were done.

Description of Actual Data Sample:

Initial N: 20 men enrolled, 13 controls
Attrition (final N): 16 completed 10-week trial, 13 controls. Two died and two relocated or developed AIDS-related complications
Age: Mean age subjects: 41±2 years
Ethnicity: Not mentioned
Anthropometrics: Controls were matched for age and weight loss
Location: California.

Summary of Results:

	Weight (kg)	Body Fat (Percentage)	FFM (kg)	Energy Intake (kcal)	Protein Intake (g/day)
Supplemented, baseline	68.4±2.0	16.3±0.7	57.2±1.5	2,395±177	95.1±7.2
Supplemented, five weeks	69.0±1.8	16.8±0.6	57.4±1.3	--	--
Supplemented, 10 weeks	68.9±1.8	16.6±0.6	57.4±1.3	2,214±160	90.4±7.7
Non-supplemented, baseline	63.4±2.6	14.8±1.4	56.2±1.3	2,557±231	97.2±11.0
Non-supplemented, 12 weeks	62.8±2.7	15.0±1.7	55.8±1.4	2,320±291	90.0±19.2

Other Findings

Prior weight loss was 13.7±1.8kg (17.4±1.6% of body weight)
Baseline food intake (2,395±177kcal per day and 95.1±7.2g protein per day), body weight, percentage fat and fat-free mass were unchanged over the 10-week supplementation period
Serum triglycerides were reduced in hypertriglyceridemic subejcts, confirming compliance with fish oil supplementation and suggesting that their hypertriglyceridemia was at least, in part due to overproduction
Serum TNF and IL-1 were undetectable before or after fish oil supplementation
Serum interferon-alpha was measurable, but did not change
In vitro production of IL-1 and TBF by PBMC was markedly reduced both at baseline and after fish oil supplementation, even in the presence of new AIDS complications, compared with normal controls
The metabolic measurement DNL fell and weight was gained (2.1±1.3kg) in subjects who did not develop new AIDS-related complications, but further increases in DNL and further weight loss were observed in subjects who developed a new AIDS complication (P<0.05 for interaction between new complication and change in DNL)
No changes in body weight, food intake, serum triglycerides, serum cytokines or DNL were observed in the unsupplemented group.

Author Conclusion:

In summary, dietary fish oil supplementation in men with advanced AIDS-related weight loss did not increase food intake, body weight or lean body mass and did not prevent exacerbation of an abnormal fat-synthesizing metabolic milieu when new AIDS complications supervened. In contrast, in subjects not developing AIDS-related complications during the supplementation period, metabolic evidence consistent with reduced tissue cytokine activity was observed in conjunction with weight gain.
Our finding that a functional in vivo metabolic index that is sensitive to cytokine activity (DNL) is superior to ex vivo measures of cytokines is relevant to the design of future studies with potentially more powerful anticytokine agents
Finally, the possibility that fish oil supplementation is effective at stabilizing or increasing body weight in stable AIDS patients or when given at an earlier stage of HIV disease also needs to be evaluated in larger trials
Many questions clearly remain regarding the role of cytokines and anticytokine therapies in the AIDS-wasting syndrome.

Funding Source:

Government:	NIH
University/Hospital:	University of California

Reviewer Comments:

Authors note that PBMC studies are of limited use and questionable interpretability for assessing cytokine production in AIDS patients
Small numbers of subjects in groups
No power calculations done.

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?		N/A
	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?	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.)	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?		???
	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?	???
	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)?	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?		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