EAL

DF: Cardiovascular Disease (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To compare the effects of soluble fiber with those of insoluble fiber on plasma lipid, lipoprotein and apolipoprotein concentrations within a CVD secondary prevention program.

Inclusion Criteria:

Adult men with ischemic heart disease who attended University Hospital Saint Joan, Reus, Spain and were outpatients not currently receiving any hypolipidemic drug therapy.

Inclusion criteria included

Fasting plasma LDL-cholesterol less than or equal to 3.35mmol per L (130mg per dL)
Triacylglycerol concentrations less than or equal to 2.84mmol per L (250mg per dL).

Other criteria

Less than age 75
Clinically stable
No medical or social conditions that impaired their ability to participate in study trial
Patients treated with anti-platelet drugs (N=28), beta blockers (N=12), calcium channel-blocking drugs (N=6), angiotension-converting enzyme inhibitors (N=6), nitrates (N=7), and diuretics (N=3) were included. Neither drugs nor doses were altered during study,
No evidence of alcohol, tobacco or recreational-drug use.

Exclusion Criteria:

Criteria were derived from medical history and a complete physical examination and included:

Diabetes mellitus
Congestive heart failure
Renal insufficiency
Thyroid or endocrine disease
Blood pressue greater than 140 (systolic) /90 (diastolic) mmHg
Current use of lipid-lowering drugs.

Description of Study Protocol:

Recruitment

Pateints meeting criteria were contacted. Of 50 eligible outpatients, 31 met inclusion criteria at end of adaptation phase. No monetary inducement was offered.

Design

A four-week adaptation period occured before baseline
Patients were randomly assigned, per a computer-generated random number sequence, to two different fiber-supplement periods of eight weeks each (consuming either P. ovata husk or an equivalent amount of insoluble fiber)
A washout period of eight weeks occured between the first and second periods of the study to test possible interactions between treatment and sequence order (carryover effect)
Compliance was monitored by interviewing patients and counting unopened sachets returned at each follow-up visit
Non-compliance was defined as any deviation from instructions of greater than 20% regarding diet and fiber supplement consumption
Vitamin and mineral salt status were evaluated before and after treatment
Information on adverse effects was solicited by open-ended questions at each visit on unusual symptoms, discomfort or side effects.

Blinding Used

Allocation was concealed in sealed study folders held in a central secured location until informed consent was obtained
The dietitian who scheduled study visits and the lab personnel responsible for analyses were blinded to patient group assignment.

Intervention

Patients received three five-gram sachets daily, of which approximately 70% (3.5g) was the soluble fiber (test additive) or an equivalent insoluble fiber (control additive). Patients were instructed to mix each sachet of soluble fiber in 150ml water or for the insoluble fiber to consume directly with a spoon. In both cases, participants were encouraged to drink 250ml water. Sachets were consumed 15 minutes before the three main meals. Sachets were provided before the start and at the middle (four weeks) of each of the two periods.

From the start of the adaptation period of the trial, subjects consumed recommended low-fat diet and cholesterol under strictly-controlled conditions in which compliance was assessed by a research dietitian. Diet was isocaloric and contained 30% of total energy as fat (less than 7% as saturated fatty acids) and less than 300mg cholesterol daily. Weekday lunches were prepared by the hospital kitchen and consumed in the hospital's restaurant. All breakfasts, dinners and weekend lunches were consumed on premises under supervision of research dietitian. Three-day food records (total of seven per patient) were maintained to monitor dietary compliance.

P. ovata husk (epidermis and collapsed adjacent layers removed from dried ripe seeds) is manufatured as a palatable orange-flavored, sugar-free product. The insoluble fiber used as control was hemocellulose and lignin klason, obtained from P. ovata seeds.

Statistical Analysis

Descriptive values are expressed as means ±SDs, according to a crossover design
Statistical analysis included paired T-test for comparison of anthropometric measures and biochemical and lipid concentrations in response to treatment and treatment sequence for a two-period crossover design and by chi-squared test for categorical variables
Possible interaction between treatments and treatment sequence and the differences between the means was also tested by paired T-test. All analyses were performed with SPSS package.

Data Collection Summary:

Timing of Measurements

Lab work done before adaptation period, at end of adaptation (considered baseline) and at the beginning and end of each supplement period.

Dependent Variables

Total cholesterol (mmol per L)
Triacylglycerol (mmol per L)
Apo B (g per L)
Apo-A-I (g per L)
Apo B:apo A-I
LDL cholesterol (mmol per L), calculated using the Friedewald algorithm
HDL cholesterol (mmol per L).

Independent Variables

Soluble fiber supplement (P. ovata husk)
Insoluble fiber supplement (hemicellulose and lignin klason).

Control Variables

Isocaloric diet containing 30% of total energy as fat (less than 7% at saturated fatty acids) and less than 300mg cholesterol daily.

Description of Actual Data Sample:

Initial N: 31 men (50 were considered eligible initally, but 19 were excluded because they did not meet the lipid criteria at the end of the four-week adaptation period)
Attrition (final N): 28
Age: 61.4±8.6 years
Ethnicity: Not mentioned [Note: Done in Spain]
Other relevant demographics: Not mentioned
Anthropometrics: Not mentioned
Location: Reus, Spain, Unviersity Hospital Saint Joan.

Summary of Results:

Variables	P. Ovata Husk, Before	P. Ovata Husk, After Eight Weeks	Insoluble Fiber, Before	Insoluble Fiber, After Eight Weeks	Change Between Groups Percentage	P²
Total cholesterol (mmol/L)	5.06±0.67³	5.06±0.68	4.91±0.48	5.09±0.65⁴	-3.76	0.57
Triacylglycerols (mmol/L)	1.62±0.91	1.45±0.83	1.59±0.90	1.50±0.88	-2.79	0.46
Apo B (g/L)	0.92±0.17	0.90±0.18	0.88±0.13	0.91±0.16	-5.24	0.24
Apo A-I (g/L)	1.21±0.16	1.26±0.15	1.20±0.12	1.23±0.13⁴	1.22	0.21
Apo B: apo A-I	0.77±0.19	0.73±0.19	0.74±0.15	0.74±0.16	5.83	0.15
LDL Cholesterol (mmol/L)	3.22±0.61	3.26±0.67	3.10±0.45	3.35±0.61⁷	-6.90	0.18
HDL Cholesterol (mmol/L)	1.12±0.27	1.15±0.27	1.10±0.20	1.06±0.23	6.71	0.006
Total: HDL Cholesterol	4.78±1.41	4.65±1.33	4.63±1.09	5.05±1.43⁷	-10.61	0.002
LDL: HDL Cholesterol	3.04±0.98	3.01±1.02	2.91±0.70	3.33±1.09⁷	-14.24	0.003

¹ N=28
² Comparisons between treatments were tested by paired T-test
³ x±SD (all such values)
^4,7 Significantly different from before insoluble-fiber treatment (paired T-test) ⁴P< 0.05, ⁷P< 0.01
^5,6 Significantly different from before P. ovata husk treatment (paired T-test) ⁵P< 0.05, ⁶P<0.01.

Other Findings

The P. ovata husk did not produce an LDL-cholesterol-lowering effect, as noted in other studies.
Both fibers (soluble and insoluble) significantly reduced the patients' waist circumference (95.3±3.0 at baseline, 93.6±6.1 after P. ovata husk and 93.3±3.2 after insoluble fiber) and waist-to-hip ratio (0.962±0.057 at baseline, 0.940 after P. ovata husk and 0.940±0.055 after insoluble fiber), an aspect not previously reported.

Author Conclusion:

Results indicate that soluble P. ovata husk consumption, in combination with a low-saturated fat, low-cholesterol diet induced a more favorable effect on the lipoprotein profile (reduction in CVD risk factors) than did the addition to the diet of an equivalent amount of insoluble fiber.

Funding Source:

Government:	Instituto de Salud Carlos III
University/Hospital:	FIS

Reviewer Comments:

There is a detailed explanation included of genotype-fiber treatment interaction and gene polymorphisms
Limitations are discussed and suggestions for further studies are noted.

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?	???
	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?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	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.)	Yes
	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%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	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?	???
	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)?	???
	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?	???
	10.2.	Was the study free from apparent conflict of interest?	Yes