DF: Cardiovascular Disease (2008)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To examine if a dietary fiber supplement known to lower fasting plasma cholesterol concentrations can also lower the post-prandial plasma cholesterol, glucose and insulin concentration, when administered just before a meal.

Inclusion Criteria:
  • Free of significant medical disorders
  • None undergoing treatment with any type of drug.

 

Exclusion Criteria:

Not noted.

Description of Study Protocol:

Recruitment

  • Experiment One: Volunteers; not noted
  • Experiment Two: Volunteers; not noted other than "same as experiment #1."

Design

Two experiments done.

  • Experiment One
    • Four days with four different trials in random order, of three fiber supplements and a control
    • Subjects (middle-aged) received water-soluble fiber in tablet form before a breakfast and a lunch.
  • Experiment Two
    • Three-week study comparing the effects of consuming two fiber supplements taken three times a day before meals
    • Subjects received a powdered fiber supplement before meals daily for three weeks, with a glucose tolerance test at the end of a chronic study.
  • Plasma concentrations of cholesterol and its fractions, total TAG, glucose and insulin were measured.

Blinding Used

  • Experiment  One: None; subjects were aware of allocation to test treatment
  • Experiment Two: Subjects did not know which group; none other noted.

Intervention

Experiment One: A different supplement trial taken each of four days by each subject.

  • Treatment A: Two grams water-soluble fiber; purified psyllium
  • Treatment B: One grams psyllium and one 1.0g purified citrus pectin 
  • Treatment C: Two grams water-soluble fiber; purified psyllium (a repeat of treatment A)
  • Treatment D: Control is no supplement
  • Treatments were given in randomized order, one treatment per day over four days.

Experiment Two: One of two fiber supplements taken three times daily before meals for three days. The supplements consisted of:

  • Treatment A: Eight to 33g of a refined fiber extract, providing six grams dietary fiber
  • Treatment B: Two grams alpha-cellulose (BP grade), zero to four grams flavor and zero to six grams citric acid (control, minimum fiber response).

Statistical Analysis

Experiment One

  • For each blood characteristic, analysis of covariance was done (ANOVA and ANACOVA)
  • Response curves were described and analyzed as orthogonal comparisons, tenned curve characteristics
  • Linear and quadratic characteristics were analyzed.

 Experiment Two

  • Covariant adjustment of results for fasting values was done
  • The results of Experiment One had indicated that haemoconcentration may affect responses, therefore concurrent PCV values were used as covariates.
Data Collection Summary:

Timing of Measurements

  • Experiment One
    • On each of the four days, blood samples were drawn without stasis in the fasting state two minutes before breakfast; at 30 minutes, one, two and four hours subsequent to starting breakfast; at two minutes before starting lunch; at one, two and four hours subsequent to the start of lunch.
  • Experiment Two
    • On Days One and 22, glucose tolerance tests were performed following a 12-hour fast
    • Sampling times were recorded relative to the start of the consumption of the glucose solution.

Dependent Variables

  • Plasma lipids
  • Glucose 
  • Insulin.

Independent Variables

Fiber supplements or controls as noted above for each experiment.

Control Variables

In Experiment Two, concurrent PCV values were used as covariates because Experiment One suggested possible haemoconcentration may affect responses.

Description of Actual Data Sample:

Initial N

  • Experiment One: 12
  • Experiment Two: 16.

Attrition (Final N)

None noted for either experiment.

Age

  • Experiment One: 50.6±8.6 (SD) years; range, 29 to 62 years
  • Experiment Two: 42.2±11.6 (SD) years; range, 20 to 60 years

Ethnicity

Not noted for either group.

Other Relevant Demographics

Not noted.

Anthropometrics

  • Experiment One: Mean BMI was 28.2kg per m2 (SD 5.40)
  • Experiment Two: Mean BMI was 25.4kg per m2 (SD 3.81).

Location

Suffolk (Cloinical Investigation Unit).

Summary of Results:

Both tables below are for Experiment Two.

Table 1. (Experiment Two)
Plasma lipid responses on Day 22 (mmol per L) with covariance adjustment for fasting values on Day One (A), unadjusted values (B) and values adjusted for fasting values on both Days One and 22 (C) for subjects receiving sugar-beet fiber (A) and controls (B). SED is standard error of difference between means.

Time After Meals: 

Zero Minutes A

Zero Minutes B

128 Minutes A

128 Minutes B

256 Minutes A

256 Minutes B

128 Minutes C

256 Minutes C

Total Cholesterol

A

5.40

5.36

5.47

5.43

5.47

5.33

5.72

5.69

B

5.90

5.94

5.90

5.93

6.02

6.16

5.64

5.80

SED

0.083

0.455

0.119

0.400

0.141

0.328

0.237

0.317

HDL Cholesterol

A

1.30

1.27

1.48

1.45

1.33

1.27

1.51

1.37

B

1.43

1.46

1.46

1.49

1.47

1.53

1.43

1.43

SED

0.103

0.164

0.051

0.136

0.083

0.120

0.020

0.082

LDL Cholesterol

A

3.51

3.60

3.44

3.52

3.51

3.50

3.63

3.71

B

3.87

3.79

3.91

3.83

3.86

3.86

3.72

3.65

SED

0.100

0.354

0.124

0.386

0.126

0.365

0.137

0.201

TAG

A

1.12

1.02

1.06

0.93

1.30

1.16

1.15

1.33

B

1.28

1.38

1.21

1.35

1.50

1.64

1.12

1.46

SED

0.223

0.214

0.267

0.267

0.205

0.247

0.117

0.114 

Table 2. (Experiment Two)
Fasting and post-prandial plasma glucose and insulin concentrations in subjects treated with sugar-beet fiber (A) and controls (B) at various times after a bolus glucose dose (Day One) or a fiber supplement and a bolus glucose dose (Day 22).

Time (Minutes):

Zero

16

32

64

128

256
Glucose (mmol/L)

Day One

 

 
A

 5.17

6.52

 7.6

7.48

 5.28

4.42
B

 5.03

6.88

 7.41

6.28

 4.50

4.31
SED
0.344
0.383
0.434
1.014
0.433
0.229
Day 22   A
4.89
6.2
6.91
6.72
4.51
4.27
B
4.82
6.68
7.53
6.01
4.20
4.49
SED
0.092
0.185
0.351
0.781
0.540
0.238
Insulin (µU/ml)  Day One   A
6.8
26.4
41.1
48.3
25.4
5.7
B
7.1
28.9
45.2
56.7
17.8
5.6
SED
1.11
7.41
12.40
14.95
4.98
0.73
Day 22   A
7.9
36.0
46.3
48.2
21.5
6.8
B
9.1
46.1
63.9
54.7
14.9
7.7
SED
1.24
10.99
11.61
13.29
6.66
0.856

Other Findings

  • Sugar-beet dietary fiber (six grams), taken three times daily as a powder before meals for three weeks, lowers the concentrations of total and LDL cholesterol, following a 12-hour fast on the 22nd day.
  • Change in haemoconcentration, measured by plasma albumin or PCV, was found to influence the PP measurements in both experiments. If no account is taken of this effect, the improvement in glucose tolerance caused by dietary fiber could be underestimated.
Author Conclusion:

Low doses of psyllium gum have no acute effect on carbohydrate and lipid markers of IHD risk during the post-prandial period in volunteers with mildly increased risk.

Funding Source:
Industry:
Pharmaco
Pharmaceutical/Dietary Supplement Company:
Reviewer Comments:
  • Two related, but different experiments are described within this article
  • Many details are given about many things (time of day subjects entered and left clinic), but other details are missing (inclusion and exclusion criteria)
  • The results from Experiment One are discussed extensively within the text and shown in graph form and were not converted to a table here because of the small number and short duration of the trial
  • There is extensive discussion about the findings, implications and related factors, although limitatins are not directly addressed.
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? No
  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? No
  2.2. Were criteria applied equally to all study groups? ???
  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%.) No
  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? Yes
  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? ???
  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? No
  6.6. Were extra or unplanned treatments described? No
  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? ???
  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? 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