EAL

DLM: Plant Stanols and Sterols (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To assess the effect of consumption of a yoghurt-based drink enriched with 1-2 g plant sterols/day on serum lipids, transaminases, vitamins and hormone status in patients with primary moderate hypercholesterolemia.

Inclusion Criteria:

Outpatients attending Lipid Clinics of Rome and Milan Universities. All subjects had normal fasting glucose levels and exhibited normal liver, renal and thyroid functions.

Exclusion Criteria:

None of the patients suffered from CHD, HTN, DM or obesity. None used drugs with documented lipid-modifying effects, such as diuretics, beta-blockers, corticosteroids, sex steroids or antifungal agents.

Description of Study Protocol:

Week -8: RD trained individuals to follow AHA Step I dietary recommendations

Part 1 Randomization: to either yoghurt drink with 1 g plant sterol extract or yogurt

Week 0: 3 day food record

Week 2: fasting blood sample

Week 4: 3 day food record, fasting blood sample

Week 6: end of 2 week washout period, 3 day food record, fasting blood samples, crossed over for additional 4 weeks

Week 8: fasting blood samples

Week 10: 3 day food record, fasting blood samples

Week 12: end of follow-up periods, 3 day food record, fasting blood samples

Part 2 Randomization: after 4 week washout period, 11 subjects randomly chosen to be treated with 2 g/sterols per day for 8 weeks to determine efficacy, safety and tolerability

Data Collection Summary:

At each visit, BP taken, subjects asked about physical activity, adverse effects, transient diseases, drug use. Serum TC, TG, HDL-C, LDL-C calculated using Friedewald’s equation, serum transaminases, hormones gonadotropins, testosterone, oestradiol) and fat soluble vitamins (A, D, E). Double blind.

Description of Actual Data Sample:

30 hypercholesterolemic subjects in first study, 11 in second.

Summary of Results:

Compliance was more than 95% during all treatment periods.

Part 1:

When compared with baseline values the consumption of yoghurt enriched with plant sterols was shown to significantly reduce serum TC (-6.7%, P = 0.0005) and LDL-C levels (-11.1%, P = 0.0009) and LDL-C:HDL-C (-15.1%, P = 0.05). No differences were observed in HDL-C and TG levels. The period effect and the carry-over effect were not statistically significant. Nutritional analysis shows that patients were able to keep their nutrient intake low in fat and cholesterol over 12 weeks.

Part 2:

The results of the effects of 2 g plant sterols/day on serum lipids show that the cholesterol-lowering effect of plant sterols is dose-dependent; a greater reduction in TC, LDL-C and LDL-C: HDL-C was observed after the daily dose of 2 yoghurts (2 g plant sterols). Percentage decreases in TC, LDL-C and LDL-C:HDL-C were respectively 11.2% (P < 0.001), 15.6% (P < 0.001) and 13.3% (P = 0.03). No statistically significant effects were observed in HDL-C or TG levels. There were only slight, not statistically significant, differences in serum transaminases or vitamin A and E levels between those at baseline and those at the end of the treatment period. However, a significant increase in the vitamin D level was seen after the treatment with plant sterols (P = 0.008). There were no significant changes in serum hormone (FSH, sex hormone-binding globulin, oestradiol and testosterone) values before and after the treatment period.

Author Conclusion:

The results obtained in these short-term studies suggest that a simple nutritional self-care treatment with a low-fat yoghurt based drink moderately enriched with plant sterols may effectively lower TC and LDL-C levels in patients with primary moderate hypercholesterolemia who are considered unresponsive to dietary treatment alone. Cholesterol-lowering treatment with plant sterols appears to be safe. However, the adverse effects of treatment with plant sterols on serum transaminase, vitamin and hormone values need to be confirmed in longer-term studies.

Funding Source:

Industry:

Valio Ltd

Food Company:

University/Hospital:

University of Rome 'La Sapienza', University of Milan (Italy),

Not-for-profit

Reviewer Comments:

Well controlled study with high rates of compliance. The authors note that the increase in serum vitamin D level may be due to the fact that the treatment period of the second part of the study began in spring when more vitamin D is synthesized in the skin. Small number of subjects in study 2.

After 4 weeks of 1.0 g sterols:

TC Baseline: 6.83 +/- 0.4 mmol/L (264.32 +/- 15.48 mg/dL)
TC Ending: 6.37 +/- 0.5 mmol/L (246.52 +/- 19.35 mg/dL)
% Change: -6.7% (p =0.0005)
LDL-C Baseline: 4.67 +/- 0.4 mmol/L (180.73 +/- 15.48 mg/dL)
LDL-C Ending: 4.15 +/- 0.7 mmol/L (160.61 +/- 27.09 mg/dL)
% Change: -11.1% ( p = 0.0009)
HDL-C and TG: no statistically significant changes

After 4 weeks of 2.0 g sterols:

TC Baseline: 6.70 +/- 0.31 mmol/L (259.29 +/- 12.00 mg/dL)
TC Ending: 5.95 +/- 0.48 mmol/L (230.27 +/- 18.58 mg/dL)
% Change: 11.2% (p < 0.001)
LDL-C Baseline: 4.42 +/- 0.53 mmol/L (171.05 +/- 20.51 mg/dL)
LDL-C Ending: 3.73 +/- 0.67 mmol/L (144.35 +/- 25.93 mg/dL)
% Change: 15.6% (p < 0.001)
HDL-C and TG: no statistically significant changes

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?	N/A
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	N/A
	1.3.	Were the target population and setting specified?	N/A
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?	N/A
	2.2.	Were criteria applied equally to all study groups?	N/A
	2.3.	Were health, demographics, and other characteristics of subjects described?	N/A
	2.4.	Were the subjects/patients a representative sample of the relevant population?	N/A
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)	N/A
	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.)	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?	N/A
	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?	N/A
	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?	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.)	N/A
	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?	N/A
	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?	N/A
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	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?	N/A
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	N/A
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	N/A
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	N/A
	7.5.	Was the measurement of effect at an appropriate level of precision?	N/A
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	N/A
	7.7.	Were the measurements conducted consistently across groups?	N/A
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?	N/A
	8.2.	Were correct statistical tests used and assumptions of test not violated?	N/A
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	N/A
	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?	N/A
	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?	N/A
	9.2.	Are biases and study limitations identified and discussed?	N/A
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	N/A
	10.2.	Was the study free from apparent conflict of interest?	N/A