Milk products supplemented with Phytosterols or omega-3 oils and biomarkers of cardiovascular disease

• Register: ISRCTN
• Last refreshed on: 8 May 2023
• Main ID: ISRCTN78753338
• Date of registration: 16/03/2017
• Prospective Registration: No
• Primary sponsor: Instituto Catalán de Ciencias Cardiovasculares (ICCC) - Hospital de la Santa Creu i Sant Pau
• Public title: Milk products supplemented with Phytosterols or omega-3 oils and biomarkers of cardiovascular disease
• Scientific title: Scientific basis of cardiovascular effects derived from the regular consumption of milk products supplemented with Phytosterols or omega-3 oils at systemic level in subjects at low cardiovascular risk with moderated hypercholesterolemia and overweight or obesity.
• Date of first enrolment: 15/02/2012
• Target sample size: 35
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN78753338
• Study type: Interventional
• Study design: Double-blind randomized two-arm longitudinal crossover study (Prevention)
• Phase: Not Applicable

Countries of recruitment

Spain

Contacts

• Name: Lina Badimon

Key inclusion & exclusion criteria

Inclusion criteria: 1. Healthy adult males and females between 25 and 70 years old
2. Overweight or grade 1 obese (body mass index greater than 25 kg/m^2)
3. Signed informed consent
Exclusion criteria: 1. Previous history of cardiovascular disease (ischaemic heart disease - angina or recent or old myocardial infarction, cerebral vascular accident, or peripheral vascular disease)
2. No documented cardiovascular disease (ischaemic heart disease - angina or recent or old myocardial infarction or previous or cerebral vascular accident, peripheral vascular disease)
3. Any disease affecting lipid metabolism
4. Any severe chronic disease
5. Lactose intolerance
6. Being in the phase of weight loss or expressing a desire for weight loss in the 4 months of the study
3. Alcohol consumption >60 g/day
7. Under treatment with fibrates or statins

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Arteriosclerosis
Circulatory System
Atherosclerosis

Intervention(s)

All subjects were submitted to two 28-day treatment sequences, separated by a 4 weeks washout period. Before the initiation of the intervention, individuals were submitted to a 2-week run-in period. During the run-in and wash-out periods, participants received 250 mL/day commercially available plain low-fat milk (without PhyS or ?-3), with the same composition to that used for preparing the PhyS-enriched- and ?-3 enriched milks.

At the end of the run-in period, subjects were randomly allocated to receive one of the two treatment sequences:
Study arm 1: Phytosterol (PhyS)-enriched milk in the first intervention period and ?-3 enriched milk in the second intervention period
Study arm 2: Omega-3 (?3)-enriched milk in the first intervention period and PhyS-enriched milk in the second intervention period

Participants were instructed to consume a pack of milk (250 mL) per day, distributed in one or more portions according to their normal habits, replacing their habitual milk-products consumption. Subjects were requested to maintain their habitual diet at levels consistent with maintenance of a stable body weight and to continue their normal pattern of physical activity throughout the study period.

Lipid content varied from 0.4 g per 100 ml milk in the control low-fat milk to 0.8 g in the ?3-enriched milk and 0.9 g in the PhyS-enriched milk. The 20.6% of the lipid content in the ?3-enriched milk were omega-3 fatty acids, mainly consisting in EPA and DHA (150 mg EPA+DHA / 100 mL milk) that represented the 90.8% of the total omega-3 fatty acid content. In addition to lipid content, every 100 mL PhyS-enriched milk contained 0.64 g plant sterols (expressed as free PhyS). According to the provider’s information, the supplemented vegetable oil-based sterols (VEGAPURE® 95E) were

Primary Outcome(s)

1. Triglyceride and cholesterol levels, measured using biochemical analysis
2. Oxidative profile: measure of the lipidic peroxidation in plasma and LDL, the plasma antioxidant behavior and LDL resistance to oxidation
3. Fatty acids (FA) and lipidomic pattern measured in plasma and LDL samples respectively and analyzed by LC/MS/MS. The analysis of FA is performed after the derivatization of the samples to convert FAs into thrimethylaminoethyl esther iodide derivates. LDL lipidomic profile is analyzed in mixture with an internal lipid standard mixture
4. Proteomic profile:
4.1. Analysis of the differential proteomic profile of the lipid and lipid-free fraction of serum and plasma samples measured by 2DE electrophoresis, followed by protein identification by mass spectrometry identification (MALDI-TOF)
4.2. Validation of the results by western blot analysis and enzyme-linked immunosorbent assay (ELISA) kits
Measured at baseline and after each intervention period

Secondary Outcome(s)

1. Alcohol intake, smoking and dietary habits, taken from participants' medical records
2. Dietary habits, assessed using a questionnaire at baseline
3. Inflammatory variables related to atherosclerosis
4. Gene expression measured by RT-PCR and arrays either in the plasma or the blood cellular fraction after the intake of supplemented milk
5. Circulating microparticles assessed using blood samples or the cells of the vascular wall
6. Potential gene polymorphisms associated with the response to the interventions at protemic and lipidomic levels
Measured at baseline and after each intervention period

Secondary ID(s)

ICCC-9 FITOCARD

Source(s) of Monetary Support

Ministerio de Economía y Competitividad, Instituto de Salud Carlos III

Ethics review

Status:
Approval date:
Contact:

Ethics Committee for Clinical Research from the Hospital de la Santa Cruz y San Pablo, 05/07/2011, ref: 10/2011

Results

• Results available: Yes
• Date Completed: 20/07/2012