Dyslipidemias, Hypercholesterolemia
Conditions
Brief summary
Hypercholesterolemia is an important risk factor for cardiovascular disease, asociated primarily with high plasma levels of LDL lipoprotein, which in turn depend on the endogenous hepatic synthesis of cholesterol and its absorption at intestinal level. It has been demonstrated that there reducing plasma LDL is beneficial, mainly with the use of statins, which are the first treatment option for a moderate hypercholesterolemia. Phytosterols reduce the intestinal absorption of cholesterol by reducing its incorporation into lipid micelles. Consequently, phytosterols have become a relevant alternative treatment against low hypercholesterolemia. The target population are 40 to 65 years old individuals with low hypercholesterolemia.
Detailed description
Different protocols have demonstrated that phytosterol intake fluctuates between 1000 to 2000 mg per day decreasing LDL by around 10%, independently of levels of blood triglycerides and HDL (high density lipoproteins) concentrations. In fact, the National Cholesterol Education Program and the American Heart Association recommend the addition of 2 g/day of phytosterols to daily diet of adults. This is also recommended by the FDA (Food and Drug administration). Phytosterols delivery has been proven effective when administrated in lipid matrixes such as margarines and dressings and low-fat such as skimmed milk and yogurt, proving to have an hypolipidemic effect. The investigational products consist of powder milk and a drinking yoghurt with the addition of esterified phytosterols, with a total daily intake of 1.95 g/day (1.17 g/day of free equivalent). Primary objective: To evaluate the impact in Chilean population of phytosterols incorporated into dairy products in reduction of LDL cholesterol. Secondary objectives: 1. To evaluate potential changes in blood cholesterol concentration according to nutritional state and age. 2. To determine the appearance of symptoms and/or effects during the intervention period. The trial has been designed to evaluate the effect of phytosterols incorporated to low fat dairy products in Chile, through the consumption of one glass of milk powder and 90 mL of drinking yoghurt, which results in a daily consumption of 1.95 g/day of esterified phytosterols. This amount falls within demonstrated effective doses reported in literature.
Interventions
DIETARY_SUPPLEMENTPhytosterol
Day 1: Anthropometry, laboratory test, dietary intake (24 hour recall and food frequency questionnaire) and presence of symptoms and side effects will be determined, a logbook will be provided to record product consumption, symptoms, medications and side effects. Then will be randomly assigned to one of the groups. Days 7 & 21: 24 hour recall, review of symptoms, side effects and adherence as registered in the logbook. Days 15 & 30: Anthropometry, vital signs, venous blood sample, review of symptoms, side effects and adherence to intervention as registered on logbook, dietary intake (24-hour recall), delivery of monetary compensation proportional to the study days will be given before being discharged.
DIETARY_SUPPLEMENTPlacebo
Day 1: Anthropometry, laboratory test, dietary intake (24 hour recall and food frequency questionnaire) and presence of symptoms and side effects will be determined, a logbook will be provided to record product consumption, symptoms, medications and side effects. Then will be randomly assigned to one of the groups. Days 7 & 21: 24 hour recall, review of symptoms, side effects and adherence as registered in the logbook. Days 15 & 30: Anthropometry, vital signs, venous blood sample, review of symptoms, side effects and adherence to intervention as registered on logbook, dietary intake (24-hour recall), delivery of monetary compensation proportional to the study days will be given before being discharged.
Sponsors
Pontificia Universidad Catolica de Chile
University of Chile
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Individuals between 40 to 65 y old. 2. Males and females. 3. Body mass index between 20 to 35 kg/m2 4. Mild hypercholesterolemia (LDL between 130 to 190 mg/dl) without requirement of immediate pharmacological treatment. 5. Without symptoms of atherosclerotic vascular disease. 6. Regular consumption of dairy foods (at least once a day). 7. Sedentary lifestyle defined as less than 20 min, three times per week of moderate to intense physical activity)
Exclusion criteria
1. Individuals with sitosterolemia. 2. Use of hypolipidemic drugs within the past 6 weeks before initiated the study. 3. Presence of type 1 or 2 diabetes; nephrotic syndrome or chronic kidney disease at stage III (estimated glomerular filtration rate\<60 ml/min) or higher; gastrointestinal, liver, hepatobiliary, endocrine diseases or any condition potentially effecting lipid metabolism. 4. History of heart failure, unstable angina, cerebrovascular accident, heart failure, uncontrolled arrhythmias, high blood pressure (systolic\>160 mm/Hg or diastolic\>100 mm/Hg), cardiac surgery or other vascularization procedure. 5. Blood triglycerides higher than 400 mg/dl. 6. History of cancer disease over the last 5 years. 7. Pregnant and lactating women. 8. Lactose intolerant individuals or presence of related symptoms 9. Individuals with cow´s milk protein allergy. 10. Vegetarians 11. Regular use of drugs for obesity treatment, or affecting lipid metabolism. 12. Regular use of nutritional supplements. 13. Smokers having more than 5 units per day. 14. Individuals drinking more than 3 standard units per day of alcoholic beverages (\>3 glasses of wine, 2 beers o 1 strong alcohol).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Serum LDL Cholesterol | 1 month |
Countries
Chile
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phytosterols 1. Milk powder: subjects will be instructed to consume 22 g/day of the product, with 0.65 g of esterified phytosterols (0.39 g of free equivalent sterols). The product will be reconstituted with 200 ml of water at time of consumption, preferably at breakfast or tea time. The total amount of product will be provided at the beginning of the study (day 1), together with instructions, material for preparation, and storage.
2. Drinking yoghurt: the daily volume consumed will be 90 ml/day with 1.3 grs of esterified phytosterols (0.78 g of free equivalent phytosterols). Subjects will be instructed to consume this beverage with main meal (not later than 15 min after it. The product should be kept refrigerated. Products will be distributed to subjects on a weekly basis. | 24 |
| Placebo 1. Milk powder: subjects will be instructed to consume 22 g/day of the product, without phytosterols. The product will be reconstituted with 200 ml of water at time of consumption, preferably at breakfast or tea time. The total amount of product will be provided at the beginning of the study (day 1), together with instructions, material for preparation, and storage.
2. Drinking yoghurt: the daily volume consumed will be 90 ml/day without phytosterols. Subjects will be instructed to consume this beverage with main meal (not later than 15 min after it. The product should be kept refrigerated. Products will be distributed to subjects on a weekly basis. | 28 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 |
Baseline characteristics
| Characteristic | Placebo | Total | Phytosterols |
|---|---|---|---|
| Age, Continuous | 53.2 years STANDARD_DEVIATION 6.6 | 53.2 years STANDARD_DEVIATION 6.32 | 53.2 years STANDARD_DEVIATION 6.1 |
| Body mass index | 27.9 kg/m^2 STANDARD_DEVIATION 3.2 | 27.9 kg/m^2 STANDARD_DEVIATION 3.3 | 27.9 kg/m^2 STANDARD_DEVIATION 3.5 |
| LDL-cholesterol | 146.3 mg/dl STANDARD_DEVIATION 15.6 | 147.7 mg/dl STANDARD_DEVIATION 16.9 | 149.5 mg/dl STANDARD_DEVIATION 18.6 |
| Region of Enrollment Chile | 28 participants | 52 participants | 24 participants |
| Sex: Female, Male Female | 14 Participants | 31 Participants | 17 Participants |
| Sex: Female, Male Male | 14 Participants | 21 Participants | 7 Participants |
| Total Cholesterol | 226.4 mg/dl STANDARD_DEVIATION 19.3 | 228.9 mg/dl STANDARD_DEVIATION 21 | 231.9 mg/dl STANDARD_DEVIATION 22.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 2 / 28 |
| serious Total, serious adverse events | 0 / 24 | 0 / 28 |
Outcome results
Primary
Serum LDL Cholesterol
Time frame: 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phytosterols | Serum LDL Cholesterol | 122.2 mg/dl | Standard Deviation 34.6 |
| Placebo | Serum LDL Cholesterol | 113.5 mg/dl | Standard Deviation 33.8 |