Clinical trial NCT02644109: Effect On Serum Cholesterol Of Dairy Products With Addition Of Esterified Phytosterols
Official title: Effect On Serum Cholesterol Of Dairy Products With Addition Of Esterified Phytosterols In Chilean Subjects With Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Dyslipidemias
Hypercholesterolemia
Lead sponsor: University of Chile
Sponsor class: OTHER
Collaborators: name: Pontificia Universidad Catolica de Chile
First posted: 2015-12-31
Enrollment: 52
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Serum LDL Cholesterol
timeFrame: 1 month
Secondary outcomes:
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Instituto de Nutricion y Tecnologia de los Alimentos, Universidad de Chile
state: Región Metropolitana de Santiago
city: Santiago
country: Chile
facility: Department of Nutrition, Diabetes and Metabolism. Pontificia Universidad Catolica de Chile
Study officials:
affiliation: University of Chile
name: Sandra Hirsch, MD
role: STUDY_DIRECTOR
References:
citation: Stone NJ, Robinson JG, Lichtenstein AH, Goff DC Jr, Lloyd-Jones DM, Smith SC Jr, Blum C, Schwartz JS; 2013 ACC/AHA Cholesterol Guideline Panel. Treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: synopsis of the 2013 American College of Cardiology/American Heart Association cholesterol guideline. Ann Intern Med. 2014 Mar 4;160(5):339-43. doi: 10.7326/M14-0126.
citation: Korpela R, Tuomilehto J, Hogstrom P, Seppo L, Piironen V, Salo-Vaananen P, Toivo J, Lamberg-Allardt C, Karkkainen M, Outila T, Sundvall J, Vilkkila S, Tikkanen MJ. Safety aspects and cholesterol-lowering efficacy of low fat dairy products containing plant sterols. Eur J Clin Nutr. 2006 May;60(5):633-42. doi: 10.1038/sj.ejcn.1602362.
citation: Mannarino E, Pirro M, Cortese C, Lupattelli G, Siepi D, Mezzetti A, Bertolini S, Parillo M, Fellin R, Pujia A, Averna M, Nicolle C, Notarbartolo A. Effects of a phytosterol-enriched dairy product on lipids, sterols and 8-isoprostane in hypercholesterolemic patients: a multicenter Italian study. Nutr Metab Cardiovasc Dis. 2009 Feb;19(2):84-90. doi: 10.1016/j.numecd.2008.03.012. Epub 2008 Aug 31.
citation: Ortega RM, Palencia A, Lopez-Sobaler AM. Improvement of cholesterol levels and reduction of cardiovascular risk via the consumption of phytosterols. Br J Nutr. 2006 Aug;96 Suppl 1:S89-93. doi: 10.1079/bjn20061708.
citation: Nestel P, Cehun M, Pomeroy S, Abbey M, Weldon G. Cholesterol-lowering effects of plant sterol esters and non-esterified stanols in margarine, butter and low-fat foods. Eur J Clin Nutr. 2001 Dec;55(12):1084-90. doi: 10.1038/sj.ejcn.1601264.
citation: Miettinen TA, Puska P, Gylling H, Vanhanen H, Vartiainen E. Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population. N Engl J Med. 1995 Nov 16;333(20):1308-12. doi: 10.1056/NEJM199511163332002.