Effect On Serum Cholesterol Of Dairy Products With Addition Of Esterified Phytosterols

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.

• Phytosterol (Dietary supplement), also known as ACTICOL: 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.
• Placebo (Dietary supplement): 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.

Primary outcomes

• Serum LDL Cholesterol [1 month]

Sex: All, ages: 40 Years to 65 Years, accepts healthy volunteers

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).

Participant flow

Outcome results

• Serum LDL Cholesterol (Primary), Mean, mg/dl: Phytosterols 122.2 +/- 34.6; Placebo 113.5 +/- 33.8

Adverse events

Other adverse events by term

• 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. PMID 24474185
• Results publication: 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. PMID 16404415
• Results publication: 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. PMID 18762410
• Results publication: 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. PMID 16923260
• Results publication: 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. PMID 11781675
• Results publication: 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. PMID 7566021

• Sandra Hirsch, MD, Study director, University of Chile