BMILK: Impact of Buttermilk on Cholesterol Concentration and Homeostasis

Sponsor

Laval University (Other)

Overall Status

Completed

CT.gov ID

NCT01248026

Collaborator

Dairy Farmers of Canada (Other)

Enrollment

Location

Arms

Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The role of low-density lipoprotein cholesterol (LDL-C) in the pathogenesis of cardiovascular disease (CVD) and the clinical benefit of lowering LDL-C in high-risk patients have both been well established. The key contribution of the intestine to whole body cholesterol homeostasis and thus to regulating plasma cholesterol concentrations has also been recognized over the last years. It is now clear that cholesterol homeostasis and hence plasma LDL-C concentrations are maintained by a fine-tuned balance between intestinal cholesterol absorption and endogenous cholesterol synthesis.

Cholesterol is a highly hydrophobic molecule and for that reason, its absorption is almost entirely dependent on its solubilizing capacity in bile acid micelles within the intestine. Recent in vitro studies from our laboratory have shown that buttermilk, a unique by-product of butter manufacturing resulting from the churning of cream, has a strong inhibitory effect on cholesterol micelle solubility. This phenomenon is likely due to the presence of unique milk fat globule membrane (MFGM) fragments present in buttermilk that are produced during the manufacturing of dairy cream into butter. Most of the work done so far on the subject has focused on phospholipids purified from MFGM, while overlooking the complex and entire MFGM mixture of bioactive proteins and polar lipids found in buttermilk. To the best of our knowledge, no study has yet documented the impact of whole buttermilk on plasma cholesterol concentration in human.

The general objective of this research project is to investigate for the first time the impact of buttermilk on plasma cholesterol and other risk factors for CVD in humans. More specifically, we propose to investigate the impact of buttermilk consumption on plasma LDL-C and other CVD risk factors as well as on plasma surrogates of cholesterol absorption and synthesis.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Disease	Other: Buttermilk	N/A

Detailed Description

The proposed research will be undertaken as a double-blind randomized cross-over study with participants being subjected to 2 consecutive treatments of 4 weeks each, in random order, during which they will consume 45g of buttermilk and a macro- and micronutrient matching placebo. The treatments will be different in their content of MFGM (present in buttermilk, absent in placebo). Buttermilk and placebo will be fully characterized and formulated in ready-to-use pouches, each pouch containing 22.5 g of artificially flavored products that will have to be mixed in a fixed amount of water for consumption. Participants will have to consume two pouches every day. Based on a 2500 kcal/day regimen, we have calculated that these placebo and buttermilk formulation will contribute to approximately 200 kcal (from 5% and 10%) of the daily energy intake of participants, who will be asked to maintain other aspects of their nutritional habits constant throughout the study.

Fluctuations in female hormones have been shown to influence metabolic variables. For that reason, outcomes at the end of each dietary phase will be measured during the follicular phase of menstrual cycle (day 3 to day 9) in pre-menopausal women. This is another argument for using a 4-wk intervention, which essentially corresponds to the mean duration of the menstrual cycle of most women. Pre-menopausal women will start the first diet during the first week of their menstrual cycle.

Study Design

Study Type:

Interventional

Actual Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Impact of Buttermilk on Cholesterol Concentration and Homeostasis

Study Start Date :

Jan 1, 2011

Actual Primary Completion Date :

Aug 1, 2011

Actual Study Completion Date :

Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Buttermilk	Other: Buttermilk Consumption of the 2 experimental periods buttermilk (45 g/d) placebo (45 g/d,) Other Names: chocolat buttermilk ready-to-use pouches
Placebo Comparator: Placebo	Other: Buttermilk Consumption of the 2 experimental periods buttermilk (45 g/d) placebo (45 g/d,) Other Names: chocolat buttermilk ready-to-use pouches

Arm

Intervention/Treatment

Experimental: Buttermilk

Other: Buttermilk

Consumption of the 2 experimental periods buttermilk (45 g/d) placebo (45 g/d,)

Other Names:

chocolat buttermilk ready-to-use pouches

Placebo Comparator: Placebo

Other: Buttermilk

Consumption of the 2 experimental periods buttermilk (45 g/d) placebo (45 g/d,)

Other Names:

chocolat buttermilk ready-to-use pouches

Outcome Measures

Primary Outcome Measures

Change in plasma LDL-Cholesterol concentrations [At the beginning of the study and the end of the 2 four-week periods]

Secondary Outcome Measures

Change in blood lipids (Total cholesterol, HDL-Cholesterol, Triglycerides) [At the beginning of the study and the end of the 2 four-week periods]
Change in blood pressure [At the beginning of the study and the end of the 2 four-week periods]
Change in surrogates of cholesterol absorption and synthesis [At the beginning of the study and the end of the 2 four-week periods]
Change in anthropometric measures (waist and hip circumferences) [At the beginning of the study and the end of the 2 four-week periods]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy men and women aged between 18 and 65 years
For pre-menopausal women: regular menstrual cycle for the last 3 months (25- 35 days), using or not contraceptive agents
LDL-Cholesterol concentration between 3.2 and 4.5 mmol/L
A 10-yr calculated Framingham risk below 10%.
Stable body weight (+/- 2 kg) for 6 months before the beginning of the study
Smoking or not

Exclusion Criteria:

Previous history of cardiovascular disease, type 2 diabetes and monogenic dyslipidemia
Subjects taking medications for hyperlipidemia or hypertension
Endocrine disorders
Body mass index > 35 kg/m2
Food allergies
Men and women with extreme nutritional habits such as vegetarism or alcohol consumption > 2 drinks/day