Clinical trial NCT01248026: Impact of Buttermilk on Cholesterol Concentration and Homeostasis
Official title: Impact of Buttermilk on Cholesterol Concentration and Homeostasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Disease
Keywords: Cardiovascular disease
Buttermilk
Blood lipids
Cholesterol absorption
Cholesterol synthesis
Lead sponsor: Laval University
Sponsor class: OTHER
Collaborators: name: Dairy Farmers of Canada
First posted: 2010-11-25
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in plasma LDL-Cholesterol concentrations
timeFrame: At the beginning of the study and the end of the 2 four-week periods
Secondary outcomes:
measure: Change in blood lipids (Total cholesterol, HDL-Cholesterol, Triglycerides)
timeFrame: At the beginning of the study and the end of the 2 four-week periods
measure: Change in blood pressure
timeFrame: At the beginning of the study and the end of the 2 four-week periods
measure: Change in surrogates of cholesterol absorption and synthesis
timeFrame: At the beginning of the study and the end of the 2 four-week periods
measure: Change in anthropometric measures (waist and hip circumferences)
timeFrame: At the beginning of the study and the end of the 2 four-week periods
Other outcomes:
Locations:
city: Quebec
country: Canada
facility: Institute of Nutraceutical and Functional Foods (INAF), Laval University
Study officials:
affiliation: Faculty of Medicine, Laval University
name: Patrick Couture, MD, FRCP (C, PhD)
role: STUDY_DIRECTOR
References:
citation: Conway V, Couture P, Richard C, Gauthier SF, Pouliot Y, Lamarche B. Impact of buttermilk consumption on plasma lipids and surrogate markers of cholesterol homeostasis in men and women. Nutr Metab Cardiovasc Dis. 2013 Dec;23(12):1255-62. doi: 10.1016/j.numecd.2013.03.003. Epub 2013 Jun 17.