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Effect of buttermilk consumption on blood pressure in moderately hypercholesterolemic men and women


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Milk fat globule membrane (MFGM) found in buttermilk is rich in unique bioactive proteins. Several studies suggest that MFGM proteins possess biological activities such as cholesterol-lowering, antiviral, antibacterial, and anticancer properties, but data in humans are lacking. Furthermore, to our knowledge, no study has yet investigated the antihypertensive potential of MFGM proteins from buttermilk. The aim of this study was to investigate the effects of buttermilk consumption on blood pressure and on markers of the renin-angiotensin-aldosterone (RAS) system in humans. Men and women (N = 34) with plasma low-density lipoprotein cholesterol < 5 mmol/L and normal blood pressure (< 140 mm Hg) were recruited in this randomized, double-blind, placebo-controlled, crossover study. Their diets were supplemented with 45 g/d of buttermilk and with 45 g/d of a macro-/micronutrient-matched placebo in random order (4 wk for each diet). Buttermilk consumption significantly reduced systolic blood pressure (-2.6 mm Hg; P = 0.009), mean arterial blood pressure (-1.7 mm Hg; P = 0.015), and plasma levels of the angiotensin I-converting enzyme (-10.9%; P = 0.003) compared with the placebo, but had no effect on plasma concentrations of angiotensin II and aldosterone. Short-term buttermilk consumption reduces blood pressure in normotensive individuals.
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Brief report
Effect of buttermilk consumption on blood pressure in moderately
hypercholesterolemic men and women
erie Conway Ph.D.
, Patrick Couture M.D., Ph.D.
, Sylvie Gauthier Ph.D.
Yves Pouliot Ph.D.
, Benoı
t Lamarche Ph.D.
STELA Dairy Research Center, Laval University, Quebec, Canada
Institute of Nutrition and Functional Foods, Laval University, Quebec, Canada
Lipid Research Center, CHUQ Research center, Quebec, Canada
article info
Article history:
Received 19 April 2013
Accepted 24 July 2013
Buttermilk bioactive peptides
Blood pressure
Reninangiotensinaldosterone system
Milk fat globule membrane
Objectives: Milk fat globule membrane (MFGM) found in buttermilk is rich in unique bioactive
proteins. Several studies suggest that MFGM proteins possess biological activities such as cholesterol-
lowering, antiviral, antibacterial, and anticancer properties, but data in humans are lacking.
Furthermore, to our knowledge, no study has yet investigated the antihypertensive potential of
MFGM proteins from buttermilk. The aim of this study was to investigate the effects of buttermilk
consumption on blood pressure and on markers of the reninangiotensinaldosterone (RAS) system
in humans.
Methods: Men and women (N ¼34) with plasma low-density lipoprotein cholesterol <5 mmol/L
and normal blood pressure (<140 mm Hg) were recruited in this randomized, double-blind,
placebo-controlled, crossover study. Their diets were supplemented with 45 g/d of buttermilk
and with 45 g/d of a macro-/micronutrient-matched placebo in random order (4 wk for each diet).
Results: Buttermilk consumption signicantly reduced systolic blood pressure (2.6 mm Hg; P¼
0.009), mean arterial blood pressure (1.7 mm Hg; P¼0.015), and plasma levels of the angiotensin
I-converting enzyme (10.9%; P¼0.003) compared with the placebo, but had no effect on plasma
concentrations of angiotensin II and aldosterone.
Conclusion: Short-term buttermilk consumption reduces blood pressure in normotensive
Ó2014 The Authors. Published by Elsevier Inc. All rights reserved.
Hypertension is a major risk factor for cardiovascular disease
(CVD) and renal dysfunction, and as a leading cause of death
worldwide, is associated with 7.1 million deaths per year [1].A
healthy diet is an important element in the primary prevention
and management of hypertension [2]. The development of dairy-
based functional foods for blood pressure (BP) management has
been of major interest in the past years. Milk peptides have been
shown to lower BP in many clinical trials, and have been
extensively reviewed [36]. Indeed, small milk peptides with
hydrophobic and aromatic amino acid residues have been
targeted for the development of functional foods inhibiting
angiotensin-converting enzyme (ACE) activityda key enzyme
involved in BP regulation. Milk fat globule membrane (MFGM)
components, found in large quantities in buttermilk, have been
of growing interest over the past years because of their unique
nutritional properties [7]. However, no study has yet investigated
the antihypertensive potential of MFGM proteins from butter-
milk. The aim of this study was to investigate for the rst time
the effects of buttermilk consumption on BP and on the markers
of the reninangiotensinaldosterone (RAS) system in normo-
tensive patients.
Materials and methods
White men and women were recruited in Quebec City at the Institute of
Nutrition and Functional Foods between January and April 2011. Participants
group age was between 18 and 65 y, with body mass index (BMI) 35 kg/m
plasma low-density lipoprotein cholesterol concentrations <5 mmol/L, a 10-y
This is an open-access article distributed under the terms of the Creative
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*Corresponding author. Tel.: þ1 418 656 2131; fax: þ1 418 656 5877.
E-mail address: (B. Lamarche).
0899-9007/$ - see front matter Ó2014 The Authors. Published by Elsevier Inc. All rights reserved.
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Nutrition 30 (2014) 116119
calculated Framingham risk <10% [8], normal BP (<140/90 mm Hg) [1], and with
a stable weight. Participants with a previous history of CVD, type 2 diabetes,
monogenic dyslipidemia, endocrine disorders, using medications for hyperlip-
idemia or hypertension, practicing extremenutritional habits (i.e., vegetarianism,
alcohol consumption >2 drinks/d), and elite athletes were not eligible.
Study design
We used a randomized, double-blind, placebo-controlled, crossover study
design, according to which participants were randomly subjected to two
consecutive 4-wk treatments with buttermilk or placebo [9]. During the study
period, participants were instructed to maintain their usual diet, medication,
weight, alcohol consumption, tea/coffee consumption (with a limit of 2 cups/d),
and smoking habits. The use of vitamins and natural health product supplements
was strictly forbidden throughout the trial. Any deviation from those recom-
mendations would lead to exclusion from the study.
The study protocol was approved by The Clinical Research Ethics Committee
of Laval University, and informed consent was obtained from all participants
included (registered at as NCT01248026).
Study products and diet instructions
The buttermilk and placebo formulations were articially avored with
chocolate, and provided in amounts equal to two servings of low-fat milk (45 g/
d of skim milk solids). Sucralose was added to both formulations to improve taste
and acceptability. The placebo product was formulated using dairy ingredients to
match the buttermilk composition, with the exception of the presumed active
components (i.e., MFGM components). The presence of MFGM components in
buttermilk was conrmed by sodium dodecyl sulphatepolyacrylamide gel
electrophoresis (SDS-PAGE) and high-performance liquid chromatograph for
minor proteins and phospholipids, respectively. The general composition of the
test products is presented in Table 1. The major difference between test products
pertained to their content in polar lipids. Indeed, the buttermilk product con-
tained more than 440% more polar lipids than the placebo. The SDS-PAGE prole
also revealed a higher MFGM protein content in the buttermilk product versus
placebo [9].
Participants were instructed to mix 22.5g pouches of chocolate-avored
buttermilk or a placebo with 250 mL of water, which they consumed just
before breakfast and dinner each day, for a total consumption of 45 g/d of
buttermilk or a placebo. Participants also were required to restrain their dairy
consumption to a maximum of two servings daily.
Biochemical assessments
Blood samples were taken at screening and on two consecutive days at the
end of each 4-wk test period (i.e., wks 4 and 8). The average of the two post-
treatment values was used in all analyses. Plasma levels of ACE were measured
with enzyme-linked immunosorbent assay (ELISA) kits (Quantikine; R&D Sys-
tems, Inc., Minneapolis, MN; coefcient of variation [CV] <10 %). Plasma con-
centrations of angiotensin II (ANG) and aldosterone (ALDOS) were assessed using
ELISA kits (Enzo Life Sciences, Inc., Plymouth Meeting, PA; both CV 18 %).
Anthropometric and blood pressure assessments
Anthropometric measures were taken at the beginning and at the end of each
test period according to standardized procedures. BP was measured on the right
arm using an automated mercury sphygmomanometer after a 10-min rest in a
seated position. Systolic BP (SBP) and diastolic BP (DBP) measures were analyzed
using the mean of three readings at 3-min intervals. Mean arterial pressure
(MAP) was calculated as:
Statistical analysis
Data are reported as mean (SD). Mixed models for repeatedmeasures in SAS
9.2 (SAS Institute Inc., Cary, NC, USA) wereused to assess the effect of buttermilk on
the study outcomes. Changes in the study outcomes (buttermilk versus placebo)
were analyzed in models using treatment as a xed effect and adjusting for sex and
values on placebo. There was no treatment bysequence interaction on any of the
outcomes assessed. Signicance was accepted at P<0.05.
Of the 40 participants randomized, 6 did not complete the
intervention and were excluded from statistical analysis. No
change in body weight and in hip and waist circumferences was
recorded during the duration of the trial, and there were no side
effects associated with the consumption of buttermilk compared
with a placebo. Self-reported compliance was >97% for both
treatments. There was no difference in sodium intake between
the two dietary phases (not shown). As shown previously [9],
buttermilk consumption in these participants reduced plasma
cholesterol and triglycerides (TG) concentrations by 3.1% (P¼
0.019) and 10.7% (P¼0.007), respectively, compared with
Table 1
Composition of the ready-to-use buttermilk and placebo products (for a daily dose of 45g) and data on blood pressure and biomarkers of the RAS system in 34
normotensive men and women
Mean SD Mean SD
Composition (45 g of powder)
Energy (kcal) 179.2 177.8 0.8%
Lactose (g) 23.0 1.0 22.8 1.0 0.9%
Total proteins (g) 13.0 0.8 12.8 1.0 1.5%
Total fat (g) 4.0 0.4 4.0 0.4 0.0%
SFA (g) 2.30 2.08 9.6%
MUFA (g) 0.98 0.84 14.3%
PUFA (g) 0.14 0.12 14.3%
Total phospholipids (mg) 34.6 187.5 þ441.9%
Ashes (g) 3.6 0.4 4.0 0.0 þ11.1%
Water (g) 1.4 0.4 1.4 0.0 0.0%
Systolic blood pressure (mm Hg) 110.9 11.2 108.3 11.6 2.3% 0.009
Diastolic blood pressure (mm Hg) 65.6 8.6 64.4 8.3 1.8% 0.069
Mean arterial pressure (mm Hg) 80.7 8.8 79.0 8.9 2.1% 0.015
ACE level (ng/mL)
157.5 48.0 138.8 42.1 10.9% 0.003
ANG-II level (pg/mL) 29.3 51.1 27.8 46.5 5.1% 0.126
ALDOS level (pg/mL)
224.6 154.2 226.6 129.0 þ0.9% 0.780
ACE, angiotensin I converting enzyme; ALDOS, aldosterone; ANG, angiotensin; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; RAS, renin
angiotensinaldosterone; SFA, saturated fatty acid
Values are means SD.
Values are expressed as percentages of change compared with placebo.
P-values were obtained using the PROC MIXED procedure in SAS.
Lactose, total proteins, total fat, ashes, and water values are presented as means and SD (n ¼3).
Analyses were performed on log-transformed values.
V. Conway et al. / Nutrition 30 (2014) 116119 117
SBP and MAP both decreased signicantly following butter-
milk treatments compared with the placebo (Table 1). Re-
ductions in SBP and MAP averaged 2.6 mm Hg (2.3%; P¼
0.009) and 1.7 mm Hg (2.1%; P¼0.015), respectively. The
reduction in DBP (1.2 mm Hg) did not reach statistical signi-
cance (1.8%; P¼0.069).
Plasma concentration of ACE, ANG II, and ALDOS were
analyzed as markers of the RAS system (Table 1). Buttermilk
consumption signicantly reduced plasma levels of ACE
compared with placebo (10.9%; P¼0.003), but had no effect on
ANG II (P¼0.126) and ALDOS concentrations (P¼0.780). No
signicant correlation was found between the change (%) in
plasma concentration of ACE, ANG II, and ALDOS and the percent
change in SBP, DBP, and MAP.
The small but signicant reduction in SBP (2.6 mm Hg; P¼
0.009) after 4 wk of buttermilk consumption in participants with
normal BP is close in magnitude to changes that have been
observed after consumption of dairy peptides [5,6]. Indeed, a
meta-analysis of available studies showed that supplementation
with lactotripeptides reduces SBP by an average of 3.7 mm Hg
over a mean duration of approximately 7 wk, with effects being
slightly higher among Asians (6.9 mm Hg) than among white
subjects (1.2 mm Hg ) [5]. Study duration appears to inuence the
magnitude of the effect of milk tripeptide supplementation on BP.
Indeed, a meta-analysis showedreduction in SBP of 1.3, 2.2,and 3.3
mm Hg after 2, 4, and 8 wk of supplementation, respectively, with
milk tripeptide [6].Therefore,itispossiblethatlongersupple-
mentation with buttermilk might also lead to more important re-
ductions in BP. This needs to be veried in future studies.
We observed a signicant reduction in the plasma concen-
tration of ACE (11%; P¼0.003) after 4-wk supplementation
with buttermilk compared with placebo, although there was no
change in the plasma levels of ALDOS and ANG II levels. The
signicant reduction observed in plasma concentration of ACE is
of interest because elevated levels of soluble ACE reect
enhanced ACE activity [10], and have been associated with an
increased risk for coronary heart disease [11]. This data provides
indirect evidence that the small but signicant reduction in BP
with buttermilk may be partly attributable to down-regulated
ACE activity. However, other mechanisms such as direct relaxa-
tion of vascular muscles, as well as opioid action and antioxidant
activities, have been proposed as alternative mechanisms un-
derlying the BP-lowering effects of milk peptides, and may be
partly responsible for the BP-lowering effect of buttermilk con-
sumption [12]. For that matter, in our previous work, we also
demonstrated the antioxidant capacity of specic buttermilk
peptides compared with milk and whey hydrolysates [13].
Some [14], but not all [15,16] studies have shown that in-
dividuals with a higher baseline SBP tend to respond more
favorably to BP-lowering treatments than normotensive in-
dividuals. Further studies are required to examine if patients
with higher BPs also would show benets from buttermilk
consumption. To the best of our knowledge, studies have yet to
document the effect of milk peptides on BP in normotensive
individuals [3].
The short duration of the study and the use of a sphygmo-
manometer to measure BP, as opposed to ambulatory BP mea-
sures, are two important limitations of this study. As indicated
previously, the data are restricted to individuals with normal
BP, and further studies are required to replicate these data in
hypertensive populations. This study represents a secondary
analysis of a trial designed to investigate the effect of buttermilk
supplementation the plasma lipid levels [9]. Although the BP-
lowering effect seen in the present study is most likely due to
the MFGM components found in buttermilk, other minor com-
pounds of buttermilk may have contributed to these effects.
In conclusion, data from this randomized trial reports that
short-term supplementation with buttermilk (45 g/d)dpossibly
through its high MFGM content and its effect on the ACE sys-
temdlowers SBP in normotensive individuals. Combined with
the buttermilk-induced reduction in plasma levels of total
cholesterol and TGs in the same individuals [9], these data indi-
cate that buttermilk may represent a new safe food modality to
manage blood cholesterol and BP as part of healthy eating. Further
studies are required to validate these observations.
We acknowledge all the nurses, laboratory staff, and partici-
pants at the Institute of Nutrition and Functional Foods. We also
acknowledge Pharmalab Inc. for helping us with the formulation
and packaging of the ready-to-use test products (buttermilk and
placebo) consumed in the present study. This project was funded
by a grant from the AAFC/Dairy Research Cluster. Patrick Couture
and Benoı
t Lamarche have received funding in the past from the
Dairy Farmers of Canada, Patrick Couture and Benoı
t Lamarche
also have received funding from Dairy Australia, and Agriculture
and Agri-Food Canada. Benoı
t Lamarche is the chair of the Expert
Scientic Advisory Committee (ESAC) that reviews funding ap-
plications as part of the funding program of the Dairy Farmers of
Canada. He also has received funding from Danone. Sylvie
Gauthier and Yves Pouliot have received funding from the Dairy
Farmers of Canada.
[1] Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al.
Seventh report of the Joint National Committee on Prevention, detection,
evaluation, and treatment of high blood pressure. Hypertension 2003;42:
[2] Matsui T, Tanaka M. Antihypertensive peptides and their underlying
mechanisms. In: Bioactive proteins and peptides as functional foods and
nutraceuticals. 1st ed. Oxford, UK: Wiley-Blackwell; 2010. p. 4354.
[3] Boelsma E, Kloek J. Lactotripeptides and antihypertensive effects: a critical
review. Br J Nutr 2009;101:77686.
[4] Pripp AH. Effect of peptides derived from food proteins on blood pressure:
a meta-analysis of randomized controlled trials. Food Nutr Res 2008;52:
[5] Cicero AFG, Gerocarni B, Laghi L, Borghi C. Blood pressure lowering effect of
lactotripeptides assumed as functional foods: a meta-analysis of current
available clinical trials. J Hum Hypertens 2011;25:42536.
[6] Xu J-Y, Qin L-Q, Wang P-Y, Li W, Chang C. Effect of milk tripeptides on blood
pressure: a meta-analysis of randomized controlled trials. Nutrition
[7] Dewettinck K, Rombaut R, Thienpont N, Le TT, Messens K, Van Camp J.
Nutritional and technological aspects of milk fat globule membrane ma-
terial. Int Dairy J 2008;18:43657.
[8] Third report of the National Cholesterol Education Program (NCEP) expert
panel on detection, evaluation, and treatment of high blood cholesterol in
adults (Adult Treatment Panel III) Final report. Circulation 2002;106:
[9] 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 Cardiovas; 2013
(in press).
[10] Ljungberg L, Alehagen U, Länne T, Björck H, De Basso R, Dahlström U, et al.
The association between circulating angiotensin-converting enzyme and
cardiovascular risk in the elderly: a cross-sectional study. J Renin-Angio-
Aldo S 2011;12:2819.
[11] Fleming I. Signaling by the angiotensin-converting enzyme. Circ Res
[12] L
no R, Otte J, van Camp J. Physiological, chemical and techno-
logical aspects of milk-protein-derived peptides with antihypertensive and
ACE-inhibitory activity. Int Dairy J 2006;16:127793.
V. Conway et al. / Nutrition 30 (2014) 116119118
[13] Conway V, Gauthier SF, Pouliot Y. Antioxidant activities of buttermilk
proteins, whey proteins, and their enzymatic hydrolysates. J Agric Food
Chem 2012;61:36472.
[14] Sumner DJ, Meredith PA, Howie CA, Elliott HL. Initial blood pressure as a
predictor of the response to antihypertensive therapy. Brit J Clin Pharmaco
[15] Gill JS, Beevers DG, Zezulka AV, Davies P. Relation between initial blood
pressure and its fall with treatment. The Lancet 1985;325:5679.
[16] Czernichow S, Zanchetti A, Turnbull F, Barzi F, Ninomiya T, Kengne A-P, et al.
The effects of blood pressure reduction and of different blood pressure-
lowering regimens on major cardiovascular events according to baseline
bloodpressure: meta-analysis of randomizedtrials. J Hypertens2011;29:416.
V. Conway et al. / Nutrition 30 (2014) 116119 119
... Cultured buttermilk is another type of buttermilk obtained by intentional acidification of skim milk done by buttermilk starter cultures. It is very similar to yogurt in the sense that it is cultured using live beneficial bacteria and can be consumed as a thick and creamy beverage (Conway et al. 2014a(Conway et al. , 2014b. ...
... Generally, cream is not ripened in this case. SCBM has high fat content as compared to skim milk, which can be decreased by centrifuging it or ultrafiltration (Conway et al. 2014a(Conway et al. , 2014b. SCBM also consists of huge amount of proteins, which are drawn by churning from the fat globule-milk serum interface (King 1955). ...
... PLs are part of a very specific structure found in dairy products, the milk fat globule membrane (MFGM) [9], which is released into BM during the churning of cream into butter. The unique composition of PLs in MFGM (phosphatidylcholine-PC, phosphatidylethanolamine-PE, phosphatidylserine-PS, phosphatidylinositol-PI, and sphingomyelin-SM), along with the MFGM proteins, is responsible for its various health benefits [10][11][12]. For example, daily dietary supplementation with BM led to a decrease in concentration of total and LDL cholesterol in moderately hypercholesterolemic men and women [10]. ...
Full-text available
Despite its nutritional properties, buttermilk (BM) is still poorly valorized due to its high phospholipid (PL) concentration, impairing its techno-functional performance in dairy products. Therefore, the objective of this study was to investigate the impact of ultra-high-pressure homogenization (UHPH) on the techno-functional properties of BM in set and stirred yogurts. BM and skimmed milk (SM) were pretreated by conventional homogenization (15 MPa), high-pressure homogenization (HPH) (150 MPa), and UHPH (300 MPa) prior to yogurt production. Polyacrylamide gel electrophoresis (PAGE) analysis showed that UHPH promoted the formation of large covalently linked aggregates in BM. A more particulate gel microstructure was observed for set SM, while BM gels were finer and more homogeneous. These differences affected the water holding capacity (WHC), which was higher for BM, while a decrease in WHC was observed for SM yogurts with an increase in homogenization pressure. In stirred yogurts, the apparent viscosity was significantly higher for SM, and the pretreatment of BM with UHPH further reduced its viscosity. Overall, our results showed that UHPH could be used for modulating BM and SM yogurt texture properties. The use of UHPH on BM has great potential for lower-viscosity dairy applications (e.g., ready-to-drink yogurts) to deliver its health-promoting properties.
Cultured buttermilk is a dairy beverage with a high nutritive value. In the current study, functional cultured buttermilk was formulated using probiotic Lactobacillus plantarum and flaxseed fortification to improve the potential health benefits. The cultured buttermilk samples were analysed for pH, lactic acidity, colour, phase separation, viscosity, microbiology and sensory properties. The results showed non-significant changes in acidity and pH. However, flaxseed fortification decreased phase separation and increased viscosity of buttermilks. In addition, a significant difference in colour attributes was revealed between samples. Sensory characteristics of cultured buttermilks were acceptable to produce a functional food.
Low-quality dietary patterns impair cardiometabolic health by increasing the risk of obesity-related disorders. Cardiometabolic risk relative to dairy-food consumption continues to be a controversial topic, due to recommendations that endorse low-fat and nonfat dairy foods over full-fat varieties despite accumulated evidence that does not strongly support these recommendations. Controlled human studies and mechanistic preclinical investigations support that full-fat dairy foods decrease cardiometabolic risk by promoting gut health, reducing inflammation, and managing dyslipidemia. These gut- and systemic-level cardiometabolic benefits are attributed, at least in part, to milk polar lipids (MPLs) derived from the phospholipid- and sphingolipid-rich milk fat globule membrane that is of higher abundance in full-fat dairy milk. The controversy surrounding full-fat dairy food consumption is discussed in this review relative to cardiometabolic health and MPL bioactivities that alleviate dyslipidemia, shift gut microbiota composition, and reduce inflammation. This summary, therefore, is expected to advance the understanding of full-fat dairy foods through their MPLs and the need for translational research to establish evidence-based dietary recommendations.
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Milk fat globules (MFGs) are secreted from the mammalian gland and are composed of a triacylglycerol core surrounded by a triple membrane structure, the milk fat globule membrane (MFGM). The MFGM contains complex lipids and proteins reported to have nutritional, immunological, neurological and digestive functions. Human and ruminant milk are shown to share a similar MFG structure but with different size, profile and abundance of protein and polar lipids. This review summarizes the reported data on human, bovine, caprine and ovine MFG composition and concentration of bioactive components in different MFG-size fractions. A comprehensive understanding of compositional variations between milk from different species and MFG size fractions may help promote various milk sources as targeted supplements to improve human development and health. MFG size and MFGM composition are species-specific and affected by lactation, diet and breed (or maternal origin). Purification and enrichment methods for some bioactive proteins and lipids present in the MFGM have yet to be established or are not scaled sufficiently to be used to supplement human diets. To overcome this problem, MFG size selection through fractionation or herd selection may provide a convenient way to pre-enrich the MFG fraction with specific protein and lipid components to fulfill human dietary and health requirements.
Milk is an evolutionary benefit for humans. For infants, it offers optimal nutrients for normal growth, neural development, and protection from harmful microbes. Humans are the only mammals who drink milk throughout their life. Lipids in colostrum originate mostly from milk fat globule membrane (MFGM) droplets extruded from the mammary gland. The MFGM gained much interest as a potential nutraceutical, due to their high phospholipid (PL), ganglioside (GD), and protein contents. In this review, we focused on health effects of MFGM ingredients and dairy food across the life span, especially on neurodevelopment, cardiometabolic health, and frailty in older adults. The MFGM supplements to infants and children reduced gastrointestinal and respiratory tract infections and improved neurodevelopment due to the higher content of protein, PL, and GD in MFGM. The MFGM formulas containing PL and GD improved brain myelination and fastened nerve conduction speed, resulting in improved behavioral developments. Administration of MFGM-rich ingredients improved insulin sensitivity and decreased inflammatory markers, LDL-cholesterol, and triglycerides by lowering intestinal absorption of cholesterol and increasing its fecal excretion. The MFGM supplements, together with exercise, improved ambulatory activities, leg muscle mass, and muscle fiber velocity in older adults. There are great variations in the composition of lipids and proteins in MFGM products, which make comparisons of the different studies impossible. In addition, investigations of the individual MFGM components are required to evaluate their specific effects and molecular mechanisms. Although we are currently only beginning to understand the possible health effects of MFGM products, the current MFGM supplementation trials as presented in this review have shown significant clinical health benefits across the human life span, which are worth further investigation.
From 25% to 50% of adults are affected by prehypertension. Prehypertension increases the risk of hypertension and affects the heart and systemic vascular system. Food mixed tree essence of Dendropanax morbifera called Hwangchil in Korean and immature fruit of Rubus coreanus, called Bokbunja (HDR-2), have been studied for safety and effectiveness against prehypertension studies. This study was a randomized double-blind placebo-controlled multicenter clinical trial lasting 19 months from October 2017 to May 2019. The 88 subjects who enrolled in the study were divided into two groups. The treatment group was provided HDR-2 and the other group took a placebo. Both HDR-2 and placebo were in the form of capsules, and the dose was 900 mg per day. Subjects took HDR-2 or placebo capsules once a day for 8 weeks before dinner. The primary observational indicators were systolic blood pressure (SBP) and diastolic blood pressure (DBP), and the secondary observational indicators were mean arterial pressure (MAP), mean pulse pressure, pulse rate, angiotensin-converting enzyme activity, renin activity, aldosterone, and highly sensitive-C reactive protein. The number of measurements was three times: the first visit in the screening week, the second visit in 4 weeks, and the third visit was after 8 weeks. Significant study results showed that the SBP and MAP of the HDR-2 group after 8 weeks were lower than those of the placebo group. Adverse events were not significantly different between the two groups. In conclusion, these results suggest that HDR-2 may be a useful intervention for the management of prehypertension. The protocol was registered in the Korean Clinical Trial Registration system (; registration number: KCT0004300).
This paper describes the successful development of new low-immunoreactive buttermilk (BM)-based formulations which were fermented with 31 lactic acid bacteria (LAB) and Bifidobacterium strains. The aim of this study was to create a new formula, which can serve as potential candidates for the immunotherapy of allergy. The preparations were tested for their content of biologically active compounds, such as proteins, peptides, phospholipids, and short-chain fatty acids (SCFA), as well as for the survivability of LAB and sensory quality. The results showed that the BM was a matrix rich in nutritional components and displayed higher than expected susceptibility to the reduction of protein IgE-immunoreactivity (to 98%) and high bacterial-protecting capacity. The overall sensory quality of the examined products was influenced by the profile of SCFA and free peptides, but two formulations fermented with Lactobacillus delbrueckii ssp. Bulgaricus-151 and Lactobacillus casei-LcY were the most advantageous with desirable sensory, immunoreactive, and biochemical properties.
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In this review paper, the latest literature on the functional properties of phospholipids in relation to inflammation and inflammation-related disorders has been critically appraised and evaluated. The paper is divided into three sections: Section one addresses the relationship between the anti-inflammatory bioactivities of different phospholipids in relation to their structures and compositions. Sections two and three are dedicated to the structures, functions and anti-inflammatory properties of dietary phospholipids from animal and marine sources. Most of the dietary phospholipids of animal origin come from meat, egg and dairy products. To date, there is very limited work published on meat phospholipids, undoubtedly due to the negative perception that meat consumption is an unhealthy option due to its putative associations with several chronic diseases. These assumptions are addressed with respect to the phospholipid composition of meat products. Recent research trends indicate that dairy phospholipids possess anti-inflammatory properties, which has led to an increased interest into their molecular structures and reputed health benefits. Finally, the structural composition of phospholipids of marine origin is discussed. Extensive research has been published in relation to ω-3 polyunsaturated fatty acids (PUFAs) and inflammation, however this research has recently come under scrutiny and has proved to be unreliable and controversial in terms of the therapeutic effects of ω-3 PUFA, which are generally in the form of triglycerides and esters. Therefore, this review focuses on recent publications concerning marine phospholipids and their structural composition and related health benefits. Finally, the strong nutritional value of dietary phospholipids are highlighted with respect to marine and animal origin and avenues for future research are discussed.
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Sphingolipids (SL) are important components of the milk fat globule membrane (MFGM) found in buttermilk. While studies in animal models suggest that dietary SL may have cholesterol-lowering properties, data in human are lacking. The aim of this study was to investigate the impact of buttermilk consumption on plasma lipids and surrogate markers of cholesterol (C) homeostasis in humans. Men and women (n = 34) with serum LDL-C <5.0 mmol/L at screening (mean LDL-C = 3.8 mmol/L) were recruited in this double-blinded randomized crossover placebo controlled study. Their diets were supplemented with 45 g/d of buttermilk and with 45 g/d of a macro/micronutrient matched placebo (4 weeks each in random order). Serum lipid concentrations and surrogate markers of cholesterol homeostasis were measured post diet and compared using mixed models for repeated measures. Consumption of buttermilk led to reduction in serum cholesterol (-3.1%, P = 0.019), LDL-C (-3.1%, P = 0.057) and triacylglycerol (-10.7%, P = 0.007). Buttermilk consumption increased plasma lathosterol concentrations (+12.1%, P = 0.001), but multiple regression analysis indicated that variations in β-sitosterol concentrations (P = 0.002) were the only significant predictor of the LDL-C response to buttermilk consumption. Buttermilk consumption may be associated with reduced cholesterol concentrations in men and women, primarily through inhibition of intestinal absorption of cholesterol. This trial is registered at as NCT01248026.
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A polymorphism in the angiotensin-converting enzyme gene (ACE I/D polymorphism) has been associated with increased risk for cardiovascular disease (CVD). This polymorphism affects the level of circulating ACE, but there is great individual variation, even between those with the same genotype. Few previous studies have investigated the link between circulating ACE and cardiovascular risk. The aim of this study was to investigate this association, and to examine the relationship between ACE level, ACE genotype and CVD. The study population consisted of 322 men and 350 women aged 69-87. Plasma ACE level was determined using enzyme-linked immunosorbent assay (ELISA), and ACE genotype was analysed using PCR followed by gel electrophoresis. In men, ACE levels increased with increasing number of cardiovascular risk factors (p = 0.003). There was a significant association in men between increased ACE level and both diabetes (p = 0.007) and smoking (p = 0.037). This study shows that cardiovascular risk factors (such as smoking and diabetes) are associated with higher levels of circulating ACE in men. High ACE levels may represent one of the cellular mechanisms involved in producing the vascular damage associated with cardiovascular risk factors.
The milk fat globule membrane (MFGM) has gained a lot of attention recently, due to the growing interest in its nutritional and technological properties. The whole membrane as well as the separate lipid and protein components have great potential for new product applications with unique nutritional and technological properties. This review focuses on the nutritional and technological aspects of the MFGM material, but also gives an overview of the gathered information about the composition, structure and isolation methods of the MFGM from different dairy sources.
The oxygen radical absorbance capacities (ORAC) and metal chelating capacities (MCC) of protein concentrates prepared from buttermilk and cheese whey by ultrafiltration were compared with those of skim milk protein. Samples were also heat-denatured and hydrolyzed by pepsin for 2 h followed by trypsin for 3 h. The highest MCC was obtained for hydrolyzed skim milk protein. ORAC values ranged from 554.4 to 1319.6 µmol Trolox equivalents per g of protein, with the highest value obtained for hydrolyzed buttermilk protein. Liquid-phase isoelectric focusing (IEF) of this hydrolysate yielded peptide fractions with lower ORAC values. LC-MS analysis of the hydrolyzed skim milk and buttermilk proteins and IEF fractions of the latter showed that peptides derived from milk fat globule membrane proteins, primarily butyrophilin, could be responsible for the superior antioxidant activity of buttermilk. These results suggest overall that hydrolyzed buttermilk protein could be used as a source of natural antioxidants.
Introduction Hypertension and the Renin - Angiotensin System Design of ACE Inhibitory Peptides Antihypertensive Mechanism of Small Peptides Future Prospects References
Among the bioactive peptides derived from milk proteins, those with blood pressure-lowering effects are receiving special attention due to the prevalence and importance of hypertension in the Western population. A few antihypertensive products based on milk-protein-derived peptides with clinically proven health benefits already exist. This paper reviews the current literature on milk-derived peptides with antihypertensive effects. The structure-activity characteristics of angiotensin converting enzyme (ACE) inhibitory peptides are discussed, as well as their bioavailability, potential physiological affects and the existence of mechanisms of action other than ACE inhibition. The paper also focuses on the technological aspects of the production of bioactive dairy products with antihypertensive peptides, either by fermentation with selected microorganisms or by in vitro-hydrolysis and enrichment. Finally, the stability of the peptides during production and processing is addressed, including the potential interactions with other food components and their influence on peptide bioactivity and bioavailability.