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Ági A. Fekete PhD student
Milk Proteins and Cardiovascular Health
Supervisors: Prof. Julie Lovegrove Prof. Ian Givens
TSB, DRINC & MRC Event 2014
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Milk and dairy products & CVD
• Saturated fatty acids have a detrimental impact on CVD risk factors
• Milk and dairy products are rich in SFA
• Emerging observational studies indicate that the consumption of milk and dairy products are inversely associated with incidence of CVD
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By 2030 ~ 23.6 million people will die from CVD
Milk proteins
Fat 1.7%
Protein 3.4%
Carbohydrate 4.7%
Water, minerals & vitamins 90.2 %
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In 2008 ~ 17.3 million death in the world
By 2030 ~ 23.6 million people will die from CVD
Milk proteins
Bovine milk contains ~32-34g/L protein
αs1 casein 40%
αs2 casein 10%
β casein 24%
κ casein 13%
β-lactoglobulin 11%
α-lactalbumin 2% Casein 80%
Whey 20%
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In 2008 ~ 17.3 million death in the world
Milk proteins
Weight management Bone health
Mood, memory and stress control
Cardiovascular health
Dental health
Immune defence Digestive health
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Protein and health
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Protein and health
“Our overall assessment of this paper is that the conclusions and analyses are biased, and flawed. While there is growing consensus that a moderate protein intake between 1.0 and 1.5 g/kg/d may confer health benefits beyond those afforded by the current RDA for protein, we also recognize there are gaps in the current knowledge base and encourage discussion of important contradictory evidence/data...Unfortunately, the article by Levine et al. presents conclusions not supported by their own analyses or the greater literature.”
Prof Donald K Layman, University of Illinois; Prof Arne Astrup, Copenhagen University; Prof Peter M Clifton, University of South Australia; Dr Heather Leidy,
University of Missouri; Dr Douglas Paddon-Jones, University of Texas; Prof Stuart M Phillips, McMaster University
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Protein and health
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In 2008 ~ 17.3 million death in the world
Milk protein Blood Pressure
Is there any link between them?
Milk and blood pressure
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Milk and blood pressure
Blood pressure (mmHg)
Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
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Milk and blood pressure
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In 2008 ~ 17.3 million death in the world
By 2030 ~ 23.6 million people will die from CVD
Prospective studies on milk consumption and BP
Study Population BP in subjects with
highest milk intakes
Ackley et al., 1983
Jorde & Bonas, 2000
Shaper et al., 1991
Vivjer et al., 1992
Ness et al., 2001
Abbott et al.,1996
Iso et al., 1999
Elwood et al., 2004
Djousse, 2006
PREDIMED study 2009
5,050
7,735
1,340
1,265
5,765
3,150
34,486
2,512
4,797
2,290
- 6.3% of SD
- 5.5% of SD
- 8.3% of SD
-10.0% of SD
- 5.5% of SD
- 6.3% of SD
- 7.5% of SD
- 10.0% of SD
- 6.4% of SD
- 10.5% of SD
Milk and blood pressure
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In 2008 ~ 17.3 million death in the world
By 2030 ~ 23.6 million people will die from CVD
Weight of evidence: RCTs evaluating the impact of milk proteins on BP
Comprehensive literature review
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Ile-Pro-Pro (IPP), Val-Pro-Pro (VPP). LTP are found to possess antihypertensive effect in vitro and in human studies as well.
Meta-analysis
Casein-derived lactotripeptides (LTP)
In the 1990s, Japanese researchers isolated peptides from fermented milk, which is comprised of chains of three amino acids
Ile-Pro-Pro (IPP), Val-Pro-Pro (VPP) found to possess antihypertensive effect in vitro and in human studies
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In 2008 ~ 17.3 million death in the world
By 2030 ~ 23.6 million people will die from CVD
The inclusion criteria of the meta-analysis on LTPs
Study design
• Randomised, placebo controlled trials
Subjects
• Male and female, age 18 or above
Intervention
• Products containing casein-derived lactotripeptides (VPP, IPP)
Types of outcome measure
• Change of SBP and DBP from baseline compared to placebo group
Date of publication
• -2013
Meta-analysis
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In 2008 ~ 17.3 million death in the world
Meta-analysis
When all possible biases considered:
Small but significant reduction in SBP and non-significant reduction in DBP
Conclusion of the meta-analysis:
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In 2008 ~ 17.3 million death in the world
Meta-analysis
Estimated effects of population-wide shifts in systolic BP distributions on mortality
Appel L J et al. Hypertension 2006;47:296-308
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Human dietary intervention study: Milk proteins on BP and vascular function
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In 2008 ~ 17.3 million death in the world
By 2030 ~ 23.6 million people will die from CVD
Pal and Ellis (2010) Obesity 18, 1354-1359
n=70 overweight subjects were assigned to 54 g whey, casein or glucose ingestion for 12 weeks
Statistically significant difference from baseline *p<0.05
Letters indicate statistically significance between groups *p<0.05
Comparative effects of whey and casein on blood pressure
Impact of milk proteins on BP and vascular function
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By 2030 ~ 23.6 million people will die from CVD
Impact of milk proteins on BP
Dairy bioactive peptides
-ve
↑BP
Possible mechanism of milk bioactive peptides
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In 2008 ~ 17.3 million death in the world
Milk protein Vascular function
Is there any link between them?
Milk and blood pressure
Vascular function is a CVD risk marker
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Vascular function
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In 2008 ~ 17.3 million death in the world
By 2030 ~ 23.6 million people will die from CVD
• The endothelium plays an important role in vascular function.
• Endothelial dysfunction is an imbalance between the production of endothelium-derived relaxing and contracting factors.
• Arterial stiffness is a manifestation of vascular dysfunction.
Vascular function
Vascular function
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In 2008 ~ 17.3 million death in the world
By 2030 ~ 23.6 million people will die from CVD
Pal and Ellis (2010) Obesity 18, 1354-1359
Only whey reduced significantly AI% (measure arterial stiffness)
Statistically significant difference from baseline *p<0.05
Letters indicate statistically significance between groups *p<0.05
n=70 overweight subjects were assigned to 54 g whey, casein or glucose ingestion for 12 weeks
Comparative effects of whey and casein on vascular function
Impact of milk proteins on BP and vascular function
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By 2030 ~ 23.6 million people will die from CVD
Way2Go study
Way2Go Research: Long-term (chronic) study
Diet diary completion
Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6
Wash out period
(4 weeks)
Wash out period
(4 weeks)
Treatment period (8 weeks)
whey or casein or maltodextrin
Treatment period (8 weeks)
maltodextrin or whey or casein
Treatment period (8 weeks)
casein or maltodextrin or whey
Run-in period
(2 weeks)
Blood draw, 24 h ambulatory blood pressure monitor, vascular testing
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In 2008 ~ 17.3 million death in the world
By 2030 ~ 23.6 million people will die from CVD
Inclusion criteria
• A signed consent form
• Blood pressure: 120/80-159/99
• Age: 30-75 years
• BMI 20-40 kg/m2
• Glucose <7 mmol/l
• Chol <8 mmol/l
• TAG <4 mmol/l
• Normal liver and kidney function
• Haemoglobin (>130 g/l)
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In 2008 ~ 17.3 million death in the world
By 2030 ~ 23.6 million people will die from CVD
Arterial stiffness measures
Pulse wave analysis (PWA)
Applanation tonometry
Digital volume pulse (DVP)
Infra-red light-transmitting
unit
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In 2008 ~ 17.3 million death in the world
By 2030 ~ 23.6 million people will die from CVD
Flow Mediated Dilatation (FMD)
Ultrasound (macrocirculation)
Vascular reactivity measure
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In 2008 ~ 17.3 million death in the world
Way2Go study
Way2Go Research: Short-term (postprandial) study
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In 2008 ~ 17.3 million death in the world
Lunch: • Philadelphia cheese + butter sandwich • Study drink
Postprandial study food – a challenge for the cardiovascular system
Breakfast: • 4 shortbread fingers • 2.5 pieces of croissant with butter • Study drink
Nutritional composition
Energy 2.6 MJ
Protein 35.8 g
Carbohydrate 46 g
Fat (SFA) 30 g (14 g)
Nutritional composition
Energy 4.5 MJ
Protein 39.2 g
Carbohydrate 92.1 g
Fat (SFA) 59 g (25 g)
Nutritional composition based on DISRUPT study (Jackson et al., 2010)
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In 2008 ~ 17.3 million death in the world
By 2030 ~ 23.6 million people will die from CVD
Meta-analysis
Conclusion
Consumption of milk and dairy products seem to be beneficial for vascular health
Dairy products should be incorporated into a healthy, balanced diet
More research required to clarify how milk and dairy products exert their beneficial effects on human health
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Acknowledgements
Katy Fingleton – placement student
Carlotta Giromini – visiting PhD student
Karen Jenkins – research nurse
Rada Mihaylova – research nurse
Prof. Ian Givens
Prof. Julie Lovegrove