Dairy Products: Pro- or Anti

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13/05/2013
Dairy Products: Pro- or AntiInflammatory Foods? An
Overview
Marie-Ève Labonté, Patrick Couture, Benoît Lamarche
INAF, Université Laval
Inflammation
STELA Symposium 2013
Delta Centre-Ville, Montréal, Qc
May 14th 2013
Medzhitov, Nature, 2008:454;428-435
Inflammation: common feature of several
multifactorial disorders
Sources of inflammatory markers
Atherosclerosis
Cardiovascular
diseases
Inflammation
IL-6
IL-1β
TNF-α
MCP-1
Metabolic
syndrome
CRP
Type 2 diabetes
Scrivo R, Autoimmun Rev, 2011;10:369-74
Adjusted relative risk of a first
cardiovascular event
Rader, NEJM, 2000;343:1179-82
Meta-analysis on CRP and the risk of
coronary heart disease, stroke and
mortality
Women’s Health Study
The Emerging Risk Factors Collaboration
Ridker PM et al. NEJM. 2002;347:1557-65
Lancet 2010;375:132-40
↑ in the risk associated with a 3-fold ↑ in CRP
concentrations*
2.5
2.0
Relative risk*
Adiponectin
P trend
< 0.001
1.5
Coronary heart disease
37%
Ischaemic stroke
27%
Vascular mortality
55%
Non-vascular mortality
54%
1.0
0.5
0.0
1
2
3
4
5
Quintiles of blood CRP concentrations
*Ajusted for: age, smoking, type 2 diabetes, blood pressure, hormonal therapy
*Ajusted for: age, sex, study, systolic blood pressure, smoking, history of type 2 diabetes,
body mass index, triglycerides, cholesterol (total, non-HDL, HDL), alcohol consumption
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13/05/2013
Factors influencing the inflammatory
profile
Introduction
●
Effects of nutritional factors on inflammatory
markers:
o Anti-inflammatory :
Inflammatory
profile
o Fruits and vegetables
o Whole grains
o Fish
o Fiber
o n-3 fatty acids
o Vitamin C and E
o Carotenoids
o Proinflammatory :
o Saturated and trans fatty acids
o Western dietary patterns
Nanri, Asian Pac J Cancer Prev, 2007;8:167-77
?
Calder PC et al. Br J Nutr. 2011;106:S5-78
Food products allowed and/or forbidden
in the hypotoxic diet
Dairy products: All dairy products derived from animals are forbidden,
including cheese. This also includes milk and cheese from ewes and goats.
Translated from: http://jacquelinelagace.net/2012/05/29/aliments-permis-dans-leregime-hypotoxique/
Cell culture studies: ↑ production of proinflammatory cytokines
Solis-Pereyra et al. AJCN. 1997;66:521S-5S
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Observational studies
Observational studies
●
ATTICA study
Main observation:
Panagiotakos et al. J Am Coll Nutr. 2010;29:357-64
1.2
-0.8
0
0.5
1
Dairy product consumption
Difference vs.
< 8 servings of dairy/week
0%
0.8
Inflammatory
0.4
biomarkers
(CRP, IL-6,
0
TNF-α)
-0.4
Servings of
dairy products
per week:
-5%
-10%
8-11
11-14
> 14
-15%
-20%
-25%
-30%
-35%
CRP
Esmaillzadeh et al. Public Health Nutr. 2010;13:1395-402
Panagiotakos et al. J Am Coll Nutr. 2010;29:357-64
Salas-Salvado et al. Eur J Clin Nutr. 2008;62:651-9
Objective of the presentation
●
Systematic review:
IL-6
TNF-α
Systematic review: eligibility criteria
●
Inclusion criteria
o
o
o
o
Randomized controlled trials
Published in English
Bovine dairy products (milk, cheese, yogurt)
Adult men and women
o Low-dairy (control) intervention
Labonté et al. Am J Clin Nutr 2013;97:706-17
●
●
Exclusion criteria
o
o
o
o
o
PLI study: “produits laitiers et inflammation”
o Randomized crossover nutritional intervention trial
o Healthy men and women with low-grade systemic
inflammation
Pregnant or lactating women
Inflammation-related disorders (eg, cancer, arthritis)
Lack of a low-dairy intervention
Goat milk or soy beverages only
High-fat or high-sugar dairy products only (eg, butter, cream, ice
cream)
Characteristics of the studies included in
the systematic review
●
Number of studies  8
●
Experimental design:
o Parallel  6/8
o Crossover  2/8
●
Subjects:
o Overweight or obese
o ♂ + ♀  7/8
o ♀  1/8
●
Nutritional interventions:
o 2 to 3 diets
o 4 to 48 weeks
Labonté et al. AJCN. 2013
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13/05/2013
Number
of
studies
Inflammation =
Antiinflammatory
Proinflammatory
Neutral
Primary outcome
1
1
0
0
Secondary outcome
5
2
0
3
Undefined outcome
2
TOTAL
1
8
0
4
0
Inflammation as the primary outcome or not
●
Heterogeneity + lack of detail regarding tested dairy
products
●
Difference in the amount of dairy products between the
“test” and “control” interventions
●
Differences in the nature and the number of inflammatory
markers analyzed in each study
●
Sensitivity/coefficients of variation of the assays
●
Lack of transparency in the report of items associated with
the risk of biased results
4
Inflammation =
2 isoenergetic diets of 12 weeks:
> 3.5 vs < 0.5 servings of dairy products/d
60%
*
Number
of
studies
Observed effects
Antiinflammatory
Proinflammatory
Neutral
Primary outcome
1
1
0
0
●
Reductions in
adiposity indexes
Secondary outcome
5
2
0
3
20%
●
Adequate power
Undefined outcome
2
1
0
1
0%
●
Differences in the
amount of calcium,
milk-derived
proteins and
bioactive peptides
TOTAL
8
4
0
4
-20%
*
-40%
-60%
*
* *
Zemel and Sun. J Nutr. 2008;138:1047-52
CRP
Adiponectin
+8%
-29%
+18%
Hypoenergetic
study
Isoenergetic
study
-11%
< 1 serving
3 servings
●
Sample size calculation  body weight or waist
circumference
Isoenergetic
study
*P < 0.02
40%
Hypoenergetic
study
Difference post- vs. pre-diet
(high-dairy diet)
●
1
Stancliffe et al. AJCN. 2011;94:422-30
●
Methodological factors limiting the
generalizability of results:
Observed effects
< 1 serving
< 1 serving
3 servings
3 servings
Zemel et al. Obes Res. 2005;13:1218-25
Zemel et al. Int J Obes. 2005;29:391-7
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13/05/2013
Number of
studies
Interventions
Combination of different dairy products:
5/8
 Specification of the fat percentage
1/5
●
●
products
●
Fat-free yogurt
1/8
Low-fat milk
1/8
●
Smoothies made with non-fat dry milk
1/8
●
●
Specific products:
●
No distinction between specific dairy products:
o milk vs. yogurt vs. cheese
o low-fat vs. high-fat dairy products
Servings of dairy products/d
Consumption
Prescribed
Actual
●
●
products
●
●
●
●
●
●
products
●
●
●
●
Thompson,
Obes Res,
2005
3 diets:
• 4
• 4 + fiber
• 2 (control)
Wennersberg, 2 diets:
AJCN,
• 3-5
2009
• Habitual diet
●
• 3.1
• 3.1
• 1.4
∆ 1.7
• 1.8-2.5
• 0.8-1.1
∆ 0.7-1.7
Difference of ≥ 3 servings in dairy products
intake between “test” and “control” interventions:
o 4/6 studies  significant anti-inflammatory effects
Cochrane Collaboration’s tool for the
assessment of the risk of bias
Unclear or high risk
of bias
(number of studies)
Random sequence generation
6/8
Allocation concealment
4/8
Blinding of:
Participants
6/8
Personnel
8/8
Outcome assessors
8/8
Incomplete outcome data
2/8
Selective reporting
7/8
Other possible bias:
Baseline imbalance
4/8
Carry-over effect
1/2
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In summary
In summary
●
●
Cell culture studies:
Randomized controlled nutritional intervention
trials:
o ↑ production of proinflammatory cytokines
●
Observational studies:
o Inverse associations between dairy product consumption
and inflammation
Future perspectives
●
Additional nutritional intervention studies:
o Adequately powered
o Specifically designed to assess the effects of dairy
products on inflammation
o Better characterization of the type and amount of
dairy products tested
o Mechanisms underlying the inflammatory response
o Inflammation-related gene expression
o Dairy product consumption has no adverse effect on
the inflammatory profile of overweight or obese adults
o Several methodological factors and limitations do not
allow differentiation between a beneficial or simply
neutral impact of dairy products on inflammation
Acknowledgements
Systematic review:
Benoît Lamarche
Patrick Couture
Sophie Desroches
Caroline Richard
PLI study:
Team Lamarche:
Benoît Lamarche
Patrick Couture
Marie-Claude Lépine
Amélie Charest
Audrey Cyr
Clinical unit:
Steeve Larouche
Danielle Aubin
Myriam Bouchard
Laboratory:
Johanne Marin
Participants
Colleagues from U of Manitoba
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Dairy Products: Pro- or Anti

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