13/05/2013. Dairy Products: Pro- or Anti- Inflammatory Foods? An Overview. Inflammation. Adjusted relative risk of a first cardiovascular event

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1 Relative risk* 13/05/2013 Dairy Products: Pro- or Anti- Inflammatory Foods? An Overview Marie-Ève Labonté, Patrick Couture, Benoît Lamarche INAF, Université Laval STELA Symposium 2013 Delta Centre-Ville, Montréal, Qc May 14 th 2013 Inflammation Medzhitov, Nature, 2008:454; Inflammation: common feature of several multifactorial disorders Sources of inflammatory markers Atherosclerosis Cardiovascular diseases Inflammation Type 2 diabetes Metabolic syndrome IL-6 IL-1β TNF-α MCP-1 CRP Scrivo R, Autoimmun Rev, 2011;10: Adiponectin Rader, NEJM, 2000;343: Adjusted relative risk of a first cardiovascular event Women s Health Study Ridker PM et al. NEJM. 2002;347: Quintiles of blood CRP concentrations *Ajusted for: age, smoking, type 2 diabetes, blood pressure, hormonal therapy P trend < Meta-analysis on CRP and the risk of coronary heart disease, stroke and mortality The Emerging Risk Factors Collaboration Lancet 2010;375: in the risk associated with a 3-fold in CRP concentrations* Coronary heart disease 37% Ischaemic stroke 27% Vascular mortality 55% Non-vascular mortality 54% *Ajusted for: age, sex,, systolic blood pressure, smoking, history of type 2 diabetes, body mass index, triglycerides, cholesterol (total, non-hdl, HDL), alcohol consumption 1

2 13/05/2013 Factors influencing the inflammatory profile Inflammatory profile Introduction Effects of nutritional factors on inflammatory markers: o Anti-inflammatory : 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: Calder PC et al. Br J Nutr. 2011;106:S5-78? Dairy Food allowed and/or forbidden in the hypotoxic diet : All dairy derived from animals are forbidden, including cheese. This also includes milk and cheese from ewes and goats. Translated from: Cell culture studies: production of proinflammatory cytokines Solis-Pereyra et al. AJCN. 1997;66:521S-5S 2

3 Difference vs. < 8 servings of dairy/week 13/05/2013 Observational studies Main observation: Inflammatory 0.4 biomarkers (CRP, IL-6, 0 TNF-α) Dairy product consumption Esmaillzadeh et al. Public Health Nutr. 2010;13: Panagiotakos et al. J Am Coll Nutr. 2010;29: Salas-Salvado et al. Eur J Clin Nutr. 2008;62:651-9 Observational studies 0% -5% -10% -15% -20% -25% -30% -35% ATTICA Panagiotakos et al. J Am Coll Nutr. 2010;29: CRP IL-6 TNF-α Servings of dairy per week: > 14 Objective of the presentation Systematic review: Labonté et al. Am J Clin Nutr 2013;97: PLI : produits laitiers et inflammation o Randomized crossover nutritional intervention trial o Healthy men and women with low-grade systemic inflammation Systematic review: eligibility criteria Inclusion criteria o Randomized controlled trials o Published in English o Bovine dairy (milk, cheese, yogurt) o Adult men and women o Low-dairy (control) intervention Exclusion criteria o Pregnant or lactating women o Inflammation-related disorders (eg, cancer, arthritis) o Lack of a low-dairy intervention o Goat milk or soy beverages only o High-fat or high-sugar dairy only (eg, butter, cream, ice cream) Labonté et al. AJCN 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 3

4 Isoenergetic Hypoenergetic Difference post- vs. pre-diet (high-dairy diet) Isoenergetic Hypoenergetic 13/05/2013 Inflammation = Number of studies Observed effects Neutral Primary outcome Secondary outcome Undefined outcome TOTAL Difference in the amount of dairy between the Stancliffe et al. AJCN. 2011;94: isoenergetic diets of 12 weeks: > 3.5 vs < 0.5 servings of dairy /d Inflammation = Number of studies Observed effects Antiinflammatory Proinflammatory Antiinflammatory Proinflammatory Neutral Primary outcome % 40% *P < 0.02 * Reductions in adiposity indexes Secondary outcome % 0% -20% -40% -60% * * * * Adequate power Differences in the amount of calcium, milk-derived proteins and bioactive peptides Undefined outcome TOTAL Sample size calculation body weight or waist circumference Zemel and Sun. J Nutr. 2008;138: CRP Adiponectin -11% +8% -29% +18% < 1 serving 3 servings < 1 serving 3 servings < 1 serving 3 servings Zemel et al. Obes Res. 2005;13: Zemel et al. Int J Obes. 2005;29:

5 13/05/2013 Difference in the amount of dairy between the Interventions Combination of different dairy : Specification of the fat percentage Specific : Number of studies 5/8 1/5 Fat-free yogurt 1/8 Low-fat milk 1/8 Smoothies made with non-fat dry milk 1/8 No distinction between specific dairy : o milk vs. yogurt vs. cheese o low-fat vs. high-fat dairy Difference in the amount of dairy between the Thompson, Obes Res, 2005 Wennersberg, AJCN, diets: fiber 2 (control) Prescribed 2 diets: 3-5 Habitual diet Servings of dairy /d Consumption Actual Difference of 3 servings in dairy intake between : o 4/6 studies significant anti-inflammatory effects Difference in the amount of dairy between the 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 5

6 13/05/2013 In summary Cell culture studies: o production of proinflammatory cytokines Observational studies: o Inverse associations between dairy product consumption and inflammation In summary Randomized controlled nutritional intervention trials: 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 on inflammation Future perspectives Additional nutritional intervention studies: oadequately powered ospecifically designed to assess the effects of dairy on inflammation obetter characterization of the type and amount of dairy tested omechanisms underlying the inflammatory response o Inflammation-related gene expression Acknowledgements Systematic review: Benoît Lamarche Patrick Couture Sophie Desroches Caroline Richard PLI : Team Lamarche: Benoît Lamarche Patrick Couture Marie-Claude Lépine Amélie Charest Audrey Cyr Colleagues from U of Manitoba Clinical unit: Steeve Larouche Danielle Aubin Myriam Bouchard Laboratory: Johanne Marin Participants 6