Dairy matrix effects on T2 diabetes and cardiometabolic health?

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Department of Nutrition, Exercise and Sports Dairy matrix effects on T2 diabetes and cardiometabolic health? Arne Astrup Head of department, professor, MD, DMSc. Department of Nutrition, Exercise and Sports University of Copenhagen 4 September 2018 Dias 1

Department of Nutrition, Exercise and Sports EFSA: As low as possible 4 September 2018 Dias 2

People don t want to hear the truth because they don t want their illusions destroyed. Friedrich Nietzsche

The lipid hypothesis and CHD SATURATED FAT HIGH BLOOD CHOLESTEROL? ATHEROSCLEROSIS CHD

Hierarchy in Scientific Evidence High Systematic Reviews (Meta-analysis) Randomized Controlled Trials Other Controlled Trials Prospective Cohort studies Case Control studies Prevalence studies Low Ecological studies Animal studies

Saturated fat intake and CVD risk -the most recent evidence Department of Nutrition, Exercise and Sports

Department of Nutrition, Exercise and Sports BMJ 2015;351:h3978 doi:10.1136/bmj.h3 Similar conclusion in a previous meta-analysis of prospective cohort studies and CVD. (Siri-Tarino et al.,am J Clin Nutr 2010;91:535 46)

Department of Nutrition, Exercise and Sports Ann Intern Med. 2014;160:398-406

Department of Nutrition, Exercise and Sports Randomized controlled trials: Saturated fat versus PUFA

Department of Nutrition, Exercise and Sports Meta-analysis for mortality from coronary heart disease in trials testing replacement of saturated fat with vegetable oils rich in linoleic acid. Main analysis: trials provided replacement foods (vegetable oils) and were not confounded by any concomitant interventions.

Department of Nutrition, Exercise and Sports Can we predict the health effects of foods based on the information on the label? Or just by the content of saturated fat?

Department of Nutrition, Exercise and Sports From simgle nutrients to whole foods: the importance of the food matrix

4 September 2018 Dias 13 Department of Nutrition, Exercise and Sports

4 September 2018 Dias 14 Department of Nutrition, Exercise and Sports

Updated meta-analysis of fermented dairy and CVD and mortality Relative % author year exposure gender risk (95% CI) Weight Kahn 1984 Cheese Women/Men 0.99 (0.94, 1.04) 2.77 Mann 1997 Cheese Women/Men 1.02 (0.90, 1.17) 0.51 Fortes 2000 Cheese Women/Men 1.30 (0.36, 4.68) 0.01 Engberink 2009 Cheese Women/Men 0.95 (0.90, 1.00) 2.62 Bonthuis 2010 Yoghurt Women/Men 1.08 (0.96, 1.20) 0.73 Bonthuis 2010 High-fat cheese Women/Men 0.93 (0.68, 1.27) 0.10 Goldbohm 2011 High-fat fermented dairy Men 0.97 (0.95, 0.99) 6.64 Goldbohm 2011 Low-fat fermented dairy Men 1.00 (0.99, 1.01) 8.86 Goldbohm 2011 High-fat fermented dairy Women 0.97 (0.95, 1.00) 5.58 Goldbohm 2011 Low-fat fermented dairy Women 1.00 (1.00, 1.01) 8.82 Dalmeijer 2012 Fermented dairy Women/Men 1.00 (0.98, 1.01) 7.99 Total 29 cohort studies are available for meta-analysis. Inverse Soedamah-Muthu 2013 Fermented dairy Women/Men 0.92 (0.87, 0.98) 2.00 Van Aerde 2013 Fermented dairy Women/Men 1.00 (0.98, 1.01) 7.62 associations were found between total fermented (included sour milk Michaelsson 2014 Cheese Women 0.88 (0.86, 0.89) 7.66 products, Michaelsson yogurt 2014 Cheese or cheese) Men with mortality (RR 0.98, 95% 0.98 (0.96, CI: 0.99) 7.36 0.97- Michaelsson 2014 Soured milk yogurt Women 1.00 (0.99, 1.00) 9.16 0.99; I 2 =94.4%) and risk of CVD (RR 0.98, 95% CI: 0.97-0.99; Michaelsson 2014 Soured milk and yogurt Men 1.00 (0.99, 1.00) 9.19 Praagman 2015 Fermented dairy (without cheese) Women/Men 1.00 (0.99, 1.01) 8.90 I 2 =87.5%). Also stratified analysis of total fermented dairy of cheese Praagman 2015 Cheese Women/Men (0.96, 1.04) 3.46 shown a Overall lower (I-squared = 94.4%, p = 2% 0.000) lower risk of CVD (RR 0.98, 95% CI: 0.98 0.95-1.00; (0.97, 0.99) 100.00 I 2 =82.6%). NOTE: Weights are No from random effects associations analysis were found for total dairy, high-fat/ low-fat dairy or milk with the health outcomes..3.75 1 1.5 2 relative risk Guo J, Astrup A, Lovegrove JA, et al. Milk and dairy consumption and risk of cardiovascular diseases and all-cause mortality: dose-response meta-analysis of prospective cohort studies. Eur J Epidemiol 2017;32:269-87.

Dairy and body weight regulation

Effect of high vs low dairy on weight loss Department of Human Nutrition

Effect of high vs low dairy on fat loss Department of Human Nutrition

Effect of high vs low dairy on fat free mass Department of Human Nutrition

Cheese intake lowers diabetes risk

Clinical Trial: DASH vs. full-fat dairy DASH on blood pressure and lipids and lipoproteins The DASH (Dietary Approaches to Stop Hypertension) diet is rich in fruit, vegetables, and low-fat dairy foods DASH significantly lowers blood pressure but has mixed effects on blood lipids Improves LDL cholesterol but worsens other CVD risk factors such as triglycerides and HDL cholesterol This study was designed to test the effects of substituting full-fat for low-fat dairy foods in the DASH diet Replacing sugars, mostly from fruit juices, which constituted 59% of total fruit intake in the DASH, to whole milk, cheese, and yogurt The full-fat dairy DASH diet contained 14% of calories from saturated fat, provided mainly by dairy, whereas the low-fat DASH contained 8% of calories from saturated fat Chiu et al. AJCN 2016

Full-fat dairy DASH and standard DASH confer the same blood pressure benefit Chiu et al. AJCN 2016

Full-fat dairy DASH resulted in better overall lipid profile than standard DASH Chiu et al. AJCN 2016

DASH vs. full-fat dairy DASH on blood pressure and lipids and lipoproteins Despite a higher saturated fat content (14% vs. 8%) full-fat dairy DASH resulted in a better overall lipid profile than standard DASH LDL cholesterol was not different between full-fat dairy DASH and standard DASH Full-fat dairy DASH improved LDL particle size compared to standard DASH HDL cholesterol worsened on standard DASH Full-fat dairy DASH improved plasma triglycerides compared to standard DASH These findings indicate that full-fat dairy foods could be incorporated in the DASH dietary pattern without impairing its positive healthy effects on blood pressure, and is perhaps superior in terms of blood lipid profile Chiu et al. AJCN 2016

Normal weight subjects Obese subjects Type 2 diabetic patients Increment in brain glucose concentration 1.46 mmol/l 1.06 mmol/l (73% of normal weight subjects) 0.71 mmol/l (49% of normal weight subjects) Steady state 12 mmol/l plasma glucose concentration Normal weight, obese and type 2 diabetic participants underwent 1H MR spectroscopy scanning to measure change in intracerebral glucose levels during a 2-hour hyperglycemic clamp (glucose ~220 mg/dl). The change in intracerebral glucose in the lean subjects is used as a reference (100%), and it is was lower in the overweight and the diabetic after controlling for age and sex. Modified from Hwang et al

A Systematic Review and meta-analysis of Dietary Carbohydrate Restriction in Patients with Type 2 Diabetes Ole Snorgaard, Grith Møller Poulsen, Henning Keinke Andersen and Arne Astrup Within the first year of intervention, LCD was followed by a 0.34 %- point lower [95% CI: 0.06, 0.63] HbA1c compared to HCD. A greater reduction in carbohydrate restriction was associated with greater reduction in HbA1c (R = -0.85, P<0.01).

Normoglycemic Subjects Lost More Weight On A Low-Fat Diet. Subjects w/t2d More Responsive To a High-Fat Diet Favors Low Fat Diet Variable: Fasting Plasma Glucose Favors High Fat Diet *P < 0.05 from zero # P < 0.05 between glycemic groups 27

PREDIMED 2017: Subjects With Elevated Fasting Glucose Lost Significantly More Weight on Ad Libitum, High Fat Diets NEW ANALYSIS PREDIMED 5-Year Body Weight Change (2016) Ad Libitum, High Fat Mediterranean Diets (2017) (n=746) (n=329) (n=597) (n=174)

4 September 2018 Dias 29 Department of Nutrition, Exercise and Sports

Department of Nutrition, Exercise and Sports 4 September 2018 Dias 30 Figure 1. Overall effect/association between dairy (cheese and yogurt) intake and health outcomes. favorable effect/association; adverse effect/association; no effect/association.

Conclusions The totality of evidence i.e. meta-analyses of both observational studies and RCT s cannot find any harmful effects of dairy on body fat, metabolic syndrome, type 2 diabetes, or CVD. Yogurt and cheese does not exert the detrimental effects on blood lipids and blood pressure as previously predicted by its sodium and saturated fat content. Dairy, in particular full-fat, exerts beneficial effects on LDL-cholesterol, blood pressure and postprandial triglycerides as compared to butter. Meta-analysis of observational studies support that full fat yogurt and cheese (and perhaps other fermented dairy) may protect from CVD and type 2 diabetes. The effects of yogurt and cheese on body composition, diabetes and CVD risks can be attributed to the food matrix with nutrients i.e. protein, calcium, SCFA from fermentation, and perhaps peptides, phospholipids. Whereas the low-fat version might by helpful for non-diabetic overweight and obese individuals, the full-fat versions are optimal for type 2 diabetics. A diet including yogurt and cheese should be recommended for all to prevent and manage type 2 diabetes and cardiovascular disease.

Evidence based information? Department of Nutrition, Exercise and Sports