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The impact of dairy products on anthropometric and cardiometabolic indicators -A sub-study of Dietary The impact of dairy products on anthropometric and cardiometabolic indicators -A sub-study of Dietary Intervention Randomized Controlled Trial (Direct-Dairy) Danit R Shahar First conference of the Israeli Dairy Council Research Foundation 18/2/09 The S. Daniel Abraham International Center for health and Nutrition and the Department of Epidemiology and Health Sciences Evaluation, Ben-Gurion University of the Negev

Background n n n Dietary calcium modulation of blood pressure has been well established Background n n n Dietary calcium modulation of blood pressure has been well established through numerous well-controlled studies over the last 20 years Recent studies suggest that dairy products may contribute to weight reduction in animal and human models Although findings are debatable

Mean Systolic and Diastolic Blood Pressures at Base Line and during Each Intervention Week, Mean Systolic and Diastolic Blood Pressures at Base Line and during Each Intervention Week, According to Diet, for 379 Subjects with Complete Sets of Weekly Blood-Pressure Measurements Nutrient Targets, Menu Analyses, and Average Daily Servings of Foods, According to Diet Appel L et al. N Engl J Med 1997; 336: 1117 -1124

Calcium and Dairy Acceleration of Weight and Fat Loss during Energy Restriction in Obese Calcium and Dairy Acceleration of Weight and Fat Loss during Energy Restriction in Obese Adults Obesity Research (12: 582 -590 (2004 n n A randomized controlled trial among 32 obese adults Isocaloric diets differed in calcium intake (400 to 500 mg of dietary calcium/d supplemented with placebo), a high-calcium diet (standard diet supplemented with 800 mg of calcium/d), or high-dairy diet (1200 to 1300 mg of dietary calcium/d supplemented with placebo) Effects of dietary treatments on body fat reduction. Changes in body fat are expressed as a percentage of original body fat measured by DXA

Does dairy calcium intake enhance weight loss among overweight diabetic patients? Danit R Shahar, Does dairy calcium intake enhance weight loss among overweight diabetic patients? Danit R Shahar, Relly Abel, Asher Elhayany, Hillel Vardi, Drora Fraser Diabetes care, 2007 The study was supported by a grant from Tnuva Research Institute, Rehovot, Israel.

Objective n To examine the impact of low-fat dairy consumption, particularly dairy calcium, on Objective n To examine the impact of low-fat dairy consumption, particularly dairy calcium, on weight loss and type II diabetes indicators among overweight type II diabetic patients

Percent change (from baseline) in health indicators after 6 months by dairy calcium intake Percent change (from baseline) in health indicators after 6 months by dairy calcium intake tertiles at 6 months (GLM analysis with age and change in energy intake from baseline in the model) P=0. 03 P=0. 02

Logistic regression model to predict percent weight loss above the median value (>8 percent) Logistic regression model to predict percent weight loss above the median value (>8 percent) in 6 months Variable Weight change percent > 8% OR P-value 95% CI Percent change in energy intake from baseline 1. 0 0. 49 0. 99– 1. 02 LGI diet * 0. 97 0. 07 0. 94– 1. 01 MMD diet * 1. 6 0. 15 0. 85– 3. 01 Non-dairy calcium intake 1. 0 0. 67 0. 99– 1. 01 Middle tertile of dairy calcium intake † 1. 5 0. 36 0. 65– 3. 41 Highest tertile of dairy calcium intake † 2. 4 0. 04 1. 10– 5. 50 Dietary fiber intake 1. 0 0. 19 0. 98– 1. 11

The Dietary Intervention Randomized Controlled Trial - DIRECT n=322 Low-fat diet Mediterranean diet Low-carb The Dietary Intervention Randomized Controlled Trial - DIRECT n=322 Low-fat diet Mediterranean diet Low-carb diet 2 years Evaluation Of dietary adherence In this two-year trial we randomized 322 moderately obese subjects (BMI=31 kg/m 2, age=52 years, 86% men) to one of three diets: low-fat restricted-calorie, Mediterranean restricted-calorie or low-carb non-restricted- calorie. weight parameters Metabolic & inflammatory biomarkers Diabetics

Location The Nuclear Research Center Isolated workplace Rational n On site clinic n Most Location The Nuclear Research Center Isolated workplace Rational n On site clinic n Most procedures done in the workplace n Exclusive, regulated source of lunch

Mean weight loss was 2. 9 kg for low-fat, 4. 4 kg for Mediterranean, Mean weight loss was 2. 9 kg for low-fat, 4. 4 kg for Mediterranean, and 4. 7 kg for low-carb (-3. 3 kg, -4. 6 kg, and -5. 5 kg, respectively, among 272 completers) Weight loss phase Weight loss maintenance phase

Data used in Direct-Dairy FFQ from baseline, 6, 12 and 24 months n Monthly Data used in Direct-Dairy FFQ from baseline, 6, 12 and 24 months n Monthly weight and waist circumference along the 24 months of the study n Cardiometabolic indicators including blood pressure, lipid measurements, glucose, insulin and inflammatory markers at baseline, 6, and 24 months. New data to be collected: n Serum vitamin D (25(OH)D and 1, 25(OH)2 D) at baseline and at 6 months n Sun exposure questionnaire n Data regarding dairy intake at baseline, 6, 12 and 24 months n

Baseline characteristics by dairy intake tertiles Baseline characteristics by dairy intake tertiles

Changes in weight by tertiles of dairy calcium P=0. 045 P=0. 037 0. 095 Changes in weight by tertiles of dairy calcium P=0. 045 P=0. 037 0. 095 * P for linear trend at 6, 12 and 24 months is 0. 028, 0. 011, and 0. 57 • Data is adjusted for age, gender, physical activity, energy intake change, diet group

Changes in waist circumference by tertiles of dairy calcium P for linear trend at Changes in waist circumference by tertiles of dairy calcium P for linear trend at 6, 12 and 24 months is 0. 92, 0. 16, and 0. 07 Data is adjusted for age, gender, physical activity, energy intake change, diet group

Dairy intake and Vitamin D n n Calcitrophic hormones, parathyroid hormone and 1, 25(OH)2 Dairy intake and Vitamin D n n Calcitrophic hormones, parathyroid hormone and 1, 25(OH)2 D respond to low (increased lipid storage) and high calcium diets (inhibits adiposity) (Zemel 2004) Human adipocytes possess membrane (nongenomic) vitamin D receptors that transduce a rapid [Ca 2+] response to 1, 25(OH)2 D (Zemel, 2003); The treatment of human adipocytes with 1, 25(OH)2 D results in the coordinated activation of fatty acid synthase expression and activity and the suppression of lipolysis, leading to an expansion of adipocyte lipid storage. This mechanism, although based on reasonable physiological plausibility needs to be proven in larger human groups and in epidemiological studies.

Other suggested mechanisms n n Reduced absorption of fat in the gut Intracellular calcium Other suggested mechanisms n n Reduced absorption of fat in the gut Intracellular calcium has a regulatory role in fat metabolism by influencing lipolysis, fat oxidation and lipogenesis Possible effect on appetite and energy expenditure Few studies showed an increase in fecal excretion of fat when calcium intake increased

Conclusions n n n We have demonstrated in our study that higher dairy intake Conclusions n n n We have demonstrated in our study that higher dairy intake among overweight patients on 3 dietary regimens enhances the weight loss process This remained true even after controlling for change in total energy and diet type We did not find any association between dairy calcium intake and other cardiometabolic indicators isuch as waist circumference, Hb. A 1 C, HDL, LDL, and blood pressure It is important to take into consideration the possible negative effect of dairy products-Giovannucci et al. showed that calcium intake exceeding 1, 500 mg/day may be associated with a higher risk of advanced and fatal prostate cancer Parodi in a review of 40 case control and 12 cohort studies did not find any association between dairy product consumption and the risk of breast cancer

Thanks n n KAMAG participants KAMAG researchers particularly Dr Iris Shai and Dr Dan Thanks n n KAMAG participants KAMAG researchers particularly Dr Iris Shai and Dr Dan Schwarzfuchs The S. Daniel Abraham International Center for Health and Nutrition teem, particularly Prof Drora Fraser, Hillel Vardi and Osnat Rosenthal Thanks you for listening