Functional properties and health benefits of orange juice

Functional properties and health benefits of orange juice Thais Cesar, PhD Pharmaceutical School, Sao Paulo State University UNESP Araraquara SP, Brazil

Orange juice Functional Properties: 1. Essential nutrients for a healthy diet 2. Protection against cardiovascular disease 3. No association with gain of weight or obesity 4. Decrease of insulin resistance 5. Improvement of antioxidant capacity 6. Decrease of inflammation markers 7. Improves satiety

Orange juice Natural source of vitamins and minerals: Vitamin C, Folic Acid, Potassium Easily incorporated into a healthy diet plan 100% fruit juices, as Orange Juice, are associated with a lower BMI and a healthier diet in children and adults O Neil et al Nutr Res 2011, Nutr J 2012

% RDA - 2000 kcal diet Nutritional contribuition 100 80 60 40 20 0 kcal Carb Ca K Vit C Folate 6% 12% 18% 9.6% 100% 12.5% 8 oz of orange juice USDA Nutrient Database (2005 e 2007) release 2.1b 4

Orange juice Citrus flavonoids Hesperidin & Naringin 15.6 mg/240ml 1.9 mg/240ml Cholesterol-lowering potential in animal and human (Kurowska et al, 2000; Roza et al, 2007)

Orange juice and Coronary Heart Disease Naringenin and Hesperitin in vivo 1) activity ACAT1, ACAT2, MTP 2) lipoproteins assembly (VLDL) 3) LDL receptor ( Plasma Clearance of LDL) total Cholesterol and LDL-C (Roza 2007, Wilcox 2001; Borradaile 2002; Aptekman and Cesar, 2010) 6

Orange juice and Coronary Heart Disease Clinical study Orange Juice: transfer of Cholesterol to HDL in normolipidemic and hypercholesterolemic individuals (Cesar et al, Nut Res 2010, 30: 689) 7

Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B in normal and moderately hypercholesterolemic subjects Hypothesis: OJ consumption ( 12 months) is associate with low risk factors for CVD in subjects with normal and moderately high cholesterol blood levels. Aptekmann and Cesar; Lipids in Health and Disease 2013, 12:119 http://www.lipidworld.com/content/12/1/119

Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B Subjects: employees OJ factory with free daily access to OJ 103 men (18 66 y) 26 women (18 65 y) OJ Consumption: 41% = 2 cups (480 ml) OJ/d 59% = non-consumers

Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B Anthropometric Normolipidemic Hypercholesterolemic Orange juice Non-consum. Consumers Non-consum. Consumers Weight (kg) 75.9 11.4 70.8 10.0 78.5 13.8 83.0 10.5 BMI ( kg/m 2 ) 25.1 3.63 23.8 2.89 26.6 2.8 27.0 3.4 Body fat (%) 27.8 5.03 25.1 7.52 28.0 5.7 27.0 4.1 Waist circ.(cm) 90.4 9.96 87.5 9.33 96.3 8.2 97.5 9.3 No differences between OJ consumers and non-consumers

Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B Dietary Normolipidemic Hypercholesterolemic Orange juice Non-consum. Consumers Non-consum. Consumers Energy (MJ/d) 11.5 5.04 11.6 2.51 12.0 2.88 11.8 2.0 Carbohydrate (g/d) 327 111 346 113 382 123 367 72 Total fat (g/d) 95 32 99 28 90 38 91 27 Vitamin C (mg/d) 138 115 227 121* 174 120 273 158* Folate (µg/d) 393 138 500 148* 423 146 538 166* Increase of Vitamin C (+60%) and Folate (+27%) in OJ consumers

Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B Biochemical Normolipidemic Hypercholesterolemic Orange juice Non-consumers Consumers Non-consumers Consumers Triglicerides (mmol/l) 1.15 0.37 1.11 0.55 1.86 0.63 2.16 1.12 Total Cholesterol (mmol/l) 5.08 0.70 4.54 0.78* 6.77 0.41 6.40 0.58* HDL-C (mmol/l) 1.20 0.29 1.16 0.31 1.14 0.27 1.16 0.23 LDL-C (mmol/l) 3.35 0.61 2.74 0.80* 4.78 0.48 4.20 0.86* Apo B (g/l) 0.90 0.19 0.79 0.21* 1.27 0.17 1.12 0.17* Homocysteine (µmol/l) 9.95 2.81 9.17 2.31 11.1 2.53 10.0 2.31-8% Cholesterol, -15% LDL-C, -14% LDL/HDL, -12% Apo B in OJ consumers

Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B Conclusions OJ consumption was not associated with: weight, BMI, waist or body fat blood serum Triglyceride or Homocysteine But, OJ consumption was associated with reduction of: total cholesterol LDL-cholesterol LDL/HDL ratio apo B

Orange juice High carbohydrate intake associated with Insulin Resistance (sub-normal response of Insulin) (NCEP Report, 2004; IDF 2005) Controversia: Sugar OJ increases the Insulin Resistance? 1 cup (8 oz) = 22g sugar (sucrose : glucose : fructose/ 2:1:1) OJ flavonoids prevent oxidative and inflammatory stress, safe energy source (Ghanim et al, 2007) 14

Insulin resistance IR is commonly associated with obesity and large waist circumference Development of IR: hyperlipidemia diabetes mellitus type 2 hypertension cardiovascular disease Pre-condition to Metabolic Syndrome

Metabolic syndrome Adipose Tissue: Release pro-inflammatory mediators: PAI1, TNF-α, IL-6, C-Reactive Protein (CRP) Free Fat Acids Oxidative Stress & Adipokines Pro-thrombotic Pro-inflammatory (Grundy et al, 2005) Atherosclerosis Diabetes 16

Insulin resistance Biochemical and Clinical Charac. Normal Weight Overweight/Obese N = 37 N = 28 Orange Juice (750mL/d) 1 o day 60 o day 1 o day 60 o day Glucose mg/dl 79 6.8 79 5.0 80 8.5 81 6.9 Insulin IU/mL 6.8 3.1 5.0 2.3* 8.5 4.3 6.9 3.4* Insulin Resistance Index 1.3 0.6 1.0 0.5* 1.7 1.0 1.4 0.7* HOMA index % 26 % 18% Overall: IR 22 % Preliminary data, Cesar et al

Oxidative Stress Biochemical and Clinical Charact. Normal weight Overweight N = 17 N = 17 Orange Juice (750mL/d) 1 o day 60 o day 1 o day 60 o day C-Reactive Protein, mg/dl 0.32 0.3 0.28 0.6* 0.38 0.5 0.27 0.5* Antioxidant capacity % 10.6 3.9 27.9 7.5* 12.1 7.1 26.6 8.5* Blood Pressure Systolic, mmhg 119 ± 8 114 ± 11* 128 ± 10 123 ± 12 Diastolic, mmhg 75 ± 5 74 ± 9 83 ± 9 79 ± 7* Preliminary data, Cesar et al

Oxidative Stress and Inflammation in patients with C hepatitis Chronic C Hepatitis Patients Normal weight N = 46 Orange Juice (500mL/d) 1 o day 60 o day TBARS % 5.7 ± 2.1 2.9 ± 1.9** Antioxidant Capacity % 12.1 ± 10.7 19.7 ± 8.5* C reactive protein, mg/ml 4.6 ± 2.1 0.9 ± 1.4** Preliminary data, Cesar et al

Inflammation in patients with C hepatitis treated with OJ Liver Enzymes Normal Level High Level Orange Juice 1 o day 60 o day 1 o day 60 o day Alanine Transaminase (U/L) Aspartate Transaminase (U/L) 11 45 > 46 27 ± 12 26 ± 13 82 ± 31 67 ± 22* 11 39 > 40 31 ± 7 32 ± 8 81 ± 12 66 ± 12* -Glutamyl Transpeptidase 7 58 > 58 (U/L) 35 ± 13 34 ± 16 182 ± 132 135 ± 87*

Fresh or Pasteurized OJ? Which one is better? OJ processing can influence the concentration of citric bioactive compounds and therefore may affect their bioavailability in human body. Fresh OJ is perceived as a superior flavor beverage, but pasteurization process is needed for the consumers safety.

OJ commercially processing 8oz fresh OJ: 125mg Vit C and 76µg Folate 8oz processed OJ: 86mg Vit C and 46µg Folate (Bai, et al, 2010) OJ bioactive compounds and flavonoids: Can processing methods influence the satiety (appetite) and energy intake?

Biochemical markers and appetite after acute intake of OJ Effect of acute intake of fresh and pasteurized OJ on markers of satiety in individuals with normal weight and overweight. Test drink: sugars + H 2 O Glucose Leptin Insulin Adiponectin

µmol/l µmol/l mg/dl mg/dl 140 Glucose (BMI < 25kg/m 2 ) 140 Glucose (BMI 25kg/m 2 ) 130 120 110 Test Fresh OJ Past OJ 130 120 110 Test Fresh OJ Past OJ 100 100 90 90 80 80 70 0 50 100 150 200 250 300 min 70 0 50 100 150 200 250 300 min Normal Weight Obese 140 120 100 Insulin (BMI < 25kg/m 2 ) Test Fresh OJ Past OJ 140 120 100 Insulin (BMI 25kg/m 2 ) Test Fresh OJ Past OJ 80 80 60 60 40 40 20 20 0 0 50 100 150 200 250 300 min 0 0 50 100 150 200 250 300 min

35000 30000 25000 20000 15000 Normal weight a a,b b A Obese A A Glucose (AUC after 300 min) 10000 5000 0 Test Fresh OJ Past OJ Test Fresh OJ Past OJ Insulin (AUC after 300 min) 40000 35000 30000 25000 20000 15000 10000 a Normal weight b b B Obese B B 5000 0 Test Fresh OJ Past OJ Test Fresh OJ Past OJ

Biochemical markers and appetite after acute intake of OJ Appetite Energy Expenditure Leptin appetite stimulators appetite inhibitors in the hypothalamic ARC and postsynaptic sites satiety Leptin CNTF (cytokine) Adiponectin Insulin-sensitizing property Inverse association with IR and Diabetes (obesity) Adipocytes

ng/ml ng/ml 25000 20000 Normal weight A Obese 15000 10000 5000 a b a,b A A Leptin (AUC after 300 min) 0 Test Fresh OJ Past OJ Test Fresh OJ Past OJ Normal Obese 4000 A Normal weight A A Obese Adiponectin (AUC after 300 min) 3000 2000 B B B 1000 0 Test Fresh OJ Past OJ Test Fresh OJ Past OJ Normal Obese

Conclusions Consumption of Orange Juice (long and short-term): No effect on the Nutritional Status of regular consumers Reduced markers related to insulin resistance and cardiovascular disease Increased the antioxidant capacity Decrease inflammation markers in blood and liver Improve the satiety Is good for your health!