Staying on Trend: The Powerful Flavonoid Consumers Need Navindra P. Seeram, Ph.D. Bioactive Botanical Research Laboratory

Transcription

1 FLRIDA DEPARTMENT F CITRUS Staying on Trend: The Powerful Flavonoid Consumers Need Navindra P. Seeram, Ph.D. Bioactive Botanical Research Laboratory 1

2 utline 1. Introduction Florida Department of Citrus Dr. Navindra Seeram* 2. verview Plant Natural Products: Flavonoids & Polyphenols Role of Flavonoid-Rich Plant Foods in Human Health and Disease 3. range Juice and Hesperidin Published human studies supporting health effects 4. Summary & Conclusions *Dr. Seeram is an Associate Professor in the Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island. Dr. Seeram received an honorarium for the sole purpose of this presentation and has no other conflicts of interest of note.

3 Plant Medicines Plants have been used as medicines by ancient cultures for centuries e.g. Traditional Chinese Medicine, Ayurveda, etc. The WH estimates 80% of developing countries currently use plants as basis of medicinal systems Used as foods, extracts, teas, tinctures, herbs and spices, etc.

4 Examples of Pharmaceuticals from Plants Salicin, constituent of willow bark; Aspirin: acetyl derivative

5 Dietary Plant Polyphenols Stilbenes Resveratrol H Phenolic polymers C C C C C H H H H H H H H Casuariin Ellagitannins Proanthocyanidin H Procyanidin trimer (flavanol) H H Isoflavonoid Coumestans Daidzein Isoflavone s Coumestrol H H Flavonoids Flavones Flavonols Flavanones Flavanols (Catechins) Anthocyanins H Apigenin H Quercetin H Naringenin H (+)-Catechin H Cyanidin + Phenolic acids Cinnamic acid C C CH 3 Ferulic acid H H H H H Chlorogenic acid Lignans H CH 3 Secoisolariciresinol H 3 C

6 Examples of Polyphenol-Rich Plants Grape Seed & Red Wine Extracts & Resveratrol Green Tea Flavanols/Catechins Cranberry & PACs Green Tea Extract Grape Seed Extract

7 Citrus Fruits and Hesperidin Hesperidin Dietary Supplement Hesperidin Powder Supplement

8 What is Hesperidin? Flavonoid found in citrus fruits and juices: lemon, lime, grape fruit, and oranges (blond and blood) Hesperidium = modified berry with leathery rind Isolated in 1828 from white inner layer of citrus peels mg/100 ml pure orange juice (source: Phenol-Explorer) Also found in some other plants e.g. peppermint, Welsh onion (a type of scallion)

9 Citrus Flavonoids* Flavanones Naringenin Hesperetin Neohesperidose (Nh) Rutinose (Ru) Polymethoxylated flavones Nobiletin Tangeretin Apigenin Luteolin Diosmetin Flavonols Quercetin Kampferol Flavanone glycosides Narirutin Naringin Hesperidin Neohesperidin *Anthocyanins found in red grapefruit & blood orange

10 Nutrient-Rich 100% range Juice (J) EXCELLENT SURCE >20% Daily Value Vitamin C Calcium (fortified juices) Vitamin D (fortified juices) GD SURCE 10-19% Daily Value Potassium Folate Thiamin LESSER AMUNTS <10% Daily Value Magnesium Vitamin B6 Vitamin A Niacin 8 oz. serving

11 Also 100% J Is the most commonly consumed and commercially produced food product that contains Hesperidin Hesperidin is naturally found in the pulp & peel and thus is extracted into 100% J during its production 100% juice contains no added sugar 100% juice can help all ages meet daily fruit intake recommendations SURCE: What We Eat in America, NHANES , available online at

12 Health Benefits of 100% J & Hesperidin Cardiometabolic: endothelial function, blood pressure and vascular health Glucose homeostasis & blood sugar control Immune system Cognition Gut health: antiinflammatory effects in colon

13 Animal vs. Human Clinical Studies Cell-Culture Rodents Humans

14 What happens when we consume food bioactives? Absorption Distribution Metabolism Excretion

15 Flavonoid Bioavailability & Metabolism ral Ingestion Peripheral Tissues Small Intestine Small intestine Blood Circulation Kidneys Colon Microflora Bile Liver Phase I + II metabolism Urine Feces Enterohepatic Circulation Phase II Conjugation: Glucuronidation; Sulfation; Methylation

16 Review of Published Human Studies with 100% J and/or Hesperidin

17 Cardiovascular: Vasodilation & BP J and Hesperidin increased blood flow. J was more potent than Hesperidin in acute vasodilation suggesting synergistic effects of compounds in J. Hesperidin contributes to the vascular protective effects of J in healthy volunteers. CDP= control + placebo CDH= control + Hesperidin -Morand et al. Am J Clin Nutr. 2011;93(1):73-80.

18 -Napoleone et al. Thrombosis Res. 2013;132(2): Cardiovascular: Coagulant Both J and red J decreased pro-coagulant activity of whole blood. Effect of J intake on whole blood (WB) procoagulant activity without (A), with TNFa (B) or with LPS (C) Since the flavonoid and nutrient content of blond J and red J were similar, the authors concluded the effect of J is independent of its anthocyanin content (as previously hypothesized).

19 Cardiovascular: Endothelial Function ALL of the J drinks attenuated the adverse effects of high-fat meals on endothelial function measured by a smaller reduction in blood flow compared to the control. Control -Rendeiro et al. Br J Nutr. 2017;116(12):

20 Cardiovascular: Endothelial Function All J drinks sustained plasma nitrite levels No dose-response relation was observed suggesting 100% J containing 128 mg flavanones is sufficient (potentially obtainable w/in recommended intakes) to attenuate effects of high fat intake on vascular function. -Rendeiro et al. Br J Nutr. 2017;116(12):

21 Inflammation/Immune/Genetic 500 ml J or Hesperidin (146 mg) changed white blood cell gene expression to an anti-inflammatory and antiatherogenic profile. - Milenkovic et al. PLoS ne. 2011;6(11):e ml J vs. isocaloric drink with or without Hesperitin daily x 1 month did not affect immune system. -Perche et al. Clin Nutr 2014; 33(1): Increased total antioxidant capacity of whole blood with 200ml 3/d x 4wk of J. -Constans J, et al. Clin Nutr. 2015;34(6):

22 Cognition Randomized, double-blind, cross-over study in 24 healthy overweight men (30-65 yr) evaluated 240 ml of flavanonerich J (272 mg) compared to an energy-matched placebo consumed on different days separated by a 2-week washout. Psychomotor speed improved in J group and was higher than placebo at 2 and 6 hrs -Alharbi et al. Eur J Nutr. 2016;55(6):

23 Cognition -Alharbi et al. Eur J Nutr. 2016;55(6): Flav-rich J attenuated diminishing subjective alertness over time compared to placebo Non-significant trends (p=0.09) for improvement in global score for J, whereas placebo declined

24 Cognition -Kean RJ, et al. Am J Clin Nutr. 2015;101(3): Global cognitive function was significantly better following consumption of 500mL of flavrich J compared to low-flav J Executive function z-score (combining all tests) was higher in flav-rich J but did not reach statistical significance

25 Epidemiological studies - Cardiovascular Prospective cohort in Italy (45-64yr), 14 year follow-up Increased flavanone intake decreased CV risk score and changes in CV risk score over time Higher flavanone intake associated with a 52% lower cardiovascular events and 41% lower all-cause mortality (HR 0.48 (0.29, 0.77) and HR 0.59 (0.40, 0.85) p<0.005, adjusted models) -Ponzo et al. J Trans Med. 2015;13(1):218

26 Epidemiological studies - Diabetes Nurses' Health Study and NHSII - Higher urinary flavonones were significantly associated with a 39% lower T2D risk in the short-term follow-up. (R 0.61 (0.39, 0.98; p-trend 0.03) -Sun et al. J Nutr. 2015;145(6): Korean National Health and Nutrition Examination Survey Males with impaired fasting glucose consumed significantly less hesperidin and total flavanones than males with normal fasting blood glucose. (energy, macronutrient, vitamin C intake did not differ) -Yeon et al. Clinica Chimica Acta. 2015;439(Suppl C):

27 Epidemiological studies - Depression Nurse s Health Study and NHSII Incidence of depression was 10% lower in women with higher intake of flavanones. (HR 0.90 ( ), p-trend ) A weekly serving of citrus fruit or a daily serving of citrus fruit & citrus juices lowered depression incidence by 7 15%. (fruit HR 0.93 (0.88, 0.99); fruit & juices HR 0.85 (0.75, 0.97), p-trends 0.05) -Chang et al. Am J Clin Nutr. 2016;104(3):

28 Kinetics & Metabolism In-vitro digestion of orange fruit, homogenized orange fruit, and J pasteurized (flash vs. normal). Although the whole and homogenized fruit had more flavanones, carotenoids and vitamin C, the liberation and bioavailability was much greater for all compounds in the processed J. -Aschoff et al. J Agric Food Chem. 2015;63(2): In a randomized, cross-over study in 12 adults, no differences in urinary excretion of Hesperidin from J vs whole orange, although whole fruit had 2.3x higher amounts of flavanones. Authors state possible saturation occurs with absorption R whole fruit matrices inhibit absorption. -Aschoff et al. Mol Nutr Food Res. 2016;60(12):

29 Kinetics & Metabolism No difference in absorption or excretion of flavanones from J versus whole orange fruit in a randomized crossover study of 20 healthy adults. In adults consuming J only, individual variation in urinary excretion was very large (0-59%). No effects of BMI, sex, or contraceptive use associated with the variation in flavanone excretion. -Brett et al. Br J Nutr. 2009;101(5):

30 Kinetics & Metabolism Male endurance athletes consumed 500 ml J 1 time during training and again when training was stopped for 1 week. Bioavailability of Hesperidin metabolites from J (measured by urinary excretion) was greater during training compared to when training ceased. -Pereira-Caro et al. Am J Clin Nutr. 2017; 106(3):

31 Summary & Conclusions Several human studies support the cardiovascular beneficial effects of 100% J and Hesperidin Also other biological effects include: glucose regulatory, cognition, anti-oxidant and anti-inflammatory effects Hesperidin contributes to the health benefits of 100% J

32 FLRIDA DEPARTMENT F CITRUS Acknowledgment & Questions Visit FDC at Booth #2022 Dr. Navindra Seeram University of Rhode Island nseeram@uri.edu Dr. Tami Turner Florida Department of Citrus TTurner@citrus.myflorida.com