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The Health Effects of Sea Buckthorn Berries and Oil in Humans

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The Health Effects of Sea Buckthorn Berries and Oil in Humans THE HEALTH EFFECTS OF SEA BUCKTHORN BERRIES AND OIL PETRA LARMO Department of Biochemistry and Food Chemistry, University of Turku Turku 2011 Supervised by Professor Heikki Kallio, Ph.D. Department of Biochemistry and Food Chemistry University of Turku Turku, Finland Professor Raija Tahvonen, Ph.D. Biotechnology and Food Research MTT Agrifood Research Finland Jokioinen, Finland Docent Baoru Yang, Ph.D. Department of Biochemistry and Food Chemistry University of Turku Turku, Finland Reviewed by Professor Philip Calder, Ph.D. Institute of Human Nutrition School of Medicine University of Southampton Southampton, United Kingdom Adjunct Professor Jukka Marniemi, Ph.D. Department of Chronic Disease Prevention National Institute of Health and Welfare (THL) Turku, Finland Opponent Professor John W. Finley, Ph.D. Department of Food Science Lousiana State University Baton Rouge, United States of America ISBN 978-951-29-4459-0 (PRINT) ISBN 978-951-29-4460-6 (PDF) Painosalama Oy – Turku, Finland Contents 3 CONTENTS ABSTRACT ................................................................................................................... 5 LIST OF ABBREVIATIONS ...................................................................................... 6 LIST OF ORIGINAL PUBLICATIONS ................................................................... 8 1 INTRODUCTION .................................................................................................. 9 2 REVIEW OF THE LITERATURE ....................................................................... 11 2.1 COMPOUNDS OF SEA BUCKTHORN BERRIES ASSOCIATED WITH POTENTIAL HEALTH EFFECTS ................................................................ 11 2.1.1 Flavonoids, phenolic acids and lignans ............................................ 11 2.1.2 Vitamin C .............................................................................................. 16 2.1.3 Inositols ................................................................................................. 17 2.1.4 Berry and seed oils ............................................................................... 17 2.1.4.1 Triacylglycerols, glycerophospholipids and fatty acids ..... 18 2.1.4.2 Vitamin E ................................................................................... 19 2.1.4.3 Carotenoids ............................................................................... 22 2.1.4.4 Phytosterols............................................................................... 24 2.2 THE EFFECTS OF SEA BUCKTHORN BERRIES AND OIL ON THE HEALTH .......................................................................................................... 25 2.2.1 Antioxidative and cytoprotective effects .......................................... 25 2.2.1.1 In vitro cytoprotection by antioxidant activity ..................... 25 2.2.1.2 Animal studies on cytoprotection and antioxidant action . 28 2.2.2 Inflammation and immunomodulation ............................................ 34 2.2.3 Proliferation, apoptosis and cancer ................................................... 38 2.2.4 Antimicrobial properties ...................................................................... 42 2.2.5 Wounds, skin and mucosa ................................................................... 44 2.2.6 Gastric ulcer ........................................................................................... 49 2.2.7 Hepatotoxicity and liver fibrosis ......................................................... 51 2.2.8 Risk factors associated with cardiovascular diseases and diabetes52 2.2.8.1 Endothelium ............................................................................. 52 2.2.8.2 Platelet aggregation and thrombosis ..................................... 53 2.2.8.3 Circulating lipids ...................................................................... 54 2.2.8.4 Hypertension and blood glucose ........................................... 58 2.2.9 Safety ....................................................................................................... 59 2.3 SUMMARY ....................................................................................................... 61 3 AIMS OF THE STUDIES .................................................................................... 65 4 PARTICIPANTS, MATERIALS AND METHODS ....................................... 66 4.1 CLINICAL TRIAL 1: EFFECTS OF SEA BUCKTHORN BERRIES ON INFECTIONS AND INFLAMMATION (I), AND ON CIRCULATING LIPID MARKERS AND FLAVONOLS (II) ................................................. 66 4 Contents 4.1.1 Study design and participants (I-II) .................................................. 66 4.1.2 Study products (I-II) ............................................................................ 66 4.1.3 Number and duration of the common cold and other infections (I) . 67 4.1.4 C-reactive protein (I), lipid markers and flavonols (II) .................. 67 4.1.5 Statistical analyses (I-II) ...................................................................... 68 4.2 CLINICAL TRIAL 2: EFFECTS OF SEA BUCKTHORN OIL ON DRY EYE (III-IV) AND ON CIRCULATING AMINOTRANSFERASES AND BIOMARKERS OF INFLAMMATION (V) ................................................. 69 4.2.1 Study design and participants (III-V) ................................................ 69 4.2.2 Study products (III-V) ......................................................................... 69 4.2.3 Clinical tests and symptoms of dry eye (III) .................................... 69 4.2.4 Fatty acids of the tear film (IV) .......................................................... 70 4.2.5 Inflammatory markers and aminotransferases (V) ......................... 71 4.2.6 Statistical analyses (III-V) .................................................................... 71 5 RESULTS AND DISCUSSION ......................................................................... 73 5.1 EFFECTS OF SEA BUCKTHORN BERRIES ON INFECTIONS AND INFLAMMATION (I) .................................................................................... 73 5.1.1 Common cold and other infections (I) .............................................. 73 5.1.2 Concentrations of C-reactive protein (I) ........................................... 75 5.2 EFFECTS OF SEA BUCKTHORN BERRIES ON CIRCULATING LIPID MARKERS AND FLAVONOLS (II) ............................................................ 76 5.2.1 Total, HDL and LDL cholesterol and triacylglycerols (II) .............. 76 5.2.2 Quercetin, kaempferol, isorhamnetin and their correlation with CRP (II) .................................................................................................. 77 5.3 EFFECTS OF SEA BUCKTHORN OIL ON DRY EYE AND POTENTIAL MECHANISMS OF EFFECT (III-V) ............................................................. 78 5.3.1 Clinical tests and symptoms of dry eye (III) .................................... 78 5.3.2 Fatty acids of the tear film (IV) .......................................................... 79 5.4 EFFECTS OF SEA BUCKTHORN OIL ON INFLAMMATORY MARKERS AND AMINOTRANSFERASES (V) ........................................ 81 5.4.1 Concentrations of cytokines and C-reactive protein (V) ................ 81 5.4.2 Aminotransferases (V) ......................................................................... 81 5.5 SUMMARY ..................................................................................................... 82 6 CONCLUSIONS ..................................................................................................... 84 ACKNOWLEDGEMENTS ....................................................................................... 85 REFERENCES ............................................................................................................. 87 APPENDIX: ORIGINAL PUBLICATIONS ........................................................ 103 Abstract 5 ABSTRACT Sea buckthorn (Hippophaë) berries are ingredients of the Chinese traditional medicine. In addition to China, they are nowadays cultivated for food in several European countries, Russia, Canada, the USA, and Japan. Sea buckthorn berries are a rich source of flavonoids, mainly flavonol glycosides and proanthocyanidins. Depending on the genetic background, growth conditions, and ripeness of the berries, vitamin C concentrations up to over 1 g/100 ml juice, have been reported. Sea buckthorn berries contain inositols and methyl inositols, components of messenger molecules in humans. Sea buckthorn seed oil is rich in essential α- linolenic and linoleic acids, whereas the most abundant fatty acids in the berry oil are palmitoleic, palmitic and oleic acids. Other potentially beneficial lipophilic compounds of sea buckthorn seeds and berries include carotenoids, phytosterols, tocopherols and tocotrienols. The effects of sea buckthorn fractions on inflammation, platelet aggregation, oxidation injuries, the liver, skin and mucosa, among others, have been reported. The aim of the thesis work was to investigate the health effects of sea buckthorn berries and oil in humans. The physiological effects of sea buckthorn berries, berry components, and oil have mostly been studied in vitro and in animal models, leaving a demand for more clinical trials. In the first randomized, placebo-controlled trial of this thesis healthy adults consumed 28 g/day of sea buckthorn berries for three months. The main objective was to investigate the effects on the common cold. In addition, effects on other infections,
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