Advertisement

Phytochemistry Reviews

, Volume 18, Issue 4, pp 1025–1049 | Cite as

Citrus fruits and inflammaging: a systematic review

  • Alessandro Maugeri
  • Santa Cirmi
  • Paola Lucia Minciullo
  • Sebastiano Gangemi
  • Gioacchino Calapai
  • Vincenzo Mollace
  • Michele NavarraEmail author
Article
First Online:

Abstract

Inflammaging is a low-grade, chronic, asymptomatic, controlled and systemic pro-inflammatory status that appears during the aging process and is linked to many age-related diseases. Growing evidence indicates that Mediterranean diet is a reliable instrument to counteract inflammaging, due to its high content of flavonoids, whose main source are Citrus fruits. Our objective was to summarize and critically discuss the rich clinical evidence on the properties of Citrus fruits and their derivatives focusing on a series of age-related diseases and their potential use to maintain health in aging populations. A systematic review of articles using MEDLINE, Web of Sciences and Scopus was performed independently by two reviewers. Search terms included keywords related to Citrus fruits or their derivatives and inflammation. No language restriction was applied. The last search was performed on November 15th, 2018. The study selection and systematic review were carried out in accordance with the PRISMA statement. Prior to the beginning of the review, Authors defined a checklist for inclusion criteria. Three reviewers independently performed the extraction of articles. Eighty-five papers met our inclusion criteria and were eligible for inclusion in the final review.  Citrus fruits seem to possess capabilities in counteracting inflammation-based age-related diseases, thus representing a possible weapon to fight inflammaging. This review may be used as a scientific basis for further studies on the role of Citrus fruits consumption and inflammaging.

Keywords

Aging Anti-inflammatory Inflammation Orange Bergamot 

Abbreviations

AML

Amyotrophic lateral sclerosis

AUC

Area under curve

BJ

Bergamot juice

BJe

Bergamot juice extract

BMI

Body mass index

CI

Confidence interval

Cmax

Maximum plasma concentration

HPJ

High polyphenol concentration orange juice

HPV-16

Human papillomavirus 16

HR

Hazard ratio

IBD

Inflammatory bowel disease

LUTS

Lower urinary tract symptoms

MetS

Metabolic syndrome

NPJ

Normal polyphenol concentration orange juice

OR

Odds ratio

PAI-1

Plasminogen activator inhibitor-1 activity

PRISMA

Preferred reporting items for systematic reviews and meta-analyses

RR

Risk ratio

ROS

Reactive oxygen species

Tmax

Time to reach the maximum plasma concentration

This is a preview of subscription content, log in to check access.

Notes

References

  1. Agudo A, Slimani N, Ocke MC et al (2002) Consumption of vegetables, fruit and other plant foods in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts from 10 European countries. Public Health Nutr 5:1179–1196PubMedGoogle Scholar
  2. Berlin JM, Eisenberg DP, Berlin MB et al (2011) A randomized, placebo-controlled, double-blind study to evaluate the efficacy of a citrus bioflavanoid blend in the treatment of senile purpura. J Drugs Dermatol 10:718–722PubMedGoogle Scholar
  3. Berthon BS, Wood LG (2015) Nutrition and respiratory health—feature review. Nutrients 7:1618–1643PubMedPubMedCentralGoogle Scholar
  4. Bondonno NP, Lewis JR, Prince RL et al (2016) Fruit intake and abdominal aortic calcification in elderly women: a Prospective Cohort Study. Nutrients 8:159PubMedPubMedCentralGoogle Scholar
  5. Bosetti C, La Vecchia C, Talamini R et al (2000) Food groups and risk of squamous cell esophageal cancer in northern Italy. Int J Cancer 87:289–294PubMedGoogle Scholar
  6. Botterweck AAM, van den Brandt PA, Goldbohm RA (1998) A prospective cohort study on vegetable and fruit consumption and stomach cancer risk in the Netherlands. Am J Epidemiol 148:842–853PubMedGoogle Scholar
  7. Bravi F, Bosetti C, Dal Maso L et al (2006) Food groups and risk of benign prostatic hyperplasia. Urology 67:73–79PubMedGoogle Scholar
  8. Brookie KL, Best GI, Conner TS (2018) Intake of raw fruits and vegetables is associated with better mental health than intake of processed fruits and vegetables. Front Psychol 9:487PubMedPubMedCentralGoogle Scholar
  9. Butland BK, Fehily AM, Elwood PC (2000) Diet, lung function, and lung function decline in a cohort of 2512 middle aged men. Thorax 55:102–108PubMedPubMedCentralGoogle Scholar
  10. Caengprasath N, Ngamukote S, Makynen K et al (2013) The protective effects of pomelo extract (Citrus grandis L. osbeck) against fructose-mediated protein oxidation and glycation. EXCLI J 12:491–502PubMedPubMedCentralGoogle Scholar
  11. Cai Y, Xing GQ, Shen T et al (2017) Effects of 12-week supplementation of Citrus bergamia extracts-based formulation CitriCholess on cholesterol and body weight in older adults with dyslipidemia: a randomized, double-blind, placebo-controlled trial. Lipids Health Dis 16:251PubMedPubMedCentralGoogle Scholar
  12. Calabrese V, Guagliano E, Sapienza M et al (2007) Redox regulation of cellular stress response in aging and neurodegenerative disorders: role of vitagenes. Neurochem Res 32:757–773PubMedGoogle Scholar
  13. Cardinali DP, Hardeland R (2017) Inflammaging, metabolic syndrome and melatonin: a call for treatment studies. Neuroendocrinology 104:382–397PubMedGoogle Scholar
  14. Carraro JCC, Hermsdorff HHM, Mansego ML et al (2016) Higher fruit intake is related to TNF-alpha hypomethylation and better glucose tolerance in healthy subjects. J Nutrigenet Nutrigenom 9:95–105Google Scholar
  15. Cartee GD, Hepple RT, Bamman MM et al (2016) Exercise promotes healthy aging of skeletal muscle. Cell Metab 23:1034–1047PubMedPubMedCentralGoogle Scholar
  16. Cases J, Romain C, Dallas C et al (2015a) Regular consumption of Fiit-ns, a polyphenol extract from fruit and vegetables frequently consumed within the Mediterranean diet, improves metabolic ageing of obese volunteers: a randomized, double-blind, parallel trial. Int J Food Sci Nutr 66:120–125PubMedGoogle Scholar
  17. Cases J, Romain C, Dallas C et al (2015b) A 12-week randomized double-blind parallel pilot trial of Sinetrol XPur on body weight, abdominal fat, waist circumference, and muscle metabolism in overweight men. Int J Food Sci Nutr 66:471–477PubMedGoogle Scholar
  18. Celano M, Maggisano V, De Rose RF et al (2015) Flavonoid fraction of citrus reticulata juice reduces proliferation and migration of anaplastic thyroid carcinoma cells. Nutr Cancer 67:1183–1190PubMedGoogle Scholar
  19. Cerletti C, Gianfagna F, Tamburrelli C et al (2015) Orange juice intake during a fatty meal consumption reduces the postprandial low-grade inflammatory response in healthy subjects. Thromb Res 135:255–259PubMedGoogle Scholar
  20. Cevenini E, Monti D, Franceschi C (2013) Inflamm-ageing. Curr Opin Clin Nutr Metab Care 16:14–20PubMedGoogle Scholar
  21. Chan JM, Wang FR, Holly EA (2005) Vegetable and fruit intake and pancreatic cancer in a population-based case–control study in the San Francisco Bay area. Cancer Epidemiol Biomark Prev 14:2093–2097Google Scholar
  22. Chang SC, Cassidy A, Willett WC et al (2016) Dietary flavonoid intake and risk of incident depression in midlife and older women. Am J Clin Nutr 104:704–714PubMedPubMedCentralGoogle Scholar
  23. Chang CC, Lee WT, Lee YC et al (2017) Investigating the association between diet and risk of head and neck cancer in Taiwan. Oncotarget 8:98865–98875PubMedPubMedCentralGoogle Scholar
  24. Chen H, Ward MH, Graubard BI et al (2002) Dietary patterns and adenocarcinoma of the esophagus and distal stomach. Am J Clin Nutr 75:137–144PubMedGoogle Scholar
  25. Chen CO, Rasmussen H, Kamil A et al (2017) Orange pomace improves postprandial glycemic responses: an acute, randomized, placebo-controlled, double-blind, crossover trial in overweight men. Nutrients 9:E130PubMedGoogle Scholar
  26. Chia WK, Ali R, Toh HC (2012) Aspirin as adjuvant therapy for colorectal cancer-reinterpreting paradigms. Nat Rev Clin Oncol 9:561–570PubMedGoogle Scholar
  27. Cirmi S, Bisignano C, Mandalari G et al (2016a) Anti-infective potential of Citrus bergamia Risso et Poiteau (bergamot) derivatives: a systematic review. Phytother Res 30:1404–1411PubMedGoogle Scholar
  28. Cirmi S, Ferlazzo N, Lombardo GE et al (2016b) Chemopreventive agents and inhibitors of cancer hallmarks: may citrus offer new perspectives? Nutrients 8:E698PubMedGoogle Scholar
  29. Cirmi S, Ferlazzo N, Lombardo GE et al (2016c) Neurodegenerative diseases: might citrus flavonoids play a protective role? Molecules 21:E1312PubMedGoogle Scholar
  30. Cirmi S, Maugeri A, Ferlazzo N et al (2017) Anticancer potential of citrus juices and their extracts: a systematic review of both preclinical and clinical studies. Front Pharmacol 8:420PubMedPubMedCentralGoogle Scholar
  31. Cirmi S, Navarra M, Woodside JV et al (2018) Citrus fruits intake and oral cancer risk: a systematic review and meta-analysis. Pharmacol Res 133:187–194PubMedGoogle Scholar
  32. Citraro R, Navarra M, Leo A et al (2016) The Anticonvulsant activity of a flavonoid-rich extract from orange juice involves both NMDA and GABA-benzodiazepine receptor complexes. Molecules 21:E1261PubMedGoogle Scholar
  33. Constans J, Bennetau-Pelissero C, Martin JF et al (2015) Marked antioxidant effect of orange juice intake and its phytomicronutrients in a preliminary randomized cross-over trial on mild hypercholesterolemic men. Clin Nutr 34:1093–1100PubMedGoogle Scholar
  34. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867PubMedPubMedCentralGoogle Scholar
  35. Coyne KS, Wein AJ, Tubaro A et al (2009) The burden of lower urinary tract symptoms: evaluating the effect of LUTS on health-related quality of life, anxiety and depression: EpiLUTS. BJU Int 103(Suppl 3):4–11PubMedGoogle Scholar
  36. Curro M, Risitano R, Ferlazzo N et al (2016) Citrus bergamia juice extract attenuates beta-amyloid-induced pro-inflammatory activation of THP-1 cells through MAPK and AP-1 Pathways. Sci Rep 6:20809PubMedPubMedCentralGoogle Scholar
  37. Da Pozzo E, De Leo M, Faraone I et al (2018) Antioxidant and antisenescence effects of bergamot juice. Oxid Med Cell Longev 2018:9395804PubMedPubMedCentralGoogle Scholar
  38. Dauchet L, Ferrieres J, Arveiler D et al (2004) Frequency of fruit and vegetable consumption and coronary heart disease in France and Northern Ireland: the PRIME study. Br J Nutr 92:963–972PubMedGoogle Scholar
  39. de Oliveira AP, Bernardes ACE, Fernandes FLF et al (2017) Effects evaluation of thermogenic herbal medicines in anthropometric parameters of patients with obesity and overweight. Rbone Rev Bras De Obes Nutricao E Emagrecimento 11:667–676Google Scholar
  40. De Stefani E, Boffetta P, Deneo-Pellegrini H et al (2005a) The role of vegetable and fruit consumption in the aetiology of squamous cell carcinoma of the oesophagus: a case–control study in Uruguay. Int J Cancer 116:130–135PubMedGoogle Scholar
  41. De Stefani E, Boffetta P, Ronco AL et al (2005b) Dietary patterns and risk of cancer of the oral cavity and pharynx in Uruguay. Nutr Cancer Int J 51:132–139Google Scholar
  42. Delle Monache S, Sanita P, Trapasso E et al (2013) Mechanisms underlying the anti-tumoral effects of Citrus Bergamia juice. PLoS ONE 8:e61484PubMedPubMedCentralGoogle Scholar
  43. Devaraj S, Jialal I, Rockwood J et al (2011) Effect of orange juice and beverage with phytosterols on cytokines and PAI-1 activity. Clin Nutr 30:668–671PubMedGoogle Scholar
  44. Fairfield KM, Hankinson SE, Rosner BA et al (2001) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids—a prospective analysis. Cancer 92:2318–2326PubMedGoogle Scholar
  45. Feng BJ, Jalbout M, Ben Ayoub W et al (2007) Dietary risk factors for nasopharyngeal carcinoma in Maghrebian countries. Int J Cancer 121:1550–1555PubMedGoogle Scholar
  46. Ferlazzo N, Visalli G, Smeriglio A et al (2015) Flavonoid fraction of orange and bergamot juices protect human lung epithelial cells from hydrogen peroxide-induced oxidative stress. Evid Based Complement Altern Med eCAM 2015:957031Google Scholar
  47. Ferlazzo N, Cirmi S, Calapai G et al (2016a) Anti-inflammatory activity of Citrus bergamia derivatives: where do we stand? Molecules 21:1273PubMedCentralGoogle Scholar
  48. Ferlazzo N, Cirmi S, Russo M et al (2016b) NF-kappaB mediates the antiproliferative and proapoptotic effects of bergamot juice in HepG2 cells. Life Sci 146:81–91PubMedGoogle Scholar
  49. Ferlazzo N, Visalli G, Cirmi S et al (2016c) Natural iron chelators: protective role in A549 cells of flavonoids-rich extracts of Citrus juices in Fe(3+)-induced oxidative stress. Environ Toxicol Pharmacol 43:248–256PubMedGoogle Scholar
  50. Filocamo A, Bisignano C, Ferlazzo N et al (2015) In vitro effect of bergamot (Citrus bergamia) juice against cagA-positive and-negative clinical isolates of Helicobacter pylori. BMC Complement Altern Med 15:256PubMedPubMedCentralGoogle Scholar
  51. Fortes C, Forastiere F, Farchi S et al (2000) Diet and overall survival in a cohort of very elderly people. Epidemiology 11:440–445PubMedGoogle Scholar
  52. Foschi R, Pelucchi C, Dal Maso L et al (2010) Citrus fruit and cancer risk in a network of case–control studies. Cancer Causes Control CCC 21:237–242PubMedGoogle Scholar
  53. Franceschi C (1989) Cell proliferation, cell death and aging. Aging 1:3–15PubMedGoogle Scholar
  54. Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol Ser A Biol Sci Med Sci 69(Suppl 1):S4–S9Google Scholar
  55. Franceschi S, Favero A, LaVecchia C et al (1995) Influence of food groups and food diversity on breast cancer risk in Italy. Int J Cancer 63:785–789PubMedGoogle Scholar
  56. Franceschi C, Bonafe M, Valensin S et al (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254PubMedGoogle Scholar
  57. Franceschi C, Capri M, Monti D et al (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105PubMedGoogle Scholar
  58. Franceschi C, Garagnani P, Vitale G et al (2017) Inflammaging and ‘Garb-aging’. Trends Endocrinol Metab TEM 28:199–212PubMedGoogle Scholar
  59. Franceschi C, Garagnani P, Parini P et al (2018) Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol 14:576–590PubMedGoogle Scholar
  60. Frape DL, Jones AM (1995) Chronic and postprandial responses of plasma-insulin, glucose and lipids in volunteers given dietary fiber supplements. Br J Nutr 73:733–751PubMedGoogle Scholar
  61. Frasca D, Blomberg BB, Paganelli R (2017) Aging, obesity, and inflammatory age-related diseases. Front Immunol 8:1745PubMedPubMedCentralGoogle Scholar
  62. Freedman ND, Park Y, Subar AF et al (2007) Fruit and vegetable intake and esophageal cancer in a large prospective cohort study. Int J Cancer 121:2753–2760PubMedGoogle Scholar
  63. Fusco R, Cirmi S, Gugliandolo E et al (2017) A flavonoid-rich extract of orange juice reduced oxidative stress in an experimental model of inflammatory bowel disease. J Funct Foods 30:168–178Google Scholar
  64. Galvan-Portillo M, Torres-Sanchez L, Lopez-Carrillo L (2002) Dietary and reproductive factors associated with benign breast disease in Mexican women. Nutr Cancer Int J 43:133–140Google Scholar
  65. Gao X, Bermudez OI, Tucker KL (2004) Plasma C-reactive protein and homocysteine concentrations are related to frequent fruit and vegetable intake in hispanic and non-hispanic white elders. J Nutr 134:913–918PubMedGoogle Scholar
  66. Ghanim H, Sia CL, Upadhyay M et al (2010) Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and Toll-like receptor expression. Am J Clin Nutr 91:940–949PubMedPubMedCentralGoogle Scholar
  67. Gonzalez CA, Lujan-Barroso L, Bueno-de-Mesquita HB et al (2012) Fruit and vegetable intake and the risk of gastric adenocarcinoma: a reanalysis of the european prospective investigation into cancer and nutrition (EPIC-EURGAST) study after a longer follow-up. Int J Cancer 131:2910–2919PubMedGoogle Scholar
  68. Gorinstein S, Caspi A, Libman I et al (2004) Preventive effects of diets supplemented with sweetie fruits in hypercholesterolemic patients suffering from coronary artery disease. Prev Med 38:841–847PubMedGoogle Scholar
  69. Gorinstein S, Caspi A, Libman I et al (2006) Red grapefruit positively influences serum triglyceride level in patients suffering from coronary atherosclerosis: studies in vitro and in humans. J Agric Food Chem 54:1887–1892PubMedGoogle Scholar
  70. Gougeon R, Harrigan K, Tremblay JF et al (2005) Increase in the thermic effect of food in women by adrenergic amines extracted from citrus aurantium. Obes Res 13:1187–1194PubMedGoogle Scholar
  71. Griep LMO, Stamler J, Chan Q et al (2013) Association of raw fruit and fruit juice consumption with blood pressure: the INTERMAP Study. Am J Clin Nutr 97:1083–1091Google Scholar
  72. Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140:883–899PubMedPubMedCentralGoogle Scholar
  73. Gugliandolo E, Fusco R, D’Amico R et al (2019) Treatment with a flavonoid-rich fraction of bergamot juice improved lipopolysaccharide-induced periodontitis in rats. Front Pharmacol 9:1563PubMedPubMedCentralGoogle Scholar
  74. Gupta B, Bray F, Kumar N et al (2017) Associations between oral hygiene habits, diet, tobacco and alcohol and risk of oral cancer: a case–control study from India. Cancer Epidemiol 51:7–14PubMedGoogle Scholar
  75. Habauzit V, Verny MA, Milenkovic D et al (2015) Flavanones protect from arterial stiffness in postmenopausal women consuming grapefruit juice for 6 mo: a randomized, controlled, crossover trial. Am J Clin Nutr 102:66–74PubMedGoogle Scholar
  76. Hansen L, Dragsted LO, Olsen A et al (2010) Fruit and vegetable intake and risk of acute coronary syndrome. Br J Nutr 104:248–255PubMedGoogle Scholar
  77. Harmell AL, Jeste D, Depp C (2014) Strategies for successful aging: a research update. Curr Psychiatry Rep 16:476PubMedPubMedCentralGoogle Scholar
  78. Hashemi M, Khosravi E, Ghannadi A et al (2015) Effect of the peels of two Citrus fruits on endothelium function in adolescents with excess weight: a triple-masked randomized trial. J Res Med Sci 20:721–726PubMedPubMedCentralGoogle Scholar
  79. Hausman DB, Johnson MA, Davey A et al (2011) Body mass index is associated with dietary patterns and health conditions in georgia centenarians. J Aging Res 2011:138015PubMedPubMedCentralGoogle Scholar
  80. Igase M, Okada Y, Ochi M et al (2018) Auraptene in the peels of citrus Kawachiensis (Kawachibankan) contributes to the preservation of cognitive function: a randomized, placebo-controlled, double-blind study in healthy volunteers. J Prevent Alzheimer’s Dis 5:197–201Google Scholar
  81. Impellizzeri D, Bruschetta G, Di Paola R et al (2015) The anti-inflammatory and antioxidant effects of bergamot juice extract (BJe) in an experimental model of inflammatory bowel disease. Clin Nutr 34:1146–1154PubMedGoogle Scholar
  82. Impellizzeri D, Cordaro M, Campolo M et al (2016) Anti-inflammatory and antioxidant effects of flavonoid-rich fraction of bergamot juice (BJe) in a mouse model of intestinal ischemia/reperfusion injury. Front Pharmacol 7:203PubMedPubMedCentralGoogle Scholar
  83. Jansen RJ, Robinson DP, Stolzenberg-Solomon RZ et al (2011) Fruit and vegetable consumption is inversely associated with having pancreatic cancer. Cancer Causes Control 22:1613–1625PubMedPubMedCentralGoogle Scholar
  84. Jedrychowski W, Maugeri U, Popiela T et al (2010) Case–control study on beneficial effect of regular consumption of apples on colorectal cancer risk in a population with relatively low intake of fruits and vegetables. Eur J Cancer Prev 19:42–47PubMedGoogle Scholar
  85. Joshipura KJ, Ascherio A, Manson JE et al (1999) Fruit and vegetable intake in relation to risk of ischemic stroke. JAMA J Am Med Assoc 282:1233–1239Google Scholar
  86. Jung SK, Kim K, Tae K et al (2013) The effect of raw vegetable and fruit intake on thyroid cancer risk among women: a case–control study in South Korea. Br J Nutr 109:118–128PubMedGoogle Scholar
  87. Kadiri S, Arije A, Salako BL (1999) Traditional herbal preparations and acute renal failure in South West Nigeria. Trop Doct 29:244–246PubMedGoogle Scholar
  88. Kamalifard M, Khalili AF, Namadian M et al (2017) Comparison of the effect of lavender and bitter orange on depression in menopausal women: a triple-blind randomized controlled trial. Int J Womens Health Reprod Sci 5:224–230Google Scholar
  89. Kang S, Song S, Lee J et al (2018) Clinical investigations of the effect of citrus unshiu peel pellet on obesity and lipid profile. Evid Based Complement Altern Med 1:1–6Google Scholar
  90. Kean RJ, Lamport DJ, Dodd GF et al (2015) Chronic consumption of flavanone-rich orange juice is associated with cognitive benefits: an 8-wk, randomized, double-blind, placebo-controlled trial in healthy older adults. Am J Clin Nutr 101:506–514PubMedGoogle Scholar
  91. Keevil JG, Osman HE, Reed JD et al (2000) Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation. J Nutr 130:53–56PubMedGoogle Scholar
  92. Kim HJ, Chang WK, Kim MK et al (2002) Dietary factors and gastric cancer in Korea: a case–control study. Int J Cancer 97:531–535PubMedGoogle Scholar
  93. Kirkwood TBL (2017) Why and how are we living longer? Exp Physiol 102:1067–1074PubMedGoogle Scholar
  94. Kornadt AE, Kandler C (2017) Genetic and environmental sources of individual differences in views on aging. Psychol Aging 32:388–399PubMedGoogle Scholar
  95. Lai HTM, Threapleton DE, Day AJ et al (2015) Fruit intake and cardiovascular disease mortality in the UK Women’s Cohort Study. Eur J Epidemiol 30:1035–1048PubMedGoogle Scholar
  96. Lamport DJ, Pal D, Macready AL et al (2016) The effects of flavanone-rich citrus juice on cognitive function and cerebral blood flow: an acute, randomised, placebo-controlled cross-over trial in healthy, young adults. Br J Nutr 116:2160–2168PubMedGoogle Scholar
  97. Larsson SC, Andersson SO, Johansson JE et al (2008) Fruit and vegetable consumption and risk of bladder cancer: a prospective cohort study. Cancer Epidemiol Biomark Prev 17:2519–2522Google Scholar
  98. Ledikwe JH, Smiciklas-Wright H, Mitchell DC et al (2004) Dietary patterns of rural older adults are associated with weight and nutritional status. J Am Geriatr Soc 52:589–595PubMedGoogle Scholar
  99. Levi F, Pasche C, La Vecchia C et al (1998) Food groups and risk of oral and pharyngeal cancer. Int J Cancer 77:705–709PubMedGoogle Scholar
  100. Levi F, Pasche C, La Vecchia C et al (1999) Food groups and colorectal cancer risk. Br J Cancer 79:1283–1287PubMedPubMedCentralGoogle Scholar
  101. Levi F, Pasche C, Lucchini F et al (2000) Food groups and oesophageal cancer risk in Vaud, Switzerland. Eur J Cancer Prev 9:257–263PubMedGoogle Scholar
  102. Li WQ, Kuriyama S, Li QA et al (2010) Citrus consumption and cancer incidence: the Ohsaki cohort study. Int J Cancer 127:1913–1922PubMedGoogle Scholar
  103. Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 6:e1000100PubMedPubMedCentralGoogle Scholar
  104. Lin J, Kamat A, Gu J et al (2009) Dietary intake of vegetables and fruits and the modification effects of GSTM1 and NAT2 genotypes on bladder cancer risk. Cancer Epidemiol Biomark Prev 18:2090–2097Google Scholar
  105. Lissowska J, Pilarska A, Pilarski P et al (2003) Smoking, alcohol, diet, dentition and sexual practices in the epidemiology of oral cancer in Poland. Eur J Cancer Prev 12:25–33PubMedGoogle Scholar
  106. Liu YT, Dai JJ, Xu CH et al (2012) Greater intake of fruit and vegetables is associated with lower risk of nasopharyngeal carcinoma in Chinese adults: a case–control study. Cancer Causes Control 23:589–599PubMedGoogle Scholar
  107. Lowe G, Woodward M, Rumley A et al (2003) Total tooth loss and prevalent cardiovascular disease in men and women: possible roles of citrus fruit consumption, vitamin C, and inflammatory and thrombotic variables. J Clin Epidemiol 56:694–700PubMedGoogle Scholar
  108. Lowery EM, Brubaker AL, Kuhlmann E et al (2013) The aging lung. Clin Interv Aging 8:1489–1496PubMedPubMedCentralGoogle Scholar
  109. Mannucci C, Navarra M, Calapai F et al (2017) Clinical pharmacology of Citrus bergamia: a systematic review. Phytother Res 31:27–39PubMedGoogle Scholar
  110. Mannucci C, Calapai F, Cardia L et al (2018) Clinical pharmacology of Citrus aurantium and Citrus sinensis for the treatment of anxiety. Evid Based Complement Altern Med eCAM 2018:3624094Google Scholar
  111. Marino A, Paterniti I, Cordaro M et al (2015) Role of natural antioxidants and potential use of bergamot in treating rheumatoid arthritis. PharmaNutrition 3:53–59Google Scholar
  112. Martucci M, Ostan R, Biondi F et al (2017) Mediterranean diet and inflammaging within the hormesis paradigm. Nutr Rev 75:442–455PubMedPubMedCentralGoogle Scholar
  113. Maserejian NN, Wager CG, Giovannucci EL et al (2013) Intake of caffeinated, carbonated, or citrus beverage types and development of lower urinary tract symptoms in men and women. Am J Epidemiol 177:1399–1410PubMedPubMedCentralGoogle Scholar
  114. Maugeri A, Ferlazzo N, De Luca L et al (2019) The link between the AMPK/SIRT1 axis and a flavonoid-rich extract of Citrus bergamia juice: a cell-free, in silico, and in vitro study. Phytother Res 120:9437Google Scholar
  115. Meyer MS, Applebaum KM, Furniss CS et al (2008) Human papillomavirus-16 modifies the association between fruit consumption and head and neck squamouss cell carcinoma. Cancer Epidemiol Biomark Prev 17:3419–3426Google Scholar
  116. Mizrahi A, Knekt P, Montonen J et al (2009) Plant foods and the risk of cerebrovascular diseases: a potential protection of fruit consumption. Br J Nutr 102:1075–1083PubMedGoogle Scholar
  117. Molendijk M, Molero P, Ortuno Sanchez-Pedreno F et al (2018) Diet quality and depression risk: a systematic review and dose–response meta-analysis of prospective studies. J Affect Disord 226:346–354PubMedGoogle Scholar
  118. Mollace V, Sacco I, Janda E et al (2011) Hypolipemic and hypoglycaemic activity of bergamot polyphenols: from animal models to human studies. Fitoterapia 82:309–316PubMedGoogle Scholar
  119. Murphy MM, Barraj LM, Rampersaud GC (2014) Consumption of grapefruit is associated with higher nutrient intakes and diet quality among adults, and more favorable anthropometrics in women, NHANES 2003–2008. Food Nutr Res 58:1–11Google Scholar
  120. Musumeci L, Maugeri A, Cirmi S et al (2019) Citrus fruits and their flavonoids in inflammatory bowel disease: an overview. Nat Prod Res 16:1–15Google Scholar
  121. Navarra M, Ursino MR, Ferlazzo N et al (2014) Effect of Citrus bergamia juice on human neuroblastoma cells in vitro and in metastatic xenograft models. Fitoterapia 95:83–92PubMedGoogle Scholar
  122. Navarra M, Ferlazzo N, Cirmi S et al (2015a) Effects of bergamot essential oil and its extractive fractions on SH-SY5Y human neuroblastoma cell growth. J Pharm Pharmacol 67:1042–1053PubMedGoogle Scholar
  123. Navarra M, Mannucci C, Delbo M et al (2015b) Citrus bergamia essential oil: from basic research to clinical application. Front Pharmacol 6:36PubMedPubMedCentralGoogle Scholar
  124. Navarra M, Femia AP, Romagnoli A et al (2019) A flavonoid-rich extract from bergamot juice prevents carcinogenesis in a genetic model of colorectal cancer, the Pirc rat (F344/NTac-Apc(am1137)). Eur J Nutr 1:11Google Scholar
  125. Nyberg F, Agrenius V, Svartengren K et al (1998) Dietary factors and risk of lung cancer in never-smokers. Int J Cancer 78:430–436PubMedGoogle Scholar
  126. O’Neil CE, Nicklas TA, Rampersaud GC et al (2012) 100% Orange juice consumption is associated with better diet quality, improved nutrient adequacy, decreased risk for obesity, and improved biomarkers of health in adults: National Health and Nutrition Examination Survey, 2003–2006. Nutr J 11:107PubMedPubMedCentralGoogle Scholar
  127. Olsen GW, Mandel JS, Gibson RW et al (1991) Nutrients and pancreatic-cancer—a population-based case–control study. Cancer Causes Control 2:291–297PubMedGoogle Scholar
  128. Ostan R, Lanzarini C, Pini E et al (2015) Inflammaging and cancer: a challenge for the Mediterranean diet. Nutrients 7:2589–2621PubMedPubMedCentralGoogle Scholar
  129. Owczarek D, Rodacki T, Domagala-Rodacka R et al (2016) Diet and nutritional factors in inflammatory bowel diseases. World J Gastroenterol 22:895–905PubMedPubMedCentralGoogle Scholar
  130. Pappas A, Liakou A, Zouboulis CC (2016) Nutrition and skin. Rev Endocr Metab Disord 17:443–448PubMedGoogle Scholar
  131. Pittaluga M, Sgadari A, Tavazzi B et al (2013) Exercise-induced oxidative stress in elderly subjects: the effect of red orange supplementation on the biochemical and cellular response to a single bout of intense physical activity. Free Radic Res 47:202–211PubMedGoogle Scholar
  132. Polesel J, Talamini R, Negri E et al (2010) Dietary habits and risk of pancreatic cancer: an Italian case–control study. Cancer Causes Control 21:493–500PubMedGoogle Scholar
  133. Puglia C, Offerta A, Saija A et al (2014) Protective effect of red orange extract supplementation against UV-induced skin damages: photoaging and solar lentigines. J Cosmet Dermatol 13:151–157PubMedGoogle Scholar
  134. Pupillo E, Bianchi E, Chio A et al (2018) Amyotrophic lateral sclerosis and food intake. Amyotroph Later Scler Frontotemporal Degener 19:267–274Google Scholar
  135. Qureshi MM, Singer MR, Moore LL (2009) A cross-sectional study of food group intake and C-reactive protein among children. Nutr Metab (Lond) 6:40Google Scholar
  136. Ramon JM, Serra L, Cerdo C et al (1993) Dietary factors and gastric-cancer risk—a case–control study in Spain. Cancer 71:1731–1735PubMedGoogle Scholar
  137. Rangel-Huerta OD, Aguilera CM, Martin MV et al (2015) Normal or high polyphenol concentration in orange juice affects antioxidant activity, blood pressure, and body weight in obese or overweight adults. J Nutr 145:1808–1816PubMedGoogle Scholar
  138. Rangel-Huerta OD, Aguilera CM, Perez-de-la-Cruz A et al (2017) A serum metabolomics-driven approach predicts orange juice consumption and its impact on oxidative stress and inflammation in subjects from the BIONAOS study. Mol Nutr Food Res 61:11Google Scholar
  139. Rendeiro C, Dong HL, Saunders C et al (2016) Flavanone-rich citrus beverages counteract the transient decline in postprandial endothelial function in humans: a randomised, controlled, double-masked, cross-over intervention study. Br J Nutr 116:1999–2010PubMedGoogle Scholar
  140. Risitano R, Curro M, Cirmi S et al (2014) Flavonoid fraction of Bergamot juice reduces LPS-induced inflammatory response through SIRT1-mediated NF-kappaB inhibition in THP-1 monocytes. PLoS ONE 9:e107431PubMedPubMedCentralGoogle Scholar
  141. Rosenblatt KA, Thomas DB, Jimenez LM et al (1999) The relationship between diet and breast cancer in men (United States). Cancer Causes Control 10:107–113PubMedGoogle Scholar
  142. Russel MG, Engels LG, Muris JW et al (1998) ‘Modern life’ in the epidemiology of inflammatory bowel disease: a case–control study with special emphasis on nutritional factors. Eur J Gastroenterol Hepatol 10:243–249PubMedGoogle Scholar
  143. Sacerdote C, Matullo G, Polidoro S et al (2007) Intake of fruits and vegetables and polymorphisms in DNA repair genes in bladder cancer. Mutagenesis 22:281–285PubMedGoogle Scholar
  144. Sanchez-Moreno C, Cano MP, de Ancos B et al (2003a) Effect of orange juice intake on vitamin C concentrations and biomarkers of antioxidant status in humans. Am J Clin Nutr 78:454–460PubMedGoogle Scholar
  145. Sanchez-Moreno C, Cano MP, de Ancos B et al (2003b) High-pressurized orange juice consumption affects plasma vitamin C, antioxidative status and inflammatory markers in healthy humans. J Nutr 133:2204–2209PubMedGoogle Scholar
  146. Sanchez-Moreno C, Cano MP, de Ancos B et al (2004) Pulsed electric fields-processed orange juice consumption increases plasma vitamin C and decreases F2-isoprostanes in healthy humans. J Nutr Biochem 15:601–607PubMedGoogle Scholar
  147. Schär MY, Curtis PJ, Hazim S et al (2015) Orange juice-derived flavanone and phenolic metabolites do not acutely affect cardiovascular risk biomarkers: a randomized, placebo-controlled, crossover trial in men at moderate risk of cardiovascular disease. Am J Clin Nutr 101:931–938PubMedPubMedCentralGoogle Scholar
  148. Schuurman AG, Goldbohm RA, Dorant E et al (1998) Vegetable and fruit consumption and prostate cancer risk: a cohort study in the Netherlands. Cancer Epidemiol Biomark Prev 7:673–680Google Scholar
  149. Shayganni E, Bahmani M, Asgary S et al (2016) Inflammaging and cardiovascular disease: management by medicinal plants. Phytomed Int J Phytother Phytopharmacol 23:1119–1126Google Scholar
  150. Silveira JQ, Dourado GKZS, Cesar TB (2015) Red-fleshed sweet orange juice improves the risk factors for metabolic syndrome. Int J Food Sci Nutr 66:830–836PubMedGoogle Scholar
  151. Stare J, Maucort-Boulch D (2016) Odds ratio, hazard ratio and relative risk. Metodoloski Zvezki 13:59Google Scholar
  152. Steevens J, Schouten LJ, Goldbohm RA et al (2011) Vegetables and fruits consumption and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study. Int J Cancer 129:2681–2693PubMedGoogle Scholar
  153. Testai L, Calderone V (2017) Nutraceutical value of citrus flavanones and their implications in cardiovascular disease. Nutrients 9:502PubMedCentralGoogle Scholar
  154. Toth PP, Patti AM, Nikolic D et al (2016) Bergamot reduces plasma lipids, atherogenic small dense LDL, and subclinical atherosclerosis in subjects with moderate hypercholesterolemia: a 6 months prospective study. Front Pharmacol 6:299PubMedPubMedCentralGoogle Scholar
  155. Tripepi G, Jager KJ, Dekker FW et al (2007) Measures of effect: relative risks, odds ratios, risk difference, and ‘number needed to treat’. Kidney Int 72:789–791PubMedGoogle Scholar
  156. Visalli G, Ferlazzo N, Cirmi S et al (2014) Bergamot juice extract inhibits proliferation by inducing apoptosis in human colon cancer cells. Anticancer Agents Med Chem 14:1402–1413PubMedGoogle Scholar
  157. Wang T, Liu Q, Tjhioe W et al (2017) Therapeutic potential and outlook of alternative medicine for osteoporosis. Curr Drug Targets 18:1051–1068PubMedGoogle Scholar
  158. Ward MH, Lopez-Carrillo L (1999) Dietary factors and the risk of gastric cancer in Mexico City. Am J Epidemiol 149:925–932PubMedGoogle Scholar
  159. Wyss-Coray T (2016) Ageing, neurodegeneration and brain rejuvenation. Nature 539:180–186PubMedPubMedCentralGoogle Scholar
  160. Xia S, Zhang X, Zheng S et al (2016) An update on inflammaging: mechanisms, prevention, and treatment. J Immunol Res 2016:8426874PubMedPubMedCentralGoogle Scholar
  161. Yamaguchi M, Igarashi A, Uchiyama S et al (2006) Effect of beta-crytoxanthin on circulating bone metabolic markers: intake of juice (Citrus unshiu) supplemented with beta-cryptoxanthin has an effect in menopausal women. J Health Sci 52:758–768Google Scholar
  162. Ye WM, Yi YN, Luo RX et al (1998) Diet and gastric cancer: a case–control study in Fujian Province, China. World J Gastroenterol 4:516–518PubMedPubMedCentralGoogle Scholar
  163. Yoshizaki N, Fujii T, Hashizume R et al (2016) A polymethoxyflavone mixture, extracted from orange peels, suppresses the UVB-induced expression of MMP-1. Exp Dermatol 25(Suppl 3):52–56PubMedGoogle Scholar
  164. Yuan C, Lee HJ, Shin HJ et al (2015) Fruit and vegetable consumption and hypertriglyceridemia: Korean National Health and Nutrition Examination Surveys (KNHANES) 2007–2009. Eur J Clin Nutr 69:1193–1199PubMedGoogle Scholar
  165. Zeegers MPA, Goldbohm RA, van den Brandt PA (2001) Consumption of vegetables and fruits and urothelial cancer incidence: a prospective study. Cancer Epidemiol Biomark Prev 10:1121–1128Google Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Chemical, Biological, Pharmaceutical and Environmental SciencesUniversity of MessinaMessinaItaly
  2. 2.Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly
  3. 3.Department of Biomedical and Dental Sciences and Morphofunctional ImagingUniversity of MessinaMessinaItaly
  4. 4.Department of Health SciencesUniversity “Magna Graecia” of CatanzaroCatanzaroItaly

Personalised recommendations

Cite article

Buy options