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Higher serum carotenoids associated with improvement of non-alcoholic fatty liver disease in adults: a prospective study

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Abstract

Purpose

Previous studies have suggested that serum carotenoids might be inversely associated with non-alcoholic fatty liver disease (NAFLD), but little data came from longitudinal studies. We prospectively examined the associations between serum-carotenoid levels and NAFLD severity and the intermediary effects of retinol-binding protein 4 (RBP4), HOMA insulin-resistance index (HOMA-IR), body mass index (BMI), and serum triglycerides in middle-aged and elderly Chinese adults.

Methods

This prospective study included 3336 Chinese adults (40–75 years). We assessed serum concentrations of carotenoids at baseline and determined serum RBP4, triglycerides, and HOMA-IR levels at year 3. Abdominal ultrasonography was conducted to assess the presence and degree of NAFLD at years 3 and 6.

Results

The 2687 subjects who completed both NAFLD tests were classified into stable, improved and progressed groups according to changes in the degree of NAFLD between two visits. Analyses of covariance showed that ln-transformed serum concentrations of α-carotene, β-cryptoxanthin, β-carotene, lycopene, lutein/zeaxanthin, and total carotenoids were positively associated with NAFLD improvement (all p-trend < 0.05). After multivariable adjustment, mean differences in serum carotenoids were higher by 29.6% (β-carotene), 18.2% (α-carotene), 15.6% (β-cryptoxanthin), 11.5% (lycopene), 8.9% (lutein/zeaxanthin), and 16.6% (total carotenoids) in the improved vs. progressed subjects. Path analyses indicated the carotenoid–NAFLD association was mediated by lowering serum RBP4, triglycerides, HOMA-IR, and BMI, which were positively associated with the prevalence and progression of NAFLD.

Conclusions

In middle-aged and elderly adults, higher serum-carotenoid concentrations were favorably associated with NAFLD improvement, mediated by reducing serum RBP4, triglycerides, HOMA-IR, and BMI.

Trial registrations

This study has been registered at http://www.clinicaltrials.gov as NCT03179657.

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Abbreviations

NAFLD:

Non-alcoholic fatty liver disease

ROS:

Reactive oxygen species

TG:

Triglycerides

RBP4:

Retinol-binding protein 4

HOMA-IR:

HOMA insulin-resistance index

BMI:

Body mass index

ALT:

Alanine aminotransferase

GFI:

Goodness of fit index

IL:

Interleukin

References

  1. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ (2012) The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 142:1592–1609. https://doi.org/10.1053/j.gastro.2012.04.001

    Article  Google Scholar 

  2. Starley BQ, Calcagno CJ, Harrison SA (2010) Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology 51:1820–1832. https://doi.org/10.1002/hep.23594

    Article  PubMed  Google Scholar 

  3. Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW, Feng Y (2015) The role of oxidative stress and antioxidants in liver diseases. Int J Mol Sci 16:26087–26124. https://doi.org/10.3390/ijms161125942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Salomone F, Godos J, Zelber-Sagi S (2016) Natural antioxidants for non-alcoholic fatty liver disease: molecular targets and clinical perspectives. Liver Int 36:5–20. https://doi.org/10.1111/liv.12975

    Article  CAS  PubMed  Google Scholar 

  5. Johnson EJ (2002) The role of carotenoids in human health. Nutr Clin Care 5:56–65. https://doi.org/10.1046/j.1523-5408.2002.00004.x

    Article  PubMed  Google Scholar 

  6. Marcotorchino J, Romier B, Gouranton E, Riollet C, Gleize B, Malezet-Desmoulins C, Landrier JF (2012) Lycopene attenuates LPS-induced TNF-alpha secretion in macrophages and inflammatory markers in adipocytes exposed to macrophage-conditioned media. Mol Nutr Food Res 56:725–732. https://doi.org/10.1002/mnfr.201100623

    Article  CAS  PubMed  Google Scholar 

  7. Yilmaz B, Sahin K, Bilen H, Bahcecioglu IH, Bilir B, Ashraf S, Halazun KJ, Kucuk O (2015) Carotenoids and non-alcoholic fatty liver disease. Hepatobiliary Surg Nutr 4:161–171. https://doi.org/10.3978/j.issn.2304-3881.2015.01.11

    Article  PubMed  PubMed Central  Google Scholar 

  8. Palozza P, Simone R, Catalano A, Boninsegna A, Bohm V, Frohlich K, Mele MC, Monego G, Ranelletti FO (2010) Lycopene prevents 7-ketocholesterol-induced oxidative stress, cell cycle arrest and apoptosis in human macrophages. J Nutr Biochem 21:34–46. https://doi.org/10.1016/j.jnutbio.2008.10.002

    Article  CAS  PubMed  Google Scholar 

  9. Jiang W, Guo MH, Hai X (2016) Hepatoprotective and antioxidant effects of lycopene on non-alcoholic fatty liver disease in rat. World J Gastroenterol 22:10180–10188. https://doi.org/10.3748/wjg.v22.i46.10180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bonet ML, Canas JA, Ribot J, Palou A (2015) Carotenoids and their conversion products in the control of adipocyte function, adiposity and obesity. Arch Biochem Biophys 572:112–125. https://doi.org/10.1016/j.abb.2015.02.022

    Article  CAS  PubMed  Google Scholar 

  11. Blondin SA, Yeung EH, Mumford SL, Zhang C, Browne RW, Wactawski-Wende J, Schisterman EF (2013) Serum retinol and carotenoids in association with biomarkers of insulin resistance among premenopausal women. ISRN Nutr 2013:619516. https://doi.org/10.5402/2013/619516

    Article  CAS  PubMed  Google Scholar 

  12. Riso P, Visioli F, Grande S, Guarnieri S, Gardana C, Simonetti P, Porrini M (2006) Effect of a tomato-based drink on markers of inflammation, immunomodulation, and oxidative stress. J Agric Food Chem 54:2563–2566. https://doi.org/10.1021/jf053033c

    Article  CAS  PubMed  Google Scholar 

  13. Murillo AG, DiMarco DM, Fernandez ML (2016) The potential of non-provitamin a carotenoids for the prevention and treatment of non-alcoholic fatty liver disease. Biology. https://doi.org/10.3390/biology5040042

    Article  PubMed  PubMed Central  Google Scholar 

  14. Cao Y, Wang C, Liu J, Liu ZM, Ling WH, Chen YM (2015) Greater serum carotenoid levels associated with lower prevalence of nonalcoholic fatty liver disease in Chinese adults. Sci Rep 5:12951. https://doi.org/10.1038/srep12951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ruhl CE, Everhart JE (2003) Relation of elevated serum alanine aminotransferase activity with iron and antioxidant levels in the United States. Gastroenterology 124:1821–1829. https://doi.org/10.1016/s0016-5085(03)00395-0

    Article  CAS  PubMed  Google Scholar 

  16. Erhardt A, Stahl W, Sies H, Lirussi F, Donner A, Haussinger D (2011) Plasma levels of vitamin E and carotenoids are decreased in patients with nonalcoholic steatohepatitis (NASH). Eur J Med Res 16:76–78. https://doi.org/10.1186/2047-783X-16-2-76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Villaca Chaves G, Pereira SE, Saboya CJ, Ramalho A (2008) Non-alcoholic fatty liver disease and its relationship with the nutritional status of vitamin A in individuals with class III obesity. Obes Surg 18:378–385. https://doi.org/10.1007/s11695-007-9361-2

    Article  PubMed  Google Scholar 

  18. Miranda-Vilela AL, Akimoto AK, Alves PC, Pereira LC, Goncalves CA, Klautau-Guimaraes MN, Grisolia CK (2009) Dietary carotenoid-rich pequi oil reduces plasma lipid peroxidation and DNA damage in runners and evidence for an association with MnSOD genetic variant -Val9Ala. Genet Mol Res 8:1481–1495. https://doi.org/10.4238/vol8-4gmr684

    Article  CAS  PubMed  Google Scholar 

  19. Sugiura M, Nakamura M, Ogawa K, Ikoma Y, Yano M (2016) High serum carotenoids are associated with lower risk for developing elevated serum alanine aminotransferase among Japanese subjects: the Mikkabi cohort study. Br J Nutr 115:1462–1469. https://doi.org/10.1017/s0007114516000374

    Article  CAS  PubMed  Google Scholar 

  20. Tiniakos DG, Vos MB, Brunt EM (2010) Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu Rev Pathol 5:145–171. https://doi.org/10.1146/annurev-pathol-121808-102132

    Article  CAS  Google Scholar 

  21. Schwenzer NF, Springer F, Schraml C, Stefan N, Machann J, Schick F (2009) Non-invasive assessment and quantification of liver steatosis by ultrasound, computed tomography and magnetic resonance. J Hepatol 51:433–445. https://doi.org/10.1016/j.jhep.2009.05.023

    Article  PubMed  Google Scholar 

  22. Liu J, Shi WQ, Cao Y, He LP, Guan K, Ling WH, Chen YM (2014) Higher serum carotenoid concentrations associated with a lower prevalence of the metabolic syndrome in middle-aged and elderly Chinese adults. Br J Nutr 112:2041–2048. https://doi.org/10.1017/s000711451400316x

    Article  CAS  PubMed  Google Scholar 

  23. Liu YT, Dai JJ, Xu CH, Lu YK, Fan YY, Zhang XL, Zhang CX, Chen YM (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 23:589–599. https://doi.org/10.1007/s10552-012-9923-z

    Article  PubMed  Google Scholar 

  24. Ainsworth BE, Haskell WL, Herrmann SD, Meckes N, Bassett DR Jr, Tudor-Locke C, Greer JL, Vezina J, Whitt-Glover MC, Leon AS (2011) 2011 compendium of physical activities: a second update of codes and MET values. Med Sci Sports Exerc 43:1575–1581. https://doi.org/10.1249/MSS.0b013e31821ece1225

    Article  PubMed  Google Scholar 

  25. Zhang CX, Ho SC (2009) Validity and reproducibility of a food frequency Questionnaire among Chinese women in Guangdong province. Asia Pac J Clin Nutr 18:240–250

    CAS  PubMed  Google Scholar 

  26. Burri BJ, Dopler-Nelson M, Neidllinger TR (2003) Measurements of the major isoforms of vitamins A and E and carotenoids in the blood of people with spinal-cord injuries. J Chromatogr A 987:359–366. https://doi.org/10.1016/S0021-9673(02)01908-8

    Article  CAS  PubMed  Google Scholar 

  27. Yao-Borengasser A, Varma V, Bodles AM, Rasouli N, Phanavanh B, Lee MJ, Starks T, Kern LM, Spencer HJ 3rd, Rashidi AA, McGehee RE Jr, Fried SK, Kern PA (2007) Retinol binding protein 4 expression in humans: relationship to insulin resistance, inflammation, and response to pioglitazone. J Clin Endocrinol Metab 92:2590–2597. https://doi.org/10.1210/jc.2006-0816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  CAS  Google Scholar 

  29. Zeng MD, Fan JG, Lu LG, Li YM, Chen CW, Wang BY, Mao YM (2008) Guidelines for the diagnosis and treatment of nonalcoholic fatty liver diseases. J Dig Dis 9:108–112. https://doi.org/10.1111/j.1751-2980.2008.00331.x

    Article  PubMed  Google Scholar 

  30. Latowski D, Kuczynska P, Strzalka K (2011) Xanthophyll cycle—a mechanism protecting plants against oxidative stress. Redox Rep 16:78–90. https://doi.org/10.1179/174329211x13020951739938

    Article  CAS  PubMed  Google Scholar 

  31. Krinsky NI, Johnson EJ (2005) Carotenoid actions and their relation to health and disease. Aspects Med 26:459–516. https://doi.org/10.1016/j.mam.2005.10.001

    Article  CAS  Google Scholar 

  32. Angulo P, Lindor KD (2002) Non-alcoholic fatty liver disease. J Gastroenterol Hepatol 17(Suppl):S186–S190

    Google Scholar 

  33. McCullough AJ (2002) Update on nonalcoholic fatty liver disease. J Clin Gastroenterol 34:255–262. https://doi.org/10.1097/00004836-200203000-00013

    Article  PubMed  Google Scholar 

  34. Kaulmann A, Bohn T (2014) Carotenoids, inflammation, and oxidative stress—implications of cellular signaling pathways and relation to chronic disease prevention. Nutr Res 34:907–929. https://doi.org/10.1016/j.nutres.2014.07.010

    Article  CAS  PubMed  Google Scholar 

  35. Akdemir B, Bahcecioglu I, Tuzcu M, Orhan C, Ispiroglu M, Ozercan I, Ilhan N, Celik N, Sahin K (2016) Effect of lycopene and genistein on hepatic inflammation and fibrosis in thioacetamide induced liver injury in rats. Br J Med Med Res 18:1–11. https://doi.org/10.9734/bjmmr/2016/27654

    Article  Google Scholar 

  36. Wardi J, Reifen R, Aeed H, Zadel L, Avni Y, Bruck R (2001) Beta-carotene attenuates experimentally induced liver cirrhosis in rats. Isr Med Assoc J 3:151–154

    CAS  PubMed  Google Scholar 

  37. Ahn J, Lee H, Jung CH, Ha T (2012) Lycopene inhibits hepatic steatosis via microRNA-21-induced downregulation of fatty acid-binding protein 7 in mice fed a high-fat diet. Mol Nutr Food Res 56:1665–1674. https://doi.org/10.1002/mnfr.201200182

    Article  CAS  PubMed  Google Scholar 

  38. Ni Y, Zhuge F, Nagashimada M, Ota T (2016) Novel action of carotenoids on non-alcoholic fatty liver disease: macrophage polarization and liver homeostasis. Nutrients 8:391. https://doi.org/10.3390/nu8070391

    Article  CAS  PubMed Central  Google Scholar 

  39. Fenni S, Hammou H, Astier J, Bonnet L, Karkeni E, Couturier C, Tourniaire F, Landrier J-F (2017) Lycopene and tomato powder supplementation similarly inhibit high-fat diet induced obesity, inflammatory response, and associated metabolic disorders. Mol Nutr Food Res. https://doi.org/10.1002/mnfr.201601083

    Article  PubMed  Google Scholar 

  40. Sugiura M, Nakamura M, Ogawa K, Ikoma Y, Yano M (2015) High serum carotenoids associated with lower risk for the metabolic syndrome and its components among Japanese subjects: Mikkabi cohort study. Br J Nutr 114:1674–1682. https://doi.org/10.1017/s0007114515003268

    Article  CAS  PubMed  Google Scholar 

  41. Suzuki K, Ito Y, Hashimoto S, Kawado M, Inoue T, Ando M, Watanabe Y, Inaba Y, Tajima K, Nakachi K, Tamakoshi A (2009) Association of serum retinol and carotenoids with insulin-like growth factors and insulin-like growth factor binding protein-3 among control subjects of a nested case-control study in the Japan Collaborative Cohort Study. Asian Pac J Cancer Prev 10 Suppl:29–35

    PubMed  Google Scholar 

  42. Sugiura M, Nakamura M, Ikoma Y, Yano M, Ogawa K, Matsumoto H, Kato M, Ohshima M, Nagao A (2006) The homeostasis model assessment-insulin resistance index is inversely associated with serum carotenoids in non-diabetic subjects. J Epidemiol 16:71–78. https://doi.org/10.2188/jea.16.71

    Article  PubMed  Google Scholar 

  43. Gunanti IR, Marks GC, Al-Mamun A, Long KZ (2014) Low serum concentrations of carotenoids and vitamin E are associated with high adiposity in Mexican–American children. J Nutr 144:489–495. https://doi.org/10.3945/jn.113.183137

    Article  CAS  PubMed  Google Scholar 

  44. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH (2004) Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40:1387–1395. https://doi.org/10.1002/hep.20466

    Article  Google Scholar 

  45. Johnson EJ, Russell RM (1992) Distribution of orally administered beta-carotene among lipoproteins in healthy men. Am J Clin Nutr 56:128–135

    Article  CAS  PubMed  Google Scholar 

  46. Brown ED, Micozzi MS, Craft NE, Bieri JG, Beecher G, Edwards BK, Rose A, Taylor PR, Smith JC Jr (1989) Plasma carotenoids in normal men after a single ingestion of vegetables or purified beta-carotene. Am J Clin Nutr 49:1258–1265

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful to other team staff for their contribution in the data collection and for facilitating both the recruitment of participants and the interviews.

Funding

This study was jointly supported by the National Natural Science Foundation of China (No. 81472965 and 81372976), the 5010 Program for Clinical Researches (No. 2007032) by the Sun Yat-sen University, Guangzhou, P. R. China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Author notes

  1. Mian-li Xiao and Geng-dong Chen contributed equally to this article.

Authors and Affiliations

  1. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China

    Mian-li Xiao, Geng-dong Chen, Fang-fang Zeng, Rui Qiu, Jie-sheng Lin, Yi Cao, Hua-bin Li, Wen-hua Ling & Yu-ming Chen

  2. Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, China

    Fang-fang Zeng

  3. The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Wen-qi Shi

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  1. Mian-li Xiao
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Contributions

YMC conceived and designed the research; MLX, GDC, FFZ, RQ, WQS, JSL, and YC collected the data; MLX performed the statistical analysis; MLX and YMC wrote the paper; WHL analyzed RBP4 and revised the paper; and YMC had primary responsibility for final content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yu-ming Chen.

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None of the authors reported a conflict of interest related to the study.

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Xiao, Ml., Chen, Gd., Zeng, Ff. et al. Higher serum carotenoids associated with improvement of non-alcoholic fatty liver disease in adults: a prospective study. Eur J Nutr 58, 721–730 (2019). https://doi.org/10.1007/s00394-018-1678-1

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