. 2019 Apr 18;11(4):872.

doi: 10.3390/nu11040872.

Oxidative Stress and Non-Alcoholic Fatty Liver Disease: Effects of Omega-3 Fatty Acid Supplementation

Jinchunzi Yang¹, Marta Fernández-Galilea^{2

3

4}, Leyre Martínez-Fernández⁵, Pedro González-Muniesa^{6

7

8

9}, Adriana Pérez-Chávez¹⁰, J Alfredo Martínez^{11

12

13

14}, Maria J Moreno-Aliaga^{15

16

17

18}

Affiliations

¹ Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. jyang@alumni.unav.es.
² Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. mfgalilea@unav.es.
³ Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. mfgalilea@unav.es.
⁴ IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain. mfgalilea@unav.es.
⁵ Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. lmartinez.7@alumni.unav.es.
⁶ Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. pgonmun@unav.es.
⁷ Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. pgonmun@unav.es.
⁸ IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain. pgonmun@unav.es.
⁹ CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, 28029 Madrid, Spain. pgonmun@unav.es.
¹⁰ Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. aperez.39@alumni.unav.es.
¹¹ Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. jalfmtz@unav.es.
¹² Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. jalfmtz@unav.es.
¹³ IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain. jalfmtz@unav.es.
¹⁴ CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, 28029 Madrid, Spain. jalfmtz@unav.es.
¹⁵ Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. mjmoreno@unav.es.
¹⁶ Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. mjmoreno@unav.es.
¹⁷ IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain. mjmoreno@unav.es.
¹⁸ CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, 28029 Madrid, Spain. mjmoreno@unav.es.

PMID: 31003450
PMCID: PMC6521137
DOI: 10.3390/nu11040872

Oxidative Stress and Non-Alcoholic Fatty Liver Disease: Effects of Omega-3 Fatty Acid Supplementation

Jinchunzi Yang et al. Nutrients. 2019.

. 2019 Apr 18;11(4):872.

doi: 10.3390/nu11040872.

Authors

Affiliations

¹ Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. jyang@alumni.unav.es.
² Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. mfgalilea@unav.es.
³ Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. mfgalilea@unav.es.
⁴ IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain. mfgalilea@unav.es.
⁵ Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. lmartinez.7@alumni.unav.es.
⁶ Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. pgonmun@unav.es.
⁷ Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. pgonmun@unav.es.
⁸ IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain. pgonmun@unav.es.
⁹ CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, 28029 Madrid, Spain. pgonmun@unav.es.
¹⁰ Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. aperez.39@alumni.unav.es.
¹¹ Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. jalfmtz@unav.es.
¹² Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. jalfmtz@unav.es.
¹³ IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain. jalfmtz@unav.es.
¹⁴ CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, 28029 Madrid, Spain. jalfmtz@unav.es.
¹⁵ Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. mjmoreno@unav.es.
¹⁶ Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain. mjmoreno@unav.es.
¹⁷ IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain. mjmoreno@unav.es.
¹⁸ CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, 28029 Madrid, Spain. mjmoreno@unav.es.

PMID: 31003450
PMCID: PMC6521137
DOI: 10.3390/nu11040872

Abstract

Aging is a complex phenomenon characterized by the progressive loss of tissue and organ function. The oxidative-stress theory of aging postulates that age-associated functional losses are due to the accumulation of ROS-induced damage. Liver function impairment and non-alcoholic fatty liver disease (NAFLD) are common among the elderly. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and evolve to hepatic cirrhosis or hepatic carcinoma. Oxidative stress, lipotoxicity, and inflammation play a key role in the progression of NAFLD. A growing body of evidence supports the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFA), mainly docosahaexenoic (DHA) and eicosapentaenoic acid (EPA), on metabolic diseases based on their antioxidant and anti-inflammatory properties. Here, we performed a systematic review of clinical trials analyzing the efficacy of n-3 PUFA on both systemic oxidative stress and on NAFLD/NASH features in adults. As a matter of fact, it remains controversial whether n-3 PUFA are effective to counteract oxidative stress. On the other hand, data suggest that n-3 PUFA supplementation may be effective in the early stages of NAFLD, but not in patients with more severe NAFLD or NASH. Future perspectives and relevant aspects that should be considered when planning new randomized controlled trials are also discussed.

Keywords: aging; non-alcoholic fatty liver disease; omega-3 fatty acids; oxidative stress.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Multiple parallel hits NAFLD pathogenesis model. Non-alcoholic fatty liver disease (NAFLD). Non-alcoholic steatohepatitis (NASH). Endoplasmic reticulum (ER).

**Figure 2**
Flowchart of selection process based on n-3 PUFA and oxidative stress.

**Figure 3**
Flowchart of selection process based on n-3 PUFA and NAFLD/NASH.

See this image and copyright information in PMC

Cited by

Use of a Micronutrient Cocktail to Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Adults with Obesity: A Randomized, Double-Blinded Pilot Clinical Trial.
Perva IT, Simina IE, Bende R, Motofelea AC, Chirita Emandi A, Andreescu N, Sima A, Vlad A, Sporea I, Zimbru C, Tutac PC, Puiu M, Niculescu MD. Perva IT, et al. Medicina (Kaunas). 2024 Aug 21;60(8):1366. doi: 10.3390/medicina60081366. Medicina (Kaunas). 2024. PMID: 39202647 Free PMC article. Clinical Trial.
Dietary novel alkaline protease from Bacillus licheniformis improves broiler meat nutritional value and modulates intestinal microbiota and metabolites.
Yi W, Liu Y, Fu S, Zhuo J, Wang J, Shan T. Yi W, et al. Anim Microbiome. 2024 Jan 6;6(1):1. doi: 10.1186/s42523-023-00287-z. Anim Microbiome. 2024. PMID: 38184648 Free PMC article.
A Diterpenoid, 14-Deoxy-11, 12-Didehydroandrographolide, in Andrographis paniculata Reduces Steatohepatitis and Liver Injury in Mice Fed a High-Fat and High-Cholesterol Diet.
Liu YT, Chen HW, Lii CK, Jhuang JH, Huang CS, Li ML, Yao HT. Liu YT, et al. Nutrients. 2020 Feb 18;12(2):523. doi: 10.3390/nu12020523. Nutrients. 2020. PMID: 32085637 Free PMC article.
Multi-omic network analysis identified betacellulin as a novel target of omega-3 fatty acid attenuation of western diet-induced nonalcoholic steatohepatitis.
Padiadpu J, Garcia-Jaramillo M, Newman NK, Pederson JW, Rodrigues R, Li Z, Singh S, Monnier P, Trinchieri G, Brown K, Dzutsev AK, Shulzhenko N, Jump DB, Morgun A. Padiadpu J, et al. EMBO Mol Med. 2023 Nov 8;15(11):e18367. doi: 10.15252/emmm.202318367. Epub 2023 Oct 20. EMBO Mol Med. 2023. PMID: 37859621 Free PMC article.
Activation of Kupffer cells in NAFLD and NASH: mechanisms and therapeutic interventions.
Xu GX, Wei S, Yu C, Zhao SQ, Yang WJ, Feng YH, Pan C, Yang KX, Ma Y. Xu GX, et al. Front Cell Dev Biol. 2023 May 16;11:1199519. doi: 10.3389/fcell.2023.1199519. eCollection 2023. Front Cell Dev Biol. 2023. PMID: 37261074 Free PMC article. Review.

See all "Cited by" articles

References

1. Da Costa J.P., Vitorino R., Silva G.M., Vogel C., Duarte A.C., Rocha-Santos T. A synopsis on aging—Theories, mechanisms and future prospects. Ageing Res. Rev. 2016;29:90–112. doi: 10.1016/j.arr.2016.06.005. - DOI - PMC - PubMed
1. Kirkwood T.B.L. Systems biology of ageing and longevity. Philos. Trans. R. Soc. B Biol. Sci. 2011;366:64–70. doi: 10.1098/rstb.2010.0275. - DOI - PMC - PubMed
1. Picca A., Fanelli F., Calvani R., Mulè G., Pesce V., Sisto A., Pantanelli C., Bernabei R., Landi F., Marzetti E. Gut Dysbiosis and Muscle Aging: Searching for Novel Targets against Sarcopenia. Mediat. Inflamm. 2018;2018:7026198. doi: 10.1155/2018/7026198. - DOI - PMC - PubMed
1. North B.J., Sinclair D.A. The intersection between aging and cardiovascular disease. Circ. Res. 2012;110:1097–1108. doi: 10.1161/CIRCRESAHA.111.246876. - DOI - PMC - PubMed
1. Gunasekaran U., Gannon M. Type 2 Diabetes and the Aging Pancreatic Beta Cell. Aging. 2011;3:565–575. doi: 10.18632/aging.100350. - DOI - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Oxidative Stress and Non-Alcoholic Fatty Liver Disease: Effects of Omega-3 Fatty Acid Supplementation

Affiliations

Oxidative Stress and Non-Alcoholic Fatty Liver Disease: Effects of Omega-3 Fatty Acid Supplementation

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials