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Takeda Y, Furuhashi M, Sakuma I, Hiramitsu S, Okada M, Ueda S, Kumashiro N, Sakurai M. Comparison of the effects of pemafibrate and omega-3 fatty acid ethyl on fatty liver index in patients with dyslipidemia treated with statin: a sub-analysis from the PROUD48 study. Front Endocrinol (Lausanne) 2025; 16:1549687. [PMID: 40375947 PMCID: PMC12078148 DOI: 10.3389/fendo.2025.1549687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Accepted: 04/02/2025] [Indexed: 05/18/2025] Open
Abstract
Background Fatty liver index (FLI) calculated by using body mass index, waist circumference and levels of triglycerides and γ-glutamyl transpeptidase is a noninvasive biomarker for diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD), which is one of the high-risk conditions of atherosclerotic cardiovascular diseases. To compare the effects of pemafibrate and omega-3 fatty acid ethyl on FLI, we conducted a sub-analysis study of the Pemafibrate Reduction of triglyceride-rich lipoproteins compared with Omega-3 fatty acid ethyl for Unmet needs in Dyslipidemic patients on target to apoB-48 (PROUD48) study. Methods 57 participants in the pemafibrate 0.4 mg per day treatment group (PEMA, men/women: 37/20, mean 64 years) and 60 participants in the omega-3 fatty acid ethyl 4 g per day treatment group (OMEGA-3, men/women: 35/25, mean 63 years) in the PROUD48 study were included in the present study. Changes in FLI and prevalence of MASLD from baseline to week 16 in PEMA and OMEGA-3 were investigated. Results Median FLI was significantly decreased by both PEMA (69.7 to 47.6, P < 0.001) and OMEGA-3 (64.8 to 59.5, P < 0.001). There was a significant difference in change in FLI between PEMA and OMEGA-3 (-18.3 ± 14.1 vs. -5.5 ± 9.4, P < 0.001). The proportions of MASLD estimated by FLI (baseline/week 16) in PEMA and OMEGA-3 were 93.0/68.4% (P = 0.002) and 90.0/85.0% (P = 0.582), respectively. Conclusions Pemafibrate is superior to omega-3 fatty acid ethyl in lowering effects of FLI and MASLD in patients with dyslipidemia receiving statin treatment, suggesting that pemafibrate is a beneficial agent for hypertriglyceridemia and reduction of the risk for MASLD.
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Affiliation(s)
- Yasutaka Takeda
- Department of Diabetology & Endocrinology, Kanazawa Medical University, Uchinada, Japan
| | - Masato Furuhashi
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Ichiro Sakuma
- Caress Sapporo Hokko Memorial Clinic, Sapporo, Japan
| | | | | | - Shinichiro Ueda
- Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus, Nishihara, Japan
| | - Naoki Kumashiro
- Department of Diabetology & Endocrinology, Kanazawa Medical University, Uchinada, Japan
| | - Masaru Sakurai
- Department of Social and Environmental Medicine, Kanazawa Medical University, Uchinada, Japan
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Ciobârcă D, Cătoi AF, Gavrilaș L, Banc R, Miere D, Filip L. Natural Bioactive Compounds in the Management of Type 2 Diabetes and Metabolic (Dysfunction)-Associated Steatotic Liver Disease. Pharmaceuticals (Basel) 2025; 18:279. [PMID: 40006091 PMCID: PMC11859434 DOI: 10.3390/ph18020279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 02/11/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
Type 2 diabetes (T2D) and metabolic (dysfunction)-associated steatotic liver disease (MASLD) affect a growing number of individuals worldwide. T2D and MASLD often coexist and substantially elevate the risk of adverse hepatic and cardiovascular clinical outcomes. Several common pathogenetic mechanisms are responsible for T2D and MASLD onset and progression, including insulin resistance, oxidative stress, and low-grade inflammation, among others. The latter can also be induced by gut microbiota and its derived metabolites. Natural bioactive compounds (NBCs) have been reported for their therapeutic potential in both T2D and MASLD. A large amount of evidence obtained from clinical trials suggests that compounds like berberine, curcumin, soluble fibers, and omega-3 fatty acids exhibit significant hypoglycemic, hypolipidemic, and hepatoprotective activity in humans and may be employed as adjunct therapy in T2D and MASLD management. In this review, the role of the most studied NBCs in the management of T2D and MASLD is discussed, emphasizing recent clinical evidence supporting these compounds' efficacy and safety. Also, prebiotics that act against metabolic dysfunction by modulating gut microbiota are evaluated.
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Affiliation(s)
- Daniela Ciobârcă
- Department 2, Faculty of Nursing and Health Sciences, “Iuliu Hatieganu” University of Medicine and Pharmacy, 23 Gheorghe Marinescu Street, 400337 Cluj-Napoca, Romania; (D.C.); (L.G.)
| | - Adriana Florinela Cătoi
- Department of Pathophysiology, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 2-4 Victor Babes Street, 400012 Cluj-Napoca, Romania
| | - Laura Gavrilaș
- Department 2, Faculty of Nursing and Health Sciences, “Iuliu Hatieganu” University of Medicine and Pharmacy, 23 Gheorghe Marinescu Street, 400337 Cluj-Napoca, Romania; (D.C.); (L.G.)
| | - Roxana Banc
- Department of Bromatology, Hygiene, Nutrition, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania; (R.B.); (D.M.); (L.F.)
| | - Doina Miere
- Department of Bromatology, Hygiene, Nutrition, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania; (R.B.); (D.M.); (L.F.)
| | - Lorena Filip
- Department of Bromatology, Hygiene, Nutrition, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania; (R.B.); (D.M.); (L.F.)
- Academy of Romanian Scientists (AOSR), 3 Ilfov Street, 050044 Bucharest, Romania
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Zhou L, Sun D, Bai H. Efficacy of fish oil supplementation on metabolic dysfunction-associated steatotic liver disease: a meta-analysis. Front Nutr 2025; 12:1524830. [PMID: 39927279 PMCID: PMC11804523 DOI: 10.3389/fnut.2025.1524830] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 01/08/2025] [Indexed: 02/11/2025] Open
Abstract
Objective Globally, the occurrence of Metabolic dysfunction-associated steatotic liver disease (MASLD) is on a steady rise. Fish oil has anti-inflammatory effects and can improve lipid metabolism. The article aims to assess the impact of fish oil supplementation on MASLD. Methods We conducted a systematic search of Cochrane, Embase, PubMed, and Web of Science up to September 31, 2024, for randomized control trials (RCTs). The risk of bias of the included RCTs was evaluated using the Cochrane Collaboration's tool. Outcomes measured were aspects of liver injury, lipid profile, insulin resistance, anthropometric measurements, and more. Results Seven randomized controlled trials (RCTs) involving 439 participants were incorporated into the analysis. In general, the risk of bias in these RCTs was either low or not clearly defined. Pooled analysis showed that triglycerides [TG, pooled standard mean difference (SMD): -0.40 (95% CI: -0.58 to -0.21)], aspartate transaminase [AST, SMD: -0.29 (95% CI: -0.48 to -0.10)], HOMA-IR [SMD: -2.06 (95% CI: -3.36 to -0.49)] and waist circumference [Waist-C, SMD: -0.31 (95% CI: -0.54 to -0.08)] were significantly improved. But showed no significant benefits on alanine transaminase [ALT, SMD: -0.15 (95% CI: -0.45 to 0.15)], gamma-glutamyl transpeptidase [GGT, SMD: -0.07 (95% CI: -0.26 to 0.12)], body mass index [BMI, SMD: 0.16 (95% CI: -0.34 to 0.02)], high-density lipoprotein cholesterol [HDL, SMD: 0.02 (95% CI: -0.18 to 0.22)], low-density lipoprotein cholesterol [LDL, SMD: -0.01 (95% CI: -0.20 to 0.18)], Total Cholesterol [TC, SMD: -0.34 (95% CI: -0.70 to 0.01)] and so on. Conclusion The current evidence supports the fish oil supplementation in improving MASLD. Fish oil supplementation may also regulate blood lipids and improve glucose metabolism disorders. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier CRD42024513246.
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Affiliation(s)
- Like Zhou
- Department of Gastroenterology, Weihai Maternal and Child Health Hospital, Weihai, China
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Wen H, Deng H, Yang L, Li L, Lin J, Zheng P, Bjelakovic M, Ji G. Vitamin E for people with non-alcoholic fatty liver disease. Cochrane Database Syst Rev 2024; 10:CD015033. [PMID: 39412049 PMCID: PMC11481097 DOI: 10.1002/14651858.cd015033.pub2] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2024]
Abstract
RATIONALE Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is the most common liver disease worldwide, affecting an estimated 3 in 10 people. The available treatment is far from optimal. Diet and lifestyle changes to promote weight loss and weight loss maintenance are the basic management of NAFLD, but these are difficult to achieve and maintain. Vitamin E has shown beneficial effects on oxidative stress, which plays a major role in the pathogenesis of NAFLD. However, there is uncertainty about the effects of vitamin E for people with NAFLD. OBJECTIVES To evaluate the beneficial and harmful effects of vitamin E alone, or vitamin E in combination with other vitamins or minerals, versus placebo or no intervention in people with NAFLD. SEARCH METHODS We used recommended Cochrane search methods. The latest search was performed on 2 February 2024. ELIGIBILITY CRITERIA We included randomised clinical trials that compared vitamin E alone, or in combination with other vitamins or minerals, at any dose, duration, and route of administration, versus placebo or no intervention, in people with NAFLD of any age, sex, or ethnic origin. We included participants with imaging techniques or histology-proven NAFLD and minimal alcohol intake, and participants with steatohepatitis who had liver biopsies. OUTCOMES Our critical outcomes were all-cause mortality, liver-related mortality, and serious adverse events. Our important outcomes were liver-related morbidity, health-related quality of life, non-serious adverse events, biochemical response, and imaging assessment of the degree of fatty liver. RISK OF BIAS We used Cochrane's RoB 2 tool to assess risk of bias for each of the predefined outcomes. SYNTHESIS METHODS We used standard Cochrane methods. We used GRADE to assess the certainty of evidence. INCLUDED STUDIES We included 16 randomised clinical trials involving 1066 paediatric and adult participants with NAFLD. Experimental groups received vitamin E alone (14 trials) or vitamin E in combination with vitamin C (2 trials). Control groups received placebo in 13 trials and no intervention in three trials. Daily dosages of oral vitamin E ranged from 298 international units (IU) to 1000 IU. Co-interventions were lifestyle and low-calorie diet interventions in 13 trials, ursodeoxycholic acid in one trial, unchanged diet and physical activity in one trial, and baseline treatments for type 2 diabetes in one trial. Nine trials had more than two intervention groups, but we used only the groups in which vitamin E alone or vitamin E in combination with vitamin C were compared with placebo or no intervention. In total, 7.9% (84/1066) of participants dropped out. Follow-up ranged from 2 months to 24 months. SYNTHESIS OF RESULTS Vitamin E versus placebo or no intervention The effects of vitamin E versus placebo or no intervention on all-cause mortality (risk ratio (RR) 3.45, 95% confidence interval (CI) 0.57 to 20.86; 3 trials, 351 participants; very low certainty evidence) and serious adverse events (RR 1.91, 95% CI 0.30 to 12.01; 2 trials, 283 participants; very low certainty evidence) are very uncertain. There were no data on liver-related mortality or liver-related morbidity. The effects of vitamin E versus placebo or no intervention on physical health-related quality of life (mean difference (MD) 0.74, 95% CI -0.52 to 2.01; 2 trials, 251 participants; higher scores indicate better quality of life; very low certainty evidence); psychosocial health-related quality of life (MD -0.57, 95% CI -4.11 to 2.97; 2 trials, 251 participants; higher scores indicate better quality of life; very low certainty evidence); and non-serious adverse events (RR 0.86, 95% CI 0.64 to 1.17; 2 trials, 283 participants; very low certainty evidence) are also very uncertain. There were no data on proportion of participants without a decrease in liver enzymes. Vitamin E likely slightly reduces serum alanine transaminase (ALT) (MD -9.29, 95% CI -13.69 to -4.89; 11 trials, 708 participants; moderate certainty evidence) and aspartate aminotransferase (AST) (MD -4.90, 95% CI -7.24 to -2.57; 11 trials, 695 participants; moderate certainty evidence) levels compared with placebo or no intervention. Vitamin E may slightly reduce serum alkaline phosphatase (ALP) levels (MD -5.21, 95% CI -9.88 to -0.54; 5 trials, 416 participants; very low certainty evidence), but the evidence is very uncertain. Vitamin E plus vitamin C versus placebo There were no data on all-cause mortality, liver-related mortality, serious adverse events, liver-related morbidity, health-related quality of life, and non-serious adverse events. The effects of vitamin E plus vitamin C on reducing serum ALT (MD -0.50, 95% CI -4.58 to 3.58; 2 trials, 133 participants; very low certainty evidence), AST (MD 0.09, 95% CI -3.39 to 3.57; 1 trial, 88 participants; very low certainty evidence), and gamma-glutamyl transferase (GGT) levels (MD 1.58, 95% CI -3.22 to 6.38; 1 trial, 88 participants; very low certainty evidence) are very uncertain. We identified three ongoing trials, and six trials are awaiting classification. AUTHORS' CONCLUSIONS Given the very low certainty evidence, we do not know if long-term treatment (18 months to 24 months) with vitamin E administered alone affects all-cause mortality, serious adverse events, quality of life, or non-serious adverse events in people with NAFLD when compared with placebo or no intervention. We found no data on liver-related mortality, liver-related morbidity, or proportion of participants without a decrease in liver enzymes. Vitamin E likely reduces ALT and AST slightly when compared with placebo, but whether this has any impact on the clinical course in people with NAFLD is unknown. The trials on vitamin E plus vitamin C did not report on all-cause mortality, liver-related mortality, serious adverse events, liver-related morbidity, health-related quality of life, or non-serious adverse events. Given the very low certainty evidence, we do not know the effects of vitamin E plus vitamin C on liver enzymes in people with NAFLD when compared with placebo. FUNDING Three trials disclosed no external funding. Five trials were industry funded. Five trials were funded by organisations with no vested interests. Three trials did not provide any information on clinical trial support or sponsorship. REGISTRATION Protocol: doi.org/10.1002/14651858.CD015033.
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Affiliation(s)
- Hongzhu Wen
- Department of Gastroenterology, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hongyong Deng
- EBM Center of TCM, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lili Yang
- Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lujin Li
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiang Lin
- Department of Gastroenterology, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Peiyong Zheng
- Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Milica Bjelakovic
- Clinic of Gastroenterohepatology, University Clinical Centre Nis, Nis, Serbia
| | - Guang Ji
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Banaszak M, Dobrzyńska M, Kawka A, Górna I, Woźniak D, Przysławski J, Drzymała-Czyż S. Role of Omega-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic (DHA) as modulatory and anti-inflammatory agents in noncommunicable diet-related diseases - Reports from the last 10 years. Clin Nutr ESPEN 2024; 63:240-258. [PMID: 38980796 DOI: 10.1016/j.clnesp.2024.06.053] [Citation(s) in RCA: 19] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 06/11/2024] [Accepted: 06/27/2024] [Indexed: 07/11/2024]
Abstract
BACKGROUND & AIMS Fatty acids are a fundamental component of the human diet, particularly polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The importance of omega-3 fatty acids has been studied in the context of many diseases due to their pleiotropic effects, focusing on the anti-inflammatory effects of EPA and DHA. Currently, the results of these acids in noncommunicable diseases are being increasingly assessed in a broader context than just inflammation. However, the mechanisms underlying the modulatory and anti-inflammatory effects of omega-3 fatty acids remain the subject of intensive research. Therefore, we reviewed the literature covering articles from the last decade to assess not only the anti-inflammatory but, above all, the modulatory effect of EPA and DHA acids on noncommunicable diet-related diseases. METHODS The PubMed, Web of Science and Scopus databases were searched for studies regarding the effects of omega-3 fatty acids on diet-related disorders from the last 10 years. RESULTS The available research shows that EPA and DHA supplementation has a beneficial impact on regulating triglycerides, total cholesterol, insulin resistance, blood pressure, liver enzymes, inflammatory markers and oxidative stress. Additionally, there is evidence of their potential benefits in terms of mitochondrial function, regulation of plasma lipoproteins, and reduction of the risk of sudden cardiovascular events associated with atherosclerotic plaque rupture. CONCLUSIONS Omega-3 polyunsaturated fatty acids (EPA, DHA) have many beneficial effects among patients with diet-related disorders. More well-designed randomised controlled trials are needed to fully determine the usefulness of EPA and DHA in treating and preventing noncommunicable diet-related diseases.
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Affiliation(s)
- Michalina Banaszak
- Poznan University of Medical Sciences, Department of Bromatology, Rokietnicka 3, Poznan, Poland; Poznan University of Medical Sciences Doctoral School, Bukowska 70, Poznan, Poland.
| | - Małgorzata Dobrzyńska
- Poznan University of Medical Sciences, Department of Bromatology, Rokietnicka 3, Poznan, Poland
| | - Anna Kawka
- Department of Bioactive Products, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznanskiego 8, Poznan, Poland
| | - Ilona Górna
- Poznan University of Medical Sciences, Department of Bromatology, Rokietnicka 3, Poznan, Poland
| | - Dagmara Woźniak
- Poznan University of Medical Sciences, Department of Bromatology, Rokietnicka 3, Poznan, Poland
| | - Juliusz Przysławski
- Poznan University of Medical Sciences, Department of Bromatology, Rokietnicka 3, Poznan, Poland
| | - Sławomira Drzymała-Czyż
- Poznan University of Medical Sciences, Department of Bromatology, Rokietnicka 3, Poznan, Poland
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Schuchardt JP, Beinhorn P, Hu XF, Chan HM, Roke K, Bernasconi A, Hahn A, Sala-Vila A, Stark KD, Harris WS. Omega-3 world map: 2024 update. Prog Lipid Res 2024; 95:101286. [PMID: 38879135 DOI: 10.1016/j.plipres.2024.101286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 05/31/2024] [Accepted: 06/05/2024] [Indexed: 07/06/2024]
Abstract
In 2016, the first worldwide n3 PUFA status map was published using the Omega-3 Index (O3I) as standard biomarker. The O3I is defined as the percentage of EPA + DHA in red blood cell (RBC) membrane FAs. The purpose of the present study was to update the 2016 map with new data. In order to be included, studies had to report O3I and/or blood EPA + DHA levels in metrics convertible into an estimated O3I, in samples drawn after 1999. To convert the non-RBC-based EPA + DHA metrics into RBC we used newly developed equations. Baseline data from clinical trials and observational studies were acceptable. A literature search identified 328 studies meeting inclusion criteria encompassing 342,864 subjects from 48 countries/regions. Weighted mean country O3I levels were categorized into very low ≤4%, low >4-6%, moderate >6-8%, and desirable >8%. We found that the O3I in most countries was low to very low. Notable differences between the current and 2016 map were 1) USA, Canada, Italy, Turkey, UK, Ireland and Greece (moving from the very low to low category); 2) France, Spain and New Zealand (low to moderate); and 3) Finland and Iceland (moderate to desirable). Countries such as Iran, Egypt, and India exhibited particularly poor O3I levels.
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Affiliation(s)
- Jan Philipp Schuchardt
- The Fatty Acid Research Institute, 5009 W. 12(th) St. Ste 5, Sioux Falls, SD 57106, United States; Institute of Food and One Health, Leibniz University Hannover, Am kleinen Felde 30, 30167 Hannover, Germany.
| | - Philine Beinhorn
- Institute of Food and One Health, Leibniz University Hannover, Am kleinen Felde 30, 30167 Hannover, Germany
| | - Xue Feng Hu
- Department of Biology, University of Ottawa, Ottawa, ON, Canada
| | - Hing Man Chan
- Department of Biology, University of Ottawa, Ottawa, ON, Canada
| | - Kaitlin Roke
- Global Organization for EPA and DHA Omega-3s (GOED), 222 South Main Street, Suite 500, Salt Lake City, UT 84101, United States
| | - Aldo Bernasconi
- Global Organization for EPA and DHA Omega-3s (GOED), 222 South Main Street, Suite 500, Salt Lake City, UT 84101, United States
| | - Andreas Hahn
- Institute of Food and One Health, Leibniz University Hannover, Am kleinen Felde 30, 30167 Hannover, Germany
| | - Aleix Sala-Vila
- The Fatty Acid Research Institute, 5009 W. 12(th) St. Ste 5, Sioux Falls, SD 57106, United States; Hospital del Mar Medical Research Institute, Dr. Aiguader 88, 08003 Barcelona, Spain
| | - Ken D Stark
- Department of Kinesiology and Health Sciences, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada
| | - William S Harris
- The Fatty Acid Research Institute, 5009 W. 12(th) St. Ste 5, Sioux Falls, SD 57106, United States; Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, 1400 W. 22nd St., Sioux Falls, SD 57105, United States
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Li X, Pan C, Ma W, Yang T, Wang C, Han W, Zhang W, Li H, Li Z, Zhao T, Guo XF, Li D. Effects of dietary supplementation of fish oil plus vitamin D 3 on gut microbiota and fecal metabolites, and their correlation with nonalcoholic fatty liver disease risk factors: a randomized controlled trial. Food Funct 2024; 15:2616-2627. [PMID: 38356413 DOI: 10.1039/d3fo02319b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2024]
Abstract
We previously reported that fish oil plus vitamin D3 (FO + D) could ameliorate nonalcoholic fatty liver disease (NAFLD). However, it is unclear whether the beneficial effects of FO + D on NAFLD are associated with gut microbiota and fecal metabolites. In this study, we investigated the effects of dietary supplementation of FO + D on gut microbiota and fecal metabolites and their correlation with NAFLD risk factors. Methods: A total of 61 subjects were randomly divided into three groups: FO + D group (2.34 g day-1 of eicosatetraenoic acid (EPA) + docosahexaenoic acid (DHA) + 1680 IU vitamin D3), FO group (2.34 g day-1 of EPA + DHA), and corn oil (CO) group (1.70 g d-1 linoleic acid). Blood and fecal samples were collected at the baseline and day 90. Gut microbiota were analyzed through 16S rRNA PCR analysis, and fecal co-metabolites were determined via untargeted ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Results: The relative abundance of Eubacterium (p = 0.03) and Lactobacillus (p = 0.05) increased, whereas that of Streptococcus (p = 0.02) and Dialister (p = 0.04) decreased in the FO + D group compared with the CO group. Besides, changes in tetracosahexaenoic acid (THA, C24:6 n-3) (p = 0.03) levels were significantly enhanced, whereas 8,9-DiHETrE levels (p < 0.05) were reduced in the FO + D group compared with the CO group. The changes in 1,25-dihydroxyvitamin D3 levels in the fecal samples were inversely associated with insulin resistance, which was determined using the homeostatic model assessment model (HOMA-IR, r = -0.29, p = 0.02), and changes in 8,9-DiHETrE levels were positively associated with adiponectin levels (r = -0.43, p < 0.05). Conclusion: The present results indicate that the beneficial effects of FO + D on NAFLD may be partially attributed to the impact on gut microbiota and fecal metabolites.
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Affiliation(s)
- Xueqi Li
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
- Binzhou Center for Disease Control and Prevention, Binzhou, China
| | - Chi Pan
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
| | - Wenjun Ma
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
| | - Ting Yang
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
| | - Chong Wang
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
| | - Weiwei Han
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
| | - Wei Zhang
- Affiliated Hospital of Qingdao University, Qingdao, China
| | - Hui Li
- Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zhongxia Li
- Byhealth Institute of Nutrition & Health, Guangzhou, China
| | - Ting Zhao
- Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiao-Fei Guo
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
| | - Duo Li
- Institute of Nutrition & Health, Qingdao University, Qingdao, China.
- School of Public Health, Qingdao University, Qingdao, China
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8
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Safaei P, Bayat G, Mohajer A. Comparison of fish oil supplements and corn oil effects on serum lipid profile: a systematic review and meta-analysis of randomized controlled trials. Syst Rev 2024; 13:54. [PMID: 38317191 PMCID: PMC10840298 DOI: 10.1186/s13643-023-02426-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 12/11/2023] [Indexed: 02/07/2024] Open
Abstract
BACKGROUND The present study aimed to investigate the effects of fish oil supplements compared to corn oil on serum lipid profiles by performing a meta-analysis of randomized controlled trials (RCTs). METHODS Online databases including PubMed, Web of Science, and Scopus were searched until 30 December 2022. Pooled effect sizes were reported as the weighted mean difference (WMD) with 95% confidence intervals (CI). The Cochrane Collaboration's risk-of-bias tool was utilized to evaluate the quality of the studies. Lipid parameters, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL), were assessed in the meta-analysis. RESULTS Overall, 16 eligible trials were included in this systematic review and meta-analysis. The results revealed that the fish oil supplements significantly reduced TG (WMD: - 25.50 mg/dl, 95% CI: - 42.44, - 8.57, P = 0.000) levels compared to corn oil. Also, in this study, fish oil supplements had a positive and significant effect on HDL (WMD: 2.54 mg/dl, 95% CI: 0.55, 4.52). There were no significant changes in TC and LDL. CONCLUSIONS Our findings showed the effects of fish oil supplements on reducing TG and increasing HDL-c compared to corn oil. Further larger and well-designed RCTs are required to confirm these data.
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Affiliation(s)
- Payam Safaei
- Division of Food Safety and Hygiene, Department of Environmental Health Engineering, School of Public Heath, Tehran University of Medical Sciences, Tehran, Iran
| | - Ghazal Bayat
- Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Afsaneh Mohajer
- Division of Food Safety and Hygiene, Department of Environmental Health Engineering, School of Public Heath, Tehran University of Medical Sciences, Tehran, Iran.
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9
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Zamanian MY, Sadeghi Ivraghi M, Khachatryan LG, Vadiyan DE, Bali HY, Golmohammadi M. A review of experimental and clinical studies on the therapeutic effects of pomegranate ( Punica granatum) on non-alcoholic fatty liver disease: Focus on oxidative stress and inflammation. Food Sci Nutr 2023; 11:7485-7503. [PMID: 38107091 PMCID: PMC10724645 DOI: 10.1002/fsn3.3713] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 09/06/2023] [Accepted: 09/12/2023] [Indexed: 12/19/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is frequently linked to metabolic disorders and is prevalent in obese and diabetic patients. The pathophysiology of NAFLD involves multiple factors, including insulin resistance (IR), oxidative stress (OS), inflammation, and genetic predisposition. Recently, there has been an emphasis on the use of herbal remedies with many people around the world resorting to phytonutrients or nutraceuticals for treatment of numerous health challenges in various national healthcare settings. Pomegranate (Punica granatum) parts, such as juice, peel, seed and flower, have high polyphenol content and is well known for its antioxidant capabilities. Pomegranate polyphenols, such as hydrolyzable tannins, anthocyanins, and flavonoids, have high antioxidant capabilities that can help lower the OS and inflammation associated with NAFLD. The study aimed to investigate whether pomegranate parts could attenuate OS, inflammation, and other risk factors associated with NAFLD, and ultimately prevent the development of the disease. The findings of this study revealed that: 1. pomegranate juice contains hypoglycemic qualities that can assist manage blood sugar levels, which is vital for avoiding and treating NAFLD. 2. Polyphenols from pomegranate flowers increase paraoxonase 1 (PON1) mRNA and protein levels in the liver, which can help protect liver enzymes and prevent NAFLD. 3. Punicalagin (PU) is one of the major ellagitannins found in pomegranate, and PU-enriched pomegranate extract (PE) has been shown to inhibit HFD-induced hyperlipidemia and hepatic lipid deposition in rats. 4. Pomegranate fruit consumption, which is high in antioxidants, can decrease the activity of AST and ALT (markers of liver damage), lower TNF-α (a marker of inflammation), and improve overall antioxidant capacity in NAFLD patients. Overall, the polyphenols in pomegranate extracts have antioxidant, anti-inflammatory, hypoglycemic, and protective effects on liver enzymes, which can help prevent and manage NAFLD effects on liver enzymes, which can help prevent and manage NAFLD.
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Affiliation(s)
- Mohammad Yassin Zamanian
- Department of Physiology, School of MedicineHamadan University of Medical SciencesHamadanIran
- Department of Pharmacology and Toxicology, School of PharmacyHamadan University of Medical SciencesHamadanIran
| | | | - Lusine G. Khachatryan
- Department of Pediatric Diseases, N.F. Filatov Clinical Institute of Children's HealthI.M. Sechenov First Moscow State Medical University (Sechenov University)MoscowRussia
| | - Diana E. Vadiyan
- Institute of Dentistry, Department of Pediatric, Preventive Dentistry and OrthodonticsI.M. Sechenov First Moscow State Medical University (Sechenov University)MoscowRussia
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10
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Das A, Tang YLM, Althumiri NA, Garcia-Larsen V, Schattenberg JM, Alqahtani SA. Fatty acid composition but not quantity is an important indicator of non-alcoholic fatty liver disease: a systematic review. Eur J Clin Nutr 2023; 77:1113-1129. [PMID: 37661229 DOI: 10.1038/s41430-023-01335-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 08/14/2023] [Accepted: 08/17/2023] [Indexed: 09/05/2023]
Abstract
BACKGROUND There is still paucity on the effects of dietary and supplemental fatty acid on non-alcoholic fatty liver disease (NAFLD). The aim of this review is to systematically review and summarise the effect of fatty acids intake on liver-related outcomes in adult patients with NAFLD. METHODS The review was conducted using Cochrane CENTRAL Library, Scopus, Embase, MEDLINE, PubMed, and Web of Science. A total of 2786 records were identified, and of these, 36 studies (31 were randomised control trials (RCTs), and 5 were case-control studies) were included. Quality assessment was conducted using the Revised Cochrane Risk of Bias tool and Joanna Briggs Institute checklists. RESULTS Of 36 articles, 79% of RCTs and 66% of case-control studies had a low risk of bias. Potential heterogeneity has been observed in assessment of liver-related outcomes. According to the RCTs, there was moderate evidence (3/6 studies) that a diet characterised by a high MUFA, PUFA and low SFA showed reduced liver fat and stiffness. The using of culinary fats that are high in MUFA (4/6 studies) reduces liver steatosis. n-3 PUFA supplementation in combination with a hypocaloric or heart healthy diet with a low SFA improved liver enzyme level (5/14 studies) and steatosis score (3/14 studies). CONCLUSIONS Effects on NAFLD parameters, including liver fat content (assessed via magnetic resonance imaging/spectroscopy), stiffness and steatosis score (assessed by ultrasonography), were primarily related to fatty acid composition independent of energy intake. Further investigation is needed to determine the mechanism of specific fatty acid on the accumulation of liver fat.
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Affiliation(s)
- Arpita Das
- Department of Nutrition and Dietetics, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
| | - Yu Lung Malcolm Tang
- Department of Nutrition and Dietetics, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia
| | | | - Vanessa Garcia-Larsen
- Program in Human Nutrition, Department of International Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Jörn M Schattenberg
- Metabolic Liver Research Program, I. Department of Medicine, University Medical Centre, Mainz, Germany
| | - Saleh A Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
- Liver Transplantation Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
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11
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Ahmadi AR, Shirani F, Abiri B, Siavash M, Haghighi S, Akbari M. Impact of omega-3 fatty acids supplementation on the gene expression of peroxisome proliferator activated receptors- γ, α and fibroblast growth factor-21 serum levels in patients with various presentation of metabolic conditions: a GRADE assessed systematic review and dose-response meta-analysis of clinical trials. Front Nutr 2023; 10:1202688. [PMID: 38035345 PMCID: PMC10684744 DOI: 10.3389/fnut.2023.1202688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Accepted: 11/01/2023] [Indexed: 12/02/2023] Open
Abstract
There is some debate about the effects of omega-3 fatty acids on the regulation of adipose tissue related genes. This systematic review and meta-analysis aimed to evaluate the effects of omega-3 fatty acids supplementation on the gene expression of peroxisome proliferator activated receptors (PPAR-α and PPAR-γ) and serum fibroblast growth factor-21 (FGF-21) levels in adults with different presentation of metabolic conditions. To identify eligible studies, a systematic search was conducted in the Cochrane Library of clinical trials, Medline, Scopus, ISI Web of Science, and Google Scholar up to April 2022. Eligibility criteria included a clinical trial design, omega-3 fatty acids supplementation in adults, and reporting of at least one of the study outcomes. Effect sizes were synthesized using either fixed or random methods based on the level of heterogeneity. Fifteen studies met the inclusion criteria. Omega-3 fatty acids supplementation significantly increased the PPAR-γ (10 studies) and PPAR-α (2 studies) gene expression compared to the control group (WMD: 0.24; 95% CI: 0.12, 0.35; p < 0.001 and 0.09; 95% CI: 0.04, 0.13; p < 0.001, respectively). Serum FGF-21 (8 studies) levels exhibited no significant change following omega-3 fatty acids supplementation (p = 0.542). However, a dose-response relationship emerged between the dose of omega-3 fatty acids and both PPAR-γ gene expression and serum FGF-21 levels. Overall, this study suggests that omega-3 fatty acids supplementation may have positive effects on the regulation of adipose tissue related genes in patients with various presentation of metabolic condition. Further research is needed to validate these findings and ascertain the effectiveness of this supplementation approach in this population. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?, CRD42022338344.
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Affiliation(s)
| | - Fatemeh Shirani
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Behnazi Abiri
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mansoor Siavash
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Sasan Haghighi
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mojtaba Akbari
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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12
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Barroso LN, Salarini J, Leite NC, Villela-Nogueira CA, Dávalos A, Carmo MDGT, Ferreira Peres WA. Effect of fish oil supplementation on the concentration of miRNA-122, FGF-21 and liver fibrosis in patients with NAFLD: Study protocol for a randomized, double-blind and placebo-controlled clinical trial. Clin Nutr ESPEN 2023; 57:117-125. [PMID: 37739645 DOI: 10.1016/j.clnesp.2023.06.027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 06/22/2023] [Accepted: 06/25/2023] [Indexed: 09/24/2023]
Abstract
BACKGROUND & AIMS To date, no specific drugs are available for non-alcoholic fatty liver disease (NAFLD), though the effect of fish oil supplementation on improving fibrosis in patients with NAFLD has been evaluated. N-3 polyunsaturated fatty acids (n-3 PUFA) may modulate the concentration of microRNAs (miRNAs) and fibroblast growth factor (FGF)-21, which have been identified as non-invasive markers of liver fibrosis. The present study aims to evaluate whether n-3 PUFA supplementation can modulate miRNA-122 and FGF-21 and improve liver fibrosis and steatosis, measured by transient hepatic elastography (THE), in individuals with NAFLD. METHODS A randomized, double-blind, placebo-controlled clinical trial will be conducted to evaluate the effect of 4 g/day supplementation of fish oil (2100 mg EPA and 924 mg DHA) in patients with NAFLD over a 6-month period. Fifty-two patients aged >19 years will be randomly assigned to either a placebo (olive oil) or treatment (fish oil) group. Anthropometric data, food intake, physical activity, body composition, resting energy expenditure (evaluated using indirect calorimetry), liver enzymes, platelets, lipids and glucose profile, inflammatory markers (such as C-reactive protein, neutrophil/lymphocyte, platelet/lymphocyte, and monocyte/lymphocyte ratios), miRNA-122 and FGF-21 concentration, and incorporation of fatty acids into the erythrocyte membrane (analyzed using gas chromatography) as well as the degree of liver fibrosis and steatosis assessed using THE (Fibroscan® Touch 502, Paris, France) and liver biomarkers Steato-Brazilian Longitudinal Study of Adult Health, Fatty Liver Index, NAFLD Fibrosis Score, Fibrosis-4 score, and FibroScan-AST score will be evaluated at the beginning and end of the treatment. Continuous variables with normal distribution will be compared between placebo and intervention groups using Student's T test for independent samples; continuous non-parametric variables will be compared using Dunn or Mann-Whitney test. Associations between categorical variables will be analyzed using the chi-square test, and within-group differences will be evaluated using the Wilcoxon signed-ranks test. The criterion for determining significance will be set at 5%. CONCLUSION The present study protocol will investigate the supplementation of EPA-rich fish oil as an alternative treatment for NAFLD and its feasibility in affecting the concentration of miRNA-122 and FGF-21 markers. Its findings will offer valuable contributions to the literature. REGISTRATION ReBEC number RBR-8dp876.
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Affiliation(s)
- Lygia N Barroso
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil; School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Jessica Salarini
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil; School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Nathalie Carvalho Leite
- School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Cristiane A Villela-Nogueira
- School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Alberto Dávalos
- Laboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA), Madrid, Spain
| | - Maria das Graças Tavares Carmo
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Wilza Arantes Ferreira Peres
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil.
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Jackson MI, Jewell DE. Feeding of fish oil and medium-chain triglycerides to canines impacts circulating structural and energetic lipids, endocannabinoids, and non-lipid metabolite profiles. Front Vet Sci 2023; 10:1168703. [PMID: 37691632 PMCID: PMC10484482 DOI: 10.3389/fvets.2023.1168703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Accepted: 07/26/2023] [Indexed: 09/12/2023] Open
Abstract
Introduction The effect of medium-chain fatty acid-containing triglycerides (MCT), long-chain polyunsaturated fatty acid-containing triglycerides from fish oil (FO), and their combination (FO+MCT) on the serum metabolome of dogs (Canis familiaris) was evaluated. Methods Dogs (N = 64) were randomized to either a control food, one with 7% MCT, one with FO (0.18% eicosapentaenoate and 1.3% docosahexaenoate), or one with FO+MCT for 28 days following a 14-day washout period on the control food. Serum metabolites were analyzed via chromatography followed by mass spectrometry. Results Additive effects of serum metabolites were observed for a number of metabolite classes, including fatty acids, phospholipids, acylated amines including endocannabinoids, alpha-oxidized fatty acids, and methyl donors. Some effects of the addition of FO+MCT were different when the oils were combined compared with when each oil was fed separately, namely for acylcarnitines, omega-oxidized dicarboxylic acids, and amino acids. Several potentially beneficial effects on health were observed, including decreased circulating triglycerides and total cholesterol with the addition of FO (with or without MCT) and decreases in N-acyl taurines with the addition of MCT, FO, or FO+MCT. Discussion Overall, the results of this study provide a phenotypic characterization of the serum lipidomic response to dietary supplementation of long-chain n3-polyunsaturated and medium-chain saturated fats in canines.
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Affiliation(s)
- Matthew I. Jackson
- Pet Nutrition Center, Hill's Pet Nutrition, Inc., Topeka, KS, United States
| | - Dennis E. Jewell
- Pet Nutrition Center, Hill's Pet Nutrition, Inc., Topeka, KS, United States
- Department of Grain Science and Industry, Kansas State University, Manhattan, KS, United States
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14
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Kosmalski M, Frankowski R, Deska K, Różycka-Kosmalska M, Pietras T. Exploring the Impact of Nutrition on Non-Alcoholic Fatty Liver Disease Management: Unveiling the Roles of Various Foods, Food Components, and Compounds. Nutrients 2023; 15:2838. [PMID: 37447164 DOI: 10.3390/nu15132838] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 06/18/2023] [Accepted: 06/19/2023] [Indexed: 07/15/2023] Open
Abstract
There is a need to introduce standardized treatment options for non-alcoholic fatty liver disease (NAFLD) due to its global prevalence and the complications of this disease. Many studies have revealed that food-derived substances may be beneficial in dealing with this disease. Therefore, this review aims to evaluate the recently published studies on the food-derived treatment options for NAFLD. A comprehensive search of the PubMed database using keywords such as "NAFLD", "nutrition", "food", "derived", "therapy", and "guidelines" yielded 219 relevant papers for our analysis, published from 2004 to 2023. The results show the significant benefits of food-derived treatment in NAFLD therapy, including improvements in liver histology, hepatic fat amounts, anthropometric measures, lipid profile, and other metabolic measures. The availability of the substances discussed makes them a significant adjuvant in the treatment of this disease. The usefulness of Viusid as additional therapy to diet and physical activity should be emphasized due to improvements in liver histology; however, many other substances lead to a decrease in liver fat amounts including, e.g., berberine or omega-3 fatty acids. In addition, the synbiotic Protexin seems to be useful in terms of NAFLD treatment, especially because it is effective in both obese and lean subjects. Based on the latest research results, we suggest revising the therapeutic recommendations for patients suffering from NAFLD.
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Affiliation(s)
- Marcin Kosmalski
- Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
| | - Rafał Frankowski
- Students' Research Club, Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
| | - Kacper Deska
- Students' Research Club, Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
| | | | - Tadeusz Pietras
- Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland
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15
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Wang T, Zhang X, Zhou N, Shen Y, Li B, Chen BE, Li X. Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc 2023; 12:e029512. [PMID: 37264945 PMCID: PMC10381976 DOI: 10.1161/jaha.123.029512] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Accepted: 04/03/2023] [Indexed: 06/03/2023]
Abstract
Background Previous results provide supportive but not conclusive evidence for the use of omega-3 fatty acids to reduce blood lipids and prevent events of atherosclerotic cardiovascular disease, but the strength and shape of dose-response relationships remain elusive. Methods and Results This study included 90 randomized controlled trials, reported an overall sample size of 72 598 participants, and examined the association between omega-3 fatty acid (docosahexaenoic acid, eicosapentaenoic acid, or both) intake and blood lipid changes. Random-effects 1-stage cubic spline regression models were used to study the mean dose-response association between daily omega-3 fatty acid intake and changes in blood lipids. Nonlinear associations were found in general and in most subgroups, depicted as J-shaped dose-response curves for low-/high-density lipoprotein cholesterol. However, we found evidence of an approximately linear dose-response relationship for triglyceride and non-high-density lipoprotein cholesterol among the general population and more evidently in populations with hyperlipidemia and overweight/obesity who were given medium to high doses (>2 g/d). Conclusions This dose-response meta-analysis demonstrates that combined intake of omega-3 fatty acids near linearly lowers triglyceride and non-high-density lipoprotein cholesterol. Triglyceride-lowering effects might provide supportive evidence for omega-3 fatty acid intake to prevent cardiovascular events.
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Affiliation(s)
- Tianjiao Wang
- School of Pharmacy, Faculty of MedicineMacau University of Science and TechnologyMacauChina
| | - Xin Zhang
- School of Pharmacy, Faculty of MedicineMacau University of Science and TechnologyMacauChina
| | - Na Zhou
- School of Pharmacy, Faculty of MedicineMacau University of Science and TechnologyMacauChina
| | - Yuxuan Shen
- Department of Epidemiology and Biostatistics, School of Public HealthJilin UniversityChangchunChina
| | - Biao Li
- Department of Epidemiology and Biostatistics, School of Public HealthJilin UniversityChangchunChina
| | - Bingshu E. Chen
- Department of Public Health Sciences and Canadian Cancer Trials GroupQueen’s UniversityOntarioKingstonCanada
| | - Xinzhi Li
- School of Pharmacy, Faculty of MedicineMacau University of Science and TechnologyMacauChina
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Assessing the Highest Level of Evidence from Randomized Controlled Trials in Omega-3 Research. Nutrients 2023; 15:nu15041001. [PMID: 36839358 PMCID: PMC9959429 DOI: 10.3390/nu15041001] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 02/13/2023] [Accepted: 02/14/2023] [Indexed: 02/19/2023] Open
Abstract
Over the years, there has been heightened interest in the health benefits of n-3 polyunsaturated fatty acids (PUFA) in reducing chronic diseases such as, cardiovascular disease (CVD), cancer, type 2 diabetes, and acute macular degeneration (AMD). Due to inconsistent findings in the evidence, a review to critically examine the plethora of evidence from randomized controlled trials (RCTs) in n-3 PUFA research was undertaken. The aim of this review is to study the highest level of evidence and to identify gaps in n-3 PUFA research. RCTs were originally designed for pharmaceutical research and later adopted for nutrition and food-related research. RCTs with active diseases assume that n-3 PUFA will have "drug" like effects, and this high expectation may have led to the inconsistent evidence in the literature. The inconsistency in the literature may be related to varying doses of n-3 PUFA, sources of n-3 PUFA (food vs. supplement; plant vs. marine), type of n-3 PUFA (mixture vs. purified), trial duration, population characteristics, sample size, and genetic variation. For future research, there is a need to distinguish between primary and secondary prevention, and to focus RCTs on primary prevention of chronic diseases by n-3 PUFA which is lacking in the literature.
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Metabolomics Profiling of Age-Associated Metabolites in Malay Population. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2023; 2023:4416410. [PMID: 36785791 PMCID: PMC9922189 DOI: 10.1155/2023/4416410] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 01/08/2023] [Accepted: 01/19/2023] [Indexed: 02/05/2023]
Abstract
Aging is a complex process characterized by progressive loss of functional abilities due to the accumulation of molecular damages. Metabolomics could offer novel insights into the predictors and mechanisms of aging. This cross-sectional study is aimed at identifying age-associated plasma metabolome in a Malay population. A total of 146 (90 females) healthy participants aged 28-69 were selected for the study. Untargeted metabolomics profiling was performed using liquid chromatography-tandem mass spectrometry. Association analysis was based on the general linear model. Gender-associated metabolites were adjusted for age, while age-associated metabolites were adjusted for gender or analyzed in a gender-stratified manner. Gender-associated metabolites such as 4-hydroxyphenyllactic acid, carnitine, cortisol, and testosterone sulfate showed higher levels in males than females. Deoxycholic acid and hippuric acid were among the metabolites with a positive association with age after being adjusted for gender, while 9(E),11(E)-conjugated linoleic acid, cortisol, and nicotinamide were negatively associated with age. In gender-stratified analysis, glutamine was one of the common metabolites that showed a direct association with age in both genders, while metabolites such as 11-deoxy prostaglandin F2β, guanosine monophosphate, and testosterone sulfate were inversely associated with age in males and females. This study reveals several age-associated metabolites in Malays that could reflect the changes in metabolisms during aging and may be used to discern the risk of geriatric syndromes and disorders later. Further studies are required to determine the interplay between these metabolites and environmental factors on the functional outcomes during aging.
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Coelho-Júnior HJ, Calvani R, Picca A, Savera G, Tosato M, Landi F, Marzetti E. Protein Intake from Various Foods Sources Is Negatively Associated with Cardiometabolic Risk Markers in Italian Older Adults. J Nutr Health Aging 2023; 27:853-860. [PMID: 37960908 DOI: 10.1007/s12603-023-1981-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 06/01/2023] [Indexed: 11/15/2023]
Abstract
OBJECTIVES To examine the relationships between protein intake from various food sources and cardiometabolic risk markers in Italian older adults. DESIGN Cross-sectional study. SETTING Unconventional settings across Italy (e.g., exhibitions, health promotion campaigns). PARTICIPANTS People 65+ years who provided a written informed consent. MEASUREMENTS Blood pressure (BP), blood glucose, total blood cholesterol, and anthropometric indices were assessed. Daily protein intake was estimated for 12 food items listed in a food frequency questionnaire. RESULTS Three-thousand four-hundred twenty-four older adults (mean age: 72.7 ± 5.7 years; 55% women) were included in the study. Results of linear regression analysis indicated that protein intake from several food sources was negatively associated with BP, waist and hip circumferences, and waist-to-hip ratio in both sexes. Blood glucose levels were inversely associated with many protein sources in women. Positive associations were observed between some protein sources and total blood cholesterol in both men and women. CONCLUSION Our findings suggest that dietary protein is differentially associated with cardiometabolic risk factors depending on sex and food sources.
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Affiliation(s)
- H J Coelho-Júnior
- Hélio José Coelho-Júnior, Emanuele Marzetti, Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy, (H.J.C.-J.), (E.M.); +39 (06) 3015-4859
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Jafarirad S, Goodarzi R, Mohammadtaghvaei N, Dastoorpoor M, Alavinejad P. Effectiveness of the pomegranate extract in improving hepatokines and serum biomarkers of non-alcoholic fatty liver disease: A randomized double blind clinical trial. Diabetes Metab Syndr 2023; 17:102693. [PMID: 36535123 DOI: 10.1016/j.dsx.2022.102693] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 12/06/2022] [Accepted: 12/11/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM Pomegranate as a functional food has various properties and effects on health. The aim of the study was to evaluate the effect of pomegranate extract on serum levels of liver enzymes, hepatokines, interleukin-6 (IL-6), and total antioxidant capacity in non-alcoholic fatty liver disease (NAFLD). METHODS In this double-blind randomized clinical trial, 44 patients with NAFLD were divided into two groups: pomegranate extract tablets and placebo. The intervention period was 12 weeks. At the beginning and end of the study, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), fetuin-A, fibroblast growth factor 21 (FGF-21), interleukin-6 (IL-6), and total antioxidant capacity were assessed in both groups. RESULTS Pomegranate extract reduced the level of ALT (P < 0.001), AST (P < 0.001), GGT (P < 0.001), fetuin-A (P < 0.001), FGF-21(P < 0.001) and IL-6 (P = 0.04) compared to the placebo. Pomegranate extract also led to an increase in total antioxidant capacity (P˂0.001) but had no effect on ALP. CONCLUSION It seems that the pomegranate extract improves several markers of NAFLD, and can be useful as a treatment supplement. The clinical trial approved by Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences (grant No. NRC-9811). TRIAL REGISTRATION Iranian Registry of Clinical Trials (IRCT), IRCT20140107016123N14, https://www.irct.ir/trial/42739.
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Affiliation(s)
- Sima Jafarirad
- Nutrition and Metabolic Diseases Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Department of Nutrition, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Reza Goodarzi
- Nutrition and Metabolic Diseases Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Department of Nutrition, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Narges Mohammadtaghvaei
- Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Maryam Dastoorpoor
- Department of Biostatistics and Epidemiology, Menopause Andropause Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Pejman Alavinejad
- Research Institute for Infectious Disease of Digestive System, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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20
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Elisia I, Yeung M, Kowalski S, Wong J, Rafiei H, Dyer RA, Atkar-Khattra S, Lam S, Krystal G. Omega 3 supplementation reduces C-reactive protein, prostaglandin E 2 and the granulocyte/lymphocyte ratio in heavy smokers: An open-label randomized crossover trial. Front Nutr 2022; 9:1051418. [PMID: 36532545 PMCID: PMC9751896 DOI: 10.3389/fnut.2022.1051418] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 11/17/2022] [Indexed: 01/19/2024] Open
Abstract
OBJECTIVES Given the current controversy concerning the efficacy of omega 3 supplements at reducing inflammation, we evaluated the safety and efficacy of omega 3 on reducing inflammation in people with a 6-year lung cancer risk >1.5% and a C reactive protein (CRP) level >2 mg/L in a phase IIa cross-over study. MATERIALS AND METHODS Forty-nine healthy participants ages 55 to 80, who were still smoking or had smoked in the past with ≥30 pack-years smoking history, living in British Columbia, Canada, were randomized in an open-label trial to receive 2.4 g eicosapentaenoic acid (EPA) + 1.2 g docosahexaenoic acid (DHA)/day for 6 months followed by observation for 6 months or observation for 6 months first and then active treatment for the next 6 months. Blood samples were collected over 1 year for measurement of plasma CRP, plasma and red blood cell (RBC) membrane levels of EPA, DHA and other fatty acids, Prostaglandin E2 (PGE2), Leukotriene B4 (LTB4) and an inflammatory marker panel. RESULTS Twenty one participants who began the trial within the active arm completed the trial while 20 participants who started in the control arm completed the study. Taking omega 3 resulted in a significant decrease in plasma CRP and PGE2 but not LTB4 levels. Importantly, the effect size for the primary outcome, CRP values, at the end of the intervention relative to baseline was medium (Cohen's d = 0.56). DHA, but not EPA levels in RBC membranes inversely correlated with PGE2 levels. Omega 3 also led to a significant reduction in granulocytes and an increase in lymphocytes. These high-dose omega 3 supplements were well tolerated, with only minor gastrointestinal symptoms in a subset of participants. CONCLUSION Omega 3 fatty acids taken at 3.6 g/day significantly reduce systemic inflammation with negligible adverse health effects in people who smoke or have smoked and are at high risk of lung cancer.ClinicalTrials.gov, NCT number: NCT03936621.
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Affiliation(s)
- Ingrid Elisia
- The Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, BC, Canada
| | - Michelle Yeung
- The Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, BC, Canada
| | - Sara Kowalski
- The Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, BC, Canada
| | - Jennifer Wong
- The Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, BC, Canada
| | - Hossein Rafiei
- The Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, BC, Canada
| | - Roger A. Dyer
- Analytical Core for Metabolomics and Nutrition, BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Sukhinder Atkar-Khattra
- Department of Integrative Oncology, British Columbia Cancer Research Institute, Vancouver, BC, Canada
| | - Stephen Lam
- Department of Integrative Oncology, British Columbia Cancer Research Institute, Vancouver, BC, Canada
| | - Gerald Krystal
- The Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, BC, Canada
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21
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Abdallah M, Brown L, Provenza J, Tariq R, Gowda S, Singal AK. Safety and efficacy of dyslipidemia treatment in NAFLD patients: a meta-analysis of randomized controlled trials. Ann Hepatol 2022; 27:100738. [PMID: 35781090 DOI: 10.1016/j.aohep.2022.100738] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 06/24/2022] [Accepted: 06/24/2022] [Indexed: 02/07/2023]
Abstract
INTRODUCTION AND OBJECTIVES Practicing physicians often hesitate to use statins and/or other lipid-lowering therapies in NAFLD due to concern for hepatotoxicity. The aim of this study is to examine the safety of lipid lowering therapies in NAFLD patients. MATERIALS AND METHODS Data from randomized control trials (RCT) among NAFLD patients were pooled to examine the effect of lipid-lowering therapies on liver chemistry, lipid profile, and liver histology. Results are reported as the mean difference of the change (pretreatment-posttreatment) between the treatment and control group. RESULTS A total of 21 placebo-controlled RCT on 1900 patients (304 receiving statins, 520 other lipid-lowering therapies, and 61 combinations) were treated for 26 weeks [Interquartile range (IQR): 17.5-52 weeks]. Pooled data showed an improved lipid profile without any worsening of ALT, AST, total bilirubin, or alkaline phosphatase at the end of the treatment period. NAFLD activity score improved with other lipid-lowering agents but not with statins. There was no change in individual components of NAFLD activity score or fibrosis stage. CONCLUSION This meta-analysis of randomized controlled trials examining statins and/or other lipid-lowering therapies in NAFLD patients showed no evidence of worsening liver chemistry. Studies with longer use of lipid-lowering therapies are suggested to examine the benefit of liver histology among patients with NAFLD.
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Affiliation(s)
- Mohamed Abdallah
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, United States
| | - Landon Brown
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
| | - John Provenza
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Raseen Tariq
- Department of Medicine, University of Rochester, NY, United States
| | - Smitha Gowda
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, United States
| | - Ashwani K Singal
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, United States; Division of Transplant Hepatology, Avera Transplant Institute, Sioux Falls, SD, United States.
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22
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Qian Z, Zhang Y, Yang N, Nie H, Yang Z, Luo P, Wei X, Guan Y, Huang Y, Yan J, Ruan L, Zhang C, Zhang L. Close association between lifestyle and circulating FGF21 levels: A systematic review and meta-analysis. Front Endocrinol (Lausanne) 2022; 13:984828. [PMID: 36093108 PMCID: PMC9453313 DOI: 10.3389/fendo.2022.984828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Accepted: 08/03/2022] [Indexed: 11/19/2022] Open
Abstract
Background The impact of lifestyle factors on circulating fibroblast growth factor 21 (cFGF21) remains unclear. We conducted this systematic review and meta-analysis to evaluate the association between lifestyle factors and cFGF21 levels. Methods We included studies that evaluated the effects of different lifestyles on cFGF21 concentration in adults, which included smoking, exercise, diets, alcohol consumption and weight loss. Random effects models or fixed effects models were used for meta-analysis to calculate the standardized mean difference (SMD) and 95% confidence interval according to the heterogeneity among studies. Study quality was assessed using the Newcastle-Ottawa Scale for cohort studies, the Joanna Briggs Institution Checklist for cross-sectional studies, and the PEDro scale for experimental studies. Results A total of 50 studies with 1438 individuals were included. Overall, smoking, a hypercaloric carbohydrate-rich diet, a hypercaloric fat-rich diet, amino acid or protein restriction, excessive fructose intake and alcohol consumption significantly upregulated cFGF21 levels (p<0.05), whereas fish oil intake and calorie restriction with sufficient protein intake significantly decreased cFGF21 (p<0.05). Compared to the preexercise cFGF21 level, the cFGF21 level significantly increased within 3 hours postexercise (p<0.0001), while it significantly decreased in the blood sampled >6 h postexercise (p=0.01). Moreover, higher exercise intensity resulted in higher upregulation of cFGF21 at 1-hour post exercise (p=0.0006). Conclusion FGF21 could serve as a potential biomarker for the assessment of different lifestyle interventions. When it is used for this purpose, a standard study protocol needs to be established, especially taking into consideration the intervention types and the sampling time post-intervention. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021254758, identifier CRD42021254758.
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Affiliation(s)
- Zonghao Qian
- Institute of Gerontology, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Gerontology Center of Hubei Province, Wuhan, China
| | - Yucong Zhang
- Institute of Gerontology, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Gerontology Center of Hubei Province, Wuhan, China
| | - Ni Yang
- Institute of Gerontology, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Gerontology Center of Hubei Province, Wuhan, China
| | - Hao Nie
- Institute of Gerontology, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Gerontology Center of Hubei Province, Wuhan, China
| | - Zhen Yang
- Institute of Gerontology, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Gerontology Center of Hubei Province, Wuhan, China
| | - Pengcheng Luo
- Institute of Gerontology, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Gerontology Center of Hubei Province, Wuhan, China
| | - Xiuxian Wei
- Institute of Gerontology, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Gerontology Center of Hubei Province, Wuhan, China
| | - Yuqi Guan
- Institute of Gerontology, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Gerontology Center of Hubei Province, Wuhan, China
| | - Yi Huang
- Institute of Gerontology, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Gerontology Center of Hubei Province, Wuhan, China
| | - Jinhua Yan
- Institute of Gerontology, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Gerontology Center of Hubei Province, Wuhan, China
| | - Lei Ruan
- Institute of Gerontology, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Gerontology Center of Hubei Province, Wuhan, China
| | - Cuntai Zhang
- Institute of Gerontology, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Gerontology Center of Hubei Province, Wuhan, China
| | - Le Zhang
- Institute of Gerontology, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Gerontology Center of Hubei Province, Wuhan, China
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Mokkala K, Gustafsson J, Vahlberg T, Vreugdenhil ACE, Ding L, Shiri-Sverdlov R, Plat J, Laitinen K. Serum CathepsinD in pregnancy: Relation with metabolic and inflammatory markers and effects of fish oils and probiotics. Nutr Metab Cardiovasc Dis 2022; 32:1292-1300. [PMID: 35304048 DOI: 10.1016/j.numecd.2022.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 02/14/2022] [Accepted: 02/16/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND AND AIMS Elevated circulating levels of CathepsinD (CatD) have been linked to metabolic deviations including liver inflammation. We investigated 1) whether supplementation with probiotics and/or fish oil affects CatD and 2) whether the CatD concentration would associate with gestational diabetes (GDM), low-grade inflammation, lipid metabolism, body fat % and dietary composition. METHODS AND RESULTS Overweight/obese pregnant women (n = 438) were randomized into fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo groups. Fish oil contained 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid and probiotics were Lacticaseibacillusrhamnosus HN001 (formerly Lactobacillusrhamnosus HN001) and Bifidobacteriumanimalis ssp. lactis 420, 1010 colony-forming units each). Serum CatD levels were analysed by ELISA, GlycA and lipid metabolites by NMR, high sensitive C-reactive protein (hsCRP) by immunoassay, and intakes of energy yielding nutrients and n-3 and n-6 fatty acids from food diaries at both early and late pregnancy. GDM was diagnosed by OGTT. CatD concentrations did not differ between the intervention groups or by GDM status. Multivariable linear models revealed that body fat % and GlycA affected CatD differently in healthy women and those with GDM. CONCLUSION The serum CatD concentration of pregnant women was not modified by this dietary intervention. Serum CatD was influenced by two parameters, body fat and low grade inflammation, which were dependent on the woman's GDM status. CLINICAL TRIAL REG. NO: NCT01922791, clinicaltrials.gov (secondary analysis).
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Affiliation(s)
- Kati Mokkala
- Institute of Biomedicine, Integrative Physiology and Pharmacology, University of Turku, Turku, Finland
| | - Johanna Gustafsson
- Institute of Biomedicine, Integrative Physiology and Pharmacology, University of Turku, Turku, Finland
| | - Tero Vahlberg
- Institute of Clinical Medicine, Biostatistics, University of Turku, Turku, Finland
| | - Anita C E Vreugdenhil
- Department of Pediatrics, School of Nutrition and Translation Research in Metabolism (NUTRIM), Maastricht University, 6229 ER, Maastricht, the Netherlands
| | - Lingling Ding
- Department of Molecular Genetics, School of Nutrition and Translation Research in Metabolism (NUTRIM), Maastricht University, 6229 ER, Maastricht, the Netherlands
| | - Ronit Shiri-Sverdlov
- Department of Molecular Genetics, School of Nutrition and Translation Research in Metabolism (NUTRIM), Maastricht University, 6229 ER, Maastricht, the Netherlands
| | - Jogchum Plat
- Department of Nutrition and Movement Sciences, School of Nutrition and Translation Research in Metabolism (NUTRIM), Maastricht University, 6229 ER, Maastricht, the Netherlands
| | - Kirsi Laitinen
- Institute of Biomedicine, Integrative Physiology and Pharmacology, University of Turku, Turku, Finland; Department of Obstetrics and Gynecology, Turku University Hospital, Turku, Finland.
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Do B Vitamins Enhance the Effect of Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Diseases? A Systematic Review of Clinical Trials. Nutrients 2022; 14:nu14081608. [PMID: 35458173 PMCID: PMC9032763 DOI: 10.3390/nu14081608] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 04/07/2022] [Accepted: 04/08/2022] [Indexed: 02/04/2023] Open
Abstract
Studies have suggested that B vitamins or omega-3 polyunsaturated fatty acids (PUFAs) may deter the development of cardiovascular disease (CVD). This systematic review aims to examine whether the combined supplementation of both B vitamins and omega-3 PUFAs could provide additional beneficial effects to prevent CVD beyond the effect of each supplement based on clinical trials published up to December 2021. The overall findings are inconsistent and inconclusive, yet the combined supplementation of these two nutrients may be more effective at reducing plasma homocysteine, triglyceride, and low-density lipoprotein-cholesterol than the individual components. The underlying mechanisms mainly include alleviating endothelial dysfunction, inhibiting atherosclerosis and lesion initiation, reducing oxidative stress, suppressing activation of pro-inflammatory cytokines, regulating endothelial nitric oxide synthase, and interfering with methylation of genes that promote atherogenesis. Although biologically plausible, the existing literature is insufficient to draw any firm conclusion regarding whether B vitamins can further enhance the potential beneficial effects of omega-3 PUFA intake on either primary or secondary prevention of CVD. The inconsistent findings may be largely explained by the methodological challenges. Therefore, well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are warranted.
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An Open-Label Exploratory Clinical Trial Evaluating the Effects of GLS (Coptidis Rhizoma-Evodiae Fructus 2 : 1) on Fibroblast Growth Factor 21 in Patients with Nonalcoholic Fatty Liver Disease. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:4583645. [PMID: 35368766 PMCID: PMC8967510 DOI: 10.1155/2022/4583645] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 02/25/2022] [Accepted: 03/02/2022] [Indexed: 01/24/2023]
Abstract
Methods In a 12-week, open-label, exploratory clinical trial, 126 NAFLD patients were randomly divided into the GLS group (lifestyle intervention plus GLS) or the polyene phosphatidylcholine (PPC) group (lifestyle intervention plus PPC). Random numbers generated by DPS software were used in combination with opaque, sealed envelopes for allocation concealment. At baseline as well as at the end of the study, anthropometric parameters, glucose, lipids, hepatic enzymes, and FGF 21 were measured, with hepatic fat accumulation assessed by ultrasound (US) and US-based controlled attenuation parameter (CAP). Results 119 patients completed the study. Baseline parameters did not significantly differ between the two groups (P > 0.05). Compared with PPC, GLS decreased more significantly in hepatic fat accumulation, body weight index, waist circumference, waist-to-hip ratio, serum glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, and FGF 21 (P < 0.05). The effects of GLS on waist circumference, waist-to-hip ratio, CAP, and gamma-glutamyl transferase (GGT) were positively correlated with serum FGF 21 (r = 0.343, 0.342, 0.315, and 0.374, respectively, P < 0.05). The GGT and FGF-21 changes were also confirmed by multiple linear regression analysis (B, 0.777; 95% CI: 0.307–1.247, P < 0.05). Conclusion GLS has a significant hepatoprotective effect on NAFLD patients, causing a decrease in FGF-21 secretion in response to the damage itself.
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Pasupuleti RR, Tsai PC, Ponnusamy VK, Chen NC. Green sample pre-treatment technique coupled with UHPLC-MS/MS for the rapid biomonitoring of dietary poly-unsaturated (omega) fatty acids to predict health risks. CHEMOSPHERE 2022; 291:132685. [PMID: 34743796 DOI: 10.1016/j.chemosphere.2021.132685] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 09/05/2021] [Accepted: 10/23/2021] [Indexed: 06/13/2023]
Abstract
Polyunsaturated fatty acids (PUFAs) consumption indicates beneficial effects on cardiovascular disease (CVD) and physiological processes in humans. However, the inappropriate ratio of omega-(ω)-PUFA levels in human blood is considered as raising the risk of CVD. Therefore, monitoring dietary ω-FAs in human serum is vital for early diagnosis for individuals to predict CVD risk. This work reports a fast green sample pre-treatment protocol for sensitive and simultaneous monitoring of ω-3-FAs and ω-6-FAs in serum by novel in-syringe-based ultrasonication-assisted alkaline hydrolysis coupled with vortex-induced liquid-liquid microextraction (IS-USAH-VI-LLME) technique connected with UHPLC-MS/MS analysis. Factors affecting extraction recoveries of ten ω-PUFAs by the presented method were well-studied. ω-3 and ω-6 PUFAs demonstrated excellent linearities between the concentrations between 0.1-10,000 ng mL-1 with good regression coefficients between 0.9910-0.9997. The detection and quantification limits were between 0.05-0.35 and 0.16-1.07 ng mL-1, demonstrating that the presented method is highly sensitive and versatile. The precision of the technique was <8.2% that deemed acceptable in clinical analysis. Further, the proposed method was applied for ω-PUFAs analysis in human blood samples, and spiked recoveries showed between 80.32-119.34% with <9.82% precision. Results proved that the developed method is green, sensitive, and reliable to simultaneously determine ten ω-PUFAs in human blood samples for clinical diagnosis applications for predicting health hazards.
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Affiliation(s)
- Raghavendra Rao Pasupuleti
- Department of Medicinal and Applied Chemistry, Kaohsiung Medical University (KMU), Kaohsiung City, 807, Taiwan
| | - Pei-Chien Tsai
- Department of Medicinal and Applied Chemistry, Kaohsiung Medical University (KMU), Kaohsiung City, 807, Taiwan
| | - Vinoth Kumar Ponnusamy
- Department of Medicinal and Applied Chemistry, Kaohsiung Medical University (KMU), Kaohsiung City, 807, Taiwan; Research Center for Environmental Medicine, Kaohsiung Medical University (KMU), Kaohsiung City, 807, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital (KMUH), Kaohsiung City, 807, Taiwan; Department of Chemistry, National Sun Yat-sen University (NSYSU), Kaohsiung City, 804, Taiwan; Program of Aquatic Science and Technology, College of Hydrosphere Science, National Kaohsiung University of Science and Technology (NKUST), Kaohsiung City, 811, Taiwan.
| | - Nai-Ching Chen
- Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City, 833, Taiwan.
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Guo XF, Wang C, Yang T, Ma WJ, Zhai J, Zhao T, Xu TC, Li J, Liu H, Sinclair AJ, Li D. Concentrated fish oil ameliorates non-alcoholic fatty liver disease by regulating FGF21-adiponectin axis. Nutrition 2022; 99-100:111659. [DOI: 10.1016/j.nut.2022.111659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 03/14/2022] [Accepted: 03/15/2022] [Indexed: 10/18/2022]
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Guo XF, Wang C, Yang T, Ma WJ, Zhai J, Zhao T, Xu TC, Li J, Liu H, Sinclair AJ, Li D. The effects of fish oil plus vitamin D3 intervention on non-alcoholic fatty liver disease: a randomized controlled trial. Eur J Nutr 2022; 61:1931-1942. [DOI: 10.1007/s00394-021-02772-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 12/03/2021] [Indexed: 01/10/2023]
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Jensen KN, Heijink M, Giera M, Freysdottir J, Hardardottir I. Dietary Fish Oil Increases the Number of CD11b+CD27− NK Cells at the Inflammatory Site and Enhances Key Hallmarks of Resolution of Murine Antigen-Induced Peritonitis. J Inflamm Res 2022; 15:311-324. [PMID: 35058705 PMCID: PMC8765547 DOI: 10.2147/jir.s342399] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 12/01/2021] [Indexed: 12/11/2022] Open
Abstract
Purpose To determine the effects of dietary omega-3 polyunsaturated fatty acids (PUFAs) on recruitment of natural killer (NK) cells and resolution responses in antigen-induced peritonitis in mice. Methods Mice were fed fish oil-enriched or control diets, immunized twice and challenged intraperitoneally with methylated bovine serum albumin. Prior to and at different time-points following inflammation induction, expression of surface molecules on peritoneal cells was determined by flow cytometry, concentration of soluble mediators in peritoneal fluid by ELISA or Luminex, and of lipid mediators by LC-MS/MS, and number of apoptotic cells in mesenteric lymph nodes by TUNEL staining. Results Mice fed the fish oil diet had higher number of CD11b+CD27− NK cells as well as a higher proportion of CD107a+ NK cells in their peritoneum 6 h after inflammation induction than mice fed the control diet. They also had higher numbers of CCR5+ NK cells and higher concentrations of CCL5 and CXCL12. Additionally, a higher fraction of apoptotic neutrophils but lower fraction of CD47+ neutrophils were present in the peritoneum of mice fed the fish oil diet 6 h after inflammation induction and the fish oil fed mice had a shorter resolution interval. They also had lower concentrations of pro-inflammatory mediators but higher concentrations of the anti-inflammatory/pro-resolution mediators TGF-β, IGF-1, and soluble TNF RII, as well as higher ratios of hydroxyeicosapentaenoic acid (HEPE) to hydroxyeicosatetraenoic acid (HETE) than mice fed the control diet. Conclusion The results demonstrate that dietary fish oil increases the number of mature NK cells at the inflamed site in antigen-induced peritonitis and enhances several key hallmarks of resolution of inflammation, casting light on the potential mechanisms involved.
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Affiliation(s)
- Kirstine Nolling Jensen
- Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland
- Department of Immunology, Landspitali – The National University Hospital of Iceland, Reykjavik, Iceland
| | - Marieke Heijink
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands
| | - Martin Giera
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands
| | - Jona Freysdottir
- Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland
- Department of Immunology, Landspitali – The National University Hospital of Iceland, Reykjavik, Iceland
| | - Ingibjorg Hardardottir
- Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland
- Department of Immunology, Landspitali – The National University Hospital of Iceland, Reykjavik, Iceland
- Correspondence: Ingibjorg Hardardottir Tel +354 525 4885 Email
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Cantero I, Abete I, Bullón-Vela V, Crujeiras AB, Casanueva FF, Zulet MA, Martinez JA. Fibroblast growth factor 21 levels and liver inflammatory biomarkers in obese subjects after weight loss. Arch Med Sci 2022; 18:36-44. [PMID: 35154523 PMCID: PMC8826683 DOI: 10.5114/aoms/98948] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 10/14/2018] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION Previous studies have hypothesized fibroblast growth factor 21 (FGF-21) as a potential biomarker of the inflammation associated with liver diseases, which is also receiving considerable attention for its potential application concerning the management of obesity and co-morbidities. This study aimed to analyze the response of FGF-21 after a weight loss intervention and the relationships with other putative inflammatory liver biomarkers. MATERIAL AND METHODS Sixty-six obese participants from the RESMENA study were evaluated at baseline and following a 6-month energy restriction treatment. Anthropometric, body composition by DXA, routine laboratory measurements, which included transaminases and γ-glutamyl transferase (GGT) were analyzed by standardized methods. Moreover, FGF-21, M30 fragment (M30) and plasminogen activator inhibitor-1 (PAI-I) were analyzed as recognized liver inflammatory related biomarkers with specific ELISA kits. RESULTS Most measurements related to hepatic damage, inflammation and adiposity status improved at the end of the 6-month nutritional intervention. In addition, ΔFGF-21 shifts showed statistical relationships with changes in ΔM30, ΔGGT and ΔPAI. The reduction of M30 showed significant associations with changes in transaminases. Furthermore, PAI-I changes were associated with ΔM30 and ΔGGT regardless of weight loss. A linear regression model was set up to assess the influence of ΔPAI-I and ΔM30 on the variability of ΔFGF-21 (23.8%) adjusted by weight loss. CONCLUSIONS These results demonstrated interactions of some liver inflammatory mediators, specifically M30 and PAI-I with FGF-21. Thus, more investigation about FGF-21 is required given that this protein could be a biomarker of the obesity-inflammation-liver process.
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Affiliation(s)
- Irene Cantero
- Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain
- Centre for Nutrition Research, University of Navarra, Pamplona, Spain
| | - Itziar Abete
- Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain
- Centre for Nutrition Research, University of Navarra, Pamplona, Spain
- CIBER in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Spain
- Navarra Institute for Health Research (IdiSNA), Spain
| | - Vanessa Bullón-Vela
- Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain
- Centre for Nutrition Research, University of Navarra, Pamplona, Spain
| | - Ana B. Crujeiras
- CIBER in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Spain
- Laboratory of Molecular Endocrinology and Epigenomics in Endocrinology and Nutrition, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela University (USC), Santiago de Compostela, Spain
| | - Felipe F. Casanueva
- CIBER in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Spain
- Laboratory of Molecular Endocrinology and Epigenomics in Endocrinology and Nutrition, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela University (USC), Santiago de Compostela, Spain
| | - M. Angeles Zulet
- Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain
- Centre for Nutrition Research, University of Navarra, Pamplona, Spain
- CIBER in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Spain
- Navarra Institute for Health Research (IdiSNA), Spain
| | - J. Alfredo Martinez
- Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain
- Centre for Nutrition Research, University of Navarra, Pamplona, Spain
- CIBER in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Spain
- Navarra Institute for Health Research (IdiSNA), Spain
- IMDEA Food, Madrid, Spain
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Kizilaslan N, Zekiye Erdem N, Katar M, Gevrek F. The Effects of Probiotics and Omega-3 Fatty Acids in Liver Steatosis Induced in Rats by High-Fructose Corn Syrup. Int J Clin Pract 2022; 2022:7172492. [PMID: 35685520 PMCID: PMC9159191 DOI: 10.1155/2022/7172492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 12/13/2021] [Indexed: 11/17/2022] Open
Abstract
AIMS This study was designed to reveal the effect of probiotics and omega-3 fatty acids in a fatty liver model in rats induced by high-fructose corn syrup (HFCS). METHODS In the study, 40 male Wistar Albino rats were used, and these rats were divided into five groups. HFCS was added to the drinking water (30% solution) of four groups (Groups 2, 3, 4, and 5) for three weeks, and the animals were fed ad libitum. At the end of three weeks, the rats in Groups 3, 4, and 5 were administered omega-3 fatty acids (400 mg/kg) and probiotics (1.5 × 109 cfu/mL/day) with the gavage method for four weeks. The body weights of rats were weighed and recorded before starting the experiment, at the end of the third week, and before the animals were sacrificed at the last week, all at the same hour. By subtracting the remaining amount of food and water from the daily food and water amount, the amount of food and water consumed was calculated. These values were recorded for seven weeks. At the end of the seven weeks, the rats were sacrificed after blood specimens and tissues were taken. RESULTS Analyzing the changes in the food intake of each group within itself throughout the experiment, it was observed that there was an increase in the food intake in the control group; from the starting week to the last week, the food intake amount of the HFCS group began to decrease particularly after the second week; and it began to decrease after the third week in the groups that were administered probiotics and omega-3 fatty acids. The changes in the sacrifice weights in the HFCS + omega-3 fatty acid, HFCS + probiotic, and HFCS + probiotic + omega-3 fatty acid groups were found to be lower than that in the HFCS group. The maximum levels of glucose, ALT, ALP, serum cholesterol, triglyceride and AST were found to be in the HFCS group. It was determined that the minimum mean steatosis level was in the control group, while the maximum steatosis level was in the HFCS group. CONCLUSIONS As a result, there was a protective effect of probiotic and omega-3 fatty acid.
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Affiliation(s)
- Nildem Kizilaslan
- Tokat Gaziosmanpasa University, Faculty of Health Sciences, Department of Nutrition and Dietetics, Tokat, Turkey
| | - Nihal Zekiye Erdem
- Istanbul Medipol University, School of Health Sciences, Department of Nutrition and Dietetics, Istanbul, Turkey
| | - Muzaffer Katar
- Tokat Gaziosmanpasa University, Faculty of Medicine, Department of Biochemistry, Tokat, Turkey
| | - Fikret Gevrek
- Tokat Gaziosmanpasa University, Faculty of Medicine, Department of Histology, Tokat, Turkey
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Jeyakumar SM, Vajreswari A. Pharmaconutrition strategy to resolve SARS-CoV-2-induced inflammatory cytokine storm in non-alcoholic fatty liver disease: Omega-3 long-chain polyunsaturated fatty acids. World J Clin Cases 2021; 9:9333-9349. [PMID: 34877270 PMCID: PMC8610854 DOI: 10.12998/wjcc.v9.i31.9333] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/18/2021] [Accepted: 08/17/2021] [Indexed: 02/06/2023] Open
Abstract
Inflammation is one of the primary factors associated with the causation and/or progression of several lifestyle disorders, including obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). NAFLD is a spectrum of disorders, and starts with simple steatosis, progresses to non-alcoholic steatohepatitis, and then advances to fibrosis, cirrhosis and finally, hepatocellular carcinoma, due to perpetual cycles of insults caused by inflammation and other cellular stress. Emerging evidence has documented that patients with NAFLD have severe coronavirus disease 2019 (COVID-19), and patients with COVID-19 have a higher liver injury and mortality. Although the exact cause or mechanism is not known, inflammatory cytokine storm is a characteristic feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is known to be associated with higher mortality among COVID-19 patients. Therefore, the COVID-19 pandemic seems to be a major concern in NAFLD patients, who have contracted SARS-CoV-2 infection and develop COVID-19. This is evident in patients at any stage of the NAFLD spectrum, as the inflammatory cytokine storm may cause and/or aggravate the progression or severity of NAFLD. Thus, there is a need for resolution of the inflammatory cytokine storm in these patients. A large body of evidence has demonstrated the efficacy of omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA) in NAFLD conditions, due to their anti-inflammatory, immunomodulatory and anti-viral properties. Therefore, intervention with ω-3 LCPUFA, an effective pharmaconutrient along with the standard treatment for COVID-19 may be useful in the management of the NAFLD spectrum in COVID-19 patients with pre-existing NAFLD conditions by resolving the inflammatory cytokine storm and thereby attenuating its progression. Although there are challenges in implementation, optimistically they can be circumvented and the pharmaconutrition strategy may be potentially helpful in tackling both the pandemics; NAFLD and COVID-19 at least in this subset of patients.
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Affiliation(s)
- Shanmugam M Jeyakumar
- Department of Clinical Pharmacology, ICMR-National Institute for Research in Tuberculosis, Chennai 600031, Tamil Nadu, India
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Herrera Vielma F, Valenzuela R, Videla LA, Zúñiga-Hernández J. N-3 Polyunsaturated Fatty Acids and Their Lipid Mediators as A Potential Immune-Nutritional Intervention: A Molecular and Clinical View in Hepatic Disease and Other Non-Communicable Illnesses. Nutrients 2021; 13:3384. [PMID: 34684386 PMCID: PMC8539469 DOI: 10.3390/nu13103384] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 09/11/2021] [Accepted: 09/14/2021] [Indexed: 02/06/2023] Open
Abstract
In recent years, the beneficial effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) intake on human health has been widely accepted in the field of immunonutrition. Today, we find a diversity of supplements based on n-3 PUFAs and/or minerals, vitamins and other substances. The main objective of this review is to discuss the importance of n-3 PUFAs and their derivatives on immunity and inflammatory status related to liver disease and other non-communicable illnesses. Based on the burden of liver diseases in 2019, more than two million people die from liver pathologies per year worldwide, because it is the organ most exposed to agents such as viruses, toxins and medications. Consequently, research conducted on n-3 PUFAs for liver disease has been gaining prominence with encouraging results, given that these fatty acids have anti-inflammatory and cytoprotective effects. In addition, it has been described that n-3 PUFAs are converted into a novel species of lipid intermediaries, specialized pro-resolving mediators (SPMs). At specific levels, SPMs improve the termination of inflammation as well as the repairing and regeneration of tissues, but they are deregulated in liver disease. Since evidence is still insufficient to carry out pharmacological trials to benefit the resolution of acute inflammation in non-communicable diseases, there remains a call for continuing preclinical and clinical research to better understand SPM actions and outcomes.
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Affiliation(s)
- Francisca Herrera Vielma
- Department of Biomedical Basic Sciences, School of Health Sciences, University of Talca, Talca 3460000, Chile;
| | - Rodrigo Valenzuela
- Department of Nutrition, Faculty of Medicine, University of Chile, Santiago 8380000, Chile;
| | - Luis A. Videla
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Science, Faculty of Medicine, University of Chile, Santiago 8380000, Chile;
| | - Jessica Zúñiga-Hernández
- Department of Biomedical Basic Sciences, School of Health Sciences, University of Talca, Talca 3460000, Chile;
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Komolafe O, Buzzetti E, Linden A, Best LM, Madden AM, Roberts D, Chase TJ, Fritche D, Freeman SC, Cooper NJ, Sutton AJ, Milne EJ, Wright K, Pavlov CS, Davidson BR, Tsochatzis E, Gurusamy KS. Nutritional supplementation for nonalcohol-related fatty liver disease: a network meta-analysis. Cochrane Database Syst Rev 2021; 7:CD013157. [PMID: 34280304 PMCID: PMC8406904 DOI: 10.1002/14651858.cd013157.pub2] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND The prevalence of non-alcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases risks of liver cirrhosis, hepatocellular carcinoma, and the requirement for liver transplantation. Uncertainty surrounds relative benefits and harms of various nutritional supplements in NAFLD. Currently no nutritional supplement is recommended for people with NAFLD. OBJECTIVES • To assess the benefits and harms of different nutritional supplements for treatment of NAFLD through a network meta-analysis • To generate rankings of different nutritional supplements according to their safety and efficacy SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, the World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or status) for people with NAFLD, irrespective of method of diagnosis, age and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS We performed a network meta-analysis with OpenBUGS using Bayesian methods whenever possible and calculated differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios with 95% credible intervals (CrIs) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS We included in the review a total of 202 randomised clinical trials (14,200 participants). Nineteen trials were at low risk of bias. A total of 32 different interventions were compared in these trials. A total of 115 trials (7732 participants) were included in one or more comparisons. The remaining trials did not report any of the outcomes of interest for this review. Follow-up ranged from 1 month to 28 months. The follow-up period in trials that reported clinical outcomes was 2 months to 28 months. During this follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. We did not calculate effect estimates for mortality because of sparse data (zero events for at least one of the groups in the trial). None of the trials reported that they measured overall health-related quality of life using a validated scale. The evidence is very uncertain about effects of interventions on serious adverse events (number of people or number of events). We are very uncertain about effects on adverse events of most of the supplements that we investigated, as the evidence is of very low certainty. However, people taking PUFA (polyunsaturated fatty acid) may be more likely to experience an adverse event than those not receiving an active intervention (network meta-analysis results: OR 4.44, 95% CrI 2.40 to 8.48; low-certainty evidence; 4 trials, 203 participants; direct evidence: OR 4.43, 95% CrI 2.43 to 8.42). People who take other supplements (a category that includes nutritional supplements other than vitamins, fatty acids, phospholipids, and antioxidants) had higher numbers of adverse events than those not receiving an active intervention (network meta-analysis: rate ratio 1.73, 95% CrI 1.26 to 2.41; 6 trials, 291 participants; direct evidence: rate ratio 1.72, 95% CrI 1.25 to 2.40; low-certainty evidence). Data were sparse (zero events in all groups in the trial) for liver transplantation, liver decompensation, and hepatocellular carcinoma. So, we did not perform formal analysis for these outcomes. The evidence is very uncertain about effects of other antioxidants (antioxidants other than vitamins) compared to no active intervention on liver cirrhosis (HR 1.68, 95% CrI 0.23 to 15.10; 1 trial, 99 participants; very low-certainty evidence). The evidence is very uncertain about effects of interventions in any of the remaining comparisons, or data were sparse (with zero events in at least one of the groups), precluding formal calculations of effect estimates. Data were probably because of the very short follow-up period (2 months to 28 months). It takes follow-up of 8 to 28 years to detect differences in mortality between people with NAFLD and the general population. Therefore, it is unlikely that differences in clinical outcomes are noted in trials providing less than 5 to 10 years of follow-up. AUTHORS' CONCLUSIONS The evidence indicates considerable uncertainty about effects of nutritional supplementation compared to no additional intervention on all clinical outcomes for people with non-alcohol-related fatty liver disease. Accordingly, high-quality randomised comparative clinical trials with adequate follow-up are needed. We propose registry-based randomised clinical trials or cohort multiple randomised clinical trials (study design in which multiple interventions are trialed within large longitudinal cohorts of patients to gain efficiencies and align trials more closely to standard clinical practice) comparing interventions such as vitamin E, prebiotics/probiotics/synbiotics, PUFAs, and no nutritional supplementation. The reason for the choice of interventions is the impact of these interventions on indirect outcomes, which may translate to clinical benefit. Outcomes in such trials should be mortality, health-related quality of life, decompensated liver cirrhosis, liver transplantation, and resource utilisation measures including costs of intervention and decreased healthcare utilisation after minimum follow-up of 8 years (to find meaningful differences in clinically important outcomes).
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Affiliation(s)
| | - Elena Buzzetti
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Audrey Linden
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Lawrence Mj Best
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Angela M Madden
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
| | - Danielle Roberts
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Thomas Jg Chase
- Department of General Surgery, Homerton University Hospital NHS Foundation Trust, London, UK
| | | | - Suzanne C Freeman
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Nicola J Cooper
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Alex J Sutton
- Department of Health Sciences, University of Leicester, Leicester, UK
| | | | - Kathy Wright
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Chavdar S Pavlov
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Brian R Davidson
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Emmanuel Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Kurinchi Selvan Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
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Rausch JA, Gillespie S, Orchard T, Tan A, McDaniel JC. Secondary data analysis investigating effects of marine omega-3 fatty acids on circulating levels of leptin and adiponectin in older adults. Prostaglandins Leukot Essent Fatty Acids 2021; 170:102302. [PMID: 34077887 PMCID: PMC9022442 DOI: 10.1016/j.plefa.2021.102302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 05/13/2021] [Accepted: 05/21/2021] [Indexed: 11/12/2022]
Abstract
BACKGROUND Higher leptin and lower adiponectin levels have been linked to progressing systemic inflammation and diseases of aging. Among older adults with obesity and an inflammatory conditions, we quantified effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on leptin, adiponectin, and the leptin-to-adiponectin ratio (LAR). We also examined associations among adipokine and cytokine levels. METHODS Using a randomized, double-blind, placebo-controlled design, participants (mean age 61.3 ± 2.1) received 1.5 g EPA + 1.0 g DHA (n = 14) or mineral oil (n = 18) daily. Plasma adipokine and cytokine levels were quantified by electrochemiluminescence at all study intervals. RESULTS While no between-group differences were detected, there was a reduction in the LAR (by 23%, p=.065) between weeks 4 and 8 among the EPA+DHA group. Adiponectin levels were negatively associated with IL-1β levels at week 4 (p=.02) and TNF-α levels at week 8 (p=.03). CONCLUSION Potential benefits of EPA+DHA supplementation among aging populations warrant further study.
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Affiliation(s)
- J A Rausch
- The Ohio State University, College of Nursing, 1585 Neil Avenue, Columbus, Ohio 43210.
| | - S Gillespie
- The Ohio State University, College of Nursing, 1585 Neil Avenue, Columbus, Ohio 43210
| | - T Orchard
- The Ohio State University, College of Education and Human Ecology, 1585 Neil Avenue, Columbus, Ohio 43210
| | - A Tan
- The Ohio State University, College of Nursing, 1585 Neil Avenue, Columbus, Ohio 43210
| | - J C McDaniel
- The Ohio State University, College of Nursing, 1585 Neil Avenue, Columbus, Ohio 43210
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Beyond the Paradigm of Weight Loss in Non-Alcoholic Fatty Liver Disease: From Pathophysiology to Novel Dietary Approaches. Nutrients 2021; 13:nu13061977. [PMID: 34201382 PMCID: PMC8226973 DOI: 10.3390/nu13061977] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 06/02/2021] [Accepted: 06/07/2021] [Indexed: 12/13/2022] Open
Abstract
Current treatment recommendations for non-alcoholic fatty liver disease (NAFLD) rely heavily on lifestyle interventions. The Mediterranean diet and physical activity, aiming at weight loss, have shown good results in achieving an improvement of this liver disease. However, concerns related to compliance and food accessibility limit the feasibility of this approach, and data on the long-term effects on liver-related outcomes are lacking. Insulin resistance is a central aspect in the pathophysiology of NAFLD; therefore, interventions aiming at the improvement of insulin sensitivity may be preferable. In this literature review, we provide a comprehensive summary of the available evidence on nutritional approaches in the management of NAFLD, involving low-calorie diets, isocaloric diets, and the novel schemes of intermittent fasting. In addition, we explore the harmful role of single nutrients on liver-specific key metabolic pathways, the role of gene susceptibility and microbiota, and behavioral aspects that may impact liver disease and are often underreported in clinical setting. At present, the high variability in terms of study populations and liver-specific outcomes within nutritional studies limits the generalizability of the results and highlights the urgent need of a tailored and standardized approach, as seen in regulatory trials in Non-Alcoholic Steatohepatitis (NASH).
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Sepidarkish M, Rezamand G, Qorbani M, Heydari H, Estêvão MD, Omran D, Morvaridzadeh M, Roffey DM, Farsi F, Ebrahimi S, Shokri F, Heshmati J. Effect of omega-3 fatty acids supplementation on adipokines: a systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr 2021; 62:7561-7575. [PMID: 33998914 DOI: 10.1080/10408398.2021.1915743] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Although a large body of literature reported the beneficial effects of omega-3 fatty acids (omega-3 FAs) consumption on adipokines levels, but recent findings from clinical trials are not univocal. The aim of this systematic review and meta-analysis was to evaluate the effect of omega-3 FAs supplements on adipokines. METHODS We searched Medline, Web of Science, Scopus, Embase, and Cochrane Library from inception to August 2020 without any particular language limitations. Outcomes were summarized as standardized mean difference (SMD) with 95% confidence intervals (CIs) estimated from Hedge's g and random effects modeling. RESULTS Fifty-two trials involving 4,568 participants were included. Omega-3 FAs intake was associated with a significant increase in plasma adiponectin levels (n = 43; 3,434 participants; SMD: 0.21, 95% CI: 0.04, 0.37; p = 0.01; I2= 80.14%). This meta-analysis indicates that supplementing participants with omega-3 fatty acids more than 2000 mg daily and more than 10 weeks resulted in a significant and more favorable improvement in plasma adiponectin levels. However, omega-3 FAs intake had no significant effect on leptin levels (SMD: -0.02, 95% CI: -0.20, 0.17, I2= 54.13%). CONCLUSION The evidence supports a beneficial effect of omega-3 FAs intake on serum adiponectin levels but does not appear to impact on leptin concentrations. Larger well-designed RCTs are still required to evaluate the effect of omega-3 FAs on leptin in specific diseases.
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Affiliation(s)
- Mahdi Sepidarkish
- Department of Biostatistics and Epidemiology, School of Public Health, Babol University of Medical Sciences, Babol, Iran
| | - Gholamreza Rezamand
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mostafa Qorbani
- Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.,Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hafez Heydari
- Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - M Dulce Estêvão
- Universidade do Algarve, Escola Superior de Saúde, Campus de Gambelas, Faro, Portugal
| | - Dalia Omran
- Department of Endemic Medicine and Hepatology, Thabet hospital for Endemic diseases, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mojgan Morvaridzadeh
- Department of Nutritional Science, School of Nutritional Science and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Darren M Roffey
- Vancouver General Hospital, Vancouver Coastal Health, Vancouver, Canada
| | - Farnaz Farsi
- Student Research Committee, Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Sara Ebrahimi
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia
| | - Fatemeh Shokri
- Department of Health Education and Promotion, Iran University of Medical Sciences, Tehran, Iran
| | - Javad Heshmati
- Department of Nutritional Science, School of Nutritional Science and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Rausch J, Gillespie S, Orchard T, Tan A, McDaniel JC. Systematic review of marine-derived omega-3 fatty acid supplementation effects on leptin, adiponectin, and the leptin-to-adiponectin ratio. Nutr Res 2020; 85:135-152. [PMID: 33482602 DOI: 10.1016/j.nutres.2020.11.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 10/22/2020] [Accepted: 11/10/2020] [Indexed: 12/13/2022]
Abstract
Increasing evidence suggests that adipokines, leptin and adiponectin, produced and secreted by adipocytes, are involved in regulating systemic inflammation and may be important targets for interventions to reduce the chronic systemic inflammation linked to some conditions common in aging (e.g., atherosclerosis). Lower leptin levels and higher adiponectin levels in peripheral circulation have been associated with less systemic inflammation. While some studies have shown that marine-derived omega-3 fatty acids (eicosapentaenoic acid [EPA] and/or docosahexaenoic acid [DHA]) have effects on leptin and adiponectin in the context of inflammation, the extent of their effects remain unclear. The purpose of this systematic review was to summarize findings from randomized, controlled trials that measured effects of EPA+DHA supplementation on circulating levels of leptin and adiponectin to determine the state of the science. PubMed, CINAHL, Web of Science, Scopus, and Cochrane Trials were searched up to June 2018 for studies meeting inclusion criteria. Thirty-one studies included in this review were conducted in 16 countries. Eighteen studies reported lower leptin and/or higher adiponectin levels with EPA+DHA supplementation versus placebo at study end point (9 reported statistically significant differences), but doses, supplementation duration, and population characteristics varied across studies. In 9 studies reporting significantly lower leptin and/or higher adiponectin levels the EPA+DHA dose was 0.52 to 4.2 g/day for 4 to 24 weeks. Additional studies are warranted which assess dose parameters and patient populations similar to studies reporting significant effects of EPA+DHA on leptin or adiponectin in order to evaluate the extent of reproducibility before recommending EPA+DHA as a therapy to target these adipokines.
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Affiliation(s)
- Jamie Rausch
- Indiana University Fort Wayne, School of Nursing, Fort Wayne, IN, 46805, USA.
| | | | - Tonya Orchard
- Ohio State University, College of Education and Human Ecology, Columbus, OH, 43210, USA
| | - Alai Tan
- Ohio State University, College of Nursing, Columbus, OH, 43210, USA
| | - Jodi C McDaniel
- Ohio State University, College of Nursing, Columbus, OH, 43210, USA
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Cansanção K, Citelli M, Carvalho Leite N, López de las Hazas MC, Dávalos A, Tavares do Carmo MDG, Peres WAF. Impact of Long-Term Supplementation with Fish Oil in Individuals with Non-Alcoholic Fatty Liver Disease: A Double Blind Randomized Placebo Controlled Clinical Trial. Nutrients 2020; 12:nu12113372. [PMID: 33147705 PMCID: PMC7693661 DOI: 10.3390/nu12113372] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 10/27/2020] [Accepted: 10/30/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic disease affecting up to 25% of the population worldwide. n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) have been associated with improved clinical parameters of NAFLD. Our purpose was to conduct a pilot study to evaluate the effects of n-3 PUFA supplementation in a randomized, double-blind, placebo-controlled clinical study performed on NAFLD individuals diagnosed by ultrasound. Patients received n-3 PUFA (n = 13) or placebo (n = 11) supplementation for six months. Circulating miR-122 expression (determined by quantitative real time-polymerase chain reaction (qRT-PCR), liver fibrosis (FibroScan®), red blood cells (RBC) fatty acids (gas chromatography), and biochemical tests were performed at baseline and after intervention. After the intervention, in the n-3 PUFA group, docosahexaenoic acid (DHA) and omega index increased significantly in RBC (p = 0.022 and p = 0.012, respectively), in addition to a significant reduction in alkaline phosphatase (ALP) (p = 0.002) and liver fibrosis (p = 0.039). However, there was no change in the expression of circulating miR-122 in both groups. Our results showed that omega-3 PUFA were incorporated in erythrocytes after six months of fish oil supplementary intake, and that n-3 PUFA were effective in reducing ALP and liver fibrosis without altering the expression of circulating miR-122 in individuals with NAFLD.
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Affiliation(s)
- Kátia Cansanção
- Institute of Nutrition Josué de Castro of Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21.941-902, Brazil; (K.C.); (M.d.G.T.d.C.)
| | - Marta Citelli
- Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20559-900, Brazil;
| | - Nathalie Carvalho Leite
- Department of Internal Medicine, University Hospital Clementino Fraga Filho, School of Medicine of UFRJ, Rio de Janeiro 21.941-902, Brazil;
| | - María-Carmen López de las Hazas
- Laboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM+CSIC, 28049 Madrid, Spain; (M-C.L.d.l.H.); (A.D.)
| | - Alberto Dávalos
- Laboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM+CSIC, 28049 Madrid, Spain; (M-C.L.d.l.H.); (A.D.)
| | - Maria das Graças Tavares do Carmo
- Institute of Nutrition Josué de Castro of Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21.941-902, Brazil; (K.C.); (M.d.G.T.d.C.)
| | - Wilza Arantes Ferreira Peres
- Institute of Nutrition Josué de Castro of Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21.941-902, Brazil; (K.C.); (M.d.G.T.d.C.)
- Correspondence: ; Tel.: +55-21-393864-32
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Morvaridzadeh M, Fazelian S, Agah S, Khazdouz M, Rahimlou M, Agh F, Potter E, Heshmati S, Heshmati J. Effect of ginger (Zingiber officinale) on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials. Cytokine 2020; 135:155224. [PMID: 32763761 DOI: 10.1016/j.cyto.2020.155224] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 06/10/2020] [Accepted: 07/25/2020] [Indexed: 12/22/2022]
Abstract
The aim of this systematic review and meta-analysis was to investigate the efficacy of ginger supplementation on circulating levels of C-reactive protein (CRP), high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), soluble intercellular adhesion molecule (sICAM), and interleukin-6 (IL-6) concentrations in randomized controlled trials (RCTs). The search included PubMed-Medline, EMBASE, Scopus, Web of Science and Cochrane Library databases to identify randomized clinical trials on the effect of ginger supplementation on circulation levels of CRP, hs-CRP, IL-6, sICAM, and TNF-α published up until February 1st, 2020. We did not restrict articles based on language of publication. Standard mean differences and 95% confidence intervals were calculated for net changes in inflammatory mediators using a random-effects model. Sixteen RCTs comprising 1010 participants were found to be eligible for this meta-analysis. There was a significant reduction of circulating CRP (SMD: -5.11, 95% CI: -7.91, -2.30, I2 = 98.1%), hs-CRP (SMD: -0.88, 95% CI: -1.63, -0.12, I2 = 90.8%) and TNF-α levels (SMD: -0.85, 95% CI: -1.48, -0.21, I2 = 89.4%) following ginger supplementation. However, meta-analysis results did not show any significant impact of ginger supplementation on IL-6 (SMD: -0.45, 95% CI: -1.29, 0.38, I2 = 89.2%), and sICAM levels (SMD: -0.05, 95% CI: -0.36, 0.26, I2 = 00.0%). This systematic review and meta-analysis of RCTs demonstrates a significant impact of ginger in lowering circulating CRP, hs-CRP and TNF-α levels. Large-scale RCTs are still needed to draw concrete conclusions about the effect of ginger on other inflammatory mediators.
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Affiliation(s)
- Mojgan Morvaridzadeh
- Department of Nutritional Science, School of Nutritional Science and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Siavash Fazelian
- Clinical Research Development Unit, Ayatollah Kashani Hospital, Shahrekord University of Medical Sciences, Shahrekord, Iran.
| | - Shahram Agah
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Khazdouz
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Mehran Rahimlou
- Nutrition Department, Faculty of Paramedicine, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran
| | - Fahimeh Agh
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Eric Potter
- Baylor Scott & White Research Institute, Dallas, TX, USA.
| | - Shilan Heshmati
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Javad Heshmati
- Department of Nutritional Science, School of Nutritional Science and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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All-Cause Mortality and Cardiovascular Death between Statins and Omega-3 Supplementation: A Meta-Analysis and Network Meta-Analysis from 55 Randomized Controlled Trials. Nutrients 2020; 12:nu12103203. [PMID: 33092130 PMCID: PMC7590109 DOI: 10.3390/nu12103203] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 10/17/2020] [Accepted: 10/19/2020] [Indexed: 12/14/2022] Open
Abstract
Statins and omega-3 supplementation have shown potential benefits in preventing cardiovascular disease (CVD), but their comparative effects on mortality outcomes, in addition to primary and secondary prevention and mixed population, have not been investigated. This study aimed to examine the effect of statins and omega-3 supplementation and indirectly compare the effects of statin use and omega-3 fatty acids on all-cause mortality and CVD death. We included randomized controlled trials (RCTs) from meta-analyses published until December 2019. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated to indirectly compare the effect of statin use versus omega-3 supplementation in a frequentist network meta-analysis. In total, 55 RCTs were included in the final analysis. Compared with placebo, statins were significantly associated with a decreased the risk of all-cause mortality (RR = 0.90, 95% CI = 0.86–0.94) and CVD death (RR = 0.86, 95% CI = 0.80–0.92), while omega-3 supplementation showed a borderline effect on all-cause mortality (RR = 0.97, 95% CI = 0.94–1.01) but were significantly associated with a reduced risk of CVD death (RR = 0.92, 95% CI = 0.87–0.98) in the meta-analysis. The network meta-analysis found that all-cause mortality was significantly different between statin use and omega-3 supplementation for overall population (RR = 0.91, 95% CI = 0.85–0.98), but borderline for primary prevention and mixed population and nonsignificant for secondary prevention. Furthermore, there were borderline differences between statin use and omega-3 supplementation in CVD death in the total population (RR = 0.92, 95% CI = 0.82–1.04) and primary prevention (RR = 0.85, 95% CI = 0.68–1.05), but nonsignificant differences in secondary prevention (RR = 0.97, 95% CI = 0.66–1.43) and mixed population (RR = 0.92, 95% CI = 0.75–1.14). To summarize, statin use might be associated with a lower risk of all-cause mortality than omega-3 supplementation. Future direct comparisons between statin use and omega-3 supplementation are required to confirm the findings.
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Lee CH, Fu Y, Yang SJ, Chi CC. Effects of Omega-3 Polyunsaturated Fatty Acid Supplementation on Non-Alcoholic Fatty Liver: A Systematic Review and Meta-Analysis. Nutrients 2020; 12:nu12092769. [PMID: 32932796 PMCID: PMC7551292 DOI: 10.3390/nu12092769] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 09/06/2020] [Accepted: 09/08/2020] [Indexed: 02/06/2023] Open
Abstract
(1) Aim: Non-alcoholic fatty liver disease (NAFLD) is a prevalent disease worldwide. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) bear anti-inflammatory action and can ameliorate hyperlipidemia. We wish to appraise the effects of n-3 PUFAs supplement on NAFLD. (2) Methods: We searched CENTRAL, Embase, and MEDLINE on 29 March 2020 for randomized control trials (RCTs) on the effects of n-3 PUFAs supplementation in treating NAFLD. The Cochrane Collaboration's tool was used to assess the risk of bias of included RCTs. (3) Results: We included 22 RCTs with 1366 participants. The risk of bias of included RCTs was generally low or unclear. n-3 PUFAs supplementation significantly reduced liver fat compared with placebo (pooled risk ratio 1.52; 95% confidence interval (CI) 1.09 to 2.13). n-3 PUFAs supplementation also significantly improved the levels of triglyceride, total cholesterol, high-density lipoprotein, and body-mass index, with pooled mean difference and 95% CI being -28.57 (-40.81 to -16.33), -7.82 (-14.86 to -0.79), 3.55 (1.38 to 5.73), and -0.46 (-0.84 to -0.08), respectively. (4) Conclusions: The current evidence supports the effects of n-3 PUFAs supplementation in improving fatty liver. n-3 PUFAs supplementation may also improve blood lipid levels and obesity.
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Affiliation(s)
- Cheng-Han Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan;
| | - Yun Fu
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan;
| | - Shih-Jyun Yang
- Department of Dermatology, Chang Gung Memorial Hospital, Keelung 20401, Taiwan;
| | - Ching-Chi Chi
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan;
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
- Correspondence: ; Tel.: +886-3-328-1200 (ext. 3556)
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Jackson MI, Jewell DE. Docosahexaenoate-enriched fish oil and medium chain triglycerides shape the feline plasma lipidome and synergistically decrease circulating gut microbiome-derived putrefactive postbiotics. PLoS One 2020; 15:e0229868. [PMID: 32163448 PMCID: PMC7067441 DOI: 10.1371/journal.pone.0229868] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 02/15/2020] [Indexed: 12/14/2022] Open
Abstract
The purpose of this study was to examine the influence of medium-chain fatty acid-containing triglycerides (MCT), long-chain polyunsaturated fatty acid-containing triglycerides, and their combination on the plasma metabolome of cats (Felis catus), including circulating microbiome-derived postbiotics. After a 14-day lead-in on the control food, cats were randomized to one of four foods (control, with 6.9% MCT, with fish oil [FO; 0.14% eicosapentaenoate, 1.0% docosahexaenoate], or with FO+MCT; n = 16 per group) for 28 days. Analysis of plasma metabolites showed that the addition of FO and MCT led to synergistic effects not seen with either alone across a number of lipid classes, including fatty acids, acylcarnitines, and acylated amines including endocannabinoids. Notably, the FO+MCT group had an increase in ketone body production relative to baseline and beyond that seen with MCT alone. N-acyl taurines, the accumulation of which has been implicated in the onset of type 2 diabetes, were significantly decreased in the FO+MCT group. Significant decreases in the gut microbiome-derived postbiotic classes of indoles/indolic sulfates and phenols/phenolic sulfates were observed only the FO+MCT group. Overall, the combination of MCT and FO led to number of changes in plasma metabolites that were not observed with either oil alone, particularly in postbiotics.
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Affiliation(s)
- Matthew I. Jackson
- Pet Nutrition Center, Hill’s Pet Nutrition, Inc., Topeka, Kansas, United States of America
- * E-mail:
| | - Dennis E. Jewell
- Pet Nutrition Center, Hill’s Pet Nutrition, Inc., Topeka, Kansas, United States of America
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Musa-Veloso K, Venditti C, Lee HY, Darch M, Floyd S, West S, Simon R. Systematic review and meta-analysis of controlled intervention studies on the effectiveness of long-chain omega-3 fatty acids in patients with nonalcoholic fatty liver disease. Nutr Rev 2019; 76:581-602. [PMID: 29917092 PMCID: PMC6367993 DOI: 10.1093/nutrit/nuy022] [Citation(s) in RCA: 86] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Context Treatment options for nonalcoholic fatty liver disease (NAFLD) are needed. Objective The aim of this review was to systematically assess the effects of omega-3 long-chain
polyunsaturated fatty acids (n-3 LC-PUFAs), particularly eicosapentaenoic acid and
docosahexaenoic acid, on liver-related and metabolic outcomes in adult and pediatric
patients with NAFLD. Data Sources The online information service ProQuest Dialog was used to search 8 literature
databases. Study Selection Controlled intervention studies in which the independent effects of n-3 LC-PUFAs could
be isolated were eligible for inclusion. Data Extraction The 18 unique studies that met the criteria for inclusion were divided into 2 sets, and
data transcriptions and study quality assessments were conducted in duplicate. Each
effect size was expressed as the weighted mean difference and 95%CI, using a
random-effects model and the inverse of the variance as a weighting factor. Results Based on the meta-analyses, supplementation with n-3 LC-PUFAs resulted in statistically
significant improvements in 6 of 13 metabolic risk factors, in levels of 2 of 3 liver
enzymes, in liver fat content (assessed via magnetic resonance imaging/spectroscopy),
and in steatosis score (assessed via ultrasonography). Histological measures of disease
[which were assessed only in patients with nonalcoholic steatohepatitis (NASH)] were
unaffected by n-3 LC-PUFA supplementation. Conclusions Omega-3 LC-PUFAs are useful in the dietary management of patients with NAFLD.
Additional trials are needed to better understand the effects of n-3 LC-PUFAs on
histological outcomes in patients with NASH. Systematic Review Registration PROSPERO CRD42017055951.
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Affiliation(s)
- Kathy Musa-Veloso
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Carolina Venditti
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Han Youl Lee
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Maryse Darch
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Seth Floyd
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Spencer West
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
| | - Ryan Simon
- Intertek Scientific & Regulatory Consultancy, Health, Environmental & Regulatory Services (HERS), Mississauga, Ontario, Canada
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Programming mediated by fatty acids affects uncoupling protein 1 (UCP-1) in brown adipose tissue. Br J Nutr 2019; 120:619-627. [PMID: 30176958 DOI: 10.1017/s0007114518001629] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Brown adipose tissue (BAT) has recently been given more attention for the part it plays in obesity. BAT can generate great amounts of heat through thermogenesis by the activation of uncoupling protein 1 (UCP-1), which can be regulated by many environmental factors such as diet. Moreover, the build-up of BAT relates to maternal nutritional changes during pregnancy and lactation. However, at present, there is a limited number of studies looking at maternal nutrition and BAT development, and it seems that the research trend in this field has been considerably declining since the 1980s. There is much to discover yet about the role of different fatty acids on the development of BAT and the activation of UCP-1 during the fetal and the postnatal periods of life. A better understanding of the impact of nutritional intervention on the epigenetic regulation of BAT could lead to new preventive care for metabolic diseases such as obesity. It is important to know in which circumstances lipids could programme BAT during pregnancy and lactation. The modification of maternal dietary fatty acids, amount and composition, during pregnancy and lactation might be a promising strategy for the prevention of obesity in the offspring and future generations.
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46
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Tang M, Floyd S, Cai H, Zhang M, Yang R, Dang R. The status of ω-3 PUFAs influence chronic unpredicted mild stress-induced metabolic side effects in rats through INSIG/SREBP pathway. Food Funct 2019; 10:4649-4660. [PMID: 31292598 DOI: 10.1039/c9fo00076c] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Metabolic disturbances, including lipid metabolism, bone metabolism, and glycometabolism, are common in depression. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), which are reported to possess antidepressant effect, have also been shown to regulate metabolism. To further clarify the potential link between ω-3 PUFAs and stress-induced metabolic disturbances, metabolic-related parameters including body weight, visceral fat, fatty acid composition and serum parameters, such as serum lipids, free fatty acid (FFA), glucose (GLU), calcium and phosphorus in rats were measured. Moreover, hepatic insulin induced gene (INSIG)/sterol regulatory element binding protein (SREBP) pathway was also investigated. After 5 weeks of chronic unpredicted mild stress (CUMS) administration, rats were induced to a depressive-like state and exhibited decreased serum high-density lipoprotein (HDL-c), body weight and visceral fat, accompanied by altered C18:2n6c and ω-3/ω-6 PUFAs. Supplement of ω-3 PUFAs showed robust antidepressant effects and has beneficial effects on lipid profile. On the contrary, ω-3 PUFAs deficiency induced the visceral fat accumulation and decreased the serum calcium and phosphorus in stressed rats. Additionally, CUMS significantly increased hepatic expressions of SREBP-cleavage activating protein (SCAP)/SREBP-1 and decreased the expression of INSIG-1. This disturbance of SREBPs system is aggravated by ω-3 PUFAs deficiency and alleviated by ω-3 PUFAs supplementation. This study discloses the novel findings that ω-3 PUFAs deficiency will exacerbate the metabolic disturbances in stressed rats. Furthermore, supplementation of ω-3 PUFAs on individuals with a high risk of depression might be an effective way to prevent metabolic disorders accompanied by depression with the involvement of INSIG/SREBP pathway.
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Affiliation(s)
- Mimi Tang
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China.
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Schillemans T, Shi L, Liu X, Åkesson A, Landberg R, Brunius C. Visualization and Interpretation of Multivariate Associations with Disease Risk Markers and Disease Risk-The Triplot. Metabolites 2019; 9:E133. [PMID: 31284606 PMCID: PMC6680952 DOI: 10.3390/metabo9070133] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 07/01/2019] [Accepted: 07/03/2019] [Indexed: 12/31/2022] Open
Abstract
Metabolomics has emerged as a promising technique to understand relationships between environmental factors and health status. Through comprehensive profiling of small molecules in biological samples, metabolomics generates high-dimensional data objectively, reflecting exposures, endogenous responses, and health effects, thereby providing further insights into exposure-disease associations. However, the multivariate nature of metabolomics data contributes to high complexity in analysis and interpretation. Efficient visualization techniques of multivariate data that allow direct interpretation of combined exposures, metabolome, and disease risk, are currently lacking. We have therefore developed the 'triplot' tool, a novel algorithm that simultaneously integrates and displays metabolites through latent variable modeling (e.g., principal component analysis, partial least squares regression, or factor analysis), their correlations with exposures, and their associations with disease risk estimates or intermediate risk factors. This paper illustrates the framework of the 'triplot' using two synthetic datasets that explore associations between dietary intake, plasma metabolome, and incident type 2 diabetes or BMI, an intermediate risk factor for lifestyle-related diseases. Our results demonstrate advantages of triplot over conventional visualization methods in facilitating interpretation in multivariate risk modeling with high-dimensional data. Algorithms, synthetic data, and tutorials are open source and available in the R package 'triplot'.
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Affiliation(s)
- Tessa Schillemans
- Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden
| | - Lin Shi
- Department of Biology and Biological Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden
| | - Xin Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, SE-710049 Xi'an, China
| | - Agneta Åkesson
- Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden
| | - Rikard Landberg
- Department of Biology and Biological Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden
- Department of Public Health and Clinical Medicine, Umeå University, SE-901 87 Umeå, Sweden
| | - Carl Brunius
- Department of Biology and Biological Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.
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Shen W, Weaver AM, Salazar C, Samet JM, Diaz-Sanchez D, Tong H. Validation of a Dietary Questionnaire to Screen Omega-3 Fatty Acids Levels in Healthy Adults. Nutrients 2019; 11:nu11071470. [PMID: 31261632 PMCID: PMC6682879 DOI: 10.3390/nu11071470] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 06/25/2019] [Accepted: 06/26/2019] [Indexed: 01/17/2023] Open
Abstract
To facilitate a clinical observational study to identify healthy volunteers with low (defined as ≤4%) and high (defined as ≥5.5%) omega-3 indices, a dietary questionnaire to rapidly assess habitual dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was developed. This study aimed to determine the validity of this newly developed dietary questionnaire. One hundred and eight volunteers were included and were assessed for habitual dietary intake of EPA and DHA using the questionnaire. The United States Department of Agriculture food products database and nutrition fact label was referenced for calculation. Blood samples were collected for the analysis of fatty acids in whole blood specimens and to derive omega-3 indices. A linear correlation was observed between reported dietary consumption of EPA, DHA, EPA+DHA and the whole blood levels of EPA, DHA, and the omega-3 indices (r = 0.67, 0.62, 0.67, respectively, p < 0.001 for all). The findings also suggested that the questionnaire was substantially better at identifying volunteers with high omega-3 indices (sensitivity 89%, specificity 84%, and agreement 86%) compared to volunteers with low omega-3 indices (sensitivity 100%, specificity 66%, and agreement 42%). In conclusion, this newly developed questionnaire is an efficient tool for the assessment of omega-3 indices in study populations and is particularly effective in identifying individuals with high omega-3 indices.
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Affiliation(s)
- Wan Shen
- Oak Ridge Institute of Science and Education, 100 ORAU Way, Oak Ridge, TN 37830, USA.
- Department of Public and Allied Health, 119 Health and Human Services, Bowling Green State University, Bowling Green, OH 43403, USA.
| | - Anne M Weaver
- Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, 104 Mason Farm Road, Chapel Hill, NC 27514, USA
| | - Claudia Salazar
- Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, 104 Mason Farm Road, Chapel Hill, NC 27514, USA
| | - James M Samet
- Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, 104 Mason Farm Road, Chapel Hill, NC 27514, USA
| | - David Diaz-Sanchez
- Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, 104 Mason Farm Road, Chapel Hill, NC 27514, USA
| | - Haiyan Tong
- Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, 104 Mason Farm Road, Chapel Hill, NC 27514, USA.
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Yang J, Fernández-Galilea M, Martínez-Fernández L, González-Muniesa P, Pérez-Chávez A, Martínez JA, Moreno-Aliaga MJ. Oxidative Stress and Non-Alcoholic Fatty Liver Disease: Effects of Omega-3 Fatty Acid Supplementation. Nutrients 2019; 11:E872. [PMID: 31003450 PMCID: PMC6521137 DOI: 10.3390/nu11040872] [Citation(s) in RCA: 185] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 04/12/2019] [Accepted: 04/15/2019] [Indexed: 02/06/2023] Open
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.
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Affiliation(s)
- Jinchunzi Yang
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
| | - Marta Fernández-Galilea
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain.
| | - Leyre Martínez-Fernández
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
| | - Pedro González-Muniesa
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain.
- CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, 28029 Madrid, Spain.
| | - Adriana Pérez-Chávez
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
| | - J Alfredo Martínez
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain.
- CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, 28029 Madrid, Spain.
| | - Maria J Moreno-Aliaga
- Centre for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
- IDISNA, Navarra's Health Research Institute, 31008 Pamplona, Spain.
- CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, 28029 Madrid, Spain.
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Shojasaadat F, Ayremlou P, Hashemi A, Mehdizadeh A, Zarrin R. A randomized controlled trial comparing effects of a low-energy diet with n-3 polyunsaturated fatty acid supplementation in patients with non-alcoholic fatty liver disease. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2019; 24:21. [PMID: 31007691 PMCID: PMC6450133 DOI: 10.4103/jrms.jrms_282_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/28/2018] [Revised: 08/25/2018] [Accepted: 12/30/2018] [Indexed: 01/06/2023]
Abstract
BACKGROUND Weight loss is the cornerstone of NAFLD management, but weight maintenance is difficult. Some studies have suggested that n-3 polyunsaturated fatty acid (n-3 PUFA) might have beneficial effects in NAFLD. We aim to compare the effects of a low-energy diet with n-3 PUFA supplementation on liver enzymes, body composition, and cardiometabolic risk factors in NAFLD. MATERIALS AND METHODS The study was a randomized controlled trial conducted in Urmia in Iran from October 2016 to May 2017. One hundred and fourteen eligible patients were randomly assigned to one of the three following groups: low-energy diet group, n-3 PUFA supplementation (fish oil) group (1500 mg/d), or control group for 12 weeks. Liver enzymes, lipid profile, insulin resistance, and body composition were assessed before and after the intervention. RESULTS One hundred and four patients completed the study. All groups lost weight, but the reductions were greater in the diet group (-2.97 ± 2.79 kg, P = 0.001). The diet group had significant decreases in fat mass compared to other groups. Insulin resistance, total cholesterol, and low-density lipoprotein cholesterol significantly decreased only in the diet group, and patients who lost weight ≥4% showed significantly larger decreases in serum liver enzymes. N-3 PUFA had no beneficial effects on the study outcomes. CONCLUSION We found that 1500 mg/d n-3 PUFA supplied for 12 weeks, in contrast to 3.40 ± 2.98% weight loss, does not improve liver enzymes, body composition, and cardiometabolic risk factors in NAFLD patients.
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Affiliation(s)
- Fatemeh Shojasaadat
- Department of Nutrition, School of Medicine, Urmia University of Medical Sciences, Food and Beverages Safety Research Center, Urmia, Iran
| | - Parvin Ayremlou
- Urmia Imam Khomeini University Hospital, Urmia University of Medical Sciences, Urmia, Iran
| | - Asad Hashemi
- Department of Gastroenterology and Hepatology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Alireza Mehdizadeh
- Department of Endocrinology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Rasoul Zarrin
- Department of Nutrition, School of Medicine, Urmia University of Medical Sciences, Food and Beverages Safety Research Center, Urmia, Iran
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