June 22, — An estimated one-quarter of adults in the U. have nonalcoholic fatty liver disease NAFLD , an excess of fat in liver cells that can cause chronic inflammation and liver damage, increasing the risk RNA Modification May Protect Against Liver Disease.

July 19, — An RNA modification may offer protection against non-alcoholic fatty liver, a condition that results from a build-up of fat in the liver and can lead to advanced liver disease, according to a new Shipment Tracking for 'Fat Parcels' in the Body.

Numerous diseases are related to Omega-3 and Omega-6 Fatty Acids May Play Opposite Roles in Childhood Asthma. Print Email Share. Trending Topics. Breast Cancer. Child Development.

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AI Discovers That Not Every Fingerprint Is Unique. A 75 gram serving of fatty fish like salmon, sardines, trout, herring and mackerel provide between. Given that red meat is associated with worsening insulin resistance and liver fat storage in NAFLD , it seems advisable to swap some of you red meat intake for these fish options if your goal is to improve liver health.

A different type of omega-3, ALA, has not been as well studied in the world of fatty liver but happens to be found in a few extremely nutritious foods. These include flax, chia and hempseed as well as walnuts and soy-based foods like edamame and tofu. Each of the foods listed above also contain a host of other unique compounds such as the liver-friendly lignans in flax and the flavonoid family isoflavone compounds in soy.

They also all fit and contribute to a style of eating that reduces triglycerides, inflammation and insulin resistance and are exceptional choices to include in a liver friendly diet.

Understanding the protective role of omega-3 fatty acids is only one of a number of nutrition lessons you need to be aware of to help fight back against fatty liver disease. If customized nutrition guidance combined with accountability and support sound like what you need, reach out to discuss working with me 1-on PREVIOUS POST.

Interestingly, our data indicate an additive synergistic effect of Omega-3 supplementation and protective variants of HSD17B13 and MTARC1. Replication of the results in the subgroup of individuals with lipidomic data confirmed this to a large extent, however, for some genetic variants the number of cases was too small to draw a conclusion.

To prevent the lack of significance due to a small sample size, analyzing larger cohorts is recommended, particularly for homozygous minor allele carriers.

One explanation for the hepatoprotective association between Omega-3 intake and liver disease may be that Omega-3 fatty acids improve insulin sensitivity, which is strongly associated with protection against NAFLD In addition, Omega-3 fatty acids may directly affect liver fat metabolism Studies have suggested that Omega-3 fatty acids may increase the breakdown of fat in the liver, leading to a reduction in the accumulation of liver fat, which is consistent with the results of our study Omega-3 fatty acids may also have anti-inflammatory properties, and liver inflammation is a key component in the development and progression of liver diseases The anti-inflammatory, insulin-sensitizing, and lipid-metabolizing effects of Omega-3 fatty acids may contribute to their potential benefits in the prevention of liver diseases, although the exact mechanisms are not fully understood.

This is the largest study to date to demonstrate a primary preventive effect in a prospective and well-characterized cohort. Moreover, gene-dietary interactions have not been studied at a population-based level before and this research may uncover personalized treatment strategies for individuals at risk for metabolic liver diseases.

Deciphering gene-environment interactions in metabolic liver disease holds promise for the development of patient-tailored dietary strategies. Nevertheless, our study has limitations. First, we used ICD diagnoses as outcomes in our study, which were continuously updated.

In spite of this, we confirmed the negative association between Omega-3 supplementation and hepatic steatosis using MRI data. However, we recommend the replication of genetic findings in a larger cohort.

Second, the frequency of Omega-3 intake was not available for analysis except for the statement that it was taken regularly. We attempted to mitigate these limitations by assessing the blood metabolites indicative of Omega-3 use which strongly supports the reported intake Figure 2 , Supplementary Table S2.

Furthermore, Omega-3 supplementation may indicate an overall healthier lifestyle, which could not be entirely excluded. To correct for factors associated with a healthier lifestyle, we included pre-existing conditions, physical activity, dietary factors, other vitamin supplements, and socioeconomic status Table 1.

Moreover, we cannot completely exclude the influence of different cooking oils on Omega-3 serum levels by correcting for dietary factors. In addition, the lack of analysis on specific Omega-3 associated fatty acids such as eicosapentaenoic acid EPA or docosahexaenoic acid DHA is a limitation that should be addressed in cohorts with corresponding data to provide a nuanced understanding of the relationship between Omega-3 fatty acids and liver health.

Bias due to misclassification was minimized by sensitivity analyses with different endpoints Tables 2 — 4. To further mitigate the risk of residual confounding, we performed sensitivity analyses in subgroups in which the association persisted robustly Tables 3 , 4.

Our study raises the question of whether Omega-3 supplementation should be recommended to people at a high risk of liver disease. Supplementation with Omega-3 fatty acids was particularly beneficial for women.

However, these associations need to be confirmed in randomized trials before recommending Omega-3 for protection against liver disease. In conclusion, this study demonstrated the primary preventive associations of Omega-3 supplementation with the development of incident liver disease, which warrants further evaluation in clinical trials.

The studies involving human participants were reviewed and approved by the Northwest Multicenter Research Ethics Committee. MV: conceptualization, methodology, software, formal analysis, writing—original draft, and validation.

KC and ES: resources, writing—review and editing, and validation. KSS, LH, and MR: writing—review and editing. KMS: conceptualization, writing—review and editing, and funding acquisition. CS: conceptualization, software, writing—review and editing, supervision, funding acquisition, and validation.

All authors contributed to the article and approved the submitted version. KMS is supported by the Federal Ministry of Education and Research BMBF and the Ministry of Culture and Science of the German State of North Rhine-Westphalia MKW under the Excellence strategy of the federal government and the Laender.

This research was conducted using the UK Biobank Resource under application number Access to the UK Biobank data was provided by MV and CS. Copyright © , NHS England. All rights reserved.

This work uses data provided by patients and collected by the NHS as part of their care and support. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. NAFLD, Non-alcoholic fatty liver disease; FDA, Food and Drug Administration; EPA, eicosapentaenoic acid; DPA, docosapentaenoic acid; DHA, docosahexaenoic acid; UKB, UK Biobank; ICD, International Classification of Diseases and Related Health Problem; BMI, body mass index; PNPLA3, patatin-like phospholipase domain-containing protein 3; TM6SF2, transmembrane 6 superfamily member 2; HSD17B13, hydroxysteroid beta dehydrogenase; MTARC1, mitochondrial amidoxime reducing component 1; SD, standard deviation; CI, confidence interval; HR, hazard ratio; SNP, single nucleotide polymorphism.

Byrne CD, Targher G. NAFLD: A multisystem disease. J Hepatol. doi: PubMed Abstract CrossRef Full Text Google Scholar. Ratziu V, Bellentani S, Cortez-Pinto H, Day C, Marchesini G. Sahasrabuddhe V, Gunja MZ, Graubard BI, Trabert B, Schwartz LM, Park Y, et al. Nonsteroidal anti-inflammatory drug use, chronic liver disease, and hepatocellular carcinoma.

J Natl Cancer Inst. Noureddin M, Vipani A, Bresee C, Todo T, Kim IK, Alkhouri N, et al. NASH leading cause of liver transplant in women: updated analysis of indications for liver transplant and ethnic and gender variances.

Am J Gastroenterol. Pacifico L, Bonci E, di Martino M, Versacci P, Andreoli G, Silvestri LM, et al. A double-blind, placebo-controlled randomized trial to evaluate the efficacy of docosahexaenoic acid supplementation on hepatic fat and associated cardiovascular risk factors in overweight children with nonalcoholic fatty liver disease.

Nutr Metab Cardiovas Dis. Scorletti E, Bhatia L, Mccormick KG, Clough GF, Nash K, Hodson L, et al. Parker HM, Cohn JS, O'connor HT, Garg ML, Caterson ID, George J, et al.

Effect of fish oil supplementation on hepatic and visceral fat in overweight men: a randomized controlled trial. 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.

Shahidi F, Ambigaipalan P. Omega-3 polyunsaturated fatty acids and their health benefits. Annu Rev Food Sci Technol. Stockwell T, Chikritzhs T, Holder H, Single E, Elena M, Jernigan D, et al. International Guide for Monitoring Alcohol Consumption and Harm. Geneva: World Health Organization.

Google Scholar. Wilman HR, Kelly M, Garratt S, Matthews PM, Milanesi M, Herlihy A, et al. Characterisation of liver fat in the UK Biobank cohort. PLoS ONE. Townsend P. Townsend Deprivation Index. National Database for Primary Care Groups and Trusts. Colchester, UK: UK Data Service.

Li L, Huang Q, Yang L, Zhang R, Gao L, Han X, et al.

The Bonferroni correction was performed to avoid type I error due to multiple testing. We further examined the distribution of Omega-3 intake in patients with lipidomic data and additionally repeated the analyses Supplementary Table S3. Figure 2.

Metabolic profile - visualization of the lipidomic profile of Omega-3 users compared with non-users and distribution of Omega-3 serum levels.

In UKB 40, individuals underwent liver MRIs to determine proton density fat fractions. A total of 31, individuals who received liver MRIs were included in the study. The UKB provided genetic analyses of , individuals. We investigated carriers of known liver-associated variants. Variants examined were patatin-like phospholipase domain-containing protein 3 PNPLA3 rs, transmembrane 6 superfamily member 2 TM6SF2 rs, hydroxysteroid beta dehydrogenase 13 HSD17B13 rs, and mitochondrial amidoxime reducing component 1 MTARC1 rs We examined wildtype, heterozygous, and homozygous minor allele carriers.

The primary outcome was the development of incident liver disease KK77 or a new diagnosis of hepatocellular carcinoma C As a secondary outcome, we replicated the results using multivitamin supplements, vitamin C, or vitamin B Covariates included in the multivariate cox proportional hazards model were age, sex, BMI, ethnicity, diabetes mellitus, hypertension, ischaemic heart disease, dyslipidemia, number of medications taken, as well as intake of insulin, biguanides, statins and aspirin.

We further included nutritional factors with the help of daily vegetable and fruit consumption, and weekly consumption of fish and meat. We determined socioeconomic status using the Townsend Index as a covariate In the multivariate cox proportional hazards model, we considered influencing confounders as covariates.

Results are expressed as mean ± standard deviation ±SD. Statistical analyses and graphical visualization were performed using R version 4. A total of , individuals were included, , participants without intake of Omega-3 non-users and 38, with regular self-reported as daily, weekly, or monthly intake of Omega-3 Omega-3 users Figure 1 , Supplementary Table S2.

First, we validated the reported Omega-3 intake by using lipidomic data Figure 2. Table 1 provides a comparison of the basic characteristics between two groups: those with no Omega-3 intake and those with Omega-3 intake.

Interestingly, patients with Omega-3 took more medications at baseline, but were more active, ate more vegetables and fish, and came from a socioeconomically advantageous background Table 1.

We replicated this association in a subgroup of UKB patients who underwent MRI. Table 2. Omega-3 intake and the development of incident liver disease and hepatocellular carcinoma in individuals without prior liver disease in UKB.

Men with regular Omega-3 intake showed a It is important to consider potential confounding factors, such as other supplements or medications, that may have an impact on the outcome being studied, to improve the accuracy of the results and draw more valid causal inferences.

Therefore, we studied the intake of multivitamins, vitamin C, or vitamin B12 nutritional supplements in the UKB. Vitamin C and vitamin B12 have shown associations with liver health in previous studies 13 — Nevertheless, our results showed no significant benefit for incident liver disease Table 4.

Table 4. Intake of different nutritional supplements and the development of incident liver disease in individuals without prior liver disease in UKB. Common genetic variants in PNPLA3 and TM6SF2 have been shown to increase the risk and severity of NAFLD, whereas single nucleotide polymorphisms SNPs in MTARC1 and HSD17B13 have protective effects 16 — Similar to the results in the general population, Omega-3 intake resulted in a Importantly, this association was not observed in homozygous carriers of the minor allele of PNPLA3 rs In contrast, minor allele carriers of TM6SF2 rs showed no significant risk reduction.

We next analyzed whether Omega-3 supplementation has an additive protective effect on common protective genetic variants. Similar results were obtained for MTARC1 rs, suggesting additive hepatoprotective effects or potential synergistic effects Table 3. Additionally, we repeated the analyses in the smaller subset of patients with measured Omega-3 levels and found comparable results Supplementary Table S3.

Finally, we examined the individuals who received an analysis of the lipidomic data and evaluated the differences between Omega-3 users and non-users in more detail Supplementary Table S3.

Dietary modification is a cornerstone in the treatment of NAFLD. However, research on how targeted dietary interventions can be used for primary prevention is limited. This study aimed to investigate the relationship between Omega-3 fatty acid consumption and the development of liver disease in a large and diverse population-based cohort, including both non-alcoholic and alcoholic liver disease.

We found that regular Omega-3 fatty acid consumption was associated with a significant risk reduction in liver disease development, particularly for non- alcoholic liver disease. Notably, our investigation included a comprehensive analysis of both general and genetic risk factors for liver disease, and we verified the participants' self-reported Omega-3 intake using lipidomic data.

Our findings indicate that regular Omega-3 fatty acid consumption is associated with a significant reduction in the risk of liver disease, particularly NAFLD. This is consistent with previous studies demonstrating the potential benefits of Omega-3 supplementation in treating NAFLD 5 , 8.

We further showed that ICD coded NAFLD was significantly reduced in Omega-3 users. Moreover, a significant reduction in the risk of MRI-confirmed steatosis has been observed. In the UKB, we developed a unique approach to study the interaction between genetics and Omega-3 intake.

Especially for heterozygous PNPLA3 rs minor allele carriers, regular Omega-3 intake showed a benefit. Minor allele carriers of the rare variant TM6SF2 rs, which is harmful to the liver 17 , did not show statistically significant associations, which may have been due to a lack of power.

The HSD17B13 and MTARC1 variants, which have been linked to lower rates of NAFLD 20 , 21 , showed opposite associations. Both heterozygous and homozygous minor allele carriers showed a significant risk reduction for MTARC1 rs and HSD17B13 rs Interestingly, our data indicate an additive synergistic effect of Omega-3 supplementation and protective variants of HSD17B13 and MTARC1.

Replication of the results in the subgroup of individuals with lipidomic data confirmed this to a large extent, however, for some genetic variants the number of cases was too small to draw a conclusion. To prevent the lack of significance due to a small sample size, analyzing larger cohorts is recommended, particularly for homozygous minor allele carriers.

One explanation for the hepatoprotective association between Omega-3 intake and liver disease may be that Omega-3 fatty acids improve insulin sensitivity, which is strongly associated with protection against NAFLD In addition, Omega-3 fatty acids may directly affect liver fat metabolism Studies have suggested that Omega-3 fatty acids may increase the breakdown of fat in the liver, leading to a reduction in the accumulation of liver fat, which is consistent with the results of our study Omega-3 fatty acids may also have anti-inflammatory properties, and liver inflammation is a key component in the development and progression of liver diseases The anti-inflammatory, insulin-sensitizing, and lipid-metabolizing effects of Omega-3 fatty acids may contribute to their potential benefits in the prevention of liver diseases, although the exact mechanisms are not fully understood.

This is the largest study to date to demonstrate a primary preventive effect in a prospective and well-characterized cohort. Moreover, gene-dietary interactions have not been studied at a population-based level before and this research may uncover personalized treatment strategies for individuals at risk for metabolic liver diseases.

Deciphering gene-environment interactions in metabolic liver disease holds promise for the development of patient-tailored dietary strategies. Nevertheless, our study has limitations.

First, we used ICD diagnoses as outcomes in our study, which were continuously updated. In spite of this, we confirmed the negative association between Omega-3 supplementation and hepatic steatosis using MRI data.

However, we recommend the replication of genetic findings in a larger cohort. Second, the frequency of Omega-3 intake was not available for analysis except for the statement that it was taken regularly.

We attempted to mitigate these limitations by assessing the blood metabolites indicative of Omega-3 use which strongly supports the reported intake Figure 2 , Supplementary Table S2.

Furthermore, Omega-3 supplementation may indicate an overall healthier lifestyle, which could not be entirely excluded. To correct for factors associated with a healthier lifestyle, we included pre-existing conditions, physical activity, dietary factors, other vitamin supplements, and socioeconomic status Table 1.

Moreover, we cannot completely exclude the influence of different cooking oils on Omega-3 serum levels by correcting for dietary factors. In addition, the lack of analysis on specific Omega-3 associated fatty acids such as eicosapentaenoic acid EPA or docosahexaenoic acid DHA is a limitation that should be addressed in cohorts with corresponding data to provide a nuanced understanding of the relationship between Omega-3 fatty acids and liver health.

Bias due to misclassification was minimized by sensitivity analyses with different endpoints Tables 2 — 4. To further mitigate the risk of residual confounding, we performed sensitivity analyses in subgroups in which the association persisted robustly Tables 3 , 4. Our study raises the question of whether Omega-3 supplementation should be recommended to people at a high risk of liver disease.

Supplementation with Omega-3 fatty acids was particularly beneficial for women. However, these associations need to be confirmed in randomized trials before recommending Omega-3 for protection against liver disease. In conclusion, this study demonstrated the primary preventive associations of Omega-3 supplementation with the development of incident liver disease, which warrants further evaluation in clinical trials.

The studies involving human participants were reviewed and approved by the Northwest Multicenter Research Ethics Committee. MV: conceptualization, methodology, software, formal analysis, writing—original draft, and validation. KC and ES: resources, writing—review and editing, and validation.

KSS, LH, and MR: writing—review and editing. KMS: conceptualization, writing—review and editing, and funding acquisition. CS: conceptualization, software, writing—review and editing, supervision, funding acquisition, and validation. All authors contributed to the article and approved the submitted version.

KMS is supported by the Federal Ministry of Education and Research BMBF and the Ministry of Culture and Science of the German State of North Rhine-Westphalia MKW under the Excellence strategy of the federal government and the Laender.

This research was conducted using the UK Biobank Resource under application number Access to the UK Biobank data was provided by MV and CS. Copyright © , NHS England. All rights reserved. This work uses data provided by patients and collected by the NHS as part of their care and support. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. NAFLD, Non-alcoholic fatty liver disease; FDA, Food and Drug Administration; EPA, eicosapentaenoic acid; DPA, docosapentaenoic acid; DHA, docosahexaenoic acid; UKB, UK Biobank; ICD, International Classification of Diseases and Related Health Problem; BMI, body mass index; PNPLA3, patatin-like phospholipase domain-containing protein 3; TM6SF2, transmembrane 6 superfamily member 2; HSD17B13, hydroxysteroid beta dehydrogenase; MTARC1, mitochondrial amidoxime reducing component 1; SD, standard deviation; CI, confidence interval; HR, hazard ratio; SNP, single nucleotide polymorphism.

Byrne CD, Targher G. NAFLD: A multisystem disease. J Hepatol. doi: PubMed Abstract CrossRef Full Text Google Scholar. Ratziu V, Bellentani S, Cortez-Pinto H, Day C, Marchesini G.

Sahasrabuddhe V, Gunja MZ, Graubard BI, Trabert B, Schwartz LM, Park Y, et al. Nonsteroidal anti-inflammatory drug use, chronic liver disease, and hepatocellular carcinoma.

J Natl Cancer Inst. Noureddin M, Vipani A, Bresee C, Todo T, Kim IK, Alkhouri N, et al. NASH leading cause of liver transplant in women: updated analysis of indications for liver transplant and ethnic and gender variances.

Am J Gastroenterol. Pacifico L, Bonci E, di Martino M, Versacci P, Andreoli G, Silvestri LM, et al. A double-blind, placebo-controlled randomized trial to evaluate the efficacy of docosahexaenoic acid supplementation on hepatic fat and associated cardiovascular risk factors in overweight children with nonalcoholic fatty liver disease.

Nutr Metab Cardiovas Dis. Scorletti E, Bhatia L, Mccormick KG, Clough GF, Nash K, Hodson L, et al. Parker HM, Cohn JS, O'connor HT, Garg ML, Caterson ID, George J, et al.

Effect of fish oil supplementation on hepatic and visceral fat in overweight men: a randomized controlled trial. 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.

Shahidi F, Ambigaipalan P. The findings, published Wednesday by researchers from Oregon State University OSU in PLOS ONE, offer something that no available drug can accomplish, as millions of people in the developed world try, and fail, to sustain weight loss or eat an optimal diet.

Supplements of docosahexaenoic acid DHA , one of the most critically important of the omega 3 fatty acids, were shown to stop the progression of nonalcoholic steatohepatitis NASH , into more serious and life-threatening health problems such as cirrhosis or liver cancer.

Characterized by liver inflammation, oxidative stress and fibrosis, NASH is a substantial risk factor for cirrhosis and liver cancer. It is predicted to be the leading cause of liver transplants by , and the U.

Food and Drug Administration FDA currently has no approved medical treatments for it. Based in large part on consuming the "western diet," one that is high in fat, sugar and cholesterol, nearly 80 million adults and 13 million children in the United States are obese, and about 30 percent of the nation's population is estimated to have some form of chronic fatty liver disease.

Over one year study period, cirrhosis and liver-related deaths occurred in 20 percent and 12 percent of NASH patients, respectively. And when humans with NASH are examined, they have very low levels of omega 3 fatty acids. When those levels are raised, the disease progression stops.

Omega 3 fatty acids regulate important biological pathways, including fatty acid synthesis, oxidation, and breakdown of triglycerides, or fats in the blood.

DHA appears to be one of the most significant of the omega 3 fatty acids, and plays a role in repairing liver damage. The highest levels of DHA are found in oily fish such as salmon, mackerel, tuna and sardines, and to a much lesser extent in some foods such as poultry, liver, egg yolks, and some types of algae.

It is increasingly being included in some prenatal vitamin and mineral formulas because of studies showing its critical importance to a developing fetus. DHA is a readily available supplement and safe to use. Referring to the use of DHA supplementation to address problems with NASH, the researchers said in their study that "this scenario will likely be used clinically since patient compliance to low-fat, low-sucrose dietary recommendations has historically been poor.

The current medical approach to NASH is based on lifestyle management, including diet and exercise. If successful and sustained, research indicates such approaches can completely reverse liver damage.

However, in this study researchers noted that "this treatment, while ideal for clinical use, is likely not sustainable in NASH patients due to poor compliance.