Omega-3 polyunsaturated fatty acids and cancer: lessons learned from clinical trials

Nabavi, Seyed Fazel; Bilotto, Stefania; Russo, Gian Luigi; Orhan, İlkay Erdoğan; Habtemariam, Solomon; Daglia, Maria; Devi, Kasi Pandima; Loizzo, Monica Rosa; Tundis, Rosa; Nabavi, Seyed Mohammad

doi:10.1007/s10555-015-9572-2

Cited by 139 publications

(93 citation statements)

References 259 publications

(269 reference statements)

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“…32,41 A tendency to prolonged survival through V3FA was observed in all 4 settings (HFD vs CD, injection before vs after treatment) we tested, indicating that V3FA may be beneficial, but certainly not harmful, with regard to CRLM. The largest effect on survival was seen when cancer cells were injected before treatment, thus when the early CRLM development was fully exposed to V3FA.…”

Section: Discussionmentioning

confidence: 82%

Omega-3 Fatty Acids Protect Fatty and Lean Mouse Livers After Major Hepatectomy

et al. 2017

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Objective: The aim of this study was to assess the effect of V3 fatty acids (V3FA) on fatty and lean liver in hepatic surgery. Background: The global spread of energy-dense diets has led to an endemic rise in fatty liver disease and obesity. Besides metabolic pathologies, steatosis enhances hepatic sensitivity to ischemia reperfusion (I/R) and impedes liver regeneration (LR). Steatosis limits the application of liver surgery, still the main curative option for liver cancer. V3FA are known to reverse steatosis, but how these lipids affect key factors defining surgical outcomes-that is, I/R, LR, and liver malignancy-is less clear. Methods: We established a standardized mouse model of high fat diet (HFD)-induced steatosis followed by V3FA treatment and the subsequent assessment of V3FA effects on I/R, LR, and liver malignancy (n ¼ 5/group), the latter through a syngeneic metastasis approach. Fatty liver outcomes were compared with lean liver to assess steatosis-independent effects. Nonparametric statistics were applied. Results: V3FA reversed HFD-induced steatosis and markedly protected against I/R, improved LR, and prolonged survival of tumor-laden mice. Remarkably, these beneficial effects were also observed in lean liver, albeit at a smaller scale. Notably, mice with metastases in fatty versus lean livers were associated with improved survival. Conclusions: V3FA revealed multiple beneficial effects in fatty and lean livers in mice. The improvements in I/R injury, regenerative capacity, and oncological outcomes await confirmatory studies in humans.

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Section: Discussionmentioning

confidence: 82%

Omega-3 Fatty Acids Protect Fatty and Lean Mouse Livers After Major Hepatectomy

et al. 2017

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“…ω‐3 PUFAs are reported to have protective effects on cells in many common disease, such as cardiovascular diseases, metabolic diseases, and cancers; many potential mechanisms have been proposed . We analysed the target genes of the 12 differentially expressed miRNAs to further explore the effects of ω‐3 PUFAs.…”

Section: Resultsmentioning

confidence: 99%

Modulation of apoptosis‐related microRNAs following myocardial infarction in fat‐1 transgenic mice vs wild‐type mice

Chen

Sang

et al. 2018

J Cellular Molecular Medi

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BackgroundmicroRNAs (miRNAs) post‐transcriptionally regulate cardiac repair following myocardial infarction (MI). Omega‐3 polyunsaturated fatty acid (ω‐3 PUFAs) may support cardiac healing after MI, but the mechanism is unclear.MethodsThe fat‐1 transgenic mouse expresses a ω‐3 fatty acid desaturase which converts ω‐6 PUFAs to ω‐3 PUFAs in vivo. MI was induced in fat‐1 transgenic (n = 30) and wild‐type (WT) mice (n = 30) using permanent ligation. Other transgenic and WT mice underwent sham procedure (n = 30 and n = 30, respectively). One week after occlusion, cardiac function was measured by echocardiography and the infarct size was assessed using histology and miRNA microarray profiling. Expression of selected miRNA was confirmed using quantitative real‐time PCR.ResultsOne week following MI, the fat‐1 transgenic myocardium had better cardiac function, a smaller fibrotic area, and fewer apoptotic cardiomyocytes than WT myocardium. Post‐MI profiling showed 33 miRNAs that were significantly up‐regulated, and 35 were down‐regulated, in fat‐1 group compared to the WT group (n = 3 and n = 2 mice, respectively). Among selected apoptosis‐associated miRNAs, 9 miRNAs were up‐regulated (miR‐101a‐3p, miR‐128‐3p,miR‐133a‐5p,miR‐149‐5p,miR‐192‐5p,miR‐1a‐3p,miR‐208a‐3p,miR‐29c‐5p,miR‐30c‐2‐3p), and 3 were down‐regulated (miR‐210‐3p,miR‐21a‐3p,miR‐214‐3p) in fat‐1 transgenic mice compared with WT mice. Kyoto encyclopaedia of genes and genomes (KEGG) pathway analysis indicated likely roles for these miRNAs in MI. Furthermore, Bcl‐2 expression was increased, and caspase‐3 decreased, in infarcted fat‐1 transgenic mouse hearts compared to WT hearts.Conclusionsω‐3 PUFAs may have a protective effect on cardiomyocytes following MI through their modulation of apoptosis‐related miRNAs and target genes.

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“…Multiple health benefits have been claimed for these long-chain omega-3 PUFAs, including secondary prevention of ischaemic heart disease,2 treatment of rheumatoid arthritis3 and anticancer activity,4 some of which are supported by evidence from randomised trials 5 6…”

Section: Introductionmentioning

confidence: 99%

A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota

Watson

Mitra

Croden

et al. 2017

Gut

374

238

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ObjectiveOmega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22).DesignA randomised, open-label, cross-over trial of 8 weeks’ treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week ‘washout’ period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry.ResultsBoth omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects.ConclusionOmega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure.Trial registration numberISRCTN18662143.

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Omega-3 polyunsaturated fatty acids and cancer: lessons learned from clinical trials

Cited by 139 publications

References 259 publications

Omega-3 Fatty Acids Protect Fatty and Lean Mouse Livers After Major Hepatectomy

Omega-3 Fatty Acids Protect Fatty and Lean Mouse Livers After Major Hepatectomy

Modulation of apoptosis‐related microRNAs following myocardial infarction in fat‐1 transgenic mice vs wild‐type mice

A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota

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