Table 2.

Summary of the researches from the last ten years that have studied the effect of the combination between polyphenols and fish oils for improving neurodegenerative pathologies, cancer, and other health effects.

Bioactive	Dose	Model	Health Effects of the Combination	Reference
Neurodegenerative Diseases
In vitro studies
EPA, Lyc-O-mato, carnosic acid, and lutein.	0.125 µM EPA, 0.1 µM Lyc-O-mato, 0.2 µM carnosic acid and 0.2 µM lutein.	BV-2 immortalized murine microglial cell line.	Synergistic inhibition of the production of proinflammatory mediators: Inhibition redox-sensitive NF-κB activation; Inhibition of superoxide production; Upregulation COX-2 and iNOS; More release of PGE2 and NO; Attenuation IL-6 and CD40.	[68]
Polyphenols (resveratrol, quercetin, and apigenin), omega-3 and omega-9 fatty acids (α-ALA, EPA, DHA, and OA) and α-tocopherol.	Polyphenols: 1.5 to 6.25 µM; Fatty acids: 6.25 to 50 µM. α-Tocopherol: 400 µM.	N2a Neuronal cells.	Cytoprotective against 7-Ketocholesterol-induced neurotoxicity.	[69]
In vivo studies
Resveratrol and DHA.	50 mg/kg/day of each supplement (alone and combined); 6 weeks.	Adult C57Bl/6 mice.	Modulation of steroid hormone biosynthesis, JAK-STAT signaling pathway, ribosome, graft-versus-host disease pathways in the hippocampus; Decreased IL-6 and Apolipoprotien E (ApoE) expression.	[70]
LMN diet rich in polyphenols and PUFAs.	LMN diet; 5 months.	Tg2576 male and female mice as a model of AD.	Delays the Aβ plaque formation and decreases Aβ1–40 and Aβ1–42 plasma levels in adult mice.	[71]
LMN diet rich in polyphenols and PUFAs.	LMN diet; 10, 20, 30, or 40 days.	129S1/SvImJ adult male mice.	Enhancement of cholinergic and catecholaminergic transmissions; Nrf2 activation and increased protein levels of SOD-1 and GPx.	[72]
Resveratrol, prebiotic fiber, and DHA.	Resveratrol 50 mg/L drinking water; DHA and prebiotics in powdered food (100 g of prebiotic, 300 g of DHA, and 600 g of standard diet per 1 kg of food); Administration from post-natal day 21 to 43.	Adolescent male and female Sprague–Dawley rats suffering from mild traumatic brain injury.	Modify premorbid characteristics Prevented injury-related deficits in longer-term behavior measures, medial prefrontal cortex spine density, and levels of Aqp4, Gfap, Igf1, Nfl, and Sirt1 expression in the prefrontal cortex.	[73]
Multivitamins, zinc, polyphenols, omega-3 fatty acids, and probiotics.	Bioactive mixture for 2 two weeks; 48 days.	Crickets.	A combination of multivitamins, zinc, and omega-3 fatty acids was the most effective for improving memory and cognitive performance.	[74]
Human studies
Smartfish® (omega-3 EPA and DHA, and resveratrol, vitamin D, and whey protein).	200 mL/day Smartfish® drink containing 1000 mg DHA, 1000 mg EPA, pomegranate and chokeberry, 10 mg vitamin D3 and resveratrol, whey protein, fiber, and fruit juice; 4–17 months.	Patients with minor cognitive impairment (MCI), with pre-MCI, or with Alzheimer disease (AD).	Increase amyloid-β phagocytosis and resolvin D1 in patients with MCI.	[75]
Smartfish® (omega-3 EPA and DHA, and resveratrol, vitamin D, and whey protein).	200 mL/day Smartfish® drink containing 1500 mg DHA and 1500 mg EPA, 10 μg vitamin D3, 150 mg resveratrol, and 8 g whey protein isolate; 6 months.	Older adults (68–83 years) without any specific pathology.	Limited beneficial effects improving cognitive function.	[76]
NEWSUP (high in plant polyphenols and omega-3 fatty acids, high fortification of micronutrients, and high protein content).	NEWSUP; 23 weeks.	Children aged 15 months to 7 years; primary population: children younger than 4.	Increased working memory, hemoglobin concentration among children with anemia, decreased body mass index z score gainm, and increased lean tissue accretion with less fat; Increased index of cerebral blood flow (CBFi).	[77]
Cancer
In vivo studies
Curcumin and fish oil.	1% (w/w) curcumin; 4% (w/w) menhaden fish oil; 3 weeks nutraceutical supplementation + genotoxic carcinogen injections + 17 weeks.	Lgr5-EGFP-IREScreERT2 knock-in mice.	Only fish oils + curcumin reduced nuclear β-catenin in aberrant crypt foci and synergistically increased targeted apoptosis in DNA damaged Lgr5+ stem cells; Only fish oils + curcumin up-regulated p53 signaling in Lgr5+ stem cells from mice exposed to a carcinogen.	[78]
Human studies
PureVida™ (EPA/DHA/hydroxytyrosol/curcumin).	3 capsules of PureVida™/day; Each capsule: 460 mg of fish oil (EPA and DHA), 125 mg of Hytolive® powder (12.5 mg of natural hydroxytyrosol), and 50 mg extract of curcumin (47.5 mg curcuminoids); 1 month.	Post-menopausal breast cancer patients.	Decrease in CRP; Reduction of pain from aromatase inhibitors of hormonal therapies.	[79]
Mediterranean diet.	Mediterranean-type dietary pattern; Population-based case–control study; January 2015 to December 2016; Catania, Italy.	Prostate cancer (PCa) cases and controls.	High adherence to diet inversely associated with the likelihood of prostate cancer: PCa cases consume a lower amount of vegetables, legumes, and fish.	[80]
Exercise and physical activity
In vivo studies
Fish oil and curcumin.	5% fish oil (EPA: 13.2%; DHA: 8.6%; DPA: 4.9%), 1% curcumin in diet; 10 days supplement + 7 day hindlimb unloading.	C57BI/6 mice.	Decreased loss of muscle cross-sectional area; An enhanced abundance of HSP70 and anabolic signaling (Akt phosphorylation, p70S6K phosphorylation) while reducing Nox2.	[81]
Human studies
Beverages based on almonds and olive oil and enriched with α-tocopherol and DHA.	1 L daily supplementation of almond and olive oil and α-tocopherol based beverage enriched with a DHA functional beverage five days a week; 5 weeks.	Young/senior male athletes.	Increased PUFAs and reduced SFAs in plasma; Increased DHA in erythrocyte; Increased blood cell polyphenol concentration in senior athletes; Protects against oxidative damage but enhances nitrative damage in young athletes; Gene expression of antioxidant enzymes in peripheral blood mononuclear cells after exercise in young athletes (GPx, CAT, and Cu–Zn SOD).	[82]
Beverages based on almonds and olive oil and enriched with α-tocopherol and DHA.	1 L daily supplementation of almond and olive oil and α-tocopherol based beverage enriched with a DHA functional beverage five days a week; 5 weeks.	Young/senior male athletes.	Increased TNFα levels depending on age and exercise;Attenuated the increase in plasma NEFAs, sICAM3 and sL-Selectin induced by exercise; Exercise increased PGE2 plasma levels in supplemented young athletes; Exercise increased NFkβ-activated levels in PBMCs mainly in supplemented young athletes.	[83]
Antioxidant/anti-inflammatory cocktail (polyphenols, vitamin E, selenium, and omega-3).	Daily antioxidant/anti-inflammatory cocktail (741 mg of polyphenols, 138 mg of vitamin E, 80 μg of selenium, and 2.1 g of omega-3); 60 days of hypoactivity.	Healthy, active male subjects.	Ineffectiveness regarding oxidative muscle damage, mitochondrial content, and protein balance and a disturbance of essential signaling pathways (protein balance and mitochondriogenesis) during the remobilization period.	[84]
Age-related eye disease
In vitro studies
Resvega (30 mg of trans resveratrol and 665 mg of omega-3 EPA and DHA, among other nutrients).	288 ng of Resvega (30 mg of trans resveratrol and 665 mg of omega-3, among other nutrients); 48 h.	ARPE-19 cells.	Induced autophagy by increased autolysosome formation and autophagy flux; Change p62 and LC3 protein levels; Cytoprotection under proteasome inhibition	[85]
In vivo studies
Resvega (30 mg of trans resveratrol and 665 mg of omega-3, among other nutrients).	100 µL of Resvega once a day; 38 days.	C57BL6/J mice.	Less vascular endothelial growth factor (VEGF) protein expression levels and less MMP-9 activity; Mitigate choroidal neovascularization and retinal disease.	[86]
Others
Dermatologic food (EPA + DHA + polyphenols).	Dermatologic food; 8 weeks.	Adult atopic dog.	Reductions in clinical scores of atopic dermatitis.	[87]
Olive oil polyphenols and fish oil.	Prospective birth cohort Assessment of Lifestyle and Allergic Disease During INfancy (ALADDIN) Families recruited: September 2004–November 2007; Stockholm area, Sweden.	Placentas.	Altered histone acetylation in placentas.	[88]
Omega-3 fatty acids, and polyphenols, fiber.	Mother–neonate pairs from the prospective and observational MAMI birth cohort. Recruited: 2015–2017 Spanish–Mediterranean area; 18 months.	Gut microbiota from mother–neonate pairs.	Higher abundance of the Ruminococcus species in maternal gut microbiota; Higher relative abundance of Faecalibacterium prausnitzii considered as a biomarker of colonic health, associated with anti-inflammatory properties; Modulation of neonatal microbiota.	[89]