Advances in Technologies for Highly Active Omega-3 Fatty Acids from Krill Oil: Clinical Applications
Abstract
:1. Introduction
2. Krill Oil Composition
2.1. Lipid Fraction
2.2. Fatty Acid Composition
2.3. Astaxanthin
2.4. Sterols
2.5. Vitamins
2.6. Flavonoids
2.7. Minerals
3. Mechanism of Action
4. Krill Oil Extraction Technologies
4.1. Conventional Extraction Techniques
4.2. Unconventional Extraction Techniques
5. Bioavailability and Bioaccessibility of Krill Oil Omega-3
6. Krill and Metabolic Disorders
7. Krill and Inflammatory Bowel Diseases and Gut Microbiota
8. Inflammation
Arthritic Diseases
9. Neuroprotection
9.1. Neurodegeneration and Alzheimer Disease
9.2. Depression
10. Cancer
11. Exercise Performance
12. Discussion and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Krill Sample | Polar Lipids | Monoacylglycerols | Diacylglycerols | Sterols | Free Fatty Acids | Triacyl Glycerols | Ref. |
---|---|---|---|---|---|---|---|
Euphausia superba in South Georgia | 41.25 | 1.4 | 0.43 | 16.17 | 14.36 | 21.50 | [19] |
Euphausia superba in Gerlache Strait | 44 | 0.9 | 3.6 | 1.4 | 8.5 | 40.4 | [16] |
Euphausia superba in Scotia Sea | 45.7 | 0.4 | 1.3 | 1.7 | 16.1 | 33.3 | [27] |
Euphausia superba US AMLR Elephant Islands | ND | 66–72 | ND | 4–6 | 1.1–1.8 | 22–38.4 | [16] |
Euphausia superba US AMLR Elephant Islands Extracted with ethanol | 69.8 | ND | ND | 1.1 | 28.5 | 0.6 | [28] |
Euphausia superba US AMLR Elephant Islands Extracted with hexane | 48.6 | ND | ND | 0.6 | 13.5 | 37.6 | [29] |
Krill oil from Aker BioMarine | 80.7 | ND | 0.93 | 2.8 | 3.46 | 11.85 | [30] |
Fatty Acid | Krill |
---|---|
C14:0 Myristic acid | 5.0–13.0 |
C16:0 Palmitic acid | 17.0–24.6 |
C16:1 (n-7) Palmitoleic acid | 2.5–9.0 |
C18:1 (n-7) Cis-11-octadecenoic acid | 4.7–8.1 |
C18:1 (n-9) Elaidic acid | 6.0–14.5 |
C18:2 (n-6) Linoleic acid | ND–3.0 |
C18:3 (n-3) Alpha linolenic acid | 0.1–4.7 |
C20:5 (n-3) Eicosapentaenoic acid | 14.3–28.0 |
C22:5 (n-3) Docosapentaenoic Acid | ND–0.07 |
C22:6 (n-3) Docosahexaenoic acid (DHA) | 7.1–15.7 |
Classification of Health Benefits | Model | Diets | Duration of Supplementation | Outcomes | References |
---|---|---|---|---|---|
Metabolic disorders | Sprague Dawley rats HFD | 100 and 200 g/krill oil (KO) | 2 weeks | ↓ serum lipid levels | [104] |
HFD mice | 1.25–2.5–5% KO | 8 weeks | ↓ liver TGs, cholesterol and serum cholesterol and glucose | [105] | |
hTNFα over-expressing mice | Krill powder (4.3% of proteins) | 8 weeks | ↓ liver and plasma TGs, hepatic expression SREBP2, ↑ β-oxidation, ↓ inflammation | [106] | |
LDLR-KO mice fed with a western diet + Pacific krill | 8-HEPE (100 mg/kg) | 18 weeks | ↓ plasma LDL and total cholesterol, ↑ HDL, ↓ hepatic TG levels | [107] | |
Dyslipidemic and diabetic non-human primates | 150 mg/Kg/day | ↓ plasma total and LDL-cholesterol, and TGs, ↑ HDL-cholesterol | [108] | ||
C57BL/6J mice fed with HFD | 5% krill powder | 12 weeks | ↓ body weight gain, the fat accumulation in tissue adipose and liver, ↓ serum LDL, ↑ glucose tolerance. ↓ oxidative damage in liver | [114] | |
Rats HFD | 2.5% krill | 12 weeks | ↓ body weight gain | [109] | |
Obesity model in castrated New Zealand white rabbits | 600 mg/day | 8 weeks | ↑ insulin sensitivity and secretion, ↓ fasting blood glucose | [110] | |
HFD combined with thermoneutral animal housing | KO (containing EPA ~13%, DHA ~8%) | 24 weeks | ↓ liver steatosis | [152] | |
Randomized controlled study on 36 individuals | 4 g/day | 8 weeks | ↑ EPA, DHA and DPA in krill group | [111] | |
Human with borderline or high TG levels | 0.5, 1, 2, or 4 g/day for | 6 and 12 weeks | ↓ plasma TGs | [112] | |
Randomized cross-over clinical trial on 25 moderately hyperTGmic subjects | 1000 mg/day | 4 weeks | ↑ plasma HDL and apolipoprotein AI levels | [113] | |
11 obese men | 4 g/day per os | 24 weeks | ↓ anthropometric parameters and blood AEA and 2-AG | [122] | |
63 obese subjects | 2 g/day | 4 weeks | ↓ 2-AG levels, no significant effect on antropometric | [123] | |
Pretectionagainst myocardial infarct | MI and euthanasia after 7 days | KO containing 0.47 g/100 g EPA + DHA | 14 days of pretreatment with KO before MI | ↓ heart and lung hypertrophy, and and inflammation | [118] |
Vascular function | 34 participants with type 2 diabetes | 1 g/day in PUFA | 4 weeks | ↑ endothelial function ↓ blood C peptide levels and HOMA scores | [119] |
Gut microbiota and IBD | ICR mice fed with HFD | fish oil (600 μg/g/day), KO (600 μg/g/day) and their mixture (300 + 300 μg/g/day | 12 weeks | ↓ obesity, ↑ positive phyla (i.e., Bacterioides and Lactobacilli) | [124] |
Obesity and hyperlipidemia induced by HFD+ high sugar diet | 100, 200, 600µg/g/day | 12 weeks | ↑ microbiotic alteration and cardiometabolic parameters | [125] | |
100, 200 and 600 mg/kg | 7 weeks | ↑ abundance of Lactobacillus spp. and short-chain fatty acids producers | [126] | ||
Dextran sulfate sodium (DSS)-induced colitis in mice | mixture of KO, Lactobacillus reuteri and vitamin | 4 weeks | ↑ clinical and histological scores, restore epithelial restitution, ↓ proinflammatory cytokines | [110] | |
DSS-induced colitis in mice | 5% | 4 weeks | ↓ disease activity index and TNF-α and IL-1β levels | [128] | |
DSS-induced colitis in mice | KO-entrapped liposomes (containing 42% w/w phospholipids, ≥26.5 w/w% total Omega-3, ≥8.5% w/w DHA, ≥14.5% w/w EPA, and 0.125±0.025 w/w% astaxanthin) | 8 weeks | ↓TNF and IL6 and the systemic levels of endotoxin, ↑ hydrophobic protective barrier | [129] | |
C. rodentium infected mice | 1.5 g KO | 4 weeks | ↓ inflammatory pathway, ↓of Rickettsiales and several species of Lactobacillus | [130] | |
Arthritic disease | Mice experimental models of inflammatory arthritis | KO diet, in which EPA + DHA were 0.44 g/100 g of KO diet | 2 months | ↓ infiltration of inflammatory cells and hyperplasia at synovial layer | [132] |
hTNF-α over-expressing mice | 6 weeks | ↓ markers of fatty acid oxidation | [133] | ||
Randomized, double blind, placebo controlled clinical trials on 90 patients with CVD and/or osteoarthritis and/or rheumatoid arthritis | 300 mg/day | ↓ CRP levels and pain (about 29%), stiffness (about 20%) and functional impairment (about 23%). | [134] | ||
Randomized, double-blind, parallel-group, placebo-controlled study, 50 patients with mild knee pain | 2 g/day | 30 days | ↓ knee pain, ↑ motion of both the knees | [135] | |
260 Australian patients affected by knee OA | 2 g/day | 6 months (ongoing) | ↑ knee pain and in size of knee synovitis/effusion | [11] | |
Neurodegeneration | Human neuronal SH-SY5Y cell line | ↓ oxidative stress and mitochondrial protection | [137] | ||
Aged rats | 20, 50 mg/kg/day | 7 days | ↑ cholinergic trasmission, muscarinic receptors and choline transporters | [139] | |
LPS -induced mice model of Alzheimer | 80 mg/kg/day | 4 weeks | ↓ iNOS, COX-2, NFkB, ROS and malondialdehyde levels, amyloid beta (1–42) peptide | [141] | |
Senescence-accelerated prone mouse strain 8 (SAMP8) | 1% of KO | 12 weeks | ↑ cognitive function and the anxiety, ↓ memory deficit and learning, ↓ β-amyloid Aβ42 accumulation | [142] | |
Amyloid Aβ25-35-induced mouse model of Alzheimer | 100, 200 or 500 mg/Kg/day | 14 days | ↓ latency in the Morris water maze test, ↓ Bax/Bcl-2 ratio in the brain and ↓ levels of ROS, malondialdehyde and NO | [143] | |
Randomized, double-blind clinical trial on 45 healthy elderly males (61–72 years-old) | sardine-oil, KO or placebo | 12 weeks | ↑ cognitive capacity | [144] | |
KO 0.2 g/rat/day, or imipramine 20 mg/kg/day | 7 weeks | ↑ cognitive abilities, in behaviour features and Bdnf | [145] | ||
KO or vitamine B12 or imipramine or saline 5 mL/kg | 14 days | ↓ malondialdehyde and hydrogen peroxide levels, catalase activity, ↑ glutathione peroxidase levels, superoxide dismutase activities and glutathione levels | [146] | ||
Immobility-induced murine depression model | PBS, or cotinine (a nicotine-derivative) 5 mg/kg, or cotinine plus KO 143 mg/kg | 4 weeks | ↓ depression-like behaviours | [147] | |
Randomized, controlled, double-blind clinical trial on 264 adolescent (13–15 years) | cohort I: 400 mg/day of EPA + DHA or placebo, and after 3 months increased the dose to 800 mg/day of EPA + DHA. cohort II: 800 mg/day of EPA + DHA | 1 year | no evidence about an effect on depressive feelings, low adherence | [148,149] | |
Cancer | Several human and murine colorectal cancer cells | 0.03 and 0.12 µL/100 µL | 24–48 h | ↓ cell proliferation, ↓ expression of EGFR, pEGFR, pERK1/2 and pAKT | [154] |
Exercise performance | Double-blind on 17 rowers members of the Polish National Rowing Team | 1 g/day of KO | 6 weeks | ↑ erythrocytes or serum levels of superoxide dismutase, TNF-α and thiobarbituric acid | [155] |
Randomized clinical trial on 37 young athletes | 2 g/day of KO | 6 weeks | ↑ levels of peripheral blood mononuclear cell IL-2 production and natural killer cell cytotoxic activity, 3 h post-exercise | [156] | |
Double-blind, placebo-controlled clinical trial | 3 g/day of KO or placebo during the resistance training | 8 weeks | ↑ in the lean body mass (about 2.1% vs. baseline) | [157] | |
ESPO-572® (75% of PCSO-524® and 25% KO) 600 mg/day | 26 days | ↑ mitigation of exercise-induced muscle damage and cytokine-induced tissue degradation | [158] | ||
47 triathletes randomized supplemented before the race. | 4 g/day of a KO (Superba BoostTM) | 5 weeks | ↑ exercise performance, especially during high-resistance efforts | [159] |
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Colletti, A.; Cravotto, G.; Citi, V.; Martelli, A.; Testai, L.; Cicero, A.F.G. Advances in Technologies for Highly Active Omega-3 Fatty Acids from Krill Oil: Clinical Applications. Mar. Drugs 2021, 19, 306. https://doi.org/10.3390/md19060306
Colletti A, Cravotto G, Citi V, Martelli A, Testai L, Cicero AFG. Advances in Technologies for Highly Active Omega-3 Fatty Acids from Krill Oil: Clinical Applications. Marine Drugs. 2021; 19(6):306. https://doi.org/10.3390/md19060306
Chicago/Turabian StyleColletti, Alessandro, Giancarlo Cravotto, Valentina Citi, Alma Martelli, Lara Testai, and Arrigo F. G. Cicero. 2021. "Advances in Technologies for Highly Active Omega-3 Fatty Acids from Krill Oil: Clinical Applications" Marine Drugs 19, no. 6: 306. https://doi.org/10.3390/md19060306