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Abstract
Omega-3 polyunsaturated fatty acids are essential fatty acids because humans cannot synthesize them de novo and must obtain them in their diet. Fish and fish oil are rich sources of omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Significant evidence of the beneficial role of dietary intake of omega-3 fatty acids in blood flow has been reported and putative mechanisms for improvement of blood flow include anti-thrombotic effects, lowered blood pressure, improved endothelial function, and anti-atherogenic effects. Edible oils containing omega-3 fatty acids were registered as functional ingredients in the Korea Health Functional Food Code. Although omega-3 fatty acids have been evaluated by the Korea Food and Drug Administration (KFDA) based on scientific evidence, periodic reevaluation may be needed because emerging data related to omega-3 fatty acids have accumulated. Therefore, in this study, we reevaluated scientific evidence for the effect of omega-3 fatty acids as a functional ingredient in health functional food on improvement of blood flow. A comprehensive literature search was conducted for collection of relevant human studies using the Medline and Cochrane, KISS, and IBIDS databases for the years 1955–2012. Search keywords were used by combination of terms related to omega-3 fatty acids and blood flow. The search was limited to human studies published in Korean, English, and Japanese. Using the KFDA's evidence based evaluation system for scientific evaluation of health claims, 112 human studies were identified and reviewed in order to evaluate the strength of the evidence supporting a relation between omega-3 fatty acids and blood flow. Among 112 studies, significant effects on improvement of blood flow were reported in 84 studies and the daily intake amount was ranged from 0.1 to 15 g. According to this methodology of systematic review, we concluded that there was possible evidence to support a relation between omega-3 fatty acid intake and blood flow. However, because inconsistent results have recently been reported, future studies should be monitored. (J Nutr Health 2013; 46(3): 226 – 238)
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Fig. 2.
Evidence table of systematic review for omega-3 fatty acids and effects on improvement of blood flow (Type 1, RCT; Type 2, Cohort study; Type 3, non-RCT/case-control study etc; Type 4, animal study; Type 5, in vitro study; ●, significant improvement in the blood flow-related biomarkers; ●, no significant improvement in the blood flow-related biomarkers).
Fig. 3.
Effects of omega-3 fatty acids on improvement of blood flow according to daily dose (●, significant improvement in the blood flow-related biomarkers; ●, no significant improvement in the blood flow-related biomarkers).
Fig. 4.
Effects of omega-3 fatty acids on improvement of blood flow according to purity (Low: purity ＜90%; high: purity ≥ 90%; ●, significant improvement in the blood flow-related biomarkers; ●, no significant improvement in the blood flow-related biomarkers).
Table 1.
Characteristics of studies included for systematic review
| Reference | Study type 1) | Target | Subject No. | Purity 2) | Dose (g) | Result 3) | Quality score |
|---|---|---|---|---|---|---|---|
| Baldassarre et al. 20068) | RCT | Healthy | 64 | Low | 1.8 | + | 5 |
| Blonk et al. 19909) | RCT | Healthy | 45 | Low | 1.5, 3.0 | + | 3 |
| Engler et al. 200410) | RCT | Healthy | 20 | High | 1.2 | + | –1 |
| Fahs et al. 201011) | RCT | Healthy | 20 | High | 0.9 | + | –2 |
| Finnegan et al. 200312) | RCT | Patients | 150 | Low | 0.7, 1.5 | + | –2 |
| Green et al. 199013) | RCT | Patients | 27 | Low | 4.32 | + | –4 |
| Grundt et al. 200414) | RCT | Patients | 300 | Low | 0.882 | + | 0 |
| Herrmann et al. 199515) | RCT | Patients | 53 | Low | 9.12 | + | 4 |
| Park et al. 200216) | RCT | Healthy | 33 | High | 4 | + | –3 |
| Passfall et al. 199317) | RCT | Patients | 12 | Low | 2.16 | + | –1 |
| Prisco et al. 199518) | RCT | Healthy | 20 | Low | 3.44 | + | 2 |
| Møller et al. 199219) | RCT | Healthy | 40 | Low | 1.06 | Ø | –3 |
| Freese et al. 199720) | Non-RCT | Healthy | 46 | Low | 5.2 | + | 0 |
| Piolot et al. 200321) | Non-RCT | Healthy | 32 | Low | 3 | + | 1 |
| Rillaerts et al. 198922) | Non-RCT | Patients | 12 | Low | 2.7 | + | –2 |
| Walser et al. 200623) | Non-RCT | Healthy | 13 | Low | 5 | + | –2 |
| Haglund et al. 199024) | Non-RCT | Healthy | 20 | Low | 4.5 mL | + | –3 |
| Agren et al. 198825) | RCT | Healthy | 62 | Low | 0.8 | + | –1 |
| Andrioli et al. 199926) | RCT | Healthy | 60 | Low | 3.6 | + | –4 |
| Bach et al. 198927) | RCT | Healthy | 30 | Low | 1.26, 2.52 | + | –4 |
| Coates et al. 200928) | RCT | Healthy | 33 | Low | 0.2 | + | 4 |
| Derosa et al. 200929) | RCT | Patients | 333 | High | 3 | + | 4 |
| Mann et al. 201030) | RCT | Healthy | 30 | Low | 0.79, 1.02 | + | 0 |
| Mann et al. 199731) | Non-RCT | Healthy | 29 | Low | 2.894 | + | –2 |
| Mesa et al. 200432) | RCT | Healthy | 42 | Low | 5.5, 5.7 | + | –3 |
| Mori et al. 199233) | RCT | Patients | 32 | Low | 4.6 | + | 0 |
| Myrup et al. 200134) | RCT | Patients | 36 | Low | 2, 2.6 | + | –2 |
| Schmidt et al. 198835) | RCT | Patients | 36 | Low | 4.5 | + | –3 |
| Serebruany et al. 201136) | RCT | Patients | 30 | Low | 0.84, 1.62 | + | –3 |
| Tremoli et al. 199537) | RCT | Healthy | 16 | Low | 2.25 | + | –3 |
| Tremoli et al.199438) | RCT | Healthy | 29 | Low | 2.25 | + | 0 |
| Véricel et al. 199939) | RCT | Healthy | 20 | Low | 0.18 | + | –1 |
| von Schacky et al. 198540) | RCT | Healthy | 7 | High | 6 | + | –3 |
| Westerveld et al. 199341) | RCT | Patients | 24 | High | 0.9, 1.8 | + | 0 |
| Woodcock et al. 198442) | RCT | Patients | 19 | Low | 1.8 | + | –4 |
| Wright et al. 200843) | RCT | Patients | 60 | High | 3 | + | 1 |
| Zucker et al. 198844) | RCT | Healthy | 9 | Low | 5.4 | + | 0 |
| Zucker et al. 198844) | Non-RCT | Patients | 6 | Low | 5.4 | + | 0 |
| Zucker et al. 198844) | RCT | Patients | 10 | Low | 5.4 | + | 0 |
| Toft et al. 199745) | RCT | Healthy | 78 | Low | 3.4 | + | 3 |
| Cobiac et al. 199146) | Non-RCT | Healthy | 31 | Low | 4.5 | + | 3 |
| Croset et al. 199047) | Non-RCT | Healthy | 16 | High | 0.1 | + | 5 |
| De Caterina et al. 199348) | Non-RCT | Patients | 14 | Low | 3.77 | + | –1 |
| Driss et al. 198449) | Non-RCT | Healthy | 19 | Low | 0.15 | + | –3 |
| Grundt et al. 199950) | RCT | Healthy | 57 | Low | 3.4 | + | –1 |
| Landgraf-Leurs et al. 199051) | Non-RCT | Patients | 13 | Low | 7.7 | + | –4 |
| Okumura et al. 200252) | Non-RCT | Healthy | 15 | Low | 1.8 | + | –4 |
| von Schacky et al. 198553) | Non-RCT | Healthy | 6 | Low | 4.64 mL | + | –2 |
| Sanders et al. 198354) | RCT | Healthy | 5 | Low | 1.63, 3.28, 6550 | + | –4 |
| Sanders et al. 198354) | RCT | Healthy | 5 | Low | 5.96 mL | + | –4 |
| Haglund et al. 199455) | Non-RCT | Healthy | 12 | Low | 0.96 | + | –3 |
| Fumeron et al. 199156) | RCT | Healthy | 36 | Low | 6 | + | –4 |
| Goyens et al. 200657) | RCT | Healthy | 37 | Low | 1.6 | + | 3 |
| Green et al. 198558) | RCT | Patients | 18 | Low | 1.8 | + | 0 |
| Hansen et al. 199359) | RCT | Patients | 31 | Low | 3.4, 3.6 | + | 0 |
| Hendra et al. 199060) | RCT | Patients | 80 | Low | 3 | + | 0 |
| Pirich et al. 199961) | RCT | Patients | 26 | Low | 0.354 | + | 1 |
| Rizza et al. 200962) | RCT | Healthy | 50 | Low | 1.7 | + | 0 |
| Vognild et al. 199863) | RCT | Healthy | 266 | Low | 3.45 mL | + | –1 |
| Phang et al. 201264) | Non-RCT | Healthy | 30 | High | 2 | + | 3 |
| Phang et al. 201265) | Non-RCT | Healthy | 30 | High | 2 | + | 3 |
| Axelrod et al. 199466) | RCT | Patients | 20 | Low | 2.6 | + | –1 |
| Berrettini et al. 199667) | RCT | Patients | 40 | Low | 2.58 | + | 2 |
| Flaten et al. 199068) | RCT | Healthy | 64 | Low | 1.4 | + | –3 |
| Haberka et al. 201169) | RCT | Patients | 40 | Low | 0.84 | + | –3 |
| Honstra et al. 199070) | RCT | Healthy | 84 | Low | 4.7 | + | –4 |
| Lau et al. 199571) | RCT | Patients | 45 | Low | 2.8 | + | –2 |
| Lindman et al. 200472) | RCT | Patients | 219 | Low | 1.44 | + | –2 |
| McVeigh et al. 199473) | RCT | Patients | 20 | Low | 3 | + | –3 |
| Mehta et al. 198874) | RCT | Patients | 8 | Low | 5.4 | + | 0 |
| Moertl et al. 201175) | RCT | Patients | 49 | Low | 0.882, 3.528 | + | –1 |
| Mori et al. 199776) | RCT | Healthy | 138 | Low | 0.8, 1.6 | + | 2 |
| Solomon et al. 199077) | RCT | Patients | 10 | Low | 4.6 | + | 0 |
| Wensing et al. 199978) | RCT | Healthy | 67 | Low | 1.2 | + | –1 |
| Woodman et al. 200379) | RCT | Patients | 59 | High | 4 | + | 1 |
| Grundt et al. 200380) | RCT | Patients | 300 | Low | 0.882 | Ø | –3 |
| Johansen et al. 199981) | RCT | Patients | 54 | Low | 2.42 | + | –4 |
| Krishnan et al. 200782) | RCT | Patients | 60 | Low | 0.6 | + | –4 |
| Brox et al. 198183) | Non-RCT | Healthy | 10 | Low | 25 mL | + | –4 |
| Mehta et al. 198884) | Non-RCT | Patients | 8 | Low | 5.4 | + | –4 |
| Nordøy et al. 199485) | Non-RCT | Healthy | 6 | Low | 4.86 | + | –1 |
| Wojenski et al. 199186) | Non-RCT | Healthy | 9 | High | 3, 4 | + | –1 |
| Agren et al. 199787) | RCT | Healthy | 55 | Low | 1.05, 1.68, 2.28 | Ø | 0 |
| Almdahl et al. 199388) | RCT | Patients | 18 | Low | 5.04 | Ø | –2 |
| Conquer et al. 199689) | RCT | Healthy | 24 | Low | 1.62 | Ø | 5 |
| Conquer et al. 199990) | RCT | Healthy | 20 | Low | 3 | Ø | 6 |
| Demke et al. 198891) | RCT | Patients | 31 | Low | 1.7 | Ø | 3 |
| Donnelly et al. 199292) | RCT | Patients | 16 | Low | 1.08 | Ø | 3 |
| Gajos et al. 201193) | RCT | Patients | 54 | Low | 0.84 | Ø | –1 |
| Goodfellow et al. 200094) | RCT | Patients | 28 | Low | 1.7 | Ø | 0 |
| Grundt et al. 200395) | RCT | Patients | 300 | Low | 0.882 | Ø | –2 |
| Hagve et al. 199396) | RCT | Healthy | 16 | Low | 5.1 | Ø | –4 |
| Haines et al. 198697) | RCT | Patients | 41 | Low | 4.6 | Ø | –2 |
| Hellsten et al. 199398) | RCT | Healthy | 41 | Low | 2 | Ø | –1 |
| Montegaard et al. 201099) | RCT | Patients | 8 | Low | 0.74, 3.84 | Ø | –3 |
| Neff et al. 2011100) | RCT | Healthy | 49 | Low | 2 | Ø | 0 |
| Nilsen et al. 1991101) | RCT | Patients | 20 | Low | 5.04 | Ø | –1 |
| Poppitt et al. 2009102) | RCT | Patients | 102 | Low | 1 | Ø | 2 |
| Prisco et al. 1994103) | RCT | Healthy | 20 | Low | 3.44 | Ø | 3 |
| Saifullah et al. 2007104) | RCT | Patients | 27 | Low | 0.671 | Ø | 6 |
| Sanders et al. 2011105) | RCT | Healthy | 367 | High | 0.45, 0.9, 1.8 | Ø | 7 |
| Sirtori et al. 1992106) | RCT | Patients | 12 | Low | 4.5 | Ø | –1 |
| DeCaterina et al. 1990107) | Non-RCT | Patients | 30 | Low | 4.3 | Ø | –1 |
| Din et al. 2008108) | Non-RCT | Healthy | 28 | Low | 0.7 | Ø | –1 |
| Nelson et al. 1997109) | Non-RCT | Healthy | 12 | Low | 6 | Ø | –4 |
| Boberg et al. 1992110) | RCT | Patients | 14 | Low | 3 | Ø | 0 |
| Park et al. 2009111) | RCT | Healthy | 158 | Low | 0.135, 0.27, 0.54 | Ø | 0 |
| Brox et al. 2001112) | RCT | Healthy | 120 | Low | 2.6, 3.3 | + | 3 |
| Brox et al. 1983113) | RCT | Patients | 17 | Low | 30 mL | + | –2 |
| Hwang et al. 1997114) | RCT | Healthy | 32 | Low | 9 | + | 4 |
| Hwang et al. 1997114) | RCT | Healthy | 36 | Low | 6, 15 | + | 4 |
| Gajos et al. 2010115) | RCT | Patients | 63 | High | 0.84 | Ø | 3 |
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