Table 2.
The effect of eicosapentaenoic acid and docosahexaenoic acid (EPA & DHA) on plasma concentration of small dense low density lipoprotein (LDL), LDL particle number, and LDL particle size
| Author, Year | Intervention | Dose per day | Treatment duration | Subjects | Method of assessment | Main outcomes | Final effects of specific diet ingredients or nutraceuticals on LDL (number, size and concentration) |
|---|---|---|---|---|---|---|---|
| Ouellette et al. 2014 [61] | Fish oil supplementation | 5 g/day | 6 weeks | 210 healthy adults | 2–16% PAGE | The n-3 PUFA supplementation had no effect on plasma LDL-C concentrations and LDL particle size | LDL particle size — |
| Oelrich et al. 2013 [62] | Fish oil supplementation, Soy oil supplement (placebo) | 4 g/day (800 mg EPA and DHA) | 12 weeks | 60 hypertriglyceridemic adults | Gradient gel electrophoresis | In comparison to the baseline, four particle sizes in terms of LDL1 (+ 20 ± 5%), LDL2 (+ 64 ± 13%), and LDL3 (+ 26 ± 6%) significantly increased in all fish oil groups. | LDL particle size ↑ |
| Petersen et al. 2002 [63] | Fish oil supplementation, Corn oil supplement (placebo) | 4 g/day (2.6 g EPA and DHA + 13.4 mg vitamin E) | 8 weeks | 42 diabetic patients with moderate hypertriglyceridemia | Ultracentrifugation | Small dense LDL particles did not significantly change compared with control group. | Small dense LDL |
| Suzukawa et al. 1995 [64] | Fish oil, Corn oil (placebo) | 4 g/day (3.4 g of n-3) | 6 weeks | 20 hypertensive adults | ND | Fish oil increased LDL size (+ 0.16 nm) compared to the baseline. | LDL particle size ↑ |
| Asztalos et al. 2016 [65] | EPA, DHA, Olive oil (placebo) |
EPA 600 mg/day EPA 1800 mg/day DHA 600 mg/day Olive oil placebo 6 g/day |
6 weeks | 121 healthy individuals with normal lipid profiles | Denka-Seiken Corporation (for LDL-C and sdLDL-C, Tokyo, Japan) | In all 4 groups no significant change in sdLDL-C (p = 0.82) | Small dense LDL — |
| Satoh et al. 2007 [66] | EPA | 1.8 g/d | 3 months | 44 obese patients with metabolic syndrome | The Quantimetrix Lipoprotein LDL system (LDL3–7:sdLDL) | sdLDL (− 5 mmol/l) and sdLDL proportion (− 1.27%) significantly decreased in EPA group compared with baseline but no significant differences between the two groups. | Small dense LDL ↓ |
| Mori et al. 1999 [67] |
EPA, DHA, Olive oil (placebo) |
4 g/d | 6 weeks | 59 overweight adults with mildly hypercholesterolemic | Using commercially available 3–13% nondenaturing native gels | There was no statistically significant difference in LDL particle size between and within groups. | LDL particle size — |
| Kelley et al. 2007 [68] |
DHA, Olive oil (placebo) |
7.5 g/d DHA oil (~ 3 g/d DHA), or 7.5 g/d olive oil | 90 days | 34 healthy or mildly hyperlipidemic men | NMR | Participants who consumed DHA had lower the number of small dense LDL particles (21%) whereas the change was not statistically significant compared to the placebo. Mean LDL particle size significantly increased (0.6 nm or 3%) compared with baseline. |
LDL particle size ↑ LDL particle number ↓ |
| Maki et al. 2005 [69] |
DHA, Olive oil (placebo) |
1.52 g/day DHA | 6 weeks | 57 subjects with below average levels of HDL | Vertical Auto Profile II (VAP-II) | DHA had no effect on small dense LDL. In addition, the percentage of cholesterol concentration in small dense LDL was significantly reduced in the DHA group than the control (− 9.7 vs. -3.0%). |
Small dense LDL — Cholesterol concentration in small dense LDL ↓ |
| Kawakami et al. 2015 [70] |
FO, Corn oil (placebo) |
10 g FO (5.49 g of ALA), 10 g corn oil (0.09 g of ALA) |
12 weeks | 15 healthy males | sd-LDL-EX “SEIKEN” |
In the intervention group, concentration of sd-LDL significantly reduced after 4 (− 25.8%) and 12 weeks (− 21.2%) in compared with the baseline. In addition, sd-LDL concentrations significant decreased than placebo after 4 weeks. |
Small dense LDL ↓ |
| Harper et al. 2006 [71] | FO supplementation, Olive oil capsules (placebo) |
5.2 g/d FO (3 g/d of ALA), Or 5.2 g of olive oil |
26 weeks | 56 patients without known coronary heart disease | Ultracentrifugal separation by enzymatic determination of cholesterol with 400 sequential spectrophotometric measurements | FO had no effect on atherogenic LDL subfractions (LDL3 and LDL4). However, FO significantly increased on less atherogenic LDL subfractions (LDL1 and LDL2) as compared to the olive oil (+ 0.08 and + 0.01 mmol/l) and the baseline (+ 0.06 and + 0.1 mmol/l). |
Small dense LDL — LDL subfractions (LDL1 and LDL2) ↓ |
sdLDL small dense Low-Density Lipoprotein, LDL-C Low-density lipoprotein cholesterol, High Density Lipoprotein Cholesterol, PUFA polyunsaturated fatty acid, ALA α-Linolenic acid, EPA Eicosapentaenoic acid, DHA Docosahexaenoic acid, NMR Nuclear magnetic resonance, FO Flaxseed oil, mg milligrams, mmol/l millimoles per litre, nm nanometer