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Table 2 Intervention studies on the effects of fat intake on LDL particle size

From: The effects of fat consumption on low-density lipoprotein particle size in healthy individuals: a narrative review

Author (Year) Study/Method Subjects Age Duration Treatment Results
Campos et al. (1995) [80] Randomized
Crossover
PAGGE
UC
43 males Mean, 50 years (SD, ± 11) 12 weeks Each diet was consumed for 6 wk.
Low-fat diet: 24.2% E fat (6% E SFA, 11.6% E MUFA, 4.3% E PUFA), 58.8% E CHO, 16.8% E PRO.
High-fat diet: 45.2% E fat (18.1% E SFA, 12.4% E MUFA, 11.8% E PUFA), 39.2% E CHO, 16.3% E PRO.
Calories, cholesterol, fiber, and P:S were kept constant.
↓LDL-C
(Low-fat diet)
↑mean peak LDL diameter ↓LDL peak density ↑large, buoyant LDL particle mass (LDL I and LDL II) ↓sdLDL particle mass (LDL III and LDL IV)
(High-fat diet)
Krauss et al. (1995) [77] Randomized Crossover
PAGGE
UC
105 males 28 to 79 years
mean, 48.9 (SD, ± 11.1)
12 weeks Each diet was consumed for 6 wk.
Low-fat diet: 23.9% E fat (5.4% E SFA, 12.3% E MUFA, 4% E PUFA), 60% E CHO, 16.1% E PRO.
High-fat diet: 46% E fat (18.3% E SFA, 12.4% E MUFA, 12.5% E PUFA), 38.6% E CHO, 16.2% E PRO.
↓LDL-C
(Low-fat diet)
↑large, buoyant LDL particle mass (LDL I and LDL II) ↓sdLDL particle mass (LDL III and LDL IV)
(High-fat diet)
Thirty-six subjects (about one-third) switched from pattern A (or intermediate pattern) to pattern B by following the low-fat diet.
Carmena et al. (1996) [81] Intervention
PAGGE
18 males 30 to 69 years
mean, 57.1
(SD, ± 17.2)
6 weeks The SFO diet was consumed for 3 wk., followed by 3 wk. on the OO diet.
Sunflower seed oil (SFO) diet: 31% E fat (6.8% E SFA, 10.9% E MUFA, 13.3% E PUFA), 48% E CHO, 11% E PRO.
Olive oil (OO) diet: 30.5% E fat (6.9% E SFA, 21.6% E MUFA, 4.7% E PUFA), 48% E CHO, 11% E PRO.
Vitamin E, beta-carotene, and vitamin C were significantly higher in the SFO diet.
↓LDL-C
↑LDL size
(SFO diet compared to OO diet)
Kasim-Karakas et al. (1997) [82] Intervention
PAGGE
14 females Mean, 61 years
(SD, ± 11)
4 months Consumption of a “habitual diet”, followed by the intakes of a 31% fat diet for 4 wk., followed by the 24% fat diet for 6 wk., then the 14% fat diet for 6 wk.
Habitual diet: 33% E fat (10% E SFA, 13% E MUFA, 8% E PUFA), 51% E CHO, 71 g PRO.
31% fat diet: 31% E fat (10% E SFA, 12% E MUFA, 9% E PUFA), 53% E CHO, 17% E PRO.
24% fat diet: 23% E fat (6% E SFA, 10% E MUFA, 7% E PUFA), 60% E CHO, 18% E PRO.
14% fat diet: 14% E fat (3% E SFA, 7% E MUFA, 4% E PUFA), 67% E CHO, 19% E PRO.
↓LDL-C
(14% fat diet)
↔LDL particle size
(all diets compared)
Clifton et al. (1998) [26] Randomized
Double-blind
PAGGE
54 males
51 females
Males: 30–66 years
mean, 50 years (SD, ± 7.5)
Females: 23–76 years
mean, 51.1 years (SD, ± 9.5)
8 weeks Consumption of a “self-selected” low fat baseline diet for 2 wk., followed by the addition of a fat-containing (high fat phase) or fat free (low fat phase) liquid supplement to the baseline diet for 3 wk. each.
Low fat baseline diet: 26.2% E fat (9% E SFA, 9% E MUFA, 5.4% E PUFA), 51.1% E CHO, 19.7% E PRO.
Low fat phase: 20.7% E fat (7.5% E SFA, 7.1% E MUFA, 4.3% E PUFA), 59.3% E CHO, 20% E PRO.
High fat phase: 35.7% E fat (14.9% E SFA, 12.1% E MUFA, 3.7% E PUFA), 46.3% E CHO, 18% E PRO.
The high fat phase had significantly higher cholesterol (748 mg) compared to the low fat phase (182 mg)
↑LDL-C
(high fat phase compared to low fat phase)
↑smaller LDL particles
(men compared to women, in both low fat and high fat phases)
↔LDL particle size
(low fat compared to high fat phase)
Dreon et al. (1998) [71] Randomized
Crossover
PAGGE
UC
103 males 28–79 years
mean, 48.9 years (SD, ± 11.1)
12 weeks Consumption of each experimental diet for 6 wk.
Low-fat diet: 24.2% E fat, 5.9% E SFA (0.1% E lauric acid, 0.3% E myristic acid, 3.7% E PA, 1.5% E SA), 11.8% E MUFA (11.7% E OA), 4.2% E PUFA (0.1% E AA, 0.3% E ALA, 3.9% E LA), 59% E CHO, 16.6% E PRO.
High-fat diet: 45.5% E fat, 18.4% E SFA (0.5% E lauric acid, 2.3% E myristic acid, 4% E SA, 9% E PA), 12.5% E MUFA (11.7% E OA), 11.8% E PUFA (0.6% E ALA, 10.8% E LA), 38.8% E CHO, 16.3% E PRO.
Significant differences in reported intakes of cholesterol, P:S, and fiber.
↑LDL-C
(High-fat diet)
↔plasma lipoproteins
[SA, MUFA (and OA), PUFA (and LA)]
↑large LDL particle mass
↑LDL peak particle diameter
(High-fat diet, high SFA, myristic and palmitic acids)
↓sdLDL mass
(High-fat diet; total SFA; myristic acid)
Dietary protein, carbohydrate, cholesterol, P:S, and fiber were not associated with plasma lipoproteins.
Lagrost et al. (1999) [83] Randomized
PAGGE
32 total
14 males
18 females
20–60 years (mean, 41 years) 23 weeks Three different diets were consumed for 6 wk. each, with 2 to 3 wk. washout periods.
Lauric acid diet: 41.5% E fat, 22.2% E SFA (10.6% E lauric acid, 4.2% E myristic acid, 5.9% E PA), 11% E MUFA (10.3% E OA), 4.6% E PUFA (4.4% E LA), 43.9% E CHO, 14.3% E PRO.
Palmitic acid diet: 41% E fat, 18.9% E SFA (13.2% E PA, 2.2% E myristic acid, 1.9% E lauric acid), 11.4% E MUFA (10.6% E OA), 4.6% E PUFA (4.4% E LA), 44.7% E CHO, 14.3% E PRO.
Oleic acid diet: 41.8% E fat, 11.8% E SFA (5.7% E PA, 2.5% E lauric acid, 1.9% E myristic acid), 19.9% E MUFA (19% E OA), 5.4% E PUFA (5.2% E LA), 44.3% E CHO, 14% E PRO.
Nutrient compositions were similar for each diet, except about 8.5% E was supplied by lauric (+ 2.2% E myristic acid), palmitic, or oleic acids.
↓LDL-C
(Oleic acid diet compared to lauric acid and palmitic acid diets). There were no significant differences between lauric acid and palmitic acid diets.
↔LDL particle mean size
(all diets compared)
Dreon et al. (1999)
[84]
Randomized
Crossover
PAGGE
UC
38 males 32–71 years
mean, 52.5 years
(SD, ± 12.1)
20 days Participants displayed phenotype A by following both a low- and high-fat diet for 4–6 wk. in a previous study.
Consumption of their usual diet and very-low-fat diet for 10 d each.
Usual diet: 31.8% E fat (10.8% E SFA, 11.8% E MUFA, 6.9% E PUFA), 52.1% E CHO, 14% E PRO.
10%-Fat diet: 10.4% E fat (2.7% E SFA, 3.7% E MUFA, 2.6% E PUFA), 75.7% E CHO, 14.5% E PRO.
↓LDL-C
↓mass larger LDL-I
↑mass smaller LDL-III and LDL-IV subfractions
↓LDL particle size
↓LDL peak diameter
(10%-Fat diet compared to usual diet)
Twelve individuals (about one-third) converted to phenotype B, whereas 26 remained phenotype A.
Pedersen et al. (2000) [27] Randomized
Double-blind Crossover
UC
18 males 20–28 years (mean, 24 years) Up to 33 weeks Three identical diets were consumed for 3 wk. each (5–12 wk. washout periods), except that 19% E was from either extra virgin olive oil, physically refined rapeseed oil, or chemically refined sunflower oil.
Olive oil (OO) diet: 35% E fat (11% E SFA, 21% E MUFA, 3% E PUFA), 53% E CHO, 12% E PRO.
Rapeseed oil (RO) diet: 35% E fat (9% E SFA, 18% E MUFA, 7% E PUFA), 52% E CHO, 13% E PRO.
Sunflower oil (SO) diet: 35% E fat (10% E SFA, 9% E MUFA, 15% E PUFA), 53% E CHO, 12% E PRO.
OO diet contained significantly more squalene and less campesterol and sitosterol compared to RO and SO diets.
↓LDL-C
(RO and SO diets compared to OO diet)
↔LDL subfraction average size
(all diets compared)
↑number of larger and medium-sized LDL subfractions (LDL-1 to LDL-3)
(OO diet compared to RO and SO diets)
↑number of medium-sized and sdLDL subfractions (LDL-4 to LDL-5)
(OO diet compared to RO diet)
↔number of smallest, dense LDL particles (LDL-6)
(all diets compared)
Kratz et al. (2002) [85] Randomized
Parallel
PAGGE
56 total
30 males
26 females
18 to 43 years (69 initial participants)
mean, 25.8 years (SD, ± 5.5)
6 weeks Baseline diet rich in SFA was consumed for 2 wk., followed by participants assigned to one of three treatment diets for 4 wk.
Baseline diet: 38% E fat (19% E SFA, 11.2% E MUFA, 5.2% E n-6 PUFA, 0.4% E n-3 PUFA, 45.1% E CHO, 16.9% E PRO.
Refined olive oil diet: 38.7% E fat (10.7% E SFA, 23.2% E MUFA, 3% E n-6 PUFA, 0.4% E n-3 PUFA, 47% E CHO, 14.3% E PRO.
Rapeseed oil diet: 38.4% E fat (9.1% E SFA, 19.1% E MUFA, 6.5% E n-6 PUFA, 2.5% E n-3 PUFA, 47.3% E CHO, 14.3% E PRO.
Sunflower oil diet: 38.3% E fat (10% E SFA, 8.7% E MUFA, 18.2% E n-6 PUFA, 0.3% E n-3 PUFA, 47.6% E CHO, 14.2% E PRO.
The diets were identical, save for fatty acid composition.
↓LDL size
↓LDL peak particle diameter
(all 3 diets compared to baseline diet)
↔LDL size
(all 3 treatment diets compared)
Sharman et al. (2002) [33] Intervention
PAGE (nongradient)
20 males Ketogenic diet: mean, 36.7 years (SD, ± 11.6)
Control diet: mean, 35 years (SD, ± 13)
6 weeks Twelve subjects switched from their usual dietary pattern to a ketogenic diet, whereas 8 subjects continued their usual dietary pattern (controls) for 6 wk.
Ketogenic diet: 61% E fat (25% E SFA, 25% E MUFA, 11% E PUFA), 8% E CHO, 30% E PRO.
Habitual diet: 25% E fat (12% E SFA, 9% E MUFA, 4% E PUFA), 59% E CHO, 15% E PRO.
All nutrients were significantly different between diets, except for energy and alcohol consumption.
↔LDL-C
(both diets after 6 wk)
↑LDL peak particle diameter (ketogenic diet after 3 wk)
↑LDL-1 percentage
(ketogenic diet)
All 7 initial pattern A subjects remained pattern A after the ketogenic diet (no significant changes in percentages of any LDL subclasses, or the mean and peak LDL particle size).
Most initial pattern B subjects (3 out of 5) changed to pattern A after the ketogenic diet.
Rivellese et al. (2003) [86] Randomized
PAGGE
UC
162 total
86 males
76 females
30–65 years
SFA diet: mean, 48 years (SD, ± 8) (n-3 group) and mean, 49 years (SD, ± 7) (placebo)
MUFA diet: mean, 49 years (SD, ± 7) (n-3 group and placebo)
90 days Consumption of a diet high in SFA or MUFA, followed by a second random assignment to capsule supplements of fish oil (3.6 g n-3 FA, containing 2.4 g EPA and DHA) or placebo capsules (with same amount of olive oil). The test period was preceded by a 2 wk. “stabilisation period” on their “habitual” diets and placebo capsules.
SFA diet: 37.1% E fat (17.6% E SFA, 13.1% E MUFA, 4.7% E PUFA), 44.1% E CHO, 15.2% E PRO.
MUFA diet: 37.1% E fat (9.6% E SFA, 21.2% E MUFA, 4.6% E PUFA), 45.9% E CHO, 14.8% E PRO.
↑LDL-C
(SFA diet compared to MUFA diet)
↑LDL-C
(n-3 supplementation in both diets)
↔LDL size
(all diets compared)
Archer et al. (2003) [87] Randomized
PAGGE
65 males Mean, 37.5 years (SD, ± 11.2) 6–7 weeks Subjects consumed one of the diets for 6–7 wk. in an ad libitum manner.
Low fat, high CHO diet: 25.8% E fat (6% E SFA, 13.3% E MUFA, 5.1% E PUFA. 58.3% E CHO, 15.9% E PRO.
High MUFA diet: 40.1% E fat (8.2% E SFA, 22.5% E MUFA, 7.6% E PUFA, 44.7% E CHO, 15.2% E PRO.
↓LDL-C
(both diets; no significant difference between diets)
↓LDL peak particle diameter
(High CHO diet; in subjects with large LDL peak particle diameters at baseline)
↑percentage of small LDL particles
(High CHO diet; no significant difference between diets)
Smith et al. (2003) [88] Randomized
Single-blind
Parallel
UC
51 total
26 males
25 females
18–28 years Moderate MUFA diet:
Males: mean, 21 years (SD, ± 3)
Females: mean, 20 (SD, ± 1)
High MUFA diet:
Males: mean, 20 years (SD, ± 2)
Females: mean, 20 years (SD, ± 2)
24 weeks Consumption of a SFA-rich reference diet for 8 wk., followed by either a moderate- or high-MUFA diet for 16 wk.
SFA reference diet (one for each MUFA diet): 39.8% E/37.7% E fat (15.4% E/14.5% E SFA, 12.5% E/11.9% E MUFA, 7.3% E/6.7% E PUFA, 47.9% E/50% E CHO, 10.5% E/10.7% E PRO
Moderate-MUFA diet: 39.7% E fat (12.1% E SFA, 15.1% E MUFA, 7.2% E PUFA), 47.7% E CHO, 11.2% E PRO
High-MUFA diet: 37.1% E fat (9.7% E SFA, 16.6% E MUFA, 6.9% E PUFA, 50.3% E CHO, 11% E PRO
MUFA intakes were not significantly different between the two MUFA diets. MUFA intakes were significantly higher and SFA intakes were significantly lower than the reference diets.
↓LDL-C
(moderate- and high-MUFA diets compared to baseline, after SFA reference diet)
↑LDL-1 percentage
(moderate-MUFA diet compared to SFA reference diet)
↔proportions of LDL subfractions
(between each diet)
Volek et al. (2003) [89] Randomized
Crossover
PAGE (nongradient)
10 females Mean, 26.3 years (SD, ± 6.1) 12 weeks Each diet was consumed for 4 wk., with a 4 wk. break between diets.
Very low CHO diet: 60% E, 118 g fat (41 g SFA, 35 g MUFA, 20 g PUFA), 10% E CHO (43 g), 29% E PRO (128 g).
Low fat diet: 19% E, 34 g fat (10 g SFA, 9 g MUFA, 6 g PUFA), 62% E CHO (249 g), 17% E PRO (68 g).
↑LDL-C
(very low CHO diet compared to baseline and low fat diet)
↔relative percentages or concentrations of LDL subclasses
(after consumption of each diet)
Three of ten participants with pattern B displayed larger peak LDL size after following the very low CHO diet.
Goyens et al. (2005) [78] Randomized Double-blind
Parallel
NMR
54 total
21 males
33 females
29 total (NMR analyses)
14 males
15 females
Males: mean, 52.6 years (SD, ± 13.7)
Females: mean, 47.7 years (SD, ± 11.1)
10 weeks A 4 wk. period, followed by consumption of one of the following diets for 6 wk.
Control diet: 33.5% E fat (11.6% E SFA, 12.8% E MUFA, 8% E PUFA, 7.3% E LA and 0.4% E ALA), 50.5% E CHO, 14.5% E PRO.
Low-LA diet: 34% E fat (12.4% E SFA, 16.9% E MUFA, 3.7% E PUFA, 3% E LA, 0.4% E ALA, 49.8% E CHO, 14.9% E PRO.
High-ALA diet: 32.6% E fat (10.4% E SFA, 12.6% E MUFA, 8.6% E PUFA, 7.1% E LA, 1.1% E ALA, 50.4% E CHO, 15.5% E PRO.
↓LDL-C
(High-ALA diet compared to control diet)
↔mean LDL particle size
(all groups compared)
Thijssen et al. (2005) [90] Randomized Crossover
NMR
45 total
18 males
27 females
22 total (NMR analyses)
9 males
13 females
28–66 years mean, 51 years
(SD, ± 10)
17 weeks Consumption of each diet for 5 wk., with a washout period of ≥1 wk. between diets.
Stearic acid diet: 38.2% E fat, 18% E SFA (7.7% E SA), 12.9% E MUFA (6.8% E OA), 4.7% E PUFA (2.1% E LA, 0.2% E ALA), 45.8% E CHO, 14% E PRO.
Oleic acid diet: 37.7% E fat, 11% E SFA (1.2% E SA), 19.1% E MUFA (13.1% E OA), 5% E PUFA (2.4% E LA, 0.2% E ALA), 46.3% E CHO, 14% E PRO.
Linoleic acid diet: 38% E fat, 11.2% E SFA (1.2% E SA), 12.5% E MUFA (6.6% E OA), 11.8% E PUFA (9.3% E LA, 0.2% E ALA), 46.3% E CHO, 13.8% E PRO.
The diets did not differ, save for the difference of 7% E from SA, OA, or LA.
↔LDL-C
↔LDL particle size and subclass concentrations
(all 3 diets compared)
Faghihnia et al. (2010) [91] Randomized Crossover
PAGGE
UC
63 total
61 males
2 females
At least 20 years
mean, 47.9 years (SD, ± 11.2)
8 weeks Each diet was consumed for 4 wk.
High-fat low-carbohydrate diet:
40% E fat (13% E SFA, 11% E MUFA, 14% E PUFA), 45% E CHO, 15% E PRO.
Low-fat high-carbohydrate diet: 20% E fat (5% E SFA, 10% E MUFA, 5% E PUFA), 65% E CHO, 15% E PRO.
There were no differences in cholesterol and simple:complex CHO ratios.
↓LDL-C
↓large and medium LDL particle concentrations
↑small and very small LDL particle concentrations
↓mean LDL peak particle diameter
(Low-fat high-carbohydrate diet compared with the high-fat low-carbohydrate diet)
Egert et al. (2011) [92] Randomized
Parallel
PAGGE
37 total
12 males
25 females
18–34 years mean, 22.6 years (SD, ± 4.2) 6 weeks Consumption of a 2 wk. wash-in SFA-rich diet followed by consumption of one of the treatment diets for 4 wk.
Wash-in SFA-rich diet: 40.8% E fat (18.1% E SFA, 13.1% E MUFA, 6.6% E n-6 PUFA, 1.1% E n-3 PUFA), 42.6% E CHO, 15.7% E PRO.
Low-fat diet (MUFA-rich): 28.7% E fat (7.2% E SFA, 13.9% E MUFA, 5.3% E n-6 PUFA, 0.9% E n-3 PUFA), 54.4% E CHO, 15.6% E PRO.
High-fat diet (MUFA-rich): 40.2% E fat (9.9% E SFA, 19.8% E MUFA, 7% E n-6 PUFA, 1.6% E n-3 PUFA), 43.1% E CHO, 15.6% E PRO.
Both diets were isocaloric, rich in MUFA, with similar FA, CHO, cholesterol, fiber, and antioxidant proportions.
↓LDL-C
↓LDL size of the major fraction (both diets compared to the wash-in SFA-rich diet; no significant difference between treatment diets)
Mangravite et al. (2011) [79] Randomized Crossover
IM
40 males Mean, 45 years
(SD, ± 15)
13 weeks Consumption of a baseline diet for 3 wk., followed by intakes of two intervention diets for 3 wk. each. There were 2 wk. washout periods after the baseline diet and between intervention diets.
Baseline diet: 38% E fat (15% E SFA, 15% E MUFA, 6% E PUFA), 50% E CHO, 13% E PRO (no beef protein).
Lower carbohydrate, high-saturated fat (LCHSF) diet: 38% E fat (15% E SFA, 15% E MUFA, 5% E PUFA), 31% E CHO, 31% E PRO (10% E beef protein).
Lower carbohydrate, low-saturated fat (LCLSF) diet: 38% E fat (8% E SFA, 21% E MUFA, 6% E PUFA), 31% E CHO, 32% E PRO (11% E beef protein).
↓LDL-C
↓total LDL
↓medium LDL concentrations
(LCLSF diet compared to LCHSF and baseline diets)
↓small LDL concentrations (LCLSF diet compared to LCHSF diet)
↔large LDL
↔very small LDL
↔LDL peak diameter
↔LDL subclass phenotype
(all diets compared)
Faghihnia et al. (2012) [93] Randomized Crossover
UC
14 males 24–67 years
mean, 44.5 years
(SD, ± 14.4)
11 weeks Consumption of a baseline diet for 3 wk., followed by intakes of two experimental diets for 3 wk. each. There was a 2 wk. washout period between experimental diets.
Baseline diet: 38% E fat (15% E SFA, 15% E MUFA, 6% E PUFA), 50% E CHO, 13% E PRO.
Low CHO, high SFA diet: 38% E fat (15% E SFA, 15% E MUFA, 5% E PUFA), 31% E CHO, 31% E PRO (10% E beef protein).
Low CHO, low SFA diet: 38% E fat (8% E SFA, 21% E MUFA, 6% E PUFA), 31% E CHO, 31% E PRO (11% E beef protein).
↓LDL-C
(low CHO, low SFA diet compared to low CHO, high SFA diet)
↑LDL total mass concentration
↑LDL subclass I (large), II (medium), and III (small) mass concentrations
(low CHO, high SFA diet compared to low CHO, low SFA diet)
↔LDL subclass IV (very small)
(compared to each diet)
Guay et al. (2012) [94] Randomized
Double-blind
Crossover
PAGGE
12 males 18 to 50 years
mean, 27.1 years
(SD, ± 3.9)
2 weeks plus 6 days Consumption of two experimental diets for 3 d each, separated by a 2 wk. washout period.
Low fat diet: 25% E fat (6% E SFA, 12% E MUFA, 4.9% E PUFA), 61.8% E CHO, 15% E PRO.
High fat diet: 37% E fat (15% E SFA, 12.7% E MUFA, 4.3% E PUFA), 49.8% E CHO, 15% E PRO.
The experimental diets consisted of the same calories, proteins, fiber, MUFA, and PUFA.
↑LDL-C
↑LDL particle size
↔LDL peak particle diameter
↑percentage of large (not significant) and medium LDL particles
↓percentage of small LDL particles
(High fat diet compared with low fat diet)
Wang et al. (2015) [95] Randomized
Crossover
NMR
45 total
27 males
18 females
21–70 years
mean, 45 years
(SD, ± 13.3)
14 weeks A 2 wk. intake of an average American diet, followed by dietary treatments for 5 wk. each. There was a 2 wk. “compliance break” between treatments.
Average American diet (AAD): 34% E fat (13% E SFA, 12% E MUFA, 7% E PUFA), 51% E CHO, 16% E PRO.
Lower-fat diet (LF): 24% E fat (7% E SFA, 11% E MUFA, 6% E PUFA), 59% E CHO, 16–17% E PRO.
Moderate-fat diet (MF): 34% E fat (6% E SFA, 17% E MUFA, 9% E PUFA), 49% E CHO, 16–17% E PRO.
Diets were designed to meet calorie needs.
↓LDL-C
↓large LDL particle number
↓mean LDL particle size
(LF and MF compared to AAD; no significant difference between LF and MF)
↓total LDL particle number
(MF compared to LF; no significant difference compared to AAD)
↑small LDL particle number
(LF and MF compared to AAD; there was also a significant increase with LF compared to MF)
Dias et al. (2017) [96] Randomized
Parallel
NMR
26 total
11 males
15 females
21–65 years (29 subjects recruited)
SFA-rich diet:
median, 32 years
n-6 PUFA-rich diet:
median, 28 years
4 weeks plus 10 days Consumption of 4 × 1 g fish oil capsules (100 mg EPA and 500 mg DHA each) for 4 wk., followed by one of the treatment diets for 10 d while consuming the fish oil capsules.
SFA + LC n-3 PUFA diet: 38.8% E fat (50.4 g SFA/100 g, 34.6 g MUFA/100 g, 13.5 g PUFA/100 g, 9.1 g LA/100 g, 4 g LC n-3 PUFA/100 g), 37.6% E CHO, 17.8% E PRO.
n-6 PUFA + LC n-3 PUFA diet: 38.6% E fat (25.4 g SFA/100 g, 32.3 g MUFA/100 g, 39.1 g PUFA/100 g, 34.5 g LA/100 g, 4.6 g LC n-3 PUFA/100 g), 34% E CHO, 21% E PRO.
↓LDL-C
↓total LDL particle concentration
↓very large, medium-large, and small LDL particle concentrations
(n-6 PUFA + LC n-3 PUFA diet compared to SFA + LC n-3 PUFA diet)
Dias et al. (2017) [97] Randomized
Parallel
NMR
26 total
6 males
20 females
18–65 years 6 weeks Diets were consumed for 6 wk. The diets contained 400 mg EPA and 2000 mg DHA.
SFA-rich diet: 40.9% E fat (18.9% E SFA, 13.8% E MUFA, 4.4% E PUFA, 2.9% E LA, 1.13% E n-3 PUFA), 38.1% E CHO, 16.6% E PRO.
n-6 PUFA-rich diet: 42.4% E fat (12.6% E SFA, 13.2% E MUFA, 14.4% E PUFA, 12.7% E LA, 1% E n-3 PUFA), 41.6% E CHO, 18.1% E PRO.
↔LDL-C
↔LDL particle size concentrations
(between diets)
Ulven et al. (2019) [98] Randomized
Double-blind
NMR
99 total
Control diet:
52 total
21 males
31 females
Exp. diet:
47 total
20 males
27 females
25–70 years
Control diet:
mean, 55.2 years (SD, ± 9.8)
Exp. diet:
mean, 53.6 years (SD, ± 9.7)
10 weeks A 2 wk. duration which consisted of the control food items, followed by the consumption of 1 of 2 intervention diets for 8 wk.
Control diet: 42.8% E fat (18% E SFA, 15.4% E MUFA, 5.6% E PUFA), 36.6% E CHO, 15% E PRO.
Experimental diet: 42.9% E fat (11.5% E SFA, 15.7% E MUFA, 12% E PUFA), 34.2% E CHO, 16.5% E PRO.
There was a 6.5% E lower SFA and a 6.4% E higher PUFA in the experimental diet.
PRO, CHO, and fiber intakes were also significantly different.
↓LDL-C
↓Large, medium and small LDL particle concentrations (Experimental diet compared to control diet)
Bergeron et al. (2019) [99] Randomized
Parallel (high or low SFA arm)
Crossover
IM
113 total
High-SFA arm:
62 total
27 males
35 females
Low-SFA arm:
51 total
17 males
34 females
21–65 years
High-SFA arm:
mean, 45 years (SD, ± 12)
Low-SFA arm:
mean, 42 years (SD, ± 13)
Up to 28 weeks A 2 wk. baseline diet, followed by random assignment to a low-SFA (~ 7% E) or high-SFA (~ 14% E) arm. Within each SFA arm, 3 experimental diets were consumed for 4 wk. each, with a 2–7 wk. washout period between experimental diets.
High-SFA arm:
Red meat diet: 35% E fat (13% E SFA, 12% E MUFA, 5% E PUFA), 41% E CHO, 24% E PRO (11.5% E red meat).
White meat diet: 34% E fat (14% E SFA, 13% E MUFA, 5% E PUFA), 42% E CHO, 24% E PRO (11.5% E white meat).
Nonmeat diet: 35% E fat (14% E SFA, 12% E MUFA, 6% E PUFA), 41% E CHO, 24% E PRO (15.4% E vegetable protein).
Low-SFA arm:
Red meat diet: 35% E fat (8% E SFA, 21% E MUFA, 5% E PUFA), 39% E CHO, 26% E PRO (12.5% E red meat).
White meat diet: 31% E fat (7% E SFA, 18% E MUFA, 6% E PUFA), 46% E CHO, 23% E PRO (11% E white meat).
Nonmeat diet: 34% E fat (7% E SFA, 20% E MUFA, 5% E PUFA), 41% E CHO, 25% E PRO (16% E vegetable protein).
↑LDL-C
↑large LDL particle concentrations
(High SFA compared with low SFA, independent of protein source)
↔small- and medium-sized LDL particle concentrations
(High SFA intake compared with low SFA intake)
Buren et al. (2021) [100] Randomized
Crossover
PAGGE
17 females 19–27 years
median, 23.8 years
23 weeks Each diet was consumed for 4 wk., separated by a 15 wk. washout period.
Ketogenic low-carbohydrate high-fat (LCHF) diet: 77% E fat (33% E SFA), 4% E CHO (not exceeding 25 g, excluding fiber), 19% E PRO.
Control diet: 33% E fat, 44% E CHO, 19% E PRO.
↑LDL-C
↑sdLDL-C
↑large,buoyant LDL-C
(LCHF diet compared to control diet)
  1. Abbreviations: AA arachidonic acid, ALA alpha-linolenic acid, CHO carbohydrate, d days, DHA docosahexaenoic acid, E energy, EPA eicosapentaenoic acid, FA fatty acids, g grams, IM ion mobility, LA linoleic acid, LC long chain, LDL-C low-density lipoprotein cholesterol, MUFA monounsaturated fatty acids, NMR nuclear magnetic resonance, OA oleic acid, PA palmitic acid, PAGGE polyacrylamide gradient gel electrophoresis, PRO protein, P:S, ratio of polyunsaturated to saturated fatty acids, PUFA polyunsaturated fatty acids, SA stearic acid, SD standard deviation, sdLDL small, dense low-density lipoprotein, SFA saturated fatty acids, UC ultracentrifugation, wk. weeks, ↑, increase; ↓, decrease; ↔, no significant difference between groups