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

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)