Effects of probiotics consumption on lowering lipids and CVD risk factors: A systematic review and meta-analysis of randomized controlled trials

Figures & data

Figure 1. PRISMA flow chart of the included studies.

Table I. Characteristics of included clinical trials.

Studies	Participants (n) P/C	Design; Location	Age, mean (SD), P/C	Sex, M/F	Probiotic (weeks)	Probiotics strains	Dose (CFU/g and/or quantity/d)	Placebo group	Measured outcomes
1. Agerholm-Larsen et al. 2000	OW (56/14)	DB, PC, P; Denmark	ND / 39.4 (2.1)	20/50	Yogurt (8)	Streptococcus (S.) thermophilus and Enterococcus (E.) faecium	540 mL/d	Placebo yogurt with delta acidlactone	TC, LDL, HDL-C, TG
2. Andreasen et al. 2010	T2DM (21/24)	DB, PC, P; Denmark	55 (ND) / 60 (ND)	45/0	Capsule (4)	L. acidophilus	10^10	Placebo capsule	CRP, TNF-alpha
3. Asemi et al. 2013	Healthy (37/33)	SB, PC, P; Iran	24.2 (3.3) / 25.7 (3.1)	0/70	Yogurt (9)	S. thermophilus, L. bulgaricus, L. acidophilus, and Bifidobacterium (B.) animalis	10^7	Placebo yogurt	TC, LDL, HDL-C, TG
4. Ataie-Jafari et al. 2008	HC (7/7)	SB, PC, Cr; Iran	ND / ND	4/10	Yogurt (16)	L. acidophilus and B. lactis	10^6	Placebo yogurt	TC, LDL, HDL-C, TG
5. Barreto et al. 2014	Metabolic syndrome (12/12)	SB, PC, P; Brazil	62 (ND) / 63 (ND)	20/4	Fermented milk ()	L. plantarum	1.25 × 10^7 CFU/g; 80 mL/d	Non-fermented milk	TC, LDL, HDL-C, TG
6. Ejtahed et al. 2011	T2DM (30/30)	DB, PC, P; Iran	50.87 (1.40) / 51.00 (1.34)	23/37	Yogurt (6)	L. acidophilus and B. lactis	10^6 for each strain	Conventional yogurt	TC, LDL, HDL-C, TG
7. Fuentes et al. 2012	HC (30/30)	DB, PC, P; Spain	ND / ND	ND	Capsule (12)	L. plantarum	1.2 × 10^9	Placebo capsule	TC, LDL, HDL-C, TG
8. Inoue et al. 2003	HTN (18/17)	SB, PC, P; Japan	56.2 (2.1) / 53.9 (3.3)	20/15	Fermented milk (12)	L. casei and Lactococcus lactis	10–12 mg, 100 mL per day	Lactic acid placebo with the same taste	TC, TG
9. Jones et al. 2012	HC (56/58)	DB, PC, P; Canada	51.89 (ND) / 48.79 (ND)	41/73	Yogurt (6)	L. reuteri	5 × 10^9 CFU, twice daily	Placebo yogurt	TC, LDL, HDL-C, TG
10. June et al. 2013	OB (28/ 29)	DB, PC, P; Korea	ND / ND	22/35	Capsule (12)	L. gasseri	10^10	Placebo capsules	TC, LDL, HDL-C, TG
11. Kadooka et al. 2010	OB (43/44)	DB, PC, P; Japan	48.3 (9.3) / 49.2 (9.1)	59/28	Fermented milk (12)	L. gasseri	5 × 10^10 CFU	Placebo yogurt	BMI, WC
12. Lee et al. 2014	OB (25/25)	DB, PC, P; Korea	ND / ND	ND	Capsules (8)	S. thermophiles, L. plantarum, L. acidophilus, L. rhamnosus, B. lactis, B. longum, and B. breve.	5 × 10^9 CFU, two capsules per day	Placebo capsules	BMI, WC
13. Mizushima et al. 2004	HTN (23/23)	DB, PC, P; Japan	44.3 (10.3) / 48.5 (8.9)	46/0	Sour milk (4)	L. helveticus and Saccharomyces cerevisiae	160 g/d	Placebo acidified milk	HDL-C, TC, TG
14. Naruszewicz et al. 2002	Smokers (18/18)	DB, PC, P; Sweden	42.3 (2.8) / 41.8 (2.8)	18/18	Sour milk (6)	L. plantarum	5 × 10^7 CFU	Placebo milk manufactured in the same company	TC, LDL, HDL-C, TG
15. Simons et al. 2006	HC (23/21)	DB, PC, P; Australia	50 (12) / 53 (11)	16/28	Capsule (10)	L. fermentum	8 × 10^9 CFU	Placebo capsule	TC, LDL, HDL-C, TG

BMI = body mass index; CFU = colony-forming unit; Cr = crossover; CRP = C-reactive protein; DB = double blinded; HC = hypercholesterolemic patients; HDL-C = high-density lipoprotein cholesterol; HTN = hypertensive patients; LDL-C = low-density lipoprotein cholesterol; ND = not determined; OB = obese subjects; OW = overweight subjects; P = parallel; P/C = Probiotic group/Control group; PC = placebo controlled; SB = single blinded; T2DM = diabetic patients; TC = total cholesterol; TG = triglyceride; TNF = tumor necrosis factor; WC = waist circumference.

Figure 3. BMI and inflammatory markers plot. (A) BMI; (B) waist circumference; (C) C-reactive protein; (D) tumor necrosis factor alpha.

Table II. The subgroup analyses of the effect of probiotics on total cholesterol and LDL-C by probiotics administration criteria.

	Total cholesterol					LDL-C
Subgroups	Studies (n)	I^2	Q test	Mean difference (95% CI)	P between	Studies (n)	I^2	Q test	Mean difference (95% CI)	P between
Form of probiotics					0.67					0.65
Capsule	3	76.2%	8.4	–0.21 (–0.70, 0.28)		4	79.9%	9.9	–0.30 (–1.01, 0.41)
Milk or yogurt	10	4.8%	6.3	–0.31 (–0.42, –0.20)***		11	0%	1.8	–0.47 (–0.70, –0.25)***
Probiotics dosage					0.40					0.79
Large dose (≥ 10^9 CFU)	4	71.3%	36	–0.30 (–0.50, –0.10) ***		5	72.1%	10.8	–0.37 (–0.64, –0.16)***
Small dosage (< 10^9 CFU or milk)	6	0%	21	–0.32 (–0.41, –0.24)		5	0%	1.6	–0.44 (–0.72, –0.16)***
Number of strains of probiotics					0.69					0.47
Single strain of probiotics	4	64.3%	8.4	–0.22 (–0.65, 0.21)		6	55.1%	11.2	–0.34 (–0.68, –0.00)**
Multiple strains of probiotics	6	20.6%	6.3	–0.31 (–0.47, –0.16)***		4	0%	0.8	–0.52 (–0.85, –0.18)***
Duration of probiotics administration					0.93					0.81
Probiotic use for < 8 weeks	2	0%	0.1	–0.22 (–0.50, –0.05)		4	0%	0.4	–0.45(–0.72, –0.17)***
Probiotic use for ≥ 8 weeks	8	50.5%	14.1	–0.32 (–0.53, –0.11)***		6	58.1%	11.9	–0.24 (–0.78, –0.01)**
Health status of study sample					0.68					0.30
Hypercholesterolemic patients	7	33.6%	9.0	–0.30 (–0.38, –0.21)***		5	7.6%	4.3	–0.29 (–0.56, –0.03)***
Hypertension	3	28.1%	2.8	–0.51 (–0.73, –0.28)***		4	51.6%	6.2	–0.55 (–0.97, –0.14)***
By specific probiotic strains					0.63					0.64
Acidophilus strain	3	50.9%	4.1	–0.50 (–0.95, –0.05)**		3	0%	0.8	–0.52 (–0.85, –0.18)***
Non-acidophilus strains	7	52.4%	10.5	–0.26 (–0.46, –0.06)**		5	62.8%	10.8	–0.26 (–0.75, 0.02)
By baseline level
< 5.5 mmol/L TC or < 3.5 mmol/L LDL	5	34.5%	18	–0.20 (–0.38, –0.02)*	0.02*	3	10%	2.2	–0.18 (–0.33, –0.03)*	0.08
≥ 5.5 mmol/L TC or ≥ 3.5 mmol/L LDL	5	0%	7	–0.54 (–0.75, –0.33)***		6	0%	3.4	–0.38 (–0.38, –0.16)***

*Effect size significant at P < 0.05; **effect size significant at P < 0.01; ***effect size significant at P < 0.001.

LDL-C = low-density lipoprotein cholesterol.

Table III. The subgroup analyses of the effect of probiotics on HDL-C and triglycerides by probiotics administration criteria.

	HDL-C					Triglyceride
Subgroups	n	I^2	Q test	Mean difference (95% CI)	P between	n	I^2	Q test	Mean difference (95% CI)	P between
Form of probiotics					0.83					0.28
Capsule	3	0%	1.7	0.05 (–0.030.01, 0.12)		3	0%	1.9	–0.12 (–0.36, 0.12)
Milk or yogurt	7	0%	1.7	0.02 (–0.01, 0.05)		9	75.7%	32.9	–0.02 (–0.18, 0.33)
Probiotics dosage					0.89					0.47
Large dose (≥ 10^9 CFU)	4	0%	1.9	0.04 (–0.03, 0.11)		5	80.3%	20.3	0.12 (–0.29, 0.54)
Small dosage (< 10^9 CFU/milk form)	5	43%	1.7	0.02 (–0.01, 0.05)		7	0%	5.1	–0.03 (–0.11, 0.04)
Number of strains of probiotics					0.75					0.43
Single strain of probiotics	5	0%	2.2	0.05 (–0.02, 0.12)		6	76.1%	20.9	0.11 (–0.25, 0.47)
Multiple strains of probiotics	4	0%	1.0	0.02 (–0.01, 0.05)		6	0%	4.3	–0.09 (–0.11, 0.04)
Duration of probiotics administration					0.73					0.14
Probiotic use for < 8 weeks	3	0%	0.5	0.06 (–0.04, 0.16)		4	72.7%	11.0	0.25 (–0.14, 0.63)
Probiotic use for ≥ 8 weeks	6	0%	2.7	0.02 (–0.01, 0.05)		8	0%	6.4	0.00 (–0.12, 0.69)
Health status of study sample					0.99					0.76
Hypercholesterolemic patients	5	0%	1.9	0.02 (0.0, 0.05)		4	0%	5.9	–0.02 (–0.10, 0.05)
Hypertension	4	0%	1.9	0.03 (–0.05, 0.10)		12	85.6%	20.9	–0.06 (–0.47, 0.59)
By specific probiotic strains					0.29					0.07
Acidophilus strain	3	0%	1.0	0.02 (–0.08, 0.12)		3	0%	1.14	–0.23 (–0.47, 0.02)
Non-acidophilus strains	6	0%	2.8	0.03 (0.0, 0.05)		8	77.0%	30.45	0.11 (–0.13, 0.36)

HDL-C = high-density lipoprotein cholesterol.

Figure 4. Funnel plots. (A) Total cholesterol; (B) low-density lipoprotein cholesterol; (C) high-density lipoprotein cholesterol; (D) triglyceride; (E) BMI; (F) Waist.

Table IV. Egger test results on lipids, BMI, and waist circumference.

Egger test	t (95% CI)	P
Cholesterol	0.56 (–0.74, 1.31)	0.56
LDL	0.35 (–3.39, 4.58)	0.74
HDL	0.04 (–0.69, 0.71)	0.97
TG	0.09 (–1.66, 1.81)	0.93
BMI	0.08 (–4.88, 5.07)	0.94
Waist circumference	1.20 (–4/35, 7.71)	0.35

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