Effect of peptides derived from food proteins on blood pressure: a meta-analysis of randomized controlled trials

Figures & data

Figure 1.  Selection of randomized placebo-controlled trials for meta-analysis.

Table 1. Baseline characteristics of clinical trials included for meta-analysis with mean and standard deviation values

	Active intervention					Placebo control
Source	n	SBP (mmHg)	DBP (mmHg)	Age	Male (%)	n	SBP (mmHg)	DBP (mmHg)	Age	Male (%)
Hata et al. 10	17	159 (46)	89 (39)	77 (31)	23	13	151 (34)	87 (33)	73 (38)	31
Kawasaki et al. 11	17	146 (10)	91 (7)	46 (13)	94	12	146 (8)	92 (6)	49 (10)	92
Kawase et al. 12	10	124 (10)	NA	NA	100	10	124 (10)	NA	NA	100
Fujita et al. 13	30	150 (9)	94 (10)	62 (8)	60	31	149 (7)	93 (9)	61 (10)	58
Seppo et al. 14	10	148 (13)	94 (6)	49 (6)	30	7	148 (13)	93 (3)	46 (13)	29
Seppo et al. 15	22	155 (13)	97 (6)	51 (7)	46	17	152 (13)	96 (6)	48 (7)	53
Mizushima et al. 16	23	148 (10)	95 (10)	44 (10)	100	23	145 (13)	92 (10)	48 (9)	100
Toumilehto et al. 17	30	153 (10)	98 (7)	51 (10)	NA	29	157 (11)	98 (7)	54 (9)	NA
Aihara et al.* 8	20	137 (6)	85 (11)	53 (11)	65	20	137 (5)	85 (5)	50 (12)	65
Aihara et al.** 8	20	147 (9)	92 (9)	52 (12)	80	20	149 (7)	93 (12)	52 (10)	80
Jauhiainen et al. 18	53	149 (7)	94 (6)	51 (12)	66.0	55	150 (9)	93 (6)	55 (11)	62
Mizuno et al.* 9	12	134 (3)	82 (5)	NA	NA	12	133 (3)	82 (2)	NA	NA
Mizuno et al.** 9	21	149 (5)	88.6 (5)	NA	NA	20	150 (5)	89 (5)	NA	NA
Sano et al. 19	72	138 (7)	85 (5)	51 (10)	40.3	72	138 (6)	85 (5)	50 (10)	38.9
Cadée et al. 20	24	138 (12)	87 (10)	56 (11)	25	24	137 (15)	85 (10)	56 (12)	16.7
Lee et al. 21	27	144 (9)	91 (6)	55 (10)	52	26	141 (12)	90 (6)	48 (12)	62
Pins et al. 22	15	137 (11)	84 (7)	46 (13)	47	15	135 (9)	82 (6)	47 (14)	47

*Data from participants with high-normal blood pressure.

**Data from participants with mild hypertension.

Table 2. Daily intervention of bioactive components from different food sources and duration of clinical trials included for meta-analysis

Source	Daily intervention	Active component	Food source	Placebo	Duration (weeks)
Hata et al. 10	100 ml fermented milk	1.5 mg VPP and 1.1 mg IPP peptide	Milk	100 ml artificially acidified milk	8
Kawasaki et al. 11	100 ml beverage with hydrolyzed sardine muscle	3 mg VY peptide	Fish	100 ml beverage without hydrolyzed sardine muscle	4
Kawase et al. 12	400 ml fermented milk with whey protein concentrate	Whey protein concentrate	Milk	400 ml artificially acidified milk	8
Fujita et al. 13	10 tablets with active Katsuobushi oligopeptide	1.5 g Katsuobushi oligopeptide	Bonito (fish)	10 tablets with inactive Katsuobushi powder	5
Seppo et al. 14	150 ml fermented milk with strain that increase production of bioactive peptides	1.5 mg VPP and 1.1 mg IPP peptide	Milk	150 ml ordinary fermented milk	8
Seppo et al. 15	150 ml fermented milk with process to increase production of bioactive peptides	2.5 mg VPP and 2.25 mg IPP peptide	Milk	150 ml ordinary fermented milk	8
Mizushima et al. 16	160 g fermented milk	1.92 mg VPP and 1.15 mg IPP peptide	Milk	160 g artificially acidified milk	4
Toumilehto et al. 17	150 ml fermented milk with Lb. helveticus	2.5 mg VPP and 2.5 mg IPP peptide	Milk	150 ml ordinary fermented milk	10
Aihara et al. 8	12 g dried product from fermented milk	8.3 mg VPP and 4.7 mg IPP peptide	Milk	12 g dried product made without fermentation	4
Jauhiainen et al. 18	300 ml milk fermented with Lb. helveticus	30 mg VPP and 22.5 mg IPP peptide	Milk	300 ml ordinary fermented milk	10
Mizuno et al. 9	Two tablets of hydrolyzed casein	3.6 mg of VPP + IPP peptide	Milk	Tablets without hydrolyzed casein
Sano et al. 19	200 ml fruit juice with hydrolyzed casein	1.47 mg VPP and 1.6 mg IPP peptide	Milk	200 ml fruit juice without hydrolyzed casein	12
Cadée et al. 20	Tablets containing C12 Peptide (DMV International, The Netherlands)	3.8 g C12 peptide	Milk	Placebo tablets	4
Lee et al. 21	125 ml skimmed milk based beverage with whey powder	Whey powder	Milk	125 ml skimmed milk based beverage	12
Pins et al. 22	Hydrolyzed whey powder mixed with water	Hydrolyzed whey powder	Milk	Unhydrolyzed whey powder mixed with water	6

*Data from participants with high-normal blood pressure.

**Data from participants with mild hypertension.

Table 3. Calculating the effect of trials based on within or between subject comparison of intervention and placebo control treatment

	Intervention					Placebo control					Effect of trial
		SBP		DBP			SBP		DBP		SBP		DBP
Study	n	Mean	SD	Mean	SD	n	Mean	SD	Mean	SD	Effect	SE	Effect	SE
	Within subject comparison of blood pressure
Hata et al. 10	17	−14.1	12.8	−6.9	10.3	13	−4.4	13.0	−2.2	6.9	−9.7	4.7	−4.7	3.3
Seppo et al. 14	10	−14.9	9.4	−8.8	6.8	7	−4.1	11.4	−2.0	5.2	−10.8	5.0	−6.9	3.1
Seppo et al. 15	19	−15.4	8.3	−9.3	4.8	17	−9.4	13.2	−5.5	7.4	−6.0	3.6	−3.8	2.1
Mizushima et al. 16	23	−5.2	11.3	−2.0	8.0	23	−3.7	10.6	−0.3	8.3	−1.5	3.2	−1.7	2.4
Toumilehto et al. 17	30	−15.8	13.2	−10.3	6.5	29	−13.5	11.9	−9.8	7.5	−2.3	3.3	−0.5	1.8
Aihara et al.* 8	20	−5.0	8.9	−6.0	6.7	20	−2.0	8.9	−1.0	8.9	−3.0	2.8	−5.0	2.5
Aihara et al.** 8	20	−10.0	15.7	−7.5	15.7	20	0.5	11.2	−0.5	8.9	−10.5	4.3	−7.0	4.0
Jauhianinen et al. 18	53	−5.1	9.4	−1.1	5.6	55	−3.1	11.5	−2.1	6.1	−2.0	2.0	1.0	1.1
Cadée et al. 20	24	−10.7	7.8	−6.9	5.9	24	−3.6	11.8	−2.7	7.8	−7.1	2.9	−4.2	2.0
	Between subject comparison of blood pressure
Kawasaki et al. 11	17	137.1	12.0	85.3	8.6	12	142.5	11.5	91.0	8.7	−5.4	4.4	−5.7	3.2
Kawase et al. 12	10	118.0	9.5	−	−	10	125.0	14.−2	−	−	−7.0	5.4	−	−
Fujita et al. 13	30	137.5	11.5	86.5	8.2	31	148.5	9.9	92.0	8.4	−11.0	2.7	−5.5	2.1
Mizuno et al.* 9	12	131.1	5.8	79.8	6.0	12	133.1	5.5	79.2	4.3	−2.0	2.3	0.6	2.1
Mizuno et al.** 9	21	135.0	10.9	83.9	8.8	20	147.2	10.8	87.3	7.3	−12.2	3.4	−3.4	2.5
Sano et al. 19	72	132.3	7.3	81.2	4.8	72	136.4	8.0	83.7	5.6	−4.1	1.3	−2.5	0.9
Lee et al. 21	27	143.7	13.5	90.4	6.5	26	137.0	14.4	87.7	6.6	6.7	3.8	2.7	1.8
Pins et al. 22	15	126.0	6.2	77.0	5.4	15	133.0	7.4	80.0	5.8	−7.0	2.5	−3.0	2.1

*Data from participants with high-normal blood pressure.

**Data from participants with mild hypertension.

Figure 2.  Standard forest plot from meta-analysis on systolic blood pressure. Cochran's Q-test for homogeneity was Q=30.52, p-value = 0.02.

Figure 3.  Standard forest plot from meta-analysis on diastolic blood pressure. Cochran's Q-test for homogeneity was Q=29.10, p-value = 0.08.

Figure 4.  Funnel plots of mean effects on systolic and diastolic blood pressure to detect signs of publication bias.

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