Additive Beneficial Effects of Lactotripeptides Intake With Regular Exercise on Endothelium-Dependent Dilatation in Postmenopausal Women

Yoshizawa, Mutsuko; Maeda, Seiji; Miyaki, Asako; Misono, Maiko; Choi, Youngju; Shimojo, Nobutake; Ajisaka, Ryuichi; Tanaka, Hirofumi

doi:10.1038/ajh.2009.270

Cited by 64 publications

(67 citation statements)

References 21 publications

(24 reference statements)

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“…A positive effect was observed in the US, 7 Japanese 8 and southern European subjects, 9 but not in northern Europeans. 10 In Japanese subjects only, investigations confirmed an effect of LTP on flow-mediated dilation, 11 artery compliance, 12 and central BP. 13 Because the antihypertensive effect of LTPs seems to be strongly related to the ethnicity of patients, 6 it would be beneficial to increase our understanding of the effect of these nutraceuticals on different cardiovascular parameters in European subjects.…”

Section: Introductionmentioning

confidence: 99%

Lactotripeptides effect on office and 24-h ambulatory blood pressure, blood pressure stress response, pulse wave velocity and cardiac output in patients with high-normal blood pressure or first-degree hypertension: a randomized double-blind clinical trial

et al. 2011

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Contrasting data partially support a certain antihypertensive efficacy of lactotripeptides (LTPs) derived from enzymatic treatment of casein hydrolysate. Our aim was to evaluate this effect on a large number of hemodynamic parameters. We conducted a prospective double-blind randomized clinical trial, which included 52 patients affected by high-normal blood pressure (BP) or first-degree hypertension. We investigated the effect of a 6-week treatment with the LTPs isoleucine-proline-proline and valineproline-proline at 3 mg per day, assumed to be functional food, on office BP, 24-h ambulatory BP monitoring (ABPM) values, stress-induced BP increase and cardiac output-related parameters. In the LTP-treated subjects, we observed a significant reduction in office systolic BP (SBP; À5 ± 8 mm Hg, P¼0.013) and a significant improvement in pulse wave velocity (PWV; À0.66 ± 0.81 m s À1 , P¼0.001; an instrumental biomarker of vascular rigidity). No effect on 24-h ABPM parameters and BP reaction to stress was observed from treatment with the combined LTPs. LTPs, but not placebo, were associated with a mild but significant change in the stroke volume (SV), SV index (markers of cardiac flow), the acceleration index (ACI) and velocity index (VI) (markers of cardiac contractility). No effect was observed on parameters related to fluid dynamics or vascular resistance. LTPs positively influenced the office SBP, PWV, SV, SV index, ACI and VI in patients with high-normal BP or first-degree hypertension.

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Section: Introductionmentioning

confidence: 99%

Lactotripeptides effect on office and 24-h ambulatory blood pressure, blood pressure stress response, pulse wave velocity and cardiac output in patients with high-normal blood pressure or first-degree hypertension: a randomized double-blind clinical trial

et al. 2011

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“…Cicero et al (55) also reported a significant improvement in pulse wave velocity (20·66 (SD 0·81) m/s; P¼0·001), stroke volume, stroke volume index, acceleration index and velocity index after 6 weeks of treatment with LTP (3 mg/d) in fifty subjects, though these changes were relative to baseline. Yoshizawa et al (48,49) investigated the combined effect of exercise and LTP consumption on endothelium-dependent dilatation and carotid arterial compliance in postmenopausal women. They found significant improvements in both flow-mediated dilatation and arterial compliance in response to LTP, LTP þ exercise, and exercise þ placebo groups, but not in the placebo group, and concluded that whilst LTP had a beneficial effect on vascular function, the addition of exercise produced a synergistic effect.…”

Section: á a Fekete Et Almentioning

confidence: 99%

The impact of milk proteins and peptides on blood pressure and vascular function: a review of evidence from human intervention studies

2013

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CVD are the leading cause of death worldwide. Hypertension, a major controllable risk factor of CVD, is intimately associated with vascular dysfunction, a defect which is also now recognised to be a major, modifiable risk factor for the development of CVD. The purpose of the present review was to critically evaluate the evidence for the effects of milk proteins and their associated peptides on blood pressure (BP) and vascular dysfunction. After a detailed literature search, the number of human trials evaluating the antihypertensive effects of caseinderived peptides (excluding isoleucine-proline-proline and valine-proline-proline) was found to be limited; the studies were preliminary with substantial methodological limitations. Likewise, the data from human trials that examined the effects of whey protein and peptides were also scarce and inconsistent. To date, only one study has conducted a comparative investigation on the relative effects of the two main intact milk proteins on BP and vascular function. While both milk proteins were shown to reduce BP, only whey protein improved measures of arterial stiffness. In contrast, a growing number of human trials have produced evidence to support beneficial effects of both milk proteins and peptides on vascular health. However, comparison of the relative outcomes from these trials is difficult owing to variation in the forms of assessment and measures of vascular function. In conclusion, there is an accumulating body of evidence to support positive effects of milk proteins in improving and/or maintaining cardiovascular health. However, the variable quality of the studies that produced this evidence, and the lack of robust, randomised controlled intervention trials, undermines the formulation of firm conclusions on the potential benefits of milk proteins and peptides on vascular health.

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“…The Panel notes that 15 RCTs Cicero et al, 2010;De Leeuw et al, 2009;Engberink et al, 2008;Itakura et al, 2001;Mizushima et al, 2004;Seppo et al, 2003;Tuomilehto et al, 2004;Turpeinen et al, 2009;Usinger et al, 2010a;Van der Zander et al, 2008a;Van der Zander et al, 2008b;Van Mierlo et al, 2009 two studies;Yoshizawa et al, 2010), of which seven were designed to detect small (3-9 mm Hg) differences in SBP De Leeuw et al, 2009;Usinger et al, 2010a;Van der Zander et al, 2008a;Van der Zander et al, 2008b;Van Mierlo et al, 2009 two studies), did not observe an effect of IPP and VPP on SBP or DBP.…”

Section: Scientific Substantiation Of the Claimed Effect (Id 661 183mentioning

confidence: 99%

“…In the framework of further assessment, two additional meta-analyses (Aubin, 2011, unpublished;Cicero et al, 2011) and six RCTs (Cicero et al, 2010;Ishida et al, 2007;Nakamura et al, 2011;Turpeinen et al, 2009;Usinger et al, 2010a;Yoshizawa et al, 2010) were provided as pertinent to the claim.…”

Section: Scientific Substantiation Of the Claimed Effect (Id 661 183mentioning

confidence: 99%

“…However, the Panel notes that this study may have been underpowered with respect to BP outcomes. Yoshizawa et al (2010) included 43 healthy post-menopausal women into a placebo-controlled parallel study. Women were randomised to one of four treatment groups: capsules containing 6.7 mg/day IPP and VPP (n=12), the same treatment plus aerobic exercise (n=11), placebo (n=10) or placebo plus aerobic exercise (n=10).…”

Section: Scientific Substantiation Of the Claimed Effect (Id 661 183mentioning

confidence: 99%

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Scientific Opinion on the substantiation of health claims related to isoleucine‐proline‐proline (IPP) and valine‐proline‐proline (VPP) and maintenance of normal blood pressure (ID 661, 1831, 1832, 2891, further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

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2012

EFS2

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Following a request from the European Commission, pursuant to Article 13.1 of Regulation (EC) No 1924No /2006, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a health claim related to isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) and maintenance of normal blood pressure. The food constituent that is the subject of the claim, the tripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), is sufficiently characterised. The claimed effect, maintenance of normal blood pressure, is a beneficial physiological effect. The proposed target population is the general population. In weighing the evidence, the Panel took into account that 15 of the human intervention studies provided, of which seven were adequately powered to detect small between-group differences in systolic blood pressure, did not observe an effect of IPP and VPP on systolic blood pressure or diastolic blood pressure; that interpretation of the results from nine out of the ten studies which reported an effect of IPP and VPP on office systolic blood pressure was limited by methodological weaknesses; that the animal and in vitro/ex vivo studies did not provide additional information on the effect of IPP and VPP on blood pressure in humans; and that there is no convincing evidence for a mechanism by which IPP and VPP could exert the claimed effect in humans at the proposed dose. On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the consumption of IPP and VPP and maintenance of normal blood pressure. © European Food Safety Authority, 2012 KEY WORDSIsoleucine-proline-proline, IPP, valine-proline-proline, VPP, blood pressure, health claims. Isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) and maintenance of normal blood pressure (further assessment) 2 EFSA Journal 2012;10(6):2715 SUMMARYFollowing a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924No /2006. The Commission has agreed with EU Member States that a certain number of Article 13 health claims would be eligible for further assessment by EFSA in order to be able to take a final decision on whether or not to include these claims in the list of permitted health claims. This opinion addresses the scientific substantiation of health claims in relation to the tripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) and maintenance of normal blood pressure. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims, references that EFSA has received from Member States or directly from stakeholders and the additional information provided by the competent Authority of Germany for further assessment of this claim.The food constituent that is the subject of th...

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Additive Beneficial Effects of Lactotripeptides Intake With Regular Exercise on Endothelium-Dependent Dilatation in Postmenopausal Women

Abstract: We concluded that LTP ingestion combined with regular aerobic exercise improves endothelium-dependent dilatation to a greater extent than monotherapy with either intervention alone in postmenopausal women.

Cited by 64 publications

References 21 publications

Lactotripeptides effect on office and 24-h ambulatory blood pressure, blood pressure stress response, pulse wave velocity and cardiac output in patients with high-normal blood pressure or first-degree hypertension: a randomized double-blind clinical trial

Lactotripeptides effect on office and 24-h ambulatory blood pressure, blood pressure stress response, pulse wave velocity and cardiac output in patients with high-normal blood pressure or first-degree hypertension: a randomized double-blind clinical trial

The impact of milk proteins and peptides on blood pressure and vascular function: a review of evidence from human intervention studies

Scientific Opinion on the substantiation of health claims related to isoleucine‐proline‐proline (IPP) and valine‐proline‐proline (VPP) and maintenance of normal blood pressure (ID 661, 1831, 1832, 2891, further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

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