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Plasma concentrations and ACE-inhibitory effects of tryptophan-containing peptides from whey protein hydrolysate in healthy volunteers

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Abstract

Purpose

The tryptophan-containing dipeptides isoleucine–tryptophan (IW) and tryptophan–leucine (WL) are angiotensin-converting enzyme (ACE)-inhibitors in vitro. These peptides are released by enzymatic hydrolysis of bovine whey protein. To exhibit ACE inhibition in vivo, peptides need to be absorbed into the circulatory system. This study aimed to determine the in vivo ACE-inhibitory potency of a whey protein hydrolysate (MPH), containing IW and WL, and to quantify plasma concentrations of these peptides after oral administration of MPH in healthy volunteers. Additionally, changes in blood pressure were investigated.

Results

After intake of 5 and 50 g MPH, plasma ACE activity was reduced to 86.4 ± 5.9 and 75.1 ± 6.9% of baseline activity, respectively. Although a clear ACE inhibition was measured, no effect on blood pressure was seen. Basal plasma concentrations of the tryptophan-containing dipeptides were 2.8 ± 0.7 nM for IW and 10.1 ± 1.8 nM for WL. After intake of 5–50 g MPH, peptide concentrations were dose dependently elevated to values between 12.5 ± 8.4 and 99.1 ± 58.7 nM for IW and 15.0 ± 4.3–34.9 ± 19.4 nM for WL. Administration of intact whey protein showed a minor ACE inhibition, probably caused by release of inhibitory peptides during gastrointestinal digestion. The increase of WL in plasma after intake of intact protein was similar to that determined after intake of MPH. In contrast, resulting IW concentrations were much lower after intake of intact whey protein when compared to MPH administration.

Conclusion

After intake of MPH, plasma ACE activity decreased in parallel to the increase of IW and WL plasma concentrations. However, the resulting peptide concentrations cannot fully explain the reduction of ACE activity in plasma with a direct enzyme inhibition. Therefore, this study points to a gap in the understanding of the inhibitory action of these peptides in vivo. Thus, to further develop innovative food additives with ACE activity diminishing capabilities, it appears mandatory to better characterize the mode of action of these peptides.

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Abbreviations

IW:

Isoleucine–tryptophan

WL:

Tryptophan–leucine

W:

Tryptophan

MPH:

Whey protein hydrolysate

Intact MP:

Non-hydrolyzed whey protein

ACE:

Angiotensin-converting enzyme

RAS:

Renin–angiotensin-system

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Funding

This work was supported by a grant-in-aid from the Federal Ministry of Education and Research of Germany, BMBF (Grant Number 03V0538).

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Author notes

  1. Melanie Martin and Diana Hagemann have contributed equally to this work.

Authors and Affiliations

  1. Institute of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01307, Dresden, Germany

    Melanie Martin, Sherif Khedr, Mats Leif Moskopp & Andreas Deussen

  2. Chair of Food Chemistry, Technische Universität Dresden, 01062, Dresden, Germany

    Diana Hagemann, Thinh Trung Nguyen, Lisa Schwarz & Thomas Henle

Authors
  1. Melanie Martin
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  2. Diana Hagemann
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  3. Thinh Trung Nguyen
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  4. Lisa Schwarz
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  5. Sherif Khedr
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  6. Mats Leif Moskopp
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  7. Thomas Henle
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  8. Andreas Deussen
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Correspondence to Melanie Martin.

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The authors declare that all human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Martin, M., Hagemann, D., Nguyen, T.T. et al. Plasma concentrations and ACE-inhibitory effects of tryptophan-containing peptides from whey protein hydrolysate in healthy volunteers. Eur J Nutr 59, 1135–1147 (2020). https://doi.org/10.1007/s00394-019-01974-x

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  • DOI: https://doi.org/10.1007/s00394-019-01974-x

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