Angiotensin Converting Enzyme Inhibitory Peptides from a Lactotripeptide-Enriched Milk Beverage Are Absorbed Intact into the Circulation1

Abstract

Food products containing angiotensin converting enzyme (ACE) inhibitory peptides reportedly play a role in treatment of mild hypertension. The aim of this placebo-controlled crossover study was to assess the bioavailability of Ile-Pro-Pro and 7 other ACE-inhibiting peptides present in a lactotripeptide (LTP)-enriched yogurt beverage and whether meal intake affects Ile-Pro-Pro bioavailability. Six male and female subjects randomly consumed an LTP-enriched yogurt beverage or a placebo in the fasted state and an LTP-enriched yogurt beverage in the fed or fasted state. The area under the curve (AUC) of Ile-Pro-Pro after the LTP treatment in the fasted state was 2.1-fold of that after the placebo treatment (P < 0.001). The maximum peptide plasma concentration (C(max)) value was greater after consumption of the LTP-enriched beverage (897 +/- 157 pmol/L) than after the placebo treatment (555 +/- 0.09 pmol/L; P < 0.001) with a greater time after ingestion when reaching C(max) (T(max)) in the placebo treatment. Plasma concentrations of the peptides Leu-Trp, Phe-Tyr, Ile-Tyr, and Leu-Pro-Pro increased compared with baseline (P < 0.05) in the LTP-enriched and placebo treatment when consumed in the fasted state. However, DeltaC(max) values differed significantly between the placebo and LTP-enriched treatment only for Leu-Pro-Pro. Meal intake affected Ile-Pro-Pro concentrations. When the beverage was consumed after a meal, the AUC of Ile-Pro-Pro was 1.3-fold (P < 0.05) of the AUC derived from premeal intake. This was due to an increase in the plasma elimination half-life (P < 0.05); C(max) and T(max) were not affected by meal intake. In summary, this is the first demonstration, to our knowledge, that the tripeptide Ile-Pro-Pro selectively escapes from intestinal degradation and reaches the circulation undegraded.

The antihypertensive effect of fermented milk in individuals with prehypertension or borderline hypertension

“…However, in human studies the concentration of VPP and IPP in the products does not seem to correlate with the reduction in BP. 26 The influence of enzymatic digestion on the concentration of lactotripeptides is widely unknown and plasma concentration of VPP and IPP did not increase to an extent compatible with an antihypertensive effect after giving six healthy subjects FM in a study by Foltz et al 27 Only a modest increase of IPP was evident, whereas the concentration of VPP remained unchanged. Non-FM also increased the plasma concentration of IPP, thereby suggesting that this happens by the hydrolysis of milk proteins during digestion.…”

Dairy product consumption and the metabolic syndrome

“…In addition, in a recent placebo-controlled trial in 135 mildly hypertensive subjects by Engberink et al no effects of milk-derived peptides on blood pressure, ACE activity or plasma angiotensin II concentrations were found after 8 weeks of treatment (64) . Also, bioavailability of these peptides is questionable (58) , although one study has demonstrated the uptake of intact lactotripeptides (65) . Finally, the amount of Dairy consumption and the metabolic syndromeACE-inhibitory peptides in non-enriched dairy products may simply be too low to play a significant role in blood pressure regulation.…”

Long-term intervention with Lactobacillus helveticus fermented milk reduces augmentation index in hypertensive subjects

“…Milk-derived peptides improve vascular response in vitro probably through stimulation of endothelial nitric oxide (NO) release (Sipola et al, 2002b). It has been shown in experimental and clinical trials that the tripeptides Ile-Pro-Pro and Val-Pro-Pro can be absorbed at least partly from the intestine (Foltz et al, 2007;Jauhiainen et al, 2007b). Blood pressure-lowering effects of milk products containing Ile-Pro-Pro and Val-Pro-Pro tripeptides have been shown in several clinical trials (Seppo et al, 2003;Jauhiainen et al, 2005) and a meta-analysis of 12 randomized controlled trials found that the ingestion of tripeptides Ile-Pro-Pro and Val-Pro-Pro for 4-21 weeks decreases systolic blood pressure by 4.8 mm Hg and diastolic blood pressure by 2.2 mm Hg (Xu et al, 2008).…”