Hypotensive Peptides from Milk Proteins

Abstract

Hypertension is the major controllable risk factor associated with cardiovascular disease (CVD) events such as myocardial infarction, stroke, heart failure, and end-stage diabetes. A 5 mm Hg decrease in blood pressure has been equated with approximately 16% decrease in CVD. In the U.S. alone current annual antihypertensive drug costs are approximately dollars 15 billion. The renin-angiotensin-aldosterone system is a target for blood pressure control. Cleavage of angiotensinogen by renin produces angiotensin I which is subsequently hydrolyzed by angiotensin-I-converting enzyme (ACE) to angiotensin II (a potent vasoconstrictor). Various side effects are associated with the use of ACE inhibitory drugs in the control of blood pressure including hypotension, increased potassium levels, reduced renal function, cough, angioedema, skin rashes, and fetal abnormalities. Milk proteins, both caseins and whey proteins, are a rich source of ACE inhibitory peptides. Several studies in spontaneously hypertensive rats show that these casokinins and lactokinins can significantly reduce blood pressure. Furthermore, a limited number of human studies have associated milk protein-derived peptides with statistically significant hypotensive effects (i.e., lower systolic and diastolic pressures). The advent of effective milk protein based functional food ingredients/nutraceuticals for the prevention/control of blood pressure therefore has the potential to significantly reduce global healthcare cost.

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.…”

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

“…Most intensively studied are the tripeptides ValPro-Pro (VPP) and Ile-Pro-Pro (IPP), both with documented ACE-inhibitor effect in vitro. [8][9][10] Furthermore, FM contains proteins with opioid-like effect and possibly also g-amino butyric acid, which has been shown to have an inhibitory effect on the sympathetic nervous system in spontaneously hypertensive rats. 11,12 The type and amount of the antihypertensive compounds in FM depends on the substrate (milk) and the lactobacilli strain used for fermentation.…”

Milk proteins-derived bioactive peptides in dairy products: molecular, biological and methodological aspects

“…Pepsin and trypsin are commonly applied in enzymatic hydrolysis of proteins. They are generally used to produce ACE inhibitory peptides, namely antihypertensive peptides and calcium-binding phosphopeptides [Adt et al 2011, FitzGerald et al 2004. Other digestive enzymes and combinations of various proteinases, including alcalase, chymotrypsin, pancreatin Information adapted from references: Carrasco-Castilla et al [2012], Pihlanto [2006, 2007], Langevin et al [2012], Minkiewicz and Dziuba [2009].…”

“…The exact amount of a peptide that can be released and activated during the consumption of a balanced diet remains unknown because proteolytic enzymes are characterised by varied specifi city, therefore, the range of bioactive fragments released from a precursor protein cannot be accurately predicted [Dziuba and Darewicz 2007, Dziuba et al 2006, Phelan et al 2009]. The presence of bioactive peptides in dairy products such as cheese, fermented milk and yoghurt has been reported in numerous research studies [FitzGerald et al 2004, Gagnaire 2001, Gobbetti et al 2002, Korhonen and Pihlanto 2006, Meisel et al 1997, Nakamura et al 1995, Saito et al 2000.…”