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.

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Food proteins contain latent biofunctional peptide sequences within their primary structures which may have the ability to exert a physiological response in vivo. A large range of biofunctional peptides have been isolated from food proteins including opioid, immunomodulatory, antimicrobial, mineral binding, growth and muscle stimulating, anti-cancer, proteinase and angiotensin converting enzyme (ACE, EC 3.4.15.1) inhibitory peptides. The biofunctional peptide activity currently most studied in food proteins appears to be those that inhibit ACE. ACE plays a central role in the regulation of blood pressure (BP) through the production of the potent vasoconstrictor, angiotensin (Ang) II , and the degradation of the vasodilator, bradykinin (BK). ACE inhibitory peptides may therefore have the ability to lower BP in vivo by limiting the vasoconstrictory effects of Ang II and by potentiating the vasodilatory effects of BK. These ACE inhibitory peptides can be enzymatically released from intact proteins in vitro and in vivo during food processing and gastrointestinal digestion, respectively. ACE inhibitory peptides may be generated in or incorporated into functional foods in the development of 'natural' beneficial health products. Several products are currently on the market or are in development that contain peptide sequences which have ACE inhibitory properties. Detailed human studies are required in order to demonstrate the efficacy of these bioactive peptides prior to their widespread utilisation as physiologically beneficial functional foods/food ingredients.

The beneficial effects of food-derived antioxidants in health promotion and disease prevention are being increasingly recognized. Recently, there has been a particular focus on milk-derived peptides; as a source of antioxidants, these peptides are inactive within the sequence of the parent protein but can be released during enzyme hydrolysis. Once released, the peptides have been shown to possess radical scavenging, metal ion chelation properties and the ability to inhibit lipid peroxidation. A variety of methods have been used to evaluate in vitro antioxidant activity, however, there is no standardised methodology, which hinders comparison of data. This review provides an overview on the generation of antioxidative peptides from milk proteins, the proposed mechanisms of protein/peptide induced antioxidant activity, in vitro measurement of antioxidant activity, in vivo evaluation of plasma antioxidant capacity and the bioavailability of antioxidative peptides. The understanding gained from other food proteins is referred to where specific data on milk-derived peptides are limited. The potential applications and health benefits of antioxidant peptides are discussed with a particular focus on the aging population. The regulatory requirements for peptide-based antioxidant functional foods are also considered.