Hypotensive peptides from milk proteins

J Nutr. 2004 Apr;134(4):980S-8S. doi: 10.1093/jn/134.4.980S.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antihypertensive Agents*
  • Caseins / chemistry
  • Caseins / metabolism
  • Humans
  • Kinins
  • Milk Proteins / chemistry*
  • Milk Proteins / metabolism
  • Natriuretic Peptides
  • Neprilysin
  • Nitric Oxide
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Rats
  • Renin-Angiotensin System


  • Antihypertensive Agents
  • Caseins
  • Kinins
  • Milk Proteins
  • Natriuretic Peptides
  • Peptides
  • Nitric Oxide
  • Neprilysin