Lactotripeptides

Last updated

Lactotripeptides are two naturally occurring milk peptides: Isoleucine-Proline-Proline (IPP) and Valine-Proline-Proline (VPP). These lactotripeptides are derived from casein, which is a milk protein also found in dairy products. Although most normal dairy products contain lactotripeptides, they are inactive within the original milk proteins. Dairy peptides can be effectively released through enzymatic predigestion a process by which milk protein is enzymatically broken down into smaller pieces. Some clinical studies have suggested that these lactotripeptides help promote healthy blood pressure levels as part of a healthy diet and lifestyle. [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] However, other clinical trials have seen no effects from these compounds. [16] [17]

Contents

Proposed mechanism

Dairy peptides are proposed to inhibit the activity of the angiotensin-converting enzyme (ACE). ACE is part of the renin–angiotensin system a natural mechanism that helps regulate blood pressure in the body. In certain individuals, the renin–angiotensin system can become overactive, often due to stress, an unhealthy diet, and/or unhealthy lifestyle. Under such conditions, ACE becomes overactive and converts more angiotensin I into angiotensin II. Angiotensin II causes blood vessels to constrict, and so increases blood pressure, which has potential to lead to hypertension. But, when ACE activity is inhibited, the formation of angiotensin II is reduced. This then helps the blood vessels to relax and expand back to a normal healthy state, so blood pressure is lowered.

Clinical trials

Several human trials aimed to evaluate the effect of lactotripeptides on blood pressure. Some trials show a blood pressure-lowering effect of lactotripeptides in people with mild to moderate hypertension, [1] [2] [18] however others see no effect from these peptides. [16] [19] [20] A recent systematic review of the literature found no confirmed ACE-inhibitor effects in humans, as well as no conclusive evidence for lactotripeptides as a successful intervention; the meta-analysis cited heterogeneity in methodology and lack of inclusion of recent larger studies by prior meta-analyses to account for the variance between studies. [17]

Related Research Articles

ACE inhibitor Class of medications used primarily to treat high blood pressure

Angiotensin-converting-enzyme inhibitors are a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart.

Peptides are short chains of amino acids linked by peptide (amide) bonds. The simplest peptides are dipeptides, followed by tripeptides, tetrapeptides, etc. A polypeptide is a long, continuous, and unbranched peptide chain. Hence, peptides fall under the broad chemical classes of biological oligomers and polymers, alongside nucleic acids, oligosaccharides, polysaccharides, and others.

Arginine Amino acid

Arginine, also known as l-arginine (symbol Arg or R), is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group, an α-carboxylic acid group, and a side chain consisting of a 3-carbon aliphatic straight chain ending in a guanidino group. At physiological pH, the carboxylic acid is deprotonated (−COO), the amino group is protonated (−NH3+), and the guanidino group is also protonated to give the guanidinium form (-C-(NH2)2+), making arginine a charged, aliphatic amino acid. It is the precursor for the biosynthesis of nitric oxide. It is encoded by the codons CGU, CGC, CGA, CGG, AGA, and AGG.

Hypertension Long term high blood pressure in the arteries

Hypertension, also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure typically does not cause symptoms. Long-term high blood pressure, however, is a major risk factor for coronary artery disease, stroke, heart failure, atrial fibrillation, peripheral arterial disease, vision loss, chronic kidney disease, and dementia.

Renin–angiotensin system hormone system that is involved in the regulation of the plasma sodium concentration and arterial blood pressure.

The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure and fluid and electrolyte balance, as well as systemic vascular resistance.

Angiotensin group of peptide hormones in mammals

Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adrenal cortex to promote sodium retention by the kidneys.

Pulse pressure is the difference between systolic and diastolic blood pressure.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

Angiotensin II receptor blocker group of pharmaceuticals that modulate the renin–angiotensin system

Angiotensin II receptor blockers (ARBs), formally angiotensin II type 1 (AT1) receptor antagonists, also known as angiotensin receptor blocker, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals that bind to and inhibit the angiotensin II type 1 receptor (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system.

Essential hypertension is the form of hypertension that by definition has no identifiable cause. It is the most common type of hypertension, affecting 95% of hypertensive patients; it tends to be familial and is likely to be the consequence of an interaction between environmental and genetic factors. Prevalence of essential hypertension increases with age, and individuals with relatively high blood pressure at younger ages are at increased risk for the subsequent development of hypertension. Hypertension can increase the risk of cerebral, cardiac, and renal events.

Hypertensive heart disease includes a number of complications of high blood pressure that affect the heart. While there are several definitions of hypertensive heart disease in the medical literature, the term is most widely used in the context of the International Classification of Diseases (ICD) coding categories. The definition includes heart failure and other cardiac complications of hypertension when a causal relationship between the heart disease and hypertension is stated or implied on the death certificate. In 2013 hypertensive heart disease resulted in 1.07 million deaths as compared with 630,000 deaths in 1990.

Aliskiren first in a class of drugs called direct renin inhibitors

Aliskiren is the first in a class of drugs called direct renin inhibitors. It is used for essential (primary) hypertension. While used for high blood pressure, other better studied medications are typically recommended due to concerns of higher side effects and less evidence of benefit.

In medicine, systolic hypertension is defined as an elevated systolic blood pressure (SBP). If the systolic blood pressure is elevated (>140) with a normal (<90) diastolic blood pressure (DBP), it is called "isolated systolic hypertension".

Renin inhibitor Drugs for volume regulation

Renin inhibitors are a group of pharmaceutical drugs used primarily in treatment of essential hypertension.

Lactobacillus helveticus is a lactic-acid producing, rod-shaped bacterium of the genus Lactobacillus. It is most commonly used in the production of American Swiss cheese and Emmental cheese, but is also sometimes used in making other styles of cheese, such as Cheddar, Parmesan, Romano, provolone, and mozzarella. The primary function of L. helveticus culture is to prevent bitterness and produce nutty flavors in the final cheese. In Emmental cheese production, L. helveticus is used in conjunction with a Propionibacterium culture, which is responsible for developing the holes through production of carbon dioxide gas.

Cilnidipine chemical compound

Cilnidipine is a calcium channel blocker. Cilnidipine is approved for use in Japan, China, India, Korea, and some European countries to treat hypertension.

Pathophysiology of hypertension

Pathophysiology is a branch of medicine which explains the function of the body as it relates to diseases and conditions. The pathophysiology of hypertension is an area which attempts to explain mechanistically the causes of hypertension, which is a chronic disease characterized by elevation of blood pressure. Hypertension can be classified by cause as either essential or secondary. About 90–95% of hypertension is essential hypertension. Some authorities define essential hypertension as that which has no known explanation, while others define its cause as being due to overconsumption of sodium and underconsumption of potassium. Secondary hypertension indicates that the hypertension is a result of a specific underlying condition with a well-known mechanism, such as chronic kidney disease, narrowing of the aorta or kidney arteries, or endocrine disorders such as excess aldosterone, cortisol, or catecholamines. Persistent hypertension is a major risk factor for hypertensive heart disease, coronary artery disease, stroke, aortic aneurysm, peripheral artery disease, and chronic kidney disease.

Complications of hypertension

Complications of hypertension are clinical outcomes that result from persistent elevation of blood pressure. Hypertension is a risk factor for all clinical manifestations of atherosclerosis since it is a risk factor for atherosclerosis itself. It is an independent predisposing factor for heart failure, coronary artery disease, stroke, kidney disease, and peripheral arterial disease. It is the most important risk factor for cardiovascular morbidity and mortality, in industrialized countries.

Salt and cardiovascular disease disease

Salt consumption has been extensively studied for its role in human physiology and impact on human health. Chronic, high intake of dietary salt consumption is associated with hypertension and cardiovascular disease, in addition to other adverse health outcomes. Major health and scientific organizations, such as the World Health Organization, US Centers for Disease Control and Prevention, and American Heart Association, have established high salt consumption as a major risk factor for cardiovascular diseases and stroke.

Hypertension is managed using lifestyle modification and antihypertensive medications. Hypertension is usually treated to achieve a blood pressure of below 140/90 mmHg to 160/100 mmHg. According to one 2003 review, reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease.

References

  1. 1 2 Boelsma E, Kloek J (March 2009). "Lactotripeptides and antihypertensive effects: a critical review". The British Journal of Nutrition. 101 (6): 776–86. doi: 10.1017/S0007114508137722 . PMID   19061526.
  2. 1 2 Pripp AH (2008). "Effect of peptides derived from food proteins on blood pressure: a meta-analysis of randomized controlled trials". Food & Nutrition Research. 52: 1641. doi:10.3402/fnr.v52i0.1641. PMC   2596738 . PMID   19109662.
  3. Xu JY, Qin LQ, Wang PY, Li W, Chang C (October 2008). "Effect of milk tripeptides on blood pressure: a meta-analysis of randomized controlled trials". Nutrition (Burbank, Los Angeles County, Calif.). 24 (10): 933–40. doi:10.1016/j.nut.2008.04.004. PMID   18562172.
  4. Aihara K, Kajimoto O, Hirata H, Takahashi R, Nakamura Y (August 2005). "Effect of powdered fermented milk with Lactobacillus helveticus on subjects with high-normal blood pressure or mild hypertension". Journal of the American College of Nutrition. 24 (4): 257–65. doi:10.1080/07315724.2005.10719473. PMID   16093403.
  5. Foltz M, Meynen EE, Bianco V, van Platerink C, Koning TM, Kloek J (April 2007). "Angiotensin converting enzyme inhibitory peptides from a lactotripeptide-enriched milk beverage are absorbed intact into the circulation". The Journal of Nutrition. 137 (4): 953–8. doi: 10.1093/jn/137.4.953 . PMID   17374660.
  6. Hata Y, Yamamoto M, Ohni M, Nakajima K, Nakamura Y, Takano T (November 1996). "A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects". The American Journal of Clinical Nutrition. 64 (5): 767–71. doi: 10.1093/ajcn/64.5.767 . PMID   8901799.
  7. Hirata H, Nakamura Y, Yada H, Moriguchi S, Kajimoto O, Takahashi T. Clinical Effects of New Sour Milk Drink in Mild or Moderate Hypertensive Subjects Archived 2010-09-28 at the Wayback Machine .J New Rem & Clin 2002;51:61-9.
  8. Jauhiainen T, Vapaatalo H, Poussa T, Kyrönpalo S, Rasmussen M, Korpela R (December 2005). "Lactobacillus helveticus fermented milk lowers blood pressure in hypertensive subjects in 24-h ambulatory blood pressure measurement". American Journal of Hypertension. 18 (12 Pt 1): 1600–5. doi: 10.1016/j.amjhyper.2005.06.006 . PMID   16364832.
  9. Jauhiainen T, Korpela R (March 2007). "Milk peptides and blood pressure". The Journal of Nutrition. 137 (3 Suppl 2): 825S–9S. doi: 10.1093/jn/137.3.825S . PMID   17311982.
  10. Masuda O, Nakamura Y, Takano T (December 1996). "Antihypertensive peptides are present in aorta after oral administration of sour milk containing these peptides to spontaneously hypertensive rats". The Journal of Nutrition. 126 (12): 3063–8. doi: 10.1093/jn/126.12.3063 . PMID   9001375.
  11. Mizuno S, Matsuura K, Gotou T, et al. (July 2005). "Antihypertensive effect of casein hydrolysate in a placebo-controlled study in subjects with high-normal blood pressure and mild hypertension". The British Journal of Nutrition. 94 (1): 84–91. doi: 10.1079/BJN20051422 . PMID   16115337.
  12. Mizushima S, Ohshige K, Watanabe J, et al. (August 2004). "Randomized controlled trial of sour milk on blood pressure in borderline hypertensive men". American Journal of Hypertension. 17 (8): 701–6. doi: 10.1016/j.amjhyper.2004.03.674 . PMID   15288885.
  13. Sano J, Ohki K, Higuchi T, et al. (2005). "Effect of casein hydrolysate, prepared with protease derived from Aspergillus oryzae, on subjects with high-normal blood pressure or mild hypertension". Journal of Medicinal Food. 8 (4): 423–30. doi:10.1089/jmf.2005.8.423. PMID   16379551.
  14. Seppo L, Jauhiainen T, Poussa T, Korpela R (February 2003). "A fermented milk high in bioactive peptides has a blood pressure-lowering effect in hypertensive subjects". The American Journal of Clinical Nutrition. 77 (2): 326–30. doi: 10.1093/ajcn/77.2.326 . PMID   12540390.
  15. Tuomilehto J, Lindström J, Hyyrynen J, et al. (November 2004). "Effect of ingesting sour milk fermented using Lactobacillus helveticus bacteria producing tripeptides on blood pressure in subjects with mild hypertension". Journal of Human Hypertension. 18 (11): 795–802. doi: 10.1038/sj.jhh.1001745 . PMID   15175633.
  16. 1 2 Engberink MF, Schouten EG, Kok FJ, van Mierlo LA, Brouwer IA, Geleijnse JM (February 2008). "Lactotripeptides show no effect on human blood pressure: results from a double-blind randomized controlled trial". Hypertension. 51 (2): 399–405. doi: 10.1161/HYPERTENSIONAHA.107.098988 . PMID   18086944.
  17. 1 2 Usinger L, Reimer C, Ibsen H (2012). "Fermented milk for hypertension". Cochrane Database of Systematic Reviews (4): CD008118. doi:10.1002/14651858.CD008118.pub2. PMID   22513955.
  18. Xu JY, Qin LQ, Wang PY, Li W, Chang C (October 2008). "Effect of milk tripeptides on blood pressure: a meta-analysis of randomized controlled trials". Nutrition. 24 (10): 933–40. doi:10.1016/j.nut.2008.04.004. PMID   18562172.
  19. van Mierlo LA, Koning MM, van der Zander K, Draijer R (February 2009). "Lactotripeptides do not lower ambulatory blood pressure in untreated whites: results from 2 controlled multicenter crossover studies". The American Journal of Clinical Nutrition. 89 (2): 617–23. doi: 10.3945/ajcn.2008.26918 . PMID   19106238.
  20. van der Zander K, Bots ML, Bak AA, Koning MM, de Leeuw PW (December 2008). "Enzymatically hydrolyzed lactotripeptides do not lower blood pressure in mildly hypertensive subjects". The American Journal of Clinical Nutrition. 88 (6): 1697–702. doi: 10.3945/ajcn.2008.26003 . PMID   19064533.