Chemistry:Lactotripeptides

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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]

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]

References

  1. ↑ 1.0 1.1 "Lactotripeptides and antihypertensive effects: a critical review". The British Journal of Nutrition 101 (6): 776–86. March 2009. doi:10.1017/S0007114508137722. PMID 19061526. 
  2. ↑ 2.0 2.1 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. PMID 19109662. 
  3. ↑ "Effect of milk tripeptides on blood pressure: a meta-analysis of randomized controlled trials". Nutrition (Burbank, Los Angeles County, Calif.) 24 (10): 933–40. October 2008. doi:10.1016/j.nut.2008.04.004. PMID 18562172. 
  4. ↑ "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. August 2005. doi:10.1080/07315724.2005.10719473. PMID 16093403. http://www.jacn.org/cgi/pmidlookup?view=long&pmid=16093403. 
  5. ↑ "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. April 2007. doi:10.1093/jn/137.4.953. PMID 17374660. 
  6. ↑ "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. November 1996. 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 .J New Rem & Clin 2002;51:61-9.
  8. ↑ "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. December 2005. doi:10.1016/j.amjhyper.2005.06.006. PMID 16364832. 
  9. ↑ "Milk peptides and blood pressure". The Journal of Nutrition 137 (3 Suppl 2): 825S–9S. March 2007. doi:10.1093/jn/137.3.825S. PMID 17311982. 
  10. ↑ "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. December 1996. doi:10.1093/jn/126.12.3063. PMID 9001375. 
  11. ↑ "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. July 2005. doi:10.1079/BJN20051422. PMID 16115337. 
  12. ↑ "Randomized controlled trial of sour milk on blood pressure in borderline hypertensive men". American Journal of Hypertension 17 (8): 701–6. August 2004. doi:10.1016/j.amjhyper.2004.03.674. PMID 15288885. 
  13. ↑ "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. 2005. doi:10.1089/jmf.2005.8.423. PMID 16379551. 
  14. ↑ "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. February 2003. doi:10.1093/ajcn/77.2.326. PMID 12540390. 
  15. ↑ "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. November 2004. doi:10.1038/sj.jhh.1001745. PMID 15175633. 
  16. ↑ 16.0 16.1 "Lactotripeptides show no effect on human blood pressure: results from a double-blind randomized controlled trial". Hypertension 51 (2): 399–405. February 2008. doi:10.1161/HYPERTENSIONAHA.107.098988. PMID 18086944. 
  17. ↑ 17.0 17.1 "Fermented milk for hypertension". Cochrane Database of Systematic Reviews (4): CD008118. 2012. doi:10.1002/14651858.CD008118.pub2. PMID 22513955. 
  18. ↑ "Effect of milk tripeptides on blood pressure: a meta-analysis of randomized controlled trials". Nutrition 24 (10): 933–40. October 2008. doi:10.1016/j.nut.2008.04.004. PMID 18562172. 
  19. ↑ "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. February 2009. doi:10.3945/ajcn.2008.26918. PMID 19106238. 
  20. ↑ "Enzymatically hydrolyzed lactotripeptides do not lower blood pressure in mildly hypertensive subjects". The American Journal of Clinical Nutrition 88 (6): 1697–702. December 2008. doi:10.3945/ajcn.2008.26003. PMID 19064533. 



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