Lactotripeptides

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. 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. 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. S2CID 18513821.
  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. 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. 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.
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