ACE inhibitory casein peptide lowers blood pressure and reshapes gut microbiota in a randomized double blind placebo controlled trial

• Published in: Scientific reports Vol. 15; no. 1; pp. 13840 - 16
• Main Authors: Li, Kexin, Jiang, Peng, Li, Shuangqi, Sun, Jin, Qi, Ce
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.04.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 692/699/75/243; 692/700/2814; 692/700/565/2072; Adult; Amino acids; Angiotensin; Angiotensin II; Angiotensin-converting enzyme inhibitors; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Antihypertensive effect; Antihypertensives; Arginine; Blood pressure; Blood Pressure - drug effects; Casein; Casein hydrolysate; Caseins - chemistry; Caseins - pharmacology; Caseins - therapeutic use; Clinical trials; Double-Blind Method; Double-blind randomized placebo-controlled clinical study; Enzyme inhibitors; Enzymes; Female; Gastrointestinal Microbiome - drug effects; Gut microbiota; Humanities and Social Sciences; Humans; Hypertension; Hypertension - drug therapy; Inflammation; Intestinal microflora; Male; Microbiota; Middle Aged; multidisciplinary; Peptides; Peptidyl-dipeptidase A; Placebos; Science; Science (multidisciplinary); Valine; Hypertension; Microbiota; Casein hydrolysate; Double-blind randomized placebo-controlled clinical study; Antihypertensive effect
• DOI: 10.1038/s41598-025-98446-6
• ISSN: 2045-2322

Casein-derived peptides have been shown to reduce blood pressure in animal studies, but evidence from human trials remains limited. This study aimed to investigate the antihypertensive effect and possible mechanisms of a hydrolyzed casein peptide tablet containing GPFPIIV and FFVAPFPEVFGK (HCP-C7C12) in prehypertensive/hypertensive patients. In this double-blind, randomized, placebo-controlled clinical trial, 131 participants were recruited and randomly allocated to either the test product group (HCP) taking tablets containing HCP-C7C12 or the placebo group for an eight-week intervention. 114 participants finally completed the study. After the intervention, both the systolic blood pressure and diastolic blood pressure in the HCP group were significantly reduced ( P  < 0.01) by 9.41% and 9.53%, respectively. The antihypertensive mechanisms may involve (1) HCP-C7C12 acting as an angiotensin-converting enzyme inhibitor, reducing angiotensin II production, and (2) modulating amino acid abundance such as L-Arginine, L-valine, leucine, and phenylalanine, resulting in anti-inflammatory and antioxidant effects that improve endothelial function. Additionally, HCP-C7C12 exhibited prebiotic-like effects, activating the butyrate and propionate production pathway and increasing the abundance of gut microbes with anti-inflammatory potentials. Overall, long-term consumption of the HCP-C7C12 tablet could be advantageous for blood pressure control in prehypertensive or hypertensive individuals.