Effect of Oral carnosine supplementation on urinary TGF-β in diabetic nephropathy: a randomized controlled trial

Abstract

Background Activation of the transforming growth factor beta (TGF-β) pathway is a significant contributor to the pathogenesis of diabetic nephropathy. Carnosine is a dipeptide that can inhibit TGF-β synthesis. We tested the hypothesis that carnosine supplement added to standard therapy will result in reduced urinary TGF-β levels among patients with diabetic nephropathy. Methods We randomly assigned 40 patients with diabetic nephropathy and albuminuria 30–299 mg/day to treatment with carnosine (2 g/day) or placebo for 12 weeks. Urinary TGF-β level was determined using ELISA, urine albumin was ascertained by immunonephelometric assay, and renal function and metabolic profiles were determined at baseline and during 12 weeks of active treatment. Primary outcome was decrease in urinary levels of TGF-β. Results The 2 groups were comparable for baseline characteristics, blood pressure, urine albumin, urine TGF-β and renal function measurements. Urinary TGF-β significantly decreased with carnosine supplement (− 17.8% of the baseline values), whereas it tended to increase with placebo (+ 16.9% of the baseline values) (between-group difference P < 0.05). However, blood urea nitrogen, serum creatinine, glomerular filtration rate and other biochemical parameters remained unchanged during the study period including urinary albuminuria. Both groups were well tolerated with no serious side-effects. Conclusions These data indicated an additional renoprotective effect of oral supplementation with carnosine to decrease urinary TGF-β level that serves as a marker of renal injury in diabetic nephropathy. Trial registration Thai Clinical Trials, TCTR20200724002. Retrospectively Registered 24 July 2020.

Effect of L-Carnosine in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis

“…1), 5 studies were excluded for the following reasons: unavailable data, inappropriate study design, and unrelated outcomes. At the end of the selection process, 14 studies [5,22,33,[48][49][50][51][52][53][54][55][56][57][58] meeting the inclusion criteria were eventually selected for systematic review and meta-analysis. The PRISMA checklist is presented as a Supplementary File.…”

“…Table 2 (Ref. [5,22,33,[48][49][50][51][52][53][54][55][56][57][58]) and Supplementary Table 1 list the basic characteristics of the studies that were included. These studies were published between 2011 and 2022.…”

“…Studies in neurodegenerative disorders were found in 43% (6 out of 14) of the included studies [48][49][50][51]53,56]. Diabetes mellitus was found in 29% (4 out of 14) of the studies [22,33,52,57]. Two of the remaining four studies were on cancer [5,55], while the other two were on cardiovascular diseases [54,58].…”

“…Both genders were included in the majority of the studies. In 8 of the 14 studies, researchers looked at safety measures and reported on adverse drug reactions [5,33,49,50,52,54,56,57]. Five of the studies included were from Japan [5,51,53,56,58], two from Iran [22,50] and Italy [33,54] and one from Poland [48], USA [49], Greece [52], Egypt [55], and Thailand [57].…”

Histidine-Dipeptides in Relation to Diabetes and Obesity

“…Furthermore, in vivo, Smad3 absence helps in the improvement of glucose tolerance and glucose-stimulated insulin secretion. Carnosine diminishes TGF-β production, which helps in preventing diabetic nephropathy (Siriwattanasit et al 2021).…”