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. 2016 Jun 6:6:27224.
doi: 10.1038/srep27224.

A carnosine intervention study in overweight human volunteers: bioavailability and reactive carbonyl species sequestering effect

Luca Regazzoni  1 , Barbora de Courten  2   3 , Davide Garzon  1 , Alessandra Altomare  1 , Cristina Marinello  1 , Michaela Jakubova  4 , Silvia Vallova  4 , Patrik Krumpolec  5 , Marina Carini  1 , Jozef Ukropec  5 , Barbara Ukropcova  4   5 , Giancarlo Aldini  1
Affiliations

A carnosine intervention study in overweight human volunteers: bioavailability and reactive carbonyl species sequestering effect

Luca Regazzoni et al. Sci Rep. .

Abstract

Carnosine is a natural dipeptide able to react with reactive carbonyl species, which have been recently associated with the onset and progression of several human diseases. Herein, we report an intervention study in overweight individuals. Carnosine (2 g/day) was orally administered for twelve weeks in order to evaluate its bioavailability and metabolic fate. Two carnosine adducts were detected in the urine samples of all subjects. Such adducts are generated from a reaction with acrolein, which is one of the most toxic and reactive compounds among reactive carbonyl species. However, neither carnosine nor adducts have been detected in plasma. Urinary excretion of adducts and carnosine showed a positive correlation although a high variability of individual response to carnosine supplementation was observed. Interestingly, treated subjects showed a significant decrease in the percentage of excreted adducts in reduced form, accompanied by a significant increase of the urinary excretion of both carnosine and carnosine-acrolein adducts. Altogether, data suggest that acrolein is entrapped in vivo by carnosine although the response to its supplementation is possibly influenced by individual diversities in terms of carnosine dietary intake, metabolism and basal production of reactive carbonyl species.

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Figures

Figure 1
Figure 1. Structure of carnosine and its corresponding adducts with acrolein and 4-hydroxynonenal.
Figure 2
Figure 2
Single ion chromatograms (SICs) with corresponding mass spectra for carnosine-propanal adduct (chromatogram A) and carnosine-propanol adduct (chromatogram B) in the urine of subject #4.
Figure 3
Figure 3
Tandem mass spectra (MSMS) for carnosine-propanal adduct detected ex vivo (spectrum A) or synthesized in vitro (spectrum C) and for carnosine-propanol adduct detected ex vivo (spectrum B) or synthesized in vitro (spectrum D).
Figure 4
Figure 4. Kruskal-Wallis test Ranks resulting from the comparison of urinary concentrations of carnosine (U-CAR), carnosine-propanol (U-POL) and carnosine propanal (U-PAL) as well as the amount of adducts in reduced form (% of U-POL).
White dots for control group individuals (n = 29), grey dots for placebo group individuals (n = 14) and black dots for carnosine group individuals (n = 15). Dashed lines represent the mean rank values for each experimental group.
Figure 5
Figure 5. Correlation between urinary concentration of carnosine-propanol (U-POL) and carnosine-propanal (U-PAL) in the urine of 29 subjects.
White dots for control group individuals, grey dots for placebo group individuals and black dots for carnosine group individuals.
Figure 6
Figure 6
XY scatter plots reporting the urinary concentration of carnosine (U-CAR) versus the urinary concentration of carnosine-propanal (U-PAL, scatter plot A) or versus the urinary concentration of carnosine-propanol (U-POL, scatter plot B). White dots for control group individuals, grey dots for placebo group individuals and black dots for carnosine group individuals. Dashed lines define the limits including 99.7% of the observations expected for the control group (μ ± 3σ).
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