Acute balenine supplementation in humans as a natural carnosinase-resistant alternative to carnosine

Abstract

Balenine possesses some of carnosine’s and anserine’s functions, yet it appears more resistant to the hydrolysing CN1 enzyme. The aim of this study was to elucidate the stability of balenine in the systemic circulation and its bioavailability in humans following acute supplementation. Two experiments were conducted in which (in vitro) carnosine, anserine and balenine were added to plasma to compare degradation profiles and (in vivo) three increasing doses (1–4–10 mg/kg) of balenine were acutely administered to 6 human volunteers. Half-life of balenine (34.9 ± 14.6 min) was respectively 29.1 and 16.3 times longer than that of carnosine (1.20 ± 0.36 min, p = 0.0044) and anserine (2.14 ± 0.58 min, p = 0.0044). In vivo, 10 mg/kg of balenine elicited a peak plasma concentration (Cmax) of 28 µM, which was 4 and 18 times higher than with 4 (p = 0.0034) and 1 mg/kg (p = 0.0017), respectively. CN1 activity showed strong negative correlations with half-life (ρ = − 0.829; p = 0.0583), Cmax (r = − 0.938; p = 0.0372) and incremental area under the curve (r = − 0.825; p = 0.0433). Overall, balenine seems more resistant to CN1 hydrolysis resulting in better in vivo bioavailability, yet its degradation remains dependent on enzyme activity. Although a similar functionality as carnosine and anserine remains to be demonstrated, opportunities arise for balenine as nutraceutical or ergogenic aid.

State of the Art in the Development of Human Serum Carnosinase Inhibitors

“…In fact, total or partial resistance to carnosinase displays better bioavailability, as demonstrated in vivo for the natural peptides anserine and balenine. Such peptides are substrates of serum carnosinase, but unlike carnosine, they are detectable in human plasma upon supplementation [ 41 , 58 , 125 ]. However, carnosine showed better activity both in vitro and in vivo [ 126 , 127 , 128 ].…”

The Role of Zinc in the Development of Vascular Dementia and Parkinson’s Disease and the Potential of Carnosine as Their Therapeutic Agent

“…Pharmacological variants of carnosine, such as carnosinol, a reduced carnosine derivative that is resistant to CN1, have been developed and show promise for use in the treatment of metabolic diseases, such as obesity and diabetes [ 134 ]. Additionally, balenine, found in marine mammals and reptiles, is a more stable natural analogue than carnosine in vivo and has potential uses as a dietary or ergogenic supplement [ 135 ].…”

Binding Modes of Carnostatine, Homocarnosine, and Ophidine to Human Carnosinase 1

“…Research on OPH and H-CAR is less extensive because such chemicals do not mainly contribute to human diet. 27 The hydrolytic rate of CAR is the fastest followed by ANS, OPH, and H-CAR. 10,26 A presence of ANS was reported to reduce the hydrolysis of CAR.…”

“…CN1 is the first and major hydrolyzer for histidine-containing dipeptides in serum, whereas the remaining is continuously degraded when they permeate into tissue. , Although CAR and ANS are major substrates, CN1 can also digest CAR analogues such as OPH and H-CAR , (Figure B). Research on OPH and H-CAR is less extensive because such chemicals do not mainly contribute to human diet . The hydrolytic rate of CAR is the fastest followed by ANS, OPH, and H-CAR. , A presence of ANS was reported to reduce the hydrolysis of CAR .…”