Insulin does not stimulate β-alanine transport into human skeletal muscle

Abstract

To test whether high circulating insulin concentrations influence the transport of β-alanine into skeletal muscle at either saturating or subsaturating β-alanine concentrations, we conducted two experiments whereby β-alanine and insulin concentrations were controlled. In experiment 1, 12 men received supraphysiological amounts of β-alanine intravenously (0.11 g·kg−1·min−1 for 150 min), with or without insulin infusion. β-Alanine and carnosine were measured in muscle before and 30 min after infusion. Blood samples were taken throughout the infusion protocol for plasma insulin and β-alanine analyses. β-Alanine content in 24-h urine was assessed. In experiment 2, six men ingested typical doses of β-alanine (10 mg/kg) before insulin infusion or no infusion. β-Alanine was assessed in muscle before and 120 min following ingestion. In experiment 1, no differences between conditions were shown for plasma β-alanine, muscle β-alanine, muscle carnosine and urinary β-alanine concentrations (all P > 0.05). In experiment 2, no differences between conditions were shown for plasma β-alanine or muscle β-alanine concentrations (all P > 0.05). Hyperinsulinemia did not increase β-alanine uptake by skeletal muscle cells, neither when substrate concentrations exceed the Vmax of β-alanine transporter TauT nor when it was below saturation. These results suggest that increasing insulin concentration is not necessary to maximize β-alanine transport into muscle following β-alanine intake.

The Muscle Carnosine Response to Beta-Alanine Supplementation: A Systematic Review With Bayesian Individual and Aggregate Data E-Max Model and Meta-Analysis

“…It is likely that these large amounts of BA are required because the incorporation of ingested BA into the muscle is very low, with ∼3-6% of ingested BA estimated to contribute toward MCarn accumulation (Stegen et al, 2013;Blancquaert et al, 2015). BA uptake into the muscle seems to be rapid and efficient, however the ability of carnosine synthase to incorporate it into MCarn is far slower (Bakardjiev and Bauer, 1994;de Souza Goncalves et al, 2020) and so the remaining BA is likely to be converted toward other processes such as transamination or oxidation (Blancquaert et al, 2016). Despite this inefficiency in the use of supplemental BA to synthesize MCarn, very large increases, to the order of 200%, have been reported (Saunders et al, 2017b).…”

Increased Bioavailability of β-Alanine by a Novel Controlled-Release Powder Blend Compared to a Slow-Release Tablet

“…Whereas TauT is a high-specificity, low capacity β-alanine transporter (which needs to be coupled with a Na and Cl ions) [ 75 ] and likely saturated at high concentration of systemic β-alanine, PAT1, on the contrary, is a low-specificity, high-capacity transporter probably less saturable. Although some studies have suggested that TauT plays a dominant role in β-alanine muscle cell uptake, it has also been suggested the existence of additional uptake mechanisms: after intravenous infusion of β-alanine at saturable level, exceeding the maximum transport capacity of TauT in humans a 2.5–3-fold increase in muscle β-alanine was achieved compared to a 1.5-fold increase when sub-saturating amounts were administered [ 43 ]. This would support the idea that higher concentrations would achieve greater muscle uptake, even beyond the transport capacity of TauT.…”

“…Likewise. Another study showed that paresthesia intensity was already decreasing albeit higher concentrations (~4-fold) were reached at later time points after intravenous infusion [ 43 ]. This behavior is similar to the one found in the current study and supports the findings that paresthesia intensity is not well correlated with plasma peak concentration, it is highly variable and tolerance may be developed.…”

“…Dose selection was aimed to provide the highest amount of β-alanine in a single dose without eliciting paresthesia, reducing the number of intakes per day, which would be expected to improve compliance and adherence in chronic supplementation [ 42 ]. A previous intravenous infusion study of 9.16 ± 0.78 g at a mean rate of 60.6 ± 5.7 mg/min during 150 min (3.6 g/h and 39.7% of the total amount per hour) of β alanine elicited mild transient paresthesia, which disappeared for all subjects after the infusion was completed [ 43 ]. Therefore, we should aim to keep below this limit.…”

“…A previous in vitro release assay test on the test product was performed and showed an estimated release rate of 16.68% per hour during a total of 6 h [ 44 ]. Thus, we estimated that an 8 g dose would yield approximately 1.33 g per hour (approximately half the amount compared to the previously mentioned study [ 43 ]), which may result in similar or unperceived paresthesia within the expected intersubject variability [ 24 ].…”