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

Abstract

Background: β-Alanine is a sport supplement with increasing popularity due to its consistent ability to improve physical performance, with the downside of requiring several weeks of supplementation as imposed to the maximum daily and single dose tolerated without side effects (i.e., paresthesia). To date, the only alternative to overcome this problem has been use of a sustained-release tablet, while powders are the most commonly used format to deliver several grams of amino acids in a single dose. In this study we assessed the bioavailability, pharmacokinetics and paresthesia effect of β-alanine after administration in a novel controlled-released powder blend (test) versus a sustained-release tablet (reference). Methods: Twelve subjects (25.6 ± 3.2 y, 50% female) participated in a randomized, single-blind, crossover study. Each participant was administered orally the test (β-alanine 8 g, l-histidine 300 mg, carnosine 100 mg) or the reference product (10 tablets to reach β-alanine 8 g, Zinc 20 mg) with a 1-week washout period. β-Alanine plasma concentrations (0–8 h) were determined by LC-MS/MS and model-independent pharmacokinetic analysis was carried out. Paresthesia intensity was evaluated using a Visual Analog Score (VAS) and the categorical Intensity Sensory Score (ISS). Results: The CMAX and AUC0→∞ increased 1.6- and 2.1-fold (both p < 0.001) in the test product, respectively, which yielded 2.1-fold higher bioavailability; Ka decreased in the test (0.0199 ± 0.0107 min−1) versus the reference (0.0299 ± 0.0121 min−1) product (p = 0.0834) as well as V/F and Cl/F (both p < 0.001); MRT0→last increased in the test (143 ± 19 min) versus reference (128 ± 16 min) formulation (p = 0.0449); t1/2 remained similar (test: 63.5 ± 8.7 min, reference: 68.9 ± 9.8 min). Paresthesia EMAX increased 1.7-fold using the VAS (p = 0.086) and the ISS (p = 0.009). AUEC increased 1.9-fold with the VAS (p = 0.107) and the ISS (p = 0.019) reflecting scale intrinsic differences. Pharmacokinetic-pharmacodynamic analysis showed a clockwise hysteresis loop without prediction ability between CMAX, AUC0→∞ and EMAX or AUEC. No side effects were reported (except paresthesia). Conclusions: The novel controlled-release powder blend shows 100% higher bioavailability of β-alanine, opening a new paradigm that shifts from chronic to short or mid-term supplementation strategies to increase carnosine stores in sports nutrition.

Effect of a sustained-release formulation of β-alanine on laboratory parameters and paresthesia in recreational trained men: a randomized double-blind placebo-controlled study

“…Two thirds of the content of the granule was β-alanine and the remaining one third was coated for sustained release. The technology of the sustained-release system has been previously described ( 14 ). Participants assigned to the control group received an identically appearing microgranular powder based on uncooked wheat semolina from Triticum durum , and followed the same regimen.…”

“…Sustained-release formulations may have the advantage of tolerability of single higher doses of β-alanine, which may result in allowing the use of larger daily doses. In a study in healthy volunteers, de Salazar et al ( 14 ) reported that 8 g in a single oral dose of an innovative sustained-release β-alanine formulation (BETAFOR3MAX®) provided more efficient release kinetics with a 2-fold increase in bioavailability compared to the group that did not take the product without a significant increase in paresthesia. This dose has been the highest acute dose reported in a single administration, higher than the standard recommended daily dose of 6.4 g. In another study of Ávila-Gandía et al ( 15 ), the administration of 5 g of this same formulation, four times daily during 1 week to world tour cyclists during overreaching training, helped to attenuate 10-min time trial performance losses with no side effects or paresthesia.…”

Application of the oxycodone templated molecular imprinted polymer in adsorption of the drug from human blood plasma as the real biological environment; a joint experimental and density functional theory study

“…But, on the other hand, the half-life of that compound and the required dosage for body is low ( Pramanik and Thakkar, 2020 ). Thus, there are a variety of approaches which have been designed to regulate the release rate of drugs like the slow-release tablets ( de Salazar et al, 2021 ), the osmotic pumps ( Brunaugh et al, 2019 ), the sol-gels ( Raboh et al, 2021 ), and the MIPs ( Shi et al, 2020 ). The MIP granules are the achievements of the molecular imprinting technique (MIT) which have been developed as suitable candidates for drug delivery applications in the recent decade ( Motaharian et al, 2020 ).…”

Synthesis of a New Molecular Imprinted Polymer for Oxycodone Opioid and Its Formulation for Transdermal Controlled Drug Delivery Application: A Joint Experimental and Quantum Chemical Study

“…It is more highlighted when the release rate (and the bioavailability) of a drug is very high; while, the half‐life of that and the required dosage for body is low [2] . There are several methods designed to regulate the release rate of the drugs such as slow release tablets, [3] osmotic pumps, [4] sol‐gels, [5] and molecular imprinted polymer (MIPs) [6] …”

“…It is more highlighted when the release rate (and the bioavailability) of a drug is very high; while, the half-life of that and the required dosage for body is low. [2] There are several methods designed to regulate the release rate of the drugs such as slow release tablets, [3] osmotic pumps, [4] sol-gels, [5] and molecular imprinted polymer (MIPs). [6] The MIPs which are of the best achievements of the molecular imprinting technique (MIT), have recently been developed as suitable candidates for drug delivery applications.…”