de Salazar Lydia, Segarra Ignacio, López-Román Francisco Javier, Torregrosa-García Antonio, Pérez-Piñero Silvia, Ávila-Gandía Vicente
Sports Physiology Department, Faculty of Health Sciences, UCAM Universidad Católica San Antonio de Murcia, 30107 Guadalupe, Spain.
Department of Pharmacy, Faculty of Health Sciences, UCAM Universidad Católica San Antonio de Murcia, 30107 Guadalupe, Spain.
Pharmaceutics. 2021 Sep 19;13(9):1517. doi: 10.3390/pharmaceutics13091517.
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).
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).
The C and AUC increased 1.6- and 2.1-fold (both < 0.001) in the test product, respectively, which yielded 2.1-fold higher bioavailability; K decreased in the test (0.0199 ± 0.0107 min) versus the reference (0.0299 ± 0.0121 min) product ( = 0.0834) as well as V/F and Cl/F (both < 0.001); MRT increased in the test (143 ± 19 min) versus reference (128 ± 16 min) formulation ( = 0.0449); t remained similar (test: 63.5 ± 8.7 min, reference: 68.9 ± 9.8 min). Paresthesia E increased 1.7-fold using the VAS ( = 0.086) and the ISS ( = 0.009). AUEC increased 1.9-fold with the VAS ( = 0.107) and the ISS ( = 0.019) reflecting scale intrinsic differences. Pharmacokinetic-pharmacodynamic analysis showed a clockwise hysteresis loop without prediction ability between C, AUC and E or AUEC. No side effects were reported (except paresthesia).
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.
β-丙氨酸是一种运动补剂，因其能持续提高身体机能而越来越受欢迎，但其缺点是需要连续数周补充，且每日最大耐受剂量和单次耐受剂量会引发副作用（即感觉异常）。迄今为止，克服这一问题的唯一方法是使用缓释片，而粉末状是单次服用数克氨基酸最常用的剂型。在本研究中，我们评估了新型控释粉末混合物（测试产品）与缓释片（参比产品）给药后β-丙氨酸的生物利用度、药代动力学及感觉异常效应。
12名受试者（25.6±3.2岁，50%为女性）参与了一项随机、单盲、交叉研究。每位参与者口服测试产品（β-丙氨酸8克、L-组氨酸300毫克、肌肽100毫克）或参比产品（10片以达到β-丙氨酸8克、锌20毫克），洗脱期为1周。通过液相色谱-串联质谱法测定β-丙氨酸血浆浓度（0 - 8小时），并进行非房室药代动力学分析。使用视觉模拟评分法（VAS）和分类强度感觉评分法（ISS）评估感觉异常强度。
测试产品的Cmax和AUC分别增加了1.6倍和2.1倍（均P<0.001），生物利用度提高了2.1倍；测试产品的K值（0.0199±0.0107分钟）低于参比产品（0.0299±0.0121分钟）（P = 0.0834），V/F和Cl/F也较低（均P<0.001）；测试产品的MRT（143±19分钟）长于参比制剂（128±16分钟）（P = 0.0449）；t1/2保持相似（测试产品：63.5±8.7分钟，参比产品：68.9±9.8分钟）。使用VAS（P = 0.086）和ISS（P = 0.009）评估时，感觉异常效应增加了1.7倍。使用VAS（P = 0.107）和ISS（P = 0.019）评估时，AUEC增加了1.9倍，反映了量表内在差异。药代动力学-药效学分析显示Cmax、AUC与效应或AUEC之间存在顺时针滞后环，无预测能力。未报告其他副作用（除感觉异常外）。
新型控释粉末混合物显示β-丙氨酸的生物利用度提高了100%，开启了一个新的模式，从长期补充策略转向短期或中期补充策略，以增加运动营养中肌肽的储备。
