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 C_MAX and AUC_0→∞ increased 1.6- and 2.1-fold (both p < 0.001) in the test product, respectively, which yielded 2.1-fold higher bioavailability; K_a 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); MRT_0→last increased in the test (143 ± 19 min) versus reference (128 ± 16 min) formulation (p = 0.0449); t_1/2 remained similar (test: 63.5 ± 8.7 min, reference: 68.9 ± 9.8 min). Paresthesia E_MAX 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 C_MAX, AUC_0→∞ and E_MAX 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.

中文翻译：

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与缓释片剂相比，新型控释粉末混合物提高了 β-丙氨酸的生物利用度


背景：β-丙氨酸是一种越来越受欢迎的运动补充剂，因为它始终能够改善身体机能，但其缺点是需要补充数周才能达到每日最大剂量和单次耐受剂量，且不会产生副作用（即感觉异常）。迄今为止，克服这一问题的唯一替代方案是使用缓释片剂，而粉末是最常用的形式，可在单剂量中输送几克氨基酸。在这项研究中，我们评估了新型控释粉末混合物（测试）与缓释片剂（参考）给药后 β-丙氨酸的生物利用度、药代动力学和感觉异常效应。方法：12 名受试者（25.6 ± 3.2 岁，50% 女性）参与了一项随机、单盲、交叉研究。每位参与者口服测试品（β-丙氨酸 8 g、 l-组氨酸 300 mg、肌肽 100 mg）或参考产品（10 片以达到 β-丙氨酸 8 g、锌 20 mg），并有 1 周的清除期。通过 LC-MS/MS 测定 β-丙氨酸血浆浓度（0-8 小时），并进行模型无关的药代动力学分析。使用视觉模拟评分（VAS）和分类强度感觉评分（ISS）评估感觉异常强度。结果：测试产品的 C _MAX和 AUC _{0 → ∞}分别增加了 1.6 倍和 2.1 倍（均p < 0.001），从而产生了 2.1 倍的生物利用度；与参考产品 (0.0299 ± 0.0121 min ^-1 ) ( p = 0.0834) 以及 V/F 和 Cl/F（均p < 0）相比，测试中的 Ka_值(0.0199 ± 0.0107 min ^-1 ) 有所下降。001）； MRT _{0 →与参考制剂（128 ± 16 分钟）相比，测试制剂（143 ± 19 分钟）最后}增加（ p = 0.0449）； t _1/2保持相似（测试：63.5 ± 8.7 分钟，参考：68.9 ± 9.8 分钟）。使用 VAS ( p = 0.086) 和 ISS ( p = 0.009) 使感觉异常 E _MAX增加 1.7 倍。 AUEC 随着 VAS ( p = 0.107) 和 ISS ( p = 0.019) 增加 1.9 倍，反映了量表的内在差异。药代动力学-药效分析显示C _MAX 、AUC _{0 → ∞}和E _MAX或AUEC 之间存在顺时针滞后环，无预测能力。没有副作用的报道（除了感觉异常）。结论：新型控释粉末混合物显示出 100% 更高的 β-丙氨酸生物利用度，开启了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储备的新范例。