Fuller John C, Arp Lawrence H, Diehl Lisa M, Landin Kelly L, Baier Shawn M, Rathmacher John A
Metabolic Technologies Inc., 2711 S. Loop Dr., Suite 4400, Ames, IA 50010, USA.
Charles River Laboratories, Pathology Associates-Maryland, 15 Worman's Mill Ct., Suite I, Frederick, MD 21701, USA.
Food Chem Toxicol. 2014 May;67:145-53. doi: 10.1016/j.fct.2014.02.025. Epub 2014 Feb 24.
Calcium β-hydroxy-β-methylbutyrate-monohydrate (CaHMB) is a dietary supplement used as an ergogenic aid and in functional and medical foods. A new delivery form has been developed, β-hydroxy-β-methylbutyric free acid (HMBFA), which has improved bioavailability. While the safety of CaHMB is well documented, there are few published studies demonstrating the safety of HMBFA. Because HMBFA results in greater serum levels of β-hydroxy-β-methylbutyrate (HMB) and greater clearance rates, a 91-day subchronic toxicity study was conducted in male and female Sprague-Dawley Crl:CD rats assigned to HMBFA treatments at either 0%, 0.8%, 1.6%, or 4% of the diet by weight. No deaths or untoward clinical observations, and no negative clinical chemistry or hematology were attributed to the administration of HMBFA. Gross pathology and histopathology results showed no tissue abnormalities due to HMBFA and all measures were within a normal physiological range for the animals or were expected in the population studied. In conclusion, the no-observed-adverse-event-level (NOAEL) for HMBFA was the highest level administered, 4% of the diet, which corresponded to an intake of 2.48 and 2.83 g/kg BW d(-1) in the males and females, respectively. The equivalent human dosage using body surface area conversion would be 402 and 459 mg/kg BW d(-1) for men and women, respectively.
一水合β-羟基-β-甲基丁酸钙（CaHMB）是一种膳食补充剂，用作增强体能的辅助剂，并用于功能性食品和医疗食品中。现已开发出一种新的递送形式，即β-羟基-β-甲基丁酸游离酸（HMBFA），其生物利用度有所提高。虽然CaHMB的安全性已有充分记录，但很少有已发表的研究证明HMBFA的安全性。由于HMBFA会使血清中β-羟基-β-甲基丁酸（HMB）水平更高且清除率更高，因此对雄性和雌性斯普拉格-道利Crl:CD大鼠进行了一项为期91天的亚慢性毒性研究，这些大鼠被分配到按饮食重量计0%、0.8%、1.6%或4%的HMBFA处理组。未观察到因给予HMBFA导致的死亡或不良临床观察结果，也未发现负面的临床化学或血液学指标。大体病理学和组织病理学结果显示，未发现因HMBFA导致的组织异常，所有指标均在动物的正常生理范围内或在所研究群体的预期范围内。总之，HMBFA的未观察到不良事件水平（NOAEL）是所给予的最高水平，即饮食的4%，这分别相当于雄性和雌性大鼠的摄入量为2.48和2.83 g/kg体重/天。使用体表面积换算得出的等效人类剂量，男性和女性分别为402和459 mg/kg体重/天。
