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Food Chem Toxicol. 2014 May;67:145-53. doi: 10.1016/j.fct.2014.02.025. Epub 2014 Feb 24.

Subchronic toxicity study of β-hydroxy-β-methylbutyric free acid in Sprague-Dawley rats.

Author information

1
Metabolic Technologies Inc., 2711 S. Loop Dr., Suite 4400, Ames, IA 50010, USA. Electronic address: Fuller@mti-hmb.com.
2
Charles River Laboratories, Pathology Associates-Maryland, 15 Worman's Mill Ct., Suite I, Frederick, MD 21701, USA. Electronic address: Lawrence.Arp@crl.com.
3
Charles River Laboratories, Preclinical Services, 640 N. Elizabeth St., Spencerville, OH 45887, USA. Electronic address: Lisa.Diehl@crl.com.
4
Charles River Laboratories, Preclinical Services, 640 N. Elizabeth St., Spencerville, OH 45887, USA. Electronic address: Kelly.Landin@crl.com.
5
Metabolic Technologies Inc., 2711 S. Loop Dr., Suite 4400, Ames, IA 50010, USA. Electronic address: Baier@mti-hmb.com.
6
Metabolic Technologies Inc., 2711 S. Loop Dr., Suite 4400, Ames, IA 50010, USA; Department of Animal Science, Iowa State University, 313 Kildee Hall, Ames, IA 50010, USA. Electronic address: Rathmacher@mti-hmb.com.

Abstract

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.

KEYWORDS:

HMB free acid; Oral; Rat; Toxicity; β-Hydroxy-β-methylbutyric acid

PMID:
24576552
DOI:
10.1016/j.fct.2014.02.025
[Indexed for MEDLINE]
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