The relative bioavailability of the calcium salt of β-hydroxy-β-methylbutyrate is greater than that of the free fatty acid form in rats

Journal of Nutrition

Volumn 144, Issue 10, 2014, Pages 1549-1555

  Shreeram, Sathyavageeswaran ^a   Johns, Paul W ^b   Subramaniam, Swaminathan ^c   Ramesh, Subbarayan ^d   Vaidyanathan, Vadakkanchery ^d   Puthan, Jithesh K ^d   Mandal, Shibajee ^d   Mamidi, Vijay Kumar ^d   Gelling, Richard W ^a  

^a Abbott Nutrition Research and Development   (Singapore)

^b ABBOTT LABORATORIES   (United States)

^c Abbott Nutrition Research and Development   (India)

^d SYNGENE INTERNATIONAL LTD   (India)

Author keywords

[No Author keywords available]

Indexed keywords

BETA-HYDROXYISOVALERIC ACID; CALCIUM; FATTY ACID; PROTEIN BINDING; VALERIC ACID DERIVATIVE;

ANIMAL; AREA UNDER THE CURVE; BIOAVAILABILITY; BLOOD; COMPARATIVE STUDY; DIET SUPPLEMENTATION; DRUG EFFECTS; MALE; METABOLISM; MICROSOME; ORAL DRUG ADMINISTRATION; PHYSIOLOGY; RAT; SPRAGUE DAWLEY RAT; TANDEM MASS SPECTROMETRY;

ADMINISTRATION, ORAL; ANIMALS; AREA UNDER CURVE; BIOLOGICAL AVAILABILITY; CALCIUM; DIETARY SUPPLEMENTS; FATTY ACIDS, NONESTERIFIED; MALE; MICROSOMES; PROTEIN BINDING; RATS; RATS, SPRAGUE-DAWLEY; TANDEM MASS SPECTROMETRY; VALERATES;

EID: 84907228636     PISSN: 00223166     EISSN: 15416100     Source Type: Journal    
DOI: 10.3945/jn.114.196527     Document Type: Article

References (31)

1. Nissen S, Sharp RL, Panton L, Vukovich M, Trappe S, Fuller JC Jr. beta- Hydroxy-beta-methylbutyrate (HMB) supplementation in humans is safe and may decrease cardiovascular risk factors. J Nutr 2000;130: 1937-45.
2. Sabourin PJ, Bieber LL. Formation of beta-hydroxyisovalerate by an alpha-ketoisocaproate oxygenase in human liver. Metabolism 1983;32: 160-4.
3. Nair KS, Schwartz RG,Welle S. Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans. Am J Physiol 1992;263: E928-34.
4. Van Koevering M, Nissen S. Oxidation of leucine and alpha-ketoisocaproate to beta-hydroxy-beta-methylbutyrate in vivo. Am J Physiol 1992;262:E27-31.
5. Nissen S, Sharp R, Ray M, Rathmacher JA, Rice D, Fuller JC Jr., Connelly AS, Abumrad N. Effect of leucine metabolite beta-hydroxybeta- methylbutyrate on muscle metabolism during resistance-exercise training. J Appl Physiol (1985) 1996;81(5):2095-104.
6. May PE, Barber A, D'Olimpio JT, Hourihane A, Abumrad NN. Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine. Am J Surg 2002;183:471-9.
7. Smith HJ, Mukerji P, Tisdale MJ. Attenuation of proteasome-induced proteolysis in skeletal muscle by b-hydroxy-b-methylbutyrate in cancerinduced muscle loss. Cancer Res 2005;65:277-83.
8. Clark RH, Feleke G, Din M, Yasmin T, Singh G, Khan FA, Rathmacher JA. Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study. JPEN J Parenter Enteral Nutr 2000;24:133-9.
9. Kovarik M, Muthny T, Sispera L, Holecek M. Effects of beta-hydroxybeta- methylbutyrate treatment in different types of skeletal muscle of intact and septic rats. J Physiol Biochem 2010;66:311-9.
10. Vukovich MD, Stubbs NB, Bohlken RM. Body composition in 70-yearold adults responds to dietary beta-hydroxy-beta-methylbutyrate similarly to that of young adults. J Nutr 2001;131:2049-52.
11. Stout JR, Smith-Ryan AE, Fukuda DH, Kendall KL, Moon JR, Hoffman JR, Wilson JM, Oliver JS, Mustad VA. Effect of calcium beta-hydroxybeta- methylbutyrate (CaHMB) with and without resistance training in men and women 65+yrs: a randomized, double-blind pilot trial. Exp Gerontol 2013;48:1303-10.
12. Deutz NE, Pereira SL, Hays NP, Oliver JS, Edens NK, Evans CM, Wolfe RR. Effect of beta-hydroxy-beta-methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults. Clin Nutr 2013;32: 704-12.
13. Wilkinson DJ, Hossain T, Hill DS, Phillips BE, Crossland H, Williams J, Loughna P, Churchward-Venne TA, Breen L, Phillips SM, et al. Effects of leucine and its metabolite beta-hydroxy-beta-methylbutyrate on human skeletal muscle protein metabolism. J Physiol 2013;591: 2911-23.
14. Wilson JM, Lowery RP, Joy JM, Walters JA, Baier SM, Fuller JC, Jr., Stout JR, Norton LE, Sikorski EM, Wilson SM, et al. beta-Hydroxybeta- methylbutyrate free acid reduces markers of exercise-induced muscle damage and improves recovery in resistance-trained men. Br J Nutr 2013; 110:538-44.
15. Townsend JR, Fragala MS, Jajtner AR, Gonzalez AM, Wells AJ, Mangine GT, Robinson EH,McCormack WP, Beyer KS, Pruna GJ, et al. beta-Hydroxy-beta-methylbutyrate (HMB)-free acid attenuates circulating TNF-alpha and TNFR1 expression postresistance exercise. J Appl Physiol (1985) 2013;115(8):1173-82.
16. Fuller JC Jr., Sharp RL, Angus HF, Baier SM, Rathmacher JA. Free acid gel form of beta-hydroxy-beta-methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt. Br J Nutr 2011;105:367-72.
17. Deshpande P, Jie Z, Subbarayan R, Mamidi VK, Chunduri RH, Das T, Shreeram S. Development and validation of LC-MS/MS method for the estimation of beta-hydroxy-beta-methylbutyrate in rat plasma and its application to pharmacokinetic studies. Biomed Chromatogr 2013;27:142-7.
18. Wohnsland F, Faller B. High-throughput permeability pH profile and high-throughput alkane/water log P with artificial membranes. J Med Chem 2001;44:923-30.
19. Baxter JH, Phillips RR, Dowlati L, Goehring KC, Johns PW. Direct determination of b-hydroxy-b-methylbutyrate (HMB) in liquid nutritional products. Food Analytical Methods 2011;4:341-6.
20. Hoag SW, Hussain AS. The impact of formulation on bioavailability: summary of workshop discussion. J Nutr 2001;131(4 Suppl):1389S-91S.
21. Toutain PL, Bousquet-Melou A. Plasma clearance. J Vet Pharmacol Ther 2004;27:415-25.
22. Toutain PL, Bousquet-Melou A. Volumes of distribution. J Vet Pharmacol Ther 2004;27:441-53.
23. Bohnert T, Gan LS. Plasma protein binding: from discovery to development. J Pharm Sci 2013;102:2953-94.
24. Chao P, Uss AS, Cheng KC. Use of intrinsic clearance for prediction of human hepatic clearance. Expert Opin Drug Metab Toxicol 2010;6: 189-98.
25. Nissen SL, Abumrad NN. Nutritional role of the leucine metabolite beta-hydroxy-beta-methylbutyrate. Nutr Biochem 1997;8:300-11.
26. Di L, Kerns EH. Solution stability-plasma, gastrointestinal, bioassay. Curr Drug Metab 2008;9:860-8.
27. Birkhahn RH, Renk CM. Immune response and leucine oxidation in oral and intravenous fed rats. Am J Clin Nutr 1984;39:45-53.
28. Argilés JM, Lopez-Soriano FJ. The oxidation of leucine in tumourbearing rats. Biochem J 1990;268:241-4.
29. Daniel P, Brazier M, Cerutti I, Pieri F, Tardivel I, Desmet G, Baillet J, Chany C. Pharmacokinetic study of butyric acid administered in vivo as sodium and arginine butyrate salts. Clin Chim Acta 1989;181: 255-63.
30. Cao X, Gibbs ST, Fang L, Miller HA, Landowski CP, Shin HC, Lennernas H, Zhong Y, Amidon GL, Yu LX, et al. Why is it challenging to predict intestinal drug absorption and oral bioavailability in human using rat model. Pharm Res 2006;23:1675-86.
31. Sharp RL. Alternate dosing strategies for beta-hydroxy-beta-methylbutyrate (HMB) supplementation: effect on plasma HMB responses. Metabolic Technologies, Inc., 31 July 2013 [cited 2014 Jul 2]. Available from: http:// clinicaltrials.gov/show/NCT01914952.