Effects of β-hydroxy-β-methylbutyrate supplementation on muscle mass and strength in onabotulinumtoxin type-A-injected and contralateral quadriceps femoris in rabbits


  • Rafael Fortuna Human Performance Laboratory, University of Calgary, Calgary, Canada
  • Andrew Sawatsky
  • John C. Fuller, Jr Research, Metabolic Technologies LLC, Missoula, USA
  • Walter Herzog




botulinum toxin, Botox®, β-hydroxy-β-methylbutyrate supplementation, muscle strength, muscle mass, skeletal muscle


Objective: To determine the effects of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) on strength, muscle mass, and contractile material in muscle wasting induced by onabotulinumtoxin type-A (BoNT-A) injection into the quadriceps femoris muscles of New Zealand white rabbits.

Methods: A total of 21, female rabbits were divided into 3 groups (n = 7, each). Group 1 (Control) received intramuscular injection of saline. Groups 2 and 3 received intramuscular injection of BoNT-A (3.5 units/kg), with group 3 receiving supplementation with HMB (120 mg/kg-BW/day). Muscle morphology, mass, and strength were assessed 8 weeks later in both injected and non-injected contralateral limbs.

Results: Injected muscle strength of group 2 (BoNT-A) and group 3 (BoNT-A+HMB) was reduced by 63% and 60%, respectively, compared with Controls (p < 0.0001). Strength in contralateral muscles of group 2 was reduced by 23% vs Controls (p <0.002), while in group 3, strength was similar to Controls. Muscle mass in the injected muscles of the BoNT-A and BoNT-A+HMB groups was significantly reduced, by 46% and 48%, respectively.

Conclusion: While HMB did not prevent loss of muscle strength and mass in the BoNT-A-injected musculature, it prevented significant loss of contractile material in the injected musculature and strength loss in the contralateral non-injected musculature.

Lay Abstract

Onabotulinum toxin A (BoNT-A) is currently approved for cosmetic procedures and for the treatment of many conditions, such as migraine headaches and neuromuscular conditions associated with spasticity, such as cerebral palsy or post-stroke in USA. Once injected into the muscle BoNT-A causes muscle paralysis, which is reversible. The current study examined the local and distant detrimental effects of BoNT-A on decreasing muscle wasting and muscle function in a rabbit model, and the effects of dietary use of HMB (β-hydroxy-β-methylbutyrate), a leucine metabolite, on these detrimental effects. BoNT-A was injected into 1 leg of a rabbit model and muscle mass and strength measured in both the injected and non-injected legs. BoNT-A caused a loss of muscle mass in the injected legs. It also caused a loss of strength in the injected legs and a somewhat reduced loss of strength in the non-injected legs. This suggests that BoNT-A injections can cause a decrease in function in distant, non-target muscles. HMB partially reversed some of the detrimental side-effects of BoNT-A, being shown to be effective in maintaining muscle strength in the non-injected leg.


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How to Cite

Fortuna, R., Sawatsky, A., Fuller, Jr, J. C., & Herzog, W. (2021). Effects of β-hydroxy-β-methylbutyrate supplementation on muscle mass and strength in onabotulinumtoxin type-A-injected and contralateral quadriceps femoris in rabbits. Journal of Rehabilitation Medicine, 53(9 (September), jrm00229. https://doi.org/10.2340/16501977-2866



Original Report