This document summarizes research on the effects of beta-hydroxy-beta-methylbutyrate (HMB). HMB is a metabolite of the essential amino acid leucine that is found in small amounts naturally. Studies have found that HMB supplementation can increase muscle strength, lean body mass, and aerobic/anaerobic capacity. The mechanisms of these effects include increasing protein synthesis and decreasing protein breakdown through inhibition of the ubiquitin-proteasome system. HMB may also act on the mTOR pathway to increase protein synthesis and provide substrates to support cell membrane integrity. However, the effects of HMB appear to be greater in untrained individuals compared to highly trained athletes.

1.  

2. • Introduction & Background
• What Is HMB?
• HMB Metabolism
• Research Studies
• Mechanisms
• Conclusion
• Questions
• References
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3. Beta-hydroxyl-beta-methylbutyrate (HMB)
• Metabolite of leucine
• Discovered in 1996 by Dr. Steven Nissen
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4. Essential Amino Acids
• Phenylalanine
• Lysine
• Threonine
• Tryptophan
• Methionine
• Histidine
• Valine
• Isoleucine BCAA’s
• Leucine HMB
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5. 5

6. • Increases protein synthesis
• Decreases protein degradation
• Increases strength
• Decreases muscle fatigue
• Preserves lean muscle mass in chronic diseases
(AIDS and cancer) and in the elderly
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7. 7

8. • The body only produces 0.2 - 0.4 g/day of HMB
• The mechanism of HMB absorption from the
intestine has not been reported
• Half-life ~2.5 hrs
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9. • HMB is found naturally in certain foods such as alfalfa,
catfish, and avocado
• Research suggests supplementation of 3 g/day of HMB
WHY NOT JUST TAKE LEUCINE?
• According 1988-1994 NHANES III, mean leucine intake
through food and supplements is 6.1 g/day
• Assuming 5%-10% conversion, this represents about 0.3 - 0.6 g/day
of HMB
600 g high quality protein 60 g leucine 3 g HMB
• Thus, HMB is supplemented directly into the diet
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10. Brand Price/3g serving
Twinlab HMB Fuel $0.40
Body Tech HMB $0.41
GNC Pro Performance $0.50
MHP A-Bomb $0.76
Met-Rx HMB $1.00
Optimum Nutrition HMB $1.09
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13. Groups Exercise Regimen:
• Untrained males
Control (n=6) • 3 times/wk for 3 wks
• Free weights & weight machines
1.5 g HMB (n=6) • Sessions alternated between upper and
lower body workouts
3 g HMB (n=8) • 4 - 6 repetitions to failure at 90% of 1 RM
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14. Week 3 0 g/day HMB 1.5 g/day HMB 3 g/day HMB P-Value
Body lean change from basal (kg) +0.40 +0.80 +1.21 0.11
Net Total Lower Body Lift (kg) +144.2 +389.0 +487.6 0.009*
Net Abdomen, Total Efforts +7.5 +22.5 +25.9 0.05*
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15. Week 3 0 g/day HMB 1.5 g/day HMB 3 g/day HMB P-Value
Plasma CPK (U/mL) 666 388 304 0.05*
Plasma LDH (U/mL) 187 171 169 0.07
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16. • 7 wks long
• 28 subjects (19-22 years old)
• Two groups
• Placebo group (0 g/day HMB)
• HMB group (3 g/day HMB)
• Exercise Regimen
• Weight lifted 2-3 hrs/day, 6 days/wk
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17. Change at 7 Weeks Control 3 g/day HMB P-Value
1 RM Bench Press (kg) +5.4 +15 0.01*
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18. These results suggest that HMB supplementation:
• Increases muscle strength
• Increases lean muscle tissue
• Decreases protein damage
• Decreases muscle breakdown
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19.  19 

20. • 37 untrained, college-aged males
• 3 groups
• 0 g/day HMB
• 3 g/day HMB
• 6 g/day HMB
• Performed resistance training 3 d/wk for 8 wks at 80% 1 RM
• Body composition determined by a seven-site skin-fold
evaluation
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21. Change in FFM (kg)
3
1.9 + 0.6
2.5
2 *
1.5
1
0.0 + 0.1 -0.2 + 0.5
0.5
0
-0.5
0 g/day 3 g/day 6 g/day
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*Significantly greater increase than the 0 g/day and 6 g/day (p < 0.05)

22. 0 g/d 3 g/d 6 g/d
Percent change in training volume from the first 2-wk period (0–2 wk) to the last 2-wk period (6–8 wk).
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23. 0 g/day
3 g/day
6 g/day
Standard errors expressed as error bars. 23
*Significantly greater increase in creatine kinase activity in 0 g/day than 3 g/day or 6 g/day

24. • 3 g/d of HMB significantly increased FFM
• Higher doses of HMB may not elicit greater benefits
• HMB did not result in higher training volume
• HMB may only decrease plasma CPK levels during the initial
training period
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25. Ransone J, Neighbors K, Lefavi R, Chromiak J. (2003) The effect of beta-hydroxy
beta-methylbutyrate on muscular strength and body composition in
collegiate football players. J Strength Cond Res. 17(1):34-9.
 25 

26. • Randomized double blind crossover, placebo designed
4 weeks  3 g/d HMB
1 week  Washout period
4 weeks  Placebo
• Subjects: 35 NCAA Div. I Football Players
• All subjects had at least 4 yrs of strength-training experience
• Performed supervised exercise
• 4 hrs/day, 4 days/wk
• Prior to the start of the competitive season (summer)
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27. • No significant differences in:
• Bench press, power cleans, squats (1 RM)
• Body composition
• Body fat %
• Body weight
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28. • HMB may not be as effective in highly trained individuals
• Due to minimal muscle damage or protein breakdown
28

29. Vukovich MD, Dreifort GD. (2001) Effect of beta-hydroxy beta-methylbutyrate
on the onset of blood lactate accumulation and V(O)(2) peak in
endurance-trained cyclists. J Strength Cond Res. 15(4):491-7.
 29 

30. • 8 competitive cyclists
• Cross-over design
• Three 2-week supplementation periods:
• 3 g/day Control
• 3 g/day HMB
• 3 g/day Leucine
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31. • Performed a graded cycle ergometry test
• Measurements:
• VO2 Peak
• Onset of blood lactate accumulation (OBLA)
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32. • No significant differences in body fat or body composition.
%Δ VO2 Peak %Δ Minutes to %Δ VO2 at 2 mM
(L/min) Reach VO2 Peak Blood Lactate
(OBLA)
Control -2.6 + 2.6 -3.6 + 3.5 0.75 + 2.1
HMB 4.0 + 1.4* 3.6 + 1.5* 9.1 + 2.4*
Leucine -1.9 + 1.3 -1.2 + 1.5 2.1 + 1.5
Values are reported as means + SE
*p<0.05 compared with control and LEU groups
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33. • HMB delays the onset of fatigue
• The changes in OBLA and VO2 peak may be a result of a:
• Decrease in lactate production
• Increase in lactate removal
• OR a combination of both
• Mechanism unknown
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34. Study Subjects Duration Training Results
Volume
(hrs/wk)
Nissen et. al
Study 1 20 males 3 wks 3 Lower body strength CPK
Study 2 28 males 7 wks 15 FFM bench press
Gallagher et. al 37 males 8 wks 3 3 g/d FFM
3 & 6 g/d sign CPK at 48 hrs
No benefits at 6 g/d
Vukovich et. al 8 males 2 wks Cycling Sign. VO2 Peak OBLA
test
Ransone et. al 35 males 8 wks 16 No sign. differences
Conflicting results may be due to:
•Length of study
•Trained vs. Untrained athletes
•Type of training 34

35.  
35

36. Decreased protein
degradation
Ubiquitin
2. Proteasome
System
_
mTOR
+ +
1. HMB Muscle 3.
Pathway Cholesterol
Increased Increased
protein synthesis substrate for cell
membrane repair

37. • mTOR (Mammalian Target of Rapcamycin)
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38. • mTOR is a protein kinase that plays a central role in the
control of cell growth, primarily by controlling mRNA
translation efficiency
• mTOR turns on the cells mechanisms for protein synthesis,
including enzymes that assemble proteins, called
ribosomes
• HMB appears to act upon the mTOR pathway by yet
unknown mechanisms
• Phosphorylates its protein substrates (p70S6K), which results in
increased myofibrillar protein synthesis
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39. 39

40. • 14 male Wistar rats
• 320 mg/kg body wt HMB or saline by oral gavage for 4 wks
40
Pimental GD, et al. (2011)

41. 41

42. • The UPS is responsible for seeking and destroying damaged
or faulty proteins
• UPS activity is increased in conditions of exacerbated muscle
catabolism, such as exercise
• Thus, inhibition of the UPS, could explain the attenuation of
muscle protein losses observed during treatment with HMB
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43. • A study was performed in tumor bearing (MAC-16) mice that
were treated for 3 days with either:
• Olive Oil
• HMB
P < 0.005
Effect of HMB on proteasome functional activity, determined as the
chymotrypsin-like enzyme activity in the gastrocnemius muscle.
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Smith HJ, et al. (2005)

44. 44

45. • HMB is a substrate for HMG-CoA  Cholesterol
• Muscle is dependent on cholesterol synthesis to meet its
needs and improve cell membrane integrity
• Stressed or injured muscle cells may not produce an
adequate amount of cholesterol
• Cholesterol reduces susceptibility to stretching and rupturing
• Thus, HMB stabilizes the muscle cell membrane and keeps it
intact
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46. • Female studies
• Long-term effects
• Negative side effects
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47. • HMB has been shown to:
• Improve anaerobic capacity
• Improve aerobic capacity
• Improve body composition and increase lean body
mass
• Decrease fatigue
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48. 48

49. • Zanchi NE, Gerlinger RF, Geuimaraes-Ferriera L, de Siqueira Filho MA, Felitti V, Lira FS,
Seelaender M, Lancha AH Jr. (2011) HMB supplementation: clinical and athletic performance-
related effects and mechanisms of action. Amino Acids. 40(4):1015-25.
• Nissen S, Sharp R, et al. (1996) Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on
muscle metabolism during resistance-exercise training. J Appl Physiol. 81(5):2095-104.
• Wilson GJ, Wilson JM, Manninen AH. (2008) Effects of beta-hydroxy-beta-methylbutyrate (HMB)
on exercise performance and body composition across varying levels of age, sex, and training
experience: A review. Nutr Metab (Lond). 3;5:1.
• Gallagher PM, Carrithers JA, et al. (2000) Beta-hydroxy-beta-methylbutyrate ingestion, Part I:
effects on strength and fat free mass. Med Sci Sports Exerc. 32(12):2109-15.
• Vukovich MD, Dreifort GD. (2001) Effect of beta-hydroxy beta-methylbutyrate on the onset of
blood lactate accumulation and V(O)(2) peak in endurance-trained cyclists. J Strength Cond Res.
15(4):491-7.
• Smith HJ, Mukerji P, Tisdale MJ. (2005) Attenuation of proteasome-induced proteolysis in skeletal
muscle by {beta}-hydroxy-{beta}-methylbutyrate in cancer-induced muscle loss. Cancer Res.
1;65(1):277-83.
• Ransone J, Neighbors K, Lefavi R, Chromiak J. (2003) The effect of beta-hydroxy beta-
methylbutyrate on muscular strength and body composition in collegiate football players. J
Strength Cond Res. 17(1):34-9.
49