Download - Hmb seminar presentation pdf
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• Introduction & Background
• What Is HMB?
• HMB Metabolism
• Research Studies
• Mechanisms
• Conclusion
• Questions
• References
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Beta-hydroxyl-beta-methylbutyrate (HMB)
• Metabolite of leucine
• Discovered in 1996 by Dr. Steven Nissen
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• Phenylalanine
• Lysine
• Threonine
• Tryptophan
• Methionine
• Histidine
• Valine
• Isoleucine
• Leucine
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Essential Amino Acids
BCAA’s
HMB
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• 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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• 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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• 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 9
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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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Groups
Control (n=6)
1.5 g HMB (n=6)
3 g HMB (n=8)
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Exercise Regimen:
• Untrained males
• 3 times/wk for 3 wks
• Free weights & weight machines
• Sessions alternated between upper and
lower body workouts
• 4 - 6 repetitions to failure at 90% of 1 RM
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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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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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• 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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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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These results suggest that HMB supplementation:
• Increases muscle strength
• Increases lean muscle tissue
• Decreases protein damage
• Decreases muscle breakdown
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• 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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-0.5
0
0.5
1
1.5
2
2.5
3
0 g/day 3 g/day 6 g/day
Change in FFM (kg)
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0.0 + 0.1
1.9 + 0.6
-0.2 + 0.5
*Significantly greater increase than the 0 g/day and 6 g/day (p < 0.05)
*
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Percent change in training volume from the first 2-wk period (0–2 wk) to the last 2-wk period (6–8 wk).
0 g/d 3 g/d 6 g/d
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23 Standard errors expressed as error bars.
*Significantly greater increase in creatine kinase activity in 0 g/day than 3 g/day or 6 g/day
0 g/day
3 g/day
6 g/day
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• 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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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.
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• 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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• No significant differences in:
• Bench press, power cleans, squats (1 RM)
• Body composition
• Body fat %
• Body weight
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• HMB may not be as effective in highly trained individuals
• Due to minimal muscle damage or protein breakdown
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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.
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• 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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• Performed a graded cycle ergometry test
• Measurements:
• VO2 Peak
• Onset of blood lactate accumulation (OBLA)
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%Δ VO2 Peak (L/min)
%Δ Minutes to
Reach VO2 Peak
%Δ VO2 at 2 mM
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
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Values are reported as means + SE
*p<0.05 compared with control and LEU groups
• No significant differences in body fat or body composition.
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• 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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Study Subjects Duration Training
Volume
(hrs/wk)
Results
Nissen et. al
Study 1
Study 2
20 males
28 males
3 wks
7 wks
3
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Lower body strength CPK
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
test
Sign. VO2 Peak OBLA
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
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+
_
HMB mTOR
Pathway
Ubiquitin
Proteasome
System
Muscle
Cholesterol
Increased
substrate for cell
membrane repair
Increased
protein synthesis
Decreased protein
degradation
+ 1.
2.
3.
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• mTOR (Mammalian Target of Rapcamycin)
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• 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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40 Pimental GD, et al. (2011)
• 14 male Wistar rats
• 320 mg/kg body wt HMB or saline by oral gavage for 4 wks
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• 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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• A study was performed in tumor bearing (MAC-16) mice that
were treated for 3 days with either:
• Olive Oil
• HMB
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Smith HJ, et al. (2005)
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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• 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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• Female studies
• Long-term effects
• Negative side effects
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• 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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• 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.