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• Introduction & Background

• What Is HMB?

• HMB Metabolism

• Research Studies

• Mechanisms

• Conclusion

• Questions

• References

2

Beta-hydroxyl-beta-methylbutyrate (HMB)

• Metabolite of leucine

• Discovered in 1996 by Dr. Steven Nissen

3

• Phenylalanine

• Lysine

• Threonine

• Tryptophan

• Methionine

• Histidine

• Valine

• Isoleucine

• Leucine

4

Essential Amino Acids

BCAA’s

HMB

5

• 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

• 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

8

• 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

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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12

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

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

• 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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19

• 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)

*

22

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

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

• 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.

• 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

27

• HMB may not be as effective in highly trained individuals

• Due to minimal muscle damage or protein breakdown

28

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

• 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

32

Values are reported as means + SE

*p<0.05 compared with control and LEU groups

• No significant differences in body fat or body composition.

• 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

Volume

(hrs/wk)

Results

Nissen et. al

Study 1

Study 2

20 males

28 males

3 wks

7 wks

3

15

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

35

+

_

HMB mTOR

Pathway

Ubiquitin

Proteasome

System

Muscle

Cholesterol

Increased

substrate for cell

membrane repair

Increased

protein synthesis

Decreased protein

degradation

+ 1.

2.

3.

37

• mTOR (Mammalian Target of Rapcamycin)

• 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

38

39

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

42

• A study was performed in tumor bearing (MAC-16) mice that

were treated for 3 days with either:

• Olive Oil

• HMB

43

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

45

• Female studies

• Long-term effects

• Negative side effects

46

• 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

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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.