Page 1

A Support Guide From the Scientists Who Discovered HMB.

www.hmb.org


HMB doubles the effects of weight training.

Science instead of hype. Nutrition instead of magic. Fact over fiction. With HMB, you have the power of the truth to back your message. And it is a tremendously powerful force.

All HMB studies combined form the proof that HMB works and regularly doubles the effects of exercise on muscle growth. Science!

Often a single rumor can start a fad. A single study can cause a firestorm. And while this is just how HMB got its foothold as a nutritional supplement for weight training, it’s only the beginning of the story.

Before 0.18% Lean gain/week

HMB is no hype. And it certainly is not a one-study wonder. Once the first scientific study was out on HMB, other researchers jumped into the fray to see for themselves. And their research has continued to confirm what the very first study uncovered: 11 out of 11 published studies show a significant positive effect of HMB on lean gain. The studies averaged together show that HMB doubles the effect of resistance training on lean gain. Strength also follows suit.

164 subjects studied

After 0.42% Lean gain/week

170 subjects studied

Summary of 11 published studies.

HMB and lean gain (all published studies). (Net effect: HMB gain–Placebo gain)

Only CREATINE is in the same league as HMB, and HMB is actually effective in adding gain for those using CREATINE. (Jówko et al., Nutrition. 17:558-566, 2001) Ni

No nutritional supplement has been proven more effective in lean tissue gain and/or been proven safe like HMB.

ss en

O’ Pa Ga Jò Ra Pa Vu Kr Sl Co wk at ei nt l la nt ko ns er de on on nn oe vic on gh re e er et e e er he t t t e a a t et al al al al e t l l al t . . t ., ., a . ., ,2 ,2 al al ., ,2 a l . 19 19 l ., . 20 , 0 0 . 1 , 0 , 0 0 2 9 96 20 20 96 00 00 20 1 1 00 99 07 01 00 3 Ni

et

ss en

et

1


HMB shifts the balance of protein synthesis, tipping the scale in muscle’s favor.

When protein synthesis equals protein breakdown, there is no net gain of muscle protein. This is important in maintaining muscle mass. HMB aids in increasing muscle protein (mass) by two mechanisms.

Protein Breakdown

Protein Synthesis

s

HMB decreases protein breakdown caused by hard workouts at a molecular level by disrupting proteolysis through the ubiquitin-proteasome proteolytic pathway, the proteolytic enzyme that breaks muscle protein down.

HMB Supplementation

HMB is a metabolite of the BCAA leucine which has been shown to stimulate protein synthesis through the mTOR pathway. Potentially, HMB could play this role.

Protein Synthesis

Increase in Protein Synthesis HMB stimulates protein synthesis in muscle by multiple mechanisms, including the mTOR/p70S6k pathway, which stimulate translation initiation of protein synthesis. (Many of these effects are shared with leucine; however, HMB is more potent than leucine in promoting muscle gain).

Decrease Protein Breakdown HMB decreases protein breakdown at a molecular level caused by hard workouts. HMB results in decreasing the key regulating components of the ubiquitin-proteosome proteolytic pathway which results in LESS muscle loss. Therefore, the increase in synthesis and decrease in breakdown result in twice the gain of muscle over exercise alone. 2

+

Amino Acids

Protein Translation Initiation HMB Stimulates mTOR

Protein Breakdown

s

Increased Muscle (Protein) Gain

mRNA

= Protein Balance

Muscle Protein

mTOR

= Increased Muscle (Protein)

Decreased Muscle (Protein) Loss Amino Acids

Muscle Protein

Proteosome + Ubiquitin HMB Blocks mRNA Expression of Key Regulators

HMB minimizes muscle damage, decreases protein breakdown, and stimulates protein synthesis.


HMB reduces muscle damage associated with exercise, which shortens recovery time.

It’s as true for the casual athlete as it is for the serious competitor: people really feel a workout the next day. And for many, that workout could be as minor as a heavy set of weekend chores. Yet, HMB is shown to benefit anyone involved in strenuous activity by reducing the effects of a “workout hangover.”

HMB shortens recovery time and allows maximal intensity in the next strenuous activity. With HMB: Less Muscle Damage

After Running

With HMB, people may still notice those “muscles they never knew they had,” only they’ll feel less sore. Plus, in the next workout, they’ll have increased strength.

HMB works. HMB minimizes muscle damage during hard exercise by supplying the material muscle cells need to synthesize enough cholesterol to improve the stability of the cell membrane under stress. This reduces muscle damage (leakage) as measured by a reduction of muscle damage markers such as creatine phosphokinase (CPK) in the blood stream.

(Knitter et al., J. Applied Physiol. 89:1340-1344, 2000) After Weightlifting

And remember - it’s not hype; it’s consistently proven in clinical studies. From the serious athlete to the conscientious exerciser who works out for the health of it, the evidence is growing that HMB is a nutritional supplement that has yet to reach its full potential.

(Jówko et al., Nutrition. 17:558-566, 2001)

Muscle damage, measured by CPK leakage into the bloodstream, is reduced when HMB is taken in conjunction with running and weightlifting.

3


HMB improves aerobic performance for runners, cyclists, and triathletes.

HMB improves aerobic performance in average, everyday athletes. HMB is shown to increase maximal oxygen consumption (VO2max) and improve the respiratory compensation point (RCP). It appears that HMB may reduce metabolic acidosis, and the research also shows that it helps athletes tolerate high-intensity activity over a long period of time. Research also shows that HMB lengthens the time to the onset of blood lactate accumulation (OBLA). HMB improves the training status for endurance athletes for positive effects on endurance performance.

HMB also benefits endurance athletes. Figure 1

Lambolely et al., 2007 IJSNEM 17:56-69 Figure 2

These scientific studies support the value of HMB for aerobic benefit.

Lambolely et al., 2007 IJSNEM 17:56-69; RCP, Respiratory compensation point Figure 3

Vukovich and Dreifort., 2001 J. Strength Cond. Res. 15: 491-497; OBLA, Onset blood lactate accumulation.

4


Clinical research shows HMB is a safe, effective way for the casual athlete to maximize the health benefits of exercise.

As the body of research grows, so does the potential for HMB.

9 studies show

Invariably the first question on the heels of a discovery of a great nutritional training aid is, “But what about side effects?”

and has “health positive” attributes rather than the negative ones.

In the case of HMB, the study of the side effects is almost as astounding as the discovery of the initial benefits: lower LDL cholesterol, blood pressure, and cardiovascular risk.

HMB is safe

Health Benefits of HMB

That alone is a powerful case for expanding the use of HMB for the casual athlete, since many casual athletes exercise simply for health benefits instead of competitive ones.

After 9 studies, the results are conclusive: along with exercise, HMB aids the reduction of risk factors associated with the cardiovascular system. Finally here is a supplement that offers substantial benefits to the “mainstream” exercise community.

Nissen et al., J. Nutr. 130:1937-1945, 2000. A summary of HMB safety from 9 clinical studies.

5


REFEREED PUBLICATION LIST STRENGTH AND MUSCLE BUILDING

6

Data from this study suggest that HMB can Placebo-controlled, double-blind clinical study improve nitrogen balance in severely injured trauma patients. of HMB in critically injured patients.

2007

Peer-Reviewed Kuhls, D.A., J.A. Rathmacher, M.D. Musngi, D.A. Frisch, J. Nielson, A. Barber, A.D. Paper MacIntyre, J.E. Coates, and J.J. Fildes. ß-Hydroxy-ß-methylbutyrate (HMB) supplementation in critically ill trauma patients. J. Trauma Inj. Infect. & Crit. Care 62:125-131.

2007

Peer-Reviewed O’Connor, D.M. and M.J. Crowe. Effects of six Subjects’ ethical weeks of ß-Hydroxy-ß-methylbutyrate (HMB) backgrounds prevented Paper and HMB/Creatine supplementation on this study from being strength, power, and anthropometry of highly conducted as a doubletrained athletes. J. Strength Cond. Res. blind, placebo-controlled study; however, a placebo 21:419-423. treatment was utilized.

This 6-week study in trained Rugby players showed a numerical increase in lean tissue with HMB supplementation.

2005

Peer-Reviewed Palisin, T. and J.J. Stacy, M.D. Paper ß-Hydroxy-ß-methylbutyrate (HMB) and its use in athletics. Current Sports Med. Reports. 4:220-223.

Review.

Studies reviewed showed HMB may be beneficial in increasing lean mass in a number of groups (AIDS and cancer patients as well as athletes). No study has shown adverse effects of HMB as have been seen with other supplement regimens.

2004

Peer-Reviewed Flakoll, P., R. Sharp, S. Baier, D. Levenhagen, Paper C. Carr, and S. Nissen. Effect of ß-Hydroxy-ß-methylbutyrate (HMB) arginine, and lysine supplementation on strength, functionality, body composition, and protein metabolism in elderly women. Nutrition 20: 445-451.

Two double-blind, randomized, placebo-controlled clinical studies in elderly women.

Data from 2 independent studies demonstrate that a nutritional mixture of HMB, arginine, and lysine can enhance whole body protein synthesis and improve functionality in elderly women.

2003

Peer-Reviewed Nissen, S. and R. Sharp. The efficacy of dietary supplements in accentuating the Paper muscle mass and strength gains achieved with resistance exercise: A meta-analysis. J. Appl. Physiol. 94:651-659.

A meta-analysis of dietary supplements used to increase lean and strength.

Few supplements used as ergogenic aids have 2 or more peer-reviewed studies. Only HMB and creatine have been shown to significantly increase lean and strength gains with exercise.

2003

Peer-Reviewed Ransone, J., K. Neighbors, R. LeFavi, and J. Double-blind randomized Chromiak. The effect of ß-Hydroxy-ßcrossover study in 35 Paper methylbutyrate (HMB) on muscular strength training collegiate football players. and body composition in collegiate football players. J. Strength Cond. Res. 17:34-39.

This study was performed with highly trained athletes undergoing an intense training program. Although this study failed to show significant differences, HMB supplemented subjects gained more lean and lost body fat.

2001

Peer-Reviewed Vukovich, M.D., N.B. Stubbs and R.M. Bohlken. Body composition in 70-year-old Paper adults responds to dietary ß-Hydroxy-ßmethylbutyrate (HMB) similarly to that of young adults. J. Nutr. 131:2049-2052.

Double-blind randomized study in elderly men and women participating in a weighttraining exercise program.

In this study, HMB tended to increase muscle strength and lean mass while significantly increasing fat loss over this 8-week study in older adults.

2001

Peer-Reviewed Jówko, E., P. Ostaszewski, M. Jank, J. Sacharuk, A. Zieniewicz, J. Wilczak, and S. Nissen. Paper Creatine and ß-Hydroxy-ß-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program. Nutrition 17:558-566.

Double-blind randomized study in weight-training males.

This is the first major study to show that HMB combined with creatine supplementation results in even greater strength and lean gains than either HMB or creatine supplementation alone.


2001

Peer-Reviewed Slater, G., D. Jenkins, P. Logan, H. Lee, M. Vukovich, J.A. Rathmacher and A.G. Hahn. Paper ß-Hydroxy-ß-methylbutyrate (HMB) supplementation does not affect changes in strength or body composition during resistance training in trained men. Int. J. Sport Nutr. & Exer. Met. 11:384-396.

Double-blind randomized study in trained male athletes undergoing a weight-training program.

In highly trained athletes, HMB numerically increased strength and lean, but the increase was not significantly greater than that of the placebo group.

2000

Peer-Reviewed Gallagher, P.M., J.A. Carrithers, M.P. Godard, K.E. Schulze, and S.W. Trappe. Paper ß-Hydroxy-ß-methylbutyrate (HMB) ingestion, Part I: effects on strength and fat free mass. Med. & Sci. in Sports & Exer. 32:2109-2115.

Double-blind randomized study with male weightlifters.

In this study, either 3 or 6 grams of HMB were consumed per day. HMB increased lean mass, peak muscle torques, and decreased plasma CPK after resistance training with no added benefit seen from consuming the higher level.

2000

Peer-Reviewed Panton, L.B., J.A. Rathmacher, S. Baier, and S. Nissen. Nutritional supplementation of the Paper leucine metabolite ß-Hydroxy-ß-methylbutyrate (HMB) during resistance training. Nutrition 16:734-739.

Two double-blind randomized studies including males and females and trained and untrained weightlifters.

Two separate studies showed that regardless of gender or prior training, HMB increases strength and minimizes muscle damage when combined with a 4-week resistancetraining program.

1999

Peer-Reviewed Kreider, R.B., M. Ferreira, M. Wilson, and A.L. Almada. Effects of calcium Paper ß-Hydroxy-ß-methylbutyrate (HMB) supplementation during resistance training on markers of catabolism, body composition, and strength. Int. J. Sports Med. 20:503-509.

Randomized placebo-controlled study of 40 experienced, resistance-trained males.

In this 4-week study, trained athletes consumed either 3 or 6 grams of HMB per day. While not statistically significant, HMB consumption resulted in numerically greater lean and strength gains.

1996

Peer-Reviewed Nissen, S., R. Sharp, M. Ray, J.A. Rathmacher, D. Rice, J.C. Fuller, Jr., A.S. Paper Connelly and N. Abumrad. Effect of the leucine metabolite ß-Hydroxy-ß-methylbutyrate (HMB) on muscle metabolism during resistance-exercise training. J. Appl. Physiol. 81: 2095-2104.

Two double-blind randomized studies in weight-training males.

In these separate studies, one for 3 weeks and one for 7 weeks, it was found that feeding 3 grams of HMB to exercising humans increased lean mass, strength, and reduced muscle damage.

AEROBIC EXERCISE 2007

Placebo-controlled study Peer-Reviewed Lamboley, C.R., D. Royer, and I.J. Dionne. Paper Effects of ß-Hydroxy-ß-methylbutyrate in college students. (HMB) on aerobic performance components and body composition in college students. Int. J. Sport Nutr. Exerc. Metab. 17:56-69.

HMB supplementation significantly increased maximal oxygen consumption.

2001

Peer-Reviewed Vukovich, M.D. and G.D. Dreifort. The Double-blind switchback effect of ß-Hydroxy-ß-methylbutyrate (HMB) study with HMB, leucine, Paper on VO2 peak and lactate threshold in and placebo. endurance-trained cyclists. J. Strength and Conditioning Res. 15:491-497.

This study showed that HMB supplementation increased the cyclists endurance as measured by VO2 peak and lactate threshold.

2000

Peer-Reviewed Knitter, A., L. Panton, J.A. Rathmacher, A. Double-blind Paper Peterson and R. Sharp. Effects of randomized study in male ß-Hydroxy-ß-methylbutyrate (HMB) on and female runners. muscle damage after a prolonged run. J. Appl. Physiol. 89:1340-1344.

This study showed that HMB reduced muscle damage after a prolonged run. Decreasing the amount of muscle damage caused by running may decrease the DOMS soreness many long-distance runners experience.

7


SAFETY 2005

Peer-Reviewed Baxter, J.H., J.L. Carlos, J. Thurmond, R.N. Toxicity study conducted Rehani, J. Bultman, and D. Frost. Dietary in rats fed up to 5% HMB Paper toxicity of calcium ß-Hydroxy-ß-methylbutyrate in the diet. (CaHMB). Food & Chem. Toxicology 43:1731-1741.

The data showed that HMB at 5% of the diet can be considered the NOAEL (no observed adverse effect level). This amounted to ~3.5 and ~4.1 g/kg body weight intake per day in male and female rats, respectively. (Like a normal human consuming about 300 g per day.)

2000

Peer-Reviewed Nissen, S., R.L. Sharp, L. Panton, M. Vukovich, S. Trappe, and J.C. Fuller, Jr. Paper ß-Hydroxy-ß-methylbutyrate (HMB) supplementation in humans is safe and may decrease cardiovascular risk factors. J. Nutr. 130:1937-1945.

A summary of safety data from 9 double-blind randomized clinical trials including both men and women and young and elderly adults.

HMB supplementation was shown to have no adverse or untoward effects. This summary also shows that HMB supplementation has positive effects on LDL cholesterol (-7.3%) and systolic blood pressure (-4.4 mm Hg).

2000

Peer-Reviewed Gallagher, P.M., J.A. Carrithers, M.P. Godard, Paper K.E. Schulze, and S.W. Trappe. ß-Hydroxy-ß-methylbutyrate (HMB) ingestion, Part II: effects on hematology, hepatic and renal function. Med. & Sci. in Sports & Exer. 32:2116-2119.

Double-blind randomized study with male weightlifters.

In this 8-week study, consuming up to 6 grams of HMB per day was shown to have no adverse effects on measures of hematology and hepatic and renal function.

HOW HMB WORKS

8

2007

Peer-Reviewed Eley, H.L., Russell, S.T., Baxter, J.H., Mukerji, Protein synthesis studies Paper P., and M.J. Tisdale. Signaling pathways conducted in a cachectic initiated by ß-Hydroxy-ß-methylbutyrate to mouse model and in muscle cell culture. attenuate the depression of protein synthesis in skeletal muscle in response to cachectic stimuli. Am J Physiol Endocrinol Metab. 293: E923-E931.

The results demonstrate that HMB simulates protein synthesis in muscle by multiple mechanisms including the mTOR/p70S6k pathway. Many of these features are also shared with leucine. However, HMB is more potent than leucine in attenuating the development of cachexia and is better tolerated by oral administration.

2005

Peer-Reviewed Smith, H.J., P. Mukerji, and M.J. Tisdale. Attenuation of proteasome-induced Paper proteolysis in skeletal muscle by ß-Hydroxy-ß-methylbutyrate (HMB) in cancer-induced muscle loss. Cancer Res. 65:277-283.

Study conducted in a mouse model of cancer tumor growth.

HMB preserves lean body mass and attenuates protein degradation through down regulation of the increased expression of key regulatory components of the ubiquitinproteasome proteolytic pathway, together with stimulation of protein synthesis.

2005

Peer-Reviewed Van Someren, K.A., A.J. Edwards, and G. Howatson. Supplementation with Paper ß-Hydroxy-ß-methylbutyrate (HMB) and a-Ketoisocaproic Acid (KIC) reduced signs and symptoms of exercise-induced muscle damage in man. Int. J. Sport Nutr. & Exer. Met. 15: 413-424.

Counterbalanced crossover study in 6 nonresistance trained males given either a placebo or HMB/KIC.

A combination of HMB/KIC, 3 and .3 grams, respectively, was shown to reduce exercise-induced muscle damage.

2004

Peer-Reviewed Smith, H.J., S.M. Wyke, and M.J. Tisdale. Mechanism of the attenuation of proteolysisPaper inducing factor stimulated protein degradation in muscle by ß-Hydroxy-ß-methylbutyrate. Cancer Res. 64: 8731-8735.

In vitro study of chemical markers of proteolytic functions in muscle cell cultures.

These studies showed HMB inhibits activation of a major protease pathway in muscle thus inhibiting protein degradation in muscle.

2001

Peer-Reviewed Vukovich, M.D., G. Slater, M.B. Macchi, M.J. Randomized trials Turner, K. Fallon, T. Boston, and J. Rathmacher. in which 8 males took Paper ß-Hydroxy-ß-methylbutyrate (HMB) HMB, HMB plus glucose, kinetics and the influence of glucose ingestion glucose alone, or placebo. in humans. J. Nutr. Biochem. 12:631-639.

These metabolic studies showed that the halflife of HMB in plasma is about 2.5 hours and that up to 85% of the HMB ingested is retained in the body. Simultaneous glucose ingestion did not affect the percentage of HMB retained.

2000

Peer-Reviewed Slater, G.J., P.A. Logan, T. Boston, C.J. Gore, A. Stenhouse, and A.G. Hahn. Paper ß-Hydroxy-ß-methylbutyrate (HMB) supplementation does not influence the urinary testosterone:epitestosterone ratio in healthy males. J. Sci. Med. Sport. 3:79-83.

Results indicated that HMB does not alter testosterone levels and infer that the HMB acts through a different mechanism.

Case studies of 6 males taking HMB.


metabolic technologies incorporated

Iowa State University Research Park 2711 South Loop Drive, Suite 4400 Ames, Iowa 50010 Toll-free 1-800-478-0059 www.hmb.org

Š 2007 Metabolic Technologies

HMB  

HMB clinical studies