A Support Guide From the ScientistsWho Discovered

HMB.

www.hmb.org

164 subjectsstudied

170 subjectsstudied

Ransone et al., 2003

Nissen et al., 1996

Nissen et al., 1996

Kreider et al., 1999

Panton et al., 2000

Panton et al., 2000

Gallagher et al., 2000

Slater et al., 2001

Vukovich et al., 2001

O’Conner et al., 2007

Jòwko et al., 2001

1

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

No nutritional supplement has been proven moreeffective in lean tissue gain and/orbeen proven safe like HMB.

HMB doubles the effects of

weight training.

All HMB studies combined form theproof that HMB works and regularly doubles the effects of exerciseon muscle growth.

Science instead of hype.

Nutrition instead of magic.

Fact over fiction.

With HMB, you have the power of thetruth to back your message. And it is atremendously powerful force.

Often a single rumor can start a fad. Asingle study can cause a firestorm. Andwhile this is just how HMB got its footholdas a nutritional supplement for weighttraining, it’s only the beginning of the story.

HMB is no hype. And it certainly isnot a one-study wonder. Once the firstscientific study was out on HMB, otherresearchers jumped into the fray to see forthemselves. And their research hascontinued to confirm what the very firststudy uncovered: 11 out of 11 publishedstudies show a significant positive effect ofHMB on lean gain. The studies averagedtogether show that HMB doubles the effectof resistance training on lean gain. Strengthalso follows suit.

Only CREATINE is in the same league asHMB, and HMB is actually effective inadding gain for those using CREATINE.

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

Science!After

0.42% Lean gain/weekBefore

0.18% Lean gain/week

Summary of 11 published studies.

2

HMB minimizes muscle damage, decreasesprotein breakdown, andstimulates protein synthesis.

s= Protein Balance

s

= Increased Muscle (Protein)

HMB Supplementation

Increased Muscle (Protein) Gain Decreased Muscle (Protein) Loss

Amino Acids

MuscleProtein

MuscleProtein

Amino Acids

Protein TranslationInitiation

mTOR Proteosome+

Ubiquitin

HMB Stimulates mTOR HMB Blocks mRNA Expression of Key Regulators

mRNA +

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

HMB decreases protein breakdown caused byhard workouts at a molecular level by disruptingproteolysis through the ubiquitin-proteasomeproteolytic pathway, the proteolytic enzyme thatbreaks muscle protein down.

HMB is a metabolite of the BCAA leucinewhich has been shown to stimulate proteinsynthesis through the mTOR pathway.Potentially, HMB could play this role.

Increase in Protein SynthesisHMB stimulates protein synthesis in muscle bymultiple mechanisms, including themTOR/p70S6k pathway, which stimulatetranslation initiation of protein synthesis.(Many of these effects are shared with leucine;however, HMB is more potent than leucine inpromoting muscle gain).

Decrease Protein BreakdownHMB decreases protein breakdown at amolecular level caused by hard workouts. HMBresults in decreasing the key regulatingcomponents of the ubiquitin-proteosomeproteolytic pathway which results in LESSmuscle loss.

Therefore, the increase in synthesis anddecrease in breakdown result in twice the gainof muscle over exercise alone.

Protein Breakdown

Protein Synthesis

Protein Synthesis

Protein Breakdown

HMB shifts the balance of

protein synthesis, tipping the scale in muscle’s favor.

3

HMB reduces muscledamage associated

with exercise, which shortens recovery time.

It’s as true for the casual athlete as it is forthe serious competitor: people really feel aworkout the next day. And for many, thatworkout could be as minor as a heavy set ofweekend chores.

Yet, HMB is shown to benefitanyone involved in strenuous activity byreducing the effects of a “workout hangover.”

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

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

And remember - it’s not hype; it’s consistentlyproven in clinical studies.

From the serious athlete to the conscientiousexerciser who works out for the health of it,the evidence is growing that HMB is anutritional supplement that has yet to reachits full potential.

Muscle damage, measured by CPK leakage into the bloodstream, isreduced when HMB is taken in conjunction withrunning and weightlifting.

HMB shortens recoverytime and allows maximal intensity in the next strenuous activity.

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

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

After Weightlifting

With HMB: Less Muscle Damage

After Running

4

HMB improves aerobic performance for runners, cyclists,

and triathletes.

HMB improves aerobicperformance in average, everydayathletes. HMB is shown to increase maximaloxygen consumption (VO2max) and improvethe respiratory compensation point (RCP). Itappears that HMB may reduce metabolicacidosis, and the research also shows that ithelps athletes tolerate high-intensity activityover a long period of time.

Research also shows that HMB lengthens thetime to the onset of blood lactateaccumulation (OBLA). HMB improves thetraining status for endurance athletes forpositive effects on endurance performance.

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

HMB also benefitsendurance athletes.

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

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

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

Figure 1

Figure 2

Figure 3

5

Clinical research showsHMB is a safe, effective

way for the casualathlete to maximize the

health benefits ofexercise.

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

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

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

That alone is a powerful case for expandingthe use of HMB for the casual athlete, sincemany casual athletes exercise simply for healthbenefits instead of competitive ones.

After 9 studies, the results areconclusive: along with exercise, HMB aids thereduction of risk factors associated with thecardiovascular system.

Finally here is a supplement that offerssubstantial benefits to the “mainstream”exercise community.

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

9 studies show HMB is safe and has “health positive” attributesrather than the negative ones.

Health Benefits of HMB

6

Placebo-controlled,double-blind clinical study

of HMB in criticallyinjured patients.

Peer-ReviewedPaper

Kuhls, D.A., J.A. Rathmacher, M.D. Musngi,D.A. Frisch, J. Nielson, A. Barber, A.D.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 Data from this study suggest that HMB canimprove nitrogen balance in severely injuredtrauma patients.

Subjects’ ethicalbackgrounds prevented this study from being

conducted as a double-blind, placebo-controlledstudy; however, a placebo

treatment was utilized.

Peer-ReviewedPaper

O’Connor, D.M. and M.J. Crowe. Effects of sixweeks of ß-Hydroxy-ß-methylbutyrate (HMB)and HMB/Creatine supplementation onstrength, power, and anthropometry of highlytrained athletes. J. Strength Cond. Res.21:419-423.

2007 This 6-week study in trained Rugby playersshowed a numerical increase in lean tissuewith HMB supplementation.

Review.Peer-ReviewedPaper

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

2005 Studies reviewed showed HMB may bebeneficial in increasing lean mass in anumber of groups (AIDS and cancer patientsas well as athletes). No study has shownadverse effects of HMB as have been seenwith other supplement regimens.

Two double-blind,randomized,

placebo-controlled clinical studies

in elderly women.

Peer-ReviewedPaper

Flakoll, P., R. Sharp, S. Baier, D. Levenhagen,C. Carr, and S. Nissen. Effect ofß-Hydroxy-ß-methylbutyrate (HMB)arginine, and lysine supplementation onstrength, functionality, body composition, andprotein metabolism in elderly women.Nutrition 20: 445-451.

2004 Data from 2 independent studies demonstratethat a nutritional mixture of HMB, arginine,and lysine can enhance whole body proteinsynthesis and improve functionality in elderlywomen.

A meta-analysis of dietary supplements used to increase lean

and strength.

Peer-ReviewedPaper

Nissen, S. and R. Sharp. The efficacy ofdietary supplements in accentuating themuscle mass and strength gains achieved withresistance exercise: A meta-analysis. J. Appl.Physiol. 94:651-659.

2003 Few supplements used as ergogenic aids have 2 or more peer-reviewed studies. OnlyHMB and creatine have been shown tosignificantly increase lean and strength gainswith exercise.

Double-blind randomizedcrossover study in 35

training collegiate footballplayers.

Peer-ReviewedPaper

Ransone, J., K. Neighbors, R. LeFavi, and J.Chromiak. The effect of ß-Hydroxy-ß-methylbutyrate (HMB) on muscular strengthand body composition in collegiate footballplayers. J. Strength Cond. Res. 17:34-39.

2003 This study was performed with highlytrained athletes undergoing an intensetraining program. Although this study failedto show significant differences, HMBsupplemented subjects gained more lean andlost body fat.

Double-blind randomized study in elderly

men and womenparticipating in a weight-training exercise program.

Peer-ReviewedPaper

Vukovich, M.D., N.B. Stubbs and R.M.Bohlken. Body composition in 70-year-oldadults responds to dietary ß-Hydroxy-ß-methylbutyrate (HMB) similarly to that ofyoung adults. J. Nutr. 131:2049-2052.

2001 In this study, HMB tended to increase musclestrength and lean mass while significantlyincreasing fat loss over this 8-week study inolder adults.

Double-blind randomized study in

weight-training males.

Peer-ReviewedPaper

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

2001 This is the first major study to show thatHMB combined with creatinesupplementation results in even greaterstrength and lean gains than either HMB orcreatine supplementation alone.

REFEREED PUBLICATION LISTSTRENGTH AND MUSCLE BUILDING

7

Double-blind randomizedstudy in trained maleathletes undergoing a

weight-training program.

Peer-ReviewedPaper

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

2001 In highly trained athletes, HMB numericallyincreased strength and lean, but the increasewas not significantly greater than that of theplacebo group.

Double-blind randomized study with

male weightlifters.

Peer-ReviewedPaper

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

2000 In this study, either 3 or 6 grams of HMB were consumed per day. HMBincreased lean mass, peak muscle torques, and decreased plasma CPK after resistancetraining with no added benefit seen fromconsuming the higher level.

Two double-blindrandomized studiesincluding males and

females and trained anduntrained weightlifters.

Peer-ReviewedPaper

Panton, L.B., J.A. Rathmacher, S. Baier, andS. Nissen. Nutritional supplementation of theleucine metabolite ß-Hydroxy-ß-methylbutyrate(HMB) during resistance training. Nutrition16:734-739.

2000 Two separate studies showed that regardlessof gender or prior training, HMB increasesstrength and minimizes muscle damage when combined with a 4-week resistance-training program.

Randomized placebo-controlled study

of 40 experienced,resistance-trained males.

Peer-ReviewedPaper

Kreider, R.B., M. Ferreira, M. Wilson, andA.L. Almada. Effects of calciumß-Hydroxy-ß-methylbutyrate (HMB)supplementation during resistance training onmarkers of catabolism, body composition, andstrength. Int. J. Sports Med. 20:503-509.

1999 In this 4-week study, trained athletesconsumed either 3 or 6 grams of HMB perday. While not statistically significant, HMBconsumption resulted in numerically greaterlean and strength gains.

Two double-blindrandomized studies inweight-training males.

Peer-ReviewedPaper

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

1996 In these separate studies, one for 3 weeks and one for 7 weeks, it was found thatfeeding 3 grams of HMB to exercisinghumans increased lean mass, strength, andreduced muscle damage.

Placebo-controlled study in college students.

Peer-ReviewedPaper

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

2007 HMB supplementation significantlyincreased maximal oxygen consumption.

Double-blind switchbackstudy with HMB, leucine,

and placebo.

Peer-ReviewedPaper

Vukovich, M.D. and G.D. Dreifort. Theeffect of ß-Hydroxy-ß-methylbutyrate (HMB)on VO2 peak and lactate threshold inendurance-trained cyclists. J. Strength andConditioning Res. 15:491-497.

2001 This study showed that HMBsupplementation increased the cyclistsendurance as measured by VO2 peak andlactate threshold.

Double-blind randomized study in male

and female runners.

Peer-ReviewedPaper

Knitter, A., L. Panton, J.A. Rathmacher, A.Peterson and R. Sharp. Effects ofß-Hydroxy-ß-methylbutyrate (HMB) onmuscle damage after a prolonged run. J. Appl.Physiol. 89:1340-1344.

2000 This study showed that HMB reducedmuscle damage after a prolonged run.Decreasing the amount of muscle damagecaused by running may decrease the DOMSsoreness many long-distance runnersexperience.

AEROBIC EXERCISE

8

HOW HMB WORKS

Study conducted in amouse model of cancer

tumor growth.

Peer-ReviewedPaper

Smith, H.J., P. Mukerji, and M.J. Tisdale.Attenuation of proteasome-inducedproteolysis in skeletal muscle byß-Hydroxy-ß-methylbutyrate (HMB) incancer-induced muscle loss. Cancer Res.65:277-283.

2005 HMB preserves lean body mass andattenuates protein degradation through downregulation of the increased expression of keyregulatory components of the ubiquitin-proteasome proteolytic pathway, togetherwith stimulation of protein synthesis.

Counterbalanced crossover study in 6

nonresistance trainedmales given either a

placebo or HMB/KIC.

Peer-ReviewedPaper

Van Someren, K.A., A.J. Edwards, and G.Howatson. Supplementation withß-Hydroxy-ß-methylbutyrate (HMB) anda-Ketoisocaproic Acid (KIC) reduced signsand symptoms of exercise-induced muscledamage in man. Int. J. Sport Nutr. & Exer.Met. 15: 413-424.

2005 A combination of HMB/KIC, 3 and .3 grams, respectively, was shown to reduceexercise-induced muscle damage.

In vitro study of chemical markers ofproteolytic functions in

muscle cell cultures.

Peer-ReviewedPaper

Smith, H.J., S.M. Wyke, and M.J. Tisdale.Mechanism of the attenuation of proteolysis-inducing factor stimulated proteindegradation in muscle byß-Hydroxy-ß-methylbutyrate. Cancer Res. 64: 8731-8735.

2004 These studies showed HMB inhibitsactivation of a major protease pathway inmuscle thus inhibiting protein degradation in muscle.

Randomized trials in which 8 males took

HMB, HMB plus glucose,glucose alone, or placebo.

Peer-ReviewedPaper

Vukovich, M.D., G. Slater, M.B. Macchi, M.J.Turner, K. Fallon, T. Boston, and J. Rathmacher.ß-Hydroxy-ß-methylbutyrate (HMB)kinetics and the influence of glucose ingestionin humans. J. Nutr. Biochem. 12:631-639.

2001 These metabolic studies showed that the half-life of HMB in plasma is about 2.5 hoursand that up to 85% of the HMB ingested isretained in the body. Simultaneous glucoseingestion did not affect the percentage ofHMB retained.

Case studies of 6 malestaking HMB.

Peer-ReviewedPaper

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

2000 Results indicated that HMB does not altertestosterone levels and infer that the HMBacts through a different mechanism.

Toxicity study conducted in rats fed up to 5% HMB

in the diet.

Peer-ReviewedPaper

Baxter, J.H., J.L. Carlos, J. Thurmond, R.N.Rehani, J. Bultman, and D. Frost. Dietarytoxicity of calcium ß-Hydroxy-ß-methylbutyrate(CaHMB). Food & Chem. Toxicology43:1731-1741.

2005 The data showed that HMB at 5% of thediet can be considered the NOAEL (noobserved adverse effect level). This amountedto ~3.5 and ~4.1 g/kg body weight intakeper day in male and female rats, respectively.(Like a normal human consuming about 300g per day.)

A summary of safety datafrom 9 double-blind

randomized clinical trialsincluding both men andwomen and young and

elderly adults.

Peer-ReviewedPaper

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

2000 HMB supplementation was shown to haveno adverse or untoward effects. Thissummary also shows that HMBsupplementation has positive effects on LDLcholesterol (-7.3%) and systolic bloodpressure (-4.4 mm Hg).

Double-blind randomized study with

male weightlifters.

Peer-ReviewedPaper

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

2000 In this 8-week study, consuming up to 6grams of HMB per day was shown to haveno adverse effects on measures of hematologyand hepatic and renal function.

SAFETY

Protein synthesis studiesconducted in a cachectic

mouse model and inmuscle cell culture.

Peer-ReviewedPaper

Eley, H.L., Russell, S.T., Baxter, J.H., Mukerji,P., and M.J. Tisdale. Signaling pathwaysinitiated by ß-Hydroxy-ß-methylbutyrate toattenuate the depression of protein synthesisin skeletal muscle in response to cachecticstimuli. Am J Physiol Endocrinol Metab. 293:E923-E931.

2007 The results demonstrate that HMB simulatesprotein synthesis in muscle by multiplemechanisms including the mTOR/p70S6kpathway. Many of these features are alsoshared with leucine. However, HMB is morepotent than leucine in attenuating thedevelopment of cachexia and is bettertolerated by oral administration.

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