HMB: Effects, Benefits and Safety

HMB, or β-Hydroxy-β-methylbutyrate, is a metabolite of the branched-chain amino acid leucine. The effects of HMB on muscle metabolism during resistance training have been studied in human trials for more than 20 years. HMB has been shown to have a positive effect on muscle protein turnover, and might be beneficial as a supplement during periods of muscle-wasting illnesses and stress.

Athletes and bodybuilders have extensively used HMB as a means to increase muscle mass, decrease muscle proteolysis, increase strength and power, and to obtain potential ergogenic effects.

The purpose of this article is to summarize the mechanisms of HMB, and to review the evidence supporting claims that the body composition and performance of strength athletes can be enhanced by HMB supplementation.

What is HMB?

After ingestion, leucine is converted through transamination into alpha-Ketoisocaproic acid, or KIC, a metabolic intermediate in the metabolic pathway for leucine. After this transamination, KIC metabolizes into either isovaleryl-CoA or HMB. The majority of KIC metabolizes into isovaleryl-CoA, and only a minor amount ends up being converted into HMB. Approximately 5% of dietary leucine is ultimately converted into HMB this way.1

As stated previously, HMB is an acronym for β-Hydroxy-β-methylbutyrate, a metabolite of leucine. Leucine is a major factor in the control of protein metabolism, insulin kinetics, and glucose homeostasis. Since the 1960s, it has been established that leucine has anti-catabolic properties, and it is well known that leucine is a key factor in the initiation and maintenance of protein synthesis.2

The supplementation protocol for HMB for athletes usually calls for 3 grams of HMB, which means that in order to obtain this amount through dietary means, 60 grams of leucine would have to be consumed. This would be a challenge, since animal-originated protein sources have a leucine content of 8–14%, while plant-based protein sources generally have a leucine content below 8%, maize being the exception.

The Effect of HMB on Strength and Body Composition

A number of studies have examined the effect of HMB supplementation on strength and body composition in both untrained individuals and trained. Individual studies have produced varied results, some showing an effect of HMB, while others have concluded that HMB does not affect training-induced changes in body composition and strength at all.

Individual Studies

A 1999 study gave 40 experienced resistance-trained athletes either 0, 3 or 6 grams of HMB during 28 days of resistance training, but could not find any effects of HMB supplementation on strength, body composition or anabolic/catabolic status.3

In a 2001 study, 3 grams of HMB per day did not produce any significant changes in strength and body composition in response to resistance training compared to placebo in strength-trained men.4

One year later, a study on NCAA division I-A football players during 28 days of off-season resistance training failed to observe any effects of 3 grams of HMB on body composition, strength, or markers of muscle catabolism.5

In 2009, another study found that adding HMB to the diet of trained men during nine weeks of resistance training increased muscle mass by 0.2±2.2%, a rather trivial amount. The results did show that HMB supplementation significantly enhanced lower body strength compared to placebo. However, this study did not properly control the diet of the participants. The energy intake of the HMB group increased by 8% while the energy intake of the control group decreased by 10%, which could eliminate the difference between the groups. Energy intake is one of the major dietary factors affecting gains during a resistance training protocol.6

Studies using untrained participants have showed results that are somewhat more promising. For example, in 1996, a study demonstrated that HMB decreased markers of muscle damage and increased lean body mass and strength in a dose dependent manner in previously untrained men during weight training.7

Reviews and Meta-analyses

One old review article and two major meta-analyses on HMB supplementation have been published, analyzing the available evidence for potential effects on performance and body composition. The review article is from a time when there were only two papers on the subject published in peer-reviewed journals as full manuscripts, which makes it of limited use.8

Of the two meta-analyses, the first one from 2009 analyzed the results of nine studies, and yielded comparisons and estimates of strength, fat- and fat-free mass, and markers of muscle damage in trained and untrained men.

In untrained lifters, small but clear increases in lower body strength could be observed following HMB supplementation. Only negligible advantages for upper body strength were noted. For trained lifters, only trivial effects on both upper and lower body strength could be observed.

Overall, the 2009 meta-analysis found that the average strength increase was 3.7±2.4%, which was considered trivial.

Regarding muscle mass, the results indicated that HBM has, at best, a negligible effect, regardless of training experience.9

In 2018, another meta-analysis was published, clarifying the effects of HMB supplementation on strength and body composition in athletes.10 In this meta-analysis, the scientists gathered results from randomized controlled trials published in peer-reviewed journals which included measurements of bench press or leg press strength, body mass, fat-free mass, and fat mass. Six studies with a total of 193 participants fulfilled these inclusion criteria.

The results indicated that HMB does not have any significant effect on bench press strength or leg press strength in trained athletes. In addition, HMB supplementation did not produce any significant effects on body mass, fat-free mass or fat mass.

This lack of effect was consistent across subgroups. Regardless of HMB doses, training level, diet, and the duration of the supplementation, HMB failed to elicit any significant effects on strength or body mass.

J Sci Med Sport. 2018 Jul;21(7):727-735. Effects of beta-hydroxy-beta-methylbutyrate supplementation on strength and body composition in trained and competitive athletes: A meta-analysis of randomized controlled trials.

The forest plots above are from the 2018 meta-analysis. They visually show that the effects of HMB supplementation on bench press strength, leg press strength, fat-free mass, body mass, and fat mass are almost non-existent. The diamond at the bottom of the forest plot show the combined average result of all included studies. The horizontal points of the diamonds indicate the limits of the 95% confidence intervals. As the forest plots show, the diamond crosses the “no effect”-line in all instances, regardless of what was measured.

It is also worth mentioning a 2017 study which was published too late to be included in the 2018 meta-analysis. This study matched and randomized 16 healthy but untrained men into two groups, one of which received 3 grams of free acid HMB per day while the other was provided a placebo supplement, during six weeks of resistance training.11

The results showed that the HMB group increased their 1RM leg press strength and peak power more than the placebo group. In addition, the HMB supplementation group indicated a more favorable hormonal profile response for muscular anabolism in comparison to the group given placebo.

In summary, while there are individual studies that indicate that HMB supplementation might provide benefits in strength and fat free mass, especially in untrained individuals, the collected evidence indicate that those benefits are minor at best. The latest meta-analysis on HMB on strength and body composition in trained athletes clearly show that even if there actually is an effect of HMB, it is small enough to be very hard to detect.

The Wilson Study

In 2014, HMB went from being a promising supplement to being a white-hot supplement. That was when the study The effects of 12 weeks of β-Hydroxy-β-methylbutyrate free acid supplementation on muscle mass, strength, and power in resistance-trained individuals: a randomized, double-blind, placebo-controlled study was published. This study showed incredible gains of strength and muscle mass after 12 weeks of HMB supplementations.12 The results the participants of the study exhibited were comparable to or greater than the gains previously observed from 600 mg of testosterone weekly when combined with a resistance-training program.

Two years later, in 2016, the same lab published another HMB study, in which the combination of HMB and ATP increased the lean mass of already trained individuals by 12.7% in 12 weeks, while simultaneously and dramatically increasing strength and power.13

We could discuss the results of these who studies, and why they are so wildly superior to the results of all other published studies. However, such speculation would be without proof, and groundless speculation is not something we want to indulge in. Suffice it to say, peers do not accept these two studies as scientifically sound, and they were not included in the latest meta-analysis on HMB.

In 2017, other scientists in the field published a letter addressing a number of discrepancies in these two publications.14 The lead author of the first study replied to this letter, but despite his efforts, it did not clarify much of anything.15

The Effects of HMB on Recovery Following Exercise-induced Muscle Damage

While HMB does not seem to possess many anabolic properties, as evidenced in the meta-analyses referenced earlier, it is also widely used because of purported positive effects on recovery following exercise-induced muscle damage.

A recent meta-analysis assessed these effects by examining creatine kinase and lactate dehydrogenase, which are indirect markers of muscle damage. There are no good methods to evaluate muscle damage during and immediately following exercise directly, so studies have to resort to indirect markers.

The researchers gathered data from 10 studies measuring levels of creatine kinase and 8 studies measuring levels of lactate dehydrogenase following resistance training among healthy participants supplementing with HMB.

The results showed that, in randomized controlled trials with a total of 324 adult participants, HMB supplementation decreased both creatine kinase and lactate dehydrogenase levels significantly, indicating reduced muscle damage induced by exercise and a potential role in restoring optimal muscle function following a training session.16

The Effect of HMB on Muscle Mass and Strength in Clinical Practice

Outside of potential applications in exercise physiology, HMB supplementation might play a role in ameliorating muscle wasting and weakness in a variety of clinical conditions.

In a number of clinical conditions, including HIV, cancer cachexia, rheumatoid arthritis, hemodialysis, and chronic obstructive pulmonary disease, a recent meta-analysis found HMB supplementation to be safe and to increase strength and muscle mass in patients. However, the effect size, both for body composition and physical function outcomes, was small.17

Small effects might be of greater importance in groups affected by muscle wasting than in a healthy, athletic population, which makes HMB a potential candidate for further studies.

HMB During Periods of Energy Restriction

In a 2010 study, eight well-trained female judo athletes were divided into two groups, one of which were given 3 grams of HMB per day. During three days of energy restriction, body weight and body fat percentage decreased significantly in the HMB group, but remained unchanged in the control group. Muscle mass and performance were unchanged in both groups.

Supplementing with HMB during periods of energy restriction might help to reduce body fat, although the evidence is limited to a single, very short-term study with few participants.18

The Effect of HMB on Anabolic and Catabolic Hormones

A study where national team level volleyball players aged 13.5–18 years received 3 grams of HMB per day for 7 weeks found no hormonal effects of HMB supplementation. Testosterone, cortisol, and growth hormone remained unchanged, as did inflammatory mediators.19

In a recent study, 40 adult men received calcium HMB, free acid HMB, another leucine metabolite called a-HICA, or a placebo supplement during 8 weeks of resistance training. No significant between-group or time-group interactions were observed on measurements of creatine kinase, insulin-like growth factor-1, growth hormone, or cortisol.20

One study did find that free acid HMB may affect growth hormone/ insulin like growth factor 1 (GH/IGF-1) axis signaling, but the practical implications of these findings are unclear.21

Yet another study demonstrated that one gram of free acid HMB 30 minutes prior to resistance training augmented the growth hormone response to the training session compared to placebo. There were no between-group interactions on measurements of testosterone or insulin-like growth factor (IGF-1).22

HMB supplementation does not seem to affect anabolic or catabolic hormones in a meaningful way, either in adults or in adolescents. The exception might be the growth hormone response to resistance training sessions, but based on previous research, acute resistance training-induced elevations of growth hormone do not seem to correlate with muscle growth.23

Types of HMB

The two types of HMB available in supplement form are calcium HMB and free acid HMB. The majority of the studies on HMB have used the calcium form.

When ingested, free acid HMB increases plasma levels of HMB much more and in a much shorter amount of time than calcium HMB. Plasma clearance is also significantly greater after free acid HMB ingestion, indicating greater availability and tissue uptake.24

The 2014 study, which showed dramatic gains in strength and muscle from HMB supplementation, also used free acid HMB. This fueled speculation that free acid HMB might be superior to the calcium form and explain why many earlier studies had failed to produce robust results in the form of strength and mass gains.

A 2017 study demonstrated that despite differences in bioavailability, both calcium HMB and free acid HMB activated anabolic pathways and stimulated protein synthesis to a similar degree in healthy, young subjects, indicating that calcium HMB has comparable effects on muscle mass as the free acid variant.25

Supplementation, Dosage and Timing

Dosing

The most common dosage of HMB used in studies is 3 grams per day. This amount has not been scientifically established as the optimal dose, but the few studies using 6 grams have been unable to find any dose-dependent effects above this amount.26 27

Timing

To potentiate any acute effects of HMB on muscle protein metabolism during a training session, pre-exercise supplementation would be recommended.

Since free acid HMB and calcium HMB affect plasma HMB levels differently, supplement timing would also be different. Free acid HMB has a faster effect, which makes consuming it 30–60 minutes prior a training session prudent.

Calcium HMB, on the other hand, which raises plasma HMB levels more gradually, would have to be consumed at least an hour before a training session for the same effect. If taken with a carbohydrate source, this period of time between HMB intake and the training session might be extended to two hours.28

Interactions with Other Supplements

Creatine

Two studies have examined the effects of combining HMB with creatine during a resistance-training program.

The first of these was published in 2001, and had untrained subjects randomized into groups supplementing with either placebo, creatine, HMB, or HMB plus creatine during three weeks of resistance training.

The results showed that creatine was more effective than HMB in increasing strength and lean body mass. When creatine and HMB was combined, the effects of the supplements were additive.29

In the second study, trained rugby athletes received either 3 grams of HMB or 3 grams of HMB plus 3 grams of creatine during a six week long resistance training period.

In this study, supplementating with either HMB or HMB plus creatine did not have any effect at all on any strength or endurance markers compared with placebo.30

ATP

There are also two studies examining the effects of the combination of HMB and adenosine triphosphate (ATP) on muscle mass, strength, and power in trained individuals.

The first was published in 2013 and investigated the effects of 12 weeks of supplementation with either free acid HMB, ATP or a combination of HMB and ATP on lean mass, strength and power on trained subjects.31 This study has not been peer-reviewed and is not available in full text format, only as a poster presentation.

The results showed that both HMB and ATP increased strength and muscle mass, but that the combination of the two resulted in a synergistic effect and even greater gains.

The second study in question is the aforementioned 2016 study described under the The Wilson Study heading.32

It should be noted that this study is part of the duo of studies that are no longer recognized by the scientific community, the ones that produced astounding results.

The poster presentation from 2013 is also from the lab of the same team. This calls into question the validity of both of these studies.

HMB Safety

Supplementation with HMB does not seem be associated with any health issues or risks, in healthy individuals or in patients with cancer or AIDS, alone or in combination with other amino acids.33

One study where male and female rats were administered 3.49 and 4.16 grams per kilograms of bodyweight respectively for at least 90 days assessed the dietary toxicity of calcium HMB. No related adverse effects on body weight, food consumption, clinical chemistry, hematology, or organ weight were observed. The amounts of HMB given to the rats would equate to 38 to 45 grams in human terms.34

A recent study performed a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and an in vivo mammalian cell micronucleus test on calcium HMB. No genotoxic effects were found in any test compared to control, and it was concluded that calcium HMB has no genotoxic effects.35

Conclusion

Available scientific evidence indicates that HMB has small but significant effects in clinical practice where muscle wasting is an issue. In healthy, untrained individuals, HMB supplementation might provide some increases in lower body strength, but the effects on body composition seem trivial to non-existent. For trained athletes, HMB seems to have minor, if any, effects.

Meta-analyses examining studies with trained participants show that HMB supplementation does not have any significant effects on either strength or body composition.

There might be some benefits to be had from HMB supplementation on markers of muscle damage and recovery of muscle function following exercise, but even then, those benefits do not seem to translate into increased hypertrophy or strength gains.


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References

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  2. Biochem J. 1969 Sep;114(2):171-8. Relationship between intracellular amino acids and protein synthesis in the extensor digitorum longus muscle of rats.
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  4. Int J Sport Nutr Exerc Metab. 2001 Sep;11(3):384-96. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation does not affect changes in strength or body composition during resistance training in trained men.
  5. Journal of Exercise Physiology. 3(4): 48-59. Effects of calcium B-HMB supplemementation during training on markers of catabolism, body composition, strength, and sprint performance.
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