Hydroxymethylbutyrate (HMB) is a molecule that is generated naturally by the body as a result of the breakdown of leucine in the diet.
L-leucine is an amino acid, and it is one of the amino acids that make up the building blocks of protein.
It is most frequently used as a supplement to increase muscle mass or to prevent muscle loss in athletes, bodybuilders and other fitness enthusiasts.
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In terms of its effects on muscle, it seems to have an anti-catabolic effect, possibly promoting muscle growth.
What Is HMB?
HMB is a naturally occurring chemical that your body generates as it breaks down leucine.
Depending on the version of the molecule, it goes by a variety of different names, including the following.
Beta-hydroxy beta-methylbutyric acid
Beta-hydroxy beta-methylbutyrate
Hydroxymethylbutyrate
HMB is only produced in trace quantities by your body.
Roughly 5% of dietary leucine is oxidised into HMB, it seems to be the primary metabolite of leucine that has been shown to be more efficient in preventing the breakdown of muscle protein.
Raising the levels of HMB via supplementation has the potential to improve its effects.
As a result, many individuals use it as a dietary supplement to raise the amounts of HMB in their bodies.
According to research, HMB supplements has been related to a number of benefits, including improved exercise performance, decreased muscle breakdown, and enhanced muscle development in both untrained and older people. (1, 2)
You can get HMB from a variety of sources, including from supplement shops, health food stores, and it can also be purchased online.
It's also available in a variety of forms, including tablets, capsules, and powder.
What Does It Do?
HMB is promoted as an "anti-catabolic agent" (to decrease protein breakdown) more so than an "anabolic agent" (to increase protein synthesis).
It seems to be considerably more effective than leucine at decreasing the rate of muscle protein breakdown, but it appears to be less effective at increasing the rate of muscle protein synthesis.
The supplement HMB appears to be a promising candidate for the purpose of reducing muscle wasting during periods of rapid muscle atrophy, such as those associated with AIDS, cachexia, and bedrest.
Theoretically, it should increase muscle growth or reduce muscle loss, especially in people on a calorie restricted diet, but it has not been thoroughly tested to make any conclusions.
It seems to have a protective effect against the degenerative breakdown of muscle in individuals with AIDS.
Therefore, HMB may have the ability to increase muscle growth. Due to the possibly enhanced muscle growth, it may also improve strength, but this is theory.
How Does HMB Work?
HMB stimulates muscle protein synthesis and reduces muscle protein breakdown. (3)
It does this primarily via activation of the mTOR pathway and inhibition of the ubiquitin-proteasome pathway, along with other related and unrelated supportive mechanisms.
The possible affects and mechanisms of action of HMB are shown in the photo below.
HMB may work via various mechanisms and pathways in the body, the most important and relevant to muscle growth and performance include the following.
Below are more detailed explanations of the above pathways.
Activation of the mTOR Pathway
Activation of the mTOR pathway causes the execution of cell-type-specific instructions for growth, proliferation, and survival.
Hormones and other compounds can cause the stimulation of mTOR including the following.
Androgens such as testosterone
Growth hormone
IGF-1
Insulin
Amino acids such as leucine
Other novel compounds such as urolithin B
Further Reading: For more detail and information on specific hormones and supplements you can read more about hormones here and read more about supplements here.
HMB, the metabolite of leucine, seems to also activate the mTOR pathway, though not as strongly as leucine. (4)
This activation of the mTOR pathway is the likely reason for the increase in protein synthesis noted in some studies.
Inhibition of the Ubiquitin-Proteasome Pathway
The ubiquitin-proteasome pathway (UPP) is one of the key mechanisms for regulating the activity of various proteins by destroying them.
The proteasome is responsible for eliminating defective or misfolded proteins, known as protein breakdown and UPP plays a role in this process.
Inhibiting this pathway results in the decrease of protein breakdown, in the case of HMB, the inhibition of muscle protein breakdown.
Decreasing muscle protein breakdown can result in an increase in net protein balance.
The result of this, along with activation of mTOR, is increased net protein balance, which if it's high enough will result in increased muscle growth.
HMB inhibits the activity of the ubiquitin-proteasome pathway. (5)
Increases Growth Hormone & IGF-1
One study demonstrated the ability of HMB to increase plasma growth hormone and plasma IGF-1 levels. (6)
Growth hormone is a critical anabolic hormone, though there has been little evidence to support the theory that systematic increases in GH alone increases muscle growth in normal or trained people.
In terms of exercise performance, GH may improve aerobic performance.
In a study done on elderly men, GH usage resulted in favourable body recomposition, VO2 max and fuel metabolism improvements. (7)
HMB increased plasma GH levels significantly, as shown below.
In theory, IGF-1 may stimulate muscle protein synthesis and muscle growth. (8)
IGF-1 has potent effects on stimulation of the mTOR pathway, though no research has been done to prove its efficacy in real-world usage. HMB increases plasma IGF-1.
Overall, increases of both GH and IGF-1 have desirable effects on muscle growth, aerobic performance and other performance indicators.
HMB significantly increases plasma levels of both GH and IGF-1.
Proliferation of Satellite Cells
HMB increases the proliferation of muscular satellite cells in rapid twitch plantaris muscles.
Increased satellite cell proliferation results in an increase in differentiated myonuclei, which should improve the likelihood of the cells being able to sustain muscle hypertrophy.
Compared to control animals, muscles from HMB-treated animals had substantially higher muscle mass and fibre cross-sectional area than muscles from placebo-treated animals. (9)
Therefore, the supplementation of HMB could lead to an increase of satellite cells, enabling greater muscle growth and hypertrophy.
Though, there is little research done in humans on this matter.
Increase In Mitochondrial Biogenesis
The findings of this study offer evidence that, in addition to leucine, HMB alone has the potential to enhance mitochondrial biogenesis and function via modulation of the PPARβ/δ and CDK4 pathways. (10)
Furthermore, HMB seems to be more effective than leucine in the increase of mitochondrial biogenesis.
Mitochondrial biogenesis is the process of increasing the number of mitochondria in a cell, in this case specifically muscle cells.
Increased numbers of mitochondria enables better endurance of muscle cells and a higher uptake of glucose.
HMB increases this biogenesis of mitochondria, possibly enhancing endurance.
Benefits of HMB
A number of studies have discovered that consuming HMB may be linked with a variety of advantages, particularly in the field of body composition and muscle growth.
There are many benefits, including increased muscle growth and decreased muscle breakdown.
While a number of studies have looked at the impacts of HMB, further study is required to understand the full extent of its effects across a range of different groups.
The following are some of the potential advantages of taking HMB.
There are other possible benefits of supplementing with HMB too.
Increases Muscle Growth
HMB is frequently marketed as a supplement that promotes muscle development by supplement companies.
The theory and mechanisms also support the claim of enhanced muscle growth.
Despite this, research on HMB in this region has produced a mixed bag of findings.
Older research, dating back to the early 2000s and earlier, have discovered that HMB may be beneficial in some groups.
Specifically, this research investigated the effects of HMB in untrained persons as well as in elderly people.
More muscle development was seen in individuals who coupled taking HMB with resistance training as compared to those who just performed resistance training without supplementation of HMB. (11, 12, 13)
In addition, a review of seven trials involving 287 older people examined the effects of taking 2-3 grams of HMB daily for durations ranging from 8 weeks to 12 months on the participants' muscle mass. (14)
In comparison to those who got a placebo supplement, individuals who took HMB acquired an average of 0.78 pounds (0.35 kg) more muscle.
Interestingly, other research has shown that HMB has no effect on muscle development.
One review of six trials with a total of 193 individuals discovered that it may not enhance these variables in athletes who are trained and competitive.
Taking 3-6 grams of HMB daily for a period ranging from 3 days to 12 weeks did not result in any improvements in strength or changes in body composition in the athletes who took part in the study. (15)
For example, a review of ten trials examined the effects of HMB in 384 people over the age of 50. (16)
When comparing the effects of mixing HMB supplements with physical activity with exercise alone, the researchers discovered that the combination had little to no impact on altering body composition, strength, or exercise performance. (16)
In a nutshell, research on HMB and muscle development has shown conflicting findings.
However, some study suggests that this supplement may be beneficial for muscle development in those who are not in shape or who are older.
A possible reason for these findings is that HMB has strong anti-catabolic effects but not much of an increase in muscle protein synthesis.
Reduces Muscle Protein Breakdown
According to research, HMB may be beneficial in reducing muscle breakdown.
Theory suggests that HMB can reduce the activity of protein degradation pathways.
Laboratory studies back the theory up and show that HMB may help prevent muscle breakdown in a variety of ways inside cells, including by inhibiting genes and enzymes that promote the breakdown of muscle proteins, among other mechanisms. (3)
2,137 people were studied in 15 studies to determine the effects of ingesting HMB.
Cancer, HIV, renal failure, and malnutrition were among the health problems that these individuals were dealing with at the time of the study. (2)
The researchers discovered that consuming 3-4 grams of HMB daily for a period ranging from 7 days to 6 months was substantially more effective at preventing muscle loss than taking a placebo in the study. (2)
Additionally, studies in older individuals have indicated that consuming HMB may assist maintain muscle mass in cases of bedrest. (17)
Therefore, HMB has further evidence of its use as an anti-catabolic agent.
Improves Endurance & Adaptations
According to some studies, HMB may help athletes enhance their adaptations to exercise.
A 12-week trial of 42 combat sports athletes showed that consuming 3 grams of HMB daily resulted in substantial increases in both aerobic and anaerobic exercise capacity when compared to a placebo. (18)
Another study in 16 top rowers showed that consuming 3 grams of HMB for 12 weeks daily substantially improved aerobic exercise capacity and peak anaerobic power, as well as helping them lose weight when compared with a control group that received just a placebo. (19)
Anaerobic power means the greatest amount of power you can generate when doing high-intensity activity.
Other research has shown that consuming 3 grams of HMB daily has comparable benefits on both aerobic and anaerobic capacity in both athletes and healthy people. (20)
Other Benefits of HMB
Several additional advantages of HMB have been discovered via research.
However, there are fewer studies and/or weaker data to support these claims.
Therefore, more study on the possible advantages listed below is required before any conclusions can be made.
According to findings from animal research, HMB may be effective in slowing the progression of age-related mental deterioration. (21)
Scientists, on the other hand, must investigate these impacts on people.
Taking 1-3 grams of HMB daily in addition to a normal weightlifting routine was examined in a review of nine trials to see what impact it had.
Participants had substantially lower levels of indicators of muscle damage and experienced significantly greater recovery. (22)
Taken as a supplement, HMB has been found to decrease inflammatory markers such as TNF-, IL-8, and INF- in test tubes and humans. (23, 24)
Consuming 3 grams of HMB daily substantially reduced total cholesterol, LDL cholesterol, and systolic blood pressure in comparison to a placebo, according to a review of 9 older studies.
However, it is unclear if HMB, exercise, or a combination of the two were responsible for these outcomes, more research is needed to make any conclusions.
One 4-week study conducted on 11 individuals with diabetes (who were also on dialysis) discovered that taking a supplement containing HMB in combination with arginine and glutamine substantially increased wound healing. (25)
More high-quality research is required to investigate HMB further.
Dosage & How to Use It
HMB supplementation is often used in doses ranging from 1-3g per day with the goal of reducing muscle protein breakdown and therefore losses in muscle mass.
Given that HMB is around 20x more effective than leucine in reducing muscle protein breakdown, it is considered to be comparable to supplementing with 20-60g of leucine per day.
On a gram-for-gram basis, leucine is more effective than isoleucine in terms of boosting muscle protein synthesis in the body.
HMB is not recommended for stimulating muscle protein synthesis since leucine is anticipated to be more effective and less expensive than HMB.
To supplement HMB before to an exercise session, an HMB free acid would be used rather than a calcium salt, and the dose range outlined above would apply as before.
HMB should be consumed 30-45 minutes before an exercise for this particular purpose.
However, HMB can be consumed multiple times per day or in one single dosage, it is entirely up to you.
1-3 grams per day seems to be the typical dosage used.
HMB is readily-available at many stores and online shops, we recommend a trusted vendor such as Amazon.
Side-Effects of HMB
HMB seems to be a safe supplement to take. There are no reported side-effects associated with the usage of HMB.
However, there are no conclusive studies on the side-effects of this supplement. Thus, no long-term safety or recommendations can be made in regard to its side-effects.
Overall, HMB is probably safe to use but be aware there are no studies on this matter.
Written by Billy White
Billy White is a qualified Kinesiologist and Personal Trainer. He is an aspiring bodybuilder, fitness enthusiast, and health and fitness researcher.
He has multiple years of experience within the fitness, bodybuilding and health space. He is committed to providing the highest-quality information.
References
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This evidence-based analysis of HMB (Hydroxymethylbutyrate) features 25 references, listed below.
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6. Townsend JR, Hoffman JR, Gonzalez AM, Jajtner AR, Boone CH, Robinson EH, Mangine GT, Wells AJ, Fragala MS, Fukuda DH, Stout JR. Effects of β-Hydroxy-β-methylbutyrate Free Acid Ingestion and Resistance Exercise on the Acute Endocrine Response. Int J Endocrinol. (2015) ✔
7. Giannoulis MG, Sonksen PH, Umpleby M, Breen L, Pentecost C, Whyte M, McMillan CV, Bradley C, Martin FC. The effects of growth hormone and/or testosterone in healthy elderly men: a randomized controlled trial. J Clin Endocrinol Metab. (2006, Feb) (Randomised Controlled Trial) ✔
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9. Alway SE, Pereira SL, Edens NK, Hao Y, Bennett BT. β-Hydroxy-β-methylbutyrate (HMB) enhances the proliferation of satellite cells in fast muscles of aged rats during recovery from disuse atrophy. Exp Gerontol. (2013, Sep) ✔
10. Zhong Y, Zeng L, Deng J, Duan Y, Li F. β-hydroxy-β-methylbutyrate (HMB) improves mitochondrial function in myocytes through pathways involving PPARβ/δ and CDK4. Nutrition. (2019, Apr) ✔
11. Gallagher PM, Carrithers JA, Godard MP, Schulze KE, Trappe SW. Beta-hydroxy-beta-methylbutyrate ingestion, Part I: effects on strength and fat free mass. Med Sci Sports Exerc. (2000, Dec) (Clinical Trial) ✔
12. Nissen S, Sharp R, Ray M, Rathmacher JA, Rice D, Fuller JC Jr, Connelly AS, Abumrad N. Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on muscle metabolism during resistance-exercise training. J Appl Physiol (1985). (1996, Nov) (Clinical Trial) ✔
13. Jówko E, Ostaszewski P, Jank M, Sacharuk J, Zieniewicz A, Wilczak J, Nissen S. Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program. Nutrition. (2001, Jul-Aug) (Clinical Trial) ✔
14. Wu H, Xia Y, Jiang J, Du H, Guo X, Liu X, Li C, Huang G, Niu K. Effect of beta-hydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: a systematic review and meta-analysis. Arch Gerontol Geriatr. (2015, Sep-Oct) (Review) ✔
15. Sanchez-Martinez J, Santos-Lozano A, Garcia-Hermoso A, Sadarangani KP, Cristi-Montero C. Effects of beta-hydroxy-beta-methylbutyrate supplementation on strength and body composition in trained and competitive athletes: A meta-analysis of randomized controlled trials. J Sci Med Sport. (2018, Jul) (Review) ✔
16. Courel-Ibáñez J, Vetrovsky T, Dadova K, Pallarés JG, Steffl M. Health Benefits of β-Hydroxy-β-Methylbutyrate (HMB) Supplementation in Addition to Physical Exercise in Older Adults: A Systematic Review with Meta-Analysis. Nutrients. (2019, Sep 3) (Meta-Analysis) ✔
17. Deutz NE, Pereira SL, Hays NP, Oliver JS, Edens NK, Evans CM, Wolfe RR. Effect of β-hydroxy-β-methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults. Clin Nutr. (2013, Oct) (Randomised Controlled Trial) ✔
18. Durkalec-Michalski K, Jeszka J, Podgórski T. The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study. Nutrients. (2017, Jul) (Randomised Controlled Trial) ✔
19. Durkalec-Michalski K, Jeszka J. The efficacy of a β-hydroxy-β-methylbutyrate supplementation on physical capacity, body composition and biochemical markers in elite rowers: a randomised, double-blind, placebo-controlled crossover study. J Int Soc Sports Nutr. (2015, Jul) (Randomised Controlled Trial) ✔
20. Lamboley CR, Royer D, Dionne IJ. Effects of beta-hydroxy-beta-methylbutyrate on aerobic-performance components and body composition in college students. Int J Sport Nutr Exerc Metab. (2007, Feb) (Randomised Controlled Trial) ✔
21. Hankosky ER, Sherrill LK, Ruvola LA, Haake RM, Kim T, Hammerslag LR, Kougias DG, Juraska JM, Gulley JM. Effects of β-hydroxy-β-methyl butyrate on working memory and cognitive flexibility in an animal model of aging. Nutr Neurosci. (2017, Sep) ✔
22. Silva VR, Belozo FL, Micheletti TO, Conrado M, Stout JR, Pimentel GD, Gonzalez AM. β-hydroxy-β-methylbutyrate free acid supplementation may improve recovery and muscle adaptations after resistance training: a systematic review. Nutr Res. (2017, Sep) (Review) ✔
23. Hoffman JR, Gepner Y, Stout JR, Hoffman MW, Ben-Dov D, Funk S, Daimont I, Jajtner AR, Townsend JR, Church DD, Shelef I, Rosen P, Avital G, Chen Y, Frankel H, Ostfeld I. β-Hydroxy-β-methylbutyrate attenuates cytokine response during sustained military training. Nutr Res. (2016, Jun) (Randomised Controlled Trial) ✔
24. Miyake S, Ogo A, Kubota H, Teramoto F, Hirai T. β-Hydroxy-β-methylbutyrate Suppresses NF-ĸB Activation and IL-6 Production in TE-1 Cancer Cells. In Vivo. (2019, Mar-Apr) ✔
25. Sipahi S, Gungor O, Gunduz M, Cilci M, Demirci MC, Tamer A. The effect of oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine and glutamine on wound healing: a retrospective analysis of diabetic haemodialysis patients. BMC Nephrol. (2013, Jan 12) ✔
✔ Citations with a tick indicate the information is from a trusted source.
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