Beta-hydroxy beta-methylbutyrate

HMB – Beta-hydroxy beta-methylbutyrate – Supplement Profile

Anybody who’s been around bodybuilding over the last several years knows about Beta-hydroxy beta-methylbutyrate, or as it’s more commonly called, “HMB”. It was first patented by MTI and sold mainly through one large supplement company. The only reason I bring this up is because in an effort to really sell a lot of this stuff it was tagged as being able to build muscle. This is not exactly what HMB does and as a consequence, a lot of kids ran out and bought it with unrealistic expectations. With a very high price tag there were very high expectations. When nothing really noticeable happened after it was added to their “normal” routine, they quickly stopped buying it.

You might be wondering why, if nothing happened, would I bother to write about it? Well, the reason “nothing happened” was not necessarily the fault of the HMB. When one takes a look at how HMB actually works within the body, you get a better idea of how and when to use it.

HMB is essentially a metabolite of the amino acid leucine. Your body produces about 0.2-0.4 grams of HMB everyday depending on your daily protein, or more accurately total leucine intake. It goes from leucine, to ketoisocaproate (KIC), and from KIC to HMB via the enzyme KIC-dioxygenase. HMB appears to be converted mostly to beta-hydroxy-beta-methylglutaryl CoA (HMG-CoA). HMG-CoA is then used to make cholesterol within cells. This is important for muscle cells in that they cannot use cholesterol from the blood.

Here is where much of the misunderstanding about HMB comes in. HMB has NOT been shown to directly inhibit protein breakdown, and certainly does not cause protein synthesis. A study done in 1997 looked at the effects of giving lambs high doses of HMB (1). To their surprise, HMB did not have any effect on protein catabolism or anabolism. In essence, HMB didn’t do squat under normal conditions.

The difference between this study with the lambs and studies in people is that with people, we added high intensity exercise. Studies looking at HMB supplementation and its effects on weight training show increased gains in strength and lean mass. For example, take one of the first published studies using HMB and weight lifting (2).

In the first study, forty-one subjects were randomized among three levels of HMB supplementation (0, 1.5 or 3.0 g HMB/day) and two protein levels (normal, 117 g/day, or high, 175 g/day) and weight lifted for 1.5 h 3 days/week for 3 weeks. In study 2, twenty-eight subjects were fed either 0 or 3.0 g HMB/day and weight lifted for 2-3 h 6 days/wk for 7 weeks.

In study 1, HMB significantly decreased the exercise-induced rise in muscle breakdown as measured by urine 3-methylhistidine during the first 2 wk of exercise. (Looking at 3-methylhistidine is really the best way of knowing what’s happening to muscle tissue during training. 3-methylhistidine only shows up in the blood when contractile proteins are broken down, whereas nitrogen balance studies reflect all protein, not just muscle.) Plasma creatine phosphokinase was also decreased with HMB supplementation. Weight lifted was increased by HMB supplementation when compared with the unsupplemented subjects during each week of the study.

In study 2, fat-free mass was significantly increased in HMB-supplemented subjects compared with the unsupplemented group at 2 and 4-6 weeks of the study.

These results have been duplicated in both men and women (3), as well as after prolonged running (4). Both of these studies showed a decrease in muscle breakdown and increased efficacy of exercise. By efficacy of exercise I mean that HMB seemed to make exercise work better to promote size and strength. To me this is an important distinction. HMB does not induce the body to do something it wouldn’t normally do (such as with androstenediol), but instead, it comes in to support what the body is already trying to do. You could call HMB a substrate, which has a significant effect when the body is lacking in that substrate. Otherwise, like in the lamb study, it doesn’t do anything for muscle growth.

Now I wouldn’t be objective if I didn’t mention a study by Kreider in which no effect of HMB supplementation was found. I must admit, I think Kreider may have had his doubts going into the study. I say this only because of other papers he has published in the past being quite skeptical about most supplements. This is not a bad thing, but attitudes can surely affect the results. This is true for both skeptics and optimists, and may very well be what’s happening with the studies showing an effect of HMB. You’ll notice that Steve Nissen is involved in nearly every study showing a positive effect of HMB. He has a personal interest in the commercial success of the compound.

So, all discussion of bias aside, how does HMB effect muscle mass and strength? It isn’t through anabolism, and it appears not to be directly through anticatabolic mechanisms either. If you recall the afore-mentioned pathway for leucine metabolism, you’ll notice that the fate of ingested HMB is mainly as HMG-CoA, a substrate for cholesterol synthesis. It appears that cholesterol synthesis may be a rate-limiting step in membrane repair after intense training. First a few words about cholesterol.

Cholesterol makes up about 13% of the cell membrane. It plays an integral role in controlling the fluidity of the membrane. Any damage to the cell membrane would certainly affect the need for cholesterol and hence would initiate cholesterol synthesis within the muscle cell to be used in the repaired membrane. Keep in mind that when the integrity of the cell membrane is compromised, the cell cannot carry out intracellular functions necessary for muscle growth.

Weight training, specifically eccentrics or “negatives,” cause damage to muscle cells. Current data indicates that the earliest events associated with injury are mechanically induced and are based primarily on the strain imposed on the sarcomere (muscle cell membrane). Mechanical experiments reveal that excessive sarcomere strain is the primary cause of injury. It is thought that excessive strain permits extracellular or intracellular membrane disruption that may permit hydrolysis of structural proteins leading to the myofibrillar disruption that is commonly observed. Inflammation that occurs after injury actually further degrades muscle proteins, but prevention of the inflammation leads to a long-term loss in muscle function.

In the studies showing an effect of HMB on muscle breakdown, the differences between the HMB group and the placebo group tend to decline over time. This reflects the fact that, if the cholesterol mechanism is true, HMB serves to facilitate rates of growth only when membrane integrity is a limiting factor. This generally occurs during the first three weeks of a new or unaccustomed exercise program. After that, muscles become resistant to further damage induced by that particular program (loading regimen) and HMB supplementation loses its usefulness.

Do I recommend HMB? Yes. In spite of evidence to the contrary (Kreider’s study), I have felt that HMB has significantly helped not only myself, but also my clients who use my unique loading regimen to make faster than average gains. My program is characterized by high frequency/low volume training, hitting each body part a minimum of 3 times per week with an obligatory increase in weight from workout to workout. Obviously, this kind of regimen puts an unusual strain on a person’s adaptive capacity. It suits itself perfectly to HMB use. There are also benefits from the calcium content if trying to lose weight. More on that later?


1. Papet I, Ostaszewski P, Glomot F, Obled C, Faure M, Bayle G, Nissen S, Arnal M, Grizard J. The effect of a high dose of 3-hydroxy-3-methylbutyrate on protein metabolism in growing lambs. Br J Nutr. 1997 Jun;77(6):885-96.


Abumrad N. Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on muscle metabolism during resistance-exercise training. J Appl Physiol 1996 Nov;81(5):2095-104