HMB

HMB

20-06-2016 | 
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By popular demand, this article was prepared in two versions: in a plain version that contains facts and basic information, and a more detailed and technical version. So, if you are one of those who have never had the patience to wade through my lengthy tractates, scroll down to the summary. But if you are a science geek and you are not afraid to use your brain, just keep on reading. While you are reading, I turn the volume to the maximum and “wade through” my Red Hot Chili album.

Probably all the things that could be told about HMB (beta-hydroxy beta-methylbutyrate acid) has already been told. Maybe. Maybe not. I have to admit: this topic posed me somewhat of a challenge. Our goal is generally to present information to the readers of www.BodyBuilder.hu that have not been accessible before in Hungarian technical literature, or not in enough detail. And I think we have lived up to this expectation so far. For example, the readers of bb.hu have learned more about isoflavones, creatine or other topics than all the readers of the Hungarian and international literature I am familiar with, which is quite unique. But this is not the case regarding HMB: even around ‘98, there were exhaustive articles available on this supplement. This is not necessarily a bad thing: this could mean that no experiments with negative results have been conducted ever since (or just a few minor ones). Maybe I could write a defamatory article for a change this time (I always enjoy that :) ), but I can’t, because I have only had positive experience with Ca-HMB supplements (apart from their price). So, let’s see a fair introduction (as usual) that you have never read in other articles so far!

The development of HMB and initial studies

I think we all agree that we couldn’t care less about the immune systems of chickens or sheep, or the positive effects of HMB in various chronic diseases including kidney disease (because CaHMB binds phosphate) or AIDS (immune boosting properties; reduces catabolism), as far as they don’t entail incredible muscle gains. Hopefully all of you are more or less healthy and fit, so you only need information that is relevant to your health in particular. So I will limit this article to relevant information. Let’s settle for the fact that there are over 10 years of research behind HMB including animal and human experiments, which is more than enough to estimate the opportunities HMB can offer.

HMB basics

HMB is a metabolite of the amino acid leucine. As we all know, BCAAs are important for proper muscular function and development by reducing the catabolism of muscle protein during exhausting workout (BCAAs: branched-chain amino acids: leucine, isoleucine and valine; these are essential amino acids, therefore the body cannot produce them). So it may not be surprising that a metabolite of leucine plays a similarly important role in your system.

HMB is derived from leucine through alpha-ketoisocaproate (KIC). Its normal blood level ranges from 1 to 4 micromol/l, which may multiply by 5-10 if you take leucine. Studies have shown that about 5% of the ingested leucine will transform into HMB. A 70-kg person can produce about 0.2 to 0.4 grams of HMB a day (if the data of animal experiments can be applied to humans as well). This means, you should take about 20 to 50 grams of leucine a day to ensure grams of HMB production in your system, which is hardly feasible, unless administered by a physician. We usually take it in the form of a calcium salt (Ca-HMB), 13% of which is calcium. More than half of the ingested amount is used by the body, but a significant amount is discharged with urine. This implies there is no active reabsorption, which happens often in other cases when substances are secreted into the filtrate. The reason of this is that the reabsorption of substances of similar chemical structures (ketone bodies) is not so important. Moreover, their secretion can be vital in some special cases. A recent study has shown that 70-85% of the ingested HMB will be used by the body. This sounds better than previous 55-60% (1). Let’s hope that the recent data are more accurate. Blood levels quickly drop after ingestion: the amount of HMB circulating in the blood reduces by half after about 2 and a half hours. This means, it is recommended to split the daily amount to 3, 4, 5 or more times a day to ensure maximum efficiency. HMB diminishes muscle injuries and reduces protein breakdown (catabolism), and as a result, it can help increase muscle mass and strength.

If taken in a dosage of 3 grams a day, the results can amount to 1-2 kg less body fat and 0.5-1.2 kg of extra lean muscle per month. The 3-gram HMB dose have increased total body strength by 18% in 3 weeks, contrary to the 8% of the placebo group (2), so the strength-boosting effect is significant. The research I cited was made up by two studies. The first is shortly described above. And now the second: most of the participants had practiced physical exercise before commencing the experiment (this was not indicated in the first study). Their average bodyweight was 99.3 kg (in the first study it was 82.7 kg), and even the extremes (72 to 136 kg) were closer to those of bodybuilders or people who exercise regularly (in the first study it was 64 to 99 kg). In the second study, the placebo group consumed about 20 grams less protein. During the first 14-39 days, the lean body mass of the HMB group increased significantly better than that of the placebo group. However, by the end of the study, the difference in fat free mass (FFM) was negligible. Regarding strength gains, for certain exercises including bench press, a minimal difference persisted by the end of the experiment. There was a slight increase in the amount (not the percentage!) of body fat in both groups. You might have seen the results of the first study: you know, these data of about 0, 1.5, 3g HMB -> x, y, z muscle gains are presented in the advertising materials, too. There is less talk about the second study or other studies with similar outcomes. But let’s discuss it later.

Another interesting result of the studies is the fact that high protein intake apparently doesn’t enhance the effect of HMB. In other words, there is no synergy. It is not necessary to take more than 2 g/kilogram of bodyweight of protein a day besides HMB supplementation. It won’t enhance anabolism (even though HMB has some nitrogen sparing effect, about 18%, which doesn’t seem to follow the increase of protein intake).

Safety

You might ask: is HMB safe? I must admit, I don’t know about any study that would have shown side effects of HMB supplementation. However, I would like to remind all of you who take statins or HMG-CoA reductase inhibitors to regulate cholesterol levels, to be careful and follow the prescribed diet instead of taking HMB, or at least ask your physician. Nissen & Co. summarized the results of 9 human experiments to study the safety of HMB. In each experiment, the subjects took 3 g of HMB daily. Experiments lasted between 3 and 8 weeks, including men and women of diverse age and physical condition. There was no negative change in the characteristic markers of body and tissue functions. Moreover, for subjects with high cholesterol levels, the total cholesterol levels dropped by 5.8% and the “harmful” LDL cholesterol by 7.3% on average (in the case of subjects with low cholesterol levels this difference was smaller), which significantly reduces the risk of cardiovascular diseases (like heart attack or stroke). Studies have found that HMB supplementation is safe. What is more, a slight decrease in the systolic blood pressure (4.4 Hgmm ~ 3%) was also detected. This can also be explained by calcium intake. However, different mechanisms of action are assumed, too. HMB also reduced hematocrit levels (although not to a significant extent) and red blood cell count (this is not confirmed by other studies; on the contrary: there have been applications for increasing the amount of hemoglobin and aerobic performance), and increased the number of lymphocytes. The importance of this is not known yet. Nevertheless, animal experiments reported enhanced immunity, so this supplement can have a positive impact on the immune system (T-lymphocytes) (3). HMB is a safe supplement. It is not a steroid and not a drug, and it is flushed out of the body smoothly. It doesn’t even influence the testosterone-epitestosterone ratio (4). Now you might be surprised that I’ve written this down, because you have probably all known it before. :) Since the experiments did not cover all possible life situations, do not use if you have a serious illness, you are pregnant or breastfeeding, or consult your physician first.

HMB’s mechanism of action

1 When leucine is broken down, ketone bodies (including acetoacetic acid, acetone and butyric acid) may be produced through HMG-CoA (beta-hydroxy-beta-methylglutaryl-coenzyme A). Ketone bodies are metabolites of fatty acid breakdown that becomes prevalent if there is a trouble with the carbohydrate supply of the body. HMG-CoA is closely related to HMB, and HMB can transform into it. HMG can transform into ketone bodies through HMG-CoA lyase. Ketone bodies are not useful in large amounts. And they are produced in huge amounts particularly in the case of diabetes or starvation. In such cases they are considered harmful metabolites, which will be flushed out of the body with urine (ketonuria) and through exhalation. Now I’d prefer not to go into detail about the ketogenic diet. But what can be the advantage of producing HMB from leucine, or taking HMB as a supplement in considerable amounts?
Ketone bodies can contribute to the energy supply of the heart and the brain in the case of insufficient glucose supply, e.g. in a diet. But what is more important: the kidneys and the heart muscle actually prefer ketone bodies as energy sources. So, in principle, we may profit from this transformation as well. However, it is still unknown what, and to which extent. This metabolic process is less important.

2 HMB will transform into HMG. HMG-CoA can join in the biosynthesis of cholesterol directly. “Wait! Cholesterol? What is so great about that?” You might ask. Well, let’s take water: it matters a lot whether water is inside of your muscle tissues, making your muscles nice and round, or it is just under your skin, making you look bloated. By the same logic, it is not the same whether cholesterol is circulating in your blood vessels, forming thick, fatty clots inside of your veins or it is in the endoplasmic reticulum [a small “bag” inside of a cell, separated by cell membrane] or the cytosol [the fluid inside of a cell] of your cells or muscle fibers as an important compound of the cell membranes. Of course this is not as simple as that, because there are useful and harmful types of cholesterol, and most of the cholesterol in your blood (about two thirds) is produced by your body, inside of the cells. But I guess you are all getting the bottom line: this process is not bad for you. On the contrary: building cell membranes is an important function. On the other hand, excess cholesterol that comes from external sources (food) will reduce the cells’ own cholesterol synthesis and inhibit further cholesterol uptake into the cells, which will reduce the formation of the uptake receptor protein. As a consequence, the cholesterol level of the blood will increase. So, we can say these are two different cases. Nevertheless, I would like to remind all of you who take statins or HMG-CoA reductase inhibitors to regulate cholesterol levels, to be careful and follow the prescribed diet instead of taking HMB, or at least ask your physician. In such cases, genetic or acquired disorders can strongly interfere with cholesterol metabolism, and the interactions are not known exactly. HMB reduces cholesterol levels, but it can work differently in the case of (e.g. genetically) extreme high triglyceride or cholesterol levels.

(I would like to spare all of you [including myself] from the stages of cholesterol biosynthesis; there are about 17 or 18 more stages from HMB to cholesterol, which can then turn into cell membrane, steroid hormones [corticosteroids, sex steroids], bile acids etc. Now prohormone manufacturers would say BS like “eat HMB and your testosterone production will be doubled”; but I won’t.)

It is assumed that if the musculature is damaged by workout or other types of stress, it cannot produce enough HMG-CoA to support cholesterol synthesis and recovery, while supplementation can repair damages and maintain cholesterol synthesis and membrane functions. This is also supported by the fact that HMB intake reduces the level of creatine phosphokinase (CPK), a substance that is released from the muscles and of which level typically increases if damages (including micro-traumas) occur in the muscles. Another supporting fact is that the inhibition of cholesterol synthesis by drugs can cause myopathia or even necrosis (5. a, b, c). This may be a side effect of the above-mentioned statins. From all this we can conclude that both HMG-CoA and cholesterol biosynthesis are essential for proper muscle function ("the muscle toxicity of HMG-CoA reductase inhibitors is due to an intracellular action mediated by the inhibition of muscle cholesterol synthesis" 5. b). Following from the assumed mechanism, HMB will not work without stress or micro-traumas. This means, HMB will not work without training, stress and catabolism.

This is the more important metabolic process. What makes things a little bit more complicated is that HMG from external sources does not work the same way as the HMB that is taken to reduce cholesterol levels. The effects of HMB are more beneficial. This can mean there are other factors in its mechanism of action that are not fully understood yet.

3 We might assume that fat burning is a totally distinct and independent process from muscle building. But this is not proven by research. In some studies, the reduction of body fat took place in parallel with muscle building, while in the studies in which no muscle building was achieved, the body fat was not reduced significantly either. On fat burning: see above. It is also important to point out that though the 1st Study (2) showed about 1 to 1.8 kg of body fat was dropped on average, but, there were no significant differences compared to the placebo group or the group that took 1.5 to 3 g of HMB ("The loss of fat was not significantly different among the groups.”), unlike the increase of lean body mass.

Dosage

The most common dosage which was also used in the studies is 3 g/day. Distributors recommend 2-3 grams. But of course, dosage may vary individually, just like for any other supplement or medicine. Now you might say it made no sense to discard the formula of “kilogram of bodyweight/x grams of creatine” in the case of creatine. But that’s different: the actual maintenance dose of a 70-kg person is 2-3 grams. And creatine has very powerful sparing properties for the musculature. So, the average amount of 5-10 grams is about 3-5 times more than necessary. As you can see, there is a huge gap, so this amount can even be enough for a 100-kg person. It is like taking 6-12 grams of HMB instead of the recommended amount of 3 grams.

Luckily, there are patents. The disadvantage of patents is that they make the price of HMB higher. (This is clear, but strangely, even medical journals point this out; they must think it is way too high.) And the advantage is that they inform you on the most important data available in technical literature, methods of production and recommendations for application. So, we can find guidance on the dosage of HMB, derived from the recommendations for use in humans and animals, and do something no one has ever made in bodybuilding in Hungary so far: prepare a hypothetical recommendation of dosage. Hypothetical, because we cannot check it in real life. However, studies are quite convincing, so we may feel free to rely on them. The maximum dose is defined around 6-10 grams for cholesterol reduction or anabolic purposes in humans, but the general recommendation is 3 grams. For animals, 15, 35 or 100 mg/kgbw/day is an existing protocol. Based on some studies, 38 mg/kgbw is recommended per day. This is less than the 3-gram dose that proved to be of maximum efficiency in the previous studies for athletes of average bodyweight (70 kg). Starting out from their 3-gram dose, 40-45 mg/kgbw/day or a maximum of 3, 4 or 5 grams per day (irrespective of bodyweight) should be enough for anyone. For example, a 70-kg athlete may take 3.15 g of HMB a day, while a 100-kg athlete can take 4-4.5 grams. No side effects or hazards are reported in technical literature. However, multiples of the 3-gram dose do not entail any advantages. But taking slightly more than the doses recommended above is more likely to bring you more success. I might even risk that some of the above cited studies failed because the doses were too low. So I am telling you: increase your HMB intake slightly above the recommended amount, in proportion with your bodyweight.

The Truth Behind the Adverts

Any drawbacks? Beside the fact that a significant part of this expensive supplement will land in the toilet, a possible drawback may be the fact that there are only a few studies to support what the distributors keep telling you all along: it remains effective on an ongoing basis; you don’t need to do cycles, and it can bring you 6 to 12 kg a year. Even successful experiments lasted only for a few weeks, and most of the subjects weren’t in a good physical condition (some of them were also suffering from serious illnesses). I am sadly presenting the results of a study in which 40 athletes were given 0, 3 or 6 grams of HMB for 28 days, while their blood parameters, body composition and strength gains were monitored. The result: no catabolism-reducing effect; no change in body composition and no significant strength gains (6). You might say this was probably caused by the diet, but this is less likely. The futility of application on fit individuals, especially athletes, has been supported by several recent studies (7. a, b, c). Long-term positive effects were detectable in the case of cancer or AIDS sufferers; these illnesses entail an extreme catabolic state the body cannot adapt to. It is not a big secret why I experienced positive results: the (ir)regularity and intensity of my workout routine looked like a sinus curve, depending on my exams. Conclusion: HMB is a superfood. For cripples. Other studies had though significantly smaller, yet not negligible positive results for fit individuals, compared to the two studies cited above. So, they can expect some positive results, too, but not in each case. You better be aware of that. In several studies, the loss of body fat was more likely related to training than HMB supplementation. But the adverts fail to mention that, of course.

If you start working out after a long pause or illness, or you are a novice in weight training, HMB can be a good choice. You can start with 3-4 grams a day or more. Then, as you are getting into shape and muscle growth is slowing down, you may consider whether it is worth taking any longer. It will still have its benefits, but huge muscle gains is not one of them. At this point, you may switch to another supplement (see details below). It is recommended to split the daily amount into several smaller doses. You may take somewhat larger amounts before and after workout, because at that time, your body needs more of it (to be more accurate: it needs more of the compound HMB is a precursor of). Some studies have also shown positive effects on aerobic performance in endurance sports. So runners, cyclists or swimmers may benefit from HMB as well. Maybe. If you are a professional athlete, even a few milliseconds can bring you victory, so it may be worth trying a box of HMB or two. But don’t expect miracles. If you experience positive results, take it.

One thing seems to be proven by all studies: bodybuilders, especially in the beginning, can profit from its effects (muscle gains and fat loss) for a short time. The improvement of strength performance is though a good thing, it doesn’t automatically entail muscle gains. We all know 70-kg guys who bench press with 100-110 kg. But that’s another sport. And strength gains are not likely to continue in the long run either. A one- or two-month course may give you a good kick (see study Nr. 2). But afterwards, you should definitely switch to something else or combine HMB with something else.

Combinations

Now I am talking mostly to beginners, as you might have guessed. A good multivitamin is a must, especially if you follow a dull diet. But mega doses of vitamin C are unnecessary. Protein supplements can be useful for anyone, but you don’t need to take excess amounts. 25-50 grams a day are enough for a beginner who takes HMB. But of course, a lot depends on the quality of the food you eat. It is a good idea to combine HMB with creatine and then switch to CLA, at least 4 grams a day. (CLA is quite a controversial supplement, which may be explained by the scarce doses that were administered in the studies). The effects of HMB and creatine add up (8), so they are worth taking in combination. Or you might start with HMB and switch to creatine after you have gained some muscle, because the potential results of creatine also depend on muscle mass: the larger the mass, the greater the water retention and the anabolism. The protein-synthesis enhancing properties of ecdysteroids are proven. So, if HMB seems to have worn out, MyoMeth or a similar product can also be a good alternative to ensure continuous development. So, these are the basics you can start with, on the road to muscle gains.

HMB is an anti-catabolic supplement, with a minimum dose of 3-4 grams a day. It won’t work without workout or a catabolic state. You may need to increase the dose if you are heavier. There hasn’t been much research on this matter, and you can read my recommendations above. The positive anabolic effects of HMB can bring approximately 0.5 to 1.5 kg of extra lean body mass per month and significant fat loss for individuals who have not worked out regularly before they started to take the supplement. Fit people will experience less improvement, both regarding muscle are strength gains. It is recommended to take it in 3, 4 or 5 portions during the day, with the largest amounts before and after workout. After a one- or two-month course, as the effects subside, it is recommended to switch to another anabolic or anti-catabolic supplement, for example, ecdysteroids. Based on the studies that have been conducted on fit athletes so far, ongoing supplementation is not justified. And you will be fit sooner or later, if you hang around a lot in the gym. As you could read in the article “Creatine peak”, there is no scientific basis for 6 or 8-week creatine courses. For HMB, it seems to be the opposite. Based on the studies so far, creatine is now considered a long-term supplement which should be taken for 2, 3 or 4 months, while HMB looks more like a recreational stuff which is not worth taking for longer than 4-6 weeks. HMB has become a supplement for beginners, while creatine has kept its top position for both fit and less fit individuals.

I hope that I could help a lot for beginners to achieve their goals, and for more experienced bodybuilders, too, to save a few bucks. (Feel free to transfer it to my bank account. Contact the editorial staff for further information. :) )

Have a great workout!

András Tihanyi
Nutritionist



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