HMB: Overrated, Overpriced, or Overlooked Part 1
By: Derek Charlebois B.S. CPT

       There is one supplement that pops up in discussions every so often. Like all other supplements, the reviews for it vary from: “It is the best supplement ever,” to, “It is a waste of money.” Some positive claims people have made are it helped them add muscle, preserve muscle while cutting, and decreased DOMS. If you haven’t guessed it, or read the title yet, the supplement I am talking about is Beta-hydroxy beta-methylbutyrate AKA HMB.
       HMB became popular in the early 1990’s and was touted as the next big thing. Though it never really caught on to this promotion because of its hefty price tag and most people were not seeing “incredible” results. Times are a little different now and the price of HMB has dropped to where using sufficient amounts is not overly expensive. Due to this price drop, I have used HMB on a few different occasions: once by itself while bulking, once stacked with creatine while bulking, once stacked with creatine while at maintenance calories, and just recently stacked with creatine while cutting for my up coming competition. No doubt better results were seen while stacked with creatine, but I experienced noticeable positive effects each time on top of what I normally experience with creatine alone. The results from my last encounter with HMB are what prompted me to write this article.

My Last 4 Weeks of Cutting

      Over the last four weeks of dieting (Summer 2004), I have been consuming about 2,500 calories a day.  Here are the results from the past four weeks during which I used HMB:

Cutting 2004             Weeks Out:	15	13	11
DATE	4/4	4/28	5/2
Abdomen	8	6	5
Bicep	2	2	2
Calf	6	6	6
Kidney	15	14	11
Pectoral	7	4	3
Quadricep	12	10	9
Subscapula	10	9	8
Suprailiac	7	6	4.5
Tricep	6	5	5
TOTAL	73	62	53.5
Bodyweight	200	196	194.5
Weight change from previous	-	-4	-1.5
% Bodyfat	9.855	8.541	7.427
lbs Bodyfat	19.71	16.74	14.45
Fat Mass change from previous	-	-2.97	-2.295
lbs Lean Mass	180.3	179.3	180.1
Lean Mass Change from Previous	-	-1.03	0.795

       The number in red is the number I want to emphasize. I gained 0.795 pounds of lean mass WHILE losing 2.295 pounds of fat. Gaining muscle while losing fat? I thought that wasn’t possible? What is more impressive to me is I gained almost a full pound of lean mass over that two-week period, which would be an impressive gain even while bulking. So what changed during the second two weeks from the first two weeks in the above table? The change was the addition of HMB.
       During the first two weeks, I was getting 3 grams of HMB a day (1.5 grams per serving of NitroJet). During week three, I added 3 more grams of HMB a day for a total of 6 grams of HMB per day. During the fourth week, I added another 2 grams of HMB for a total of 8 grams of HMB a day. I should also note that these high doses of HMB (6 and 8 grams) were only taken on Monday, Tuesday, Thursday, and Friday (the days I weight trained) with 5 grams per day on Wednesday, Saturday, and Sunday (cardio and rest days).
Does this mean HMB works? Does it have merit? The above is only one person’s results (and yes I will be experimenting with HMB in the future). What do the research articles say? In this article we will examine the current research and science behind HMB to see whether my progress was affected by HMB or if it would have happened without it. Basically, we will examine if HMB is a worthy supplement.

Leucine

      Leucine, one of the three branch chain amino acids (BCAA), has received a lot of attention and continues to receive more. An example is the work done by Dr. Layman on leucine’s role in weight loss and glucose homeostasis [1]. Leucine, along with the other two BCAA, isoleucine and valine, has numerous roles in different metabolic pathways. Leucine’s roles include: being a promoter of and substrate for protein synthesis and energy, activator of the insulin-signaling pathway, and precursor to alanine and glutamine [1]. Some have suggested that the BCAA’s first priority is for synthesis of protein structures [2]. I bring these properties up because HMB is a metabolite of leucine.

Leucine Metabolism

       Leucine and the other BCAA are the only amino acids not degraded in the liver. Instead, BCAA are degraded in peripheral tissues (i.e. skeletal muscle and adipose tissue).


Takn From: Nissen, Steven and Naji, Abumrad. Nutritional Role of the Leucine Metabolite b-hydroxy-b-methlbutyrate (HMB). J. Nutr. Biochem. 8:300-311, 1997.

We see that leucine, and therefore HMB, is a substrate of cholesterol [1]. Cholesterol plays a vital part in the integrity of cell membranes.

Cholesterol and the Cell Membrane

       The membrane is the out layer of a cell, which serves as a selective barrier as to what molecules can cross into and exit the cell. This membrane also detects chemical signals from other cells and secures the cell to the extracellular matrix (fluid outside of the cell). Cell membranes are made up of a double layer of lipid molecules: phospholipids and cholesterol. If the cell membrane becomes damaged, unwanted molecules could enter and exit the cell. Therefore repairing the membrane is a must. Cholesterol also functions as a precursor for bile salts, steroid hormones, and other specific molecules [6].

Cell Membrane

       Most of the cholesterol obtained from dietary sources is excreted in the feces. Therefore, in order to obtain required cholesterol, the cells must uptake it from the blood or synthesize it themselves. Most cells cannot synthesize an adequate amount of cholesterol on their own and must receive cholesterol from the blood. The cells lining the gastrointestinal tract and the liver produce the cholesterol in the blood.
       I want to point out that even though most of the dietary cholesterol is excreted, it does impact blood cholesterol levels. The liver is the homeostatic controller of blood cholesterol. Whenever dietary cholesterol is increased, cholesterol synthesis by the liver is inhibited, due to inhibition of critical enzymes. When dietary cholesterol is decreased, the liver increases its production of cholesterol [6]. For the most part, this negative feedback system keeps plasma cholesterol levels relatively stable. But certain genetic factors and dietary habits can shifts things for better of worse (as seen in America’s current high cholesterol epidemic).

Cholesterol and Exercise

      When we exercise, we cause micro trauma to our skeletal muscle cells, as well as connective tissue. This muscle damage is caused by excessive strain to the sarcomere (muscle cell membrane) caused by the repeated concentric, and specifically eccentric contractions involved in exercise. This can result in the breakdown of structural proteins.
Damage to the cell membranes would increase the need for cholesterol to use in repairing the membrane. Therefore, synthesis inside the muscle cell would be increased.  This disruption in the integrity of the cell means the intracellular functions associated with cell growth (i.e. hypertrophy) are put on the back burner until the membrane integrity is reestablished. The cell only has so much energy. In order to synthesis cholesterol, the cell has to use energy that could have been used from protein synthesis of contractile tissue. Some researchers feel that muscle hypertrophy (increase in muscle size) increases the muscle’s requirement for cholesterol and in order to maintain this new size, sufficient cholesterol is needed [8].
      If a larger muscle needed more cholesterol to maintain its size, wouldn’t it require even more cholesterol above what is needed to maintain that size in order to further increase its size above its current size? It is well known that the larger a person gets (with regards to lean mass), the higher resting metabolic rate (RMR) is. Therefore, just as a larger person must eat more calories to maintain his/her size, muscle cells need more cholesterol to maintain their increased size. 
      Current data supports the hypothesis that supplementing with HMB supplies a source of HMG-CoA for cholesterol synthesis for immune system cells, mammary glands, and muscle cells [2]. This is important because the peripheral tissues (i.e. skeletal muscle) uptake little if any cholesterol from the blood [2, 11]. Supplementing with HMB could supply muscle cells the needed cholesterol for increased membrane and organelle synthesis (construction) and differentiation (change towards a more specialized form or function). What this means for the athlete is an increase muscle size and function.  
      An interesting note is that cholesterol synthesis inhibitors have been shown to cause severe muscle toxicity, since muscles rely on de novo synthesis of cholesterol [5]. This toxicity ranged from muscle damage [9] to muscle cell death [10]. It is quite obvious the cholesterol is vital for muscle cell survival let alone hypertrophy or preservation.  

Research

      There are not many studies on HMB. But the studies that do exist show HMB to have to some positive attributes.

Markers of Cell Damage

      There are three main markers which researchers look at when examining muscular protelysis (breakdown of protein into peptides or amino acids) or damage: creatine phosphokinase (CK), lactate dehydrogenase (LDH), and 3-methylhistidine (3-MH). Research has shown HMB supplementation to decrease of all these parameters [3, 7].
3-MH only shows up in the blood when contractile proteins break down, making it the best marker to use when examining the effects of exercise on muscle tissue. A study examining this marker found that after one week of exercising, urine 3-MH levels increased by 94% in the control group, 85% in the group supplementing with 1.5 g HMB/day, and 50% in the group supplementing with 3 g HMB/day. More interested is after two weeks of exercising, the urine 3-MH level of the control group was still 27% above their basal value, while the group supplementing with 1.5 g HMB/day value was 4% below their basal value and the 3 g HMB/day group was 15% below their basal value [12]. This shows the supplementing with HMB decreases the amount of contractile protein being broken down.
      One study showed that supplementing with HMB decreased CK levels below the initial screening values at the two week mark, while the placebo group’s CK levels were more than five times as much as their initial screening value [8].  CK levels in the blood rise from CK from muscle cells “leaking” out due to membrane damage. This study shows that supplementing with HMB decreases damage done to the membranes of muscle cells since there was less “leaking” of CK out of the cells [8].

Plasma Amino Acids and Urea

      The sum of essential amino acids (EAA) in plasma increased by 32% in subjects not supplementing with HMB, decreased by 9% in subjects supplementing with 1.5 g HMB/day, and decreased 18% in subjects supplementing with 3 g HMB/day [3].
      Urine and plasma urea nitrogen measurements are used to access a person’s nitrogen balance. High levels indicate excessive protein breakdown or dietary protein intake. A study that measured these parameters found that supplementing with 3 g HMB/day decreased urinary urea nitrogen by 42% and plasma urea nitrogen by 26%, while the placebo group’s measurements increased [8]. This shows there was less protein breakdown in the HMB group since both groups consumed about the same amount of protein [8]. 

Less Contractile Protein Breakdown

       The decrease in urinary 3-MH and plasma levels of EAA supports the theory that HMB decreases muscle proteolysis. Since the body cannot synthesis EAA, they must be acquired from dietary sources. Therefore, any increase in EAA plasma levels would most likely be due to the breakdown of muscle tissue (the body’s most abundant supply of amino acids). Two recent studies done by Smith et al. concluded “These results suggest that HMB attenuates PIF-induced activation and increased gene expression of the ubiquitin-proteasome proteolytic pathway, reducing protein degradation.” [13, 14].

Just Take Leucine?

       It appears that HMB does have many positive effects that can lead to increased gain in lean mass and decreased muscle breakdown and is therefore a valuable supplement. So if HMB is a metabolite of leucine, why not just take leucine? HMB is produced by the liver enzyme a-ketoisocaproate (KIC) oxygenase and this enzyme only accounts for 5% of leucine oxidation [4]. Therefore one would not get enough HMB to obtain the positive effects seen in the studies above (3 g/day). With a “normal” diet, one produces 0.2-0.4 grams of HMB per day [3], but up to 1 gram/day has been seen. An increase in leucine consumption would no doubt increase the amount of HMB produced, though it does not guarantee targeted amount will be created due to limited enzyme activity.

Summary and Conclusion

Effects of HMB include:

• Cholesterol synthesis for peripheral tissues, most importantly muscle cells
• Increased muscle cell integrity
• Decreased muscle proteolysis and damage, due to decreased CK, LDH, 3-MH
• Decreased muscle breakdown

• Which both lead to increased lean mass and strength

       HMB is a substrate for cholesterol synthesis. When the body lacks a substrate, processes that use the substrate suffer. Supplementing with HMB ensures you have the needed substrate for cholesterol synthesis and maintenance of cell integrity. HMB also decreases muscle breakdown. Due to these properties, HMB would be an effective supplement to use while bulking, but even more powerful when one is cutting with decreased calories and needs to preserve lean mass.

 

Works Cited

1. Layman, Donald. (2003) The Role of Leucine in Weight Loss Diets and Glucose Homeostasis. American J. Nutr. 133: 261S-267S.
2. Nissen, Steven and Naji, Abumrad. (1997) Nutritional Role of the Leucine Metabolite b-hydroxy-b-methlbutyrate (HMB). J. Nutr. Biochem. 8:300-311.
3. Nissen, S. et al. (1996) Effect of Leucine Metabolite b-hydroxy-b-methlbutyrate on muscle metabolism during resistance-exercise training. Journal of Applied Physiology. 81(5):2095-104.
4. Van Kovering M, Nissen SL. (1992) Oxidation of leucine and alpha-ketoisocaproate to b-hydroxy-b-methlbutyrate in vivo. Am J Physiol (Endocrinology Metabolism). 262:27.
5. London, S.F., Gross, K.F., and Ringel, S.P. (1991) Cholesterol Lowering Agent Myopathy (CLAM). Neurology. 41:1159-1160.
6. Widmaier, Eric. Raff, Hershal, Kevin, Strange (2004). Human Physiology: The Mechanisms of Body Function (9th Ed.) Boston: Mcgraw Hill.
7. Panton, L. B. (2000) Nutritional Supplementation of Leucine Metabolite b-hydroxy-b-methlbutyrate (HMB) During Resistance Training. Nutrition. 16:734-739.
8. Jowko, Ewa, et al. (2001) Creatine and b-hydroxy-b-methlbutyrate (HMB) Additively Increase Lean Body Mass and Muscle Strength During a Weight-Training Program. Nutrition. 17:588-566.
9. Pierno, S., De Luca, A., Tricarico, D., Roselli, A., Natuzzi, F., Ferrannini, E., Laico, M. & Camerino, D. C. (1995) Potential risk of myopathy by HMG-CoA reductase inhibitors: a comparison of pravastatin and simvastatin effects on membrane electrical properties of rat skeletal muscle fibers. J. Pharmacol. Exp. Ther. 275: 1490–1496.
10. Mutoh, T., Kumano, T., Nakagawa, H. & Kuriyama, M. (1999) Role of tyrosine phosphorylation of phospholipase C gamma1 in the signaling pathway of HMG-CoA reductase inhibitor-induced cell death of L6 myoblasts. FEBS Lett. 446: 91–94.
11. Nissen S, Panton L, Sharp RL, et al. B-Hydroxy-B-methylbutyrate (HMB) supplementation in humans is safe and may decrease cardiovascular risk factors. J Nutr 2000;130:1937–45.
12. Nissen S, Sharp R, Ray M, et al. The effect of the leucine metabolite b-hydroxy b-methylbutyrate on muscle metabolism during resistance-exercise training. J Appl Physiol 1996;81:2095–104.
13. Smith HJ, Wyke SM, Tisdale MJ. Mechanism of the attenuation of proteolysis-inducing factor stimulated protein degradation in muscle by beta-hydroxy-beta-methylbutyrate.
    Cancer Res. 2004 Dec 1;64(23):8731-5.
14. Smith HJ, Mukerji P, Tisdale MJ. Attenuation of proteasome-induced proteolysis in skeletal muscle by {beta}-hydroxy-{beta}-methylbutyrate in cancer-induced muscle loss.
    Cancer Res. 2005 Jan 1;65(1):277-83.