HMB: Overrated, Overpriced, or Overlooked Part 2
By: Derek Charlebois B.S. CPT

       In the first article of this series, we examined the mechanisms by which HMB exerts its effects. The main points of the article were that taking HMB decreases markers of muscle damage and loss of amino acids by decreasing protein degradation. This is most likely due to HMB metabolizing into a substrate of cholesterol, which can be used by muscle cells to restore their membrane integrity and also its effects on the ubiquitin-proteasome proteolytic pathway. In this article, we will closely examine three studies done on different populations with HMB. Specifically, we will look at the lean mass and strength changes experienced by the subjects.

Study A

Nissen, S. et al. Effect of Leucine Metabolite b-hydroxy-b-methlbutyrate on muscle metabolism during resistance-exercise training. Journal of Applied Physiology. 81(5):2095-104, 1996 Nov.
      This 1996 study by Nissen was one of the first studies to examine HMB’s effects on body composition. The study was done on healthy, untrained (less than three months of training) males. All subjects went through an initial screening period to obtain measurements of body composition, strength, blood screening, and a physical examination.

Study 1

       The subjects were randomized into two groups: a high protein group (175 g/day) and a normal protein group (117 g/day). Subjects in both groups were then randomized into HMB groups: 0 g/day, 1.5 g/day, and 3 g/day. The subjects did not know which HMB group they were in, but they knew which protein group they were assigned to.
       Each subject exercised three times a week, alternating between specific upper body and lower body workouts, with a day of rest in between workouts. Subjects started out by lifting at 90% of the one repetition maximum (1-RM), which should have allowed them to get a complete three to five repetitions. When a subject became stronger, the weight used was increased so he would stay within a range of three to five repetitions. Each training session was monitored by a supervisor who decided when they subjects should increase the weights they used. All subjects’ diets were controlled as specific meals were supplied to them.

Findings

Body Composition

       Two subjects withdrew during the first week; one subject committed major violations in the dietary protocol, so his data was removed. The high protein group ate an additional 2,600 (average of 866.67 a week more) calories over the three-week period than the control group. The results on body composition are as follows:

	HMB Groups (grams of HMB)			Protein Intake
Body Composition (kg)	0	1.5	3	Control- 117 g	High Protein- 175 g
Body Weight	-1.41	-0.26	-0.41	-1.00	-0.39
Body Fat	-1.82	-1.07	-1.62	-1.62	-1.38
Body Lean Mass	+0.4	+0.8	+1.21	+0.62	+0.99

     The HMB groups (control and high protein) are combined according to dosage (on left side) and all subjects are combined according to protein intake (on right side). The main points of the table are that the group with the high HMB intake (3 g/day) gained the greatest amount of lean mass and the high protein group gained more lean mass than the control group. The control HMB and protein groups lost the most fat. None of the group lost any lean mass, while losing fat, which I suspect is due to the adaptations involved in beginning resistance training. But the 3 g HMB/day group gained three times the amount of lean mass than the control group.

Results- Strength

                Results are list as total work (number of repetitions X sets) for each group.

	HMB Groups			Protein Intake
	0	1.5	3	Control	High Protein
Start	4226	4075	3837	4031	4060
End	4563	4605	4544	4575	4566
Change	337.8 (8%)	529.4 (13%)	707.1 (18.4%)	544.1	505.4

       I found these results very interesting. When the groups were compared solely on protein intake, there was not much of a difference in the total increase of strength. However, when the HMB groups were compared, the group supplementing with 3 g HMB/day made the greatest improvement. An argument that could be made on this is the 3 g HMB/day group started at an overall lower strength and therefore had more room to grow. All three of the groups ended with about the same strength, but the 3 g HMB/group made the largest improvement.

Study 2

       The second part of Nissen’s study was testing males who were already engaged in an exercise program. Again, all subjects went through an initial screening period. The 1-RM was tested for bench press, squat, and clean and press. Weight training was done six days a week (2-3 hours a day) and aerobic exercise was done three times a week. The subjects were randomly divided into one of two groups: the control or HMB, 3 g/day, group (the subjects did not know which group they were in). There was no dietary control and the subjects were told to eat as they normally do. It was estimated that the control group consumed about 180 g protein/day and the HMB group consumed 200 g protein/day.

Findings

Bench press, squat, and hang clean are listed as 1-RM.

	Control Group			HMB Group
Kg	Start	End	Change	Start	End	Change
Body Weight	100.1	101.2	1.1	99.2	101.8	2.6
Fat Mass	16.5	16.8	0.31	15.7	15.9	0.25
Lean Mass	83.6	84.4	0.8	83.5	85.9	2.4
Bench Press	315	321	5.4	299	314	15.0
Squat	380	405	25.0	388	420	32.0
Hang Clean	221	250	29.0	222	252	30.0

        My take on the strength gains is that the large increase in strength on squat and hang clean is due to improvements in motor skills and other anatomical adaptations. Most people do not know how to properly execute these exercises, so by learning to correctly perform them, one’s strength would increase quickly. Bench press, on the other hand, is an exercise that is generally performed by all males engaged in a weight training program. Therefore, I would think the increase in bench press strength is more impressive as far as the results of this study go.

Conclusion

       Fat loss was not significantly different between the two groups (0.06 kg). But the HMB group gained three times the amount of lean mass. The HMB group’s strength also increased more than the control group’s.
      Nissen concluded that supplementing with HMB increased lean mass and strength gains by decreasing muscle damage and breakdown (See part I for more information of this).
      Additional studies done by Nissen found similar results among trained and untrained men and women [2] in addition to the elderly [3].

Study B- Creatine and HMB

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.
       This 2001 study by Jowko et al. wanted to see if creatine (CR) and HMB worked through different mechanisms. It has been proposed that CR’s effects on strength are due to increasing muscle CR content and its effects on lean mass due to increasing muscle cellular volume. An increase in cell volume would in turn increase protein synthesis. HMB’s proposed action is it decreases muscle breakdown by strengthening muscle cells’ membrane integrity.  This study aimed to find whether or not CR and HMB acted additively to increases in lean mass and strength.
       The study consisted of 40 males who were involved in an exercise program, but were not highly trained. An initial screening process, similar to the examination done in the previous study we observed, was done before the start of the study. Dietary control consisted of the subjects eating three meals per day in the student cafeteria. They also reported all food consumed during “three non-consecutive 24-h periods.”
       This was a double-blind study, so neither the subjects nor the experimenters knew who was in which group. The CR group supplemented with 20 g CR/day for the first 7 days and 10 g CR/day for the rest of the study. The CR was in powder form. The HMB group took 3 g HMB/day, which were in the form of capsules. All subjects, including the placebo group, consumed a drink containing 20 g glucose for the first 7 days and a drink containing 10 g glucose for the rest of the study. The CR group’s creatine was mixed in the drink and they also took placebo pills. The placebo group also took placebo capsules with their drink. So all subjects consumed the “same” thing.
        Subjects’ 1-RM were tested prior to beginning the study. Weight training was to be done 3 times a week, with a day of rest in between. The targeted rep range was 5-15 repetitions; when the subjects could complete 15 reps, the weight was increased based on a calculation from their 1-RM. The subjects were monitored during each session: “Each session was monitored by trained supervisors who recorded the weights lifted and repetitions performed.”

Findings

       All subjects’ consumed about the same amount of calories and macronutrients.

Body Composition

Body Composition (kg)	Placebo	CR	HMB	CR + HMB
Body Weight	+1.00	+2.01	+1.34	+3.4
Body Fat	+0.17	+0.19	+0.08	+1.00
Body Lean Mass	+0.85	+1.77	+1.24	+2.39

        Notice that all groups gained lean mass during this experiment. The CR group gained more lean mass than the HMB group, but the CR + HMB group gained the most. Since the lean mass gained by the CR + HMB group is less than the CR and HMB groups gains combined, the CR + HMB group’s results showed CR and HMB to additively increase lean mass. On the other hand, the fat gained by the CR + HMB group showed that combining these two supplements had a synergistic effect on gaining fat mass. After reviewing the caloric consumption of the subjects, it does not appear that caloric intake was the cause of this gain as the other groups did not gain as much fat mass.

Strength

        I am only going to report on the three main lifts, but the subjects also performed the behind the neck press, barbell curl, and triceps extension

Kilograms	Placebo	CR	HMB	CR + HMB
Bench Press	+3.89	+8.00	+10.60	+10.56
Squat	+2.78	+11.50	+12.81	+13.89
Power Clean	+6.11	+20.00	+14.38	+23.33
Total (All exercises)	+19.72	+57.25	+58.87	+71.61

       Based on the results,  we clearly see that the groups consuming the supplements outperformed the placebo group. The strength increases seen between the CR and HMB groups were pretty close, but the CR + HMB group recorded the greatest strength increase. Again, these increases were shown to be additive.

Conclusion

       This study showed that creatine and HMB increase lean mass and strength through different mechanisms based on additive increases in lean mass and strength of the CR + HMB group. The researchers proposed that CR’s effect on cellular volume (increased protein synthesis) and HMB’s effect on membrane integrity (decreased protein breakdown) lead to these additive increases in lean mass and strength.

Study C- HMB in Cancer Patients

Patricia Eubanks May, M.D.a,b, Annabel Barber, M.D.b, James T. D’Olimpio, M.D.c, Ann Hourihane, N.P.c, Naji N. Abumrad, M.D.c. Reversal of cancer-related wasting using oral supplementation with a combination of b-hydroxy-b-methylbutyrate, arginine, and glutamine. The American Journal of Surgery 183 (2002) 471–479
       This study is unlike the previous two studies examined. Instead of testing HMB’s effects on healthy, weight-training individuals, the effects of HMB were tested among cancer patients. Cancer is associated with loss of lean mass due to elevated protein breakdown and decreased protein synthesis. Maintenance of lean mass could mean survival for cancer patients.
       In an attempt to try and decrease or halt lean mass loss, supplemental HMB, glutamine, and arginine were examined. Both arginine and glutamine have been shown to improve immune functioning and wound healing. HMB was used to try to minimize protein breakdown.
       This double-blind study consisted of two groups: a control group and treatment group. The treatment group received 3 g HMB, 14 g L-arginine, and 14 G L-glutamine each day. The control group received an equal amount of nonessential amino acids.

Findings

	Control			Treatment (HMB + ARG + GLN)
Kilograms	Start	4-Week	12-Week	Start	4-Week	12-Week
Weight	59.2	60.6	58.9	63.7	65.7	72.4
Body Fat %	18.3	17.0	18.7	17.7	18.8	17.2

*The treatment group had a lower caloric intake
After 24 weeks, the treatment group gained 1.60 kg of lean mass while the control group gained only 0.48 kg.

Conclusion

        This study found that supplementing with HMB + L-arginine + L-glutamine increased body weight and lean mass above those receiving the isocaloric mixture. This is a beneficial finding because excess calories have not been shown to stop the excess weight loss in cancer patients. Another study done by Clark et al. reported similar findings in HIV patients [5].
       I included this study because like cancer patients, those involved in strenuous exercise exhibit increased protein breakdown. While healthy athletes do not experience protein breakdown to the same degree as cancer patients, this study still shows the effect HMB can have on protein breakdown.
       Two recent studies done by Smith et al. on HMB and protein degradation concluded, “These results suggest that HMB attenuates PIF-induced activation and increased gene expression of the ubiquitin-proteasome proteolytic pathway, reducing protein degradation.” [6, 7], which sheds further light on the above “Study C”.

My Conclusion

       We see from these three diverse studies that HMB looks promising. HMB holds its own by itself, and also exhibits additive effects when paired with creatine. Also, HMB has shown the ability to reduce protein breakdown and lean mass loss in cancer patients. By examining more recent studies, it would appear the same would hold true for healthy exercising individuals.
       In the third and final installment of this series, we will examine a study that did not find HMB to be effective in promoting lean mass or strength gains. Dosing protocols will also be addressed for those wishing to use HMB.

 

References:

1. Nissen, S. et al. Effect of Leucine Metabolite b-hydroxy-b-methlbutyrate on muscle metabolism during resistance-exercise training. Journal of Applied Physiology. 81(5):2095-104, 1996 Nov.

2. Panton, L. B. Nutritional Supplementation of Leucine Metabolite b-hydroxy-b-methlbutyrate (HMB) During Resistance Training. Nutrition. 16:734-739, 2000.

3.  Vukovich MD, Stubbs NB, and Bohlken RM. Body composition in 70-year old adults responds to dietary b-hydroxy-b-methlbutyrate (HMB) similar to that of young adults. J Nutr 131:2049-2052, 1999.

4. 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.

• Clark RH, Feleke G, Din M, et al. Nutritional treatment for acquired immunodeficiency virus-associated wasting using b-hydroxy-b- methylbutyrate, glutamine and arginine: a randomized, double-blind, placebo-controlled study. J Parenter Enteral Nutr 2000;24:133–9.

6. 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.

7. 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.