Nutritional supplementation of the leucine metabolite β-hydroxy-β-methylbutyrate (hmb) during resistance training1

APPLIED NUTRITIONAL INVESTIGATION

Nutritional Supplementation of the Leucine Metabolite ␤-Hydroxy-␤-Methylbutyrate (HMB) During Resistance Training Lynn B. Panton, PhD, John A. Rathmacher, PhD, Shawn Baier, MS, and Steven Nissen, DVM, PhD From the Department of Education, East Tennessee State University, Johnson City, Tennessee, USA The effects of supplementation of the leucine metabolite ␤-hydroxy-␤-methylbutyrate (HMB) were examined in a resistance training study. Thirty-nine men and 36 women between the ages of 20 – 40 y were randomized to either a placebo (P) supplemented or HMB supplemented (3.0 g HMB/d) group in two gender cohorts. All subjects trained three times per week for 4 wk. In the HMB group, plasma creatine phosphokinase levels tended to be suppressed compared to the placebo group following the 4 wk of resistance training (HMB:174.4 ⫾ 26.8 to 173.5 ⫾ 17.0 U/L; P:155.0 ⫾ 20.8 to 195.2 ⫾ 23.5 U/L). There were no significant differences in strength gains based on prior training status or gender with HMB supplementation. The HMB group had a greater increase in upper body strength than the placebo group (HMB:7.5 ⫾ 0.6 kg; P:5.2 ⫾ 0.6 kg; P ⫽ 0.008). The HMB groups increased fat-free weight by 1.4 ⫾ 0.2 kg and decreased percent fat by 1.1% ⫾ 0.2% while the placebo groups increased fat-free weight by 0.9 ⫾ 0.2 kg and decreased percent fat by 0.5% ⫾ 0.2% (fat-free weight P ⫽ 0.08, percent fat P ⫽ 0.08, HMB compared to placebo). In summary, this is the first short-term study to investigate the roles of gender and training status on the effects of HMB supplementation on strength and body composition. This study showed, regardless of gender or training status, HMB may increase upper body strength and minimize muscle damage when combined with an exercise program. Nutrition 2000;16:734 –739. ©Elsevier Science Inc. 2000 Key words: leucine metabolite ␤-hydroxy-␤-methylbutyrate, resistance training, supplement

INTRODUCTION Leucine and certain metabolites of leucine decrease stress-related nitrogen and protein losses by inhibiting protein breakdown, which is elevated in disease and trauma.1– 4 It has been hypothesized that the leucine metabolite, ␤-hydroxy-␤-methylbutyrate (HMB), may be responsible for this inhibitory effect on protein breakdown.5 HMB is produced by the liver enzyme, ␣-ketoisocaproate (KIC) oxygenase.6 –9 This enzyme normally accounts for about 5% of leucine oxidation.10 Data in humans, sheep, and pigs indicate that the majority of HMB is metabolized in the body while the rest is excreted in the urine.5 A recently published paper examined the effects of HMB supplementation on body composition changes.11 In young men undergoing an intense 3-wk resistance training program, HMB increased strength and fat-free weight compared with subjects supplemented with a placebo.11 In addition, results from a second study with young men also found that HMB supplementation increased fat-free weight gains associated with a 7-wk resistance training program.11 The mechanism of the effect appears to be related to less muscle membrane damage. In human and animal trials that were supplemented with HMB during intense exercise there were lower levels of creatine phosphokinase (CK)11–13

Study funded by Metabolic Technologies, Inc. Correspondence to: Lynn B. Panton, PhD, East Tennessee State Univeristy, P.O. Box 70654, Johnson City, TN 37614. E-mail: [email protected] Date accepted: May 22, 2000. Nutrition 16:734 –739, 2000 ©Elsevier Science Inc., 2000. Printed in the United States. All rights reserved.

and lactate dehydrogenase (LDH)11 and a decrease in 3-methylhistidine (3-MH) excretion.11 Together these changes suggest that HMB may prevent or slow muscle membrane damage as well as partially prevent the increase in proteolysis that is associated with intense muscular work. Although the effects of HMB in trained young men have been previously investigated11,14 the roles of gender and training status have not been examined. It is hypothesized that HMB will be effective for both men and women in increasing strength while increasing fat-free weight and decreasing fat weight when combined with an exercise program. Therefore, the objectives of the present study was to further examine the effects of HMB supplementation on strength and body composition changes in both men and women following a supervised resistance training program.

METHODS Subjects Forty-three men and 41 women between the ages of 20 and 40 y were recruited to participate in a 4-wk resistance training program. Men and women were studied in two separate gender cohorts. Based on sample sizes from previous experience,11 subject size was limited to approximately 20 subjects per treatment group. Subjects were originally recruited to either a trained or untrained arm of the study. Although subjects were placed in a trained or untrained group, all subjects were familiar with a program of resistance training. Those individuals placed in the untrained group were individuals that had not participated in a resistance training program in the last 6 mo. Subjects were excluded if they had 0899-9007/00/$20.00 PII S0899-9007(00)00376-2

Nutrition Volume 16, Number 9, 2000 evidence or history of diabetes mellitus; cardiac, liver, pulmonary, or renal disease; recent joint or bone injury; or obesity. If the women were pregnant or lactating, they were also excluded from the study. In addition, only women with normal menstrual cycle phases were included in the study. Subjects were screened by blood and urine analyses before participation in the study. The objectives and risks of the study were explained to all subjects and written consents were obtained. The study was approved by the Iowa State Committee for the Protection of Human Subjects. All subjects were asked to maintain their current exercise programs in conjunction with the resistance training program required for the study. Supplementation The subjects were randomly assigned in a double blind fashion to either the HMB-supplemented group or placebo-supplemented group within each gender cohort. HMB and placebo were provided in capsule form by Metabolic Technologies (Ames, IA, USA). The HMB supplement was provided in capsules containing 250 mg of Ca-HMB and 50 mg of potassium phosphate per capsule (to partly balance extra calcium intake). The placebo was also placed in identical capsules but contained rice flour. Prior to the study, tests confirmed the placebo and HMB capsules could not be distinguished. Subjects were instructed to take four capsules with a meal, three times a day. Subjects were given weekly log sheets so they could record the times that the supplement was taken. The logs were collected each week to help ensure that supplements were being taken as directed. Blood Collection/Analysis Blood samples were collected from a superficial vein into Vacutainer blood tubes (Vacutainer Systems, Becton-Dickson, Rutherford, NJ, USA) after an overnight fast by the subjects at the beginning and after 4 wk of training. Subjects were also asked to refrain from exercise 48 h before the blood draw. Blood samples were processed on the day of collection and analyzed by Laboratory Corporation (Des Moines, IA, USA) for plasma CK. Plasma was also analyzed for human chorionic gonadotropin to be sure none of the women participating in the study were pregnant. Body Composition Body composition was measured before and after the 4 wk of training using underwater weighing procedures.15 Subjects were instructed to report for their scheduled underwater weighing test following an overnight fast and after voiding. During the underwater weighing, subjects were instructed to forcefully exhale to residual volume while underwater. Residual volumes were predicted from gender specific equations.15 Once a subject was accustomed to the underwater weighing procedures, the subject would perform multiple trials until the highest underwater weight was performed in duplicate. Percent body fat was estimated from the Siri equation.16 Skinfolds were also measured before the underwater weighing procedures to evaluate any regional changes that may have occurred. Body composition was also assessed using the sum of seven skinfold procedure outlined by Pollock and Wilmore.15 Each of the seven skinfold sites was measured twice. If the skinfold measurements differed by more than 1 mm, a third measurement was taken. Strength Testing Strength testing was conducted 1 wk before the beginning of the training program and after 2 d of orientation to the weights and exercises. The one repetition maximum test (1-RM) was used to evaluate strength.15 The 1-RM test was defined as the maximal

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amount of weight that could be moved one time through the full range of motion for the particular exercise. For the men, upper body strength was evaluated on the bench press and lower body strength on the Wynmor free-weight-loaded leg press. The women were also evaluated for upper body strength using the bench press, however, lower body strength was evaluated using the Cybex leg extension. After a warm-up, subjects chose a weight that was close to what they considered to be their 1-RM. After each successful lift and a rest period of 3 min, the weight was increased until the subjects achieved their 1-RM. Subjects then came back 3 d later to have their 1-RM repeated. This was done in an effort to control for any learning effect or for any fatigue that may have influenced their initial measurements. 1-RM measurements were repeated 3 d after the completion of the 4-wk training period. Strength Training All subjects trained three times per week on Monday, Wednesday, and Friday using free weights, Cybex resistance machines, and the Wynmor free weight loaded leg press. Eleven exercises were chosen to isolate the major muscle groups of the body which consisted of the bench press, latissmus pulldown, preacher curls, triceps pushdown, seated rows, leg extension, leg curls, standing calf raise, leg press, incline sit-ups, and back hyperextension. Subjects performed three sets of each exercise at 90% of their 1-RM. Subjects performed three to six repetitions until failure on each set. Once six repetitions were achieved on each set, the weight was increased by 5%. If subjects could not lift at least three repetitions during each set, the weight was decreased. All training sessions and lifts were supervised by trained staff; who would also make the appropriate weight changes. In addition, staff members helped with spotting of weights and ensured adherence to the protocol. All workouts were recorded on data sheets that were reviewed after each session. Every subject completed 12 workouts during the 4-wk training period. The training protocol for the women was adjusted slightly from that of the men due to the fatigue and soreness reported by the men. Women subjects also trained on Monday, Wednesday, and Friday, at the same intensity and on the same equipment, however, upper and lower body groups were exercised on alternating workouts. For example the upper body was trained on Monday and Friday and the lower body was trained on Wednesday during the first week. The following week this was reversed with the lower body being trained Monday and Friday and the upper body on Wednesday. All other procedures were similar between the men and women. Statistical Analyses Originally each gender cohort was analyzed using a 2 ⫻ 2 Analysis of Variance (ANOVA) with main effects of training status (currently trained/untrained) and supplementation (placebo/HMB). Since there was no significant effect of training status (trained/ untrained) for either the men or the women cohorts, the data were pooled and the main effect of supplementation was analyzed with an One-Way ANOVA. The data from the men and women cohorts were also combined and analyzed using a 2 ⫻ 2 ⫻ 2 ANOVA for the dependent measures of strength, body composition, and plasma CK levels using the main effects of training status, gender, and supplementation. In addition, data were also reported by supplementation since there was no significant effect of gender. Statistical analysis was performed using the general-linear models of SAS (SAS Institute Inc., 1988). Results were considered significant if P ⬍ 0.05 was obtained.

RESULTS Of the 43 men initially recruited, 39 completed the 4 wk of training. One subject was removed initially due to an abnormal

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Nutrition Volume 16, Number 9, 2000 TABLE I.

EFFECT OF 4 WK OF HMB SUPPLEMENTATION COMBINED WITH RESISTANCE TRAINING IN MEN* Placebo (n ⫽ 18)

Age (y) Height (cm) Strength Bench press (kg) Leg press (kg) Body composition Body weight (kg) %Body fat SF UWW Fat-free weight SF (kg) UWW Blood parameters Creatine phosphokinase (U/L)

HMB (n ⫽ 21)

Before

After

⌬

Before

After

⌬

25 ⫾ 1.2 179 ⫾ 1.5

NA NA

NA NA

23 ⫾ 0.6 177 ⫾ 1.1

NA NA

NA NA

70.8 ⫾ 6.6 248.4 ⫾ 18.6

78.0 ⫾ 6.5† 358.1 ⫾ 21.1†

7.0 ⫾ 1.0 131.9 ⫾ 12.6

70.9 ⫾ 4.1 222.4 ⫾ 12.2

80.8 ⫾ 4.4† 368.9 ⫾ 13.6†

9.9 ⫾ 0.9‡ 141.7 ⫾ 10.5

85.8 ⫾ 2.9

85.1 ⫾ 2.6

0.8 ⫾ 0.3

81.2 ⫾ 2.5

82.8 ⫾ 2.6

1.1 ⫾ 0.3

17.3 ⫾ 1.8 18.9 ⫾ 1.7

15.4 ⫾ 1.5 18.1 ⫾ 1.6

⫺1.0 ⫾ 0.4 ⫺0.9 ⫾ 0.3

13.0 ⫾ 1.2 18.0 ⫾ 1.3

11.9 ⫾ 1.1 16.5 ⫾ 1.3

⫺1.1 ⫾ 0.3 ⫺1.5 ⫾ 0.3

70.0 ⫾ 1.9 68.9 ⫾ 1.7

71.2 ⫾ 1.9 70.3 ⫾ 1.7

1.1 ⫾ 0.4 1.4 ⫾ 0.3

68.8 ⫾ 1.3 66.3 ⫾ 1.6

70.0 ⫾ 1.3 68.3 ⫾ 1.6

1.2 ⫾ 0.3 2.0 ⫾ 0.3

205.3 ⫾ 36.2

236.7 ⫾ 31.5

34.1 ⫾ 36.1

222.5 ⫾ 42.5

230.7 ⫾ 23.2

5.2 ⫾ 32.6

* Values are means ⫾ SE. † P ⱕ 0.05, significantly different from before values. ‡ P ⱕ 0.05, significantly different from placebo group. HMB, ␤-hydroxy-␤-methylbutyrate; NA, not applicable; SF, calculated from the sum of seven skinfolds; UWW, calculated from underwater weighing.

blood-screening test, and 3 other subjects had to drop due to injuries during the training program. Of the 41 women initially recruited for the study, 36 completed the 4 wk of training. One had to drop for unrelated medical reasons, 1 due to an injury that occurred outside the study, and 3 due to time constraints. Table I and Table II show subject characteristics and screening values for

the men and women cohorts. There were no significant differences in muscle strength or body composition between the HMBsupplemented and placebo-supplemented groups at the start of training for either the men or the women cohorts. The men, however, were heavier, taller, leaner, and stronger than the women. In men, plasma CK levels in the HMB-supplemented group

TABLE II. EFFECT OF 4 WK OF HMB SUPPLEMENTATION COMBINED WITH RESISTANCE TRAINING IN WOMEN* Placebo (n ⫽ 18)

Age (y) Height (cm) Strength Bench press (kg) Leg extension (kg) Body composition Body weight (kg) %Body fat SF UWW Fat-free weight SF (kg) UWW (kg) Blood parameters Creatine phosphokinase (U/L)

HMB (n ⫽ 18)

Before

After

⌬

Before

After

⌬

27 ⫾ 2.0 168 ⫾ 1.4

NA NA

NA NA

27 ⫾ 2.1 166 ⫾ 1.1

NA NA

NA NA

18.6 ⫾ 2.4 50.6 ⫾ 1.8

21.8 ⫾ 2.5† 65.1 ⫾ 2.4†

3.2 ⫾ 0.7 14.5 ⫾ 1.8

14.0 ⫾ 2.0 48.5 ⫾ 2.8

19.1 ⫾ 1.9† 64.6 ⫾ 14.5†

5.1 ⫾ 0.7‡ 16.0 ⫾ 1.8

62.8 ⫾ 2.1

63.2 ⫾ 8.9

0.4 ⫾ 0.2

62.3 ⫾ 2.2

62.8 ⫾ 2.3

0.5 ⫾ 0.2

19.4 ⫾ 1.9 21.9 ⫾ 1.5

18.9 ⫾ 1.9 21.7 ⫾ 1.4

⫺0.5 ⫾ 0.3 ⫺0.3 ⫾ 0.3

20.1 ⫾ 2.0 23.7 ⫾ 1.1

18.9 ⫾ 1.8 23.0 ⫾ 1.2

⫺1.2 ⫾ 0.3 ⫺0.7 ⫾ 0.3

50.1 ⫾ 1.1 48.7 ⫾ 1.2

50.7 ⫾ 4.6 49.2 ⫾ 1.3

0.6 ⫾ 0.2 0.5 ⫾ 0.2

50.0 ⫾ 1.4 47.3 ⫾ 1.3

51.1 ⫾ 1.4 48.0 ⫾ 1.3

1.1 ⫾ 0.2 0.7 ⫾ 0.2

104.6 ⫾ 13.4

153.7 ⫾ 32.9

49.9 ⫾ 27.5

102.9 ⫾ 9.8

18.0 ⫾ 28.2§

118 ⫾ 25.8

* Values are means ⫾ SE. † P ⱕ 0.05, significantly different from before values. ‡ P ⫽ 0.065, different from placebo group. § P ⫽ 0.095, different from placebo group. HMB, ␤-hydroxy-␤-methylbutyrate; NA, not applicable; SF, calculated from the sum of seven skinfolds; UWW, calculated from underwater weighing.

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FIG. 1. Change in creatine phosphokinase (CK) activity following 4 wk of HMB supplementation combined with resistance training in men and women cohorts.

increased only ⫹3.7% from baseline while the placebo group showed a ⫹15.2% plasma CK increase from baseline measures (P ⫽ 0.06). For women, the difference in plasma CK responses was even greater between the HMB-supplemented and placebo groups (HMB ⫽ ⫺12.8%; Placebo ⫽ ⫹46.9%; P ⫽ 0.06) (Table I, II, and Fig. 1). There was no significant main effect of training status (trained versus untrained) nor was there an interaction between training status and treatment (supplementation) in either the men or the women cohorts after the 4 wk of training. Therefore, Table I (men - cohort) and Table II (women - cohort) present the pooled data for each gender cohort on upper and lower body strength, body composition, and plasma CK. In the men cohort (Table II), after the 4-wk strength training program, the HMB-supplemented group had a greater increase in upper body strength compared to the placebo-supplemented group (placebo 7.0 kg and HMB 9.9 kg; P ⱕ 0.05). Following the 4 wk of training, the HMB-supplemented group had a 2.0 kg nonsignificant increase in fat-free weight (underwater weighing),

while the placebo-supplemented group also had a non-significant 1.4 kg increase in fat-free weight. In addition, the HMBsupplemented group had a 1.5% non-significant decrease in body fat percentage (underwater weighing), while the placebosupplemented group had a 0.9% decrease in body fat percentage. In the women cohort (Table II), after the 4-wk strength training program, the HMB-supplemented group had a trend toward a greater increase in upper body strength compared to the placebosupplemented group (placebo 3.2 kg and HMB 5.1 kg; P ⫽ 0.065). There were no differences in body composition measurements between the two groups after training.

Combined Analysis With no significant effect of training status nor gender on the effect of supplementation for relative changes in bench press, body composition, and plasma CK the results from the men and women cohorts were combined and an analysis of the pooled data are

TABLE III. EFFECT OF 4 WK OF HMB SUPPLEMENTATION COMBINED WITH RESISTANCE TRAINING IN MEN AND WOMEN COMBINED* Placebo (n ⫽ 36)

Strength Bench press (kg) Body composition Body weight (kg) %Body fat SF UWW Fat-free weight SF (kg) UWW (kg) Blood parameters Creatine phosphokinase (U/L)

HMB (n ⫽ 39)

Before

After

⌬

Before

After

⌬

44.7 ⫾ 5.6

49.9 ⫾ 5.9†

5.2 ⫾ 0.6

44.7 ⫾ 5.2

52.3 ⫾ 5.6†

7.5 ⫾ 0.6‡

74.3 ⫾ 2.6

73.8 ⫾ 2.5

0.6 ⫾ 0.2

72.5 ⫾ 2.2

73.3 ⫾ 2.4

0.8 ⫾ 0.2

18.3 ⫾ 1.3 20.4 ⫾ 1.1

17.2 ⫾ 1.2 19.9 ⫾ 1.1

⫺0.8 ⫾ 0.2 ⫺0.5 ⫾ 0.2

16.2 ⫾ 1.2 20.6 ⫾ 1.0

15.1 ⫾ 1.2 19.5 ⫾ 1.0

⫺1.2 ⫾ 0.2 ⫺1.1 ⫾ 0.2§

60.1 ⫾ 2.0 58.8 ⫾ 2.0

60.7 ⫾ 2.1 59.7 ⫾ 2.1

0.9 ⫾ 0.2 0.9 ⫾ 0.2

59.9 ⫾ 1.8 57.5 ⫾ 1.8

61.1 ⫾ 1.8 58.9 ⫾ 1.9

1.2 ⫾ 0.2 1.4 ⫾ 0.2§

155.0 ⫾ 20.8

195.2 ⫾ 23.5

40.2 ⫾ 22.2

174.4 ⫾ 26.8

173.5 ⫾ 17.0

3.3 ⫾ 22.2

* Values are means ⫾ SE. † P ⱕ 0.05, significantly different from before values. ‡ P ⱕ 0.05, significantly different from placebo group. § P ⫽ 0.08, different from placebo group. HMB, ␤-hydroxy-␤-methylbutyrate; SF, calculated from the sum of seven skinfolds; UWW, calculated from underwater weighing.

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Panton et al.

shown in Table III. When the data from both studies were pooled, there were significant increases in upper body strength for the HMB-supplemented group (P ⱕ 0.05) when compared with the placebo-supplemented group. Upper body strength increases over the 4 wk were 7.5 ⫾ 0.6 kg for the combined HMB-supplemented group and 5.2 ⫾ 0.6 kg for the combined placebo-supplemented group. Lower body strength measurements were not combined for analysis because different tests were used to assess lower body strength in the men and women. No changes in overall body weight were observed in the pooled data; however, there were trends for increases in fat-free weight (P ⫽ 0.08) and decreases in percent body fat (P ⫽ 0.08) in the HMB-supplemented group compared with the placebo-supplemented group. The placebosupplemented group increased fat-free weight by 0.9 ⫾ 0.2 kg and decreased percent body fat by 0.5% ⫾ 0.2% while the HMBsupplemented group increased fat-free weight by 1.4 ⫾ 0.2 kg and decreased percent body fat by 1.1% ⫾ 0.2%.

DISCUSSION This is the first study to evaluate the effects of short-term (4 wk) supplementation of HMB in resistance training women and the effects of training status (trained or untrained) in both men and women on muscle strength and body composition. The major findings of this 4-wk study were that 1) the response from HMB does not appear to be dependent on previous training levels; and 2) both, women and men appear to respond to HMB supplementation. Our results agree well with a previous study by Nissen et al.11 in which dietary supplementation with HMB showed an increase in muscular strength and fat-free weight in college-aged men undergoing a resistance training program. However, our results disagree with a more recent study involving experienced resistance trained athletes in which no improvements in muscular strength or fat-free weight occurred following 28 d of HMB supplementation.14 However, it is important to note that in the study by Kreider et al.14 that resistance training was not monitored on a day by day training basis as in the current study and the study by Nissen et al.11 Subjects trained on their own and simply kept training logs during the supplemental period. It is possible that either the training loads were inadequate for physiologic adaptations to occur or the training logs did not truly represent each subject’s actual training volume/intensity. It is generally accepted that in most survey based studies, recorded data often appear in a way that the subject believes represents what the data collection team anticipates should be occurring (i.e., recording low-fat eating on diet related surveys or training intensely during a supplemental period). Thus, in the study by Kreider et al.,14 it is possible that an inadequate training stimulus occurred in some subjects while others trained intensely enough to elicit adaptations. As a result, it cannot be excluded that the lack of changes in strength and fat-free weight in this study may have been due to an inadequate statistical power. This could be due to the small number of subjects per treatment group that could not over come the threat to external validity. For example, in the Kreider et al.14 study neither the HMBsupplemented or placebo-supplemented group showed any significant improvements in strength over the 4 wk of training. Perhaps if the training stimulus was greater there may have been differences in strength gains and fat-free weight between the HMBsupplemented and placebo-supplemented groups. This is further verified by the fact that there were no changes in plasma CK levels for any of the groups in the study by Kreider et al.14 This is in sharp contrast to the current study in which the placebo treatment for all subjects, men and women, showed increases in plasma CK levels. These results indicate that a new level of training stimulus occurred as a result of our training protocols. Therefore, one would anticipate that physiologic adaptations to resistance training with or without HMB supplementation would have occurred as we observed.

Nutrition Volume 16, Number 9, 2000 The exact mechanism of the effect of HMB on muscle metabolism is not currently known. However, it has been suggested that there is a decrease in muscle membrane damage that is evident by decreases in urine 3-MH, CK, and LDH in humans11,13 and animals12 consuming HMB. Lower levels of CK and LDH suggest that less inflammation and/or damage to the muscle membrane may have occurred as a result of an intense exercise program. Men and women in the present study tended to have lower CK levels than the placebo group indicating that, similar to the original study,11 less cell membrane damage may have occurred. It has also been postulated that supplementation with HMB can provide a source of HMG-CoA for cholesterol synthesis. Cholesterol is an important constituent of cell membranes and thus supplementation of HMB may lead to increased membrane integrity by supplying a source for increased synthesis of intracellular cholesterol during a time of need.5 There were no significant differences in strength gains nor body composition changes when the effects of HMB supplementation were compared in currently resistance training men and women and those that were not currently training (untrained for at least 6 mo). For example, HMB-supplemented trained men had a 10.4 kg increase in bench press strength while HMB-supplemented untrained men had a 9.2 kg increase (P ⫽ 0.25). These data suggest that training status did not have an effect on the response of HMB supplementation during the first month of a resistance training program. With no differential effects between trained and untrained subjects, the data from the two groups were pooled for analysis. The strength gains for both the HMB-supplemented and placebo-supplemented groups are fairly large for a 4-wk period. These strength gains are likely due to the high-intensity resistance training program (90% of 1-RM) that the subjects underwent. There may have been some increases in strength due to the learning effect, however, most of the subjects had participated in some form of strength training in the past few years. These increases in strength were similar to the increases in strength seen with football players after 3 wk of training.11 In conclusion, data from these studies suggest that HMB supplementation may be effective in maximizing the beneficial changes associated with exercise during the early adaptation period of resistance training, in some muscle groups, in both men and women, regardless of training status. Further research will need to be conducted to determine if increases in strength can be made in different muscle groups throughout the body and whether strength and improvements in body composition will be continued throughout a training program greater than 4 wk. Further studies may also be conducted to determine if increases in strength produce increases in performance such as swimming, cycling, and running.

SUMMARY These cohort studies showed that regardless of gender or training status, HMB may increase upper body strength and minimize muscle damage when combined with a 4-wk resistance training program.

ACKNOWLEDGMENTS The authors wish to thank Leigh Ann Cannon (ISU) and Janet Gammon (ISU) for their contribution. Results of the present study do not constitute endorsement of the product by the authors.

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Nutrition Volume 16, Number 9, 2000 2. Frexes-Steed M, Lacy DB, Collins J, Abumrad NN. Role of leucine and other amino acids in regulating protein metabolism in vivo. Am J Physiol (Endocrinology Metabolism) 1992;262:E925 3. Sapir DG, Walser M, Moyer ED, Rosenhein NB, Stewart PM, et al. Effects of alpha-ketoisocaproate and of leucine on nitrogen metabolism in postoperative patients. Lancet 1983;1:1010 4. Sax HC, Talamini MA, Fischer JE. Clinical use of branched-chain amino acids in liver disease, sepsis, trauma, and burns. Arch Surg 1986;121:358 5. Nissen SL, Abumrad NN. Nutritional role of the leucine metabolite ␤-hydroxy␤-methylbutyrate (HMB). J Nutr Biochem 1997;8:300 6. Sabourin PJ, Bieber LL. Formation of ␤-hydroxy-isovalerate from alphaketoisocaproate by a soluble preparation from rat liver. Devel Biochem 1981;18: 149 7. Sabourin PJ, Bieber LL. Subcellular distribution and partial characterization of an alpa-ketoisocaproate oxidase of rat liver: formation of ␤-hydroxyisovaleric acid. Arch Biochem Biophys 1981;206:132 8. Sabourin PJ, Bieber LL. Purification and characterization of an alphaketoisocaproate oxygenase of rat liver. J Biol Chem 1982;257:7460 9. Sabourin PJ, Bieber LL. The mechanism of alpha-ketoisocaproate oxygenase. Formation of ␤-hydroxyisovalerate from alpha-ketoisocaproate. J Biol Chem 1982;257:7468

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