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*
Iowa State University, Ames, IA,
Wichita State University, Wichita, KS,
Ball State University, Muncie, IN and
**
Metabolic Technologies Incorporated, Iowa State University Research Park, Ames, IA
1To whom correspondence and reprint requests should be addressed.
 |
ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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KEY WORDS: • leucine • cholesterol • blood pressure • toxicity • humans
|
INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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,
Nissen et al. 1996a
, 1996b
and 1997
, Nissen and Abumrad 1997
). The major benefit of HMB appears to be a
reduction in muscle damage and/or reduced protein catabolism, which
results in improved gains in muscle size and strength when combined
with exercise (Nissen et al. 1996b
). Although several
animal studies have shown that HMB consumption does not cause adverse
effects (Nissen et al. 1994a
and 1994b
, Peterson et al. 1999a
and 1999b
, Van Koevering et al. 1993
and 1994
), until now there has not been a comprehensive analysis of
safety data collected on HMB-fed humans.
HMB is a metabolite of the amino acid leucine and is produced
endogenously in both animals and humans. The first step in the
metabolism of leucine is transamination to 
-ketoisocaproate (KIC).
HMB is then produced from KIC by the cytosolic enzyme
KIC-dioxygenase (Sabourin and Bieber 1983
) and, at
least in pigs, is produced exclusively from leucine (Van Koevering and Nissen 1992
). Plasma concentrations of HMB
normally range from 1 to 4 µmol/L, but can increase 5- to
10-fold after leucine is fed (Nissen and Abumrad 1997
).
The cytosolic dioxygenase enzyme has been characterized extensively and
differs from the mitochondrial KIC-dehydrogenase enzyme in that the
dioxygenase enzyme is a cytosolic enzyme, whereas the dehydrogenase
enzyme is found exclusively in the mitochondrion (Sabourin and Bieber 1981
and 1983
). Recently, the KIC-dioxygenase enzyme
was found to be identical to the tyrosine dioxygenase enzyme
(Janskiewiez et al. 1996
). It has been calculated that,
under normal conditions, ~5% of leucine oxidation proceeds via this
pathway (Van Koevering and Nissen 1992
).
Numerous biochemical studies have shown that HMB is a precursor of
cholesterol (Bloch 1944
, Rabinowitz 1955
,
Rudney 1957
, Zabin and Bloch 1951
). HMB
in the cytosol of liver and muscle is first converted to cytosolic
ß-hydroxy-ß-methylglutarate-Co-A (HMG-CoA), which can then be used
for cholesterol synthesis (Rudney 1957
). Thus HMB can
serve as a precursor for cellular cholesterol synthesis especially in
tissues such as muscle that rely on de novo synthesis of cholesterol.
The working theory for HMB action is that stressed or damaged muscle
cells may not be able to make sufficient HMG-CoA to support
adequate cholesterol synthesis for cell functions, including proper
functioning of cell membranes. Therefore, supplemental HMB could be a
convenient source of HMG-CoA in these cells to maintain adequate
cholesterol synthesis and, in turn, plasma membrane function. This
contention is supported by the observation that supplementation of HMB
can markedly decrease muscle damage as evidenced by leaking of creatine
phosphokinase (CPK) out of muscle cells (Cheng et al. 1998
, Nissen et al. 1996b
, Nissen and Abumrad 1997
). Also supporting this concept are several studies
showing that inhibition of cholesterol synthesis in muscle with drugs
can result in muscle damage (Pierno et al. 1995
), poor
function (Bastiaanse et al. 1997
, Yeagle 1991
) and even muscle cell death (Mutoh et al. 1999
).
Supplemental HMB is usually taken by humans at a dosage of ~3 g/d.
Therefore, the objective of this study is to report the
safety-related data collected on HMB given in a dose of 3 g/d over
a series of nine experiments. These experiments encompassed the young,
the old, men and women, exercising and nonexercising subjects, and were
from 3 to 8 wk in duration. In each of these studies, three batteries
of tests were used to determine safety. First, comprehensive blood work
was completed at regular intervals during each study. Second, the
Circumplex test of emotion (Russell 1980
) was given
periodically during each study; and third, an adverse events
questionnaire was filled out at intervals during each study. Together,
these measurements should indicate the safety and tolerance of HMB in
the general population.
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Each study was approved by a local Institutional Review Board and signed informed consents were obtained from the subjects before participation in the respective study. Each study was conducted as a double-blind, placebo-controlled study. Exclusion criteria were ongoing chronic disease processes, smoking, illegal drug use, pregnancy and certain age and sex requirements, depending on the study.
Blood sampling.
Blood samples were collected from a superficial forearm vein into
Vacutainers (Becton Dickinson, Vacutainer Systems, Rutherford, NJ)
after an overnight fast by the subjects. Both serum and whole blood
were collected. A plasma sample was also collected, frozen and stored
at -20°C until analyzed for HMB concentration by gas
chromatography-mass spectrometry (Nissen et al. 1990b
). The serum samples were processed the day of collection
and analyzed for CPK by kinetic analysis (Integra 700 Analyzer, Roche
Diagnostics, Indianapolis, IN). The following were determined using an
automated blood chemistry analyzer (Olympus 5231, Olympus, Melville,
NY): sodium, potassium and chloride electrolytes (ion selective
electrode); lactate dehydrogenase, plasma creatinine, alkaline
phosphatase, 
-glutamyl transpeptidase (GGT), aspartate
aminotransferase (SGOT) and alanine aminotransferase (SGPT) by kinetic
analysis; calcium, phosphorous, iron, bilirubin, protein and albumin by
colorimetric methods; glucose, uric acid, blood urea nitrogen, total
cholesterol, HDL cholesterol and triglycerides by enzymatic methods.
LDL and VLDL were then calculated using the Friedewald formula
(Friedewald et al. 1972
) (Labcorp, St. Louis, MO). The
whole-blood samples were also processed on the day of collection by
Labcorp, and analyzed for hemoglobin, hematocrit, mean corpuscular
volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular
hemoglobin concentration (MCHC), platelets, and red and white blood
cell numbers using an automated cell counter (Coulter STKS, Coulter,
Fullerton, CA).
Emotional profile.
Weekly emotional profiles were measured by administration of the
Circumplex test of emotion (Russell 1980
). This test
consisted of 48 words that describe various emotions. Each word was
scored by the subject from 1 to 5 with the degree of feeling that the
word evoked: 1-very slightly or not at all; 2-a little; 3-moderately;
4-quite a bit; and 5-extremely. Groups of 6 words that characterized an
emotional category were then summed into the following categories:
1) High Activation (aroused, astonished, stimulated,
surprised, active and intense); 2) Activated Pleasant
Affect (enthusiastic, elated, excited, euphoric, lively and peppy);
3) Unactivated Pleasant Affect (relaxed, content, at
rest, calm, serene and at ease); 4) Pleasant Affect
(happy, delighted, glad, cheerful, warmhearted and pleased);
5) Low Activation (quiet, tranquil, still, inactive,
idle and passive); 6) Unactivated Unpleasant Affect
(dull, tranquil, still, inactive, idle and passive); 7)
Unpleasant (unhappy, miserable, sad, grouchy, gloomy and blue);
8) Activated Unpleasant Affect (distressed, annoyed,
fearful, nervous, jittery and anxious). A range of values between 6 and
30 were possible for each category.
Adverse events.
Weekly adverse events were measured by filling out a questionnaire. This questionnaire examined common complaints related to major organ systems. Subjects were asked if they experienced any of these symptoms over the last 3 d. In most studies, the questionnaires were given weekly.
General study protocols.
Table 1
summarizes the basic subject characteristics and protocols used during
the individual studies. Studies are referred to by study numbers one
through nine. All of the studies were conducted as randomized
double-blind, placebo-controlled studies in which neither the
researchers nor the subjects knew which treatment contained the HMB.
The subjects were informed as to the purpose of each study in the
informed consent statement. In all but Study 3, the purpose of the
study was to assess the effects of HMB on exercising subjects. In Study
3, the purpose was only to collect safety data and no exercise was
included. In each study, HMB was administered as the calcium salt of
HMB,
Ca(C5H10O3)2
· H2O. This compound contained ~13% calcium;
when consumed at 3 g/d, this amounted to ~400 mg/d of additional
calcium in the HMB-supplemented subjects. In Studies 1–3, HMB was
administered as the calcium salt mixed in either orange juice or a
protein shake. In Studies 4–9, capsules containing the HMB or placebo
(rice flour) were used. Potassium phosphate
(KH2PO4) was added to the
HMB supplement capsules to partially maintain the Ca/P ratio. This
amounted to ~135 mg of P and ~170 mg of K per day. The RDA for Ca,
P and K are 1000, 1000 and 3500 mg/d, respectively (NRC 1989
). The
placebo treatments were not balanced for any of these minerals.
|
). In
addition, written questionnaires were given at the end of Studies 1 and
2, asking the subjects to report their compliance in taking the
treatments. In Study 3, subjects were given weekly questionnaires and
asked to report any noncompliance to the treatments; in Studies 5 and
7, the subjects were asked to record each time a dosage of either the
placebo or HMB treatment was taken. In the other studies, compliance
was assessed by plasma HMB only. Study 1.
This study was conducted at Iowa State University. Subjects were assigned randomly to either a placebo (0 g HMB/d) or HMB (3.0 g HMB/d) treatment. Neither the subjects nor the researchers knew which treatment contained HMB; two equal dosages per day in 0.47 L of orange juice (one 16-oz bottle) were administered. The subjects were instructed to drink one bottle of juice in the morning and another bottle of juice in the evening. The subjects then underwent a supervised, resistance-exercise program 3 times/wk for 3 wk and alternated exercising either the upper or lower body during each exercise session. A blood sample was drawn from fasting subjects on Thursday and Friday of each week. The Circumplex survey and the adverse events questionnaire were given weekly.
Study 2.
This study was conducted at Iowa State University in healthy male athletes who were subjected to stringent exercise schedules over the 7-wk study. Subjects were assigned randomly to either a placebo or HMB treatment. The HMB treatment consisted of 3 servings/d of a protein drink mix, each containing 1 g of HMB for a total of 3 g HMB/d. Similarly, the placebo treatment consisted of 3 servings of an isocaloric carbohydrate drink mix without HMB. Subjects were instructed to drink one serving with each meal and neither the subjects nor the researchers knew which drink contained the HMB supplement. Subjects exercised a total of 6 d/wk with resistance exercise on 5 d/wk. Blood samples were obtained from fasting subjects on d 0, 17, 31 and 49 of the study. The Circumplex survey and the adverse events questionnaire were given on the blood sampling day.
Study 3.
This 4-wk study was conducted at Iowa State University and was designed to document the safety of HMB when consumed by women. The subjects enrolled into the study were instructed to maintain any exercise program they were currently involved in and not to start any new exercise programs during the study. Subjects were assigned randomly to receive either a placebo (0 g HMB/d) or HMB (3 g HMB/d) treatment. The placebo and HMB were administered twice daily in equal dosages mixed in ~180 mL of orange juice. Neither the subjects nor the researchers knew which drink contained HMB. The subjects were instructed to consume one dosage of the juice in the morning and one dosage in the evening. Blood samples were taken after an overnight fast on d 0, 5, 10, 25 and 28. Subjects also filled out Circumplex and adverse event questionnaires on the blood sampling day.
Study 4.
In this study, conducted at Iowa State University, the effect of prior training on the effects of HMB supplementation was examined in young males. Study participants were classified as trained if they currently participated in a regular resistance exercise program at least 3 times/wk. Subjects were classified as untrained if they had not participated in any regular weight lifting for at least 6 mo before the study. Subjects were assigned randomly to receive either a placebo (0 g HMB/d) or HMB (3 g HMB/d) treatment administered in capsules. Again, neither the subjects nor the researchers knew which capsules contained HMB. The placebo capsules (0 g HMB/d) contained rice flour, whereas each HMB capsule contained 250 mg of calcium HMB and 50 mg of KH2PO4. The subjects were instructed to take either four placebo or four HMB capsules 3 times/d with meals, which supplied either 0 or 3 g HMB/d. All subjects then underwent a supervised, resistance-training regimen 3 times/wk during the 4-wk study. Blood samples were obtained from fasting subjects at the beginning and again at the end of the study. Circumplex and adverse events questionnaires were given weekly during the study.
Study 5.
This study was conducted at Iowa State University with male and female runners. Subjects were paired according to their best two-mile run time and past running experience and then were assigned randomly to either a placebo (0 g HMB/d) or HMB (3 g HMB/d) treatment administered in capsules as described for Study 4. Neither the subjects nor the researchers knew which capsules contained HMB. Subjects continued to train and were instructed to take four capsules, either placebo or HMB, 3 times/d with their meals. The supplements were taken for 5 wk and all subjects were given a log to record the day and the times they took their supplement. These logs were used to verify compliance in taking the supplement. Blood samples were obtained from fasting subjects at wk 0 and 5 of the study. The Circumplex survey and the adverse events questionnaire were given weekly.
Study 6.
This 4-wk study was conducted at Iowa State University and was similar to Study 4 except that women subjects were tested. As in Study 4, similar criteria were used to classify the subjects as either trained or untrained. Subjects were then randomly administered either a placebo (0 g HMB/d) or HMB (3 g HMB/d). Treatment was as described for Study 4 and neither the subjects nor the researchers knew which capsules contained HMB. Fasting blood samples were obtained at wk 0, 2 and 4 of the study. The Circumplex survey and the adverse events questionnaires were given on d 0, 7, 15, 20, 23 and 28 of the study.
Study 7.
This study was conducted at Iowa State University in elderly subjects who were assigned randomly to either a placebo (0 g HMB/d) or HMB (3 g HMB/d) treatment for 8 wk. Neither subjects nor researchers knew which capsules contained HMB; treatments were administered as described for Study 4. All subjects underwent strength training 3 times/wk for the duration of the study. Blood samples were obtained from fasting subjects at wk 0, 4 and 8 of the study. The Circumplex and the adverse events questionnaires were again given weekly.
Study 8.
This study was similar to Study 7 but was conducted at Wichita State University (Wichita, KS). Elderly subjects were assigned randomly to either a placebo (0 g HMB/d) or HMB (3 g HMB/d) treatment for 8 wk. Neither subjects now researchers knew which capsules contained HMB; treatments were administered as described for Study 4. Subjects participating in this study had no contraindications to exercise and had their physicians approval to participate. Before the initiation of the study, subjects had no experience with resistance training. Subjects underwent strength training 2 times/wk on nonconsecutive days. On the three other days during the week, subjects reported to an indoor track for walking and stretching, which consisted of 10 min of warm-up stretching, 40 min of self-paced walking and then another 10 min of stretching for a cool-down period. Blood samples were obtained from fasting subjects at wk 0, 2, 4, 6 and 8 of the study. The Circumplex and the adverse events questionnaires were given weekly.
Study 9.
This 8-wk study was conducted at Ball State University (Muncie, IN) with untrained college-aged males. Subjects were matched on the basis of body weight and then assigned randomly to receive either a placebo [0 mg HMB/(kg body weight · d)] or HMB [38 mg HMB/(kg body weight · d)] treatment. These dosages were chosen because they are equivalent to either 0 or 3 g HMB/d in a person of average body weight. Subjects and researchers did not know which treatment contained HMB. Subjects underwent a resistance training program 3 times/wk during the study. Blood samples were taken at wk 0, 1, 2, 4 and 8 after an overnight fast. The Circumplex and the adverse events questionnaires were again given weekly.
Statistical analysis.
For blood, hematology and Circumplex data, for which multiple samples
or questionnaires were taken over the course of the study, the net
change in variables was estimated by regressing the measured values vs.
week of study and calculating the net change over the study for each
subject. Because day-to-day variations in measurement occur, this
linear estimate of change better reflects the overall change due to
treatment. For the Circumplex data, the differences (in slopes)
were analyzed by using a Student’s t test. For the
blood and hematology data, the changes were analyzed using ANOVA (SAS,
Cary, NC) with the main effects of experiment, treatment and experiment
x treatment interaction in the model. The adverse events data
were analyzed as categorical data (Agresti 1990
). For
statistical analysis, the subjects were categorized by before (yes or
no) and after treatment response (any yes = yes, all no = no)
and statistical significance between treatments determined using the
Cochran-Mantel-Haenszel test (Agresti 1990
). In the case
of Study 8, "before" treatment questionnaires were not given;
therefore, the subjects were divided into groups of either a "Yes"
or "No" answer during the treatment period and statistical
significance was determined by Fisher’s Exact test (Agresti 1990
). Statistical significance was determined for P 
0.05. A trend was determined to be 0.05 P 0.10 and
no statistical significance was determined for P
> 0.10.
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Supplementation compliance was checked by measuring plasma levels of
HMB after supplementation. In addition, in Studies 1, 2, 3, 5 and 7, a
self-reported record of compliance was also obtained from the
subjects. Basal plasma levels of HMB were between 1 and 4
µmol/L and rose to between 17 and 25 µmol/L
after an overnight fast in subjects consuming 3 g CaHMB/d
(Nissen and Abumrad 1997
). Although this is indicative
of compliance only immediately before the sampling time, this method
does give some indication of overall compliance during the studies. On
the basis of both the written responses from the subjects and plasma
HMB levels measures, no subjects were dropped from the analyses for
noncompliance.
Circumplex emotional profile.
The Circumplex Model of Affect questionnaire was administered in all of
the studies, and the summary of the results is shown in Table 2
. The only significant change measured indicated a decrease
(P < 0.05) in the category "Unactivated Unpleasant
Affect," which is described by the words dull, tired, drowsy,
sluggish, bored and droopy.
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None of the questions asked had responses that led to a significant
treatment effect (Table 3
). Analysis of the data showed no significant differences in either the
pretreatment or treatment period categories. A trend was indicated for
a decrease in the incidence of loss of appetite (P < 0.07); however, this difference was < 1.5%. A trend was also
indicated for a difference in stiff joints reported (P
< 0.08). However, because the statistical model also took into
consideration starting values, the indication was that a difference in
incidence in the starting populations existed rather than a treatment
effect.
|
Blood lipid profiles of all subjects and those subjects with total
cholesterol levels either >5.17 or <5.17 mmol/L (200 mg/dL) are shown
in Table 4
. No significant differences existed in any of the starting values
except for triglycerides in the subjects whose total cholesterol was
> 5.17 mmol/L. Significant decreases of 3.7% (P
< 0.03) for total cholesterol and 5.7% (P < 0.05) for LDL cholesterol were observed in the subjects consuming
3 g HMB/d. Because of the health risk of high levels of
cholesterol, the subjects were subclassified into two groups, those
subjects having a total cholesterol level < 5.17 mmol/L (200
mg/dL) and those subjects having a total cholesterol level > 5.17
mmol/L. The average starting values for these groups were 4.27 mmol/L
in the low cholesterol group and 5.72 mmol/L in the high cholesterol
group. Although significant decreases in total cholesterol were
observed in both groups, the difference was only 2.5% (P
< 0.04) in the low cholesterol group, whereas in the high
cholesterol group, there was a 5.8% decrease (P < 0.03) or -0.334 mmol/L (12.9 mg/dL). The decrease in total cholesterol
can be attributed to a decrease in LDL cholesterol, which declined by
4.2% (P < 0.09) and 7.3% (P < 0.01)
in the low and high cholesterol groups, respectively.
|
Resting blood pressures were measured in seven of the nine studies and
the combined results are also shown in Table 4
. In the studies,
supplementation with HMB resulted in a significant decrease in systolic
blood pressure of 4.4 mm Hg (P < 0.05 placebo vs.
HMB). When subjects were stratified into high and low risk, the
subjects with a systolic pressure of > 130 mm Hg had an even
greater decrease in systolic pressure, but the net difference between
the HMB and placebo groups remained at 4.9 mm Hg. Diastolic blood
pressures were not affected by HMB supplementation.
Blood indicators of liver function are summarized in Table 5
. There were no significant differences between the placebo and HMB
groups for any of the measured indicators [bilirubin, alkaline
phosphatase, lactate dehydrogenase (LDH), SGOT, SGPT, GGT, and iron].
There were significant experiment by treatment interactions for LDH,
GGT, and iron. In the case of LDH, this effect was likely due to the
variation in response to the exercise component in the different
studies because plasma LDH can also be derived from damaged muscle.
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. No significant differences between the placebo and HMB groups were
seen for CPK, glucose, uric acid, blood urea nitrogen (BUN),
creatinine, BUN/creatinine, sodium, chloride, phosphorous, protein,
albumin and globulin. A small but significant decrease (1.9%,
P < 0.003) in potassium, the primary intracellular
electrolyte, was seen. Additionally, there was a 5% increase
(P < 0.03) in the albumin/globulin ratio in the HMB
group. A significant experiment x treatment effect was also seen
for the albumin/globulin ratio because a response did not occur in all
experiments. Similarly, significant experiment x treatment
effects were observed for BUN, BUN/creatinine, protein and globulin,
which resulted from the fact that the responses between the placebo and
treatment groups differed from experiment to experiment with no
particular pattern.
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). The initial values and final values for hematocrit, however, were not
significantly different between the placebo and HMB groups. Final
values for hematocrit were 0.43 for both placebo and HMB groups. There
were no significant experiment x treatment interactions for any
of the hematology variables measured.
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|
DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Physiologic and biochemical measurements indicated that HMB affects primarily cholesterol metabolism. Across all experiments, decreases in total cholesterol and LDL cholesterol of 3.7 and 5.7%, respectively, were seen. If a subset of subjects whose average starting cholesterol was > 5.17 mmol/L (200 mg/dL) is examined, the decrease was even greater, and HMB resulted in a 5.8 and 7.3% decrease in total and LDL cholesterol, respectively. This amounted to a drop of ~13 points (mg/dL) in total and a drop of 11 points (mg/dL) in LDL cholesterol. In contrast, subjects with cholesterol values < 5.17 mmol/L (200 mg/dL) did not have a significant decrease in LDL cholesterol when HMB was given. This suggests that HMB is more effective in lowering cholesterol when blood levels are elevated above the current standard associated with increased risk of heart disease.
There was also a difference in HDL cholesterol response with HMB
supplementation compared with placebo although this difference appeared
to disappear when total cholesterol was elevated. The increase in HDL
cholesterol in the placebo group is likely related to the
exercise-induced rise in HDL cholesterol seen in previous studies
(Halle et al. 1999
).
A second cardiovascular risk factor affected by HMB was blood pressure.
Subjects given HMB had a decrease of ~3% in systolic blood pressure.
Diastolic blood pressure decreased similarly to the decrease seen in
the placebo-supplemented group. This change in blood pressure may
be attributed to the additional calcium intake of ~400 mg/d with the
Ca-HMB supplement. There is a variety of experimental evidence
showing that calcium supplementation can affect blood pressure
(Birkett 1998
, Kok et al. 1986
,
McCarron and Reusser 1999
, Sempos et al. 1986
). Meta-analysis of the data in these experiments
indicates that calcium lowers systolic blood pressure at the rate of
~0.39 mm Hg/(100 mg Ca·d). On the basis of this equation, the 400
mg of Ca given in the current study should have lowered systolic blood
pressure ~1.56 mm Hg. The measured effect in subjects with systolic
blood pressure >130 was much greater, i.e., 9.3 mm Hg total or 4.9 mm
Hg net, suggesting that either the CaHMB is a more biologically
available source of calcium (Sousa et al. 1996
) or that
HMB is having a more direct effect on cardiovascular function.
Blood potassium decreased < 2% in the HMB-supplemented
subjects. The reason for this small decrease is not known but is likely
due to the slightly different mineral intakes between the placebo- and
the HMB-supplemented groups. The placebo supplement was not
balanced for the calcium, phosphorus or potassium, which were contained
in the HMB treatments. Thus, the daily dose of ~400 mg of calcium,
~135 mg of phosphorus and ~170 mg of potassium could have resulted
in minor changes in ionic balance (although this represents only ~40,
14 and 5% of the estimated daily intake of Ca, P and K, respectively)
(NRC 1989
).
The only other significant difference in blood chemistry was a significantly greater albumin/globulin ratio in HMB-supplemented subjects. This was primarily the result of a relative increase in albumin and a relative decrease in globulin.
The only significant difference in blood hematology was an ~0.5%
lower hematocrit in the HMB-supplemented group. This difference was
also reflected nonsignificantly in ~1% lower red cell numbers and
hemoglobin. An explanation for these differences is not apparent, but
in all cases, the ending values were not significantly different
between the treatments. Other experiments in animals indicate that HMB
can increase hematocrit, decrease granulocytes and increase lymphocytes
(Sandberg et al. 1997
, Nissen et al. 1994c
, Siwicki et al. 1998b
).
Previous research has shown that feeding HMB to a wide variety of
animals has not had any adverse effects on health or growth
(Nissen et al. 1994a
and 1994b
, Peterson et al. 1999a
and 1999b
, Van Koevering et al. 1993
and 1994
). In fact, the most consistent effect of HMB in animals
has been a positive effect on health. In sheep, pigs, cattle, chickens
and fish, there have been positive effects noted on both immune
function and improved resistance to infectious agents (Nissen et al. 1990a
, 1994b
and 1994c
, Ostaszewski et al. 1998
, Peterson et al. 1999a
and 1999b
,
Siwicki et al. 1998a
and 1998b
).
The Circumplex Model of emotion has been used in humans to assess emotional balance. In this model, emotion is described as a continuum (circle) of positive (pleasant) and negative (unpleasant) emotions that are either activated or unactivated. By scoring how the subject feels about a word (an emotional feeling), a profile of emotional balance is estimated. In the current study, the only significant change in emotion was a decrease in "Unactivated Unpleasant Affect" when HMB was supplemented. This emotional category is described by the words dull, tired, drowsy, sluggish, bored and droopy. Subjects taking HMB appeared to have less of this negative emotion. This study did not attempt to assess the cause of this effect, but most of the studies did involve some sort of exercise component; it may be that HMB enhanced the effects of this exercise, which could translate to less of an Unactivated Unpleasant Affect.
Incidences of all adverse symptoms were quite low except for coughing and nasal congestion, which indicates many subjects had upper respiratory infections during the study. Although the responses to questions did not differ between the placebo and the HMB groups, there were some trends for differences. The HMB-supplemented subjects tended to have less diarrhea and less loss of appetite. There was also a trend for a greater number of stiff joints reported in the HMB-supplemented group. However, the HMB-supplemented group started out with a much lower incidence of stiff joints and the ending value was actually numerically lower than the placebo-supplemented group, suggesting this was simply a chance occurrence.
In summary, the only definitive effects of HMB were positive in nature, especially relating to lowering plasma cholesterol and blood pressure. These data suggest that the popular use of supplemental HMB at 3 g/d as an ergogenic aid for exercise is well tolerated and safe in humans.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
-glutamyl transpeptidase; HMB, ß-hydroxy-ß-methylbutyrate; HMG-Co-A, ß-hydroxy-ß-methylglutarate-Co-A; KIC, -ketoisocaproate; LDH, lactate dehydrogenase; MCH, mean corpuscular hemoglobin; MCHC mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; SGOT, aspartate aminotransferase; SGPT, alanine aminotransferase. 
Manuscript received January 14, 2000. Initial review completed February 15, 2000. Revision accepted April 3, 2000.
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|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
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