Molecular and Cellular Biochemistry 237: 129136, 2002.

2002 Kluwer Academic Publishers. Printed in the Netherlands.

129

Antihypertensive and metabolic effects of whole

Maitake mushroom powder and its fractions in
two rat strains

Nadeem A. Talpur,1 Bobby W. Echard,1 Arthur Yin Fan,1

Omeed Jaffari,1 Debasis Bagchi2 and Harry G. Preuss1
1
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC;
2
Department of Pharmacy Sciences, Creighton University, Omaha, NE, USA

Received 17 December 2001; accepted 21 March 2002

Abstract
Maitake mushroom has been reported to favorably influence hypertension and diabetes mellitus. The purpose of this study
was to compare the effects of whole Maitake mushroom powder and two extracts designated as ether soluble (ES) and water
soluble (WS) on Zucker fatty rats (ZFR), a model of insulin resistance, and on spontaneously hypertensive rats (SHR), a
model of genetic hypertension. In the initial study, we followed four groups of eight ZFR and SHR receiving special diets: a
baseline diet (BD), BD + whole Maitake mushroom powder (20% w/w), BD + fraction ES (0.10% w/w), and BD + WS
(0.22% w/w). Different effects of these dietary regimens on the 2 rat strains were found. At 35 days, only consumption of the
ES diet signifi- cantly decreased systolic BP (SBP) in SHR (average 197 vs. 176 mm Hg, p < 0.001), while in ZFR only the
groups consuming the whole Maitake and WS diets showed significantly decreased SBP (138 vs. 120125 mm Hg, p <
0.001). A challenge test with losartan (an angiotensin II receptor blocker) indicates that angiotensin II does not play a major
role in SBP regulation of ZFR, but does in SHR where consumption of ES relative to other groups significantly lowered
activity of this system. In SHR, glucose, cholesterol, circulating insulin and HbA1C were virtually similar among all dietary
groups; but whole Maitake (22%), ES (120%) and WS (80%) diets were associated with decreased triglycerides, and the
ES diet with lowered serum creatinine (29%). In ZFR, circulating insulin and HbA1C were significantly decreased in the
whole Maitake powder and ES groups, and tended to be lower in the WS group compared to control. In the ensuing studies,
we gavaged ZFR once daily with water (control), 44 mg fraction WS, or 44 mg fraction WS plus 100 g niacin-bound
chromium (NBC). Oral gavage of WS clearly lowered SBP and circulating glucose concentrations, more so with the addition
of chromium. We conclude that the examined forms of Maitake mushroom have antihypertensive and antidiabetic potential
which differ among rat strains. The ES fraction may decrease SBP in SHR via alteration in the renin-angiotensin system.
(Mol Cell Biochem 237: 129136, 2002)

Key words: Maitake mushroom powder and its ether and water soluble extracts, niacin-bound chromium, Zucker fatty rats,
spontaneously hypertensive rats, glucose-insulin system, hypertension

Introduction Since these chronic perturbations are many times more

Caused or potentiated by the modern lifestyle, various age-
related metabolic perturbations such as disturbances in glu-
cose/insulin metabolism have become more common [1, 2].
preva- lent in industrialized, Western countries, many
believe nu- tritional factors are involved significantly in the
pathogenesis [3]. This possibility is firmly supported by the
fact that the Western diet is high in simple sugars and
saturated and trans

Address for offprints: H.G. Preuss, Department of Physiology and Biophysics, Georgetown University Medical Center, Med-Dent Building, Room 103SE,
3900 Reservoir Road NW, Washington DC 20007, USA (E-mail: preusshg@georgetown.edu)
130
fatty acids and low in fibers nutritional settings often
asso- ciated with insulin resistance and hyperinsulinemia
[4]. In turn, insulin resistance has been postulated by many
to be a prominent factor in the development of often-
accompanying hypertension and dyslipidemias [5]. Based
on the preceding well-recognized associations, we believe
that the ability to prevent disturbances in glucose/insulin
metabolism through a safe and effective nutritional
program has the potential to ameliorate and delay the onset
of many age-related maladies and increase useful life span
[68]. In this respect, supple- mentation with Maitake
mushroom or its extracts could be important based on
previous findings [9].
The purpose of the present report is to show that whole
Maitake mushroom powder and 2 specific extracts
designated as ether (ES) and water soluble (WS) previously
designated as ES and X in another communication [9] have
beneficial physiological effects on hypertensive [10] and
diabetic rats [11], such as favorably influencing systolic
blood pressure (SBP), ameliorating glucose/insulin
perturbations, and over- coming lipid disorders.
Materials and methods
Animals and treatment
The protocol for the entire investigation was approved by
the Animal Welfare Board at Georgetown University. The
whole Maitake mushroom powder and water soluble
fraction of powdered whole Maitake mushroom designated
as WS were the generous gift of Maitake, Inc., Paramus,
NJ, USA. WS was extracted as described in an earlier
communication where this extract was labeled Fraction X
[12]. Similarly, in our laboratory, we made the ether soluble
fraction (ES) from the provided whole Maitake powder by
the procedure as de- scribed earlier [12]. In the initial
study, the Maitake constitu- ents were added to the rat chow
(dietary study). In the last series of studies, largely set up to
corroborate the initial find- ings, the WS fraction alone and
combined with chromium was mixed with water and
gavaged directly via the oral route on a daily basis (gavage
study).
Dietary study
The baseline diets contained 18% of calories from sucrose
and was low in fiber (see ref. [13] for details). We postulate
that such a diet, designed to simulate the Western diet,
inten- sifies the metabolic risk factors we were assessing.
The con- trol group was given only the baseline diet. In the
second group, 20% w/w of the baseline diet was replaced
with pow- dered Maitake mushroom. The mushroom
powder replaced cellulose, starch, and fats, dietary
constituents which have not
been shown in the proportions removed to significantly af-
fect the parameters under study [14]. To the third and fourth
diets, we added mushroom extracts in amounts estimated to
roughly approximate the same activity as in the 20% w/w
Maitake mushroom diet. The third dietary group received a
diet in which some cellulose was replaced with Fraction ES
(1.0 g/kg body wt). The fourth dietary group received a diet
in which some cellulose was replaced with Fraction WS
(2.2 g/kg body wt).
Zucker fatty rats (ZFR) and genetically spontaneously
hypertensive rats (SHR) were obtained from Charles River
(Wilmington, MA, USA). We examined 4 dietary groups
for each strain of rats group 1: 8 controls, group 2: 8
whole Maitake powder-fed rats, group 3: 8 fraction ES-fed
rats, and group 4: 8 fraction WS-fed rats. This
combination of di- etary groups allowed us to examine
specific effects of whole Maitake powder and two of its
fractions individually, water soluble (WS) and ether soluble
(ES), on rats strains with proclivities toward insulin-
resistant diabetes (ZFR) [10] and spontaneous hypertension
(SHR) [11].
Gavage studies
ZFR were again obtained from Charles River (Wilmington,
MA, USA). In two separate investigations, we examined 3
groups. The rats were gavaged twice daily with either water
(control), or an equal volume of water containing the WS
fraction (200 mg per day) or WS fraction (200 mg per day)
plus niacin-bound chromium (ChromeMate, Interhealth
Nutraceuticals, Benicia, CA, USA. (NBC)) (10 g elemen-
tal chromium per day).
Systolic blood pressure (SBP)
SBP was measured by indirect tail plethysmography using
an instrument from Narco Biosciences, Houston, TX. This
provided an indirect measure of SBP in conscious, slightly
warmed rats [15]. In both sets of studies, rats were allowed
free access to their diet and water until SBP readings were
obtained between 13.00 and 17.00 h. In the second studies,
rats received their final gavage between 10.00 and 11.00 h.
Readings on individual rats were taken 0.51 min apart. To
be accepted, the SBP measurements on a given rat had to be
virtually stable for at least 3 consecutive readings. In the
both studies, 5 weekly readings were recorded on each rat
over a 35 day period.
Body weight
Body weights were estimated at the beginning and end of
the 35 day study by routine scale measurements.
Blood chemistry
Blood was obtained at the end of each experiment (35 days
after starting the special diets) following removal of food
for 4 h. Blood was drawn from the heart of anesthetized
ZFR and SHR prior to termination of studies, and then rats
were sacri- ficed while still asleep by inhalation of a high
level of atmos- pheric CO . Chemical analyses were
2
performed by routine clinical procedures. Immunoreactive
insulin was determined by radioimmunoassay (Diagnostic
Products Corporation, Los Angeles, CA, USA).
Losartan challenge
During the last week of the first study, prior to sacrifice,
rats received losartan orally (an angiotensin II receptor
blocker) to examine SBP-regulating mechanisms more
closely. After performing baseline SBP readings, ZFR and
SHR from con- trol and each treatment group consuming
the special diets were given 3 mg losartan orally via gastric
lavage [16]. Af- ter 4 h, SBP was remeasured; and the
decreased SBP after losartan was used to estimate activity
of the renin-angiotensin system.
Assessment of lipid peroxidation (TBARS)
When the rats were sacrificed in the first study, kidneys
were removed, frozen, and stored at 20C, and eventually
used to estimate lipid peroxidation of the renal cortex via
thiobarbituric acid reacting substances (TBARS) formation
[17]. Malon- dialdehyde (MDA) and similar-type products,
formed from the breakdown of polyunsaturated fatty acids,
serve as an index for determining the extent of lipid
peroxidation. They react with thiobarbituric acid to yield a
product that corre- lates with cell injury and aging [18]. A
1.0 ml aliquots of renal homogenate, precipitated with 0.15
ml of 76% TCA, was added to 0.35 ml of 1.07%
thiobarbituric acid and incubated at 80C for 30 min. A 0.5
ml volume of cold 90% TCA was added, and the
absorbance read at 532 nm. Formation of TBARS
estimated the amount of lipid peroxidation products.
Statistical analyses
Results are presented as mean S.E.M. Statistics were per-
formed by a one way analysis of variance (ANOVA) using
repeated measures. SBP was examined by 2-way analyses
of variance (one factor being diet and the second factor
being time of examination). Where a significant effect of
diet was detected by ANOVA (p < 0.05), the Dunnetts t-
test was used
to establish which differences between means reached sta-
tistical significance (p < 0.05) [19].
Results
Dietary study
Body weight (BW)
Over 35 days, ZFR gained 34 times more BW than SHR
(Table 1). However, the final changes in BW of rats due to
eating 4 different diets were not significantly different
within each of the 2 strains (Table 1).
Systolic blood pressure (SBP)
By 5 days, the SBP of the ZFR consuming the diets
contain- ing whole Maitake powder and WS were
significantly lower than control (approximately 1520 mm
Hg) (Fig. 1). There was no statistically significant
difference in SBP between the control ZFR eating the
baseline diet and the group eating the diet containing
fraction ES at any time. By 5 days, the SBP of SHR was
significantly lower in the group eating the diet containing
fraction ES compared to control (approximately 20 mm Hg)
(Fig. 2). No significant decreases were found in SHR
consuming the diets containing whole Maitake powder and
WS.
Losartan challenge
Results are shown in Fig. 3. ZFR essentially did not show
SBP changes in response to losartan challenge. In contrast,
there was a significant decrease in SBP in all groups of
SHR. In SHR groups eating the baseline and fraction ES
diets, a sig- nificantly lesser change in SBP occurred after
losartan challenge compared to the groups consuming diets
contain- ing whole Maitake powder and WS.
Blood chemistry
Several changes in blood chemistries occurred in SHR over
the course of study (Table 2). Serum creatinine was signifi-
cantly lower in the group consuming the ES fraction. Serum
cholesterol was significantly higher in the ES and WS frac-
tion groups. Triglycerides were lower in the whole Maitake,
ES, and WS fraction groups. In ZFR, the above changes did
Table 1. Difference in body weight gains of ZFR and SHR over duration
of study for 35 days (grams)
Rats Control Maitake Fraction ES Fraction WS
ZFR 197 13.7 211 8.2 182 15.6 186 11.0
SHR 56 2.4 59 7.5 50 3.6 57 7.8
Average S.E.M. values of body weight are shown for a minimum of 4
rats in each group. See Materials and methods section for details.

Fig. 1. SBP of Zucker Fatty Rats (ZFR) groups over a month are denoted
in figure. Average S.E.M. is shown. Solid circles depict control, open
circles depict whole Maitake group, open squares depict ES group, and
open triangles depict WS group. *Significantly different from control.
not take place. However, in further contrast to SHR, circu-
lating insulin concentrations and HbA1C were statistically
significantly lower in the whole Maitake and ES fraction
groups compared to control. The lowering in the WS frac-
tion group compared to control approached significance (p
= 0.068).
Fig. 2. SBP of spontaneously hypertensive rat (SHR) groups over a month
are denoted in figure. Average S.E.M. is shown. Solid circles depict con-
trol, open circles depict whole Maitake mushroom powder group, open
squares depict ES group, and open triangles depict WS group.
*Significantly different from control.
Fig. 3. Changes in SBP (mm Hg) after losartan challenge. See Materials
and methods section for details. Average S.E.M. is shown. *Significantly
different from control. Z Zucker rats; S SHR; C control; M
Maitake mushroom powder; ES ether soluble fraction; WS water
soluble frac- tion.
Assessment of lipid peroxidation (TBARS)
Results are shown in Fig. 4. TBARS in renal tissue were
sig- nificantly higher in the SHR rats ingesting WS
compared to control. Although the average concentration
was higher in the ZFR ingesting WS compared to the group
consuming the baseline diet, statistical significance was not
achieved.
Gavage studies
In this study, we followed 3 parameters BW, SBP, and
fast- ing blood glucose levels. The BW of the control, WS,
and WS
+ NBC groups were not significantly different over the 5
week period. The measurements at the end of 5 weeks are
shown in Table 3. Compared to control, the SBP in the WS
group was statistically significantly decreased. The SBP of
the WS + NBC group was significantly lower than both the
control and WS group (Table 3). Initially all groups started
with essentially the same average SBP (control = 138 mm
Hg
5.0 (S.E.M.), WS = 141 mm Hg 3.7 (S.E.M.), WS +
NBC
= 139 mm Hg 3.1 (S.E.M.)). The differences between the
WS + NBC group and control became apparent by the first
week (146 mm Hg 3.7 (S.E.M.) vs. 127 mm Hg 2.8
(S.E.M.). The significant difference remained at every
weekly reading which followed. It was not until the second
week that the difference in averages between the control
and WF groups became significantly different, 151 mm Hg
2.6 (S.E.M.) vs. 132 mm Hg 3.1 (S.E.M.). These
significant differences remained for the duration of the
study. Unlike, the initial dietary studies, the fasting blood
sugars in the WF and WF + NBC groups remained
significantly lower than control (Ta- ble 2).
Table 2. Blood chemistry data in control and test diet-supplemented rats after 35 days

Control Maitake ES Fraction WS Fraction ANOVA p

SHR
Glucose (mg/dl) 193 9.4 192 9.9 199 20.7 180 10.5 0.497
Creatinine (mg/dl) 0.84 0.06 0.76 0.07 0.65 0.03* 0.88 0.04 0.029
Cholesterol (mg/dl) 82 2.8 93 5.0 102 6.4* 103 5.2* 0.019
Triglycerides (mg/dl) 729 83 598 57* 332 21* 404 21* 0.001
Insulin (uIU/dl) 19.2 1.9 21.3 1.0 17.4 2.2 19.8 2.0 0.386
HbA1C (%) 5.4 0.20 5.4 0.14 5.2 0.06 5.3 0.08 0.590

ZFR
Glucose (mg/dl) 215 18.8 219 13.4 190 18.0 186 14.0 0.419
Creatinine (mg/dl) 0.58 0.02 0.48 0.05 0.53 0.03 0.54 0.03 0.131
Cholesterol (mg/dl) 223 10.7 242 22.4 240 16.4 261 26.6 0.585
Triglycerides (mg/dl) 756 137 863 150 912 82 726 80 0.650
Insulin (uIU/dl) 78.7 3.7 65.8 6.1* 62.3 2.6* 71.7 3.3 0.037
HbA1C (%) 5.7 0.17 5.1 0.19* 5.2 0.09* 5.4 0.12 0.004

Average S.E.M. values are shown following 35 days of supplementation of control diet and test diet. See Materials and methods section for details. (*p <
0.05 compared to control; p < 0.10 compared to control).

Discussion
Hypertension, glucose intolerance, obesity, and lipid per-
turbations are chronic disorders common in the aging
human [5, 2024]. Nutritional factors such as excess intake
of sim-
ple sugars and saturated/trans fats coupled with low fiber
consumption, prevalent in the Western diet, can be linked
frequently to augment insulin resistance with
accompanying hyperglycemia, hyperinsulinemia,
hyperlipidemia, and hy- pertension [2527]. Probably the
best natural means to pre- vent or ameliorate these risk
factors using an experimental model is caloric restriction
[28]. Even though 3040% ca- loric restriction may
improve many risk factors in different animal models, such
a rigorous regimen is near impossible to follow for humans.
Nevertheless, other potentially more useful means to
favorably influence the glucose/insulin sys- tem are
available. For example, we and others have found that
supplementary chromium, garlic, soluble fibers, and
vanadium can overcome, to some extent, many of these
perturbations [6, 29]. Thus, natural nutrients/elements can
favorably influ- ence the glucose/insulin system and the
onset of age-related chronic disorders [29]. In this vein,
recent publications sug- gest that consumption of Maitake
mushroom promotes simi- lar benefits [12, 3035].
An interesting aspect of the present study was the differ-
ent responses of the two rat strains to whole Maitake pow-

Table 3. Various parameters in ZFR on different regimens at the end of 35

days

Parameter Control WS WS + NBC

Body wt (g) 657 28.7 653 33.1 631 24.5

SBP (mm Hg) 155 4.1 143 1.6* 133 5.7*#
Fasting glucose (mg/dl) 179 7.0 161 6.6* 151 8.4*

Fig. 4. Changes in TBARS content in nmoles MDA equivalents per 100 Average S.E.M. values are shown for 12 rats. WS water soluble frac-
mg of renal tissue from various groups. Average S.E.M. is shown. Z tion; NBC niacin-bound chromium. See Materials and methods section
Zucker rats; S SHR; C control; M Maitake mushroom powder; ES for details. (*Statistically different than control; #statistically different than
ether soluble fraction; WS water soluble fraction. WS).
der and its two fractions examined, ES and WS [12, 31]. In
the case of blood pressure regulation, the reasons behind
some of the findings and differences are not entirely clear.
Previous reports found that SBP decreased significantly in
SHR in response to the consumption of whole Maitake
mush- room and the ether soluble fraction but not to water
soluble fractions [31, 34]. There is also no ready
explanation why we could not duplicate the SBP-lowering
effects of whole Maitake powder, which was also shown by
Kabir et al. [35]. Nevertheless, we did corroborate that the
ES fraction, not the water soluble one, lowered the elevated
SBP in SHR.
Examining ZFR demonstrated that the water soluble
frac- tion also could decrease SBP, at least in another rat
strain, unlike previous assumptions [31]. Our new finding
was that whole Maitake powder and WS significantly
decreased SBP in ZFR in contrast to ES, which had no
significant effect. The ZFR is accepted as being insulin
resistant [10], and insulin resistance has been closely
correlated with elevated blood pressure [6]. Therefore, it
may not be too surprising that whole Maitake powder and
its WS, which have been associ- ated with diabetic control
[12], have such an effect. However, we found that fraction
ES also favorably influenced the glu- cose/insulin system in
this strain and did not lower SBP.
An explanation for the SBP-lowering influences of frac-
tion ES on SHR may lie in the effects of this fraction on the
renin-angiotensin system (RAS). The response of ZFR to
losartan, an angiotensin II receptor blocker, indicates that
the RAS is not significantly active in SBP regulation in this
strain. In contrast, giving similar challenges of losartan to
SHR in the whole Maitake powder and WS groups caused a
signifi- cant decrease in SBP, i.e. 5060 mm Hg. However,
the de- crease was significantly less in the ES group
compared to the whole Maitake powder and WS groups, i.e.
approximately 30 mm Hg in the SHR consuming the diet
containing frac- tion ES. The latter finding suggests that the
renin-angiotensin system was less active in SHR
consuming fraction ES. Ex- amining the blood chemistry
values allows further specula- tion about the role of the
renin-angiotensin system in the pathogenesis of the ES
fraction effect in the SHR. Serum creatinine was
significantly lower in this group. It is well known that
decreasing renin-angiotensin system activity can influences
glomerular filtration, i.e. often increasing it. Ac- cordingly,
an increased glomerular filtration rate brought about by
such an effect could explain the lower concentra- tion of
circulating creatinine.
Similar to the SBP responses, the responses of various
chemical parameters to the test agents differed between the
two strains of rats. Although a significant effect of whole
Maitake powder and fractions ES and WS were not seen on
the circulating glucose levels in the ZFR in the initial
dietary study, the lower concentrations of circulating
insulin and HbA1C suggest enhanced insulin sensitivity.
The test agents affected none of these same parameters in
the SHR. Whole
Maitake powder and fractions ES and WS lowered tri-
glycerides in SHR at the same time that the two fractions
increased the circulating levels of cholesterol. In contrast,
circulating fats were essentially unchanged in the ZFR un-
der the same conditions. None of the above effects of whole
Maitake powder and the 2 fractions can likely be attributed
to an antioxidant effect, since TBARS were similar or even
significantly elevated in the rats consuming Maitake or its
fractions.
It is not clear why triglycerides were lower in SHR
where there was little evidence of an effect on the glucose-
insulin system. This suggests another mechanism rather
than over- coming insulin resistance in the SHR. We have
found that lowering of cholesterol in rats may take months
to be accom- plished. Our findings with Maitake resemble
with the results demonstrated by Lau [36] on garlic. It has
been demonstrated by Lau [36] that circulating cholesterol
and triglyceride lev- els often increase significantly during
the first few weeks of garlic supplementation. After which,
a significant decrease is observed in both of these
parameters. It has been indicated that garlic enhances the
removal of cholesterol and triglyc- eride from the vital
organs and that is the reason these levels initially go up for
the first couple of weeks. Similar results were observed in
ZFR.
The later studies, which used gavage as the means to
give the WS extract instead of dietary means, was
performed to reexamine the effects of the Maitake WS
fraction on systolic blood pressure and circulating glucose
levels. In addition to the means to give the WS fraction,
other differences existed between these and the earlier
study. In the gavage studies, older ZFR were used that had
higher starting body weights, systolic blood pressures and
fasting blood glucose levels. The studies using gavage
corroborated that the WS fraction low- ers SBP in ZFR, and
also strengthens the hypothesis that WS can influence the
glucose-insulin system. While the first study showed a
trend in the lowering of serum insulin concentra- tions and
HbA1C, these studies showed a significant decrease in
fasting blood glucose levels. Interestingly, the addition of
NBC to the WS fraction showed greater lowering of SBP
than when WS was used alone and a tendency to lower the
fast- ing blood glucose even more than with WS alone.
A significant number of studies have been conducted on
niacin-bound chromium (NBC) in our laboratory and else-
where, which has demonstrated a number of beneficial ef-
fects in animals and humans. In a bioavailability study,
NBC was demonstrated to absorb and retain 672% greater
than chromium chloride and 311% more than chromium
picolinate in mice [37]. In a clinical study, NBC
significantly reduced serum cholesterol levels and
improved total cholesterol/HDL ratios in male athletes
compared with those taking a placebo [38]. NBC
significantly lowered both total cholesterol and LDL
cholesterol levels by 10 and 14%, respectively, in peo- ple
with elevated cholesterol levels [8]. NBC prevented
against sugar-induced hypertension, lowered glycosylated
hemoglobin and reduced liver and kidney lipid peroxidation
in SHR rats [39, 40]. NBC also improved various metabolic
parameters following long-term supplementation of NBC
[30]. NBC significantly reduced weight and lowered insulin
response to an oral glucose load in young obese women in
another clinical study [41]. In a separate clinical study, re-
searchers showed that compared to placebo, NBC caused
significant loss of body fat and sparing of muscle (lean
body mass) in overweight women [42].
In conclusion, the overall findings demonstrate that
whole powder of Maitake mushroom and two of its
fractions (ES, WS) can favorably influence glucose-insulin
metabolism, at least in the rat models simulating insulin
resistance (ZFR), and decrease SBP by different
mechanisms in the two rat strains. The different
mechanisms to lower SBP seen with fractions ES and WS
suggest that these fractions could be tools to examine the
root causes for hypertension in SHR and ZFR. More
importantly, the different responses in the two rat strains
suggests that the different forms of Maitake mushroom may
have different responses in clinical trial assessing non
diabetic hypertensive and diabetic patients.
Acknowledgements
This work was supported by a grant from Maitake, Inc.,
Paramus, NJ, USA. Whole Maitake powder and the WS
frac- tion were provide to us by Maitake, Inc., Paramus, NJ,
USA. Niacin-bound chromium, ChromeMateTM, was the
generous gift of InterHealth Nutraceuticals, Benicia, CA,
USA.
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