Lycium barbarum Fruit (Goji) Attenuates the Adrenal Steroid Response to an Exercise Challenge and the Feeling of Tiredness: A Randomized, Double-blind, Placebo-controlled Human Clinical Study

Abstract

We examined the effects of Lycium barbarum fruit (goji) intake on general well-being in a randomized, double-blind, placebo-controlled 30-day intervention trial. Plasma levels of cortisol, dehydroepiandrosterone (DHEA), glucose, urea nitrogen (BUN) and lactic acid followed by an exercise challenge were assessed at the pre- and post-intervention. Relative to the placebo group (n=19), tiredness and overall health were significantly improved in the Lycium barbarum group (n=20). Cortisol, DHEA and lactic acid levels were significantly increased by the exercise for the pre-intervention: However, at the post-intervention, Lycium barbarum intake significantly attenuated cortisol and DHEA levels. Lactic acid levels were comparable for both groups, and glucose and BUN levels were not altered. These results show that Lycium barbarum consumption attenuates the adrenal steroid response and reduces the feeling of tiredness.

Full text

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Published by Canadian Center of Science and Education 3
Lycium barbarum Fruit (Goji) Attenuates the Adrenal Steroid
Response to an Exercise Challenge and the Feeling of Tiredness: A
Randomized, Double-blind, Placebo-controlled Human Clinical Study
Harunobu Amagase (Corresponding author)
FreeLife International Inc., 4950 South 48th Street, Phoenix, AZ 85040, USA
Tel: +1-602-333-4926 E-mail: hamagase@freelife.com
Dwight M. Nance
Susan Samueli Center for Integrative Medicine
University of California at Irvine, 101 The City Drive South, Orange, CA 92868, USA
Tel: +1-714-456-2997 E-mail: dnance@uci.edu
Received: February 6, 2012 Accepted: February 17, 2012 Published: May 1, 2012
doi:10.5539/jfr.v1n2p3 URL: http://dx.doi.org/10.5539/jfr.v1n2p3
The research is financed by FreeLife International, Inc
Abstract
We examined the effects of Lycium barbarum fruit (goji) intake on general well-being in a randomized,
double-blind, placebo-controlled 30-day intervention trial. Plasma levels of cortisol, dehydroepiandrosterone
(DHEA), glucose, urea nitrogen (BUN) and lactic acid followed by an exercise challenge were assessed at the
pre- and post-intervention. Relative to the placebo group (n=19), tiredness and overall health were significantly
improved in the Lycium barbarum group (n=20). Cortisol, DHEA and lactic acid levels were significantly
increased by the exercise for the pre-intervention: However, at the post-intervention, Lycium barbarum intake
significantly attenuated cortisol and DHEA levels. Lactic acid levels were comparable for both groups, and
glucose and BUN levels were not altered. These results show that Lycium barbarum consumption attenuates the
adrenal steroid response and reduces the feeling of tiredness.
Keywords: Lycium barbarum, Goji, Exercise, Cortisol, Dehydroepiandrosterone, Lactic acid, Tiredness, General
Well-being
1. Introduction
Our previous randomized, double-blind, placebo-controlled human clinical studies showed that daily
consumption of Lycium barbarum, in the form of fruit juice, GoChi®, significantly increased subjective feelings
of general well-being and reduced fatigue (Amagase et al., 2008). Lycium barbarum consumption significantly
enhanced in vivo immune functions as indicated by increased number of lymphocytes and blood concentrations
of immunoglobulin G and interleukin (IL)-2 (Amagase et al., 2009a). In vivo anti-oxidant effects of Lycium
barbarum include a significant increase in blood concentrations of superoxide dismutase and glutathione
peroxidase and a significant reduction in lipid peroxidation (malondialdehyde) (Amagase et al., 2009b). Lycium
barbarum intake has also been shown to increase metabolic rate/energy expenditure in a dose-dependent manner
(Amagase et al., 2011b). Lycium barbarum juice used in these studies is standardized for its main active
constituents, Lycium barbarum polysaccharide (LBP). Lycium barbarum is a Solanaceous defoliated shrubbery
and has been a commonly prescribed traditional medicine in Asian countries for over 2,500 years (Amagase et
al., 2008, 2011a; Bensky et al., 1993; Chang et al., 2001, 2008). Additional effects of Lycium barbarum include
improved endurance, anti-agng, neuroprotection, anti-diabetic, anti-glaucoma, anti-tumor activity and
cytoprotection have been reported (Amagase et al., 2011a).
Adrenal steroids, such as cortisol and prohormone, dehydroepiandrosterone (DHEA), regulate a variety of

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cardiovascular, metabolic, immunologic and homeostatic functions (American Heart Association, 2009; Buford
et al., 2008; Walker, 2007). These "stress hormones" are released in response to a variety of physical, metabolic
and psychological stressors. DHEA is produced primarily in the adrenal glands and is released along with
cortisol in response to stress (Dillon, 2005). Exercise is a potent stimulus for cortisol release and exercise
increases DHEA production (Filaire et al., 1998; Tissandier et al., 2001; Copeland et al., 2002). Thus,
measurement of DHEA and cortisol levels in response to an exercise challenge may provide an index of the
physiological effects of Lycium barbarum on the response to a physical stressor.
To extend the analysis of the physiological actions of Lycium barbarum and to investigate possible mechanisms
of action as the first step, we examined the effects of Lycium barbarum intake on exercise-induced adrenal
steroid release as well as lactic acid, glucose and blood urea nitrogen (BUN) concentrations in plasma at pre- and
post-30-day-intervention trial under a randomized, double-blind, placebo-controlled manner.
2. Materials and Methods
2.1 Lycium barbarum and placebo preparation
FreeLife International Inc, located in Phoenix, Arizona, supplied a commercially available, LBP-standardized
Lycium barbarum fruit (goji) juice (GoChi; Lot No. ASA07351) which was produced from fresh ripe Lycium
barbarum fruit. Description and standardization procedures of the test material were previously described
(Amagase et al., 2008). In brief, the yield of juice as a percentage weight of the starting fresh plant material is
approximately 35%. The juice was processed in an aseptic manner and kept refrigerated before use at 2 to 8 ºC.
GoChi is standardized to contain a content of LBP equivalent to that found in at least 150 g of fresh fruit in 120
ml, the amount customarily consumed in traditional Chinese medicine (Yu et al., 2007; Amagase et al., 2011a).
Based on our previous dose-seeking study on energy expenditure (Amagase et al., 2011b) and other various
studies (Amagase et al., 2008, 2009a, 2009b), we used 120 ml of GoChi in the present studies as an established
dose.
Placebo control material (Lot No. A198) was carefully prepared as previously described (Amagase et al., 2009a)
to match the color, flavor, and taste of GoChi in a formulation of sucralose (10 mg), artificial fruit flavor (30 mg),
citric acid (60 mg), and caramel color (12 mg) in 30 mL of purified water. It was packaged in the same type of
container; however, it provided no nutritional value or LBP.
In addition, a novel trace amount of flavor was added to both active and placebo preparations to mask the
differences, so no study participants had been exposed to the flavor-masked samples specifically prepared for the
present study.
2.2 Clinical study
A 30-day intervention study was performed in a randomized, double-blind, placebo-controlled manner. To
maintain high compliance with our first exercise challenge test and make the test under a similar physical
activity condition in the office work, we recruited the participants from in-house. All randomized participants
were healthy men and women, age 18 y and older (average age = 33.6 ± 1.9 y) (Table 1A). The CONSORT chart
in Figure 1 shows the population including ethnic backgrounds. Recruitment was conducted to ensure that
participants were serious about participating in these studies and well aware of its demands. All participants in
the study were fully informed of the purpose of the study, and signed the Human Subjects Informed Consent
forms approved by the Internal Review Board organized under the Helsinki Declaration. Exclusion and inclusion
criteria were same as the previous studies (Amagase et al., 2008, 2009a, 2009b). Following enrollment, all
participants completed a 2 to 4 week wash-out period during which time they discontinued use of any dietary
supplements, including Lycium barbarum or Lycium barbarum-containing foods, if any, energy drinks,
caffeinated beverages or tea, and these restrictions were continued throughout the study based upon the
self-declaration in the daily dietary diary and verbal confirmation. Our previous studies have shown that there
were no statistically significant differences after this wash-out period in various subjective indicators. A total of
39 healthy male and female adults were randomly assigned to either the Lycium barbarum treatment or placebo
control group for this 30-day intervention study (Figure 1). Sixty-seven percent were women. Male and female
participants were randomized separately to ensure an equal number of men and women in each treatment group.
The participants, all investigators and staff involved in this study were blinded to the participant’s treatment
assignment. Tested products were assigned a number or letter code. This code remained unrevealed to the
investigators involved in the study until after completion of the data analyses. No participants were pregnant
during the study based upon standard urine pregnancy test (Kurkel Enterprises, HCG Lot No. 5-06257, Redmond,
Washington). There were no statistical differences in demographic and clinical characteristics of the study
population, and pre-study diet on the parameters of dietary intake (Table 1A), average Lycium barbarum

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consumption history, if any, and consumption patterns for other beverages such as sweetened beverages (soda),
coffee, tea and alcoholic beverages, or smoking history. Food intake was monitored throughout the study by
means of daily dietary diaries maintained by the participants. We noticed that self-reported dietary diary may not
be completely accurate in the clinical study. However, we believed that it was better than no food log to trace the
food records, and may reflect rough caloric intake during the study, as participants were aware of what they eat.
In fact, average caloric intake was somewhat realistic based on their diary (Table 1A). All participants reported
regular intake of a Western style diet. Daily energy intake was calculated by combining macronutrients intake
from the individual diary recorded in the evening with their entire food, snack and beverage intake. A review of
the participants’ daily diary, there appears to be no change in the participants’ other juice intake during the
intervention period compared to pre-intervention. All participants were monitored daily to ensure full
compliance with the protocol including restriction of dietary intake. Upon randomization, participants consumed
120 ml of Lycium barbarum juice or placebo each morning shortly after a meal in front of the researcher on
weekdays for a period of 30 days under free-living conditions. To monitor the weekend compliance, we
recovered empty bottles on the following Monday. No dropouts occurred in either group during the intervention
period. Based upon the previous studies (Amagase et al., 2008, 2009a, 2009b, 2011b), a sample size of 39
participants was deemed to be sufficient to detect effectiveness of Lycium barbarum alone with 95% confidence
and 80% power.
At the pre- and post-intervention period (Day 1 or Day 30), all participants were given physical anthropometric
measurements collected following an overnight 12 h fast and included: body weight and body mass index (BMI)
(Seca 703, Hamburg, Germany) (Figure1). All participants were administered a written questionnaire with a
rating scale (0-5) (Amagase et al., 2008) at the time of pre- (Day 1) and post-intervention (Day 30) immediately
before the exercise challenge (Figure1). The questionnaire consisted of physical and psychological
fatigue-related symptoms, such as fatigue, feelings of tiredness, musculoskeletal questions, cardiovascular
questions, and questions regarding possible side effects.
To provide a comparable short and intense exercise challenge, each participant was tested on a ramp-type
progressive electronically braked either upright (Schwinn, Model 126, Vancouver, WA) or recumbent cycle
ergometer (Schwinn, Model 226-recumbent, Vancouver, WA) (Figure 1). This exercise challenge was performed
only on Day 1 (pre-intervention) and Day 30 (post-intervention) as an acute intense physical stress. After resting
on the cycle ergometer for 1 min of unloaded pedaling to confirm the resting heart rate, the work rate (WR) was
increased by 20 to 30 watt/min adjusted according to the participant’s age and fitness level by monitoring display
of the heart rate. Workloads were individualized for each participant and were calculated to be equivalent to the
WR corresponding roughly to 70% of age-adjusted maximum heart rate as determined non-invasively based on
American Heart Association (2011) and Sharkey et al (2007). Participants were vigorously encouraged during
the high-intensity phases of the exercise protocol equal 12 to 14 minutes (Radom-Aizik et al., 2008, 2009) until
preset 200 kcal were burned. The initial result of the exercise challenge for all the participants at the
pre-intervention time point on heart rate, watts and calorie burned did not show any statistically significant
differences for the post-intervention challenge as shown in Table 1B. In the background of the participants, there
were no statistical differences in the average exercise frequency or length between the groups (Table 1A).
Changes in plasma concentrations of DHEA, cortisol, glucose and lactic acid were assessed pre- and
post-intervention immediately before and after the exercise challenge (Figure 1). Hormone concentrations were
measured by enzyme-linked immunosorbent assay (ELISA) (Diagnostic Systems Laboratories, Inc. Webster,
Texas), lactic acid levels determined in a YSI 2300 Stat Plus analyzer (YSI, Inc., Yellow Springs, Ohio), glucose
and BUN were determined by standard medical laboratory methods (LabExpress, Phoenix, Arizona).
2.3 Statistical analysis
Dietary intake data were analyzed with non-parametric Mann-Whitney U-Test (placebo vs Lycium barbarum).
For all clinical symptom questions, each question was graded and the scores analyzed for changes between pre-
and post-intervention with the nonparametric Wilcoxon matched pairs tests. A 2 x (2) mixed ANOVA (group x
test) was used for body weight, BMI, and a 2 x (2) x (2) mixed ANOVA (group x test x time) was used for
plasma levels of hormones, glucose, BUN concentrations. Descriptive statistics were calculated for placebo and
Lycium barbarum for all dependent measures and summarized as means ± SEM. The data were processed using
Statistica version 8 (StatSoft, Inc., Tulsa, Oklahoma). Differences were considered significant at P<0.05.
3. Results
Significant differences (P<0.05) between pre- and post-intervention were found in the Lycium barbarum group
(n = 20) for questions in tiredness categories as shown in Table 2. The Lycium barbarum group showed

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significant reductions in feelings of tiredness after exercise, poor circulation, and overall health conditions.
Compared to the pre-intervention results, more than 65% of people who consumed Lycium barbarum reported
they did not feel tiredness after exercise. In contrast to the Lycium barbarum group, the placebo group (n = 19)
showed no statistically significant changes following the 30-day intervention period. There were no statistically
significant changes in body weight, BMI or total body fat between the groups or pre- vs. post-intervention in
both groups (Table 2).
DHEA, cortisol and lactic acid concentrations were all significantly increased in the placebo group after the
exercise challenge for both pre- and post-treatment tests (P<0.05) (Table 3). Similarly, an increase in plasma
levels of DHEA and cortisol was observed after the initial exercise challenge in the Lycium barbarum group
before treatment; however, following Lycium barbarum treatment for 30 days the exercise-induced increase in
DHEA and cortisol levels was significantly attenuated. The exercise-induced increase in lactic acid concentration
was not changed by Lycium barbarum or placebo intake (Table 3). Blood glucose levels were comparable both
pre- and post-intervention for both groups. BUN level post- intervention was increased in both groups, but no
statistical difference was found after exercise (Table 3).
4. Discussion
The present study was the first human clinical study to show that Lycium barbarum intake significantly
attenuated the increases in plasma DHEA and cortisol concentrations produced by a short and intense exercise
challenge. Exercise represents a physical stress that challenges homeostasis. In response to this stressor, autonomic
nervous system and the hypothalamic-pituitary-adrenal axis (HPA-axis) are known to react and to participate in the
maintenance of homeostasis. This includes elevation of cortisol and cathecholamines in plasma (Mastorakos et al.,
2005). The present study results suggest that consumption of Lycium barbarum may increase adaptability to a
physical stressor such as exercise by either reducing production and function of glucocorticoids, or accelerating
metabolism of these hormones. Some of the immunomodulatory actions of Lycium barbarum may be mediated
in part through changes in the HPA-axis. Lycium barbarum intake may interact with cortisol by stimulating the
immune system as reported in a previous clinical study (Amagase, 2009a). Likewise, the reported ability of
Lycium barbarum to significantly reduce subjective feelings of tiredness or fatigue, especially after exercise,
may also be related to changes in adrenal steroid regulation. Cortisol counteracts the action of insulin by
increasing gluconeogenesis, promoting lipolysis and mobilizing extrahepatic amino acids and ketone bodies,
which leads to increased circulating glucose concentrations in the blood (Freeman et al., 2004) and prolonged
cortisol secretion causes hyperglycemia (Barseghian et al., 1982). LBP has been reported to enhance the storage
of muscle and liver glycogen, to increase the activity of lactate dehydrogenase (LDH) before and after swimming,
to inhibit the increase of blood urea nitrogen (BUN) after strenuous exercise, to accelerated the clearance of
BUN after exercise, to increase adaptability to an exercise load, to enhance resistance to fatigue and to accelerate
the elimination of lactic acid in mice (Luo et al., 2000). However, we found that plasma lactic acid and glucose
concentrations were not influenced by Lycium barbarum intake. Nonetheless, participants reported an increase in
endurance/energy in the daytime and reduced fatigue following 30 days of Lycium barbarum consumption.
These effects were consistent with previous study results (Amagase et al., 2008, 2009a). There is evidence that
elevated endogenous glucocorticoid activity can be associated with visceral obesity. This may be mediated
centrally level via the HPA-axis and peripherally via increased conversion of cortisone to cortisol by
11-ß–hydroxysteroid-dehydrogenase type 1 in adipose tissue (Masuzaki 2001; Pasquali et al., 1993). Increased
activity of the HPA-axis has been linked to metabolic syndrome or “Syndrome X”, and may contribute to the
clustering of low HDL cholesterol, high triglycerides, insulin resistance, hypertension, and visceral obesity that
characterize this syndrome, all of which represent major risk factors for cardiovascular disease, stroke, and
diabetes mellitus type II (Brunner, 2002; Brotman et al., 2003). In female weanling mice, LBP was shown to
enhance food conversion rate and to reduce body weight after 21 days of consumption (Zhang et al., 2002). We
reported a similar reduction in weight gain in adult male rats given Lycium barbarum (Nance et al., 2009). These
results suggest that LBP may modulate metabolism in vivo. In support, it was shown in a clinical trial that
Lycium barbarum intake increased energy expenditure and/or metabolic rate in humans (Amagase, 2011b). The
magnitude of the experimental effects of Lycium barbarum in the current study may in part reflect the fact that
the test participants had normal body weights and BMIs in addition to the limited consumption time period. It is
possible that the metabolic impact of Lycium barbarum juice would be more readily demonstrated in overweight
or obese participants and could be utilized to prevent or treat metabolic syndromes, including
glucocorticoid-related conditions. In support of this possibility, animal studies show dramatic effects of L
barbarum on blood glucose and insulin levels in diabetic rats that are not observed in nondiabetic controls (Zhao
et al., 2005).

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In support of a role for the anti-oxidant properties of Lycium barbarum (Amagase et al., 2009b; Wu et al., 2004;
Gong et al., 2005) in the attenuation of the effects of exercise on cortisol release are the results of Davison, et al
(2007). Similar to the current results, they showed that dietary supplementation with anti-oxidants (daily vitamin
C (L-ascorbic acid, 1000 mg) and vitamin E (RRR-alpha-tocopherol, 400 IU) supplementation) blunted the
cortisol response to a single prolonged exercise challenge (Davison et al., 2007). Also, LBP has been shown to
prevent oxidative stress following exhaustive exercise in rats (Shan et al., 2011) and the anti-inflammatory effect
of Lycium barbarum consumption was demonstrated by Reeve et al (2010) in an animal model of UV radiation
induced oxidative skin damage.
5. Conclusion
This is the first randomized trial to evaluate the effects of Lycium barbarum on exercise-induced adrenal steroid in
humans. Lycium barbarum intake significantly attenuated the increases in plasma DHEA and cortisol
concentrations produced by a short and intense exercise challenge. The Lycium barbarum group showed
significant reductions in feelings of tiredness after exercise. Our results suggest that daily consumption of Lycium
barbarum may attenuate stress-related reactivity and facilitate adaptation to physical stressors. Furthermore, as
elevated endogenous glucocorticoid activity has been linked with visceral obesity and the metabolic syndrome,
our findings suggest that altered HPA activity may be related to previously reported metabolic effects of Lycium
barbarum and its active ingredients.
Acknowledgements
The corresponding author (HA) is an employee of FreeLife International. Co-author (DMN) is a member of
FreeLife’s Independent Scientific Advisory Board.
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Abbreviations: DHEA, dehydroepiandrosterone; ACTH, adrenocorticotropic hormone; L. barbarum, Lycium
barbarum; LBP, Lycium barbarum polysaccharide; IL, interleukin; WR, work rate; ELISA, Enzyme-Linked
Immuno Sorbent Assay; BMI, body mass index; LDH, lactate dehydrogenase; BUN, blood urea nitrogen; RMR,
resting metabolic rate; HPA, hypothalamic-pituitary-adrenal.
Table 1. (A) Baseline demographic variables of non-discriminated participants in the current randomized,
double-blind, placebo-controlled human clinical study. (B) Parameters of maximal heart rate, watts and calorie
burned during the short and intense exercise challenge at pre- and post-intervention in both Lycium barbarum (L.
barbarum) and placebo groups. This exercise challenge was performed only on Day 1 (pre-intervention) and Day
30 (post-intervention) as physical stress.
A
Variable n Mean ± SEM
Age (years old) Placebo 19 31.1 ± 2.5
L
. barbarum 20 36.0 ± 2.9
Female Population (%) Placebo 19 63.2
L
. barbarum 20 70.0
Exercise (times/week) Placebo 19 0.5 ± 0.1
L
. barbarum 19 0.3 ± 0.1
Average Daily Caloric
Intake (kcal)*
Pre-intervention/wash-out period Placebo 19 1,866 ± 158
L
. barbarum 20 1,972 ± 181
during the 30-day intervention
study period
Placebo 19 1,807 ± 134
L
. barbarum 20 1,839 ± 144
Each value indicates mean ± SEM except female population. Sample numbers varied due to missing answers.
*calculated from daily food diary. Age and average daily caloric intake data were analyzed by ANOVA, and
exercise frequency data were analyzed with nonparametric Mann-Whitney U Test (Placebo vs Lycium barbarum).
There was no statistical significance between the groups.
B
n Pre-intervention n Post-intervention
Heart Rate (beat/min) Placebo 19 139.1 ± 3.0 19 145.3 ± 3.2
L. barbarum 20 141.1 ± 2.7 20 138.8 ± 2.7
Total Watts Placebo 19 82.3 ± 5.6 19 98.9 ± 8.1
L. barbarum 20 79.8 ± 4.5 20 91.2 ± 5.2
Calorie burned (kcal) Placebo 19 204.7 ± 11.2 19 223.6 ± 17.1
L. barbarum 20 190.7 ± 8.1 20 207.4 ± 11.9
Each value indicates mean ± SEM. N.S., not significant analyzed by ANOVA. There was no statistical
significance between the groups, or pre- and post-intervention.

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Table 2. Effect of Lycium barbarum (L. barbarum) or placebo on (A) anthropometric parameters and (B)
subjective indications compared to pre-intervention in a randomized, double-blind, placebo-controlled human
clinical study
A
N Pre-intervention n Post-intervention
Body weight (kg) Placebo 19 82.3 ± 5.1 19 82.5 ± 5.1
L. barbarum 20 82.4 ± 4.8 20 82.7 ± 5.0
Body mass index (BMI)
(kg/m2)
Placebo 19 29.3 ± 1.7 19 29.4 ± 1.7
L. barbarum 20 29.5 ± 1.6 20 29.7 ± 1.6
B
Tiredness Placebo 19 2.2 ± 0.3 19 1.8 ± 0.4
L. barbarum 20 2.4 ± 0.4 19 1.9 ± 0.4
Muscular complaints Placebo 18 1.9 ± 0.3 19 1.9 ± 0.3
L. barbarum 18 1.9 ± 0.3 20 1.8 ± 0.3
Physical discomfort Placebo 19 1.7 ± 0.3 19 1.4 ± 0.3
L. barbarum 20 1.9 ± 0.4 20 1.6 ± 0.4
Joint pain Placebo 19 1.4 ± 0.3 19 1.6 ± 0.4
L. barbarum 19 2.1 ± 0.4 19 1.8 ± 0.4
Stiff Shoulder Placebo 19 1.6 ± 0.4 19 1.7 ± 0.4
L. barbarum 20 2.4 ± 0.4 20 2.1 ± 0.4
Tiredness after exercise Placebo 19 1.7 ± 0.3 19 1.9 ± 0.3
L. barbarum 20 2.1 ± 0.3 20 1.4 ± 0.2a
Feeling of bad circulation Placebo 19 0.1 ± 0.1 19 0.3 ± 0.1
L. barbarum 20 1.3 ± 0.4 20 0.5 ± 0.1a
Overall health conditions
(Total Scores)
Placebo 19 60.0 ± 7.0 19 59.9 ± 8.5
L. barbarum 20 79.2 ± 8.3 20 67.3 ± 8.7a
Each value indicates mean ± SEM. Anthropometric parameters were analyzed by ANOVA. These subjective
indications were collected from the questionnaire asked immediately before the short and intense exercise
challenge on both pre- (Day 1) and post-intervention (Day 30). Sample numbers varied due to missing answers.
Lower scores reflect improvements in subjective ratings. a indicates significant difference (P<0.05) from
pre-intervention analyzed by the nonparametric Wilcoxon matched pairs tests.

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Published by Canadian Center of Science and Education 11
Table 3. Effect of Lycium barbarum (L. barbarum) or placebo on plasma dehydroepiandrosterone (DHEA),
cortisol, lactic acid, glucose and blood urea nitrogen (BUN) concentrations at pre- and post-exercise in a
randomized, double-blind, placebo-controlled human clinical study
Pre-intervention Post-intervention
n Pre-exercise n Post-exercise n Pre-exercise n Post-exercise
DHEA
(μg/dl)
Placebo 18 8.2 ± 1.1 18 10.4 ± 1.2b 18 7.3 ± 0.8 18 11.5 ± 1.0b
L.
barbarum 17 6.1 ± 1.1 18 8.4 ± 1.0b 18 5.2 ± 0.9 18 5.7 ± 0.9
Cortisol
(μg/dl)
Placebo 18 34.8 ± 6.2 18 52.2 ± 12.4b 18 23.0 ± 2.1 18 51.8 ± 15.5b
L.
barbarum 15 37.3 ± 4.3 18 47.6 ± 6.8 18 47.8 ± 11.1 18 42.4 ± 4.3
Lactic
acid
(mmol/l)
Placebo 18 2.5 ± 0.2 18 6.1 ± 0.5b 18 2.3 ± 0.3 18 6.1 ± 0.5b
L.
barbarum 18 2.4 ± 0.2 18 5.8 ± 0.4b 18 2.2 ± 0.2 18 5.8 ± 0.5b
Glucose
(mg/dl)
Placebo 19 91.3 ± 2.1 19 90.8 ± 2.8 19 90.1 ± 1.8 19 92.5 ± 3.2
L.
barbarum 20 99.2 ± 10.3 20 95.3 ± 7.8 20 98.9 ± 9.5 20 96.1 ± 7.2
BUN
(mg/dl)
Placebo 19 12.1 ± 0.9 19 12.4 ± 0.8 19 13.5 ± 1.0a 19 13.7 ± 0.9a
L.
barbarum 20 11.7 ± 0.6 20 11.9 ± 0.6 20 13.5 ± 0.6a 20 13.9 ± 0.6a
An exercise challenge on a cycle ergometer at 70% of age-adjusted maximum heart rate was given on each
individual participant at pre- (Day 1) and post-intervention (Day 30). Parameters of maximal heart rate, watts
and calorie burned during the exercise challenge were not statistically different in both pre- and post-intervention
and also in both Lycium barbarum and placebo groups. This exercise challenge was performed only at the time
of pre- and post-intervention. Intervention period of Lycium barbarum or placebo was 30 days. Each value
indicates mean ± SEM. Sample numbers varied due to missing samples. a, b indicate significant difference
(P<0.05) from pre-intervention and pre-exercise, respectively analyzed by ANOVA.

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ISSN 1927-0887 E-ISSN 1927-0895
12
Day 1 (Pre-intervention) Measurements
Assessed for eligibility in the Study
(Anthropometric parameters) (n=59)
Randomized (n=39)
•Caucasian 51%
•Hispanic 33%
•African 13%
•Asian 3%
Allocated to Active
group = L. barbarum
(n=20)
Excluded (n=20)
•Did not meet inclusion criteria
•Surgery during the study schedule
•Relocation due to job change
•Schedule conf licts
•Lost interest
Allocated to Placebo
group (n=19)
Lost to follow-up
(n=0)
Lost to follow-up
(n=0)
Analyzed (n=20) Analyzed (n=19)
Enrollment Allocation Follow-up Analysis
Intervention study period
(30 days)
Sample intake - Once a day in
the morning
Overnight
fasting
(>12 h)
Day 30 (Post-intervention) Measurements
Pre-exercise
blood withdrawal
Post-exercise
blood withdrawal
Exercise
Challenge
Pre-exercise exams
•Body weight
• Body mass index (BMI)
• Subj ective questionnai re
12-14 min
1 min
70% of Maximum level
Figure 1. CONSORT flow diagram, study design and the experimental block on Day 1 (pre-intervention) and
Day 30 (post-intervention). Participants completed pre-exercise examinations including anthropometric
parameter measurements, subjective questionnaire in about 15 min, followed by a pre-exercise blood withdrawal,
a short and intense exercise challenge on a cycle ergometer at 70% of age-adjusted maximum heart rate by
loading ride for about 12-14 min and post-exercise blood withdrawal on both Day 1 and Day 30