Goji Pilot Study

Lycium barbarum Increases Caloric Expenditure and
Decreases Waist Circumference in Healthy Overweight
Men and Women: Pilot Study
Harunobu Amagase, PhD, Dwight M. Nance, PhD
FreeLife International Inc, Phoenix, Arizona (H.A.), Susan Samueli Center for Integrative Medicine, University of California at
Irvine, Orange, California (D.M.N.)
Original Research
Lycium barbarum Increases Caloric Expenditure and
Decreases Waist Circumference in Healthy Overweight
Men and Women: Pilot Study
Harunobu Amagase, PhD, Dwight M. Nance, PhD
FreeLife International Inc, Phoenix, Arizona (H.A.), Susan Samueli Center for Integrative Medicine, University of California at
Irvine, Orange, California (D.M.N.)
Key words: Lycium barbarum, goji, waist circumference, energy expenditure, resting metabolic rate, humans
Background: Lycium barbarum (L. barbarum), a traditional Asian medicinal therapy for diabetes and other
conditions, has been shown to increase metabolic rate and to reduce body-weight gains in rodent models, as well
as to produce clinical improvements in general feelings of well-being including energy level.
Objective: To investigate the impact of L. barbarum consumption on (1) caloric expenditure and (2) changes
in morphometric parameters (waist circumference) in healthy human adults.
Method: Two separate randomized, double-blind, placebo-controlled, small clinical studies were conducted
using a standardized L. barbarum fruit juice, GoChi, and assessing its effects on (1) resting metabolic rate (RMR)
and postprandial energy expenditure (PPEE) as measured by indirect calorimetry after single-bolus intake of 3 doses
of L. barbarum (30, 60, and 120 ml) and placebo; and (2) waist circumference and other morphometric changes in a
14-day intervention trial (120-ml daily intake) in the subjects (age ¼ 34 years, body mass index ¼ 29 kg/m2).
Results: (1) A single bolus of L. barbarum intake increased PPEE 1 through 4 hours postintake over the
baseline level in a dose-dependent manner and was significantly higher than the placebo group by 10% at 1 hour
postintake of 120 ml (p , 0.05). (2) In a 14-day intervention trial, L. barbarum was found to significantly
decrease waist circumference by 5.5 6 0.8 cm (n ¼ 15) compared with the preintervention measurements and
placebo group at postintervention day 15 (p , 0.01). By contrast, the changes in the placebo group (n ¼ 14) from
preinterventions was 0.9 6 0.8 cm, which was not statistically significant.
Conclusions: These results show that L. barbarum consumption increases metabolic rate and reduces the
waist circumference, relative to placebo treated control subjects.
significant clinical improvements in general well-being,
including energy levels, sleep quality, glucose control in
diabetics, glaucoma, antioxidant properties, antiaging, neuroprotection, antifatigue/endurance, immunomodulation, antitumor activity, and cytoprotection [3–10].
Obesity is a major health problem worldwide and is widely
recognized as being associated with increased morbidity and
mortality [11,12]. Abdominal obesity is strongly associated
with increased cardiometabolic risk, cardiovascular events, and
mortality [12–14]. One criterion for the diagnosis of metabolic
INTRODUCTION
Lycium barbarum (L. barbarum) is a Solanaceous defoliated shrubbery, and the fruit (goji ) has been a commonly
prescribed traditional medicine in Asian countries for more
than 2500 years. Modern studies indicate that L. barbarum and
its main active constituents, L. barbarum polysaccharides
(LBP), possess a range of biological effects, such as
significantly increasing metabolic rate and body-weight
reduction in mice and rats [1,2]. Other observed effects include
Address reprint requests to: Harunobu Amagase, PhD, Chief Scientific Officer, FreeLife International Inc, 4950 South 48th Street, Phoenix, AZ 85040. E-mail:
[email protected]
Presented in part at the Experimental Biology meeting in New Orleans, LA, April 17–22, 2009, and Anaheim, CA, April 24–28, 2010.
Personal financial interest: All sources of financial support came from FreeLife International. Principal investigator/corresponding author is an employee of FreeLife
International, and coauthor is an independent scientific advisor to FreeLife.
Abbreviations: BMI ¼ body mass index, DXA ¼ dual-emission x-ray absorptiometry, LBP ¼ Lycium barbarum polysaccharide, PPEE ¼ postprandial energy expenditure,
RMR ¼ resting metabolic rate, VO2 ¼ breath oxygen volume.
Journal of the American College of Nutrition, Vol. 30, No. 5, 304–309 (2011)
Published by the American College of Nutrition
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L. barbarum (Goji ) Stimulates Metabolic Rate
syndrome includes measurement of abdominal obesity/waist
circumference because visceral adipose tissue is a key
component of the syndrome [14–16].
Based on the known features of L. barbarum listed here, we
have conducted two separate human clinical studies using a
randomized, placebo-controlled procedure to explore the acute
effects of L. barbarum on (1) resting metabolic rate (RMR) and
postprandial energy expenditure (PPEE) measured by indirect
calorimeter, and (2) central adiposity, as measured by waist
circumference in healthy human subjects. Given that this fruit
juice is the only available material standardized with regard to
its active component, LBP, we have used this preparation for
the present studies.
MATERIALS AND METHODS
L. barbarum and Placebo Preparation
FreeLife International Inc, Phoenix, AZ, supplied a commercially available, LBP-standardized L. barbarum fruit juice
(GoChi; lot no. ASA07120 and ASA07351) produced from
fresh, ripe L. barbarum fruit. The yield of juice as a percentage
weight of the starting fresh plant material is about 35%. Juice
was processed in an aseptic manner on an industrial scale and
kept refrigerated at 28C to 88C. Description and standardization
procedures of the test material were previously described [6]. In
brief, L. barbarum fruit juice is standardized to contain an
amount of LBP equivalent to that found in at least 150 g of fresh
fruit per daily intake (120 ml), the amount customarily
consumed in traditional Chinese medicine [17]. The caloric
level of 120 ml of the L. barbarum preparation used was 64 kcal.
Placebo control material (lot no. A198) was supplied by
FreeLife International and matched the color, flavor, and taste
of L. barbarum fruit juice 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 LBP.
Study Population
Participants were healthy men and women, aged 18 years
and older, and recruited separately for each study. In all clinical
studies, the same inclusion/exclusion criteria were used but
there were separate protocols for each study. Subjects were
excluded from the study if they exhibited any evidence of heart,
liver, lung, or kidney disease; had known allergies to L.
barbarum or other fruit juices; were pregnant or breast-feeding;
were under anticoagulant therapy such as Coumadin (warfarin);
or had any acute or chronic medical or psychiatric condition.
All subjects 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. Regarding subjects’ backgrounds, groups
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
did not differ in prestudy diet on the parameters of the dietary
intake, average L. barbarum consumption history, and
consumption patterns for other beverages, such as sweetened
beverages (soda), coffee, tea, and alcoholic beverages, or
smoking history.
Research Protocol
Two separate clinical studies were conducted in a
randomized, double-blind, placebo-controlled manner. Following enrollment in the trial, all participants completed at least 2
weeks of a washout period during which they were to
discontinue their use of any L. barbarum or L. barbarum–
containing foods, any dietary supplements, energy drinks,
caffeinated beverages, or green tea. These restrictions were
continued throughout the study based upon self-declaration in
the daily dietary diary and verbal confirmation.
1. RMR and PPEE Measurement. Energy expenditure/
caloric metabolism activity indicated by RMR and PPEE was
measured by breath oxygen volume (VO2; ml/min) using a
handheld indirect calorimeter (MedGem test kit, Health Tech
Inc, Golden, CO) [18,19]. Testing conditions were standardized across all subjects and followed previously established
recommendations [19]. RMR and PPEE were measured for 10–
15 minutes after at least 15 minutes of rest. A total of 8 subjects
(21–51 years, age ¼ 34.5 6 7 years, body mass index [BMI] ¼
28.2 6 2 kg/m2) were enrolled in and completed a randomized,
double-blind, placebo-controlled, multiple-period crossover
study. All test subjects randomly consumed 1 test-sample
preparation on a test day. They repeated the same sample in a
duplicate measurement on a different day. Test days were at
least 1 week after the previous sample intake. On a test day, a
basal metabolic rate was measured after at least a 12-hour
overnight fast. Subjects then consumed a nutritional beverage
(Boost Plus, Nestle Healthcare Nutrition Inc, Minneapolis,
MN) with a known amount of calories (360 kcal) as breakfast
and to stabilize the RMR throughout the 4-hour testing period
[20]. In addition to this nutritional beverage, a single bolus
containing 120 ml of 1 of 3 different doses of L. barbarum (30,
60, and 120 ml) or placebo control samples was given to the
subjects. Total consumption volume of the test samples was
120 ml each time, and 90 or 30 ml of placebo solution was
added to the 30- or 60-ml L. barbarum sample solution,
respectively, and mixed well immediately before consumption.
RMR was measured immediately before (baseline), 1, 2, and 4
hours after sample intake [21]. The research procedure is
shown in Fig. 1.
2. Waist Circumference and Morphometric Changes. A
randomized, placebo-controlled, double-blind clinical study
was performed over a 14-day intervention period to evaluate
the effect of L. barbarum, relative to placebo (120 ml/d), on
waist circumference and other morphometric parameters.
Subjects were randomly assigned to either the L. barbarum
treatment group or placebo control. Physical morphometric
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L. barbarum (Goji ) Stimulates Metabolic Rate
measurements were taken at the pre-, middle-, and postintervention periods following an overnight 12-hour fast and
included body weight, BMI (Seca 703, Hamburg, Germany),
waist circumference at the level of umbilicus [22,23], and
total body fat (Tanita BF-679W, Tokyo, Japan). All
participants were monitored daily to ensure full compliance
with the protocol, including sample consumption and
restriction of dietary intake. Compliance was confirmed by
the daily consumption of the samples in front of the research
coordinator and also checked by returned empty sample
bottles every day on weekdays and the Monday after the
weekend. Individuals administering the physical exams were
blinded as to the treatment conditions, and the treatment codes
were not broken until the study was completed. L. barbarum
or placebo sample consumption was combined with a diet
restriction and exercise program in overweight/obese subjects
with a BMI .25 kg/m2 (25.6–45.3 kg/m2; average BMI, 29.3
6 1.1 kg/m2). Based upon our previous studies [6–9], a
sample size of 35 subjects was deemed to be sufficient to
detect effectiveness of L. barbarum with 95% confidence and
80% power. A total of 33 healthy adults (19–60 years;
average age, 33.6 6 1.9 years) consumed 90 ml of L.
barbarum or placebo each morning with a meal and 30 ml at
bedtime for a period of 14 days. Daily 15-minute walks (after
lunch during weekdays) were implemented for all subjects.
Subjects also wore study-provided pedometers and daily steps
were recorded in a log. Caloric intake per day was restricted to
approximately 1200 kcal during the 14-day intervention
period by means of daily dietary diaries maintained by the
subjects, 67% of whom were women. Four dropped out (2 in
each group) due to personal issues not related to the sample or
study.
Statistical Analysis
Dietary intake data were analyzed with the nonparametric
Mann-Whitney U test (placebo vs L. barbarum). All
parametric data (body weight, height, BMI, waist circumference, body fat lean mass, VO2, and RMR) were analyzed by an
analysis of variance for independent and dependent groups.
Descriptive statistics were calculated for placebo and L.
barbarum for all dependent measures and summarized as
means and standard errors. The data were processed using
Statistica version 8 (StatSoft Inc, Tulsa, OK). Differences were
considered significant at p , 0.05.
Fig. 1. Testing procedure of resting metabolic rate (RMR) and
postprandial energy expenditure (PPEE) measurement. RMR and
PPEE were measured by breath oxygen volume (VO2; ml/min) using a
handheld indirect calorimeter in a randomized, double-blind, placebocontrolled, multiple-period crossover study. All test subjects consumed
1 of 8 separate test samples that were presented randomly at weekly
intervals, and each sample was tested twice. Study period was up to
120 days.
27.17 kcal/d. The placebo and all single boluses of various
dosages of L. barbarum intake with nutritional beverage (360
kcal) increased RMR calculated from VO2 measurement over
the baseline level. At 1 hour postintake, 120 ml of L.
barbarum intake increased 58.26 6 5.72 ml/min of VO2 over
the baseline level and was significantly higher than the
placebo group (24.58 6 4.04 ml/min) (p , 0.05) (Fig. 2A).
At 4 hours postintake, placebo control and all doses of
L. barbarum except 120 ml intake returned to the baseline
level. Conversely, VO2 level after 120 ml of L. barbarum
intake was maintained at a significantly higher level than
other doses of L. barbarum or placebo control group (p ,
0.05) (Fig. 2A).
The area under the curve (AUC) of VO2 during 0 to 4 hours
postintake of placebo control sample was 10.42 6 4.09 L in 4
hours. The AUC of VO2 after 120 ml of L. barbarum intake
was significantly increased by 32.19 6 3.01 L in 4 hours,
which was more than twice that of the placebo level (p , 0.05)
(Fig. 2B). This stimulus effect of L. barbarum on metabolic
rate/energy expenditure occurred in a dose-dependent manner
(Fig. 2A,B).
Waist Circumference
RESULTS
Resting Metabolic Rate and Postprandial Energy
Expenditure
The average baseline level of VO2 in all subjects was
253.58 6 13.13 ml/min, which was equivalent to 1761.04 6
306
In the 14-day intervention study, daily intake of L.
barbarum combined with exercise and dietary restriction was
found to decrease waist circumference significantly in both
midintervention and postintervention (p , 0.01) (Fig. 3). The
reduction in waist circumference in the L. barbarum group
(n ¼ 14) at postintervention on day 15 was 5.54 6 0.65 cm
compared with that at preintervention (Fig. 3). In the placebo
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L. barbarum (Goji ) Stimulates Metabolic Rate
Fig. 3. Changes of the waist circumference in human subjects during
and after the 14-day intervention period. Each value indicates mean 6
standard error of measurement (in centimeters). ** indicates significant
difference from the preintervention level and the placebo group (p ,
0.01).
exercise and diet restriction, has a significant effect on waist
circumference.
DISCUSSION
Fig. 2. Dose-response relationship of Lycium barbarum on the (A)
kinetic changes and (B) area under the curve (AUC) of the breath
oxygen level (VO2) analyzed by the indirect calorimeter during the 4
hours after consumption. Each value indicates mean 6 SEM. *
indicates significant increase from control level (p , 0.05).
group (n ¼ 15), the change in waist circumference on day 15
from the preintervention was only 0.88 6 0.83 cm, and
no significant difference was found from preintervention.
Other morphometric parameters, such as body weight, BMI,
and total body fat did not show any statistically significant
differences from the preintervention measurements in either
group. Average change in body weight on day 15 in the L.
barbarum group from the preintervention was 0.40 6 0.37 kg
and that in the placebo group was 0.10 6 0.17 kg (other data
not shown). Thus, L. barbarum, in combination with modest
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
The preliminary results shown in the present studies suggest
that L. barbarum may have provoked an increase in energy
expenditure. In addition, it may lead to a reduction in central
adiposity, as indicated by the reduction in waist circumference
when combined with moderate dietary caloric intake restriction
and mild exercise. The active compound of L. barbarum, LBP,
is reported to enhance food conversion rate in murines and to
reduce their body weight after 10–21 days of consumption
[1,2]. These results suggest that L. barbarum can modulate
metabolism in vivo and may correspond with the present
study’s result regarding the effects of L. barbarum on RMR/
PPEE and waist circumference. These metabolic effects may
also be related to the changes in adrenocortical hormone levels
that contribute to energy regulation and obesity control. Our
preliminary randomized, double-blind, placebo-controlled human pilot trial with 5 male subjects has shown that a singlebolus intake of L. barbarum (120 ml) significantly reduced
fasting salivary levels of cortisol and dehydroepiandrosterone
at 7 am by 46% and 27%, respectively, compared with the
placebo control group (p , 0.05). Because cortisol has been
reported to increase obesity and metabolic syndrome [24],
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L. barbarum (Goji ) Stimulates Metabolic Rate
reduction of cortisol by L. barbarum may be related to the
increased metabolic rate and decreased waist circumference.
Further studies are necessary to confirm the effect on cortisol
and related hormone levels, as well as to clarify an interaction
with other intrinsic factors such as thyroid hormone levels,
which also play important roles in a metabolic system.
The obesity epidemic is a major public health problem
worldwide. Adult obesity is associated with increased morbidity and mortality [11–16]. Metabolic rate/energy expenditure
was acutely and significantly increased by L. barbarum intake
compared with the placebo control, and this effect may be
dose-associated with the level of L. barbarum. The in vivo
enhancement of the metabolic rate by L. barbarum intake may
contribute to changes in waist circumference and waist-related
parameters observed in the present studies. The lack of change
in body weight may reflect (1) insufficient duration of exposure
to L. barbarum and its bioactive compounds because the
present studies were short-term trials, and (2) actions of L.
barbarum may be specific to the central adiposity, independent
from weight loss, as shown in a similar case with capsinoid
treatment [25]. Capsinoid has been reported to significantly
reduce abdominal fat without a significant body-weight
reduction. Although it has been reported that oral administration of LBP reduced serum total cholesterol, low density
lipoprotein, and triglyceride concentrations and increased high
density lipoprotein levels in rabbits and mice [26–28], detailed
analysis of the effect of L. barbarum on the fatty acid
metabolism in vivo was not performed in the present studies.
Therefore, detailed central adiposity analysis by dual-emission
x-ray absorptiometry and lipid metabolism profile tests are
required.
Although the present preliminary studies are the first
clinical report to show various unique metabolic effects of L.
barbarum, there are limitations in these studies because (1)
each study had a small number of the subjects, and (2) the
studies were short in duration, a 14-day intervention or a
single-bout intake. Therefore, a larger and more long-term
study is required to clarify further the effects of L. barbarum on
body weight, metabolic syndrome, and glucose and fat
metabolism in humans in order to confirm the efficacy and to
identify the mechanisms of actions of L. barbarum.
CONCLUSION
These are the first randomized clinical trials to evaluate the
role of L. barbarum in the metabolic parameters in humans.
Our results suggest that L. barbarum may stimulate metabolic
rate, and these effects may be related to the changes in waist
circumference produced by daily consumption of L. barbarum
in the form of fruit juice (GoChi ) for 14 days. Further studies
will determine the effects of long-term consumption of L.
308
barbarum on body weight as well as on the development and
progression of diabetes and metabolic syndrome.
ACKNOWLEDGMENTS
Authors thank Marie-Pierre St-Onge, PhD, at Columbia
University, Richard Rivlin, MD, at Cornell University, and
Cynthia Thomson, PhD, at University of Arizona, for their
generous advice to the research and reviewing this manuscript.
All sources of financial support came from FreeLife International.
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Received July 22, 2010; revision accepted August 25, 2011.
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