Pharmacokinetic and The Effect of Capsaicin in Capsicum frutescens on Decreasing Plasma Glucose Level

Pharmacokinetic and The Effect of Capsaicin in Capsicum
frutescens on Decreasing Plasma Glucose Level
Kamon Chaiyasit MSc*,
Weerapan Khovidhunkit MD, PhD**, Supeecha Wittayalertpanya MSc***
* Inter-department of Pharmacology, Graduate School, Chulalongkorn University, Bangkok, Thailand
** Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
*** Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Background: The active substance found in Capsicum frutescens (capsicum) that gives hot and spicy flavor is
capsaicin, and it seems to have many pharmacological effects.
Objective: The present research was conducted to study the effect of capsicum on plasma glucose level and to
correlate its action with the pharmacokinetic properties of capsaicin in capsicum.
Material and Method: The crossover study was performed in 12 healthy volunteers by performing the OGTT
while receiving placebo or 5 grams of capsicum. The insulin secretion and capsaicin level in plasma were
measured using the HPLC method.
Results: The results of the OGTT showed that plasma glucose levels in volunteers who received capsicum were
significantly lower than those in the placebo group at 30 and 45 minutes (p < 0.05). Furthermore, plasma
insulin levels were significantly higher at 60, 75, 105, and 120 minutes (p < 0.05). When comparing before
and after capsicum intake, the results showed the insulin levels were maintained. The pharmacokinetic
parameters of capsaicin shown as C
, T
, AUC , T are 2.47 + 0.13 ng/ml, 47.08 + 1.99 min, 103.6 + 11.3
max
max
0-t
1/2
ng.min/ml, and 24.87 + 4.97 min, respectively.
Conclusion: In conclusion, the present study found that 5 grams of capsicum presented capsaicin levels that
were associated with a decrease in plasma glucose levels and the maintenance of insulin levels. The present
result might have clinical implications in the management of type 2 diabetes.
Keywords: Capsaicin, Capsicum frutescens, Pharmacokinetic, Insulin, Plasma glucose
J Med Assoc Thai 2009; 92 (1): 108-13
Full text. e-Journal: http://www.mat.or.th/journal
Capsicum frutescens is a household vegetable
Resiniferatoxin (RTX) can activate this receptor leading
that has been consumed for a long time. The active
to many physiological effects(3-5). Akiba Y et al first
substance that gives the hot and spicy flavor was
reported the discovery of TPRV1 on the beta cells of
identified as capsaicin(1). A number of research studies
pancreas and found that capsaicin could activate this
have shown multiple pharmacological effects of
receptor resulting in an increase in insulin secretion(6).
capsaicin on a variety of physiological systems such
Chaiyata P et al found that capsicum could decrease
as cardiovascular system, gastro-intestinal tract,
the plasma glucose levels but the actual mechanism
metabolic rate, and pain relief(1,2).
was unknown(1), while Monsereenusorn et al reported
The action of capsaicin is mediated by TPRV1
that capsaicin could inhibit the glucose absorption into
(vanilloid receptor), which belongs to an ion channel
bloodstream(7-9). On the contrary, Gyula et al reported
group. Not only capsaicin but also heat, proton, and
that pure capsaicin activated glucagon secretion and
increased the plasma glucose level(10). Therefore, the
Correspondence to: Wittayalertpanya S, Department of
Pharmacology, Faculty of Medicine, Chulalongkorn
effect of capsaicin on plasma glucose levels in humans
University, Bangkok 10330, Thailand.
is still conflicting.
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There are some researches about the pharma-
Chemical and instrument
cokinetic of capsaicin on plasma glucose level in
The fresh capsicum that was used through-
testing animals but the results are inconsistent. The
out the present study came from the same lot and
aim of the present research was to study the effect of
appeared in a green color, weighed approximately 0.6
capsicum, which provides capsaicin as an active
gram per piece and was obtained from Pathum Thani,
compound, on plasma glucose and insulin levels in
Thailand. Five grams of capsicum provided 26.6
healthy volunteers and to study the pharmacokinetic
milligram of capsaicin as tested by the Department of
properties of capsaicin.
Pharmaceutical Technology, Faculty of Pharmaceutical
Science, Naresuan University.
Material and Method
Capsaicin standard was obtained from Sigma
Subject
Chemical Co, Germany. Acetonitrile, diethyl ether,
The present study was approved by the Ethic
acetic acid, and methanol (HPLC grade) were obtained
Committee of the Faculty of Medicine, Chulalongkorn
from MERCK, Germany.
University. Twelve healthy male volunteers were
High-performance liquid chromatography
recruited in the present study. All were considered
(HPLC): Spectra system isocratic pump (PC1000),
healthy by physical examination, and had no history
Spectra system autosamples (AS3000), Spectra
of capsicum allergy, gastrointestinal, liver, and renal
system fluorescence detector, Spectra system SN
diseases. They can tolerate hot spicy food well. They
4000, and Computer and a software program P1000
were nonsmokers. All of them abstained from alcohol
were from Thermo separation product. Column was use
and medications at least one month before the present
?-bondapak size 250 x 4.6 millimeters with silica C18
study(11,12). Furthermore, they had to abstain from
size 5 microns were obtained from Water Associates,
capsaicin-containing food for at least seven days
USA.
before the present study. The method and condition of
the present study were clearly explained to all partici-
Study design
pants. Informed consent was signed and obtained
After an 8-hour overnight fast, the subjects
from each person prior to entering the experiment.
were given 75 grams of glucose diluted in 150 ml of
water for oral glucose tolerance test (OGTT). Then
they were administered capsicum (5 g) contained in
a gelatin capsule or placebo. Blood samples were
collected every 15 minutes until 2 hours to measure
Table 1. Demographic and clinical laboratory data of
subjects recruited in the study (n = 12)
the glucose level. The crossover was done after a
one-week washout period.
Demographic and
Mean + SD
For insulin baseline determination, after an
clinical laboratory data
overnight fast, all subjects were given a placebo and
the serum samples were collected every 15 minutes
Sex
Male
for 2 hours. After that they were given 5 grams of
Age (year)
21.83 + 1.47
capsicum, the blood samples were collected to measure
BW (kg)
65.80 + 6.51
Ht (m)
1.74 + 0.05
the insulin level using the same process. To measure
BMI
21.80 + 1.40
capsaicin level, blood samples were collected every
PR
70.92 + 7.65
10 minutes for the first 1 hour and every 15 minutes for
SBP (mmHg)
108.33 + 10.30
the next hour.
DBP (mmHg)
75.00 + 7.07
The research was carried out according to
Hemoglobin (g/dl)
14.62 + 0.91
Good Clinical Practice (ICH/GCP) guidelines. The
Hematocrit (%)
43.81 + 2.45
research protocol was approved by the Institutional
Glucose (mg/dl)
86.50 + 5.00
Review Board of the Faculty of Medicine, Chulalongkorn
BUN (mg/dl)
11.83 + 2.75
University, Bangkok, Thailand.
Creatinine (mg/dl)
0.89 + 0.13
AST (U/L)
19.50 + 4.98
ALT (U/L)
17.58 + 7.89
Methods
Alkaline phosphatase (U/L)
59.17 + 15.28
Plasma glucose level was measured by a
Anti HIV
Negative
standard glucose oxidase assay(13). Serum Insulin
HBsAg
Negative
level was measured by an electrochemiluminescent
J Med Assoc Thai Vol. 92 No. 1 2009
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immunoassay using Elecsys 2010/1010 machine(14).
Plasma capsaicin level was measured by an HPLC
method using column C18 and mobile phase, which
was composed of water, acetonitrile and acetic acid in
the ratio of 50:50:1. A fluorescence detector was used
for capsaicin measurement.
Method for capsaicin analysis was validated
following Guidance for industry: Bioanalytical method
validation (U.S. Department of Health and Human
Series FDA, CDER, CVM. May 2001, BP).
Statistical analysis
The data including plasma glucose level,
Fig. 1
Change in plasma glucose levels after an OGTT
serum insulin level and plasma capsaicin level were
(n = 12). Comparison between capsicum and
demonstrated as mean + S.E.M. ANOVA for two-way
placebo group. The results are expressed as mean +
crossover design was used to analyze the difference
S.E.M. ( statistical significant different, p < 0.05)

in plasma glucose level at each time point between
the capsicum group and the placebo group. One-way
ANOVA was used to analyze the changes in serum
insulin level at different time points compared to that
before the test. Pair t-test was used to analyze the
difference in insulin level at each time point and the
area under the curve (AUC) of serum insulin and
plasma glucose levels between the two groups. The
result was considered significant if a p-value was less
than 0.05.
Results
Plasma glucose levels were lower in volunteers
given capsicum than those in the placebo group, which
were statistically significant at 30 and 45 min (p < 0.05)
(Fig. 1). The AUC of plasma glucose level vs. time in
the capsicum group was also significantly less than
Fig. 2
Changes in serum levels of insulin (n = 12). Com-
that in the placebo group (12,686.6 + 457.9 mg.min/dl
parison between capsicum and placebo group. The
vs. 14,265.5 + 631.5 mg.min/dl, p < 0.05). The insulin
results are expressed as mean + S.E.M. (+ significant
levels in the capsicum group were significantly higher
different, p < 0.05 between group, significant

different p < 0.05 compared with time 0)
than those in the placebo group at 60, 75, 105, and
120 min (p < 0.05), as shown in Fig. 2. Additionally,
the AUC of insulin level vs. time of in the capsicum
group was significantly higher than that in the placebo
group (526.4 + 86.9 microIU.min/dl vs. 332.3 + 69.7
Pharmacokinetic study of capsaicin in Capsicum
microIU.min/dl, p < 0.05).
frutescens
In the comparison of insulin level before and
After capsicum ingestion, capsaicin can be
after the intervention, it was found that when the
first detected in the plasma at 10 minutes. The peak
placebo was given, the insulin levels were significantly
plasma concentration (C
) of capsaicin was 2.47 +
max
decreased continuously at 60, 75, 105, and 120 min (p <
0.13 ng/ml and T
47.08 + 1.99 minutes. The amount
max
0.05). In contrast, when capsicum was given, there were
of capsaicin absorbed into the body as presented
no different changes in the insulin level compared to
by AUC was 103.6 + 11.3 ng.min/ml. The results are
0-t
that before received capsicum. This result suggested
shown in Table 2. The mean pharmacokinetic profile
that the insulin levels were maintained when capsicum
of plasma capsaicin level vs. time of all 12 healthy
was taken.
volunteers is illustrated in Fig. 3.
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Tabel 2. Pharmacokinetic parameters of capsaicin in healthy
suggested that the effect of capsaicin on insulin
volunteers (n = 12)
secretion is due to more calcium influx into the cells(6).
Beside the effect on insulin secretion, capsaicin may
Pharmacokinetic parameters
Mean + S.E.M.
decrease plasma glucose by other mechanisms since
Monsereenusorn et al found that capsaicin could
C
(ng/ml)
2.47 + 0.13
max
T
(minute)
47.08 + 1.99
inhibit glucose absorption from the intestine in canines
max
AUC (ng.min/ml)
103.60 + 11.3
and rodents(8,9).
0-t
T (minute)
24.87 + 4.97
The present study also proved the question
1/2
of whether capsaicin from capsicum can be absorbed
into the body and that can support the decreasing
plasma glucose of capsicum might be from this active
substance. Up to now, there has been no report of the
pharmacokinetic study of capsaicin in human. The
only study was performed in in situ of white guinea
pigs, which showed that the absorption of capsaicin
occurred in many parts of the gastrointestinal tract.
Capsaicin was absorbed 50% in the stomach, 80% in
the jejunum part, and 70% in the ileum part. The result
showed that capsaicin was best absorbed in the
jejunum and was a non-energy consumed absorption,
which was absorbed into a portal system excluding
mesenteric lymphangial. In the present study, the
authors developed a method for capsaicin detection
Fig. 3
Pharmacokinetic profile of capsaicin in healthy
in the circulation, which showed good accuracy and
volunteers (n = 12), (mean + S.E.M.)
precision. The lower limit of quantization of capsaicin
was 0.93 ng/ml. This research found that capsaicin
was absorbed so rapidly that it could be detected at
10 minutes after ingestion. Furthermore, capsaicin
Discussion
was rapidly metabolized as the half-life of capsaicin
The present study showed that intake of
was 24.87 + 4.97 minutes and the capsaicin level
5 grams of fresh capsicum, which contained approxi-
was maintained only to 90 minutes. These results are
mately 26.6 milligrams of capsaicin by OGTT test, was
consistent with a short T value of capsaicin in
1/2
associated with lower plasma glucose levels at 30
rats reported by Surh et al(2). The rate and extent of
and 45 minutes. In addition, those who took fresh
capsaicin absorption into the body in the terms of C
,
max
capsicum had significantly higher insulin levels and
T
and AUC were 2.47 + 0.13 ng/ml, 47.08 + 1.99
max
0-t
insulin amount compared to those in the placebo
minutes and 103.6 + 11.3 ng.min./ml, respectively. The
group. Furthermore, it has been found that the insulin
low C
of capsaicin could also be explained by the
max
levels were maintained to the basal level after intake
rapid metabolism while being absorbed. Kawada et al
capsicum compared with continuously decreased
and Leelahuta et al have previously demonstrated that
insulin level in the placebo group.
in white guinea pigs, capsaicin was metabolized by
The results of the present study are consistent
CYP2E1 into N-(4,5-dihydroxyl-3-methoxybenzyl)-
with a previous report by Tolan et al. They performed
acylamide, which is a catechol, and other substances
the test on canines under OGTT method and found
such as vanillic acid(17).
that the fresh capsicum had lower plasma glucose
The time course of capsaicin level in the plasma
levels and higher insulin levels than those in the
after ingestion was correlated to the time of plasma
placebo group. They suggested that plasma glucose
glucose decreasing and serum insulin maintaining.
decrease could be caused by capsicum inducing
The authors found that capsaicin was detectable in the
insulin-secretion(15,16). Akiba et al has reported that
bloodstream starting at 15 minutes until 90 minutes,
the capsaicin receptor (TRPV1) is expressed on the
which was followed by a decrease in plasma glucose
beta cells of the pancreas and capsaicin could induce
levels from 15 minutes until 120 minutes and the main-
insulin secretion from the pancreas. It has been
tenance in insulin level from the basal level until 120
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minutes. The significant difference in plasma glucose
rats. Biochem Biophys Res Commun 2004; 321:
levels at 45 minutes was also correlated to C
of
219-25.
max
capsaicin at 45 minutes.
7. Jonietz P. Effect of red pepper and capsaicin on
rat intestinal disaccharidases. J Sci Soc Thailand
Acknowledgement
1982; 8: 53-7.
This study was supported by the grant of
8. Monsereenusorn Y, Glinsukon T. Inhibitory effect
The 90th Anniversary of Chulalongkorn University
of capsaicin on intestinal glucose absorption in
Fund (Ratchadaphiseksomphot Endowment Fund)
vitro. Food Cosmet Toxicol 1978; 16: 469-73.
and Cerebos Awards of Thailand. The authors wish to
9. Monsereenusorn Y, Glinsukon T. Effect of capsaicin
thank Assistant Professor Dr. Sakchai Wittaya-areekul,
on plasma glucose level and intestinal glucose
Department, of Pharmaceutical Technology, Faculty
absorption in vivo. Mahidol Univ J Pharm Sci
of Pharmaceutical Science, Naresuan University for
1980; 7: 9-12.
his kindness of capsaicin measurement in Capsicum
10. Domotor A, Szolcsanyi J, Mozsik G. Capsaicin
frutescens.
and glucose absorption and utilization in healthy
human subjects. Eur J Pharmacol 2006; 534: 280-3.
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???????????????????? capsaicin ??????????????????????????????????????????????????
???????????????????????????????????
??? ?????????, ?????????? ??????????, ?????? ?????????????
????????: ????????????????????????????????????????????????? ????????????????????????????????????????????????
??????????????? capsaicin ???????? capsaicin ????????????????????? ? ????????????????????
????????????: ??????????????????????????????????????????????????? ????????????????????????? capsaicin
????????????
???????????????: ?????????????????????? 12 ?? ?????????????? OGTT ???????????????? placebo ???
???????????????? 5 ???? ?????????????????????????????????? placebo ??????????????????????????? ??????????
???????????????????????????????????????? capsaicin ???????????????????? HPLC
??????????: ?????????????????????????????????????????????????????????????? OGTT ???????????????????????
?????????????????? placebo ?????????? 30 ??? 45 ??????????????????????????????????????????? (p < 0.05)
?????????????????????????????????????????????????????????????????????????? placebo ?????????? 1 ???????, 1 ???????
15 ????, 1 ??????? 45 ???? ??? 2 ?????????????????????????????????????????????? (p < 0.05) ??????
????????????????? capsaicin ?????? ??? C ??????? 2.47 + 0.46 ????????/????????? ??? T ??????? 47.08 +
max
max
6.89 ???? ??? AUC ??????? 103.6 + 38.99 ????????.????/ ????????? ?????? T ??????? 24.87 + 17.2 ????
0-t
1/2
????: ???????????????????????????????? 5 ???????????????????????????????????????? ????????????????
??????????????????? ????????????????????? capsaicin ????????????????????????????????????????????????
?????????????????????????????????????????????????????????????????? 2 ?????
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