The Scientific World Journal
Volume 2012, Article ID 594657, 8 pages
NoniJuiceImproves SerumLipidProfiles and
OtherRisk Markers inCigarette Smokers
GaryAnderson,1andBrett J. West3
1Department of Pathology, University of Illinois College of Medicine at Rockford, 1601 Parkview Avenue, Rockford, IL 61107, USA
2Department of Family and Community Medicine, University of Illinois College of Medicine at Rockford,
1601 Parkview Avenue, Rockford, IL 61107, USA
3Department of Research and Development, Morinda Inc., 737 East 1180 South, American Fork, UT 84003, USA
Correspondence should be addressed to Brett J. West, brett email@example.com
Received 11 July 2012; Accepted 13 September 2012
Academic Editors: W. Gelderblom, S. Knasmuller, P. Maˇ cek, and R. Pohjanvirta
Copyright © 2012 Mian-Ying Wang et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
Cigarette smoke-induced oxidative stress leads to dyslipidemia and systemic inflammation. Morinda citrifolia (noni) fruit juice
has been found previously to have a significant antioxidant activity. One hundred thirty-two adult heavy smokers completed a
randomized, double blind, placebo-controlled clinical trial designed to investigate the effect of noni juice on serum cholesterol,
triglyceride, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), high-sensitivity C-reactive
protein (hs-CRP), and homocysteine. Volunteers drank noni juice or a fruit juice placebo daily for one month. Drinking 29.5mL
to 188mL of noni juice per day significantly reduced cholesterol levels, triglycerides, and hs-CRP. Decreases in LDL and homocys-
teine, as well increases inHDL, were also observed among noni juice drinkers. The placebo, which was devoid of iridoidglycosides,
an activity associated with the presence of iridoids.
Cigarette smokers continuously inhale thousands of car-
cinogens and free radicals. It is estimated that about 1017
oxidant molecules are present in each puff of cigarette smoke
. Free radicals are known to cause oxidative damage
by increasing polymorphonuclear leukocytes and by induc-
ing lipid peroxidation [2, 3]. Additionally, several markers
of oxidative stress are elevated in cigarette smokers. These
include increased release of reactive oxygen species from
phagocytes, such as superoxide from peripheral blood neu-
trophils, oxidized low density lipoprotein cholesterol (LDL),
increased lipid hydroperoxides and malondialdehyde, and
decreased plasma antioxidant capacity [4–11].
Among the many adverse health effects from cigarette
smoke are dyslipidemia and systemic inflammation. The
fact that cigarette smoke increases total cholesterol and tri-
glycerides, as well as decreases high density lipoprotein
cholesterol (HDL), has long been established. A meta-
analysis of 54 studies revealed that smokers have about 3%
higher serum cholesterol and 9% greater serum triglyceride
concentrations than nonsmokers. Smokers were also found
to have 5.7% lower HDL than nonsmokers . The
increases in total cholesterol and triglycerides, with the
corresponding decreases in HDL, were found to be dose-
dependent when the data were analyzed by smoking fre-
quency. Population-based studies have also revealed that
(CRP), are also elevated in smokers as well as those exposed
to second-hand smoke [13, 14]. Smoking-related elevations
in CRP are also accompanied with a rise in serum homocys-
teine levels .
While the molecular mechanisms of tobacco smoke
toxicity are still not fully understood, free radical-mediated
oxidative stress is believed to play a central role [16, 17].
Oxidative stress, as measured by serum malondialdehyde
2 The Scientific World Journal
concentration, is positively correlated to elevated triglyceride
and cholesterol levels in smokers . Not only does
cigarette smoke increase oxidative stress by increasing free
radicals but also by weakening of antioxidant defenses, such
tions lead to the damage of mitochondria , and cigarette
smoke may even induce liver injury via lipid peroxidation
and corresponding inflammation [21, 22]. Such alterations
are likely to lead to imbalances in lipid metabolism.
Fruits and vegetables are major sources of dietary
antioxidants. Epidemiological studies indicate that fruits
and vegetables may reduce free radical-induced oxidative
damage and lipid peroxidation in cigarette smokers .
in many tropical regions of the world. Noni fruit has a
significant history of use as both food and medicine among
Pacific Islanders and in Southeast Asia [24, 25]. Various
potential health benefits of noni fruit have been reported
activities in vitro and in vivo [29–31]. Noni juice has been
found to exert an antioxidant effect in human athletes,
resulting in increased endurance . Noni juice also
lowered plasma concentrations of superoxide anion radicals
and lipid hydroperoxides in heavy smokers . Given its
demonstrated antioxidant activity, noni juice may also
reduce some of the deleterious effects of cigarette smoke. As
such, the current study was designed to investigate the influ-
ence of noni juice on serum cholesterol, triglyceride, LDL,
HDL, high-sensitivity C-reactive protein (hs-CRP), and
homocysteine levels in current heavy smokers.
2.1. Study Ethics. The research protocol of this trial was
approved by the Institutional Review Board Committee of
the University of Illinois College of Medicine at Rockford.
Written informed consent was obtained from all study
participants. The trial was conducted in accordance with the
Declaration of Helsinki.
ers were enrolled in this trial. Inclusion criteria were ages
18 to 65 years, smoker of more than 20 cigarettes per day,
a smoking history exceeding one year, and no concurrent use
of prescription medication or antioxidant vitamins, or use
of these in the previous three months. All study participants
were interviewed and asked to complete a demographic and
health information questionnaire. Study participants were
randomly assigned to a 118mL placebo (n = 26), 29.5mL
noni juice (n = 51), or 118mL noni juice dose group (n =
55). Males and females were enrolled in equal proportions.
2.3. Noni Fruit Juice and Placebo. The European Union-
approved form of noni fruit juice (Tahitian Noni Juice,
Morinda Inc., Provo, Utah) was used for this trial. The
placebo consisted of a blend of grape and blueberry juices
and natural cheese flavor to mimic the flavor of the noni
juice. It also served as an iridoid deficient fruit juice control.
to treatment group assignments. Those in the 29.5mL group
were asked to drink the noni juice all at once in the morning
and on an empty stomach. Those in the other two groups
were asked to drink 59mL twice daily (118mL daily total),
once in the morning on an empty stomach and once before
were not asked to alter their smoking habits during the
intervention period, and an assumption was made that they
continued to smoke in the same manner (amount and
duration) as they had before enrollment in the trial.
2.5. Serum Preparation and Analysis. Ten mL of whole blood
was drawn from each participant upon enrollment and again
at completion of the intervention period. Blood samples
were drawn into tubes and held at 4◦C for 2-3 hours, then
centrifuged at 1,500×g for 20 minutes to separate the serum.
Serum samples were sent to the Central Laboratory of the
University of Illinois Chicago Medical Center for lipids, hs-
CRP, and homocysteine analyses.
2.6. Statistical Analysis and Data Interpretation. A power
analysis was performed to estimate the number of cases
needed to detect a significant effect . Since the study was
designed to compare pre- and postdata, all analyses were
conducted on paired cases in each group. To assess the influ-
ence of noni juice and placebo on the serum measurements,
averages were compared before and after the intervention in
using a paired Student’s t-test.
2.7. Chemical Analyses. Iridoid contents, specifically deacet-
determined by high performance liquid chromatography
(HPLC), according to a previously reported method .
HPLC grade acetonitrile (MeCN), methanol (MeOH), and
water were obtained from Sigma-Aldrich (St. Louis, MO,
USA). Analytical grade formic acid was purchased from
Spectrum Chemical Mfg. Corp. (New Brunswick, NJ, USA).
Deacetylasperulosidic acid (DAA) and asperulosidic acid
by HPLC, mass spectrometry, and nuclear magnetic res-
onance (NMR) to be higher than 99%. They were accurately
weighed and then dissolved in an appropriate volume of
MeOH to produce corresponding stock solutions. The work-
ing standard solutions of DAA and AA for the calibration
curves were prepared by diluting stock solutions with MeOH
in seven concentration increments ranging from 0.00174–
1.74 and 0.0016–0.80mg/mL, respectively. All stock and
working solutions were maintained at 0◦C. Samples of noni
juice and placebo were diluted with MeOH-H2O (1:1)
and then filtered through a 0.45µm nylon membrane filter.
Chromatographic separation was performed on a Waters
2690 Separations Module coupled with a 996 Photodiode
Array (PDA) detector, equipped with a C18 column (4.6mm
× 250mm; 5µm, Waters Corporation, Milford, MA, USA).
The pump was connected to two mobile phases, A; MeCN,
The Scientific World Journal3
Table 1: Comparison of baseline and posttest serum measurements among placebo and noni juice groups.
Dose group and sampling time
29.5mL noni juice
118mL noni juice
aP < 0.001 compared to placebo (posttest) and baseline,bP < 0.05 compared to placebo (posttest), andcP < 0.05 compared to baseline.
Total cholesterol (mg/dL)Triglycerides (mg/dL)hs-CRP (mg/L)
239.2 ± 9.4
246.6 ± 16.9
254.2 ± 54.2
281.7 ± 37.3
1.48 ± 2.16
2.22 ± 1.79
250.2 ± 36.75
186.2 ± 53.3a
325.9 ± 152.0
191.5 ± 131.4a
1.61 ± 1.55
1.39 ± 1.36b
242.3 ± 43.5
193.2 ± 70.5a
310.4 ± 163.4
218.8 ± 150.8b, c
1.72 ± 1.51
1.46 ± 1.39b, c
and B; 0.1% formic acid in H2O (v/v), and eluted at a
flow rate of 0.8mL/min. The mobile phase was programmed
consecutively in linear gradients as follows: 0–5min, 0% A;
40min, 30% A. The PDA detector was monitored in the
range of 210–400nm. The injection volume was 10µL for
each of the sample solutions. The column temperature was
maintained at 25◦C. Data collection and integration were
performed using Waters Millennium software version 32.
Analyses of other major secondary metabolites in noni
reported method . Scopoletin, rutin, quercetin, and
chlorogenic acid standards were accurately weighed and then
dissolved in an appropriate volume of MeOH/MeCN to pro-
duce corresponding stock and working standard solutions.
Chromatographic separation was performed on a Waters
2690 Separations Module coupled with a 996 PDA detector
and equipped with a C18 column. The mobile phase system
was composed of three solvents: A; MeCN, B; MeOH, and C;
0.1% TFA in H2O (v/v). The mobile phase was programmed
consecutively in linear gradients as follows: 0min, 10% A,
10% B, and 80% C; 15min, 20% A, 20% B, and 60% C;
26min, 40% A, 40% B, and 20% C; 28–39min, 50% A, 50%
B, and 0% C; 40–45min, 10% A, 10% B, and 80% C. The
elution was run at a flow rate of 1.0mL/min. The UV spectra
were quantified at 365nm.
Total polyphenols were determined by the Folin-
Ciocalteu method. Samples were centrifuged and diluted
1:10 with deionized water. The diluted samples (10µL)
were mixed with 800µL deionized water and 50µL Folin-
Ciocalteu (2N). Following incubation at room temperature
for a few minutes, 150µL NaCO3 (saturated) was added,
sample tubes shaken and allowed to incubate at room tem-
perature for 2 hours. Vehicle blanks and gallic acid standards
were prepared in the same manner. Following incubation,
the absorbance of the blanks, standards, and samples was
measured at 765nm in a microplate reader. Absorbance ver-
sus gallic acid concentration was used to create a calibration
curve. This curve was used to determine the total phenol
content of the samples. As noni fruit is a source of vitamin C
, concentrations of this vitamin in both the placebo and
noni juice product were also measured after pasteurization
3.1. Participant Demographics. There were no significant dif-
ferences in demographics between the groups. A 1:1 gender
ratio was maintained in each group, with mean ages ranging
from 37 to 43yr. The average number of cigarettes smoked
per day in each group was from 26 to 28.6, and average
pack-years (number of cigarettes smoked daily multiplied by
years of smoking) ranged from 32.12 to 32.49. The ethnic
compositions of each group were primarily Caucasian, 76–
juice group had a larger proportion of missed doses than
the 29.5mL group. The proportions of individuals missing
<5 doses in the 29.5mL and 118mL noni juice groups were
30% and 32%, respectively. The rates of those missing 5 to
10 doses in the same low- and high-dose groups were 2%
and 10%, respectively.
3.2. Changes in Lipid Profiles, hs-CRP, and Homocysteine.
Total cholesterol, triglycerides, and hs-CRP of the placebo
changes were observed in the placebo group during the trial,
even though there was a slight trend of increased values
after the 30-day period. In both noni juice groups, decreases
in mean cholesterol, triglyceride, and hs-CRP were observed.
Posttrial values were significantly lower than pretrial and
placebo group values. The sole exception was posttest
hs-CRP in the 29.5mL noni juice group, where it was sig-
nificantly lower than a mean posttest hs-CRP of the placebo
group (P < 0.05) but not significantly different from the
baseline average (P > 0.05). In the noni juice groups, average
total cholesterol, triglycerides, and hs-CRP decreased by
ison of posttrial values of both noni juice groups revealed no
of antioxidant activity that is reached by a daily dose of
29.5mL but may also be due to lower compliance in the
118mL noni group.
A stratified analysis of the aggregate baseline and posttest
total cholesterol, LDL, and triglyceride results of both noni
juice groups is provided in Table 2. In this analysis, strati-
fication is based on ranges of baseline, or initial, values of
4 The Scientific World Journal
Table 2: Total cholesterol (TC), LDL, and triglyceride levels within specified baseline ranges among the aggregate noni juice group (both
Total cholesterol (TC)
TC > 300mg/dL
aP < 0.001,bP < 0.05 compared to baseline.
204.4 ± 9.3
249.1 ± 21.5
328.7 ± 22.8
190.8 ± 41.6
203.9 ± 69.4a
256.4 ± 89.3b
154.6 ± 10.3
199.1 ± 20.5
287.7 ± 20.8
140.8 ± 21.6b
153.4 ± 1.4a
206.4 ± 39.3
184.1 ± 7.5
266.7 ± 48.0
553.6 ± 143.5
166.6 ± 95.3b
209.1 ± 129.3b
255.5 ± 219.7
for baseline serum cholesterol levels were 190–219mg/dL,
220–299mg/dL, and >300mg/dL, respectively. Low, middle,
and high strata for baseline triglyceride levels were 170–
199mg/dL, 200–399mg/dL, and >400mg/dL, respectively.
The purpose in such an analysis is to evaluate the effect of
noni juice relative to the degree of deviation from normal
population values. The decreases in total cholesterol, LDL,
and triglycerides that occurred in the lowest strata of ranges
were 6.6, 8.9, and 9.5%, respectively. Decreases in the same
measurements in the middle strata were 18.1, 22.9, and
21.6%, respectively. Corresponding trends in the high strata
of ranges were 22.0, 28.2, and 53.8%, respectively, but
only the total cholesterol change reached statistical signifi-
cance. This stratified analysis reveals that the magnitude of
effect increased as initial cholesterol or triglycerides levels
Stratified analysesof total cholesterol and triglycerides by
noni juice dose are provided in Table 3. Significant declines
in serum total cholesterol and triglycerides were observed in
the middle strata of each dose group. In the 29.5mL noni
juice group, significant decreases occurred in cholesterol of
A trend of greater reductions within higher baseline strata is
also apparent. Decreases in mean total cholesterol in the low,
middle, and high baseline strata of the 29.5mL group were
12.1, 17.3, and 36.4%, respectively. In the low, middle, and
high strata of this dose group, triglycerides declined by 10.5,
29.3, and 61.8%, respectively. Decreases in total cholesterol
in the low, middle, and high strata of the 118mL group
were 9.9, 29.2, and 23.6%, respectively, with corresponding
declines of 12.6, 25.2, and 41.7% in serum triglycerides.
associated with greater initial cholesterol or triglycerides
levels. The only exception was for the percent decline in
decrease was greater than that of the high stratum.
Homocysteine levels were reduced in the noni juice
groups. The aggregate mean (±standard deviation) at base-
line (19.7 ± 8.5µmol/L) declined by 23.9% to 15.0 ± 9.0
(P < 0.05). Conversely, aggregate mean HDL in the noni
juice groups increased from 49 ± 10 to 57 ± 9mg/dL (P <
3.3. Adverse Events. No adverse events were observed in the
placebo or noni juice groups during the intervention period.
3.4. Chemical Comparison of Noni Juice and Placebo. The
phytochemical compositions of the noni juice product and
placebo used in this trial are compared in Table 4. The total
polyphenol content of each of these was similar, with no
substantial difference in flavonoid (quercetin and rutin) or
chlorogenic acid concentrations. The vitamin C contents of
noni juice and placebo were not significant, with both being
less than 0.2mg/mL. Iridoids, which were present in signifi-
cant quantities in the noni juice product, were absent in the
placebo. Scopoletin was also detected in noni juice, but the
content was minor compared to the total iridoid concentra-
tion and was below the quantity previously demonstrated to
provide effective antioxidant action [38, 39].
Serum total cholesterol, LDL, triglycerides, hs-CRP, and
homocysteine were lowered in heavy smokers within 4 weeks
of noni juice ingestion. This observation is consistent with
previous reports in which supplementation with antioxidant
nutrients and plant extracts inhibited cigarette smoke-
induced dyslipidemia in vivo and in human intervention
studies [40–43]. It is also important to note that noni juice
did not produce any changes in human trials where par-
ticipants were already within normal healthy ranges. For
example, four weeks of daily supplementation of 30, 300, or
750mL noni juice did not cause any change in total choles-
terol, LDL, HDL, or triglycerides in 96 healthy volunteers
with normal lipid profiles and who were light smokers
(<5cigarettes/day) or nonsmokers . Also, no changes
occurred in total cholesterol, LDL, HDL, or triglycerides
levels in 34 diabetic patients, each with existing normal lipid
The Scientific World Journal5
Table 3: Total cholesterol (TC) and triglyceride levels within specified baseline ranges among noni juice dose groups.
29.5mL Noni juice 118mL Noni juice
Baseline Posttest BaselinePosttest
Total cholesterol (TC)
aP < 0.05 compared to baseline.
200.1 ± 7.1
236.2 ± 16.8
323.7 ± 18.6
175.8 ± 50.0a
195.3 ± 50.9a
205.7 ± 84.3
206.4 ± 10.5
262.8 ± 17.9
328.8 ± 27.8
186.0 ± 59.7
186.1 ± 74.1a
251.2 ± 87.3
184.6 ± 6.1
273.5 ± 52.2
547.4 ± 111.3
165.2 ± 136.4
193.3 ± 141.5a
208.9 ± 109.0a
185.5 ± 7.0
267.9 ± 8.8
583.6 ± 187.8
162.1 ± 58.6
200.4 ± 29.2a
340.3 ± 311.7
Table 4: Phytochemical compositions (mean ± standard deviation) of the noni juice product and placebo evaluated in the clinical trial.
Chlorogenic acid (mg/mL)
Total polyphenols (mg/mL)
Total iridoids (mg/mL)
Deacetylasperulosidic acid (mg/mL)
Asperulosidic acid (mg/mL)
0.0831 ± 0.0015
0.0349 ± 0.0004
0.6200 ± 0.0400
0.5115 ± 0.0162
0.3747 ± 0.0158
0.1122 ± 0.0070
0.0139 ± 0.0005
0.1030 ± 0.0020
0.0252 ± 0.0004
0.4900 ± 0.0600
profiles, after consuming 30mL noni juice/day for 21 days
. Considering this, it is likely that the decline in elevated
blood lipids observed in our study was due to the inhibition
of oxidative stress by noni juice.
The blood lipid profiles of heavy smokers were improved
after 4 weeks of noni juice ingestion, even when compared to
a fruit juice placebo. The phytochemical analysis of the noni
juice product and the placebo indicates that iridoids, specif-
ically deacetylasperulosidic acid and asperulosidic acid, are
the major point of difference. Iridoids are known for antiox-
idant activities . Oleuropein, a secoiridoid, is perhaps
the best characterized, relative to its antioxidant capacity
[47–49]. Similar to the results in our clinical trial, oleu-
increasing HDL in vivo. These effects were associated with
increases in antioxidant enzyme activities . Further, olive
leaf extract, a rich source of oleuropein, was found to reduce
total cholesterol in a human intervention study .
Data demonstrating the antioxidant potential of iridoid
glycosides are also emerging. Two iridoids that are struc-
turally similar to those found in noni fruit are loganic acid
and loganin. Loganic acid reduced superoxide generation in
human neutrophils activated by N-formyl-methionylleucyl-
phenylalanine and arachidonic acid in a concentration-
dependent manner . Loganin exhibited antioxidant
activities in rat renal mesangial cell cultures incubated in the
presence of advanced glycation end products, inducers of
cellular oxidative stress. Cells incubated with loganin for 48
hours exhibited increased antioxidant enzyme activity, such
as superoxide dismutase and glutathione peroxidase activi-
ties, and decreased malondialdehyde concentration .
Similar to the antioxidant activity of oleuropein in olive,
iridoids occurring in noni fruits inhibited the oxidation
of low-density lipoproteins (LDL) in vitro. Deacetylaspe-
rulosidic acid and asperulosidic acid both demonstrated
significant inhibition of copper sulfate-induced oxidation of
human LDL . Also, deacetylasperulosidic acid and aspe-
rulosidic acid prevented 4-nitroquinoline 1-oxide- (4NQO-)
induced DNA damage in vitro . 4NQO is a genotoxin
that causes the formation of 8-hydroxydeoxyguanosine
(8OHdG), a product of DNA oxidation. 4NQO exposure
leads to the formation of superoxide, hydrogen peroxide,
and hydroxyl radicals, resulting in the production of a
substantial amount of 8OHdG in DNA in mammalian and
bacterial cells [55, 56]. Treatment with deacetylasperulosidic
acid and asperulosidic acid reduced 4NQO genotoxicity in
prokaryotic cells by 98.96 and 99.22%, respectively. There-
fore, the in vitro oxidative activity of 4NQO was almost
entirely abolished by the addition of either iridoid.
The antioxidant activity of iridoids in noni and the lack
of iridoids in the placebo suggest that they are responsible
for at least some of the protective or adaptive effects of noni
juice observed in this trial. Several human studies have
revealed that cigarette smoke reduces glutathione peroxidase
to note that noni juice produced a larger decrease in plasma
a previous human trial , indicating that noni juice may
be effective in increasing the activities of glutathione perox-
idase and glutathione transferase. This possibility is further
supported by the observation that the activities of these
enzymes were doubled in streptozotocin-induced diabetic
6 The Scientific World Journal
rats fed an ethanolic extract of noni fruit for 30 days .
Therefore, it is possible that noni juice inhibits cigarette
smoke-induced oxidative stress, and subsequent dyslipi-
demia, by increasing the activity of glutathione utilizing
The authors gratefully acknowledge the contributions of Dr.
Alexandra Cheerva and Jannet Noton towards the com-
pletion of this study as well as the involvement of C. Jarakae
Jensen and Afa K. Palu. This research was supported by a
grant from Morinda Inc. (Provo, Utah), a manufacturer of
noni juice products.
 W. A. Pryor and K. Stone, “Oxidants in cigarette smoke: radi-
cals, hydrogen peroxide, peroxynitrate, and peroxynitrite,”
Annals of the New York Academy of Sciences, vol. 686, pp. 12–
 W. A. Pryor, D. G. Prier, and D. F. Church, “Electron-
spin resonance study of mainstream and sidestream cigarette
smoke: nature of the free radicals in gas-phase smoke and in
cigarette tar,” Environmental Health Perspectives, vol. 47, pp.
 J. K. Wiencke, K. T. Kelsey, A. Varkonyi et al., “Correlation
of DNA adducts in blood mononuclear cells with tobacco
vol. 55, no. 21, pp. 4910–4914, 1995.
 V. L. Van Antwerpen, A. J. Theron, G. A. Richards et al., “Vita-
min E, pulmonary functions, and phagocyte-mediated oxida-
tive stress in smokers and nonsmokers,” Free Radical Biology
and Medicine, vol. 18, no. 5, pp. 935–941, 1995.
 P. W. Ludwig and J. R. Hoidal, “Alterations in leukocyte
oxidative metabolism in cigarette smokers,” American Review
of Respiratory Disease, vol. 126, no. 6, pp. 977–980, 1982.
 Y. Yamaguchi, J. Haginaka, S. Morimoto, Y. Fujioka, and M.
Kunitomo, “Facilitated nitration and oxidation of LDL in
cigarette smokers,” European Journal of Clinical Investigation,
vol. 35, no. 3, pp. 186–193, 2005.
 W. Wei, Y. Kim, and N. Boudreau, “Association of smoking
with serum and dietary levels of antioxidants in adults:
NHANES III, 1988–1994,” American Journal of Public Health,
vol. 91, no. 2, pp. 258–264, 2001.
 S. E. Moriarty, J. H. Shah, M. Lynn et al., “Oxidation of
glutathione and cysteine in human plasma associated with
smoking,” Free Radical Biology and Medicine, vol. 35, no. 12,
pp. 1582–1588, 2003.
 I. Rahman, E. Swarska, W. MacNee, J. Stolk, and M. Henry,
and lung function in smokers and in patients with chronic
obstructive pulmonary disease?” Thorax, vol. 55, no. 3, pp.
 A. G. Rumley, M. Woodward, A. Rumley, J. Rumley, and G. D.
O. Lowe, “Plasma lipid peroxides: relationships to cardiovas-
cular risk factors and prevalent cardiovascular disease,” QJM:
An International Journal of Medicine, vol. 97, no. 12, pp. 809–
 F. B. Smith, G. D. O. Lowe, F. G. R. Fowkes et al., “Smoking,
haemostatic factors and lipid peroxides in a population case
control study of peripheral arterial disease,” Atherosclerosis,
vol. 102, no. 2, pp. 155–162, 1993.
 W. Y. Craig, G. E. Palomaki, and J. E. Haddow, “Cigarette
smoking and serum lipid and lipoprotein concentrations: an
analysis of published data,” British Medical Journal, vol. 298,
no. 6676, pp. 784–788, 1989.
(SHS) exposure is associated with circulating markers of
inflammation and endothelial function in adult men and
women,” Atherosclerosis, vol. 208, no. 2, pp. 550–556, 2010.
 M. Fr¨ ohlich, M. Sund, H. L¨ owel, A. Imhof, A. Hoffmeister,
and W. Koenig, “Independent association of various smoking
results from a representative sample of the general population
(MONICA Augsburg survey 1994/95),” European Heart Jour-
nal, vol. 24, no. 14, pp. 1365–1372, 2003.
 L. A. Bazzano, J. He, P. Muntner, S. Vupputuri, and P. K.
Whelton, “Relationship between cigarette smoking and novel
risk factors for cardiovascular disease in the United States,”
Annals of Internal Medicine, vol. 138, no. 11, pp. 891–897,
 J. A. Ambrose and R. S. Barua, “The pathophysiology of
nal of the American College of Cardiology, vol. 43, no. 10, pp.
 B. R. Winkelmann, K. Von Holt, and M. Unverdorben,
“Smoking and atherosclerotic cardiovascular disease: part I:
atherosclerotic disease process,” Biomarkers in Medicine, vol.
3, no. 4, pp. 411–428, 2009.
 Jeeyar, Hemalatha, and C. R. W. D. Silvia, “Evaluation of
effect of smoking and hypertension on serum lipid profile and
oxidative stress,” Asian Pacific Journal of Tropical Disease, vol.
1, no. 4, pp. 289–291, 2011.
non-smokers,” Inhalation Toxicology, vol. 19, no. 9, pp. 767–
 C. A. Knight-Lozano, C. G. Young, D. L. Burow et al., “Ciga-
chondrial damage in cardiovascular tissues,” Circulation, vol.
105, no. 7, pp. 849–854, 2002.
 K. Watanabe, K. Eto, K. Furuno, T. Mori, H. Kawasaki, and Y.
Gomita, “Effect of cigarette smoke on lipid peroxidation and
liver function tests in rats,” Acta medica Okayama, vol. 49, no.
5, pp. 271–274, 1995.
 A. R. El-Zayadi, “Heavy smoking and liver,” World Journal of
Gastroenterology, vol. 12, no. 38, pp. 6098–6101, 2006.
 K. A. Steinmetz and J. D. Potter, “Vegetables, fruit, and cancer.
II. Mechanisms,” Cancer Causes and Control, vol. 2, no. 6, pp.
 J. F. Morton, “The ocean-going noni, or Indian Mulberry
(Morinda citrifolia, Rubiaceae) and some of its ”colorful”
relatives,” Economic Botany, vol. 46, no. 3, pp. 241–256, 1992.
review of noni fruit juice,” Journal of Food Science, vol. 71, no.
8, pp. R100–R106, 2006.
 M. Y. Wang, B. J. West, C. J. Jensen et al., “Morinda citrifolia
(Noni): a literature review and recent advances in Noni
research,” Acta Pharmacologica Sinica, vol. 23, no. 12, pp.
 A. Hirazumi and E. Furusawa, “An immunomodulatory poly-
folia (noni) with antitumour activity,” Phytotherapy Research,
vol. 13, no. 5, pp. 380–387, 1999.
The Scientific World Journal7
 A. K. Palu, A. H. Kim, B. J. West, S. Deng, J. Jensen, and L.
White, “The effects of Morinda citrifolia L. (noni) on the
immune system: its molecular mechanisms of action,” Journal
of Ethnopharmacology, vol. 115, no. 3, pp. 502–506, 2007.
 Z. M. Zin, A. Abdul-Hamid, and A. Osman, “Antioxidative
activity of extracts from Mengkudu (Morinda citrifolia L.)
root, fruit and leaf,” Food Chemistry, vol. 78, no. 2, pp. 227–
 B. N. Su, A. D. Pawlus, H. A. Jung, W. J. Keller, J. L. McLaugh-
lin, and A. D. Kinghorn, “Chemical constituents of the fruits
of Morinda citrifolia (Noni) and their antioxidant activity,”
Journal of Natural Products, vol. 68, no. 4, pp. 592–595, 2005.
 M. Y. Wang and C. Su, “Cancer preventive effect of Morinda
citrifolia (Noni),” Annals of the New York Academy of Sciences,
vol. 952, pp. 161–168, 2001.
 A. K. Palu, R. D. Seifulla, and B. J. West, “Morinda citrifolia L.,
(noni) improves athlete endurance: its mechanisms of action,”
Journal of Medicinal Plant Research, vol. 2, no. 7, pp. 154–158,
 M. Y. Wang, M. N. Lutfiyya, V. Weidenbacher-Hoper, G.
Anderson, C. X. Su, and B. J. West, “Antioxidant activity of
noni juice in heavy smokers,” Chemistry Central Journal, vol.
3, no. 1, article 13, 2009.
 S. T. Brookes, E. Whitley, T. J. Peters, P. A. Mulheran, M.
controlled trials: quantifying the risks of false-positives and
false-negatives,” Health Technology Assessment, vol. 5, no. 33,
pp. 1–56, 2001.
 S. Deng, B. J. West, A. K. Palu, and C. J. Jensen, “Deter-
mination and comparative analysis of major iridoids in
different parts and cultivation sources of Morinda citrifolia,”
Phytochemical Analysis, vol. 22, no. 1, pp. 26–30, 2011.
 S. Deng, B. J. West, and C. J. Jensen, “A quantitative com-
parison of phytochemical components in global noni fruits
and their commercial products,” Food Chemistry, vol. 122, no.
1, pp. 267–270, 2010.
 B. J. West, S. Deng, and C. J. Jensen, “Nutrient and phy-
tochemical analyses of processed noni puree,” Food Research
International, vol. 44, no. 7, pp. 2295–2301, 2011.
 Z. Ding, Y. Dai, H. Hao, R. Pan, X. Yao, and Z. Wang, “Anti-
inflammatory effects of scopoletin and underlying mecha-
nisms,” Pharmaceutical Biology, vol. 46, no. 12, pp. 854–860,
 S. Panda and A.Kar, “Evaluation of the antithyroid, antioxida-
tive and antihyperglycemic activity of scopoletin from Aegle
marmelos leaves in hyperthyroid rats,” Phytotherapy Research,
vol. 20, no. 12, pp. 1103–1105, 2006.
 M. C ¸ay, M. Naziroˇ glu, and H. K¨ oyl¨ u, “Selenium and vitamin e
modulates cigarette smoke exposure-induced oxidative stress
in blood of rats,” Biological Trace Element Research, vol. 131,
no. 1, pp. 62–70, 2009.
 A. Gokulakrisnan, B. Jayachandran Dare, and C. Thirunavuk-
karasu, “Attenuation of the cardiac inflammatory changes and
lipid anomalies by (−)-epigallocatechin-gallate in cigarette
354, no. 1-2, pp. 1–10, 2011.
 A. R. Weseler, E. J. Ruijters, M. J. Drittij-Reijnders, K. D.
Reesink, G. R. Haenen, and A. Bast, “Pleiotropic benefit of
monomeric and oligomeric flavanols on vascular health—a
randomized controlled clinical pilot study,” PLoS ONE, vol. 6,
no. 12, Article ID e28460, pp. 1–12, 2011.
 C. Novembrino, G. Cighetti, R. De Giuseppe et al., “Effects
of encapsulated fruit and vegetable juice powder concentrates
on oxidative status in heavy smokers,” Journal of the American
College of Nutrition, vol. 30, no. 1, pp. 49–56, 2011.
 B. J. West, L. D. White, C. J. Jensen, and A. K. Palu, “A double-
blind clinical safety study of noni fruit juice,” Pacific Health
Dialog, vol. 15, no. 2, pp. 21–32, 2009.
 P. Sabitha, P. M. Adhikari, and A. Kamath, “Effect of noni
juice on lipid profile in diabetic patients,” Indian Journal of
Pharmacology, vol. 40, no. 8, pp. S37–S40, 2008.
 R. Tundis, M. R. Loizzo, F. Menichini, G. A. Statti, and
F. Menichini, “Biological and pharmacological activities of
iridoids: recent developments,” Mini-Reviews in Medicinal
Chemistry, vol. 8, no. 4, pp. 399–420, 2008.
 K. De La Torre-Carbot, J. L. Ch´ avez-Serv´ ın, O. Ja´ uregui et al.,
“Elevated circulating LDL phenol levels in men who con-
sumed virgin rather than refined olive oil are associated with
less oxidation of plasma LDL,” Journal of Nutrition, vol. 140,
no. 3, pp. 501–508, 2010.
 S. H. Omar, “Oleuropein in olive and its pharmacological
effects,” Scientia Pharmaceutica, vol. 78, no. 2, pp. 133–154,
antioxidant effects of olive oil phenols in humans: a review,”
European Journal of Clinical Nutrition, vol. 58, no. 6, pp. 955–
 H. Jemai, M. Bouaziz, I. Fki, A. El Feki, and S. Sayadi,
“Hypolipidimic and antioxidant activities of oleuropein and
its hydrolysis derivative-rich extracts from Chemlali olive
leaves,” Chemico-Biological Interactions, vol. 176, no. 2-3, pp.
 T. Perrinjaquet-Moccetti, A. Busjahn, C. Schmidlin, A.
Schmidt, B. Bradl, and C. Aydogan, “Food supplementation
with an olive (Olea europaea L.) leaf extract reduces blood
pressure in borderline hypertensive monozygotic twins,” Phy-
totherapy Research, vol. 22, no. 9, pp. 1239–1242, 2008.
 S. Wei, H. Chi, H. Kodama, and G. Chen, “Anti-inflammatory
effect of three iridoids in human neutrophils,” Natural Prod-
ucts Research. In press.
 H. Xu, J. Shen, H. Liu, Y. Shi, H. Li, and M. Wei, “Morroniside
and loganin extracted from Cornus officinalis have protective
effects on rat mesangial cell proliferation exposed to advanced
glycation end products by preventing oxidative stress,” Cana-
dian Journal of Physiology and Pharmacology, vol. 84, no. 12,
pp. 1267–1273, 2006.
 D. H. Kim, H. J. Lee, Y. J. Oh et al., “Iridoid glycosides isolated
from Oldenlandia diffusa inhibit LDL-oxidation,” Archives of
Pharmacal Research, vol. 28, no. 10, pp. 1156–1160, 2005.
 Y. Arima, C. Nishigori, T. Takeuchi et al., “4-Nitroquinoline 1-
oxide forms 8-hydroxydeoxyguanosine in human fibroblasts
through reactive oxygen species,” Toxicological Sciences, vol.
91, no. 2, pp. 382–392, 2006.
 T. Nunoshiba and B. Demple, “Potent intracellular oxidative
stress exerted by the carcinogen 4-nitroquinoline-N-oxide,”
Cancer Research, vol. 53, no. 14, pp. 3250–3252, 1993.
 H. R. Abdolsamadi, M. T. Goodarzi, H. Mortazavi, M.
Robati, and F. Ahmadi-Motemaye, “Comparison of salivary
antioxidants in healthy smoking and non-smoking men,”
Chang Gung Medical Journal, vol. 34, no. 6, pp. 607–611, 2011.
 M. R. Giuca, E. Giuggioli, M. R. Metelli et al., “Effects of
cigarette smoke on salivary superoxide dismutase and glu-
tathione peroxidase activity,” Journal of Biological Regulators
and Homeostatic Agents, vol. 24, no. 3, pp. 359–366, 2010.
 M. Greabu, A. Totan, M. Battino et al., “Cigarette smoke effect
on total salivary antioxidant capacity, salivary glutathione
8 The Scientific World Journal
peroxidase and gamma-glutamyltransferase activity,” BioFac-
tors, vol. 33, no. 2, pp. 129–136, 2008.
 R. Miri, H. Saadati, P. Ardi, and O. Firuzi, “Alterations in
oxidative stress biomarkers associated with mild hyperlipi-
demia and smoking,” Food and Chemical Toxicology, vol. 50,
no. 3-4, pp. 920–926, 2012.
 N. Li, X. Jia, C. Y. O. Chen et al., “Almond consumption
reduces oxidative DNA damage andlipidperoxidationinmale
 P. Pasupathi, G. Saravanan, P. Chinnaswamy, and G. Baktha-
vathsalam, “Effect of chronic smoking on lipid peroxidation
and antioxidant status in gastric carcinoma patients,” Indian
Journal of Gastroenterology, vol. 28, no. 2, pp. 65–67, 2009.
 U. S. Mahadeva Rao and S. Subramanian, “Biochemical eval-
uation of antihyperglycemic and antioxidative effects of Mor-
inda citrifolia fruit extract studied in streptozotocin-induced
diabetic rats,” Medicinal Chemistry Research, vol. 18, no. 6, pp.