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The Potential Health Benefits of Noni Juice: A Review of Human Intervention Studies

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Abstract and Figures

Noni juice is a globally popular health beverage originating in the tropics. Traditional Tahitian healers believe the noni plant to be useful for a wide range of maladies, and noni juice consumers throughout the world have similar perceptions. Nevertheless, human clinical trials are necessary for a precise understanding of what the health benefits of noni juice are. A review of published human intervention studies suggests that noni juice may provide protection against tobacco smoke-induced DNA damage, blood lipid and homocysteine elevation as well as systemic inflammation. Human intervention studies also indicate that noni juice may improve joint health, increase physical endurance, increase immune activity, inhibit glycation of proteins, aid weight management, help maintain bone health in women, help maintain normal blood pressure, and improve gum health. Further, these studies point to notable antioxidant activity in noni juice, more so than other fruit juices which served as trial placebos. It is this antioxidant effect and its interaction with the immune system and inflammation pathways that may account for many of the observed health benefits of noni juice. However, the existing evidence does have some limitations as far as its general application to noni juice products; all the peer-reviewed human interventions studies to date have involved only one source of French Polynesian noni juice. Geographical factors and variations in processing methods are known to produce commercial noni juice products with divergent phytochemical and nutrient compositions. Therefore, other sources of noni products may have different toxicological and pharmacological profiles.
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foods
Review
The Potential Health Benefits of Noni Juice: A Review
of Human Intervention Studies
Brett J. West 1,*ID , Shixin Deng 1, Fumiyuki Isami 2, Akemi Uwaya 2and Claude Jarakae Jensen 1
1Research and Development, Morinda, Inc., 737 East 1180 South, American Fork, UT 84003, USA;
shixin_deng@morinda.com (S.D.); jarakae_jensen@morinda.com (C.J.J.)
2Research and Development, Morinda, Inc., 3-2-2 Nishishinjuku, Shinjuku-ku, Tokyo 160–0023, Japan;
fumiyuki_isami@jp.morinda.com (F.I.); akemi_uwaya@jp.morinda.com (A.U.)
*Correspondence: brett_west@morinda.com
Received: 13 March 2018; Accepted: 6 April 2018; Published: 11 April 2018
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Abstract:
Noni juice is a globally popular health beverage originating in the tropics. Traditional
Tahitian healers believe the noni plant to be useful for a wide range of maladies, and noni juice
consumers throughout the world have similar perceptions. Nevertheless, human clinical trials
are necessary for a precise understanding of what the health benefits of noni juice are. A review
of published human intervention studies suggests that noni juice may provide protection against
tobacco smoke-induced DNA damage, blood lipid and homocysteine elevation as well as systemic
inflammation. Human intervention studies also indicate that noni juice may improve joint health,
increase physical endurance, increase immune activity, inhibit glycation of proteins, aid weight
management, help maintain bone health in women, help maintain normal blood pressure, and
improve gum health. Further, these studies point to notable antioxidant activity in noni juice,
more so than other fruit juices which served as trial placebos. It is this antioxidant effect and its
interaction with the immune system and inflammation pathways that may account for many of the
observed health benefits of noni juice. However, the existing evidence does have some limitations
as far as its general application to noni juice products; all the peer-reviewed human interventions
studies to date have involved only one source of French Polynesian noni juice. Geographical factors
and variations in processing methods are known to produce commercial noni juice products with
divergent phytochemical and nutrient compositions. Therefore, other sources of noni products may
have different toxicological and pharmacological profiles.
Keywords: noni juice; Morinda citrifolia; clinical trial; antioxidant; immune system; inflammation
1. Introduction
Noni juice has become a popular health supplement. In the first dozen years of its commercial
marketing, more than 106 million liters of Tahitian Noni
®
Juice (Morinda, Inc., American Fork, UT,
USA) were consumed in more than 80 nations [
1
]. Noni juice was one of the first whole foods approved
under the European Union’s 1997 novel food regulations [
2
]. The Chinese government has also
approved one source of noni juice as a safe new resource and has approved it as a functional food that
can enhance immunity [3].
Noni is the common name for Morinda citrifolia, a small to medium sized tree (3–10 m high) with
a pantropical distribution [
4
]. Noni fruit and leaves have a history of food use among Pacific Islanders
as well as in Southern and Southeast Asia. Although the fruit is edible, its flavor has been described as
akin to bad cheese [
5
]. Despite this, Rarotongans ate the fruit often and the Burmese used it to prepare
curries [
6
,
7
]. Australian Aborigines ate noni fruit during the cool-dry season from May to August in
the Northern Territory of Australia [
8
,
9
]. Noni leaves were eaten both in raw and cooked form in Java
Foods 2018,7, 58; doi:10.3390/foods7040058 www.mdpi.com/journal/foods
Foods 2018,7, 58 2 of 22
and Thailand [
10
]. In Tahiti, fish were wrapped in the leaves as a part of baking to impart an appealing
flavor to the cooked fish [11].
More recently, the fruit has been used to produce dietary supplements. French Polynesia has been
a major source of this juice where noni fruit puree constitutes one of the area’s largest agricultural
exports [
12
]. In fact, more than 21,000 metric tons of this puree was exported in the past decade [
13
].
The noni plant was the most important and widely used Polynesian medicinal plant prior to the
arrival of Europeans with Tahitian healers using it in many remedies [
14
]. Some uses of the fruit
include the treatment of inflammation, abscesses, angina, diabetes, ranula, abdominal fibromas, and
scorpionfish stings [
15
,
16
]. In other parts of French Polynesia, noni fruit has been reportedly used to
treat osteoarthritis, rheumatism, backache, joint problems, hemorrhoids, skin allergies, burns, and
warts [
17
]. The global popularity of the juice is attributable to its perceived health value. Indeed,
European consumers of a Tahitian-sourced noni juice beverage frequently have reported health benefits
including increased energy, improved well-being, reduction of pain, fewer infections, improved sleep,
improved digestion, as well as a reduction in allergy and asthma symptoms [18].
Published research has explored the potential health effects of the noni plant. Unfortunately,
much of this research has involved
in vitro
and animal studies, often using only noni plant extracts
or noni juice of unknown concentration [
19
,
20
]. Although the findings of these types of studies are
useful in explaining possible mechanisms of action, they may have limited application to humans as a
result of interspecies differences in absorption, distribution, metabolism, and excretion. Additionally,
the lack of standardization in noni content may also interfere with the search for valid conclusions.
Therefore, human studies are necessary to determine what precise effects noni juice may have on
human health. These studies should also provide information on phytochemical composition as noni
fruit varies considerably according to region; concurrently, disparities exist in both the ingredients
and processing methods used to produce various commercial noni juice products [
21
]. Accordingly,
this review summarizes published human intervention studies involving primarily noni fruit juice
(including mixed noni juice beverages) and discusses mechanisms of action that may explain the
health benefits described in ethnobotanical studies. Also considered are the general limitations on the
applicability of these human studies to noni juice products.
2. Clinical Safety Study
A 28-day clinical trial with 96 healthy adult volunteers was conducted to evaluate the safety of
daily ingestion of Tahitian Noni
®
Juice (TNJ), a pasteurized mixed noni juice from French Polynesia [
22
].
TNJ is composed of noni fruit juice from puree (89%) that is mixed with grape (Vitis vinifera) and
blueberry (Vaccinium corymbosum) juices with an undisclosed proprietary final percentage of noni juice
concentration [
23
]. The volunteers were divided equally into four dose groups: 0 mL (placebo), 30 mL,
300 mL, or 750 mL. Comprehensive hematology, biochemistry, and urinalysis tests were completed
with each volunteer at the start of the trial as well as at week 2, week 4 (end of TNJ ingestion), and
during a two-week follow-up (week 6). Electrocardiography tests were performed with each subject
during a pre-study screening and at week six. Hematological measurements included hemoglobin,
hematocrit, mean cell volume, red cell count, prothrombin time, activated partial thrombin time, total
and differential white cell count (basophils, eosinophils, lymphocytes, monocytes, and neutrophils),
and platelet count. Biochemistry analysis included alkaline phosphatase, alanine aminotransferase,
aspartate aminotransferase, total bilirubin, lipids (LDL, HDL, cholesterol, triglycerides), creatine kinase,
creatinine, gamma–glutamyl transferase, glucose, total protein, and uric acid. Urinalysis involved
semi-quantitative analysis for leucocytes, nitrite, urobilinogen, protein, blood, ketones, bilirubin,
glucose, pH, and specific gravity. Blood pressure, heart rate, weight, and adverse events were also
recorded also at baseline and weeks 2, 4, and 6.
Test results revealed that there were no adverse dose-related effects from TNJ ingestion. During
the entire study, no clinically significant differences were observed in any of the measurements between
the placebo and TNJ groups, apart from a reduction between 20% and 50% of total adverse events
Foods 2018,7, 58 3 of 22
(i.e., headache and other body aches) in the TNJ groups compared with the placebo group. The lower
adverse event rates in the TNJ groups suggest possible health benefits from noni. The results of this
study indicate that drinking up to 750 mL TNJ each day is safe.
3. Antioxidant and DNA Protection
A series of double-blind, placebo-controlled, 30-day intervention studies involving cigarette
smokers has demonstrated the substantial antioxidant activity of a mixed noni juice (TNJ). The first of
these involved 285 adult volunteers who smoked more than 20 cigarettes per day [
24
]. The participants
were assigned randomly to a placebo, 29.5 mL TNJ/day, or a 118 mL TNJ/day group. The placebo
was composed of grape and blueberry juices with a cheese flavor added to mimic the noni flavor.
Blood plasma levels of superoxide anion radicals (SAR) and lipid hydroperoxide (LOOH) levels were
measured at the beginning and end of the trial with participants continuing to smoke throughout the
trial. TNJ ingestion reduced average plasma SAR by 26.9% and 30.8% in the 29.5 and 118 mL groups,
respectively. Average LOOH levels in the 29.5 mL group were reduced by 24.5% while the 118 mL
group experienced a 27.3% reduction. No significant reductions in SAR or LOOH levels occurred in
the placebo group. Despite the presence of high antioxidant fruit juice in the placebo, the inhalation
of large quantities of tobacco smoke resulted in more oxidative stress than could be overcome with
grape and blueberry juices alone. Therefore, the SAR and LOOH reduction was attributable to the
antioxidant properties, whether direct or indirect, of noni juice alone or in combination with the
other ingredients.
The second smoker study was completed with 203 subjects [25]. The study intervention was the
same as that mentioned above. However, in this study, peripheral blood lymphocytes (PBLs) were
isolated from pre-and post-trial whole blood samples and evaluated for the degree of aromatic DNA
adduct formation using a
32
P-postlabeling assay. By the end of the 30-day study period, average
aromatic DNA adduct levels dropped by 44.9% (p< 0.001) among those drinking either one fluid
ounce (29.5 mL) or four fluid ounces (118 mL) of TNJ per day. There were no significant differences in
gender-specific responses. But at the lower dose, males experienced a greater decrease in aromatic
DNA adducts than females (56.1% vs. 43.1% reduction, respectively). No adverse effects were observed
in this trial.
Another randomized, double-blind, placebo-controlled study was completed with 245 heavy
cigarette smokers [
26
]. This trial measured changes to lipid peroxidation–derived DNA adducts
after 30 days of mixed noni juice beverage ingestion. Participants in this study were assigned to the
same dose groups with the same placebo and TNJ that were used in the antioxidant trial. Again, a
32
P-postlabeling assay was used following isolation of DNA from PBLs. The previous DNA protection
study measured aromatic DNA adducts which were more likely to be formed by direct reactions with
chemicals in cigarette smoke or their immediate metabolites. In this second study, measurements
were made specifically of DNA adducts resulting from cigarette smoke-induced oxidative stress
and consequent lipid peroxidation. At the completion of the trial period, the placebo group did not
experience any reduction in DNA damage. However, the lipid peroxidation–derived DNA adduct
levels in those who drank TNJ declined significantly by 46.9% to 57.4%. This effect is consistent with
both previous studies where reactive oxygen species and aromatic DNA-adduct concentrations were
significantly reduced.
4. Blood Lipid Normalization, High Sensitivity C-Reactive Protein (hs-CRP) and
Homocysteine Reduction
As with the antioxidant and DNA adduct studies, adult smokers provided further insight into
the effect of 30 days of TNJ ingestion on blood lipids and hs-CRP. In a randomized, double blind,
placebo-controlled clinical trial with 132 volunteers [
27
], heavy smokers (
20 cigarettes/day) were
chosen as subjects because smoking has been reported to increase blood lipids, systemic inflammation,
and serum homocysteine [
28
30
]. Pre- and post-study serum cholesterol, triglyceride, low density
Foods 2018,7, 58 4 of 22
lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), hs-CRP, and homocysteine
were measured for all participants who continued smoking during the trial. In this study, the dose
groups were the same as in the previously discussed smoker studies.
After drinking TNJ for 30 days, the placebo group had no significant changes in any measurements.
But among those who drank TNJ, there were significant declines in average hs-CRP (15.2%) and
homocysteine (23.9%) with an increase in HDL (from 49 to 57 mg/dL). Mean total cholesterol, LDL,
and triglycerides were also decreased among those in the TNJ groups. However, the degree of change
was dependent on initial (pre-trial) values. Larger declines in mean values were associated with
greater initial total cholesterol, LDL, or triglycerides levels. For example, decreases in average total
cholesterol in the low (190–219 mg/dL), middle (220–299 mg/dL), and high (>300 mg/dL) baseline
strata of the 29.5 mL group were 12.1, 17.3, and 36.4%, respectively. No participants in either TNJ group
experienced any changes that resulted in below normal reference values for individual blood lipid
levels. As such, the changes experienced were towards or remained within normal healthy ranges.
These results indicate that TNJ helped normalized lipid levels in heavy smokers.
A second, although smaller, study examined the cholesterol lowering activity of TNJ in
nonsmokers [
31
]. This open-label pilot study involved older adults (>40 years) who had normal
or borderline high cholesterol levels and were not taking cholesterol-lowering medication nor drinking
alcohol. Each participant drank two fluid ounces (59 mL) of TNJ twice per day for 30 days. No other
changes to lifestyle habits were made during the trial period. There was no significant difference
between pre- and post-trial total cholesterol, HDL, and LDL levels, or TC/HDL ratio. These results
suggest that the cholesterol modulating effect of TNJ in heavy smokers is likely a result of its ability to
protect against cigarette smoke-induced dyslipidemia via antioxidant activity.
5. Improvement of Joint Pain and Mobility
Topical treatment of pain and bruising is one of the most common uses of the noni plant in tropical
alternative medicine. Some animal studies suggest that noni possesses possible anti-inflammatory
activity [
32
34
]. In fact, one of the traditional names for noni in the Caribbean was “pain killer” [
35
].
Among the published anti-nociceptive and anti-inflammatory studies of noni juice are two open-label
clinical trials that demonstrate potential joint health benefits. The earlier of these two trials reported
pain reduction and improved range of motion (flexion, extension, lateral flexion, and rotation) in
patients suffering from cervical spondylosis after four weeks of ingesting 15 mL TNJ every morning
and evening [
36
]. This trial enrolled 90 patients who were assigned to one of three treatment groups:
standard physiotherapy alone, TNJ alone, and combined treatment (physiotherapy plus TNJ). Pre-and
post-treatment measurements of pain intensity and neck flexibility (cervical range of motion) were
compared within and among the treatment groups. At the start of the trial, all subjects in the TNJ
alone group fell within the 5–7 (moderate to severe) pain intensity range. By the end of the study, the
pain intensity range of this group had decreased to 0–4 (none to very moderate), with complete relief
of neck pain in 60 percent of patients. The physiotherapy alone and combined treatment groups also
experienced significant reduction in pain symptoms, with the combined treatment group experiencing
the greatest reduction in pain intensity. Range of motion improved among all three treatment groups
by the end of the trial period. For example, mean lateral flexion and rotation approximately doubled in
the TNJ alone and physiotherapy alone groups. Although improvements in the TNJ alone group were
no different than those of the standard physiotherapy alone group, a significantly greater improvement
occurred in the combined treatment group.
A second joint health trial of TNJ involved osteoarthritis patients [
37
]. In this open-label
intervention study, 82 volunteers drank three fluid ounces (88.5 mL) of TNJ (1 ounce before breakfast,
1 ounce before lunch, and 1 ounce before bedtime) every day. Those enrolled in the study were
adults (40–75 years), had an X-ray diagnosis of osteoarthritis of the hip or knee, were not taking
prescription medication for arthritis, and were willing to consume TNJ for 90 days. Blood samples
were collected from the participants for clinical laboratory analysis at enrollment and after the 90-day
Foods 2018,7, 58 5 of 22
intervention period. The Arthritis Impact Measurement Scales (AIMS2) were used to measure pre-
and post-study pain/discomfort levels. The Short Form-36, version 2 (SF-36 V2) was used to measure
pre- and post-study patient quality of life.
By the end of the intervention period, significant improvements in mean quality of life
measurements occurred. These included a reduction in the duration of arthritis pain, including
a 23.7% decrease in the frequency (in days) of severe pain, and 16.4% decrease in pain severity.
Patients also experienced an improved psychological state and mood and improved mobility. Patient
satisfaction with personal health also increased by approximately 19%. As with previous studies,
TNJ was well tolerated and appeared to be safe. No significant changes to liver or kidney functions
occurred after three months of TNJ ingestion nor were there changes to blood glucose, total cholesterol,
or triglyceride levels. It is important to note that since no placebo or control group was included in this
trial, it is difficult to determine how much of the observed outcome was a result of the placebo effect.
A double-blind placebo-controlled trial involving female university students suffering from
dysmenorrhea was completed to evaluate the efficacy of a capsule containing 400 mg milled “noni
herb powder”, calcium sulfate, gelatin, silica, and magnesium stearate [
38
]. Over the course of three
menstrual cycles, noni capsule ingestion did not improve menstrual pain when compared with the
placebo. However, there was some evidence of a significant decline in mean erythrocyte sedimentation
rate (ESR) among those taking the noni capsule. This indicated some degree of anti-inflammatory
activity, although not enough to affect pain symptoms. While this study did not involve noni fruit juice,
it highlights issues regarding noni product identity and variation in potential efficacy. The product
used in this study was identified as a “noni herb powder” with no indication as to the geographic
origin, plant part used, or harvesting and processing conditions. As will be discussed in more
detail, there is wide variability among nutrient and phytochemical compositions of commercial noni
products [
39
]. These differences preclude assumptions that results from clinical trials of a specific
noni product are applicable to other noni products. The two previously discussed trials involved the
French Polynesian-derived noni juice blend (TNJ) used in the smoker studies. However, this latter trial
evaluated a noni herb powder of relatively unknown identity. Therefore, the lack of significant pain
reduction in the latter trial does not necessarily refute the pain reduction observations of the cervical
spondylosis and osteoarthritis trials. However, it is interesting that all three trials did provide some
evidence of anti-inflammatory activity.
6. Increased Physical Endurance
Some Pacific Islanders believed that ingesting ripe noni fruit invigorated the body during
long fishing trips and ocean voyages [
40
]. Three clinical trials have been completed which lend
some credence to this use. The first of these was a 21-day, placebo-controlled intervention study
involving 40 highly trained middle and long-distance runners [
41
]. For three weeks, these athletes
drank 100 mL TNJ or a blackberry juice placebo twice per day. The athletes participated in pre-
and post-intervention time-to-fatigue treadmill tests during which the workload increased every
minute. Pre-and post-intervention medical examinations (including electrocardiogram, heart rate,
and blood pressure) and blood tests were also performed (including total protein, urea, glucose,
hemoglobin, and lactate). The TNJ group had a 21% increase in average time-to-fatigue with an
accompanying 25% decrease in average blood chemiluminescence (a marker of lipid oxidation),
whereas no changes occurred in the placebo group. An accompanying study did not reveal the
presence of any substances banned for athletic competition (including beta-blockers, diuretics, narcotics,
anabolic steroids, stimulants, or masking agents). Therefore, it appears that the increase in physical
endurance is associated with the antioxidant activity of TNJ.
A second similar trial was completed but with some modifications [
42
]. This trial equally divided
46 university athletes as well as 14 non-athlete controls into a TNJ group and a blackberry juice group.
For 30 days, these athletes drank 100 mL TNJ or blackberry juice twice per day. This trial also included
pre- and post-intervention time-to-fatigue treadmill tests, with accompanying blood analyses. The TNJ
Foods 2018,7, 58 6 of 22
group experienced a significant decrease in mean serum creatine kinase (CK) concentration, while
no such decline occurred in the blackberry juice group. This finding suggests that the improvement
in endurance is a result of the ability of TNJ to mitigate exercise-induced muscle tissue damage.
This protective effect likely involves the antioxidant properties of noni, as CK concentration increased
along with oxidative stress markers in athletes undergoing intensive training [
43
]. Indeed, intense
exercise causes increases in free radical production and inflammation [
44
] both of which are inhibited
by TNJ.
Noni juice may also have an influence on oxygen uptake during physical exertion.
Semi-professional male cyclists were enrolled in a double-blind, placebo-controlled, randomized
study to evaluate the effect of TNJ on aerobic fitness [
45
]. Volunteers drank either 120 mL of TNJ
or a placebo every day for 14 days. At the beginning of the trial and after two weeks, volunteers
completed exercise tests on a cycle ergometer (with 30 watt/min workload increase) to the point of
exhaustion, electrocardiographic alterations, or to the theoretical maximal heart rate. Oxygen uptake
was measured by spirometry. Increases in the average maximal oxygen uptake, VO
2
max, and in
oxygen uptake at 50-watt workload occurred in the TNJ group. TNJ does not contain any performance
enhancing substances.
7. Increased Immune Activity
Smoking suppresses immune function [
46
]. Exposure to tobacco smoke is a risk factor for various
bacterial and viral infections [
47
,
48
]. A smoking habit can have a significant negative impact of
peripheral blood lymphocyte subsets and their function [
49
,
50
]. The ability of noni juice to protect
lymphocyte DNA damage, as discussed above, may have a positive effect on the immune function of
smokers. But noni juice may have an influence on immune function that goes beyond the protection
of cells involved in the adaptive immune system. For example, the feeding of French Polynesian
noni fruit puree to newborn cattle (Holstein bull calves) for the first two weeks of life significantly
increased whole blood phagocytic activity against E. coli and Staphylococcus epidermis [
51
]. A follow-up
study in Holstein bull calves revealed that noni puree supplementation for the first three weeks
of life also reduced all required medical treatments by 54%, with a 61% reduction in respiratory
treatments and a 52% reduction in gastrointestinal treatments [
52
]. The immune-modulating activity
of noni juice was also observed in mice where TNJ consumption for 15 days resulted in the inhibition
of mitogen-stimulated interleukin-4 production in splenocytes and peritoneal exudate cells [
53
].
This treatment also significantly increased interferon-gamma (IFN-
γ
) production. As IFN-
γ
is
involved in macrophage activation, these results agree with the increase in phagocytic activity seen in
newborn calves.
To verify the immune-modulating potential of noni juice in humans, an intervention study
was conducted with 12 healthy adult volunteers for eight weeks, during which each consumed
330 mL of TNJ daily [
54
]. Vital signs, serum malondialdehyde (MDA) concentration, interleukin 2
(IL-2) concentration, and ex vivo natural killer-cell (NK) activity were measured before and after the
intervention period. There was no change in vital signs during the study. However, there was a
significant decrease in average MDA levels over the course of the trial due to reduced oxidative stress.
On the other hand, mean IL-2 concentration and NK activity both increased by approximately 30%.
The findings of this pilot study revealed TNJ’s potential for supporting immune function, along with
concurrent antioxidant activity, in a healthy population.
Notably, the antioxidant properties of TNJ likely contribute to its immunomodulation activity as
there is a documented connection between oxidative processes and the immune system. Reactive oxygen
species (ROS) are involved in the modulation of immune function and serve as secondary messengers in
cell signal transduction [
55
]. Multiple studies have demonstrated the ability of antioxidants, including
those from fruits, to modulate immune responses [
56
59
]. Epidemiology studies have revealed
associations between lower cancer incidence and diets rich in antioxidant nutrients, potentially stemming
Foods 2018,7, 58 7 of 22
from antioxidant-induced improvement in immune function [
60
]. Antioxidant supplementation also
improved immune function in the elderly and in other groups [61,62].
8. Control of Advanced Glycation End Products (AGEs) and Glycosylated Hemoglobin
Several
in vitro
studies have indicated that noni fruit may be helpful in controlling the formation
of advanced glycation end products (AGEs) and may subsequently reduce their adverse effects.
An extract from noni fruit collected in French Polynesia prevented AGE-induced reactive oxygen
species generation in human umbilical vein endothelial cells [
63
]. This extract also inhibited the
in vitro
formation of glucose-human serum albumin, glucose-collagen, and glucose-keratin AGEs as well
exhibited AGE-crosslink breaking activity [
64
]. Another noni fruit extract inhibited the development
of glucose-induced bovine eye lens opacity [65].
The antiglycation potential of noni fruit juice was further demonstrated in an eight-week
open-label intervention study and in a cross-sectional population study [
66
]. Both studies were
conducted within the context of iridoid content, as iridoids are major phytochemicals in noni
fruit and are well known for their anti-AGE biological activities [
67
,
68
]. Both studies utilized skin
autofluorescence as a marker for AGE accumulation in the body [
69
]. The eight-week intervention
study measured changes in the skin autofluorescence of 34 adults who daily consumed a mixed noni
juice beverage similar to TNJ, TruAge
®
Max (Morinda, Inc., American Fork, UT, USA). TruAge
®
Max
(MAX) is also composed of noni fruit puree but is mixed with cornelian cherry (Cornus officinalis
and Cornus mas) juices, and olive (Olea europaea) leaf extract. Overweight or obese, prehypertensive,
or grade 1 hypertensive males and females with impaired fasting glucose and who were not using
prescription medication were included in the trial. Previously published population reference values
revealed that the average initial skin autofluorescence of this group was typical of healthy 44-year-old
adults even though their average actual age was 40. As such, their AGE-associated age (ASA) was
four years older than their average actual age. But eight weeks of MAX supplementation reduced the
ASA of this group to 39 years, demonstrating a significant antiglycative effect.
The cross-sectional population study included 3913 people from ten locations throughout Japan.
During health education and promotion events, a questionnaire was used to collect demographic
data and information on daily ingestion rates of mixed noni juice beverages (i.e., TNJ or MAX). Daily
iridoid intake was calculated from the ingestion rates by applying the data obtained from chemical
analyses of the beverages. As with the eight-week intervention study, skin autofluorescence was used
as a marker for AGE burden in 2790 mixed noni juice consumers and 1123 controls (those who did
not drink any noni juice beverages). Regression analysis revealed that mixed noni juice intake was
associated with lower AGE levels with noni consumers having an average ASA that was 2.07 years
less than the general population. Notably, for every mg of iridoids consumed, ASA decreased by
0.017 years. Among those who never smoked, the average ASA of mixed noni juice consumers was
3.52 years less than the general population. The significant anti-AGE activity of mixed noni juice was
at least in part a result of its ability to induce antioxidant enzyme activity, specifically superoxide
dismutase and catalase [70].
Recently, some Pacific Islanders have considered noni fruit to be helpful in controlling blood sugar
levels [
71
].
In vitro
and animal studies have provided some supporting evidence for this view [
72
75
].
Even so, data from human clinical trials is limited. A small eight-week human pilot study was
conducted with Type 2 diabetes patients [
76
]. In this study, ingestion of 2 mL of TNJ per kg body
weight, twice daily, was associated with improved blood glucose profiles and a significant reduction
in glycosylated hemoglobin (HbA1c). It should be noted, however, that TNJ did not influence blood
glucose levels in those without diabetes [
22
]. Therefore, the anti-diabetic property of TNJ appears to
only involve the regulation of normal blood glucose level and is limited by feedback mechanisms, rather
than involving the pharmacological pathways that are targets of conventional diabetes medications.
Foods 2018,7, 58 8 of 22
9. Weight Management and Mitigation of Osteoporosis, Hypertension, and Gingivitis
Currently, several Pacific Islanders believe that noni plant preparations are useful for weight
management [
71
,
77
]. Multiple animal studies have demonstrated the anti-obesity potential of noni
juice [
78
]. Two clinical trials have further investigated this potential. The first of these was a 12-week,
open-label trial of a weight-loss program that included TNJ, daily calorie restriction, and exercise
interventions [79]. By the end of the trial, all participants experienced weight loss with mean percent
body fat decreasing by 8.91% (p< 0.0001). Five of 22 participants moved from overweight to the normal
weight category while another five switched from obese to overweight. However, given the other
interventions also included in the trial (i.e., exercise and calorie restriction), it is difficult to determine
the degree to which noni juice contributed to this outcome.
The second weight loss study included 90 grade 3 overweight (morbidly obese) adults who were
divided into three treatment groups [
80
]. For six weeks, all participants followed a low calorie and
low sodium diet. Participants in two separate mixed noni juice groups were assigned to drink either
TNJ or MAX for the duration of the study. Those in the control group did not consume any noni juice
beverages. Muscle mass loss was significantly lower in those drinking mixed noni juice beverages
compared to the control group. Maintenance of weight loss throughout the study was greater in those
drinking TNJ or MAX than in the control group as was reduction of waist circumference and body
mass index. The preservation of active muscle cell mass seems to be a likely mechanism by which the
improved weight loss was achieved by those in the TNJ and MAX groups. Protection of muscle tissue
is also one mechanism responsible for improved endurance, as previously discussed.
A somewhat unexpected property of noni juice was its potential influence on osteoporosis
and conductive hearing loss. A three-month placebo-controlled pilot study was conducted with
post-menopausal women wherein participants drank either two fluid ounces (59 mL) of TNJ or placebo
twice per day [
81
]. Before and after the study, the women completed the Short Form 36 (SF-36)
Quality of Life Survey and provided urine samples for deoxypyridinoline analysis (a marker for
bone turnover) as well as received hearing tests. Those who drank TNJ had slightly greater average
deoxypyridinoline crosslinks, indicating increased bone resorption. This finding was consistent with
the observed attenuation of hearing loss that also occurred in the TNJ group, as the transmission
of sound vibrations by the bones of the middle ear is influenced by the severity of osteoporosis.
These positive effects on bone health also accompanied improvements in several quality of life scores
including mental health scores.
Two additional small human pilot studies suggest that noni juice may also have a positive
impact on hypertension and gingivitis. In a one-month open-label trial, hypertensive adults drank
two fluid ounces (59 mL) of TNJ twice per day [
82
]. Pre- and post-trial diastolic and systolic
blood pressure measurements were made in triplicate and compared. By the end of the study, all
participants experienced reductions in systolic blood pressure with average diastolic and systolic
readings decreasing from 83 to 76 mm Hg and from 144 to 132 mm Hg, respectively. Accompanying
in vitro
testing suggested that pure noni juice may have some effect on angiotensin converting enzyme
(ACE) and angiotensin receptors (AR). However, this trial included a small number of participants
(
n= 10
), and there was no effect on the blood pressure of normotensive participants in other clinical
trials of TNJ. Therefore, ACE-inhibiting and AR-blocking activities are not likely to occur in real-life
conditions. If noni juice does have an impact on high blood pressure, it may involve other mechanisms
such as reduction of aortic SAR and the release of nitric oxide by macrophages [
83
]. These same
antioxidant and anti-inflammatory mechanisms are reportedly responsible for the hypotensive activity
of olive leaf extract [84,85].
To evaluate the influence of TNJ on oral health, eleven patients with moderate to severe gingivitis
or periodontitis were enrolled in a four-week pilot study [
86
]. These volunteers were divided into a
control group (n= 5) and a TNJ group. Those in the TNJ group rinsed their mouths for two minutes
with 30 mL TNJ plus 30 mL water, followed by swallowing. This was done twice per day for four
weeks. Bacterial samples were isolated from the oral cavity and gingival pouches. Papilla bleeding
Foods 2018,7, 58 9 of 22
(PBI), plaque, and approximal plaque indices were also scored for each volunteer before and after the
treatment period. Those in the TNJ group experienced a significant decline in PBI, especially when
compared to the control group. Interestingly, TNJ had only weak bacteriostatic activity
in vitro
, and
bacterial composition of patient oral cavities did not change significantly during the treatment phase.
Therefore, the study authors concluded that the improvement in clinical outcomes in the TNJ group
was likely a result of the anti-inflammatory properties of noni juice.
The human intervention studies described in this section as well as in the preceding sections are
summarized in Table 1. The experimental designs employed have ranged from small pilot studies with
few participants to double-blind placebo-controlled clinical trials involving hundreds of volunteers.
Foods 2018,7, 58 10 of 22
Table 1. Summary of human intervention studies of noni juice products.
Study Reference Study Type Study Population Number of
Subjects in Study Treatment Oral Doses Duration Main Outcomes
West et al. 2009
[22]
Double blind, placebo-
controlled clinical safety study Healthy adults 96 Mixed noni juice beverage
(TNJ) *
0 mL (placebo), 30 mL,
300 mL, and 750 mL daily 28 days
No dose-related adverse events or effects
on clinical chemistry and hematological
measurements, urinalysis,
electrocardiogram, blood pressure, heart
rate, or body weight.
Wang et al. 2009
[24]
Double blind, placebo-
controlled clinical trial
Heavy cigarette smokers
(>20 cigarettes/day) 285 Mixed noni juice beverage
(TNJ) *
0 mL (placebo), 29.5 mL,
and 118 mL daily 30 days
26.9–30.8% reduction in mean plasma
superoxide anion radicals (p< 0.001) and
24.5–27.3% mean reduction in plasma
lipid hydroperoxides (p< 0.001).
Wang et al. 2009
[25]
Clinical trial, no placebo
comparator reported
Heavy cigarette smokers
(>20 cigarettes/day) 203 Mixed noni juice beverage
(TNJ) *
0 mL (placebo), 29.5 mL,
and 118 mL daily 30 days
44.9% average reduction in aromatic
DNA adducts in peripheral blood
lymphocytes (p< 0.001).
Wang et al. 2013
[26]
Double blind, placebo-
controlled clinical trial
Heavy cigarette smokers
(>20 cigarettes/day) 245 Mixed noni juice beverage
(TNJ) *
0 mL (placebo), 29.5 mL,
and 118 mL daily 30 days
20.3–25.6% reduction in mean total
cholesterol (p< 0.05), 29.4–41.2%
reduction in mean triglycerides (p< 0.05),
15.2% reduction in mean hs-CRP
(p< 0.001), and 23.9% reduction in mean
homocysteine (p< 0.05). Mean HDL
increased from 49 to 57 mg/dL (p< 0.05).
Wang et al. 2012
[27]
Double blind, placebo-
controlled clinical trial
Heavy cigarette smokers
(>20 cigarettes/day) 132 Mixed noni juice beverage
(TNJ) *
0 mL (placebo), 29.5 mL,
and 118 mL daily 30 days
44.6–57.4% reduction in lipid
peroxidation-derived DNA adducts in
peripheral blood lymphocytes (p< 0.001).
Palu et al. 2012
[31]Open-label pilot study
Adult (>40 years age)
non-smokers with normal
to mildly elevated
cholesterol
10 Mixed noni juice beverage
(TNJ) * 59 mL twice per day 30 days
No significant difference between pre-
and post-trial total cholesterol, HDL, or
LDL levels.
Akinbo et al. 2006
[36]
Open-label, conventional
treatment-controlled trial
Cervical spondylosis
patients 90 Mixed noni juice beverage
(TNJ) * 15 mL twice per day 4 weeks
60% of patients in noni group
experienced pain relief and improvement
in range of motion. Efficacy rate was not
significantly different from conventional
treatment (p> 0.05)
Wang et al. 2011
[37]Open-label trial Osteoarthritis patients 82 Mixed noni juice beverage
(TNJ) *
3 fluid ounces (88.5 mL)
daily 90 days
23.7% reduction in frequency (in days) of
severe pain (p< 0.05) and 16.4% decrease
in pain severity (p< 0.05). Improved
psychological state and mood and
improved mobility (p< 0.001).
Palu et al. 2008
[41]Placebo-controlled clinical trial
Highly trained athletes
(middle and long-distance
runners)
40 Mixed noni juice beverage
(TNJ) * 100 mL twice per day 21 days
21% increase in mean time-to-fatigue
(p< 0.05). 25% decrease in mean blood
chemiluminescence/oxidation (p< 0.05).
Foods 2018,7, 58 11 of 22
Table 1. Cont.
Study Reference Study Type Study Population Number of
Subjects in Study Treatment Oral Doses Duration Main Outcomes
Anugweje et al.
2012 [42]Placebo-controlled clinical trial University athletes 46 Mixed noni juice beverage
(TNJ) * 100 mL twice per day 30 days
Significant reduction in mean serum
creatine kinase (from 209.8 to 148.1 IU/L,
p= 0.001) after time-to-fatigue tests.
West et al. 2013
[45]
Double blind, placebo-
controlled clinical trial Semi-professional cyclists 20 Mixed noni juice beverage
(TNJ) * 120 mL daily 14 days
Increases in oxygen uptake at 50-watt
workload (from 15.2 to 17.4 mL/kg/min,
p= 0.005) and VO2max (from 51.5 to
55.0 mL/kg/min, P= 0.009)
Ma et al. 2008 [54] Open-label pilot study Healthy adults 12 Mixed noni juice beverage
(TNJ) * 300 mL daily 8 weeks
Mean serum malondialdehyde levels
declined from 4.81 to 3.90 nmol/mL
(p< 0.01), mean serum IL-2 increased
from 52.5 to 69.2 pg/mL (p< 0.05), and
mean natural killer cell activity increased
from 27.7 to 36.0% (p< 0.05).
West et al. 2014 §
[66]Open-label pilot study
Overweight or obese
adults with grade 1
hypertension and
impaired fasting glucose
34 Mixed noni juice beverage
(MAX) 60 to 240 mL daily 8 weeks
Decrease in mean skin autofluorescence
units, a measurement of advanced
glycation end products (A.G.E.s), from
1.89 to 1.77 units (p< 0.05).
Palu et al. 2011
[79]Open-label pilot study Adults with a body mass
index greater than 25 22
Mixed noni juice beverage
,
exercise intervention,
calorie restriction, and other
dietary supplements
30 mL daily 12 weeks
Every participant in the trial experienced
weight loss. Mean percent body fat
decreased by 8.91% (p< 0.0001). It is
difficult to determine the degree to which
noni juice contributed to this outcome.
Bogdanov et al.
2015 [80]
Open-label prospective study in
3 parallel groups Obese adults (grade 3) 90
Low sodium and calorie
restricted diet, as well as 2
different mixed noni juice
beverages (TNJ, MAX) *,†
(each used by a different
group)
60 mL twice per day 42 days
After 6 weeks of calorie restriction, the
average loss of lean muscle mass was
3.1–4.1% in the two noni groups,
whereas it was 8.5% in the control group
(p= 0.0051). Maintenance of weight loss
throughout the 6-week period was
greater in the noni groups than in the
calorie restriction only group.
Langford et al.
2004 [81]Placebo-controlled pilot study Post-menopausal women 8 Mixed noni juice beverage
(TNJ) *
2 fluid ounces (59 mL)
twice per day 3 months
Improved mental health score in SF-36
clinical survey (p= 0.05). Trend of slight
increase in mean urinary
deoxypyridinoline concentration.
Attenuated hearing loss at 8000 Hz
compared to the placebo group (p= 0.05).
Foods 2018,7, 58 12 of 22
Table 1. Cont.
Study Reference Study Type Study Population Number of
Subjects in Study Treatment Oral Doses Duration Main Outcomes
Palu et al. 2008
[82]Open-label pilot study Hypertensive adults 10 Mixed noni juice beverage
(TNJ) *
2 fluid ounces (59 mL)
twice per day 4 weeks
Systolic blood pressure (BP) was reduced
in all participants. Diastolic BP was
reduced in nine participants. Mean
systolic and diastolic BPs were reduced
from 144 to 132 mmHg and from 83 to
76 mmHg, respectively.
Glang et al. 2013
[86]
Open-label pilot study with a
no-treatment control group
Adults with moderate to
severe
gingivitis/periodontitis
11 Mixed noni juice beverage
(TNJ) * 30 mL twice per day 4 weeks
Decline in mean papilla bleeding index
(from 2.25 to 1.01) was significantly
greater than that of the control group
(p= 0.01).
* Tahitian Noni
®
Juice (TNJ, manufactured by Morinda, Inc., American Fork, UT, USA); contains noni juice from puree (89%) as well as grape (Vitis vinifera) and blueberry (Vaccinium
corymbosum) juices.
TruAge Max (MAX, manufactured by Morinda, Inc., American Fork, UT, USA); contains noni juice from puree, olive (Olea europaea) leaf extract and cornelian cherry
(Cornus officinalis and Cornus mas) juices.
Tahitian Noni
®
Original Bioactive Beverage (manufactured by Morinda, Inc. American Fork, UT, USA); contains noni juice from puree (89%) as
well as grape and blueberry juices.
§
A cross-sectional population study (n= 3913 Japanese volunteers) of the anti-AGE effect of mixed noni juice beverage ingestion, was not included in
this table, as it is not an intervention study.
Foods 2018,7, 58 13 of 22
10. Noni Extract Studies
There have been several clinical trials with various noni extracts. The phytochemical compositions
of these extracts are considerably different than that of noni fruit juice. Therefore, the conclusions
drawn from these studies may not be applicable to noni juice. However, they are briefly described in
this review as they may provide some additional insight into the general health-promoting properties
of the noni plant.
A phase 1 clinical trial of freeze-dried noni fruit capsules found no evidence of toxicity but did
reveal dose-dependent improvements in physical functioning, pain, and fatigue in patients with
progressing advanced cancer for which no standard treatment was available [
87
]. A randomized,
placebo-controlled clinical trial with 100 adult patients revealed that an aqueous extract of dried
whole noni fruit prevented postoperative nausea when ingested one hour before surgery [
88
].
Ingestion of an aqueous noni fruit extract increased ranitidine absorption in healthy adult volunteers,
indicating a possible effect on gastrokinetic activity that might make it useful as a carminative and
appetite-stimulating agent and in the relief of heartburn [
89
]. A noni fruit extract exhibited analgesic
properties comparable to or better than ibuprofen in a randomized parallel clinical trial involving
51 patients who had undergone simple tooth extraction procedures [
90
]. The results of a three-month
open-label longitudinal study demonstrated the potential anti-stress (adaptogenic) effect of an herbal
mixture that included noni [
91
]. Human trials involving the topical application of noni extracts as
well as noni fruit juice indicate anti-inflammatory, anti-acne, and anti-aging activities within the
skin [9296].
11. Discussion
Considerable evidence among the results of these human studies has demonstrated that noni
juice has notable antioxidant activity, more than the other common fruit juices that were used in
the placebos. It suggests that the antioxidant effects of TNJ are universal as it has been observed in
heavy smokers, athletes, and in ordinary healthy people. This antioxidant activity may involve direct
chemical reactions between phytochemicals and reactive oxygen species or may involve the induction
of antioxidant enzyme systems. Examples of these two mechanisms were found in both
in vitro
and
in vivo studies of noni juice.
TNJ was also evaluated for its
in vitro
antioxidant activity in the LOOH and tetrazolium nitroblue
(TNB) assays [
97
]. The SAR scavenging activity of TNJ, as measured in the TNB assay, followed a
linear positive dose-response. The SAR scavenging activity of 7
µ
L/mL TNJ was also compared to
those of 13.3
µ
g/mL vitamin C, 13.3
µ
g/mL Pycnogenol
®
(Twin Labortories, Inc., New York, NY,
USA), and 22.2
µ
g/mL of grape seed powder, the latter three being well known for their antioxidant
activity. The SAR-scavenging activity of TNJ was 2.8 times greater than vitamin C, 1.4 times greater
than Pycnogenol
®
, and 1.1 times greater than grape seed powder. Notably, the total solid material
in 7
µ
L TNJ was approximately 0.7
µ
g. Therefore, a much smaller amount of noni juice solids, 3 to
5% of the total weight of the other antioxidants exhibited greater SAR-scavenging activity. As with
SAR scavenging activity,
in vitro
LOOH quenching activity followed a linear positive dose-response,
revealing a consistent antioxidant action.
Ingestion of TNJ protected the livers of Sprague-Dawley (SD) rats exposed to carbon
tetrachloride and resulted in decreased hepatotoxic lesions and significant reductions in serum
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) when compared to a placebo
group [
98
]. Further, SAR and LOOH levels were significantly lower in the liver tissue of noni-fed
rats [
99
]. Carbon tetrachloride (CCl
4
) causes extensive liver damage from lipid oxidation processes
as a result of the formation of the trichloromethyl and trichloromethyl peroxide radicals during
metabolism. These trichloromethyl radicals initiate lipid peroxidation of unsaturated fatty acids
resulting in cytotoxic and genotoxic LOOH and other decomposition products as well as increased
pro-inflammatory SAR production [
100
,
101
]. As such, the liver protective results in these
in vivo
Foods 2018,7, 58 14 of 22
studies suggest that noni juice may contain compounds that are capable of scavenging trichloromethyl
radicals or subsequent peroxidation products.
Ingestion of TNJ by ICR mice for 30 days resulted in a dose-dependent decrease in blood MDA
as well as dose-dependent increases in glutathione peroxidase and superoxide dismutase activities
in the liver [
102
]. Feeding of deacetylasperulosidic acid (DAA), a major phytochemical constituent
of noni juice, for seven days to Wistar rats resulted in a significant increase in enzymatic antioxidant
activity. Further, a dose-dependent reduction in serum MDA concentration, a downstream oxidation
product of SAR action, accompanied an increase in superoxide dismutase activity, suggesting that
DAA ingestion increased catalase activity [70].
As previously discussed, the antioxidant properties of noni juice, likely, contribute to its
immune modulating activity. This attribute may also be at least partially responsible for noni’s
anti-inflammatory activity. The relationship among inflammation, the immune system, and
reactive oxygen species (ROS) is well established in the scientific literature. Leukocytes release
pro-inflammatory cytokines and ROS which, in turn, cause a “respiratory” or oxidative burst by
NADPH oxidase. This leads to further inflammation as well as recruits and activates other leukocytes.
This inflammatory process leads to tissue damage such as that occurring in certain types of muscle
injury [
103
]. Antioxidants have been shown to suppress neutrophil chemotaxis (recruitment) and
reactive oxygen intermediates [
104
,
105
]. Antioxidants also have an influence on cyclooxygenase-2
(COX-2) expression and activity. Reactive oxygen intermediates are involved in signaling pathways that
lead to COX-2 expression in cells. Inhibition of COX-2 expression has been observed in vitro, in vivo,
and ex vivo for a variety of radical scavengers [
106
108
]. As the rate of prostaglandin synthesis by
cyclooxygenases is dependent on peroxide, antioxidants and enzymes that limit peroxide availability
may inhibit cyclooxygenase activity [
109
,
110
]. Similarly, lipoxygenase is activated by ROS [
111
].
Therefore, antioxidants may exhibit anti-inflammatory activity by way of multiple mechanisms.
The antioxidant mechanisms induced by noni juice appear to be involved, to some degree, in
all of the effects reported in human interventions studies. It is very likely that this property of noni
juice is central to its observed effects on physical fatigue, weight control, osteoporosis, hypertension,
and gingivitis. Certainly, antioxidant action is a major mechanism by which noni juice controls AGE
formation [68].
There are limitations in applying the results of the human studies discussed in this review to
noni products in general. First, these noni juice studies were conducted on one commercial source.
This source is noni fruit puree from French Polynesia, and the safety and efficacy of other sources
may not be the same. As briefly mentioned above, there is wide variability among the nutrient and
phytochemical compositions of commercial noni products. An analysis of 177 commercial noni juice
products revealed large differences among the mineral content of these products [
39
]. One reason
for this is the inclusion of different ingredients in these juice products. Another reason is the use of
varying amounts of different types of noni materials. From a safety perspective, this variability is
significant. An example of this is provided in a liver injury case involving a 14-year old boy who had
been ingesting what was purportedly a noni juice dietary supplement [
112
]. However, subsequent
chemical analysis of this supplement revealed that it contained less than 1% noni juice as well as
included other ingredients that were not declared on the product label. Ingredients other than noni
were responsible for the liver injury [
113
]. Another example is a product that was marketed as a noni
fruit extract but was devoid of any of the well-known chemical markers of noni fruit. After evaluation
in a reproductive toxicity test, this counterfeit noni extract was reported to be potentially less safe
than authentic noni fruit that had been evaluated in several other reproductive toxicity tests [
114
,
115
].
A third example is a case of liver injury from a noni product of unknown identity that was purchased
from a local market in Ecuador and brought to Europe for personal use [
116
]. This product was not
produced with the same quality controls that ensure an authentic and safe noni juice product and was
not a product approved for use by the European Union.
Foods 2018,7, 58 15 of 22
These particular instances of product adulteration are a warning that a label declaration of “noni
juice” does not guarantee that a product is either safe or authentic. Authentic noni juice made from
noni fruit puree from French Polynesia (TNJ) has been subject to thorough safety assessments by
European Union officials. Consumption of this source of noni fruit juice has been determined to be
safe as have ingredients derived from the same source [
117
,
118
]. Nutrient and chemical specifications
for these ingredients were set in place to provide an identity for what has been demonstrated to be
safe [
119
]. When noni fruit is processed into puree, the seeds and skin are removed. There are several
consequences to this in terms of phytochemical content. Among these is an increase in the safety
profile due to the prevention of possible anthraquinone contamination [
120
]. This is one reason why
processing of noni fruit into puree is a recommended and approved method.
Differences in harvesting and processing methods for noni fruit also have an impact on potential
efficacy. For example, the degree of ripeness at harvest and subsequent post-harvest aging may
influence antioxidant activity as well as vitamin C and phenolic compound content [
121
,
122
]. Also,
changes that occur during long periods of fermentation include significant losses in antioxidant
activity [
123
]. On the other hand, production of noni fruit puree does not seem to significantly affect
deacetylasperulosidic acid, scopoletin, or vitamin C content [67,124].
Geographical, or environmental, factors (soil, sunlight, temperature, precipitation, etc.) may
significantly influence noni fruit composition. Scopoletin, rutin, quercetin, and 5,15-dimethylmorindol
were detected in greatly varying concentrations in noni fruits and noni fruit juice products sourced
from 13 different nations located in the Caribbean, Central America, the Central Pacific, the South
Pacific, and Asia [
125
]. Iridoid content was also substantially different among samples of noni fruit
collected from French Polynesia, Tonga, the Dominican Republic, Okinawa, Thailand and Hawaii,
with French Polynesia containing the highest concentration and the Dominican Republic containing
the lowest [
67
]. Principle component analysis of commercial noni juice products has also revealed
regionally distinct phytochemical profiles [
126
]. Further, iridoid glucoside, scopoletin, rutin, and
fatty acid glucoside concentrations were considerably different among various samples of noni fruits,
powdered fruit capsules, noni juices, and mixed noni fruit juices. Noniosides B and C as well as
scopoletin were even absent in some samples of commercial noni juice [127].
12. Conclusions
The weight of evidence obtained from human studies point to noni juice’s greater antioxidant
activity than the other fruit juices that served as placebos. It is this activity and its interaction with the
immune system and inflammation pathways that may account for much of the observed health benefits
of noni juice. These health benefits may include protection against tobacco smoke toxicities—including
DNA protection, normalization of blood lipids, control of systemic inflammation, and reduction of
homocysteine—improvement of joint pain and mobility, increased physical endurance, increased
immune activity, control of AGE accumulation, weight management, maintenance of bone health in
women, control of blood pressure, and improved gum health.
The existing evidence does have some general limitations in its application to noni juice products.
Geographical factors, along with post-growth factors (harvesting, storage, transportation, processing,
and formulation) produce commercial noni juice products with different phytochemical and nutrient
profiles. Differences in phytochemical profiles will likely result in variations in biological activity [
128
].
As such, conclusions drawn from the human clinical trials discussed in this review may be limited
to a single source of noni juice. Noni juice products from other sources are likely to have somewhat
different toxicological and pharmacological profiles.
Author Contributions:
B.J.W., S.D., F.I., A.U., and C.J.J. were all involved in the development, review and
approval of this manuscript.
Conflicts of Interest:
The authors declare no conflict of interest. The authors are employed in the research and
development department of Morinda, Inc., a manufacturer of noni juice.
Foods 2018,7, 58 16 of 22
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... Noni juice, made from fermenting the fresh fruit juice of the noni tree (Morinda citrifolia L.), is a traditional folk medicine and tonic used by Pacific Island populations for the treatment of a broad range of health conditions and diseases [1][2][3]. Its major purported health benefits include improving cardiovascular health, reducing inflammation, providing anti-obesity and analgesic effects and protecting against tobacco-induced DNA damage [4][5][6]. Moderate anti-cancer effects have also been reported [2,7,8]. Noni juice may also improve immune health [9] and provide a feeling of overall wellbeing [10]. ...
... Many of these health benefits have been attributed to the exceptionally high antioxidant activity found in noni juice-much higher than that of any other fruit juice [4]. However, the mechanism of action for most of its biological properties remains understudied [6]. ...
... Despite the popular interest in noni juice, there have been relatively few studies investigating the typical chemical composition of this matrix in detail. Complicating this further is the fact that different brands of noni juice may have different proportions of ingredients and thus different compositions; this may lead to varying biological effects [4]. A study by Wang et al. [11] found promising anti-cancer activity against breast cancer induced in female rats, while several other reports of in vitro and in vivo activity have also been reported [12]. ...
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Fermented juice from the noni tree (Morinda citrifolia) is a traditional medicinal product used by South Pacific Islanders to treat a wide range of ailments, including cancer, inflammation and obesity, as well as improving overall wellbeing. Many of its bioactive properties have been suggested to arise from the high antioxidant capacity and phenolic content found in the juice. However, there have been limited investigations into the phenolic profiles of noni juice produced locally in the Pacific. This study aimed to investigate the chemical composition and bioactive properties of noni juice. The first phase of this study used liquid chromatography with tandem mass spectrometry (LC-MS/MS) to characterise the phenolic composition of five brands of commercial noni juice produced in the South Pacific region. A total of 21 phenolic compounds were putatively identified, with the most abundant generally being rutin, 4-hydroxybenzoic acid and gentisic acid. Vastly differing phenolic profiles were found between the noni juice brands. Significant differences were also found in their antioxidant capacities and total phenolic contents. Of the three major phenolic compounds identified, gentisic acid showed the highest antioxidant activity (640% higher than Trolox). Additionally, the noni juice showed no significant anti-acetylcholinesterase activity and no to moderate cytotoxicity against two cancer cell lines (HeLa and HT29). These results indicate that the phytochemical profiles—and hence, the expected bioactive properties—are likely to vary significantly between different noni juice brands. Furthermore, the anti-cancer activity of non-concentrated noni juice appears to be relatively low.
... Brazil. The Noni plant is an important traditional Polynesian medicinal plant and nutritional food for almost over 2000 years with more potential health benefits (Almeida, de Oliveira et al., 2019;West et al., 2018) [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] , Noni fruit itself is commonly consumed as a juice beverage, although leaves, flowers, bark, and root were also used in traditional medicine preparation (Ahmad et al., 2016) [1] . The diverse number of properties of the plant were identified, including immunostimulatory, antitumor, antidiabetic, anti-obesity, antibacterial, antiseptic, antifungal activities, and so on (Lin et al., 2017) [15] . ...
... Brazil. The Noni plant is an important traditional Polynesian medicinal plant and nutritional food for almost over 2000 years with more potential health benefits (Almeida, de Oliveira et al., 2019;West et al., 2018) [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] , Noni fruit itself is commonly consumed as a juice beverage, although leaves, flowers, bark, and root were also used in traditional medicine preparation (Ahmad et al., 2016) [1] . The diverse number of properties of the plant were identified, including immunostimulatory, antitumor, antidiabetic, anti-obesity, antibacterial, antiseptic, antifungal activities, and so on (Lin et al., 2017) [15] . ...
... The diverse number of properties of the plant were identified, including immunostimulatory, antitumor, antidiabetic, anti-obesity, antibacterial, antiseptic, antifungal activities, and so on (Lin et al., 2017) [15] . Both in vivand in vitro studies indicate that the plant exhibits great use in alternative medicine for various illnesses (West et al., 2018) [21] . Counts of 160 phytochemicals compounds in Noni were identified and with major micronutrients all of which are phenol compounds, organic acids, and alkaloids (Lin et al., 2017 [15] . ...
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Noni (Morinda citrifolia Linn.) fruit is a nutritional food with more potential health benefits for many years. In the present study, methanol solvent extract of dry noni fruit was obtained and its active components were investigated. Firstly, the extract showed antimicrobial activity against Escherichia coli, Streptococcus thermophilus, Staphylococcus aureus, Saccharomyces cerevisiae, and Candida albicans in disk diffusion assay with inhibition zone range (12.25, 12.31, 10.46, 10.77, 12.08 mm) at concentration of 860 mg/mL respectively. Then, twenty-one components were separated and identified in the extract by GC-MS. Among them, six were never reported in Noni plant. Finally, three novel components, 2-furan methanol, 2-furancarboxaldehyde, 5-methyl, and dihydro-3-(2H)-thiophen-one were obtained commercially. The dilution turbidity assay showed that they all exhibit antimicrobial activities against the above strains. Our data provides sufficient evidence of novel for its application in the food industry case of bio-preservatives and dietary sources for antimicrobial activity from the natural source.
... In 1996, due to nutraceutical and therapeutic properties, the commercial noni juice was marketed as a dietary supplement and sanctioned in 2003, by the European Commission as a new food [13] . The Chinese government has also sanctioned one source of noni juice as a harmless novel resource and has approved to be a functional food that can improve immunity [14] . Noni plant parts have very strong bioactivity to human health like; immunostimulatory, antitumor, antidiabetic [15,16] , antiobesity, anti-microbial and anti-septic, antiviral , leishmanicidal, anti-inflammatory, antinociceptive and painrelieving, antioxidant, neuroprotective [17] , abrasion healing [18] , antiallergic, anti-dyslipidemia [19] , antiangiogenic, antiemetic and anti-nauseant-gastric ulcer and esophagitis, antimutagenic, antipsychotic [20] , antianxiety [21,22] , photo protective [23] , anti-wrinkle and with periodontal bone and soft-tissue rejuvenation [2,5,[24][25][26][27][28][29][30][31] . ...
... The analysis pellet yield showed that the TCA/Ace method was the most efficient for NFF (0.48 per 36.04 mg) and NDF (0.45 per 84.87 mg) extrapolating a 1.3% and 0.05% pellet recovery rate respectively. According to our result seen in Figure 2, it shows the 16% SDS-PAGE of both NFF and NDF, several levels of protein bands were able to be separated with protein size range from 10-130 kDa respectively which was similarly to past electrophoretic profile of protein bands ranging from 14 to 55 kDa analyzed from cheese manufactured from noni puree extract [42] . Further analysis to the 16% SDS-PAGE for NFF, there were 12 protein bands with protein size range of 10-130 KDa and compared to the NDF where it could be seen with 5 protein bands with size ranges from 15-50 KDa. ...
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Polyacrylamide gel electrophoresis (PAGE), is a molecular biotechnological method used to separate organic macromolecules, usually nucleic acids and proteins, according to their electrophoretic mobility. The use of SDS-PAGE and 2D-PAGE technology were used for the first time on both noni fresh fruit (NFF) and noni dry fruit (NDF) with TCA/Ace adapted method was achieved successfully in this study. Morinda citrifolia Linn or noni fruit has multiple medicinal functions and is a good food source. Noni fruit was used for over 2000 years till today and taking so much interest in present studies to investigate the compound composition of the pulp. In this present study, the use of PAGE the NFF showed 12 band-layers ranging from 10-130KDa compared to NDF with only 5 band-layers with protein size range 15-50KDa. The 2D-PAGE of the NFF protein spots detection of (18.55 ± 0.71) and ranged from 10-72 KDa.
... Among the isolates, n-butyl β-D-glucopyranoside, (1S)-(3-ethenyl-phenyl)-1,2ethanediol showed moderate quinone reductase-1 (QR-1) inducing activities, whereas all of them showed weak or no inhibitory activities against the TNF-α-induced NF-κB and NO production. Moreover, the phytochemical biological activity, pharmacological and clinical trials health effect have been extensively summarized [8][9][10]. Although, there have been several studies with various noni fruit and extracts. ...
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Noni bio-fermented drink is a fermented fruit of Morinda citrifolia L. Noni fruit is reported to be useful for a wide range of maladies, and consumers throughout the world perceive similar benefits. However, the existing evidence does have some limitations as far as its general application to noni fruit products. This study is intended to assess the quality of noni bio-fermented drink. The fruit was fermented using wild environmental yeast by a local entrepreneur. After 3 months, the mixture was filtered, sweetened, pasteurized, and bottled. The finish product was investigated for its antioxidant activity, total phenolic content and phytochemical constituents. Antioxidant activities exhibited profound results in term of 2,2-diphenyl-1-picryhydrazyl (DPPH) assay with an IC50 value of 14.94±0.76 μg/mL which was very close to that of Trolox at 8.47±0.16 μg/mL. The low phenolic content of 0.75±0.01 mg gallic acid equivalent (GAE)/g measured by Folin-Ciocalteu reagent method. The data of mass spectra and their fragmentations from LC-MS/MS identified 53 of 59 phytochemical compounds from the drink. Iridoid glucosides; asperulosidic acid, deacetylasperulosidic acid and monotropein as well as coumarin; aesculetin, scopoletin were identified as markers of this drink. Moreover, amino acids including organic acids, sugars and sugar in glycosidic forms were elucidated. Sulfur compounds in this drink namely 2-Sulfanylpropan-1-ol; 3-sulfanylpropan-1-ol, thiodiglycol and L-Methionine were identified as the possible cause of the pungent characteristic fragrance. As a result, noni fruit bio fermented drink encompasses numerous nutrients and biological compounds with potent antioxidant activity which could be stated as wellness drink for health merit. HIGHLIGHTS Chemical profiles of Thai noni fruit bio-fermented drink was established Noni drink contains numerous phytonutrients and bioactive compounds Flavonoids and Iridoid glycosides can be identified and selected as markers for quality control LC-MS/MS is a powerful technique for identification of compounds U2T program for product development GRAPHICAL ABSTRACT
... In addition, Noni fruit is also a good source of natural polysaccharides (4). In Polynesia, India, Malaysia, Indonesia, and China, Noni fruit has been perceived as a traditional herb for over 2,000 years (5). Several in vitro and in vivo studies have reported that Noni fruit and its derived products exhibit anti-inflammatory, antidiabetic and antiproliferative activities as well as free radical scavenging activity (6,7). ...
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Introduction Morinda citrifolia L. (Noni) as an evergreen plant is a rich source of natural polysaccharides. Objective The present work aims to investigate the maturation-related changes in polysaccharides of Morinda citrifolia L. (Noni) at five stages of maturity (stages from the lowest to highest degree – 1, 2, 3, 4, and 5). Methods The chemical composition (carbohydrate, protein, uronic acid, and sulfate radical) of Noni polysaccharides was determined by different chemical assays. Ion chromatography system was used to analyze the monosaccharide composition, and the molecular weight was measured by HPGPC. The polysaccharides were also analyzed by FT-IR and their radical scavenging effect against DPPH, hydroxyl radicals and ABTS was evaluated. The UV-vis assay and gel electrophoresis assay were performed to investigate the DNA damage protective effect. Results Results indicated the significant effect of fruit maturities on the extraction yields, molecular weights, uronic acid contents, sugar levels, monosaccharide compositions and proportions, antioxidant capacities, and DNA protective effects of Noni polysaccharides. However, no fruit maturity stage had prominent impact on the sulfuric radical contents and preliminary structure characteristics. Noni polysaccharides extracted at stage 5 (N5) had the largest extraction yield (8.26 ± 0.14%), the highest sugar content (61.94 ± 1.86%) and the most potent scavenging effect on DPPH (IC 50 : 1.06 mg/mL) and ABTS (IC 50 : 1.22 mg/mL) radicals. The stronger DPPH and ABTS radical scavenging activities of N5 might be contributed by its higher content of fucose and rhamnose and smaller molecular weight. Noni polysaccharides extracted at stage 4 (N4) showed the highest uronic acid content (4.10 ± 0.12%), and the superior performance in scavenging hydroxyl radicals and protecting DNA. The greater hydroxyl radical scavenging effect of N4 might be attributed to its higher percentage of the low molecular weight counterpart. Moreover, the DNA protective effects of N4 displayed a positive correlation with its hydroxyl radical scavenging ability. Conclusion Overall, stage 4 and stage 5 could be ideal stages of fruit maturity aiming at high-quality Noni polysaccharides extraction. This study provided valuable information for the selection of suitable Noni polysaccharides to cater for various industrial applications.
... Morinda citrifolia L. (Mengkudu) has been used as a medicine for centuries in every corner of the globe due to its therapeutic capabilities, which include the treatment of rheumatic and other pain and healing benefits (Chong et al., 2018). Morinda citrifolia is also reported to exhibit a natural cure for lowering blood pressure, reducing joint swelling, stopping internal and external infections, clearing out congestion, and even preventing the growth of pre-cancer cells (West et al., 2018). The beneficial health effects observed might result from specific compounds extracted from the roots, leaves, peel and fruits such as nitric oxide, alkaloids and sterols with antioxidant potential (Chan-Blanco et al., 2006;Mohd Zin et al., 2007). ...
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Morinda citrifolia L. (Mengkudu) leaf is not well-known for its benefits compared to M. citrifolia fruit. It can be considered a good source in healing disease and anti-cancer properties due to the high content of antioxidant enzymes. The objective of this study was to determine the antioxidative activities of M. citrifolia leaves extracted at different pH (pH 3 to pH 9) and temperatures (20°C to 80°C), based on four types of antioxidant enzymes test, namely catalase (CAT), peroxidase (POD), polyphenol oxidase (PPO) and superoxide dismutase (SOD). Another analytical test is the protein determination of M. citrifolia leaves using Bovine Serum Albumin as standard. All of the tests were conducted using spectroscopy methods. Catalase (CAT) activity was monitored by reduction of absorbance due to the decomposition of hydrogen peroxide and peroxidase (POD) activity was observed by an increment of absorbance caused by the oxidation of 4-methylcatechol by hydrogen peroxide. Polyphenol oxidase (PPO) was monitored by an increment of absorbance due to the oxidation of 4-methylcatechol and superoxide dismutase (SOD) activity was determined using the NBT-based method, which monitors the amount of enzyme causing 50% inhibition of photochemical reduction of NBT. Results indicated that CAT activity and POD activity were significantly highest (p<0.05) at pH6, 0.51 U/mg for CAT, 2.58 U/mg for POD, while SOD activity was significantly higher at pH7, 0.47 U/ mg. However, no significant difference (p>0.05) was observed for PPO activity in pH treatment. For different temperature treatments, CAT activity was significantly highest (p<0.05) at 50°C, 0.36 U/mg, while PPO activity and SOD activity were found to be significantly highest (p<0.05) at 30°C, 0.64 U/mg for PPO and 0.43 U/mg for SOD. However, all-temperature treatments given did not significantly affect POD activity. Morinda citrifolia leaves have a good antioxidant potential and can be practised in the treatment of diseases associated with oxidative stress.
... For a long time, noni was considered a medicinal and edible plant by people in many tropical regions [4][5][6][7][8]. Previous studies confirmed that noni contains various functional phytochemicals used clinically as adjuvant medicine in hypertension, hyperglycemia, and cancer [9][10][11]. ...
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Scopoletin, the main component of clinical drugs and the functional component of health products, is highly abundant in noni fruit (Morinda citrifolia). Multiple enzyme genes regulate scopoletin accumulation. In the present study, differentially expressed genes of noni were analyzed by RNA sequencing (RNA-Seq) and the full-length genes by isoform-sequencing (Iso-Seq) to find the critical genes in the scopoletin accumulation mechanism pathway. A total of 32,682 full-length nonchimeric reads (FLNC) were obtained, out of which 16,620 non-redundant transcripts were validated. Based on KEGG (Kyoto Encyclopedia of Genes and Genomes) annotation and differential expression analysis, two differentially expressed genes, caffeic acid 3-O-methyltransferase (COMT) and caffeoyl-CoA O-methyltransferase (CCoAOMT), were found in the scopoletin accumulation pathway of noni. Real-time quantitative polymerase chain reaction (q-PCR), phylogenetic tree analysis, gene expression analysis, and the change in scopoletin content confirmed that these two proteins are important in this pathway. Based on these results, the current study supposed that COMT and CCoAOMT play a significant role in the accumulation of scopoletin in noni fruit, and COMT (gene number: gene 7446, gene 8422, and gene 6794) and CCoAOMT (gene number: gene 12,084) were more significant. These results provide the importance of COMT and CCoAOMT and a basis for further understanding the accumulation mechanism of scopoletin in noni.
... Palu et al. (2009) subsequently found that the molecular mechanism of TNJ in gout was attributed to its inhibitory effect on xanthine oxidase. Relevant human clinical trials have demonstrated that drinking noni juice is healthy, beneficial and safe and may be closely related to its antioxidant effects (West et al., 2018). Moreover, Li's group found that miRNAs are also involved in the therapeutic effect of noni juice on AGA. ...
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Gout is a common form of arthritis caused by the deposition of sodium urate crystals in the joints and tissues around them. MicroRNAs (miRNAs) are noncoding RNAs that have been shown to be involved in regulating the pathogenesis of gout through multiple cellular signaling pathways, which may be potential targets for the treatment of gout. In this review, we systematically discuss the regulatory roles of related miRNAs in gout, which will provide help for the treatment of gout and miRNAs is expected to become a potential biomarker for gout diagnosis.
Chapter
Cornus mas L. (cornelian cherry) is a member of the Cornaceae family. It is widely used in traditional cuisine and folk medicine in numerous countries of Europe and Asia. Anthocyanins, flavonoids, iridoids, vitamin C and minerals are the major bioactive components of this plant. In folk medicines, different parts of the plant have been used for the treatment or prevention of multifarious diseases (for instance; diabetes, diarrhoea, gastrointestinal disorders, rheumatic pain, kidney and liver diseases, sunstroke, etc.). Moreover, antioxidant, antimicrobial, anti-hyperlipidaemic, anti-diabetic, anti-obesity, cardio-protective, liver-protective and renal-protective activities of C. mas have been confirmed by various studies. Regrettably, clinical trials are very few. This chapter aims to contribute an overview of ethnomedicinal uses, chemical ingredients, pharmacological properties and usefulness as a nutritional supplement of C. mas.KeywordsCornus mas L.DiabetesDiarrhoeaMultifunctional foodCornelian cherryAnthocyanin
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Thai Traditional medicine was developed more than 700 years ago, dating back to Sukhothai (1238–1438 CE), an officially recognized healing system alongside conventional medicine in Thailand. Thai Traditional medicine is defined as “the medicinal procedures concerned with examination, diagnosis, therapy, treatment or prevention of, or promotion and rehabilitation of the health of humans or animals, obstetrics, traditional Thai massage, and also includes the production of traditional Thai drugs and the invention of medicinal devices, base on knowledge or text that has been passed on from generation to generation.” Thai Traditional medicine is diverse and intricate system of health and well-being. It bears a high resemblance in treatment philosophy and medicinal plants used in Ayurveda, the ancient science of life developed in India. Presently, there are around 17,001 practitioners in Thai Traditional medicine; 23,409 practitioners in Thai traditional pharmacy; 5735 practitioners in Thai traditional midwifery; 332 practitioners in Thai massage and 660 practitioners in Applied Thai traditional medicine. Moreover, 74 herbal remedies are implemented in the National List of Essential Medicines 2018 and divided into two categories: (1) Thai Traditional Remedy and (2) Herbal Product. Therefore, the development of medicinal plants for use in primary health care is needed to be concerned. In 2018, Thai Herbal Pharmacopoeia was established providing 80 monographs on herbal drugs and herbal drug preparations. Thai Traditional medicine is gaining popularity and has become a part of the National Health Development Plan. The Ministry of Public Health has taken important steps toward the development, promotion, and protection of traditional medicine in Thailand.
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Background: Morinda citrifolia Linn (noni), as a “pain killer”, has been used as a traditional medicine by Polynesians for over 2000 years. It was reported to have a broad range of therapeutic effects including analgesic and anti-inflammation. The in-vitro and in vivoanti-inflammatory and analgesic properties of noni juice (NJ) suggest that NJ may be a useful adjunctive treatment for osteoarthritis (OA). In this pilot study we explored whether NJ improves the symptoms and Quality of Life (QoL) for adults with OA. We also sought to evaluate the tolerability and safety of NJ for patients with OA in a primary care setting. Methods: This was an open label three-month intervention pilot study. Data were collected by pre/post intervention survey and laboratory testing. Inclusion criteria were: adults of both sexes aged 40 to 75, with a diagnosis of OA on the hip or knee by x-ray examination provided by their primary care physician, not on prescription medicine for OA, and who were willing to drink 3 oz of NJ a day for 90 days. Results: Of the 64 questions measuring different aspects of QoL asked on the pre/post survey, 49 (77%) had significant pre/post mean scale differences as measured by independent t-test. The OA patients reported being significantly more satisfied with their current health conditions including mobility, walking and bending, hand, finger, and arm functions, household tasks, social activity, arthritis pain, work ability, level of tension, and mood. The study participants were also more positive about their future health and reported taking less over-the-counter (OTC) pain relievers. Pre/post laboratory testing including: lipid panel, liver and kidney functions were in the normal ranges. High Sensitive C Reactive Protein (hsCRP), an inflammatory biomarker, was reduced by 10% after the intervention. Conclusion: As a nutritional supplement, NJ demonstrated a potential therapeutic effect and improved the symptoms and the QoL for adults with OA. A larger, double blinded, and placebo controlled clinical trial study is needed to confirm these benefits. NJ has the potential to become an adjunctive therapy for OA patients. Clinical trial registration number: NCT01070264.Key words: Morinda citrifolia (noni), Noni juice (NJ), Osteoarthritis, Quality of life (QoL), pain scales
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Vitamin C is an essential micronutrient for humans, with pleiotropic functions related to its ability to donate electrons. It is a potent antioxidant and a cofactor for a family of biosynthetic and gene regulatory enzymes. Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. Vitamin C supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin, thereby potentially protecting against environmental oxidative stress. Vitamin C accumulates in phagocytic cells, such as neutrophils, and can enhance chemotaxis, phagocytosis, generation of reactive oxygen species, and ultimately microbial killing. It is also needed for apoptosis and clearance of the spent neutrophils from sites of infection by macrophages, thereby decreasing necrosis/NETosis and potential tissue damage. The role of vitamin C in lymphocytes is less clear, but it has been shown to enhance differentiation and proliferation of B- and T-cells, likely due to its gene regulating effects. Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements. Furthermore, supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections. Prophylactic prevention of infection requires dietary vitamin C intakes that provide at least adequate, if not saturating plasma levels (i.e., 100–200 mg/day), which optimize cell and tissue levels. In contrast, treatment of established infections requires significantly higher (gram) doses of the vitamin to compensate for the increased inflammatory response and metabolic demand.
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Cultural and economic shifts in the early 19th century led to the rapid development of companies that made good profits from technologically-produced commodities. In this way, some habits changed in society, such as the overconsumption of processed and micronutrient-poor foods and devices that gave rise to a sedentary lifestyle. These factors influenced host-microbiome interactions which, in turn, mediated the etiopathogenesis of “new-era” disorders and diseases, which are closely related, such as obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, hypertension, and inflammatory bowel disease, which are characterized by chronic dysregulation of metabolic and immune processes. These pathological conditions require novel and effective therapeutic approaches. Morinda citrifolia (noni) is well known as a traditional healing plant due to its medicinal properties. Thus, many studies have been conducted to understand its bioactive compounds and their mechanisms of action. However, in obesity and obesity-related metabolic (dysfunction) syndrome, other studies are necessary to better elucidate noni’s mechanisms of action, mainly due to the complexity of the pathophysiology of obesity and its metabolic dysfunction. In this review, we summarize not only the clinical effects, but also important cell signaling pathways in in vivo and in vitro assays of potent bioactive compounds present in the noni plant which have been reported in studies of obesity and obesity-associated metabolic dysfunction.
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Background Advanced glycation end products (AGEs), senescent macroprotein derivatives formed during a normal aging process and acceleratedly under diabetic conditions, play a role in atherosclerotic cardiovascular disease. AGEs cause endothelial cell (EC) damage, an initial trigger for atherosclerosis through the interaction with a receptor for AGEs (RAGE). We have previously shown that n-butanol extracts of Morinda citrifolia (noni), a plant belonging to the family Rubiaceae, block the binding of AGEs to RAGE in vitro. In this study, we examined the effects of n-butanol extracts of noni on reactive oxygen species (ROS) generation and inflammatory reactions on AGE-exposed human umbilical vein ECs (HUVECs). Methods HUVECs were treated with 100 μg/ml AGE-bovine serum albumin (AGE-BSA) or non-glycated BSA in the presence or absence of 670 ng/ml n-butanol extracts of noni for 4 h. Then ROS generation and inflammatory and gene expression in HUVECs were evaluated by dihydroethidium staining and real-time reverse transcription-polymerase chain reaction analyses, respectively. THP-1 cell adhesion to HUVECs was measured after 2-day incubation of AGE-BSA or BSA in the presence or absence of 670 ng/ml n-butanol extracts of noni. Results N-butanol extracts of noni at 670 ng/ml significantly inhibited the AGE-induced ROS generation and RAGE, intercellular adhesion molecule-1 and plasminogen activator inhibitor-1 gene expressions in HUVECs. AGEs significantly increased monocytic THP-1 cell adhesion to HUVECs, which was also prevented by 670 ng/ml n-butanol extracts of noni. Conclusions The present study demonstrated for the first time that N-butanol extracts of noni could suppress the AGE-induced inflammatory reactions in HUVECs through its anti-oxidative properties via blocking of the interaction of AGEs with RAGE. Inhibition of the AGE-RAGE axis by n-butanol extracts of noni may be a novel nutraceutical strategy for the treatment of cardiovascular disease.
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Cigarette smoke contains more than 4500 chemicals which have toxic, mutagenic and carcinogenic effects. Strong evidences have shown that current smokers take a significantly higher risk of cardiovascular diseases, chronic obstructive pulmonary disease (COPD) and lung cancer than nonsmokers. However, less attention has been paid to the smoking induced abnormalities in the individuals defined as healthy smokers who are normal with spirometry, radiographic images, routine physical exam and categorized as healthy control group in many researches. Actually, ‘healthy smokers’ are not healthy. This narrative review focuses on the smoking related pathophysiologic changes mainly in the respiratory system of healthy smokers, including inflammation and immune changes, genetic alterations, structural changes and pulmonary dysfunction.
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Objectives: Smoking is known to suppress the immune system. It is also known that chronic renal failure affects the immune system. However, the number of studies investigating the effects of chronic renal failure and smoking together is limited. In our study, we examined whether smoking affects the diminished response of the immune system in patients with chronic renal failure. Materials and methods: We compared peripheral blood lymphocyte subsets in smoking and nonsmoking patients with chronic renal failure. We also used the Fagerström Test for Nicotine Dependence to evaluate its correlation with the lymphocyte subset count in patients who are current smokers. Results: Our study included 126 patients with chronic renal failure. According to their smoking habits, patients were divided into 2 groups: smokers and nonsmokers. The average age of patients who were smokers was 53.2 ± 1.5 years, with average age of nonsmokers being 59.2 ± 2.2 years. The average duration of smoking in smokers was 30.7 ± 2.7 packyears. We found that the percentage of cluster of differentiation 16-56 cells (natural killer cells) and lymphocyte percentage were significantly lower among smokers in our study (P < .05). We compared the lymphocyte subset panel to pack-years and found that the rate of cluster of differentiation 16-56 cells decreased as smoking duration increased. Conclusions: Our study revealed that smoking suppresses the immune system, as measured by lymphocyte subsets, in patients with chronic renal failure, similar to that shown in healthy smokers. According to our findings, patients with chronic renal failure, where infection is the primary reason for mortality and morbidity, must be questioned for smoking and referred to smoking cessation clinics. Because of its immunosuppressive effects, smoking behaviors must be solved preoperatively in transplant candidates.
Article
Since the approval of Noni juice as a novel food by the European Commission in 2003, products derived from Noni fruit (Morinda citrifolia, Rubiaceae) are becoming increasingly popular as food supplements [1]. While the knowledge on constituents of Noni fruit has considerably increased over recent years, quantitative data on Noni secondary metabolites remain scarce and the chemical composition of commercial products distributed mainly via internet is poorly established. In the present study, TLC profiles of commercial Noni juices and capsules were compared. Chromatographic markers such as 3-methyl-1,3-butanediol typically found in Noni juices were identified. The presence of sorbic acid (E200) was also revealed in one Noni juice declared as additive-free. In order to obtain quantitative data on the composition of Noni products, an HPLC-MS method has been developed and validated, which enables the quantification of various Noni constituents, including iridoid glucosides, scopoletin, rutin, fatty acid glucosides and anthraquinones. The separation is performed on a C-18 column with a gradient of acetonitrile in water containing 0.1% formic acid. Detection is carried out with ESI-MS in the negative ion mode. The method was applied to the analysis of various commercial juices and capsules. Significant differences were observed between the samples. Asperulosidic acid, deacetylasperulosidic acid and rutin were present in all products analysed, but their concentrations differed greatly between the products. The fatty acid glucosides noniosides B and C [2], as well as scopoletin, present in the fruit powder, were only detected in some commercial preparations. The mutagenic anthraquinone alizarin which has been reported from roots and leaves was not detected in the investigated samples. References: [1] Potterat, O., Hamburger, M. (2007) Planta Med. 73: 191. [2] Dalsgaard, P.W. et al. (2006) Planta Med. 72: 1322.