Citrus aurantium (C. aurantium) is the Latin name for a
plant commonly referred to as bitter orange, sour orange,
Neroli, Chongcao, or Seville orange. It is a source
of synephrine and several other biogenic amines, as well
as other bioactive phytochemicals and has been used in dietary
supplements for weight loss. In this entry,we discuss
the available evidence pertaining to safety and efficacy of
C. aurantium for weight loss, as examined in animal studies,
clinical trials, and case reports.
Bitter orange is a member of the Rutaceae family, a hybrid
between Pummelo, Citrus grandis, and Mandarin, Citrus
Native to Asia, various parts of the plant are
used throughout the world for a variety of indications.
Bitter orange and its components are commercially available
in herbal weight loss supplements, ostensibly for their
adrenergic agonistic properties (1), often in combination
with other ingredients hypothesized to promote weight
loss. Its constituent p-octopamine and synephrine alkaloids
(SAs) are usually cited as the active ingredients in
such products (2). With the banning of ephedra in the
United States in 2004, bitter orange has been increasingly
included in weight loss supplement formulations. Because
of similarities in their constituents and possible mechanisms
(both sources of natural alkaloids with sympathomimetic
activity), concerns have been raised that bitter
orange may carry risks similar to those hypothesized to
exist for ephedra (3).
Bitter Orange origin is in China and appears in writing
as far back as 300 BC.
Its ancient use has also been documented
in Japan and Rome (4). It is native to eastern
Africa, Arabia, and Syria and is cultivated in various European,
North American, and South American regions. The
leaf was historically used as a tonic, laxative, or sedative
in Mexico and South America and for insomnia, palpitations,
or stomachaches by the European Basque people
(5,6). The fruit and peel are also used for stomach aches, as
well as high blood pressure (BP), spasm, and a variety of
gastrointestinal conditions by both the Basque and practitioners
of traditional Chinese medicine (7). While the
practice arose in Ancient Egypt, neroli oil is still currently
used for aromatherapy and bergamot, a subspecies of
C. aurantium, is used for flavoring and aroma in Earl Grey
teas (8). Modern uses for C. aurantium include digestive,
cardiovascular, neuromuscular, and antiseptic indications
in countries such as China, Curacao, Haiti, India, Mexico,
Trinidad, Turkey, and the United States (9). The most
common current western use, however, is as a dietary
supplement for weight loss.
Some authors (10) state that C. aurantium contains meta synephrine
(m-synephrine, m-s), whereas others (11) state
that it contains only para-synephrine (p-synephrine, ps).
However, research (I.A. Khan, oral communication,
2005) has shown that C. aurantium naturally contains
p-synephrine and does not contain m-synephrine. Allison
and colleagues reported that at least one over-the counter
(OTC) product purportedly containing SAs from
C. aurantium contains both p-synephrine andm-synephrine
(12), raising concerns about possible adulteration and
mislabeling. There is also an ortho isomer of synephrine
(o-synephrine), whose content in C. aurantium is unknown.
p-, m-, and o-synephrine can each exist in D or L forms.
p-Synephrine, an undisputed component of C. aurantium,
is typically referred to simply as synephrine (13).
It is an -adrenergic agonist (14) that also has some –
adrenergic properties (15). p-Synephrine occurs naturally
in the human body in small quantities and might act as
a neurotransmitter (16). Under the name oxedrine, it has
been used since 1927 (17) in eyedrops. p-Synephrine is
thought to be the ingredient in C. aurantium primarily
responsible for weight loss. However, neither this nor
whether C. aurantium actually produces weight loss in
humans is firmly established.
m-Synephrine, often referred to as phenylephrine,
is an isomer of p-synephrine. To the best of our knowledge,
m-synephrine is not contained naturally in C. aurantium.
m-Synephrine is also an -adrenergic agonist that has
some -adrenergic agonist properties. It has been studied
more extensively than p-synephrine and is one of the
two most widely used OTC decongestants today (Fig. 1)
(13). p-Synephrine and m-synephrine have similar structure
to ephedrine, as well as other substances that have
some effects on reducing food intake and/or body weight
such as epinephrine and norepinephrine (Fig. 1), supporting
the conjecture that, to the extent that function follows
structure, p-synephrine and m-synephrine, may also reduce
food intake and or body weight.
The -adrenergic sympathomimetic amine, octopamine,
is also present in C. aurantium, though possibly
at appreciable levels (2). Like both forms of
synephrine, it is an -adrenergic agonist with some
Chemical structures of (A) p-synephrine, (B) m-synephrine,
(C) ephedrine, (D) epinephrine, and (E) norepinephrine.
-adrenergic properties. It is used to treat hypertension
and as a cardiotonic (13) and has also been examined for
its potential role in promoting weight loss (18).
Because of their similar properties and the overlap
of their inclusion in supplements, we will refer to these
substances collectively as synephrine alkaloids (SAs). SAs
are used clinically as decongestants (1), during surgical
procedures as a vasopressor (19), for acute treatment of
priapism (20), and in ophthalmological examinations for
pupil dilation (21). Products that contain C. aurantium or
its derivatives, including OTC weight loss supplements,
will be referred to as C. aurantium products (CAPs).
Regulatory oversight for dietary supplements is
much less rigorous than for pharmaceuticals, and extensive
evidence is not required prior to release of a product
on the public market. While a phase of requirements for
meeting good manufacturing practices is currently underway,
this may help to explain why the quality and quantity
of the evidence we have available to evaluate the safety
and efficacy of C. aurantium is minimal.
As sympathomimetic agents with both – and –
adrenergic receptor agonist properties, SAs might increase
energy expenditure and/or decrease food intake (22). In
addition, there is some evidence that adrenergic agonists,
including SAs, decrease gastric motility (23). Similar to
compounds such as cholecystokinin and other gut peptides
which both decrease gastric motility and food intake
(24), one might conjecture that SAs may also decrease food
intake via reducing gut motility. Activation of lipolysis is
a known -adrenergic activity (25) that may be fueled by
these components of C. aurantium.
Bitter Orange Weight Loss
SAs reduce food intake in rodents (26), and some studies
indicate that SAs can reduce rodent body weight
(13,26). SAs have also been shown to promote lipolysis
in adipocytes through -adrenergic stimulation (27)
and to increase lipoprotein lipase activity in the parametrial
fat pad of female hamsters (28). However, among
monosodium glutamate–treated obese mice, SAs reduced
weight gain but had no effect on body fat percent (29).
Toxicity and Mortality
Data suggest that m-synephrine (not present in bitter orange)
may prolong life in rodents. A 2-year study by the
National Toxicology Program (13) evaluated the effects
of m-synephrine on spontaneous food intake of rats and
mice. At 2 years, there were no significant differences in
survival among mice or female rats. However, for male
rats, there was a significant reduction in mortality rate,
although there was increased mortality in the early phase
of the study at the highest dose. It should be noted that
too few deaths occurred during the 2-year trial to provide
the degree of precision and power desired for a rigorous
longevity study (30). Nonetheless, similar results have
been reported for ephedrine, another sympathomimetic
Arbo et al. (32) conducted a subchronic toxicity
study in mice and the effects of p-synephrine and C. aurantium
L. extract on oxidative stress biomarkers that are
believed to be indicators of cell membrane injury (malondialdehyde)
and (glutathione and the enzyme glutathione
peroxidase) indicative of amphetamine-induced toxicity.
The study evaluated adult male CF1 mice treated with
400, 2000, or 4000 mg/kg C. aurantium dried extract and
p-synephrine 30 or 300 mg/kg over the course of 28 days.
Results showed a reduction in glutathione in mice treated
with C. aurantium 400 mg/kg and p-synephrine 30 and
300 mg/kg. Inhibition of glutathione peroxidase activity
occurred within mice treated with C. aurantium 400 and
2000 mg/kg and p-synephrine 30 and 300 mg/kg; however,
no change occurred within malondialdehyde levels.
These two findings suggest the possibility of subchronic
toxicity. No significant change in weight occurred in any
of the groups, suggesting on the positive side a lack of
severe toxicity, and on the negative side a lack of efficacy
in producing weight loss.
With regard to adverse effects, a study (33) of male
Sprague-Dawley rats reported what was believed to be
evidence of cardiotoxicity when C. aurantium fruit extracts
standardized to 4% and 6% SAs were administered. Increased
mortality has been observed among CAPs-treated
rats (33) as well as a strain of mice selected to be uniquely
susceptible to the effects of adrenergic stimulation (34).
CLINICAL TRIALS Bitter Orange Weight Loss
Few clinical trials have examined the effects of CAPs alone
or in combination with other ingredients on body weight
and/or body composition (Table 1). It should be kept in
mind that these trials are of short duration and the sample
sizes are frequently quite small. Nonetheless, these
trials suggest that body weight and/or fat loss may be
enhanced by CAPs or SAs. The mechanisms involved are
unclear but may be partially due to a suppressing effect
of appetite and/or a moderate increase in resting energy
Armstrong et al. (37) evaluated exercise and herbal
preparation containing Ma Huang, bitter orange (5 mg
SAs), and guarana over 6 weeks in a randomized, controlled
trial. Compared with controls, the intervention
group obtained significant reductions in fat mass and a
nearly significant reduction in body mass index (kg/m2)
54 Haaz et al.
Table 1 Summary of Clinical Weight Loss Trials
Reference Treatment Design Sample size Duration Results Comments
Colker et al. (10) 975 mg Citrus
caffeine and 900 mg
St. John’s wort;
placebo (with pill) and
control (no pill)
Supplement n = 9;
placebo, n = 7;
control group (no
pills), n = 4
6 wk Supplement group lost
more fat (3.1 kg; P <
0.05) than other
groups and increased
Citrus aurantium may
assist individuals in
losing body fat, due to
increased energy and
reduced energy intake
adverse events were
Kalman et al. (36) Ephedrine and
(SAs) (5 mg twice
daily) based product
vs. placebo with
exercise and diet
subjects; BMI > 27
8 wk 3.4 kg weight loss in
experimental group vs.
2.05 kg in placebo
(P < 0.05)
No adverse events;
safety and efficacy of
Armstrong et al.
Exercise program with
assignment to drug
(Ma Huang, bitter
orange, and guarana)
or placebo. Bitter
for 5 mg synephrine
study is blinded
44 days Supplement increased
fat loss (2.5 kg; P =
0.033) more than
placebo (0.5 kg))
Low statistical power,
no marked side effects
Greenway et al.
(38): Pilot 1
40 mg; green tea leaf
extract, 200 mg;
550 mg; bitter orange,
150 mg; white willow
bark extract, 50 mg;
ginger root, 10 mg;
naringin), 375 mg
Eight subjects (1:1
supplement group and
8 wk Supplement group
gained more weight
(1.04 °æ 0.27 kg; P <
0.04) than placebo
and increased RMR
(but not at 8 wk)
CAP was not
efficacious for weight
Greenway et al.
(38): Pilot 2
m-Synephrine 20 mg Prospective,
Twenty subjects (1:1
supplement group and
8 wk Supplement group lost
weight (0.8 °æ 3.4 kg;
not significant) in 8
wk, and increased
RMR in 8 wk. No
control group was
November 1, 2009)
m-Synephrine was not
efficacious for weight
Abbreviations: BMI, body mass index; CAP, Citrus aurantium product; RCT, randomized, controlled trial; RMR, resting metabolic rate.
and fat percentage. No significant changes were noted in
resting energy expenditure, blood chemistries, or dietary
intake between the placebo and experimental groups.
In a double-blind, placebo-controlled, randomized
trial, Colker et al. found that subjects receiving a
combination of C. aurantium, caffeine, and St. John’s wort,
along with diet and exercise protocols, lost a statistically
significant amount of body weight. Analysis comparing
changes in this group with those in placebo or control
groups on the same diet and exercise regimen did not
show significant differences, though loss of fat mass was
significantly greater in the experimental group (35). BP,
heart rate, electrocardiographic, blood, and urine analyses
were not significantly different between the groups.
Another randomized trial (36) of 30 overweight
adults investigated the effects of supplementation, along
with a cross-training exercise regimen and dietary education
program compared with exercise and dietary
education alone on body composition. Supplementation
included ephedrine, SAs, caffeine, and calicine.
Greater weight and fat loss occurred for the supplement
group compared with the exercise–diet only
Overall, studies indicate a weight loss of 2.4–3.4 kg
among participants using SAs, while placebo groups lost
0.94–2.05 kg, suggesting the plausibility of some weight
loss benefit from SA supplementation, beyond diet and
exercise alone. However, these studies do not separate
Bitter Orange 55
the effects of C. aurantium or SAs from other ingredients,
particularly ephedrine and caffeine.
Metabolic Rate and Cardiovascular Effects
Several studies have evaluated the effects of acute administration
of SAs on cardiovascular indicators. Kalman et al.
(39) tested a product containing 335 mg Ma Huang standardized
for 20 mg ephedrine alkaloids, 910 mg guarana
standardized for 5 mg SAs per two capsules. Twentyseven
overweight adults were randomized to treatment
or placebo for 14 days. BP, heart rate, electrocardiogram,
and Doppler echocardiograms were evaluated before and
after treatment. Ingestion of this commercial weight loss
supplement did not produce any detectable cardiovascular
Penzak et al. (10) examined cardiovascular outcomes
in 12 normotensive individuals who were administered
8 oz of Seville orange juice (containing 13–14 mg SAs)
and water in a crossover fashion, followed by a repeat
ingestion 8 hours later. No changes in cardiovascular indices
(BP, maximal arterial pressure, and heart rate) were
Thomas et al. (40) evaluated the cardiovascular effects
of 10 mg oral SAs in healthy volunteers over a 4-hour
period on impedance cardiography and forearm plethysmography.
Elevation in total peripheral resistance was observed
30–60 minutes after dosing, although other hemodynamic
indexes were not affected.
Hemodynamic effects were observed in a crossover
design, placebo-controlled study (41) with the administration
of Xenadrine, a CAP that contains a variety of other
potentially bioactive substances, including green tea extract,
cocoa extract, yerba mate, ginger root, grape seed
extract, and others. However, these increases in heart rate,
and systolic and diastolic BP were not observed with administration
of Advantra Z, which contains C. aurantium
alone, even at an eightfold higher dose.
Haller et al. (42) evaluated a dietary supplement
[Ripped Fuel Extreme Cut, containing synephrine from
C. aurantium (presumably p-synephrine) and caffeine] in
10 healthy adults (three women) aged 20–31 years. Each
subject was given one dose of the dietary supplement
under three conditions: (i) resting conditions (without
placebo); (ii) moderately intense exercise; and (iii) placebo
plus moderately intense exercise in a three-arm, randomized,
crossover study. Greater postexercise diastolic BP
was seen with the dietary supplement plus exercise than
with placebo plus exercise. There were no obvious supplement
effects on postexercise HR, systolic BP, or body
Bui et al. (43) reported the effect on BP (systolic
and diastolic) and heart rate over 6 hours after one
dose of a CAP (Nature’s Way Bitter Orange) on 15
young, healthy adults in this prospective, randomized,
double-blind, placebo-controlled, crossover study. Systolic
and diastolic BP increased significantly within the
1–5 hours time period in comparison with the placebo
group with the peak being 7.3 °æ 4.6 mm Hg, while the
4–5 hours time period increase was 2.6 °æ 3.8 mm Hg after
consumption in comparison with the placebo group
with the peak being 4.2 °æ 4.5 beats/minute, while
heart rate was significantly elevated 2–5 hours after
In one study of obese adults, increases in resting
metabolic rate (RMR) were observed with C. aurantium,
both alone and with food, beyond the thermic effect of
food (TEF) alone (44). (RMR is a measure of the energy
required to maintain basic physiological function while
the body is at rest.) However, another recent investigation
(45) found that the thermic response to CAPs increased in
women only, who had lower TEF than men at baseline.
After the intervention, TEF did not differ by gender. BP
and pulse rate were not affected, but epinephrine secretion
increased. In normal weight adults, an increase in RMR
was also found when the extract was taken with a meal
(46).Noadverse changes in pulse rate or BP were reported.
Finally, the effects of two dietary supplement formulas
onRMRand other metabolic indicators were evaluated
(47). When compared with placebo, Formula A (containing
ephedra, guarana, green tea, yohimbe, and quercetin)
and Formula B (containing C. aurantium, jing jie, fang feng,
guarana, green tea, yohimbe, and quercetin) resulted in increased
total RMR, decreased respiratory exchange ratio
toward fat burning, and increased body core temperature.
Heart rate and RMR increased at each 15-minute interval
with Formula A only. BP increased with both, but to a
greater extent with Formula A.
CASE REPORTS OF ADVERSE EVENTS
Nykamp et al. (48) describe a case of acute lateral-wall
myocardial infarction co-occurring with consumption of
CAPs in a 55-year-old woman with undetected coronary
vascular disease. She reported taking a multicomponent
dietary weight loss supplement containing 300 mg of bitter
orange over the preceding year.
Consumer Reports article (49) describes a 21-yearold
woman who took ephedra-free Xenadrine EFX (which
contains C. aurantium). After 3 weeks on the supplement,
she suffered a seizure. Her neurologist believes the bitter
orange in the supplement was the most likely the cause,
though the basis for this conclusion is unknown.
Nasir et al. (50) described exercise-induced syncope
in a healthy 22-year-old woman that occurred 1 hour after
a second dose of Xenadrine EFX, a weight loss supplement
that contains, among other compounds, ephedrine and
synephrine. The electrocardiography revealed prolongation
of the QT interval, which resolved in 24 hours.
Bouchard et al. (51) report a case of a 38-year-old
male patient with ischemic stroke that occurred after taking
a CAP for 1 week. The patient reportedly had no relevant
medical history or major atherosclerotic risk factors
and took no other medications.
Gray andWoolf (52) reported a case of CAPs use by
an adolescent with anorexia nervosa and raised concerns
that the SAs may have masked bradycardia and hypotension
while exacerbating her weight loss. Firenzuoli et al.
(53) report a case of a 52-year-old woman that had an
allergic reaction after taking a CAPs product.
Sultan et al. (54) reported a case of a 52-year-old
woman with ischemic colitis that occurred 1 week after
consumption of a CAP (Natural Max Skinny Fast,
containing bitter orange). She reported no known drug
56 Haaz et al.
Table 2 Summary of Effects, Safety, and Efficacy of Citrus aurantium
Physiological effects Effects on weight Effects on body composition Safety
Variable changes in BP in animals;
generally stable BP, heart rate, pulse
rate, blood and urine measures in
humans; inconsistent changes to
resting metabolic rate
Weight loss documented in rodents;
weakly supported in humans, as
studies used multiple supplements or
did not find significant difference
Limited support for loss of fat mass in
human studies, noting a trend or
using multiple supplements; for
animals, some increased lipase
Inconsistent mortality data in
rodents; some evidence of
elevated BP. Results not
consistent from study to study,
but this may be a function of
small sample sizes used in most
studies. Several case reports of
serious adverse events
allergies and took no other medications. Symptoms resolved
over 24–48 hours with conservative management
after the supplement was discontinued.
Health Canada reported that fromJanuary 1, 1998, to
February 28, 2004, it received 16 reports in which products
containing bitter orange or synephrine were suspected
of being associated with cardiovascular events, including
tachycardia, cardiac arrest, ventricular fibrillation, transient
collapse, and blackout. All cases were considered
Adverse events from CAPs are currently fairly rare
in scientific literature. As CAPs are used more widely in
place of ephedrine-containing products, any potentially
harmful effects may be clarified over time.
The Safety of CAPs
Some have hailed the potential therapeutic value of CAPs
(1), while others have warned about possible safety concerns
(33). The safety concerns pertain primarily to adverse
cardiovascular and cerebrovascular effects. Information
on the safety of CAPs comes from the three sources
described above: animal studies, clinical trials, and case
reports. To date, no large epidemiologic (case control or
cohort) studies have evaluated the safety of CAPs.
Of course, one cannot extrapolate the safety of CAPs
from short-term studies used for one indication (e.g., several
days for relief of nasal congestion among the general
population) to long-term studies use for another indication
(e.g., several months or years for weight loss
among obese individuals). Although substantial safetyrelated
data exist for CAPs (13,56), there is no published
human weight loss trial of CAPs with more than 20 participants
or for a duration of more than 7 weeks.
It is important to note that the majority of
studies evaluating the safety of CAPs are performed
with normotensive subjects. However, because hypertension
is a common comorbidity associated with overweight/
obesity, studies that evaluate the effects of CAPs
on BP should also be conducted with obese hypertensive
While C. aurantium extracts have been used in a variety
of cultures for thousands of years, they have not been
traditionally utilized for long periods of time, or specifically
for weight loss (1). As such, there is little, if any, basis
for making definitive statements about the intermediate
or long-term safety/risk of CAPs used for weight loss.
Table 2 summarizes the physiological effects, safety, and
weight loss efficacy of C. aurantium.
Given the dearth of weight loss trials, the optimal dose
(if one exists) of C. aurantium or its SA constituents for
weight loss is unknown. Table 3 highlights some relevant
dosage information. Although generalizing across species
and compounds is difficult and can only provide a limited
basis for conjecture, the following comparisons with
ephedrine can be made. We analyzed data (12) in which
ephedrine or SAs was given to mice. Regression of weight
and food intake on dose of ephedrine or SAs yielded
slopes (in absolute value) that were approximately four
to six times greater for ephedrine than for SAs. Based on
linear projections, it would take four to six times the dose
of SAs (in these mice) to achieve equivalent reduction in
intake and body weight as for ephedrine. In human studies
of ephedrine, doses of about 50 mg per day begin to be
effective (57). Although an extrapolation, this might suggest
a useful clinical dose for SAs as high as 240–360 mg
Table 3 Dosage Information on Citrus aurantium or Synephrine Alkaloids (SAs)
5–14 mg/day Citrus aurantium extract with SAs has been used (34–36) and no serious adverse events were reported. These doses purportedly
showed efficacy, but products tested included substances beyond C. aurantium, notably ephedrine which we know to be effective for
weight loss. We believe that these doses of SAs are very unlikely to be effective when used without ephedrine
32 mg/day The nasal decongestant Endal (60) contains 20 mg of m-s per tablet and two tablets per dose twice per day are recommended
120 mg/day Via C. aurantium extract, SAs are marketed in over-the-counter (OTC) products for weight loss. In products, such as Nutres Lipo 6
(61), the directions suggest that for “extreme fat loss” a recommended dosage is two capsules three times per day. The SA content
per capsule is 20 mg; this provided a maximal recommended dose of 120 mg/day
300 mg/day According to Clarke’s Analysis of Drugs and Poisons (62), oxedrine (p-synephrine) is used clinically at ∼300 mg/day
1000 mg/day Minimum adult lethal dose of m-s (63)
Bitter Orange 57
per day. From a safety point of view, SAs (per equal
weight) have lower potential to raise BP than ephedrine;
however, nearly all commercial preparations of SAs also
contain caffeine, which might compound any cardiovascular
effects. In the absence of caffeine, human studies
suggest that 15–30 times the dose of SAs are required to
elevate BP to the same degree as ephedrine (58,59). This
suggests that such high doses might be well tolerated,
but clearly more data are needed, particularly regarding
potential synergistic effects of CAPs components.
SAs appear to be readily absorbed after oral administration
(63). About 80% of oral doses are excreted in
the urine within 24 hours. After single oral doses, peak
plasma concentrations are typically reached in 1–2 hours.
Plasma half-life is ∼2–3 hours. Sympathomimetic drugs
for weight loss are typically given TID before meals (64)
reducing the evening dose if sleep problems arise.
Topical application (as with aromatherapy or antifungal
uses) of CAPs may result in photosensitivity for fair skinned
individuals (65) (possibly due to photosensitizing
furanocoumarins that occur in the rinds of certain
citrus species, especially immature fruits). Although
rare, this has also occurred after oral ingestion. To reduce
this risk, exposure to ultraviolet light can be minimized.
Caution is recommended for use in children, as it
may conceivably produce toxic effects (66). Some sources
advise that CAPs should be avoided by women who are
pregnant or breastfeeding (7,67), while others claim that
CAPs can be used safely during pregnancy (66). While
effects on BP are unclear, those with hypertension, tachyarrhythmia,
or narrow-angled glaucoma may consider
refraining from use of CAPs until further evidence confirms
their safety (67).CAPs could also possibly exacerbate
symptoms for those with stomach or intestinal ulcers (68).
Because CAPs may increase stomach acid, they could potentially
reduce the efficacy of acid-lowering drugs, such
as antacids and ulcer medications (69). Although a speculative
precaution, those taking medications containing
SAs, including some cold medications and monoamine oxidase
inhibitors (MAOIs), should consider the combined
dose of these products with the SAs present in CAPs formulations
and possible multiplicative effects (68,69). It has
been suggested that CAPs could interfere with the activity
of drugs that are metabolized by the liver enzyme cytochrome
P450-3A, CYP3A (70,71). A recent comment in
Experimental Biology and Medicine noted that some research
on drug effects have utilized parts of the plant or
methods of administration that may not be applicable to
oral consumption of currently marketed dietary supplements
The safety and efficacy of CAPs and SAs for weight
loss are not well established. While existing literature
demonstrates plausibility for reducing weight, previous
trials were not designed to rigorously evaluate safety and
efficacy. Doing so will require better-designed randomized
clinical trials with large sample sizes, reliable well established
outcome measures, and active surveillance of
side effects and adverse events. To better understand the
effects of CAPs or SAs specifically, studies will need to test
these components without combining them with other ingredients
postulated to have antiobesity effects. It would
also be worthwhile to examine differences between the
types of synephrine-containing compounds that are derived
from various sources and how this influences the
consistency and potency of supplements.
The writing of this entry was supported in part
by NIH grant nos. P30DK056336, AR49720–01A1, and
T32HL072757. The opinions expressed are solely the responsibility
of the authors and do not necessarily represent
the official views of the NIH or any other organization
with which the authors are affiliated.
Disclosure: Dr. Allison has received grants, honoraria,
consulting fees, and donations from numerous
companies, government agencies, and nonprofit organizations
with interests in obesity in general and dietary
supplements in particular, including organizations litigating
cases involving C. aurantium.
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