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Top Clin Nutr
Vol. 25, No. 2, pp. 136–150
Copyright c
2010 Wolters Kluwer Health |Lippincott Williams & Wilkins
APPROACHES TO OVERWEIGHT AND OBESITY
Herbal and Dietary
Supplements for Weight Loss
Raghda Ghussen Alraei, MS, RD, CDN
Overweight and obesity are growing health problems in the United States, with approximately one-
third of adults being obese and more than one-third are overweight. Many overweight individuals
turn to dietary and herbal supplements for weight loss, and millions of dollars are spent on these
products. However, there are concerns about the safety and efficacy of many supplements. Sup-
plements are believed to help weight loss by several mechanisms of action, including increasing
energy expenditure, increasing satiety, increasing fat oxidation, blocking dietary fat absorption,
modulating carbohydrate metabolism, increasing fat excretion, increasing water elimination, and
enhancing mood. This topic is changing rapidly, and this review gives a perspective of the cur-
rent state of the evidence on selected dietary and herbal supplements and combination products.
Many supplements have not been studied in randomized controlled trials and require more re-
search to determine efficacy. Nutrition and healthcare professionals need to discuss use of dietary
supplements with patients and report any adverse events to the Food and Drug Administration.
Additional regulations on production, sales, and marketing of these supplements would be needed.
Key words: dietary supplements,herbal supplements,safety and efficacy,weight loss
OVERWEIGHT and obesity are growing
health problems in the United States,
with approximately one-third of adults being
considered obese and more than one-third
overweight.1Standard treatment of obesity
includes reducing energy intake and increas-
ing energy expenditure through exercise.
However, adherence to lifestyle changes and
exercise programs are generally poor.2For
this reason, many overweight individuals turn
to dietary and herbal supplements for weight
loss.2Since 1994, with the passing of the
Dietary Supplements Health Education Act,
Author Affiliations: Department of Nutrition
Sciences, School of Health Related Professions,
UMDNJ University of Medicine & Dentistry of New
Jersey, Newark; and Department of Health and
Nutrition Sciences, Brooklyn College, The City
University of New York, Brooklyn.
The author thanks Dr Jane Ziegler for her assistance
and continued support.
Corresponding Author: Raghda Ghussen Alraei, MS,
RD, CDN. Nutrition Services, 476 73rd St, Brooklyn, NY
11209 (ghussera@umdnj.edu).
which enables manufacturers to market di-
etary and herbal products without proof
of efficacy and safety, as required for pre-
scription drugs, sales of supplements have
increased.3,4 With the availability of dietary
supplements on the market, Americans are
spending millions of dollars for weight loss
supplements. In 2002, for example, it was
estimated that $2 billion were spent on
weight loss products.5In a 2007 study, it
was estimated that 15.2% of American adults
(20.6% women and 9.7% men) had used di-
etary supplements for weight loss.6Many
supplements are labeled as “natural,” which
gives the consumers the impression that they
are safe.7However, there is concern about
the safety and efficacy of many dietary and
herbal supplements because they contain ac-
tive ingredients, which may interact with pre-
scription drugs, and can cause adverse ef-
fects. Evidence about the efficacy of many of
the supplements is inconclusive.7There are
more than 50 individual dietary supplements
and 125 combinations products listed in the
Natural Medicine Comprehensive Database as
136
Dietary and Herbal Supplements for Weight Loss 137
being used for weight loss. However, many of
the supplements have not been tested for effi-
cacy and safety or studied in randomized con-
trolled trials (RCTs).8
Claims on dietary and herbal supplements
attribute weight loss to several mechanisms
including the following8,9:
•Increase of energy expenditure:
ephedra, caffeine, guarana, bitter or-
ange, yerba mat´
e
•Increase in satiety: soluble fibers such as
guar gum, glucomannan, psyllium
•Increase of fat oxidation: hydroxyc-
itric acid (HCA), green tea, conjugated
linoleic acid (CLA), fish oil, capsaicin,
carnitine
•Blocking of dietary fat absorption: chi-
tosan
•Modulation of carbohydrate
metabolism: chromium
•Increase of fat excretion: calcium
•Increased water elimination: dandelion,
cascara
•Enhancement of mood: St. John’s wort
This article examines some of the com-
monly used dietary and herbal supplements
and reviews the available evidence from
RCTs, systematic reviews, and meta-analyses
regarding their efficacy, safety, and drug inter-
actions. Some data are also obtained from the
Natural Medicine Comprehensive Database,
which was established in 1999, and is rec-
ognized as a valuable resource for evidence-
based information on the topic of herbs, di-
etary supplements, and drugs. Information
about ingredients in supplements is organized
in monographs that list their use, safety, ef-
fectiveness, action, adverse reactions, and in-
teractions with medications, other herbs, and
dosage.10
DIETARY AND HERBAL SUPPLEMENTS
Ephedra
Ephedra sinica is an evergreen shrub that
is native to central Asia, with ephedrine,
or ephedra alkaloids,8being the active in-
gredients in the plant.1It is also called
ma huang and has been used in tradi-
tional Chinese medicine with a combina-
tion of other herbs,3although its use for
weight loss is not part of traditional Chinese
medicine.7Ephedra alkaloids are powerful
central nervous system (CNS) stimulants and
sympathomimetic agents that cause cardiac
stimulation and vasoconstriction.11 Ephedra-
containing dietary supplements were widely
used in the mid-1990s until 2004 when the
sale of these supplements was banned in
the United States.7A recent systematic re-
view sponsored by the National Institutes of
Health concluded that ephedra use was as-
sociated with a modest but statistically sig-
nificant increase in weight loss (0.9 kg per
month) compared with a placebo over a
short period of time (<6 months).7How-
ever, these controlled studies reported that
ephedra use was associated with 2.2- to 3.6-
fold increase in odds of several adverse re-
actions such as gastrointestinal (GI), auto-
nomic, and psychiatric symptoms as com-
pared with controls.1,7 Long-term studies (>6
months) have not been conducted.7,8 Sev-
eral reported adverse events, which included
heart palpitation, GI symptoms, dizziness, in-
creased blood pressure, strokes, and psychi-
atric symptoms such as anxiety, and halluci-
nations, were associated with ephedra use.12
Some reports also linked ephedra use to per-
manent disability (13 reports) and death (10
reports).12 After the review of all the ad-
verse reaction reports, the Food and Drug Ad-
ministration (FDA) concluded that ephedra-
containing products should not be recom-
mended for weight loss because they pose a
risk for illness or injury; therefore, the supple-
ment sale was banned in 2004.7
Adverse drug-supplement interactions
can occur when ephedra is combined
with monoamine oxidase inhibitors, an-
tidepressants, medications containing
pseudoephedrine or ephedrine, and caffeine,
which can result in excessive CNS stimula-
tion. Adverse interactions can also occur with
medications used for the treatment of heart
disease, hypertension, depression, Parkinson
disease, asthma, or diabetes.11
138 TOPICS IN CLINICAL NUTRITION/APRIL–JUNE 2010
Caffeine, guarana, and yerba mat´
e
Caffeine is a CNS stimulant8and is com-
monly consumed with coffee, tea, and soft
drinks. The scientific name of caffeine is 1,3,7-
trimethylxanthine.10 Caffeine use for weight
loss has been studied in combination with
ephedra and has been shown that the combi-
nation is effective in reducing weight in the
short term.10 In a double-blind RCT on 35
overweight subjects, 72 mg of ephedra and
240 mg of caffeine for 8 weeks caused a sig-
nificant decrease in body weight and body fat
in the study group compared with the control
group.13 Another RCT that tested an herbal
supplement containing 210 mg of ephedra
and 72 mg of caffeine overall for 12 weeks
found that the treatment group had a sig-
nificant decrease in mean body weight and
in the percentage of body fat.13 A more re-
cent RCT on a multinutrient supplement con-
taining a low dose of ephedra and caffeine
(40 mg of ephedra and 100 mg of caf-
feine), which was tested on 61 healthy,
overweight, postmenopausal women, found
that the treatment group lost significantly
more body weight (−7.18 kg) and body fat
(−5.33 kg) than controls.14 Adverse effects
reported from these studies included dry
mouth, insomnia, headaches, nervousness,
and palpitation.13,14 After the ban of ephedra,
many dietary supplements have been refor-
mulated and marketed as “ephedra free.”
One of these combination supplements is
a product called Hydroxycut, with caffeine
as the major ingredient. The recommended
dose provides 600 mg of caffeine (equiva-
lent to 6 cups of coffee) and it also contains
other ingredients including HCA, Gymnema
sylvestre, glucomannan, guarana, green tea
extracts (GTEs), and willow bark.15 One case
report showed the development of hyperten-
sive retinopathy in a previously healthy indi-
vidual associated with the use of this caffeine-
based product. It is not clear whether caffeine
alone was the causative agent, or whether
it worked with the other ingredients syn-
ergistically; however, it was presumed that
the causative agent had a sympathomimetic
effect.15 There are also reports that some stim-
ulant, ephedra-free products are associated
with hepatotoxicity, dysrhythmia, hyperten-
sion, and ischemic stroke.15
Guarana and yerba mat´
e are the botani-
cal sources of caffeine.8Guarana is extracted
from the seeds of Paullinia cupana, which
is a South American shrub native to the
Amazon.11,12 Guarana seeds contain 4% to
5% caffeine compared with coffee beans,
which contain 1% to 2% caffeine. In ad-
dition to its inclusion in dietary supple-
ments, guarana is added to many energy
drinks and bars.11 No studies have been con-
ducted to assess the safety and efficacy of
guarana alone or without the aid of other
substances. In a double-blind RCT, the ef-
fects of a guarana and yerba mat´
e contain-
ing supplement on weight loss and gastric
emptying were found to cause delayed gas-
tric emptying and contributed to more short-
term weight loss over 45 days in 44 healthy
overweight subjects than in controls.16 How-
ever, no significant effect was found after 1
year of treatment.16 Adverse events reported
with guarana include heart palpitations, irri-
tability, anxiety, and other CNS symptoms.12
The combination of guarana and ephedra
can cause serious adverse events, with in-
creased heart rate, increased blood pressure,
and impairment of potassium and glucose
homeostasis.17 Guarana, when taken in high
doses, can cause insomnia, anxiety, nausea,
vomiting, tremors, tachycardia, and arrhyth-
mia. Guarana, because of its high caffeine con-
tent, may interact with medications used in
the treatment of diabetes, anticoagulants, an-
tipsychotics, and other medications.11
Yerba mat´
e is prepared from the plant
Ilex paraguariensis, which is an evergreen
shrub native to South America. Only 1 study
was performed on yerba mat´
e and guarana
(mentioned earlier), with no adverse events
reported.12 More study is needed on these
products.
Bitter orange
Citrus aurantium or bitter orange is a
small citrus tree (also known as Seville
Dietary and Herbal Supplements for Weight Loss 139
orange or sour orange). The active ingredients
in bitter orange are synephrine (oxydrine) and
octopamine, which are structurally similar to
epinephrine and norepinephrine and are also
closely related to ephedrine.18 Synephrine
is a sympathomimetic amine that stimulates
the CNS.7Dietary supplements containing
synephrine have been marketed as a safe alter-
native to ephedra,18 and many supplements
labeled “ephedra free” contain synephrine.19
There is little evidence to date that bitter or-
ange supplements are effective in weight loss,
and no clinical trials have been conducted
with bitter orange alone.19 Additional studies
are needed to assess the safety and efficacy of
bitter orange.7Because of the stimulant effect
of synephrine, bitter orange has the potential
to cause adverse effects such as high blood
pressure and other cardiovascular effects.10
Adverse reactions (tachycardia, dysrhyth-
mia, cardiac arrest, and ischemic stroke)
have been reported with combination
supplements containing bitter orange and
caffeine.10,13 Bitter orange also contains the
flavonoids, furocoumarin and bergapten,
which can inhibit CYP3A4, may affect the
metabolism of some drugs, and could po-
tentially increase the serum levels of these
drugs (such as warfarin).18 Additional safety
testing and assessments of drug interactions
are needed.7
Guar gum, glucomannan, and psyllium
Guar gum, glucomannan, and psyllium are
soluble fibers that are claimed to help in
weight loss through their ability to absorb
water in the intestine, resulting in increased
satiety.8Guar gum is a dietary fiber de-
rived from the Indian cluster bean Cyamop-
sis tetragonolobus. A meta-analysis of 20
double-blind, placebo-controlled trials con-
cluded that guar gum was not effective in re-
ducing body weight. In most of these trials,
subjects were instructed not to change their
eating habits.1,8,20 Adverse effects reported
were nausea, diarrhea, and flatulence.1,12 In
3% of subjects, the GI complaints were severe
enough to cause subjects to withdraw from
the trials.12
Glucomannan is prepared from the konjac
root Amorphophallus konjac, and it is struc-
turally very similar to galactomannan present
in guar gum.20 It is a highly viscous fiber21
and is reported to be the most water-soluble
fiber, expanding up to 200 times its original
volume when used with water. In animal stud-
ies, glucomannan has been shown to form a
gel around food particles and cause slower
absorption of carbohydrates and fat.22 Three
RCTs reported that, at a dosage of 2 to 4 g/d,
glucomannan results in modest but significant
weight loss. However, these trials were small
and had methodological limitations.8No ad-
verse events were reported.8,20 Glucomannan
improves glucose and lipid contents.21 Addi-
tional well-designed RCTs are needed to deter-
mine the efficacy and safety of glucomannan
on weight loss.
Psyllium fiber is derived from the plant
Plantago psyllium. Studies on psyllium fiber
did not show any effect on weight loss; how-
ever, its use resulted in the improvement in
lipid contents and glycemic control in 125
overweight subjects with type 2 diabetes.8
Adverse effects were reported with psyllium
fiber, which included flatulence, bloating, in-
digestion, and nausea.12
Hydroxycitric Acid
Hydroxycitric acid is extracted from the
Malabar tamarind tropical fruit Garcinia cam-
bogia, which is native to India.8It has been
shown to inhibit de novo fatty acid synthesis
by inhibiting the enzyme citrate lyase, which
catalyses the first step in fatty acid synthesis.3
Hydroxycitric acid has also been suggested
that it inhibits food intake by suppressing
appetite and decreases weight gain.20 The
evidence from several RCTs regarding the
efficacy of HCA is contradictory.8Some stud-
ies reported improvements in body compo-
sitions; however, these studies had limita-
tions and poor designs or had used HCA in
combination with other herbs.11 Hydroxyc-
itric acid is also sold as supplement with cal-
cium salts3and calcium and potassium salts.23
HCA-SX is a calcium-potassium salt of HCA
with high bioavailability, which induces a
140 TOPICS IN CLINICAL NUTRITION/APRIL–JUNE 2010
concentration-dependent release of serotonin
in rats and causes appetite suppression.23 In
a study of HCA-SX use, 60 human subjects
took 4666.7 mg of HCA-SX with 2000 kcal
of diet per day and participated in a 30-
minute walking exercise session 5 d/wk for 8
weeks. These authors found that the use of
HCA-SX resulted in decreases in body weight,
body mass index, food intake, serum choles-
terol, low-density lipoprotein cholesterol, and
triglycerides, and increases in high-density
lipoprotein (HDL) and serotonin levels.23 Ad-
ditional well-designed RCTs are needed to as-
sess the efficacy and long-term safety of HCA.
Adverse events observed with HCA in
some studies include stomach pain, GI symp-
toms, headache, and upper respiratory tract
symptoms.12,20 No drug-supplement interac-
tions has been reported.11
Green tea extracts
Green tea is derived from the leaves of
Camellia sinensis.3It contains the polyphe-
nols epigallocatechin gallate (EGCG), epicate-
chin (EC), and epicatechin gallate (ECG). Of
these, EGCG is the most abundant and most
biologically active ingredient.11
Green tea is believed to help weight loss by
promoting thermogenesis and fat oxidation.8
In vitro, GTEs containing catechins and caf-
feine are more potent in stimulating brown
adipose tissue thermogenesis than by caf-
feine alone.3It has also been shown in hu-
man studies that green tea and caffeine mix-
ture can stimulate thermogenesis and fat
oxidation in the short term.24 In few stud-
ies on rats and humans, green tea supple-
ments showed positive effect on reducing
body fat.5A recent double-blind RCT of 78
obese women found that the group receiv-
ing 400 mg of GTEs, 3 times per day for 12
weeks had a slight (0.3%) reduction in body
weight. However, they also had a significant
reduction in low-density lipoprotein choles-
terol and triglycerides and marked increases
in HDL-cholesterol, adiponectin, and ghrelin
compared with the control group.25 Green
tea has also been suggested to limit weight
regain after weight loss and to offset the re-
duction in energy expenditure resulting from
weight loss.26 A randomized, double-blind,
placebo-controlled trial assessed weight loss
and weight maintenance with green tea sup-
plementation and habitual caffeine intake on
76 overweight/obese subjects, who adopted a
very low-calorie diet for 4 weeks, followed by
3 months of weight maintenance. During the
maintenance period, the study group received
green tea-caffeine mixture (270 mg of EGCG
and 150 mg of caffeine), and habitual caffeine
intake was also assessed. The results found
that those with low caffeine intake (<300
mg/d), taking the green tea-caffeine supple-
ments, still reduced body weight and body
fat during the maintenance period with an
increase in resting energy expenditure com-
pared with controls, whereas those with high
caffeine intake (>300 mg/d), no effect of the
supplement was observed. The authors con-
cluded that GTE-caffeine mixture could im-
prove weight maintenance in persons with
low habitual caffeine intake.26 A recent meta-
analysis that included 11 studies on the effect
of green tea on weight loss and weight main-
tenance found that catechins and EGCG sig-
nificantly decreased body weight and signif-
icantly maintained body weight after weight
loss.27 Interestingly, the effect was smaller
in whites than in Asians. It was also sug-
gested that habitual caffeine intake and eth-
nicity might be moderators that may influ-
ence the effect of green tea.27 Safety concerns
about GTEs were raised after reported hepa-
totoxicity from the supplements in Europe.28
Recently, regulatory agencies in France and
Spain suspended market authorization of
weight loss products containing GTEs be-
cause of hepatotoxicity. As a response, the
US Pharmacopeia Dietary Supplement Infor-
mation Expert Committee systematically re-
viewed the safety information of GTEs. A total
of 216 case reports on GTEs were analyzed,
of which 34 reports documented liver dam-
age. The implicated products that contained
GTE in these cases were Exolise, Tealine, Hy-
droxycut, TRA Complex, Camiline Arkocaps
Dietary and Herbal Supplements for Weight Loss 141
tea leaf powder, and GreenLite Polyphenon.29
Clinical and toxicological data indicated that
concentrated extracts of green tea when con-
sumed on an empty stomach, are more likely
to lead to adverse effects than when con-
sumed in the fed state.29 Therefore, it was rec-
ommended that GTE products carry the label-
ing statement: “Take with food. Discontinue
use and consult a healthcare practitioner if
you have a liver disorder or develop symp-
toms of liver trouble such as abdominal pain,
dark urine, or jaundice.”
29(p482) No safety con-
cerns are associated with the consumption of
green tea as a beverage. There is also some
speculation that GTEs may interfere with iron
absorption.11
Conjugated linoleic acid
Conjugated linoleic acid is an isomer of
linoleic acid (cis-9,trans-11) that is found nat-
urally in the rumen of cattle.3It can be found
in the human diet primarily in meat and dairy
and meat products. An average diet supplies
15 to 174 mg of CLA per day.10 In supple-
ments, it is found in a mix of 2 isomers (cis-
9,trans-11 and cis-12,trans 10).30 Conjugated
linoleic acid reduces fat mass and fat depo-
sition in obese mice, probably by increasing
lipolysis and decreasing triglycerides uptake
in the adipose tissue.8Most studies on the ef-
fects of CLA on body composition were per-
formed on animals. Mice were found to be
more responsive, with 60% less total body fat
in treated animals.30 There is little evidence
on the efficacy of CLA in reducing body fat
or body weight in humans.7A recent meta-
analysis on the efficacy of CLA in reducing fat
mass, which included 18 randomized, double-
blind, placebo-controlled studies found that
at a dose of 3.2 g/d, CLA resulted in modest
losses in body fat (0.5 kg/wk) in humans up
to 6 months as compared with those with a
placebo.30
Safety concerns about CLA are related to
several risk factors for chronic disease.30
There has been an increase in insulin resis-
tance in animals treated with CLA,3as well
as in humans with abdominal obesity and
diabetes taking the cis-12,trans-10 isomer.11
It has also shown to cause modest increase
in some inflammatory markers including C-
reactive protein, white blood cell counts, and
blood and urinary isoprostane. Although CLA
increases these inflammatory biomarkers, it
decreases inflammatory disease in several an-
imal studies.30 The effects of CLA on inflam-
matory markers and insulin resistance need to
be studied further.30 Other adverse effects in-
clude mild to moderate GI symptoms in hu-
mans taking CLA.8
Capsaicin
Capsaicin is a substance found in the Cap-
sicum species of chili pepper and red pepper.
It is suggested that it stimulates fat oxidation
and thermogenesis3and decreases appetite.31
There are reports of modest weight loss in
individuals who consume chili peppers
regularly.3No studies were performed
on the use of capsaicin alone for weight
loss.5One double-blind, placebo-controlled
study assessed the effects of a combina-
tion of supplements that included tyrosine,
capsaicin, catechins, caffeine, and calcium
on body fat loss and thermogenesis on 80
overweight/obese subjects for 8 weeks. In
the first 4 weeks, the subjects followed a
hypocaloric diet and in the next 4 weeks they
were given the bioactive supplement. In this
study, the supplement combination was sug-
gested to work in a synergistic fashion. The
results demonstrated that the supplement
increased thermogenesis and caused a slight
reduction in fat mass (0.9 kg) compared with
a placebo.31 Additional studies are needed on
capsaicin alone to assess its efficacy.
Some adverse effects such as diarrhea have
been reported.5Capsaicin may reduce the
bioavailability of aspirin.5
Carnitine
Also known as l-carnitine, it is synthesized
in the body from the amino acids lysine and
methionine. Carnitine plays a central role in
fat metabolism by transferring long-chain fatty
142 TOPICS IN CLINICAL NUTRITION/APRIL–JUNE 2010
acids to the mitochondria for β-oxidation.11 It
is also found in food, primarily in red meat,
with the average nonvegetarian diet provid-
ing 100 to 300 mg of carnitine per day. Car-
nitine deficiency is associated with muscle
weakness and fatty acid accumulation.11 Car-
nitine supplements have been used for sev-
eral medical conditions and for the enhance-
ment of athletic performance.10 The use of
carnitine for weight loss has not been ade-
quately studied to evaluate for its efficacy.
One double-blind, placebo-controlled study
was conducted on 36 overweight subjects re-
ceiving 4 g of l-carnitine per day, or a placebo
for 8 weeks. The group of subjects receiving
carnitine did not have significant changes of
body weight or fat mass.11 More research is
needed to assess the effectiveness of carni-
tine on weight loss. Five of the subjects in
this study experienced nausea and diarrhea.11
l-Carnitine may inhibit thyroid hormone ac-
tivity; therefore, the supplement should be
avoided in hypothyroidism.10,11
Pyruvate
Pyruvate is produced in the body from
the end stage of glycolysis.11 Pyruvate sup-
plements are used for athletic performance
and weight loss and are sold in the form of
sodium or calcium pyruvate.10,11 Preliminary
research suggest that pyruvate may increase
fat oxidation.10 A systematic review included
2 double-blind, controlled trials on obese sub-
jects (n=52 and n=104) with a dose of 6 g
of pyruvate per day for 6 weeks, with subjects
consuming a 2000-kcal diet and participating
in exercise program 3 d/wk. It was found that
pyruvate did not cause greater weight loss
than with the placebo.20 There is preliminary
evidence that pyruvate combined with a low-
calorie diet, or taken in place of a portion
of dietary carbohydrate, seems to increase
weight loss and decrease body fat.10 More re-
search is needed to assess the efficacy of pyru-
vate on weight loss. Adverse effects reported
with high doses of pyruvate included gastric
distress.
Chitosan
Chitosan is an amino polysaccharide that is
structurally similar to the dietary fiber cellu-
lose. It is derived from chitin, which is found
in the exoskeleton of insects and crustaceans
such as shrimp.11 It is a positively charged
polymer that is suggested to bind to the neg-
atively charged fat molecules in the intestinal
lumen.8In in vitro demonstrations, chitosan is
mixed with corn oil in a glass, which results in
the precipitation of the oil and clearing up of
the solution. It is suggested that it works as a
“fat blocker,” helping weight loss.3Evidence
regarding the efficacy of chitosan in reduc-
ing body weight is not compelling.7A recent
systematic review on the effectiveness of chi-
tosan supplements for the treatment of over-
weight found that there is some evidence that
chitosan is more effective than a placebo in
short-term treatment of overweight and obe-
sity; however, many of these studies had lim-
itations and poor design.32 Results from well-
designed trials indicate that the effect of chi-
tosan on body weight is minimal and of lit-
tle clinical significance.32 Therefore, it seems
that the ability of chitosan to bind fat in vitro
cannot translate to significant fat-binding ef-
fects in the human body.3
Adverse effects of chitosan include
GI symptoms such as constipation and
flatulence.12 Chitosan may interfere with
the absorption of fat-soluble vitamins and
some minerals. The long-term effect on bone
health, nutrient deficiencies, and malabsorp-
tion syndromes need to be determined.11
Chromium
Chromium is an essential trace mineral
that acts as a cofactor of insulin and en-
hances the action of this hormone by possi-
bly increasing affinity to receptors and insulin
binding to cells.10 Therefore, chromium plays
an important role in carbohydrate and lipid
metabolism.21 Chromium deficiency is asso-
ciated with hyperglycemia, hyperinsulinemia,
high triglycerides, and low HDL cholesterol.8
Chromium, as a supplement, is available as
Dietary and Herbal Supplements for Weight Loss 143
a complex of trivalent chromium and pi-
colinic acid (a derivative of tryptophan).7
Other forms of chromium are available as
supplements; however, chromium picolinate
has the highest bioavailability and lowest
toxicity.33 Chromium supplements have been
promoted to aid in weight loss, for muscle
building, and to lower glucose in persons
with diabetes.11 For weight loss, the dosage
used is 200 to 400 μg.8However, there is lit-
tle evidence on its efficacy on body weight.
A meta-analysis of 10 RCTs on the effect of
chromium supplementation on body weight
found a small reduction in weight (0.08–
0.2 kg/wk) in the chromium-receiving group
compared with controls, which was not clin-
ically significant.11,18 A double-blind RCT that
tested the effects of 200 μg of supplementa-
tion of chromium picolinate on 83 women,
who took controlled energy intake for 12
weeks, did not result in a reduction in body
weight or change in body composition.33 An-
other recent study on 35 overweight pre-
menopausal women assessed the effect of
the combination of chromium and CLA on
body weight and body composition, with con-
sumption of hypocaloric diets for 12 weeks.
The study found that both supplements
did not enhance diet or impact exercise-
induced changes in weight, body composi-
tion, and lipid parameters compared with a
placebo.34
No adverse events were reported with
chromium picolinate use in short-term
trials.20 However, there is concern that this
form of chromium can lead to free radical
damage on the long term. Some preliminary
analysis suggests that chromium might act
as prooxidant in euglycemic patients. Other
research suggests that chromium can be ox-
idized to hexavalent chromium. The clinical
significance of these findings is unknown.10
In high doses (¿1000 μg/d), renal failure
and rhabdomyolysis have been reported.8
Examining drug-supplement interactions,
some medications such as nonsteroidal anti-
inflammatory drugs and vitamin C have been
found to increase chromium absorption,
whereas antacids, H2blockers, and proton
pump inhibitors can decrease chromium
absorption.11
Calcium and vitamin D
Calcium is an important mineral that has
been claimed to help with weight loss in addi-
tion to many other functions. One of the pro-
posed weight loss mechanisms is that calcium
can increase fecal fat excretion.35 Evidence
on calcium supplement effects on weight loss
in human studies is inconsistent and the ef-
ficacy is limited to small trials.7Calcium con-
sumption from dairy foods has been shown to
be more effective in weight loss than calcium
from supplements.35 A systematic review
by Trowman et al,36 who performed meta-
analysis on 13 RCTs, on the effects of calcium
supplementation on body weight concluded
that calcium, from either dairy or supple-
ments, did not result in statistically signifi-
cant reduction in body weight.36 A larger,
more recent systematic review by Lanou et
al,37 which included 19 trials and separated
isocaloric from energy restricted trials, found
that 16 of the trials (8 on calcium supplements
and 8 on dairy products) reported no signifi-
cant effect of calcium on body weight. Of the
3 remaining trials, 1 supplement trial found
significant weight loss and 2 dairy trials found
significantly greater weight gain. The weight
gain is caused by increased energy intake from
the dairy.38 The majority of the calcium stud-
ies were done on postmenopausal women,
and few trials included men.38 One large ran-
domized, double-blinded, placebo-controlled
trial investigated the role of calcium plus vita-
min D supplementation in the prevention of
weight gain in postmenopausal women. The
study included 36 282 women, aged 50 to
79 years, who were randomized to 1000 mg
of calcium and 400 IU of vitamin D intakes
daily or a placebo. Changes in body weight
were monitored for 7 years. It revealed that
women who received calcium and vitamin
D had smaller favorable changes in weight
(−0.13 kg) and were 11% less likely to gain
weight (≥1–3 kg). It was concluded that cal-
cium and vitamin D had a small effect on pre-
vention of weight gain in this population.39
144 TOPICS IN CLINICAL NUTRITION/APRIL–JUNE 2010
Vitamin D is essential for maintaining cal-
cium homeostasis in the body.11 The effect of
vitamin D alone on weight has not been ad-
equately studied.38 Some population studies
have shown that people with low vitamin D
level are significantly more likely to be obese
that those with high vitamin D levels.10 One
systematic review on the effect of vitamin D
and weight loss identified 3 RCTs that were
published in 1997, 2008, and 2009, respec-
tively. The studies were on postmenopausal
women, obese men and women, and on obese
men, respectively, and compared different
dosages of vitamin D to a placebo (300 IU/d,
20 000–40 000 IU/wk, or 120 000 IU every 2
weeks, respectively). In all 3 studies, no differ-
ences in weight change with or without vita-
min D supplementation were observed.38
No safety concerns were identified with
calcium supplements.7Calcium supplementa-
tion is not recommended for individuals with
absorptive hypercalciuria, primary hyperthy-
roidism, renal insufficiency, or sarcoidosis.11
Vitamin D is toxic at doses above the tolera-
ble upper intake level of 2000 IU.11
OTHER SUPPLEMENTS
Fish oil
Fish oil is a source of omega-3 fatty acids
eicosapentaenoic acid (EPA) and docosa-
hexaenoic acid (DHA).12 It has documented
effects on reducing serum triglycerides
levels and reducing the risk of develop-
ing cardiovascular disease and decreasing
inflammation.10,12 Some evidence indicates
that taking fish oil from dietary sources could
improve weight loss and decrease blood glu-
cose in overweight individuals.10 In animal
studies, EPA and DHA reduce weight and fat
deposition by inhibiting enzymes important
for lipid synthesis, but the effect is less clear
in human studies.40 In an RCT on 75 subjects
who were randomized to receive 6 g of fish
oil per day (providing 260 mg of DHA and 60
mg of EPA), fish oil and exercise, sunflower
oil (control), or sunflower oil and exercise
for 12 weeks, the findings have shown that
both fish oil and exercise independently
reduced body fat. Also, fish oil supplements
reduced plasma lipids and increased HDL
cholesterol.40 Additional studies are needed
to assess the efficacy of fish oil on weight
loss. Supplements of fish oils in high doses
(>3 g/d) may cause some adverse effects,
including inhibition of platelet aggregation,
increased risk of bleeding, and increased
risk for hemorrhagic stroke.10 There is also
concern that some fish oil preparation may be
contaminated with toxins such as mercury,
polychlorinated biphenyls, and dioxins.10
Bean pod (Phaseolus vulgaris)
Phaseolus vulgaris extracts are used for
hypercholesterolemia, weight loss, and other
conditions.10 Extracts of bean pods are re-
ferred as “starch blockers”and are claimed to
decrease carbohydrate digestion and absorp-
tion. Research on humans with specific bean
pod extracts (Phaseolamin) taken with meals
did not show that it inhibits starch breakdown
and absorption.10 In a double-blind RCT on
24 obese men, 3000 mg of bean pods per
day was given to the study group for 8 weeks
and found that the supplement resulted in
decreases in body weight with 129% differ-
ence and also a decrease in triglycerides levels
compared with a placebo.13 The current evi-
dence for the efficacy of bean pods on weight
loss is contradictory, and additional studies
are needed.10 Adverse reactions to bean pods
include nausea, vomiting, diarrhea, and stom-
ach pain.
Cissus quadrangularis
Cissus quadrangularis (CQ) is a succu-
lent vine found in Africa and Asia and has
medicinal use in some parts of Asia. The
supplement is used for weight loss, diabetes,
and hyperlipidemia.10 There is some pre-
liminary research to suggest that CQ may
help in weight loss. Two double-blind RCTs,
which were conducted on overweight/obese
subjects by Oben et al,41,42 were identified in
a recent systematic review. Participants were
given a dose of 300 mg of CQ per day and 300
mg of CQ +500 mg of Irvingia gabonensis
Dietary and Herbal Supplements for Weight Loss 145
(IG) per day, respectively. Both studies
showed significant decreases in body weight,
body fat, and waist size in the CQ group,
with larger reductions in the combination
group (CQ +IG). There was also a significant
decrease in serum cholesterol and glucose
levels in the supplement group.13 Additional
studies are needed to assess the efficacy of
CQ on weight loss. Some adverse effects have
been reported with specific CQ combination
product (Cylaris; Iovate Health Sciences
Research, Oakville, Canada), which include
headache, flatulence, dry mouth, diarrhea,
and insomnia.10
Caralluma
Caralluma or Caralluma fimbriate is an ed-
ible cactus found in India. Traditionally, it was
used by Indian tribes to suppress hunger dur-
ing prolonged hunts.10 Currently, there is in-
sufficient evidence to rate the efficacy of car-
alluma on weight loss.10 Only 1 RCT on the
supplement was identified in a recent system-
atic review, in which 50 overweight individu-
als were randomized to either weight loss pro-
gram plus 1 g of caralluma extract, or weight
loss program alone, for 60 days. The Caral-
luma species significantly decreases waist cir-
cumference and hunger, but no significant de-
creases in body weight, body mass index, and
hip circumference compared with controls.13
Some adverse effects were reported that in-
clude GI upset, flatulence, and constipation;
however, these effects appear to improve
within the first week of use.10
Hoodia
Hoodia gordonii is a succulent plant found
in Africa. It is marketed as a natural appetite
suppressant for weight loss.43 It is claimed
to be one of the glycosides that can act on
the CNS to control hunger; however, the ex-
act mechanism is not understood.10 There
are no published human studies on hoodia.
One animal study on rats showed that com-
pounds from Hoodia species, at all dosages
(6.25–50 mg/kg), resulted in decreases in
food consumption for a period of 8 days when
compared with controls.44 Human RCTs are
needed to determine the efficacy and safety of
hoodia supplements. No adverse effects have
been reported. New reports show that certain
hoodia products sold on the Internet do not
contain the active compounds.10
Dehydroepiandrosterone
Dehydroepiandrosterone (DHEA) is the
most abundant hormone secreted by the
adrenal glands and can be converted to andro-
gens or estrogens.11 Its supplements are com-
monly used for slowing aging, weight loss,
metabolic syndrome, and increasing immune
and cognitive functions. Currently, there is in-
sufficient evidence on the efficacy of DHEA
on weight loss. Some preliminary evidence
suggests that taking 50 mg of DHEA per
day may reduce risk factors for metabolic
syndrome in overweight elderly patients. No
studies were performed on younger popula-
tion; therefore, more research is needed.10
The safety of long-term DHEA use is un-
known. High doses of 200 mg of DHEA per
day may cause masculinization in women
(deepening of voice, facial hair, acne, hair
loss, and menstrual irregularities) because of
the rise in testosterone levels.10,11
Hydroxymethyl butyrate (HMB)
Hydroxymethyl butyrate is a metabolite of
the amino acid leucine, a precursor of choles-
terol, and is produced mainly in muscles and
liver.10,11 Its supplements are used for weight
training to both increase muscle strength and
lean mass. There are no studies regarding
its use for weight loss.11 Hydroxymethyl bu-
tyrate supplements are possibly safe when
used for short term, and no adverse effects are
reported.10 More research on hydroxymethyl
butyrate is needed.
Dandelion and cascara
Dandelion (Taraxacum officinale) is a di-
uretic and cascara (Rhamnus purshiana)
is a laxative, and both can increase water
elimination.8There are no studies on either of
the supplements on their use for weight loss.
Adverse effects from their use include dehy-
dration and electrolyte imbalance.8,10
146 TOPICS IN CLINICAL NUTRITION/APRIL–JUNE 2010
Table 1. Summary of the commonly used dietary supplements for weight loss and evidence for
their efficacy and safety
Proposed mechanism Evidence of
Supplement of action efficacy Evidence of safety
Ephedra Increase energy
expenditure
There is evidence of
short-term efficacy
(<6 mo)
GI, autonomic, and
psychological
symptoms, heart
palpitations, possible
seizure, stroke, death
Sales were prohibited in
2004
Caffeine,
guarana, and
yerba mat´
e
Increase energy
expenditure
Some evidence on the
efficacy of caffeine
and ephedrine
Insufficient evidence for
guarana and yerba
mat´
e
Heart palpitation,
irritability, anxiety, dry
mouth, headache, and
insomnia
Some caffeine-based,
ephedra-free products
were associated with
liver damage,
hypertension, stroke,
and retinopathy
No adverse effects with
yerba mat´
e
Bitter orange Increase energy
expenditure
Insufficient evidence May cause hypertension.
Some reported
cardiovascular effects.
May increase toxicity
of warfarin
Glucomannan Increase satiety Insufficient evidence No adverse effects
Psyllium Increase satiety No evidence Flatulence, bloating,
nausea
Guar gum Increase satiety No evidence Nausea, diarrhea,
flatulence
Hydroxycitric
acid
Increase fat oxidation No clear evidence GI symptoms, headache
Green tea
extracts
Increase fat oxidation Some evidence from
human studies on
reducing body weight
and body fat and
improving weight
maintenance
Reported liver toxicity
May interfere with iron
absorption
Conjugated
linoleic acid
Increase fat oxidation Some evidence GI symptoms
May cause insulin
resistance
Capsaicin Increase fat oxidation
Decrease appetite
Insufficient evidence Diarrhea
May reduce the
bioavailability of
aspirin
Carnitine Increase fat oxidation Insufficient evidence Nausea, diarrhea
May inhibit thyroid
hormone
Pyruvate Increase fat oxidation Insufficient evidence
May be effective with a
low-calorie diet
Gastric distress with
high doses
(continues)
Dietary and Herbal Supplements for Weight Loss 147
Table 1. Summary of the commonly used dietary supplements for weight loss and evidence for
their efficacy and safety (Continued)
Proposed mechanism Evidence of
Supplement of action efficacy Evidence of safety
Chitosan Block dietary fat
absorption
Some evidence of small
effect on weight loss,
but not clinically
significant
Constipation, flatulence
May interfere with
absorption of
fat-soluble vitamins
and some minerals
Chromium Modulate carbohydrate
metabolism
Little evidence, not
clinically significant
No short-term adverse
effects
May lead to free radical
damage on the
long-term use
Reported renal failure
and rhabdomyolysis
with high doses
Calcium Increase fat excretion No clear evidence No adverse effects
Vitamin D Maintain calcium
homeostasis
Insufficient evidence Toxic above upper
intake level of 2000 IU
Fish oil Decrease fat deposition Evidence on decreasing
body fat in animal
studies; less clear
evidence in humans
In high doses (>3 g/d)
may increase risk of
bleeding and
hemorrhagic stroke;
supplements may
contain contaminants
and toxins
Bean pod Decrease carbohydrate
digestion and
absorption
Insufficient evidence Nausea, vomiting,
diarrhea, and stomach
pain
Cissus quad-
rangularis
Unspecified Insufficient evidence Headache, flatulence,
dry mouth, diarrhea,
and insomnia
Caralluma Suppress appetite Insufficient evidence GI upset, flatulence, and
constipation
Hoodia Suppress appetite Insufficient evidence
No human studies
No adverse reactions
reported
Dehydroepi
and
rosterone
Unspecified Insufficient evidence Masculinization in
women at high doses
(200 mg/d)
Hydroxymethyl
butyrate
May increase lean mass Insufficient evidence No adverse effects
Dandelion and
cascara
Increase water
elimination
No studies on weight
loss
Dehydration and
electrolyte imbalance
St. John’s wort Enhance mood No studies on weight
loss
Insomnia, vivid dreams,
restlessness, anxiety,
agitation, irritability,
GI discomfort,
diarrhea, fatigue, dry
mouth, dizziness, and
headache;
photosensitivity in
high doses
Interact with many
prescription drugs
Abbreviation: GI, gastrointestinal.
148 TOPICS IN CLINICAL NUTRITION/APRIL–JUNE 2010
St. John’s wort
St. John’s wort (Hypericum perforatum)is
often used in mild depression and is some-
times added to weight loss products to en-
hance mood; however, there are no data
available on its effect on weight loss.8Some
adverse effects reported include insomnia,
vivid dreams, restlessness, anxiety, agitation,
irritability, GI discomfort, diarrhea, fatigue,
dry mouth, and dizziness, as well as photosen-
sitivity in high doses. St. John’s wort is known
to interact with many prescription drugs and
reduce their levels of activity.10,11 The interac-
tion with some medications may lead to seri-
ous effects, such as cerebral vasoconstriction
disorders with antidepressants, hypertension,
hyperthermia, and coma with monoamine ox-
idase inhibitors, or severe swelling of face
with aminolevulinic acid.10
There are other supplements marketed
for weight loss, such as ginger roots, white
willow,5Laminaria,Spirulina,Guggul, and
apple cider vinegar,8but their safety and effi-
cacy have not been assessed in RCTs.
IMPLICATIONS FOR DIETETIC PRACTICE
There are many dietary and herbal sup-
plements and about 125 combination supple-
ments that have been promoted for weight
loss. Some, such as ephedra, were exten-
sively studied; however, for many others, their
efficacy and safety were never determined
by well-designed, randomized, controlled tri-
als. The supplements discussed, with evi-
dence on their efficacy and safety, are sum-
marized in Table 1. Supplements are com-
monly used by Americans for weight loss, es-
pecially women.6Their use is also common
among adolescents.45 People often perceive
that these supplements are “natural”; there-
fore, they should be safe. However, reports
about the adverse events associated with the
use of some supplements raise concern about
their safety. In addition, the potential interac-
tion of some of these supplements with other
herbs, as well as with prescribed or over-the
counter drugs, may lead to serious effects, es-
pecially in the stimulant supplements11,15 and
St. John’s wort.10
Physicians, nutritionists, and other health-
care professionals need to be educated about
the different substances used in supplements.
They need to encourage their patients to re-
port any use of dietary and herbal supple-
ments and to caution their patients against any
drug-supplement interactions. Any adverse re-
actions related to supplement use can be re-
ported to the FDA at www.fda.gov/medwatch
or 1800-FDA-1088.7Well-designed, random-
ized, double-blind, placebo-controlled studies
are needed on many dietary and herbal sup-
plements to assess their efficacy and safety.
More regulations from the FDA on produc-
tion, sales, and marketing of the dietary sup-
plements would also be beneficial to ensure
that the products actually contain the ingre-
dients listed on the labels and are free from
contaminants, as well as, most important, to
protect the public from some of the harm-
ful effects associated with some supplements
use.
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