Systematic Review and Meta-Analysis

Nutrition and Health

1–15
Comparing effectiveness of fat burners ª The Author(s) 2021
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DOI: 10.1177/0260106020982362

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cardiometabolic health: Systematic

review and meta-analysis

James E Clark1,2 and Sarah Welch1

Abstract
Background: Those who are overfat face an onslaught of advice for losing weight, including using dietary supplements
that purport to have fat burning capabilities to achieve a reduced body mass, fat mass and improvement in cardiometabolic
health in combination with exercise or diet and exercise regimens. Aim: To examine long-term effectiveness of sup-
plements for both weight loss and improvements in cardiometabolic health for these individuals. Methods: A PRISMA
methods of systematic review was conducted from August 2018 through January 2019 using Medline, PubChem, PubMed,
EBOSCO CINHAL and SPORTDiscus, and Google Scholar yielding 23,441 returns of which 21 studies (duration greater
than 8 weeks with participant populations of BMI greater than 24.9) were included for meta-analysis. Meta-analysis
examined pooled effect size and 95% confidence interval for: body mass, fat mass, fat-free mass, total cholesterol,
high-density lipoproteins, low-density lipoproteins, resting metabolic rate. Intra-study effect sizes were compared with
previously reported results for diet or diet and exercise in a 2x2 chi-square analysis for the number of studies that induced
effects greater than or less than the effect size. Results: There is a general trend to show effectiveness (effect size greater
than 0.00) for obtaining beneficial changes from use of thermogenic dietary supplements, yet the 95% confidence interval
for effect size crossed 0.00 (indicating no benefit). Chi-square comparison to exercise, or combination of diet and
exercise, indicates that responses induced from weight-loss supplements were less effective than what is obtained from
utilizing exercise, or diet and exercise, without additional weight-loss supplements. Conclusion: There appears to be
limited benefit that may be derived from the inclusion of thermogenic dietary supplements to reduce body mass and
improve cardiometabolic health for individuals who are overfat.

Keywords
Fat burners, thermogenic supplements, diet, exercise, weight loss, cardiometabolic health

Introduction chlorogenic acid or Epigallocatechin gallate (EGCG) alone

Over the last few decades there has been a growing desire
among the populous for a pill to mimic the benefits of exer-
cise, i.e. weight loss, improved health status, without the need
for exercise. In response there have come to market a number
of prescription drugs and over-the-counter (OTC) dietary
supplements that have hoped to be just this miracle in a pill.
Overall, these pills have utilized active ingredients that were
almost always sympathomimetic in chemical signature. Early
on the predominant active substance in the supplements
stemmed from ephedra alkaloids (EA), followed by a com-
bination of EA with caffeine, while more recently active
substances have included synephrine, caffeine, caffeine
anhydride (CA), ephedra extracts that are alkaloid free,
or some combination of various active ingredients( Este-
ghamati et al., 2015; Jeukendrup and Randell, 2011; National
Center for Complementary and Integrative Health [NCCIH],
2018; Rios-Hoyo and Gutierrez-Salmean, 2016; Saper et al.,
2004; Schulman, 2003; Shekelle et al., 2003; Soni et al.,
1
Scientific Health: Education and Human Performance, Brentwood, CA,
USA
2
Los Medanos College Brentwood Center, Brentwood, USA
Corresponding author:
James E Clark, Scientific Health: Education and Human Performance, 2400
Shady WIllow Lane #15D, Brentwood, CA 94513, USA.
Email: sci.health.performance@gmail.com
2 Nutrition and Health XX(X)
Figure 1. Purported action of “fat burners” and thermogenic
supplements based on competitive inhibition or synergistic acti-
vation either cortically or peripherally(Clark, 2019; Coulter et al.,
2018; Stohs et al., 2011).
2004). Recommended use for those who are overfat was
based on the purported impact on metabolism and satiety (see
Figure 1) that each of the aforementioned ingredients would
produce. The purported benefit metabolically may be through
sympathomimetic induction of greater lipolysis and possible
upregulation of uncoupling proteins to induce a thermogenic
effect, thus allowing for the purported greater reduction in
weight (in particular fat mass) from incorporating the use of
these substances beyond the recommended lifestyle modifi-
cations, i.e. changes in diet and activity level (Clark, 2019;
Donsmark et al., 2005; Gurley et al., 1998; Haller et al., 2002;
Haller et al., 2004; Jenkinson and Harbert, 2008; Nogiec and
Kasif, 2013; Stohs et al., 2011; Coulter et al., 2018)
While use of these substances have been touted, anec-
dotally and through single study reports, as having positive
benefits, claims may not always be supported by the
available scientific literature (Clark, 2019; Calfee and
Fadale, 2006; Kerksick et al., 2018; Saper et al., 2004; Liu
et al., 2017). Most studies associated with such substances
examine solely acute responses to an exercise session,
whereas the time necessary to induce weight loss and
improve health status requires prolonged alteration to
lifestyle, i.e. significant changes in both diet and addition of
exercise to activities of daily living, that goes well beyond
the time for many of the acute studies(Clark, 2019; Ekor,
2014; Heuberger and Cohen, 2019; Kerksick et al., 2018;
Liu et al., 2017; Shekelle et al., 2003). There is also the
means by which having an effect is confused with level of
effectiveness. Where single study reports may indicate that
treatment induced a change that would be significant from
the baseline measures, when compared relative to the
population norms (i.e. standard deviation), the determined
effect size does not support that indication of significance.
Nor does the individual study indicate how the populace at
large would function, a summary that can be inferred
through determining if use of treatment is favorable across
all studies, e.g. pooled effect size.
Moreover, a recent review by Heuberger (Heuberger
and Cohen, 2019) indicates that many substances currently
being banned by the World Anti-Doping Agency (WADA)
for performance enhancement have limited empirical evi-
dential support for the purported benefits that have led to
their banned status, thus suggesting that problems may
exist in the likelihood of supplements being able to provide
the purported benefit to the consumers. This idea might be
forwarded toward the purported impact that fat burners
offer to lose weight and improve health status for in-
dividuals who are overfat. For this population many
reports(NCCIH, 2018; Buchanan and Beckett, 2013; Clark,
2019; Figueiredo et al., 2015; Inchiosa, 2011; Jeukendrup
and Randell, 2011; Liu et al., 2017; Stohs and Badmaev,
2016) show a spectrum of responses thus requiring a more
systematic approach to examining adaptations attributed to
the use of these dietary supplements. The acknowledgment
for a spectrum of response comes in light of a growing body
of literature discussing limitations in the proposed theore-
tical models for mechanisms of actions to induce long-term
weight loss and possible improvements in health status(see
Figure 1) (NCCIH, 2016; Donsmark et al., 2005; Haller
et al., 2002; Stohs et al., 2011; Liu et al., 2017) or even if
these substances may in fact induce the thermogenic effect
that would induce greater lipolysis and thus improved loss
of fat mass at suggested dosages or independent of any
exercise stimulus (Clark, 2019). Additionally, these ideas
lead to many questions that must be addressed related to the
impact that such substances have within the timeline nec-
essary, i.e. more than eight weeks, to ensure a beneficial
change in body composition and health status (Clark,
2016). Of importance are the numerous reports of deleter-
ious effects that the primary active ingredients have on the
health of those consuming the supplements, both acutely
and for long periods of time (Bersani et al., 2015; Ekor,
2014; Garcia-Cortes et al., 2016; Inchiosa, 2011; Pope
et al., 2014; Shekelle et al., 2003; Soni et al., 2004). This
uncertainty about benefits leads us to question whether the
benefits outweigh the costs extending into the examination
of any long-term benefits that can stem from the underlying
stimuli coming from the use of these substances, forcing
one to examine what (if any) long-term impact these sub-
stances have on achieving body compositional changes.
And if positive changes in body composition can be
Clark and Welch
achieved, what impact does the substance have on overall
cardiometabolic health?
These are important questions given that we have pre-
viously reported that even if acute benefits might be seen
from exercise, or a combination of diet and exercise, it
takes eight weeks before all interventions show responses
will always be beneficial, i.e. effect size always favoring
treatment (Clark, 2016). Additionally, general under-
standing of pharmacodynamics would indicate that recep-
tor modifications would lead to reduced effectiveness over
prolonged usage. Thereby, one can easily assume that to
provide the continued acute stress necessary to have pro-
longed changes over the minimum time necessary to see
positive benefits, dosages would have to be increased.
Issues of dosing can become problematic given issues of
regulation of OTC supplements and medical oversight of
usage of such supplements by the populace. Moreover, we
have yet to see analysis, independent of a Hawthorne effect,
that examines the differences obtained from the diet and
exercise component of interventions relative to those
obtained from the use of the dietary supplement in con-
junction with diet and exercise modifications.
As such, it may be problematic to conclude that long-
term responses noted in weight loss or improved health
status come from the supplement and not from the other
stimuli of changes to diet or exercise regimen. Therefore,
the purpose of this systematic review is to examine through
meta-analysis of effective size, the effect that any of the
substances in currently available and formerly available
products have on allowing for body compositional changes,
and the impact that these substances have on the cardio-
metabolic health of those consuming these substances.
Ultimately, testing the idea that while many of the anec-
dotes of effect make taking these substances appealing for
the vast majority of the population, their use may not be as
positive as some have come to believe. Where we will be
testing the hypothesis that while the active ingredients in
the dietary supplements will have a greater effect on
inducing body compositional changes relative to changes
seen without dietary supplement use, they will not have
positive long-term cardiometabolic effects.
Methods
The review followed Preferred Reporting Items for Sys-
tematic Reviews and Meta-Analyses (PRISMA) methods,
Figure 2, of conducting a systematic review of articles
pertaining to the role of thermogenic agents on weight loss.
The full protocol is available upon request. Based on this
method, a systematic review of accessible articles (no limit
on publication date) were searched over a period of time
starting 1 August, 2018 and ending 31 January 2019
from Medline, PubChem, PubMed, EBOSCO CINHAL and
SPORTDiscus, and Google Scholar using Boolean search
methods (see supplemental material for an example of a
return) for combinations of the following Medical Subject
Heading (MESH) terms and supplement names: fat burners,
3
thermogenic, supplements, ephedra, Ma Huang, synephrine,
caffeine, chlorogenic acid, green tea (Epigallocatechin
gallate or EGCG), stimulants, weight loss, fat loss, safety,
cardiometabolic, and metabolic rate. From the various
searches performed, 23,441 articles were returned for initial
screening. Of these returns, 5255 were indicated as being
unique (e.g. not duplicated returns) entries in the databases
and after screening titles and key words, a total of 545
abstracts were reviewed for inclusion in the systematic
review and meta-analysis of findings based on the following
inclusion factors: human overweight/overfat/obese partici-
pants (e.g. BMI>24 kg/m2); adult population (18–60 years);
no indication of comorbidity to limit treatment response or
exercise intensities; tracking study; cohort, cross-over or
random-control at least single-blinded study; study length 
8 weeks; printed in English from a peer-reviewed journal
(not indicated as “predatory”). Each author independently
reviewed returns and provided annotations on articles and
results via a commonly accessible word document with entry
of data into a commonly accessible spreadsheet. Where
questions on inclusion were raised, SW defaulted to JEC for
judgment on inclusion with assistance from AJ when nec-
essary. Any animal model, use of test participant population
that included normal weight or athletic populations was
excluded from the next stage of review. Additionally, any
study that examined acute metabolic responses to pharma-
cological agents without analysis of long-term impact on
measures of interest was also excluded (see Figure 2).
Inclusion analysis
Studies were immediately excluded from the analysis if the
study population was not classified as being overweight,
overfat, or obese, the study examined acute responses only,
or the study utilized animal models and not human
volunteers. From this initial screening, 545 abstracts were
subsequently judged by both authors for inclusion. Of the
545 abstracts, 257 studies were read to determine if they
met the other inclusion criteria for study duration (i.e. eight
weeks) and provided central measures of tendencies and
demographic information for meta-analysis on the mea-
sures of interest for the analysis. After reading and
screening, 67 studies were deemed acceptable for a quali-
tative analysis (i.e. systematic review) of which 21 were
included in the meta-analysis based on the ability to ana-
lyze measures of interest (e.g. reported average and stan-
dard deviation). Several studies were excluded at this point
as measures of interest were indicated as percentage change
over the course of the study. Additionally, the included
studies provided details that would allow for determination
of exercise method or dietary modification that was used in
conjunction with dietary supplementation necessary for
comparison to diet and/or exercise alone. Of these, none
reported within study comparison which led to the deter-
mination to use previously reported values (Clark, 2016;
Clark, 2015) in the analysis presented here.
4 Nutrition and Health XX(X)

Figure 2. Schematic of PRISMA review of literature leading to the meta-analysis for pooled effect size and 95% confidence intervals.

Studies included provided analysis for measures of
interest including: body mass (N¼21), fat mass (N¼15),
fat-free mass (N¼10), low-density lipoprotein (N¼11),
high-density lipoprotein (N¼11), total cholesterol (N¼9),
and resting metabolic rate (N¼5). The included studies
provided a combined population of N ¼ 2359 that allowed
for analysis of measures of interest for study populations
including: body mass (N¼2359), fat mass (n¼754), fat-free
mass (n¼715), low-density lipoprotein (n¼1648), high-
density lipoprotein (n¼1602), total cholesterol (n¼871),
and resting metabolic rate (n¼204). Additionally, there was
an average duration of 20.1+22.1 weeks of intervention
(range 8 to 108 weeks, mode of 12 weeks) related to sup-
plements used in conjunction with lifestyle modification
for weight loss.
Following screening for inclusion and prior to meta-
analysis of findings, each author reviewed the methods
and results presented in 21 studies (see Table 1: Allison
et al., 2012; Auvichayapat et al., 2008; Belza et al., 2007;
Boozer et al., 2002; Boozer et al., 2001; Buchanan and
Beckett, 2013; Dixit et al., 2018; Garvey et al., 2012;
Greenway et al., 2006; Greenway et al., 2004; Hauner et al.,
2017; Heymsfield et al., 1998; Hursel and Westerterp-
Plantenga, 2009; Kovacs et al., 2004; Liu et al., 2013;
Mielgo-Ayuso et al., 2014; Nassar et al., 2008; Ngondi
et al., 2009; Said et al., 2010; Smith et al., 2017; Thom,
2007; Wang et al., 2010; Westerterp-Plantenga et al., 2005)
to ensure limitation of outcome level reporting bias to
ensure validity and reliability of analysis. Review of
methods and reporting of results indicate no outcome level
Clark and Welch 5

Table 1. Summary of studies included in meta-analysis indicating dietary supplements used in conjunction with life style changes,
length of study and general population demographics.
Supplement and dosage in addition Duration
Study Intervention methodology to lifestyle intervention (weeks) Demographics

Allison (Allison et al., 2012) Standard antiobesity treatment (i.e. caloric Phentermine/Topiramate (3.75/23 mg) 56 137 participants
restriction and low intensity aerobic M/F 18-70 years,
exercise) BMI>35 kg/m2
Phentermine/Topiramate (15/92 mg) 56 297 participants
M/F 18-70 years,
BMI>35 kg/m2
Auvichayapat (Auvichayapat Standardized diet (2000 kcal/day; 65% Green tea: 250mg 12 30 participants
et al., 2008) carbohydrates, 15% protein, 20% fat) [409 mg catechin, 28.86 mg caffeine, M 40-60 years,
3 days/ week exercise 33.58 mg EGCG, 9.28 mg epicatechin BMI>25 kg/m2
gallate] 6 tablets/d
Belza(Belza et al., 2007) Caloric restricted diet Green tea/tablet [375 mg EGCG, 150 mg 12 57 participants
(1027 kcal/day to 311 kcal/day) Caffeineþ150 mg Caffeine M/F >18 years,
Anhydrous, 1200 mg tyrosine] 9 BMI>30 kg/m2
tablets/d
Boozer (Boozer et al., 2001) Dietary restriction (fat < 30% kcal/day) Ephedra 72 mg/d þ caffeine 240 mg/d 8 35 participants
moderate level endurance training 30-min/ M/F >18 years,
day BMI 29–35 kg/m2
Boozer (Boozer et al., 2002) Dietary restriction (fat < 30% kcal/day) Ephedra 90 mg/d þ caffeine 192 mg/d 12 83 participants
moderate level endurance training 30-min/ M/F >18 years,
day BMI 25-40 kg/m2
Dixit (Dixit et al., 2018) dietary restriction (1800 kcal/day) LI85008F (6:3:1 Moringa oleifera: 16 66 participants
low intensity endurance training (30 min, 5 Murraya nigii: Curcuma longa) [900 M 21–50 years,
day/wk) mg/d] BMI 27–30 kg/m2
Garvey(Garvey et al., 2012) Participation in LEARN (lifestyle, exercise, 7.5 mg phentermine/46 mg controlled- 108 126 participants
attitudes, relationships, and nutrition) weight release topiramate (7.5/46) M/F 18–60 years,
loss program BMI 27–40 kg/m2
15 mg phentermine/92 mg controlled- 108 245 participants
release topiramate (15/92) M/F 18–60 years,
BMI 27–40 kg/m2
Greenway (Greenway et al., Caloric restricted diet (female: 1200 kcal/day, [70 mg caffieneþ24 mg ephedra] 6 24 28 participants
2004) male: 1500 kcal/day) tablets/d M/F >30 years,
low/moderate intensity endurance training BMI 25–35 kg/m2
40-min/day
Greenway (Greenway et al., Caloric restricted diet (female: 1200 kcal/day, 40 mg pantothenic acid, 200 mg (green 8 4 participants
2006) male: 1500 kcal/day) tea [95%polyphenols, 90%catechins, M/F 30–50 years,
low/moderate intensity endurance training 45%EGCG]), 550 mg guarana (198 mg BM >25 kg/m2
30-min/day Caffeine) 9 mg synephrine, 7.5 mg
salicin, 10 mg ginger root, 375 mg
Thermoblen (L-Tyrosine, L-carnitine,
naringin)2 tablets/d
40 mg pantothenic acid, 200 mg (green 8 10 participants
tea [95%polyphenols, 90%catechins, M/F 30–50 years,
45%EGCG]), 550 mg guarana (198 mg BMI>25 kg/m2
Caffeine) 9 mg synephrine, 7.5 mg
salicin, 10 mg ginger root, 375 mg
Thermoblen (L-Tyrosine, L-carnitine,
naringin)2 tablets/d & 20 mg
phenylephrine
40 mg pantothenic acid, 200 mg (green 8 10 participants
tea [95%polyphenols, 90%catechins, M/F 30–50 years,
45%EGCG]), 550 mg guarana (198 mg BMI >25 kg/m2
Caffeine) 9 mg synephrine, 7.5 mg
salicin, 10 mg ginger root, 375 mg
Thermoblen (L-Tyrosine, L-carnitine,
naringin) 2 tablets/d & 20 mg
phenylephrine
Hauner (Hauner et al., caloric restricted diet Cathine hydrochloride (Alvalin) [16 mg] 24 48 participants
2017) (-500 kcal/day to -600 kcal/day) M/F 18–65 years,
low/moderate intensity endurance training BMI 30–40 kg/m2 or
(5,000-10,000 steps/day) 27–30 kg/m2 w/
comorbidity
Cathine hydrochloride (Alvalin) [32 mg] 24 49 participants
M/F 18–65 years,
BMI 30–40 kg/m2 or
27–30 kg/m2 w/
comorbidity
Cathine hydrochloride (Alvalin) 24 47 participants
[53.3 mg] M/F 18-65y,
BMI 30-40 kg/m2 or
27-30 kg/m2 w/
comorbidity

(continued)
6 Nutrition and Health XX(X)
Table 1. (continued)
Study
Heymsfield (Heymsfield High fiber caloric restricted diet (1200 kcal/day,
et al., 1998)
Hursel (Hursel and Caloric restricted diets (500 kcal/day: 50 g
Westerterp-Plantenga,
2009)
Caloric restricted diet (500 kcal/day: 50 g
Kovacs (Kovacs et al., 2004) Caloric restricted diet (500 kcal/day x 4-wk)
Liu (Liu et al., 2013) Caloric Restricted Diet (Female: 1200 kcal/day,
Mielgo-Ayuso (Mielgo-
Ayuso et al., 2014)
Nasar (Nassar et al., 2008)
Ngondi (Ngondi et al.,
2009)
Said (Said et al., 2010)
Smith (Smith et al., 2017)
Thom (Thom, 2007)
Wang (Wang et al., 2010)
Westerp (Westerterp-
Plantenga et al., 2005)
M: male; F: female; M/F: male and female; BMI: body mass index; EGCG: Epigallocatechin gallate.
Supplement and dosage in addition Duration
Intervention methodology to lifestyle intervention (weeks) Demographics
G cambogia [3000 mg/d: Hydroxycitric 12 42 participants
50% carbohydrate, 30% protein, 20% fat) Acid 1500 mg/d] M/F > 18 years,
low/moderate intensity physical activity daily BMI>30 kg/m2
Green tea: [270 mg EGCG, 150 mg 16 20 participants
carbohydrates, 52 g protein, 9 g fat x 4-wk) Caffeine] 6 tablets/d @ 50–60 g M/F 18–60 years,
eucaloric diet (50–60 g/day or 10% of kcal/ protein/d BMI 25–35 kg/m2
day protein x 12-wk)
low/moderate intensity physical activity daily
Green Tea: [270 mg EGCG, 150 mg 16 20 participants
carbohydrates, 52 g protein, 9 g fat x 4-wk) Caffeine] 6 tablets/d @ 100-110 g M/F 18–60 years,
eucaloric diet (100–110 g/day or 20% of kcal/ protein/d BMI 25–35 kg/m2
day protein x 12-wk)
low/moderate intensity physical activity daily
Green Tea [104 mg caffeine, 573 mg 17 57 participants
eucaloric diet (x 13-wk) catechins/323 mg EGCG] 6 tablets/d M/F 18–60 years,
low/moderate intensity physical activity daily BMI 25–35 kg/m2
[200 mg caffeineþ20 mg ephedra] 3 24 17 participants
male: 1500 kcal/day) tablets/d M/F 18–60 years,
low/moderate intensity endurance training BMI 30–40 kg/m2
30-min/day [200 mg caffeineþ20 mg ephedraþ20 mg 24 18 participants
leptin] 3 tablets/day M/F 18–60 years,
BMI 30–40 kg/m2
Caloric restricted diet 300 mg/d [EGCG] 12 43 participants
(-600 kcal/day): 55% carbohydrates, 30% fat, F >18 years,
15% protein BMI 30–40 kg/m2
standard physical activity
Caloric restricted & low glycemic index diet 250 mg thermogenic agent 8 20 participants
(-600 kcal/day) F >18 years,
resistance training 3 day/week BMI>30 kg/m2
Standard antiobesity treatment (i.e. caloric 150 mg IGOB131 (Irvingia gabonensis) 6 10 46 participants
restriction and low intensity aerobic tablets/d M/F 19–50 years,
exercise) BMI>25 kg/m2
Standard antiobesity treatment (i.e. caloric “Weight Level” [60 mg Alchemilla 12 16 participants
restriction and low intensity aerobic vulgaris, 50 mg Olea europaea, 20 mg M/F 19–50 years,
exercise) Mentha longiforia, 25 mg Cuminum BM>25 kg/m2
cyminum, 7 mg Vit C, 148 mg
Tricalcium Phosphate (TCP)] 3
tablets/d
Caloric restricted diet 10 mg lorcaserinþ15 mg phenermine (1x) 12 78 participants
(-600 kcal/day) M/F 18–60 years,
moderate endurance training 30-min/day BMI>30 kg/m2 or
27–30 kg/m2 w/
comorbidities
10 mg lorcaserinþ15 mg phenermine 12 79 participants
(2x) M/F 18–60 years,
BMI>30 kg/m2 or
27–30 kg/m2 w/
comorbidities
Standard antiobesity treatment (i.e. caloric Caffeine [200/90-100 mg chlorogenic 12 15 participants
restriction and low intensity aerobic acid)] M/F >18 years,
exercise) BMI 27.5–32 kg/m2
Caffeine [200/30-40 mg chlorogenic 12 15 participants
acid)] M/F >18 years,
BMI 27.5–32 kg/m2
Standard antiobesity treatment (i.e. caloric 30 mg Catechin þ10 mg Caffeine 12 43 participants
restriction and low intensity aerobic M/F 18–55 years,
exercise) BMI 24–35 kg/m2
458 mg Catechin þ104 mg Caffeine 12 47 participants
M/F 18–55 years,
BMI 24–35 kg/m2
468 mg Catechin þ 126 mg Caffeine 12 49 participants
M/F 18–55 years,
BMI 24–35 kg/m2
886 mg Catechin þ198 mg Caffeine 12 43 participants
M/F 18–55 years,
BMI 24–35 kg/m2
Caloric restricted diet (500 kcal/day: 50 g Green tea [270 mg EGCG, 150 mg 16 19 participants low
carbohydrates, 52 g protein, 9 g fat x 4-wk) Caffeine] [45 mg EGCG, 25 mg caffeine (<300 mg/d),
eucaloric diet (x 12-wk) Caffeine] 6 tablets/d M/F 18–60 years,
low/moderate intensity physical activity daily BMI 29 kg/m2
Green tea: [270 mg EGCG, 150 mg 16 19 participants high
Caffeine] [45 mg EGCG, 25 mg caffeine (>300 mg/d),
Caffeine] 6 tablets/d M/F 18–60 years,
BMI 29 kg/m2
Clark and Welch
Table 2. Pooled effect sizes for thermogenic dietary
supplements to induce positive beneficial changes in the measures
of interest.
Number Number
of Study of Study
Populations Populations
Measure of Above Pooled Below Pooled
Interest Pooled ES (CI.95) ES ES
BM 0.85 (-0.09, 0.94) 5 27
FM 0.75 (-0.20, 0.95) 5 13
FFM -0.23 (-0.25, 0.05) 9 4
TC 0.07 (-0.20, 0.27) 6 5
LDL 0.58 (-0.13, 0.71) 2 15
HDL 0.00 (-0.133, 0.131) 13 3
RMR 0.018 (-0.67, 0.69) 2 5
ES: effect size; CI: confidence interval; BM: body mass; FM: fat mass; FFM:
fat free mass; TC: total cholesterol; LDL: low-density lipoproteins; HDL:
high-density lipoproteins; RMR: resting metabolic rate.
bias in results of the measures of interest analyzed here. As
with all reviews and meta-analyses, we were unable to
eliminate publication bias from our selection of studies and
therefore will address this bias by using a previously uti-
lized method (Clark, 2016; Clark, 2015) and analysis of
inter-study pooled effect size based on the assumption of a
random effect.
Tabulation and analysis. Studies were entered into a shared
database to include: population size, demographics, out-
come level reporting bias, study duration, supplement used
and dosage, additional treatment (i.e. exercise and diet
modification), and then the average and standard deviations
reported for all measures of interest (body mass, fat mass,
fat-free mass, cholesterol, low-density lipoprotein, high-
density lipoprotein, total cholesterol, resting metabolic
rate). Analysis was completed for within study treatment
effect size (change relative to pre-treatment) and then
pooled treatment effect size for each measure of interest
across all study populations and then relative to duration of
treatment (e.g. 8 weeks, 9–12 weeks, 13–20 weeks and > 20
weeks). Calculations for intra-study and inter-study pooled
effect size was determined following previously published
methodologies for an inter-study pooled effect size based
on random effect (Clark, 2016; Clark, 2015). Addressing
the impact of supplementation versus no supplementation
was not possible based on the studies included. As such, we
conducted comparison for effect size with studies previ-
ously screened and reported on based on the identical
methodologies used here to determine effectiveness and
effect sizes (Clark, 2016; Clark, 2015). The comparison of
effectiveness between supplementation and no supple-
mentation was done via chi-square comparison, studies
were then grouped based on the relative intra-study effec-
tiveness as having an effect size greater than or less than the
pooled effect size across all studies analyzed. Afterwards, a
2x2 (above versus below; supplement versus comparison to
7
exercise or diet and exercise) chi-square analysis of effect
size was run between studies analyzed here and those that
have been previously reported upon (Clark, 2016; Clark,
2015) to compare overall level of effectiveness between the
supplements and other lifestyle methods (e.g. diet, exercise,
or combination of diet and exercise without incorporation
of supplements) that were indicated as inducing weight loss
or improvements in cardiometabolic health. Additionally,
any adverse effects noted from the included studies were
tabulated and the percentage of occurrences was calculated
to determine most and least commonly reported adverse
effects.
Results
Effectiveness of supplements
As seen in Table 2, there is general trend for no effec-
tiveness for obtaining beneficial changes from use of
thermogenic (fat burner) dietary supplements for mea-
sures of interest, with the exception of maintaining fat free
mass (FFM). While individual studies may indicate a
positive effect, the degree of benefit when pooled across
all studies shows limitations to this indication as even for
those seeing a large effect size (i.e. change in body mass
(BM) and fat mass (FM)), the CI.95 for all measures of
interest crosses an ES of 0.00, indicating that benefit may
not always occur across the entire population regardless of
the duration of intervention or type of supplement used
(Figures 3 and 4).
Comparison of effect based on the type of supplement
showing a similar trend of no benefit was seen across all
groups (see Figure 3). Even where the pooled ES for
changes in body mass and fat mass indicate possible favor
toward inclusion of the supplements (Figure 3) the confi-
dence interval for effectiveness crosses the indication for
no favor, an ES of 0.00. Yet at the same time the inclusion
of ECGC and green tea or the combination of sympatho-
mimetic ingredients show no favor for improving fat-free
mass (Figure 3). Comparing supplements based on princi-
ple active ingredients, there appears to be no favor indi-
cated toward any single supplement type being better than
any other for eliciting changes in body mass. As indicated
by the comparison, phenyl-based substances showed a lack
of favor compared with all other substances (ES¼-0.33
(-0.05, -0.28)), versus ECGC only (ES¼-0.42 (-0.10, -0.31)),
or the combined sympathomimetic amines (ES¼-0.34
(-0.07, -0.26)). Additionally, no benefit was seen in com-
parison of the ECGC supplements relative to all other
supplements (ES¼0.15 (-0.06, 0.20)), or combined sym-
pathomimetic amines (ES¼0.03 (-0.07, 0.10)), while the
comparison the sympathomimetic amines relative to all
other supplements (ES¼0.16 (-0.05, 0.21)). Based on the
ability to elicit beneficial changes in altering fat mass,
treatment using ECGC as the dietary supplement was more
favorable than the combined supplements of sympathomi-
metic amines (ES¼0.71). Yet the CI.95 for the effectiveness
8 Nutrition and Health XX(X)

Figure 3. 95% confidence interval for effect size to induce positive changes based on the type of supplement (phenyl-related, ECGC,
sympathomimetic amine) integrated into diet and exercise programs for changes in body mass (BM), fat mass (FM) and fat-free mass
(FFM) based on duration of study interventions. Note that a loss of body mass and fat mass are indicated as positive, while maintenance
and gain of fat-free mass is indicated as negative.

Figure 4. 95% confidence interval for effect size to induce positive changes in body mass (BM), fat mass (FM) and fat-free mass (FFM)
based on duration of study interventions. Note that a loss of body mass and fat mass are indicated as positive, while maintenance and
gain of fat-free mass is indicated as negative.

indicates that this may not always hold true with a range of -
0.12 to 0.81, thus indicating no real favor between the two. It
must be deduced that once again, no treatment showed any
favor for eliciting beneficial responses for maintaining or
gaining fat-free mass.
Secondary analysis by type of dietary supplement based
on duration of use indicates the same trend of no benefit
across all durations (Figure 4). Related to the ability to
induce changes in body mass, the greatest effectiveness
was seen in 8 weeks and for studies longer than 20 weeks,
Clark and Welch 9

Figure 5. 95% confidence interval for effect size to induce positive changes in cardiometabolic measures: total cholesterol (TC), low
density lipoproteins (LDL), and high-density lipoproteins (HDL) based on the type of supplement (phenyl-related, ECGC, sympatho-
mimetic amine) integrated into diet and exercise programs.

Figure 6. 95% confidence interval for effect size to induce positive changes in cardiometabolic measures: total cholesterol (TC), low
density lipoproteins (LDL), and high-density lipoproteins (HDL) based on duration of study interventions.

ES ¼ 1.36 (-2.93 to 4.30) and 1.35 (-0.51 to 1.87) respec-
tively. While the ability to induce body composition changes
show no difference in effectiveness based on duration of
intervention for loss of fat mass, there was not an indication
for treatment favoring use of dietary supplements to retain
fat-free mass.
As for modification of cardiometabolic health, longer
duration was indicated as having better effectiveness than
shorter durations (Figure 5) as studies longer than 20 weeks
show ESs of 1.66 (-3.37 to 5.02) and 1.04 (-0.79 to 1.83) for
TC and LDL respectively. There appears to be no impact of
the use of dietary supplements in favoring changes to HDL
regardless of the duration of the intervention.
This trend of showing no favor for eliciting benefits
from dietary supplements continues when examined based
on the type of supplement (see Figure 6). Based on the
10
specific type of supplement, phenyl-based supplements
appear to elicit greater benefit than the ECGC supplements
(ES¼0.43 (-0.20, 0.64)), while the sympathomimetic
amines appear to have greater effectiveness than all other
supplements (ES¼0.74 (-0.13, 0.87)). However, in all
cases, the confidence intervals indicate the possibility of no
favor or a reversal of favor as the ranges cross 0.00. A
similar pattern is noted in relation to altering HDL, with
phenyl-based supplements eliciting greater benefit than
ECGC (ES¼0.65 (-0.21, 0.8)), whereas sympathomimetic
amines appear to have greater effectiveness than all others
combined (ES¼0.99 (-0.14, 1.07)). Along with changes in
TC levels, where phenyl-based supplements elicit a greater
benefit than ECGC (ES¼0.45 (-0.31, 0.65)), sympathomi-
metic amines appear to have greater effectiveness than all
others combined (ES¼0.79 (-0.24, 1.07)).
Comparison with diet, exercise or combination of diet
and exercise without supplementation
Analysis of study ES with previous reported ES for diet and
exercise and exercise alone shows varying benefits. Diet
and exercise were able to induce a greater number of
populations to exceed the pooled effect size for changes in
BM versus the use of the dietary supplements (whether
pooled or parsed by supplemental type), for the combina-
tion of diet and endurance exercise (w2¼4.32, p¼0.038). A
similar relationship is seen for FFM for diet and any form
of exercise (w2¼8.69, p¼0.003) that is also indicated in
favoring the use of combining diet and strictly resistance
exercise (w2¼7.63, p¼0.006) or the combination of diet and
strictly endurance exercise (w2¼4.49, p¼0.034), and trends
toward having a differential effect favoring the use of
resistance exercise alone (w2¼2.66, p¼0.10).
Diet and exercise were able to induce a greater number
of populations to exceed the pooled effect size for changes
in total cholesterol (TC) relative to use of dietary supple-
ments (whether pooled together or parsed by supplemental
type) with the combination of diet and strictly resistance
exercise (w2¼5,40, p¼0.02) or strictly endurance training
alone (w2¼4.38, p¼0.036) and trends toward having a
differential effect favoring strictly resistance training alone
(w2¼2.59, p¼0.10). There is a similar relationship seen for
the effectiveness in inducing changes in high-density
lipoproteins (HDL) for diet and strictly resistance exer-
cise (w2¼5.00, p¼0.003) and any form of exercise without
diet modification (w2¼6.11, p¼0.013) when only using
resistance exercise (w2¼5.00, p¼0.025). For the ability to
induce beneficial changes in HDL, there is a trend toward a
differential effect favoring the use of endurance exercise
alone (w2¼2.93, p¼0.09). Yet all types of interventions
elicited similar impacts on low-density lipoproteins (LDL).
Adverse effects and attrition
Of the studies included in the analysis, 10 studies (Allison
et al., 2012; Belza et al., 2007; Boozer et al., 2002; Boozer
Nutrition and Health XX(X)
et al., 2001; Dixit et al., 2018; Greenway et al., 2006;
Greenway et al., 2004; Heymsfield et al., 1998; Liu et al.,
2013; Smith et al., 2017) reported adverse effects stemming
from the use of the dietary supplements. There was an
average report of adverse events occurring in 43%+21%
of the population,with a range of reports running from 14%
to 68%. The majority of incidents involved cardiovascular
issues, followed by sleep, anxiety, and then gastrointestinal
issues. Due to lack of reporting on similar adverse events in
the diet and exercise studies included from a previous
analysis for comparison here, it is not possible to assess
differences in adverse effects between protocols. Yet it
should be noted that the reported rates of attrition and
compliance in studies were relatively similar regardless of
any reports of adverse events occurring.
Discussion
The ability to effectively and efficiently cause body mor-
phology change is the goal of any diet and exercise inter-
vention program for those who are overfat (Clark, 2012).
For many individuals who are overfat, interventions have
extended beyond diet and exercise intervention programs to
include the use of dietary supplements (i.e. thermogenic
aids, fat burners) in conjunction with diet and exercise in
which beneficial modifications have been based on the
assumption that an effective intervention would be able to
induce a reduction of 5% to 10% of body mass (NCCIH,
2018; Hasani-Ranjbar et al., 2013; Hendricks, 2017; Jeu-
kendrup and Randell, 2011; Kerksick et al., 2018). How-
ever, the indication for an effect to alter body weight does
not reflect by itself a claim for having beneficial effec-
tiveness, i.e. a CI.95 of ES>0.00, across the entirety of the
population or the duration that it might take to provide this
level of benefit to be achieved (Clark, 2015; Clark, 2016) as
the 5% to 10% body mass does not establish a means of
evaluation between various methods of treatments used
across a wide range of populations. Further, looking strictly
at a change in body mass does not in actuality specify an
indication of a change in the types of body mass that would
allow for obtaining the positive changes in health status
sought in conjunction with progress weight loss (Booth
and Laye, 2009; Clark, 2012; Clark and Goon, 2015). As
such, we have undertaken analysis here.
While some may indicate that the absolute, or relative,
weight loss can serve as the indicator of effectiveness,
examination of effectiveness (via pooled effect size across
populations) provides the means by which one is able to
determine the expected benefit from the treatment inter-
vention that includes the use of thermogenic (or fat burner)
agents. Undertaking this form of analysis here has refuted
many conclusions drawn from anecdotal claims or single
study reports of effectiveness and benefit, whether exam-
ined across the various supplements used or by the specific
type of supplement. Regardless of the intended mechanism
of action, analysis of the evidence here indicates that claims
of effectiveness may be an overstatement and shows some
Clark and Welch
support toward previous narrative and systematic reviews
on the subject (Bersani et al., 2015; Inchiosa, 2011; Jeu-
kendrup and Randell, 2011; Schulman, 2003) that did not
include meta-analysis. The overall effectiveness of com-
bining fat burners (regardless of the type) with diet and
exercise regimens does not induce beneficial effectiveness
in comparison to diet and exercise, or even exercise alone.
Furthermore, the ability of fat burner dietary supplements
to induce positive adaptations may be less effective than
exercise or a combination of diet and exercise as previously
reported (Clark, 2015; Clark, 2016).
Additionally, there is the impact on type of body mass to
be maintained (i.e. fat free mass) and the type of body mass
to be reduced (i.e. fat mass) within a given intervention. As
one goal for intervention is not only to reduce body mass,
along with improving overall health status for the indi-
vidual who is overfat (Clark, 2012). A result that can be
achieved by retention of fat-free mass while reducing fat
mass to allow for alterations of hormonal signals necessary
for an improvement in health status (Clark, 2012; Clark and
Goon, 2015). In this, all supplement interventions included
in the meta-analysis here are less effective than the exercise
or diet and exercise programs that were used for compari-
son, a phenomenon that is most likely attributed to the
previous indication that interventions meant to maintain
fat-free mass and reduce fat mass must produce a level of
muscle stimulation load to induce hypertrophy within the
skeletal muscle (Clark, 2015; Clark and Goon, 2015; Hall,
2013; Schwingshackl et al., 2013).
Therefore, if the inclination for treatment is to alter body
morphology while also improving overall health, inclusion
of fat burners may not provide the intended benefit without
an appropriate exercise stimulus, even when the stimulus
was appropriate for inducing hypertrophication of the
skeletal muscle necessary to obtain improved health status
(Booth and Laye, 2009; Clark, 2012; Clark and Goon,
2015; Hall, 2013). As analysis here indicates, within study
effectiveness may not induce a benefit beyond what can be
obtained without inclusion of the fat burner, regardless of
the type or proposed mechanism of action for the supple-
ment, a phenomenon that has a host of rationales, but goes
beyond what was examined here. Yet, one can speculate
that it may be due to long term impacts that sympathomi-
metic compounds have on the metabolism of skeletal
muscle where such supplements may interfere with the
intracellular signaling pathways necessary to induce
hypertrophy and thus truncate the desired benefit from
exercise. Should these compounds continue to be available,
this speculation deserves much more investigation in
human populations that have been examined to date.
Given the limited ability to induce positive changes in
fat-free mass, it is not surprising to see limited ability to
induce beneficial changes in health status through inducing
beneficial changes in cardiometabolic measurements
examined here (Booth and Laye, 2009; Clark and Goon,
2015; Hall, 2013). Moreover, changes induced in health
status due to supplement use were no better, and somewhat
11
worse, than those induced from exercise or a combination
of diet and exercise used for comparison. There are several
reasons why this might be the case as it relates to lipid
profiles, he most probable rationale for this effect being the
lack of proper exercise stimulus (Booth and Laye, 2009;
Clark, 2012) coupled with the impact that this type of
dietary supplement might have on metabolism within the
liver. There is some indication that dosages used of the fat
burner supplements negatively impact hepatocyte functions
due to toxic effects (NCCIH, 2018; Garcia-Cortes et al.,
2016), a point that once again goes beyond the purpose of
the meta-analysis and systematic review here, but deserves
much more attention than it has received to date.
Additionally, studies examined here report a chronic
negative impact on resting metabolic rates following sup-
plementation, an alarming indication given that supple-
ments are taken to obtain just such a benefit (i.e. increased
basal metabolic rate (BMR)) and it is direct opposition to
what was seen previously in studies involving a combina-
tion of diet and exercise, or exercise alone. While there are
reports that an acute positive impact is seen on metabolic
rates (effectiveness not reported here) (Belza and Jessen,
2005; Campbell et al., 2016; Harpaz et al., 2017; Vaughan
et al., 2014), analysis for long-term effectiveness indicates
that this acute benefit does not continue as usage continues
within an intervention program. This issue is key in the
argument both for and against the use of the fat burners, as
any intervention program developed to change body com-
position and health status must be a prolonged intervention
program similar to treatment used for other lifestyle dis-
eases (Clark, 2016).
Even with limited evidence of effectiveness for greater
benefit in comparison to exercise or diet and exercise
interventions, there is some indication that many individ-
uals would still choose such supplements due to the cult of
thinness (or an aversion to fatness), a central dogma in
many advertisements and anecdotes cited by users of these
supplements (Calfee and Fadale, 2006; Clark, 2019; Ethan
et al., 2016; NCCIH, 2018). We must also draw attention to
the ever-growing reports of adverse effects and negative
outcomes from the use of purported fat burner dietary
supplements (Bersani et al., 2015; Clark, 2019; Ekor, 2014;
Garcia-Cortes et al., 2016; Inchiosa, 2011; Rios-Hoyo and
Gutierrez-Salmean, 2016; Stein, 2002). This list of adverse
and negative outcomes includes reports related to issues of
Rhabdomyolysis, ischemic stroke, and sudden cardiac
death stemming from the use of this type of dietary sup-
plement in conjunction with diet and exercise (Bouchard
et al., 2005; Hannabass and Olsen, 2016; Pope et al., 2014;
Schulman, 2003; Shekelle et al., 2003). Additionally, and
previously noted, are the reports of hepatic and renal issues
that are associated with the use of sympathomimetic dietary
supplements.(Garcia-Cortes et al., 2016) More troubling
are the various reports of psychiatric, cognitive, and sleep
disturbances associated with the use of thermogenic and
fat-burner substances (Bersani et al., 2015; Inchiosa, 2011;
Rios-Hoyo and Gutierrez-Salmean, 2016).
12 Nutrition and Health XX(X)

Moreover, there is also a need to stipulate that phar- Conclusion

macologically speaking, extended use of sympathomimetic
Analysis indicates that the level of effectiveness across the
supplements, as with any medicinal substance, may wane
studies is limited, with the CI.95 for pooled effect size
in responsiveness and benefits with prolonged use. This
indicating no favor in the therapeutic use of dietary sup-
reduced effectiveness is most likely due to alteration of
plements. There was also no indication that the inclusion of
receptors on cells where the drug is interacting. A large
fat burners and thermogenic dietary supplements was any
portion of this argument goes well beyond what has been
more effective than exercise or a combination of diet and
analyzed here. Nonetheless, it must be made, especially in
exercise, a finding that becomes more pronounced when
light of the intended question about long-duration use of
examining any alteration in fat-free mass as it is commonly
such supplements for achieving weight loss for individuals
accepted that weight loss interventions for health
who are overfat, an issue that to date unfortunately cannot
improvement should strive to maintain, if not gain, fat-free
be addressed, as few studies examine dose responses for
mass over the length of the intervention. Analysis here
use of these substances over a duration greater than 8
showed little ability to do such and while body mass may be
weeks. Yet, it must be remembered that any prolonged
lost over the course of the intervention, the inability to
usage of drugs and pharmacological agents leads to issues
maintain fat-free mass hampers the intervention’s ability to
of tolerance and receptor modifications for the pharmaco-
induce improvements in overall health. Additionally, there
logical agent (Harpaz et al., 2017; Soni et al., 2004; Stohs
is no benefit (i.e. CI.95 crosses 0.00) in improving cardio-
et al., 2011). Tolerance necessitates possibly ever-
metabolic health to be derived from the addition of the
increasing dosages of the pharmacological agent and
thermogenic dietary supplements for individuals who are
given that supplements are poorly regulated substances,
overfat. Comparisons failed to show that the inclusion of
there is an increased risk of adverse events. This issue is
the dietary supplements indicated benefit for altering circu-
compounded based on the common adage used by con-
lating levels of cholesterol, both within the studies compared
sumers of most dietary supplements: if some is of benefit,
here and between studies that utilized just exercise or a
more must be better. When taken together may underlie the
combination of diet and exercise. Alarmingly, the action of
limited effectiveness seen chronically and may provide a
the dietary supplements should allow for an increased
rationale for the increased risk for adverse events with
metabolic rate, yet chronic use appears to induce a reduced
prolonged use. Both of these issues deserve much more
metabolic rate. A rationale for such a finding goes beyond
attention and research than has been given to such sub-
this systematic review but deserves investigation. Thus, even
stances to date. Especially given the evidence that at least 8
with a trove of anecdotal, or single study reports that purport
weeks are necessary to always have an effectiveness to
benefit from the addition of fat burners and thermogenic
induce positive adaptations for individuals who are overfat.
dietary supplements in assisting those who are overfat to
As with any review and meta-analysis, there are lim-
reduce fat mass and improve overall health, one must be
itations that must be addressed before moving forward. The
careful about accepting these purported benefits. When
most noted limitation here is that while over 20,000 returns
viewed over the long-term, lifestyle interventions that are
were screened from the databases, we are still limited in our
necessary to improve the health status and body composition
analysis based on what is published and accessible for
of those who are overfat should include exercise, or com-
review, an issue that plagues many reviews on the topic of
bined diet and exercise, which appear to be more beneficial
dietary supplements due to the nature of conducting
than a similar intervention that also includes thermogenic or
research on supplements and sponsorship by supplement
“fat-burner” agents and dietary supplements.
companies. Moreover, a number of studies solely reported
acute responses and limited our ability to extrapolate
Acknowledgement
findings into to the time frame that was sought analysis.
This limitation inhibited our ability to perform analysis and The authors would like to acknowledge AJ for initial input
draw conclusions on a number of measures of interest and on the question, assistance in determining the eligibility of
indicates the need for further research on the topic so as to studies for inclusion, and the idea that led to this study and
be able to draw such conclusions. Likewise, a number of meta-analysis.
studies utilized normal weight volunteers whose responses
would not be comparable with responses of overfat Author contribution
volunteers. Within the studies included, it was not possible James Clark and Sarah Welch were responsible for screen-
to examine gender differences in responses seen, as results ing all articles for inclusion and composition of the manu-
in studies included did not allow for extraction of data script. James Clark was responsible for completion and
based on gender. Additionally, we were hampered in interpretation of the statistical analysis.
extrapolating results to investigate differences that might
exist between the various dietary supplements or dosages Ethical approval
used beyond the categorization of studies reported here, as Review and meta-analysis were conducted under the
study and population sizes were too small to examine inter- approval of the review board for Scientific Health: Educa-
study pooled effects. tion and Human Performance.
Clark and Welch
Ethical statements
Availability of data and materials: Database with entry of
averages, standard deviations, and intervention length
along with study population size can be obtained upon
request from JEC
Declaration of conflicting interests
The authors declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of
this article.
Funding
The authors received no financial support for the research,
authorship, and/or publication of this article.
ORCID iD
James E Clark https://orcid.org/0000-0002-4614-9535
Supplemental Material
Supplemental material for this article is available online.
References
Allison DB, Gadde KM, Garvey WT, et al. (2012) Controlled-
release phentermine/topiramate in severely obese adults: A
randomized controlled trial (EQUIP). Obesity (Silver Spring,
Md) 20: 330–342.
Auvichayapat P, Prapochanung M, Tunkamnerdthai O, et al.
(2008) Effectiveness of green tea on weight reduction in obese
Thais: A randomized, controlled trial. Physiology and Beha-
vior 93: 486–491.
Belza A and Jessen AB (2005) Bioactive food stimulants of sym-
pathetic activity: Effect on 24-hour energy expenditure and fat
oxidation. European Journal of Clinical Nutrition 59:
733–741.
Belza A, Frandsen E and Kondrup J (2007) Body fat loss achieved
by stimulation of thermogenesis by a combination of bioactive
food ingredients: A placebo-controlled, double-blind 8-week
intervention in obese subjects. International Journal of Obe-
sity (2007) 31: 121–130.
Bersani FS, Coviello M, Imperatori C, et al. (2015) Adverse psy-
chiatric effects associated with herbal weight-loss products.
BioMed Research International 2015: 120679.
Booth FW and Laye MJ (2009) Lack of adequate appreciation of
physical exercise’s complexities can pre-empt appropriate
design and interpretation in scientific discovery. Journal of
Physiology (London) 587: 5527–5539.
Boozer CN, Daly PA, Homel P, et al. (2002) Herbal ephedra/
caffeine for weight loss: A 6-month randomized safety and
efficacy trial. International Journal of Obesity and Related
Metabolic Disorders 26: 593–604.
Boozer CN, Nasser JA, Heymsfield SB, et al. (2001) An herbal
supplement containing Ma Huang-Guarana for weight loss: A
randomized, double-blind trial. International Journal of Obe-
sity and Related Metabolic Disorders 25: 316–324.
Bouchard NC, Howland MA, Greller HA, et al. (2005) Ischemic
stroke associated with use of an ephedra-free dietary supple-
ment containing synephrine. Mayo Clinic Proceedings 80:
541–545.
13
Buchanan R and Beckett RD (2013) Green Coffee for Pharmaco-
logical Weight Loss. Journal of Evidence-Based Complemen-
tary and Alternative Medicine 18: 309–313.
Calfee R and Fadale P (2006) Popular ergogenic drugs and sup-
plements in young athletes. Pediatrics 117: e577–589.
Campbell BI, Colquhoun RJ, Zito G, et al. (2016) The effects of a
fat loss supplement on resting metabolic rate and hemody-
namic variables in resistance trained males: a randomized,
double-blind, placebo-controlled, cross-over trial. Journal of
the International Society of Sports Nutrition 13: 14.
Clark JE (2012) An overview of the contribution of fatness and
fitness factors, and the role of exercise, in the formation of
health status for individuals who are overweight. Journal of
Diabetes and Metabolic Disorders 11: 19.
Clark JE (2015) Diet, exercise or diet with exercise: Comparing
the effectiveness of treatment options for weight-loss and
changes in fitness for adults (18–65 years old) who are overfat,
or obese; Systematic review and meta-analysis. Journal of
Diabetes and Metabolic Disorders 14: 31.
Clark JE (2016) The impact of duration on effectiveness of exer-
cise: The implication for periodization of training and goal
setting for individuals who are overfat: A meta-analysis. Biol-
ogy of Sport 33: 309–333.
Clark JE (2019) Diets and diet therapy: Diet supplements for
exercise. In: Ferranti P, Berry EM and Anderson JR (eds)
Encyclopedia of Food Security and Sustainability. Elsevier,
161–170.
Clark JE and Goon DT (2015) The role of resistance training for
treatment of obesity related health issues and for changing
health status of the individual who is overfat or obese: A
review. Journal of Sports Medicine and Physical Fitness 55:
205–222.
Coulter AA, Rebello CJ and Greenway FL (2018) Centrally acting
agents for obesity: Past, present and future. Drugs 78:
1113–1132.
Dixit K, Kamath DV, Alluri KV, et al. (2018) Efficacy of a novel
herbal formulation for weight loss demonstrated in a 16-week
randomized, double-blind, placebo-controlled clinical trial
with healthy overweight adults. Diabetes, Obesity & Metabo-
lism 20: 2633–2641.
Donsmark M, Langfort J, Holm C, et al. (2005) Hormone-
sensitive lipase as mediator of lipolysis in contracting skeletal
muscle. Exercise and Sport Sciences Reviews 33: 127–133.
Ekor M (2014) The growing use of herbal medicines: issues relat-
ing to adverse reactions and challenges in monitoring safety.
Frontiers in Pharmacology 4: 177.
Esteghamati A, Mazaheri T, Vahidi Rad M, et al. (2015) Com-
plementary and alternative medicine for the treatment of obe-
sity: A critical review. International Journal of Endocrinology
and Metabolism 13: e19678.
Ethan D, Basch CH, Hillyer GC, et al. (2016) An analysis of
weight loss articles and advertisements in mainstream
women’s health and fitness magazines. Health Promotion Per-
spectives 6: 80–84.
Figueiredo PRLd, Siebra ALdA, Neto LJdL, et al. (2015) Obesity
and natural products. Journal of Food and Nutrition Research
3: 540–549.
Garcia-Cortes M, Robles-Diaz M, Ortega-Alonso A, et al. (2016)
Hepatotoxicity by dietary supplements: A tabular listing and
clinical characteristics. International Journal of Molecular
Sciences 17: 537.
14
Garvey WT, Ryan DH, Look M, et al. (2012) Two-year sustained
weight loss and metabolic benefits with controlled-release
phentermine/topiramate in obese and overweight adults
(SEQUEL): A randomized, placebo-controlled, phase 3 exten-
sion study. American Journal of Clinical Nutrition 95:
297–308.
Greenway F, De Jonge-Levitan L, Martin C, et al. (2006) Dietary
herbal supplements with phenylephrine for weight loss. Jour-
nal of Medicinal Food 9: 572–578.
Greenway FL, De Jonge L, Blanchard D, et al. (2004) Effect of a
dietary herbal supplement containing caffeine and ephedra on
weight, metabolic rate, and body composition. Obesity
Research 12: 1152–1157.
Gurley BJ, Gardner SF, White LM, et al. (1998) Ephedrine phar-
macokinetics after the ingestion of nutritional supplements
containing Ephedra sinica (ma huang). Therapeutic Drug
Monitoring 20: 439–445.
Hall KD (2013) Diet versus exercise in “the biggest loser” weight
loss competition. Obesity 21: 957–959.
Haller CA, Jacob P and Benowitz NL (2002) Pharmacology of
ephedra alkaloids and caffeine after single-dose dietary sup-
plement use. Clinical Pharmacology and Therapeutics 71:
421–432.
Haller CA, Jacob P and Benowitz NL (2004) Enhanced stimulant
and metabolic effects of combined ephedrine and caffeine.
Clinical Pharmacology and Therapeutics 75: 259–273.
Hannabass K and Olsen KR (2016) Fat burn X: Burning more than
fat. British Medical Journal Case Reports 2016.
Harpaz E, Tamir S, Weinstein A, et al. (2017) The effect of
caffeine on energy balance. Journal of Basic and Clinical
Physiology and Pharmacology 28: 1–10.
Hasani-Ranjbar S, Jouyandeh Z and Abdollahi M (2013) A sys-
tematic review of anti-obesity medicinal plants - an update.
Journal of Diabetes and Metabolic Disorders 12: 28.
Hauner H, Hastreiter L, Werdier D, et al. (2017) Efficacy and safety
of cathine (nor-pseudoephedrine) in the treatment of obesity: A
randomized dose-finding study. Obesity Facts 10: 407–419.
Hendricks EJ (2017) Off-label drugs for weight management.
Diabetes, Metabolic Syndrome and Obesity 10: 223–234.
Heuberger J and Cohen AF (2019) Review of WADA prohibited
substances: Limited evidence for performance-enhancing
effects. Sports Medicine 49(4): 525–539.
Heymsfield SB, Allison DB, Vasselli JR, et al. (1998) Garcinia
cambogia (Hydroxycitric Acid) as a potential antiobesity
agent. Journal of the American Medical Association
280(18): 1596–1600.
Hursel R and Westerterp-Plantenga MS (2009) Green tea catechin
plus caffeine supplementation to a high-protein diet has no
additional effect on body weight maintenance after weight
loss. American Journal of Clinical Nutrition 89: 822–830.
Inchiosa MA (2011) Experience (mostly negative) with the use of
sympathomimetic agents for weight loss. Journal of Obesity
2011; 2011: 764584.
Jenkinson DM and Harbert AJ (2008) Supplements and sports.
American Family Physician 78: 1039–1046.
Jeukendrup AE and Randell R (2011) Fat burners: Nutrition sup-
plements that increase fat metabolism. Obesity Reviews 12:
841–851.
Kerksick CM, Wilborn CD, Roberts MD, et al. (2018) ISSN exer-
cise and sports nutrition review update: research & recommen-
dations. Journal of the International Society of Sports
Nutrition 15: 38.
Nutrition and Health XX(X)
Kovacs EM, Lejeune MP, Nijs I, et al. (2004) Effects of green tea
on weight maintenance after body-weight loss. British Journal
of Nutrition 91: 431–437.
Liu AG, Smith SR, Fujioka K, et al. (2013) The effect of leptin,
caffeine/ephedrine, and their combination upon visceral fat
mass and weight loss. Obesity (Silver Spring, MD) 21:
1991–1996.
Liu Y, Sun M, Yao H, et al. (2017) Herbal medicine for the
treatment of obesity: An overview of scientific evidence from
2007 to 2017. Evidence-Based Complementary and Alterna-
tive Medicine 2017: 8943059.
Mielgo-Ayuso J, Barrenechea L, Alcorta P, et al. (2014) Effects of
dietary supplementation with epigallocatechin-3-gallate on
weight loss, energy homeostasis, cardiometabolic risk factors
and liver function in obese women: randomised, double-blind,
placebo-controlled clinical trial. British Journal of Nutrition
111: 1263–1271.
Nassar E, Morellion J, Hudson G, et al. (2008) Effects of ingesting
a thermogenic/anti-inflammatory supplement while participat-
ing in a resistance training program on indices of body com-
position and metabolic, cardiovascular, muscular, and
hemodynamic function in overweight females. Journal of the
International Society of Sports Nutrition 5: P25.
National Center for Commplentary and Integrative Health
[NCCIH] (2016) Ephedra. Available at: https://nccih.nih.
gov/health/ephedra.
National Center for Complementary and Integrative Health
[NCCIH] (2018) Dietary supplements marketed for weight
loss, bodybuilding, and sexual enhancement: What the science
says. Available at: https://nccih.nih.gov/health/providers/
digest/DietarySupplements.
Ngondi JL, Etoundi BC, Nyangono CB, et al. (2009) IGOB131, a
novel seed extract of the West African plant Irvingia gabonen-
sis, significantly reduces body weight and improves metabolic
parameters in overweight humans in a randomized double-
blind placebo controlled investigation. Lipids in Health and
Disease 8: 7.
Nogiec CD and Kasif S (2013) To supplement or not to supple-
ment: A metabolic network framework for human nutritional
supplements. PloS One 8: e68751.
Pope HG, Jr., Wood RI, Rogol A, et al. (2014) Adverse health
consequences of performance-enhancing drugs: an Endocrine
Society scientific statement. Endocrine Reviews 35: 341–375.
Rios-Hoyo A and Gutierrez-Salmean G (2016) New dietary sup-
plements for obesity: What we currently know. Current Obe-
sity Reports 5: 262–270.
Said O, Khalil K, Fulder S, et al. (2010) A double blinded- ran-
domized clinical study of “Weightlevel”, a combination of
four medicinal plants used in traditional Greco-Arab and Isla-
mic medicine. The Open Complementary Medicine Journal
2010: 1–6.
Saper RB, Eisenberg DM and Phillips RS (2004) Common dietary
supplements for weight loss. American Family Physician 70:
1731–1738.
Schulman S (2003) Addressing the potential risks associated with
ephedra use: A review of recent efforts. Public Health Reports
118: 487–492.
Schwingshackl L, Dias S, Strasser B, et al. (2013) Impact of
different training modalities on anthropometric and metabolic
characteristics in overweight/obese subjects: a systematic
review and network meta-analysis. PloS One 8: e82853.
Clark and Welch
Shekelle PG, Hardy ML, Morton SC, et al. (2003) Efficacy and
safety of ephedra and ephedrine for weight loss and athletic
performance: A meta-analysis. Journal of the American Med-
ical Association 289: 1537–1545.
Smith SR, Garvey WT, Greenway FL, et al. (2017) Coadminis-
tration of lorcaserin and phentermine for weight management:
A 12-week, randomized, pilot safety study. Obesity (Silver
Spring, MD) 25: 857–865.
Soni MG, Carabin IG, Griffiths JC, et al. (2004) Safety of ephe-
dra: Lessons learned. Toxicology Letters 150: 97–110.
Stein CM (2002) Are herbal products dietary supplements or
drugs? An important question for public safety. Clinical Phar-
macology and Therapeutics 71: 411–413.
Stohs SJ and Badmaev V (2016) A review of natural stimulant and
non-stimulant thermogenic agents. Phytotherapy Research 30:
732–740.
Stohs SJ, Preuss HG and Shara M (2011) A review of the receptor-
binding properties of p-synephrine as related to its
15
pharmacological effects. Oxidative Medicine and Cellular
Longevity 2011: 482973.
Thom E (2007) The effect of chlorogenic acid enriched coffee on
glucose absorption in healhty volunteers and its effect on
body mass when used long-term in overweight and obese
people. The Journal of International Medical Research 35:
900–908.
Vaughan RA, Conn CA and Mermier CM (2014) Effects of
commercially available dietary supplements on resting
energy expenditure: A brief report. ISRN Nutrition 2014:
650264.
Wang H, Wen Y, Du Y, et al. (2010) Effects of catechin enriched
green tea on body composition. Obesity (Silver Spring, MD)
18: 773–779.
Westerterp-Plantenga MS, Lejeune MPGM and Kovacs EMR
(2005) Body weight loss and weight maintenance in relation
to habitual caffeine intake and green tea supplementation.
Obesity Research 13: 1195–1204.