Journal of Pharmacy Practice

23(3) 245-249
A Case Report of Atrial Fibrillation ª The Author(s) 2010
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Potentially Induced by Hydroxycut: DOI: 10.1177/0897190010362104
http://jpp.sagepub.com
A Multicomponent Dietary Weight
Loss Supplement Devoid of
Sympathomimetic Amines

Abigail Karth, MD1, Noa Holoshitz, MD1, Clifford J. Kavinsky, MD, PhD1,
Richard Trohman, MD1, and Brian F. McBride, PharmD2

Abstract
Multicomponent dietary weight loss supplements comprise the single largest segment of herbal preparations available to the
public. As a result of limited de novo regulatory oversight, supplement-related adverse events are underreported secondary
to the lack of adequate pharmacodynamic, pharmacokinetic, and clinical data. Here we report the case of an obese 63-year-
old caucasian female with a 2-day history of symptomatic paroxysmal atrial fibrillation (AF) with rapid ventricular response
following a 2-week course of therapy with hydroxycut, a multicomponent dietary weight loss supplement devoid of sympatho-
mimetic amines. Upon presentation, the patient received 2 doses of intravenous diltiazem, was loaded with intravenous digoxin,
and spontaneously converted to normal sinus rhythm 36 hours following her last dose of the product. Epigallocatechin (EGCG), a
principal ingredient in the hydroxycut preparation is the suspected causative component. EGCG blocks the atrial-specific KCNA5
potassium channel. Loss of KCNA5 function has been reported in patients with familial lone AF. Thus, causal relationship between
hydroxycut and AF in this patient is probable. Given the serious risks associated with AF, patients at risk of developing AF should
avoid dietary supplements containing EGCG until more information on the adverse effects of EGCG is known.

Keywords
cardiology, critical care, ambulatory care, emergency medicine, medication safety

Introduction devoid of sympathomimetic amines entered the marketplace. In

many of these products, epigallocatecin (EGCG), a pharmacolo-
Dietary supplements represent a distinct class of biologically
gically active component of green tea extract, is a common com-
active compounds which, unlike prescription and over-the-
ponent used for weight loss. Although clinical trials of EGCG, as
counter products, have been available to the public1 without
a monotherapy, indicate show no significant impact on body
regulatory oversight since the Dietary Supplement and Health
weight and did not produce adverse effects at doses up to 1600
Education Act was passed nearly 15 years ago. In this time period,
mg. 7,8 However, multicomponent preparations containing
annual sales of such compounds have exceeded $18 billion and
EGCG have not been prospectively evaluated for safety.
are responsible for over 13 000 adverse events annually.2,3
Despite a noticeable lack of data supporting the clinical efficacy
 The objective of this report is to describe the case of a
of most dietary supplements, 81% of dietary supplement manu-
patient who presented to the emergency department with
facturers advertised unsupported health claims with 55% of these
a 48-hour history of symptomatic atrial fibrillation (AF)
claims overtly stating that their products prevented, diagnosed,
treated, or cured diseases.4,5 The current regulatory environment
combined with patient and provider unfamiliarity about the 1
Department of Medicine, Rush University Medical Center, Chicago, IL, USA
appropriate role for herbal medicine leads to a wide array of 2
Schools of Medicine and Nursing, Loyola University Chicago, Chicago, IL,
supplement-related adverse events, with ephedra containing USA
weight loss supplements (eg, Metabolife 356, Hydroxycut RFA)
Corresponding Author:
being among the most notable preparations.1,6 Brian F. McBride, PharmD, Loyola University Chicago, 2160 S. 1st Avenue,
Following the withdrawal of ephedra containing weight loss Building 102-4602, Maywood, IL 60153
supplements, new multicomponent supplement preparations Email: bf.mcbride@comcast.net

245
246 Journal of Pharmacy Practice 23(3)

Table 1. Labeled Contents of Hydroxycut

Calcium hydroxycitrate 156 mg

Chromium polynicotinate 133 mcg
Potassium hydroxycitrate 218 mg
‘‘Hydroxagen Plus’’ 1.2 g
Garcinia cambogia extract
Standardized for 60% hydroxycitric acid
Gymnema sylvestre
Standardized for 25% gymenic acid
Figure 1. Timeline of patient course. Phosphtidyl serine-enriched soy lecithin
Abbreviations: IV, intravenous; TID, 3 times daily; SSCP, substernal chest pain; Supplying:
PTA, prior to admission; DOA, date of admission; HC, hospital course. 50% Phosphatidylserine
4% Phosphatidylcholine
2% Phosphtidylethanolamine
and a rapid ventricular response following a 2-week course Rhodiola rosea extract
of hydroxycut, a dietary weight loss supplement containing Standardized for 5% rosavins
EGCG. ‘‘HydroxyTea’’ 473 mg
Green tea extract (as Camellia sinesis) (leaf)
Standardized for:
Case Report 90% polyphenols
45% epigallocatechin gallate
A 63-year-old obese caucasian female (weight ¼ 100 kg) 117 mg EGCG
presented to the emergency department with a 2-day history Caffeine anhydrous
of right-hand side neck pain which progressively worsened to White tea extract (as C sinesis) (leaf)
Standardized for:
include substernal chest pain and palpitations on the night prior
50% polyphenols
to admission (Figure 1). Her past medical history is significant 25% catechins
for primary hypothyroidism and osteoarthritis for which she 15% EGCG
was prescribed levothyroxine 200 mcg/d and meloxicam 15 Supplying 200 mg of caffeine
mg daily, respectively. The patient admitted taking hydroxycut Ginger extract (as Zingiber officinale) (root)
(Table 1) using the labeled dose (2 capsules 3 times daily; Raspberry ketone
*946 mg of EGCG/dose) for 2 weeks prior to presentation. Quercetin dehydrate (as Fava d’anta)
The patient reported a similar, less-intense symptomatology
during a previous trial of hydroxycut 3 months prior to admis-
prevention of AF recurrence. The Naranjo algorithm (Table
sion, did not seek medical attention, and reported that the
2) was employed using the patient’s clinical data, interview,
symptomatology resolved 5 days after discontinuation. Upon
and available literature concerning the constituent ingredients
presentation, the patient was alert and oriented to person, place,
in hydroxycut. The case scored an 8, which translates into a
and time with a blood pressure of 101/57 mm Hg and a heart
probable association between hydroxycut and the development
rate of 110 beats/min. On physical examination, the patient had
of AF in this patient.9
a normal S1 and S2. No S3, S4, jugular venous distension, or
thyromegaly was appreciated. The 12-lead electrocardiogram
(Figure 2A) obtained upon admission to the cardiac step-
down unit revealed an irregularly irregular rhythm with a nar-
Discussion
row QRS complex and consistent with AF. No ST segment To our knowledge, this is the first case report of proarrhythmia
depression or elevation was noted. The patient’s serum-free induced by a multicomponent dietary weight loss supplement
thyroxine level was normal at 1.5 ng/dL and her thyroid stimu- devoid of ephedra or other sympathomimetic amines. In this
lating hormone (TSH) was low at 0.237 mIU/mL. The patient case, a 63-year-old female with hypothyroidism and a normal
received 2 intravenous bolus doses of diltazem 10 mg and an free thyroxine level presented with symptomatic paroxysmal
intravenous loading dose of digoxin 500 mcg, which slowed AF and a rapid ventricular response following 2 weeks of
the ventricular rate to 80 beats/min. The patient spontaneously self-administered therapy with hydroxycut, a multicomponent
converted to normal sinus rhythm (Figure 2B) 10 hours after dietary weight loss supplement containing EGCG.
drug administration on the day of admission. On hospital day Although hydroxycut has not been evaluated in clinical
2, the patient received an echocardiogram and exercise stress trials, individual components of the preparation including
test, both of which were normal. On hospital day 3, the patient hydroxycitric acid (HCA) and EGCG have been studied with
was diagnosed with stage 1 hypertension (BP ¼ 152/96 mm largely inconclusive results. In a study of HCA, the total daily
Hg) and mixed hyperlipidemia for which treatment with valsar- dose was 25% higher than that found in hydroxycut and the
tan and simvastatin were initiated. The patient was discharged baseline weight of patients receiving placebo was 20 pounds
after 72 hours, with no recurrence of AF or medications for less than those receiving HCA.10 At the end of the study, the

246
Karth et al.
Figure 2. A, Electrocardiogram of the patient at presentation. B, Electrocardiogram of the patient after conversion to normal sinus rhythm.
change in body weight among patients receiving HCA was sig-
nificantly lower than baseline but not different from subjects
receiving placebo. The study was not powered to detect adverse
cardiovascular events and no safety studies germane to cardiac
rhythm with HCA are publicly available. With respect to
EGCG, recently published studies indicate that EGCG does not
cause weight loss.7,8 The studies reported no serious adverse
events but are not powered to detect adverse events. Further,
the Food and Drug Administration recently issued a recall of
hydroxycut secondary to hepatic toxicity.11 Based on the basic
science evidence presented below, we presume that EGCG may
have caused the effects seen in this patient. However, it is
important to note that hydroxycut is a multicomponent product
that contains ingredients other than EGCG and HCA, which
may have contributed to the effects observed in this patient.
The main limitation of this report is that we did not have the
247
product available to us for analysis of the ingredients in the pre-
paration consumed by the patient.
EGCG is an antagonist of KCNA5, the pore-forming subunit
of the protein carrying the delayed repolarizing current, IKur,
which is specifically expressed in human atria. Block of KCNA5
by EGCG results in prolongation of the atrial action potential by
blocking the channel pore.12 Similarly, mutations in KCNA5
have been reported in patients with familial AF. Like EGCG,
these mutations also prolong the duration of the atrial action
potential.13-16 Although it remains unclear if drugs which block
KCNA5 phenocopy the effect of the mutations in KCNA5, the
Antzelevitch laboratory studied the effects of 4-aminopyridine,
which like EGCG, is a selective antagonist of KCNA5 in both
healthy canine atrial tissue and atrial tissue isolated from dogs
with pacing-induced AF.17 In healthy atrial tissue, KCNA5
block by 4-aminopyridine resulted in shortening of the action
247
248
Table 2. Naranjo Algorithm for Adverse Drug Events
Assessment
1. Are there previous conclusive reports on this reaction?
Reduced KCNA5 activity causes AF, EGCG reduces KCNA5 activity.
EGCG raises urinary norepinephrine levels; but no clinical case reports
2. Did the adverse event appear after the suspected drug was given?
Event reported 2 days prior to admission or 12 days after starting hydroxycut.
3. Did the adverse reaction improve when the drug was discontinued
or a specific antagonist was given?
Spontaneously converted 10 hours after diltiazem and digoxin administration.
4. Did the adverse reaction appear when the drug was readministered?
Not attempted in this patient
5. Are there alternative causes that could have caused the reaction?
Other risk factors for paroxysmal AF ruled out
6. Did the reaction reappear when a placebo was given?
Not attempted
7. Was the drug detected in any body fluid in toxic concentrations?
Not attempted in this patient.
8. Was the reaction more severe when the dose was increased, or less severe
when the dose was decreased?
Patient reported decreasing dose to 1 caplet with a reduction in chest pain on day of admission
9. Did the patient have a similar reaction to the same or similar drugs in any previous exposure?
Patient reported a similar, less intense symptomatology when she used the
product previously but did not seek care when symptoms resolved.
10. Was the adverse event confirmed by any objective evidence?
Patient presented with ECG consistent with AF.
Total score
Abbreviations: AF, atrial fibrillation; EGCG, epigallocatechin; ECG, electrocardiogram.
potential duration and inducibility of AF. In tissue isolated from
diseased atrium, 4-aminopyridine produced a small prolongation
of the action potential. This paradoxical effect suggests a tenu- 2.
ous balance between arrhythmia suppression and atrial proar-
rhythmia with antagonists of KCNA5 including EGCG.
In conclusion, we presented the case of a patient who devel- 3.
oped AF following exposure to the multicomponent weight
loss supplement hydroxycut. Based on the available basic sci-
ence and clinical evidence, we hypothesize the EGCG is the
most likely causative agent. Given the serious clinical out- 4.
comes associated with prolonged periods of AF, patients
at risk of developing AF (ie, patients with established 5.
ischemic cardiovascular disease, diabetes, hypertension, and/
or hyperthyroidism) should be advised to avoid dietary supple-
ments, including multivitamins, which contain EGCG. 6.
Declaration of Conflicting Interests
The author(s) declared no conflicts of interest with respect to the
authorship and/or publication of this article. 7.
Funding
The author(s) received no financial support for the research and/or
authorship of this article. 8.
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248
Journal of Pharmacy Practice 23(3)
Score
Yes (þ1); No (0); Do not know or not done (0)
0
Yes (þ2); No (1); Do not know or not done (0)
þ2
Yes (þ1); No (0); Do not know or not done (0)
þ1
Yes (þ2); No (2); Do not know or not done (0)
0
Yes (1); No (þ2); Do not know or not done (0)
2
Yes (1) No (þ1) Do not know or not done (0)
0
Yes (þ1); No (0); Do not know or not done (0)
0
Yes (þ1); No (0); Do not know or not done (0)
þ1
Yes (þ1); No (0); Do not know or not done (0)
þ1
Yes (þ1); No (0); Do not know or not done (0)
þ1
8
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