Ephedrine - Scientific Review On Usage, Dosage, Side Effects - Examine

16/12/2017 Ephedrine - Scientic Review on Usage, Dosage, Side Effects | Examine.
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SUPPLEMENTS NUTRITION STORE
Ephedrine
Ephedrine is one of the four active components of the herb Ephedra. It is able to induce fat loss via increasing the
amount of fat available for fuel as well as by increasing heat expenditure. It has been implicated in increasing the
metabolic rate by up to 5% in humans. It has also been noted to cause serious side-e ects in some instances, and its
legal status varies by region.
This page features 98 unique references to scienti c papers.
History (/history/ephedrine/)
SUMMARY THINGS TO KNOW HOW TO TAKE FAQ HUMAN EFFECT MATRIX SCIENTIFIC RESEARCH
CITATIONS
Summary
All Essential Bene ts/E ects/Facts & Information
Examine.com special safety warning on ephedrine and ephedra products:

>While dietary supplements containing ephedrine alkaloids have been used with an acceptable margin of safety and
e cacy by many individuals, they can be downright dangerous for those with certain underlying medical conditions. A
number of case reports have implicated ephedrine alkaloids as the cause of serious adverse health e ects in isolated
individuals- including but not limited to heart attack, stroke, seizures, and even death.[9] It should also be noted that
supplements ephedrine alkaloids are currently banned in the United States.[10] Any decision to use ephedrine or
ephedra products should be made in close consultation with your personal physician.
Ephedrine (ih-fed-rin) is one of the four active components of the herb Ephedra. It is able to induce fat loss
(http://examine.com/top/fat-loss/) via increasing the amount of fat available for fuel as well as by increasing heat expenditure. It has
been implicated in increasing the metabolic rate (/topics/metabolic-rate/) by up to 5% in humans.
Ephedrine also interacts with muscle cells, increasing heat expenditure in them as well as fat cells. It can also prevent the breakdown
of muscle tissue to a small degree.
Ephedrine is highly synergistic with ca eine (/supplements/ca eine/), and for this reason is commonly found in something called an
ECA stack (/supplements/eca/) (Ephedrine, Ca eine (/supplements/ca eine/), and Aspirin).
https://examine.com/supplements/ephedrine/ 1/18
16/12/2017 Ephedrine - Scientic Review on Usage, Dosage, Side Effects | Examine.com
Side e ects include an increase in blood pressure (/topics/blood-pressure/) that goes away with cessation and increases in some
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blood parameters (Glucosamine (/supplements/glucosamine), insulin (/topics/insulin/)) that also go away with cessation of use. It has
been reported to be a hyperstimulant when taken in doses above what is recommended.
Ephedrine is well studied and a fairly reliable compound for short- to medium-term weight loss (less than 6 months) and mild
performance improvements, usually in trained individuals. However, it does not work under all situations; longer-term weight loss
and e ects in untrained individuals have not been studied much and sometimes produce negative results. While it has been
implicated in weight reduction independent of exercise and diet changes, e cacy is maximized with minimal side-e ects when
ephedrine is combined with diet and exercise.
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Things to Know
Also Known As
Ephedra Vulgaris, Ephedraceae, ma huang
Do Not Confuse With

Ephedrone, Epinephrine
Things to Note
Ephedrine is highly stimulatory, and the plant (Ephedra) more-so.
Is a Form Of
Fat-burner
Goes Well With

Methylxanthines such as ca eine (/supplements/ca eine/) and theophylline (a component of green tea)
Caution Notice
Ephedrine can also increase dopamine levels in the brain, and caution should be taken pairing ephedrine with MAOIs such
as yohimbine (/supplements/yohimbine/).
Ephedrine should only be used under the supervision of a Medical Doctor, especially if pre-existing cardiac complications
exist, due to potentially serious adverse e ects.
The legal status of ephedrine varies by country and is a banned substance by certain sports agencies.
Examine.com Medical Disclaimer (/disclaimer)
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How to Take
Recommended dosage, active amounts, other details
All Doses Standardized to Ephedrine HCl
In an ECA stack (/supplements/eca/), ephedrine is dosed at 20-24mg for three doses taken throughout the day.
Human studies have found success with ephedrine in isolation on fat metabolism with doses of 20-50mg thrice a day. The higher
range (150mg) may be too stimulatory for some, and can induce headaches or light hand tremors.
Ephedrine tends to be consumed with xanthine compounds like ca eine (/supplements/ca eine/) and sometimes with Aspirin. The
combination of Ephedrine and ca eine is shown repeatedly to be highly synergistic.
Frequently Asked Questions

Questions and answers regarding Ephedrine
Q:Do I need to cycle ephedrine?
A:Surprisingly, ephedrine does not appear to need cycling for the fat burning aspect of it (it may for neurological stimulation and
appetite suppression). If using an ECA stack, however, the ca eine may need to be cycled
Read full answer to "Do I need to cycle ephedrine?" (/nutrition/do-i-need-to-cycle-ephedrine/)
Human E ect Matrix
The Human E ect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what e ects ephedrine
has on your body, and how strong these e ects are.
GRADE LEVEL OF EVIDENCE
Robust research conducted with repeated double-blind clinical trials
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Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
LEVEL OF OUTCOME MAGNITUDE OF EFFECT CONSISTENCY OF RESEARCH RESULTS NOTES

EVIDENCE
? ? ?
It is thought that most weight lost with ephedrine

VERY HIGH
Fat Mass administration is due to fat mass, due to a slight muscle
See all 4 studies
(/topics/fat-mass/) Notable preserving e ect; studies that note reductions in fat mass
(/rubric/e ects/view/3b0b41a882fdd4090a29885785339d56/94a4e0f6e053b27b2fed177eaa73eb59/all/)
support this hypothesis
Metabolic Rate VERY HIGH

Ephedrine, secondary to the stimulatory properties, appears to
(/topics/metabolic- See all 6 studies
Notable reliably increased metabolic rate
rate/) (/rubric/e ects/view/3b0b41a882fdd4090a29885785339d56/e84c19cdc76165bc5a47947fc7974348/all/)
HIGH Ephedrine tends to result in reliable weight loss over time

Weight
See all 10 studies relative to control (assuming calories are held equal), which is
(/topics/weight/) Notable
mostly due to a loss of body fat
(/rubric/e ects/view/3b0b41a882fdd4090a29885785339d56/9ab6ebf4d2bae 55a1415b697cbbb9d/all/)
There may be an acute increase in blood pressure seen with

Blood Pressure LOW
ephedrine intake, although this does not appear to be overly
(/topics/blood- See all 5 studies
Minor reliable; long-term usage of ephedrine does not seem to alter
pressure/) (/rubric/e ects/view/3b0b41a882fdd4090a29885785339d56/c9578369658a996e3cc21dd06ed75dbc/all/)
blood pressure, and may reduce it secondary to weight loss
An increase in heart rate is present following ephedrine

MODERATE
Heart Rate administration which correlates well with its psychostimulatory
See all 5 studies
(/topics/heart-rate/) Minor properties; this is not 100% reliable, and heart rate increases
(/rubric/e ects/view/3b0b41a882fdd4090a29885785339d56/698f2ee95f5d5b1a12907b825f29b8ca/all/)
may not occur
Nasal Congestion VERY HIGH

(/topics/nasal- See 2 studies Ephedrine appears to result in notable nasal decongestion
Notable
congestion/) (/rubric/e ects/view/3b0b41a882fdd4090a29885785339d56/bcb3f9e02dc36a8d82 18fcadd41082/all/)
VERY HIGH An increase in HDL-C has been noted with ingestion of

HDL-C (/topics/hdl-
See 2 studies ephedrine, may be confounded with weight loss also seen in the
c/) Minor
trials
(/rubric/e ects/view/3b0b41a882fdd4090a29885785339d56/ab52cdfe7383e5bb61dad41 807bea8/all/)
- A decrease in LDL-C has been noted to be associated with

LDL-C (/topics/ldl-c/) See study ephedrine, although this may be confounded with weight loss
Minor
(also seen in the trials)
(/rubric/e ects/view/3b0b41a882fdd4090a29885785339d56/5a8244e1290e2c9924bad3bd41115434/all/)
Skeletal Muscle
-
Atrophy
See study May decrease the rate of skeletal muscle breakdown over time
(/topics/skeletal- Minor
(/rubric/e ects/view/3b0b41a882fdd4090a29885785339d56/9748f8fa030759d2490c901a5d3502f6/all/)
muscle-atrophy/)
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-
Subjective Well-
Being Appears to increase well being acutely following the rst doses
(/topics/subjective- of ephedrine, secondary to the psychostimulatory e ects
well-being/)
Minor See study
(/rubric/e ects/view/3b0b41a882fdd4090a29885785339d56/0d3a9cf9f9fc0d1184b7b398fe00f3a1/all/)
Triglycerides VERY HIGH There appears to be a decrease in triglycerides over time with
(/topics/triglycerides See 2 studies ephedrine ingestion, which may be due to either the fat burning
Minor
/) e ects of ephedrine or the weight loss that tends to ensue
(/rubric/e ects/view/3b0b41a882fdd4090a29885785339d56/96e8681e8f363183e41cd79193090ee3/all/)
Power Output - No signi cant in uence on power output with standard oral
(/topics/power- - See study doses of ephedrine (higher doses may in uence power output,
output/) but this is not well researched)
(/rubric/e ects/view/3b0b41a882fdd4090a29885785339d56/f6cfed9dba2b80222e8ec46bc0916461/all/)
-
Appetite A decrease in appetite following ephedrine intake is noted and
See study
(/topics/appetite/) Minor thought to be secondary to its psychostimulatory e ects
(/rubric/e ects/view/3b0b41a882fdd4090a29885785339d56/146f4f5c41 5c115642f86b091c125d/all/)
Ephedrine has been noted to reduce postoperative nausea, but

-
Nausea is also linked to inducing nausea secondary to its
See study
(/topics/nausea/) psychostimulatory and appetite suppressing e ects. The latter
(/rubric/e ects/view/3b0b41a882fdd4090a29885785339d56/a893d3c7d3134db7b0cc76f449adc60a/all/)
is more practical for supplementation
Studies Excluded from Consideration

Confounded with the inclusion of ca eine[1][2][3][4][5][6][7]
Confounded with both aspirin and ca eine (the ECA (/supplements/eca/) stack)[8]
Scienti c Research
Table of Contents:
1 Sources and Structure
1.1 Composition (Ephedra)
1.2 Ephedrine (Ephedrine Alkaloids)
1.3 Properties
2 Pharmacology
2.1 Digestion and Absorption
2.2 Systemic
3 Neurology
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3.1 Sensitivity
4 Fat Mass and Obesity
4.1 Mechanisms
4.2 Metabolic Rate and Oxygen consumption
4.3 Longterm Human Interventions on Fat Loss
5 Exercise Performance and Skeletal Muscle
5.1 Skeletal Muscle Hypertrophy
5.2 Power Output
5.3 Physical endurance
6 Interactions with Hormones
6.1 Estrogen
7 Cardiovascular Interactions
7.1 Blood Pressure
7.2 Heart Rate and Cardiac Health
7.3 Cardiotoxicity and Overdose
7.4 Lipoproteins and Triglycerides
8 Nutrient-Nutrient Interactions
8.1 ECA stack
8.2 Nicotine
9 Safety and Toxicity
9.1 Safety and Toxicity within Recommended Dosage Range
9.2 Case studies
9.3 Legality
1 Sources and Structure
1.1. Composition (Ephedra)
Ephedrine is found in the Ephedra Sinica plant, also known as Ma Huang or Chinese Ephedrea. This distinction is important as there is
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an entire genus called Ephedrea in the family Ephedraceae, and the ephedrine alkaloids touted as fat burners are only present in
Sinica.[11]
Ephedra in general contains more than 50 species, and is found world-wide. Many are adapted to semiarid and desert conditions,
although some are found in humid or temperate climates in the Mediterrean and North America.[11][12]
Ma Huang (Ephedra Sinica), the one sold as a fat burner, contains:
Ephedrine alkaloids (main fat burning compounds, topic of article) mostly in Ephedra Sinica, distachya, equisetina, monosperma and
gerardiana[11]
Ephedrine precursor, cathinone (norpseudoephedrine)[13] and derivative ephedroxane.[14]
Cyclopropyl analogues of amino acids (glutamate) including (2S,3R,4S)-3,4-methanoproline in the stems and leaves of many plants, and
in the seeds in high amounts.[11]Not in the stems or leaves of Ephedra altissima or Viridus.
(2S,3S,4S)-2-(carboxycyclopropyl)glycine, a cyclopropyl compound that is an agonist of some glutamate receptors (MGluR2, MGluR3) and
found in high amounts in Ephedra antisyphilitica (0.5% by stem weight). The related compound (2S,3S,4R)-2-(carboxycyclopropyl)glycine
may also be psychoactive, and is found in the berries of Ephedra foemina
Kynurenate compounds (6-hydroxykynurenate, 6-methoxykynurenate, 7-methoxykynurenate) in the stem, none in the root. Also
contains the parent compound of kynurenate acid (4-hydroxyquinoline-2-carboxylic acid) at concentrations up to 1% dry mass in
Ephedra fasciculata and funerea
Proanthocyanidin compounds, and the tannin compounds ellagitannins and gallotannins.[11]
New world ephedra plants (those found in North and South America, about half of the species by number) do not contain substantial
amounts of ephedrine alkaloids,[11] although there are uncon rmed claims that there may be a pseudoephedrine content.[15][16] The
one study to analyze various Ephedra species noted no ephedrine or pseudoephedrine in North American species.[11]
1.2. Ephedrine (Ephedrine Alkaloids)

'Ephedrine', as a molecule, possesses two chiral centers. Due to this exibility in its structure, it can exist in four states (or
stereoisomers). They are:
1R,2S (-)- Ephedrine
1S,2S (+)- Pseudoephedrine
1S,2R (+)- Ephedrine
1R,2R (-)- Pseudoephedrine
Additionally, ephedrine and pseudorephedrine can lose a methyl group to become norephedrines, or be methylated to become N-
methylephedrine. Norephedrine and Norpseudoephedrine are also known as Phenylpropinolamine, or PPA.
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1.3. Properties
Ephedrine appears to be stable in the urine for up to 9 months at temperatures ranging from -20C to 37C, and 15 hours at 60C
which simulated a weekend left in a car trunk or glovebox in a hot environment.[17][18] Ephedrine was also stable during 6 freeze-thaw
cycles (-20C to 22C).[17]
2 Pharmacology
2.1. Digestion and Absorption

Ephedrine administration at 50mg is able to reduce gastric emptying rate in humans, and potentially reduce meal absorption speeds.
[19][20]
2.2. Systemic
All below pharmacology can be reviewed here.[21]
Ephedrine is able to act with the muscle cells directly and induce thermogenesis in myocytes. It has also been reported that urinary
excretion of nitrogen is reduced during ephedrine supplementation, indicating that this interaction or a like interaction exerts a
muscle sparing e ect.
Ephedrine can also increase thermogenesis via its vasoconstrictory abilities and the phenomena of 'hot pipes', otherwise known as
vascular thermogenesis[22] as well as acting on brown adipose tissue's beta-adrenergic receptors system.
Supplementation with ephedrine increases plasma insulin, glucose, and C-peptide in a dose dependent manner, possibly due to the
state of transient insulin resistant classical stimulants induce.
Ephedrine seems to be synergistic with methylxanthine compounds (such as ca eine (/supplements/ca eine/) and theophylline), a
dose of 22mg/30mg/50mg ephedrine/ca eine/theophylline has been shown to be twice as e ective as ephedrine alone[23], and in
comparisons between di erent combinations of ephedrine and ca eine a dose of 20mg/200mg has been shown to be the most
synergistic.[24] This discovery led to the rise of the ECA stack (/supplements/eca/), which is a stack of ephedrine/ca eine/aspirin which
is dosed 20mg/200mg/91mg accordingly.
3 Neurology
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3.1. Sensitivity
Ephedrine appears to be a more potent stimulant during periods of caloric restriction, relative to higher caloric intakes.[25] The neural
stimulant e ects are further increased when paired with ca eine (/supplements/ca eine/).[26]
4 Fat Mass and Obesity
4.1. Mechanisms
Ephedrine is able to directly agonize all three subsets of -adrenergic receptors of brown adipose tissue, leading to increased
thermogenesis[27] without signi cantly activating the -adrenergic receptor class[28] and possibly antagonizing activation from
agonists of these receptors.[28] The -class of adrenergic receptors are seen as the class that stimulate lipolysis, where the alpha class
is inhibitory.[29]
The order of potency (EC50 followed by relative potency to the reference standard of isoproterenol) of the isomers of ephedrine on 1
subunits are 1R,2S(500uM, 68%) > 1S,2R(72mM, 66%) > 1S,2S(309mM, 53%) = 1R,2R(1122mM, 53%)[29] while the in uence on the 2
subunits have a similar order of potency of 1R,2S(360uM, 78%) > 1R,2R(7mM, 50%) > 1S,2S(10mM, 47%) > 1S,2R(106mM, 22%).[29] 3-
subunits only appear to be agonized in humans weakly by the 1R,2S isomer at an EC50 value of 45mM and 31% response relative to
isoproterenol while other isomers are mostly inactive.[29]
This agonism may not appear to be seen in vivo at doses of 50mg taken thrice daily.[30]
It has been shown to increase only the beta-3 subunit in white adipose tissue in rats, but enhances glycerol release from brown
adipose tissue and inhibits glucose uptake for both types of adipocyte.[31]
Ephedrine isomers are direct agonists at beta-adrenergic receptors and may directly stimulate lipolysis, but the EC50
values are fairly high and may not re ect serum levels following ingestion
4.2. Metabolic Rate and Oxygen consumption

Human studies have found that oxygen consumption via an initial ephedrine dose (20mg) increases an expected amount 30-60
minutes after ingestion in all cases (with more potency in those not adapted to stimulants), although chronic ingestion of ephedrine
alleviates the expected drop between 1-3 hours post ingestion. This suggests that ephedrine confers more bene ts to fat burning with
usage over a longer period (4-12 weeks) rather than intermittently, and the suspected mechanism is augmentation of beta-adrenergic
sensitization.[32]
Ephedrine seems to, in and of itself, increase metabolic rate via REE independent of exercise; this is dissimilar to ca eine
(/supplements/ca eine/), which requires exercise to induce it's fat-burning e ects to signi cant levels. Coincidentally, this may be the
reason why the combination of Ephedrine and Ca eine shows synergism with exercise in increased oxygen consumption.[33] The
combination of ephedrine and ca eine has been noted to be similarly e ective (trending to be more e ective) than 15mg
dexfen uramine over 12 weeks.[3]
It has been noted that ca eine ingestion does, however, increase ephedrine's e ects on REE independent of exercse[34] and that this
e ect on potentiating was also noted with green tea, suggesting that the methylxanthine class of compounds (via increasing
adrenaline) are causative of the potentiation.[23]
The previous animal studies have noted a 10% increase in REE with ephedrine supplementation, however human studies are more
variable at 3.6%,[30] 10.7% (with ca eine),[7] and 7.1%.[35] Studies using indirect calorimetry note various increases, such as
30.15.4kcal/3hours at 20mg ephedrine + 200mg ca eine, and 22.77.7kcal/3hours at half the ephedrine dosage.[24] It has also been
noted to reduce a 13% reduction in REE (from caloric restriction) into an 8% reduction, saving 5% of the metabolic rate.[6]
()
Metabolic rate, thermogenesis, and oxygen consumption are all reliably increased with ephedrine supplementation. The
increase is greater with ca eine or other xanthine compounds, is greater in obese persons, and shows most practical
signi cance during periods of caloric restriction. Estimates are around 5-12% increases in metabolic rate.
4.3. Longterm Human Interventions on Fat Loss

Some case studies have supported the idea that ephedrine (paired with ca eine) can be of use to hypothalamic obesity with long-
term success.[5]
Human studies in overweight females indicate that a 20mg x 3 dosage protocol is capable of reducing bodyweight independent of
dietary and exercise changes by 2.5kg in 4 weeks and 5.5kg in 12 weeks, suggesting a reduced return-on-investment with ephedrine
supplementation (independent of changes in oxygen consumption). In a sample of 5, 2 subjects reported slight hand tremors upon
initial supplementation.[36]
Usage of the ECA stack has been investigated, and without intentional caloric restriction in obese persons showed 2.2kg weight loss
over 8 weeks against 0.7kg for placebo.[37] When unblinded, the 2.2kg loss increased to 3.2kg.
With caloric restriction, EC shows 3.4kg greater weight loss relative to placebo over 16 weeks in obese persons[38] and 30-60mg
(paired with 300-600mg ca eine (/supplements/ca eine/)) showed 5.9kg more fat loss in 20 weeks in adolescents.[1]
Additionally, long-term use of ephedrine (5 months) is associated with continued fat loss (5.2kg) relative to control (-0.03kg).[37] In
some studies where fat loss between groups is not statistically signi cant, signi cant positive trends in body composition are seen.[6]
5 Exercise Performance and Skeletal Muscle
5.1. Skeletal Muscle Hypertrophy

Ephedrine, as a beta-adrenergic agonist, can preserve muscle mass by reducing nitrogen excretion (and titrating nitrogen balance
towards a positive state). Human interventions note a decrease in urinary nitrogen with acute ephedrine usage[39] and at least one
study that did not note weight loss was due to a loss of bodyfat concurrent with an increase in muscle gain, with 4.5kg more fat lost
and 2.8kg less muscle mass lost over 8 weeks.[6] These numbers may be in ated due to the women being obese at baseline.
Skeletal muscle may contribute up to 50% of the fat burning potential of ephedrine, as it acts mostly in brown fat stores and skeletal
muscle.[40]
5.2. Power Output

In 9 otherwise healthy resistance trained men, ingestion of 300mg ca eine (/supplements/ca eine/) with 60mg ephedra sinicus
(ephedrine content not disclosed) 60 and 150 minutes prior to muscular testing with a 1 rep max bench press and lat pulldown test
noted that despite increased attitude towards and alertness during weight lifting that there was no signi cant di erences in strength
when compared to 300mg glucose placebo.[41] Another trial assessing muscular output with weight training with a higher dose of
ephedrine (0.8mg/kg 90 minutes before leg press:bench press supersets to failure) noted 3 more reps on the leg press associated
with ephedrine over placebo (16 over 13) and when combining with ca eine this was increased to 6 reps (19 versus 16) with less
improvement (1 and 2 extra reps, respectively) with the bench press; the authors noted that fatigue during supersets may have
played a role, and these results were only signi cant during the rst superset test (with a 2 minute rest period, the subsequent two
tests were not statistically signi cance).[42]
One study using a single acute dose of 24mg ephedrine in otherwise healthy untrained men failed to note any power output
enhancement after acute dosing.[43]
Studies using ergometer assessments of power fail to nd improvements in power output associated with 60mg ephedra sinicus (and
300mg ca eine)[41] and ephedrine in isolation has been associated with improving power output during a 30s wingate test (at time
points of 5 and 10 seconds, insigni cant at other time points) when measured 90 minutes after ingestion of 1mg/kg;[44] this latter
study has been criticized for its conclusions, where the clinical signi cance was minor (less than 1% improvement when averaged over
()
all 30 seconds) and may not be worth the risks associated with high dose ephdrine consumtption.[45]
Power output improvement with lower doses of ephedrine appears unreliable, whereas higher doses (0.8-1mg/kg) have
been associated with enhanced power output when taken 90 minutes before exercise. The cost-bene t analysis of these
high doses of ephedrine has been questioned, however, with some authors arguing it may not be the best intervention
due to possible side-e ects associated with stimulant usage
5.3. Physical endurance

In a test on performing high intensity cycling until failure (where placebo managed to pedal for 12.6 minutes) the ingestion of 1mg/kg
ephedrine is associated with a trend to reduce time to exhaustion (by 19%) that failed to reach statistical signi cance, but combining
this dose with 5mg/kg ca eine improved the e ects (to 39%) and was signi cant.[46] This improvement has been replicated elsewhere
with similar dosing, and the increase in heart rate was replicated and a lower rate of percieved exertion was noted.[47]
One study assessing performance on a weighted (11kg) 10 kilometer run following ingestion of 0.8mg/kg ephedrine noted a 2.8%
improvement in run time associated with ephedrine over placebo (similar e ects in ca eine plus ephedrine) associated with
improved pace during the last 5k and no signi cant in uence on VO2 max; this was attributed to the increase in serum free fatty acids
and modulation of catecholamines (less adrenaline and more dopamine).[48]
Limited evidence, but ephedrine appears to enhance endurance exercise performance which may merely be secondary
to increased free fatty acid levels in serum and possibly a reduced rate of percieved exertion
6 Interactions with Hormones
6.1. Estrogen
Ephedrine, at 0.5mg/kg daily, exerts an anti-estrogenic e ect in mice and was more potent than Ephedra Sinica and Synephrine
(/supplements/synephrine/) at doing so.[49]
7 Cardiovascular Interactions
7.1. Blood Pressure

Many of the human studies (to be discussed) noted slight increases in blood pressure ranging from 5-23mmhg systolic with no
in uence on diastolic.[32][7] These e ects were acute and causative of the ephedrine administration.
Over a long period of time (8-12 weeks) ephedrine is associated with reduced blood pressure, although this is due to weight loss.[50][3]
Sometimes blood pressure is not signi cantly a ected at all chronically, however.[51][52][53] In regards to persons with hypertension
who may still experience the acute rise in blood pressure, treatment with ephedrine may be problematic acutely but has been argued,
over time, to be bene cial secondary to reduction in weight.[50]
With a controlled dose of ephedrine, it does not seem to change heart rate in and of itself. Variations in HR are typically causative of
excessive adrenaline levels when pairing ephedrine with an adrenaline increasing agent such as ca eine (/supplements/ca eine/) or
from anxiety.
7.2. Heart Rate and Cardiac Health
()
One human study noted decreases in serum potassium levels when ephedrine was being used (20mg x 3). The decreases were, on
average, from 4.1mmol to 3.7mmol, although the decrease was blunted with chronic administration.[36]
Other human studies[39][54] have noted less drastic increases in adrenaline levels and no changes in urinary excretion of adrenaline
markers but have noted less urinary nitrogen excretion, indicating a better nitrogen balance and thus muscle sparing potential of
ephedrine supplementation (50mg thrice a day).
7.3. Cardiotoxicity and Overdose

At high doses of 50mg/kg bodyweight (Ma Huang, or ephedra) or 25mg/kg bodyweight ephedrine, clinical and biological signs of
toxicity are apparent.[55] Doses of 12.5mg/kg bodyweight Ma Huang (equivalent to 6.25mg/kg ephedrine) paired with ca eine show
minimal toxic signs. An acute dose of 25mg/kg bodyweight (14x recommended human dose) is lethal to rats when fed by gavage.[56]
Cardiotoxicity, in rat models, appears to be more of a concern for older animals.[57]
7.4. Lipoproteins and Triglycerides

Ephedrine (thus study using ca eine) has been noted to reduce the rate of HDL-C decreases seen with hypocaloric dieting without
signi cantly a ecting overall total cholesterol.[4]
8 Nutrient-Nutrient Interactions
8.1. ECA stack

The ECA stack was rst proposed in 1989[58] and tested in 1990[59] as nutraceuticals that interacted with each other. It was already
noted at this time that xanthine compounds (of which ca eine (/supplements/ca eine/) is included) can cause the e cacy of 22mg
ephedrine in increasing the metabolic rate to approximately double[23] and in animals to more e ectively suppress the appetite.[60][61]
[62]
Ca eine (/supplements/ca eine/) is able to increase metabolic rate on its own, but its combination with ephedrine appears to be
synergistic (greater than the sum of its parts) rather than just additive. The pairing of the two results in an increased metabolic rate
greater than the two added together mathematically.[24] The mechanism appears to be through adenosine antagonism, as the other
theory (phosphodiesterase inhibtion) may not be relevant in vivo due to low cellular concentrations of ca eine relative to what is
needed to cause large inhibition.[63]
Ca eine has been noted as a synergist with ephedrine in vivo[24] and used e ectively in a wide variety of studies to induce weight loss
in conjunction with a diet or diet with exercise program.[64] and some studies suggest that it is needed for the fat loss e ects of
ephedrine to di er from placebo.[38] This may be secondary to 'non-responders' to ephedrine, which seems to be negated by
coingestion of a xanthine compound.[35] Basically, those who do not respond to ephedrine seem to respond to ephedrine with
xanthines.
The synergism between ephedrine and xanthines has been roughly quanti ed as 64% more than the expected values of the added
value of the two compounds in one study.[24] This is more of a pharmacodynamic synergism, as taking the combination of ingredients
does not appear to alter the pharmacokinetic pro le of either.[26]
One study noted the combination of ca eine (/supplements/ca eine/) and ephedrine did not in uence diastolic blood pressure while
either compound in isolation did, and that the combination did not in uence systolic blood pressure to a greater degree than either
compound in isolation.[24] This indicates that the combination is, at least, no worse than either in isolation in regards to acute blood
pressure spikes.
Although aspirin has been shown to cause greater reductions in body fat when combined with ephedrine, it does not signi cantly
a ect body weight on its own.[65] In animals, ephedrine decreased body fat percentage by 18% while ephedrine combined with aspirin
decreased body fat percentage by 27%.[65] works through prostaglandin inhibition, which increases ephedrine-induced adrenaline
release.[66] Aspirin in combination with ca eine and ephedrine has failed to acutely increase the thermic e ect of food.[8]
8.2. Nicotine
()
Ephedrine and ca eine mixtures have been used in attempts to reduce the weight gain seen with smoking cessation, and although
bene t has been noted ephedrine has failed to signi cantly modify quitting rates.[2]
9 Safety and Toxicity
9.1. Safety and Toxicity within Recommended Dosage Range

Ephedrine, paired with ca eine, appears to be a safe supplement for adolescents (16 years average, 14-17) given adequate
supervision.[1]
Some reviews note that interventions are no di erent from placebo[67] (although said meta-analysis established CI's ranging from 2-
3.5[68]) and that the bene ts of fat loss outweigh the costs.[67]
No clinically signi cant withdrawal symptoms are seen from usage of 20mg/200mg ephedrine/ca eine three times daily for 24 weeks.
[69][70]
9.2. Case studies

As a foreward, a large registry based case-crossover study comparing naive and habitual ephedrine/ca eine users found no
di erence in adverse e ects between groups, and found no overall relation with adverse cardiovascular outcomes.[71] Additionally, a
meta-analysis of 50 studies and 284 case reports reported to the FDA (out of 18,000) noted that there was an association with
ephedrine/ephedra and heart palpitations/autonomic side e ects, but that case reports are the data are insu cient to draw
conclusions about a rate less than 1 per thousand.[68] More dramatic side-e ects are seen when reviewing FDA 'reports of adverse
events'[72] but these tend to be associated with social panic; said meta-analysis[68] found only 284 out of 18,000 acceptable when
controlling for temporal relations (ephedrine consumed 24 hours prior to report) and no other confounds were present. This suggests
that 98.5% of non-medical cases were due to hypochondria, although by no means excludes possible harm.
Ephedrine has been associated with stroke in unknown dosages in persons with a history of drug abuse[73]
At least one case of human heart damage has been reported in a 44 year old male, but this was confounded with usage of a wide
variety of compounds.[74] Another case study noted usage of Ephedrea, Xenadrine, and Hydroxycut for 2 years resulting in coronary
artery aneurysm[75] which may be related to the Xenadrine formulation without Ephedrine.[76][77]
One study notes ephedrine associated with kidney stones, but takes an overly dramatic approach in the abstract.[78] Ephedrine
alkaloids were found to comprise 95% of a kidney stone by weight in a person on 4 medications with a single kidney who su ered
from kidney failure in the past. However, contacts of the author noted "over 200" other cases of kidney stones containing Ephedra
Alkaloids. The supplement used by the case subject contained 170mg Ephedra (6% ephedrine).[78]
Ephedrine has, at least once, been used to commit suicide. The exact oral dose was unknown, but was well beyond the highest
recommended therapeutic dosages.[78]
9.3. Legality
Many countries place restrictions on the sale of bulk ephedrine in order to prevent mass methamphetamine production, as ephedrine
is a substrate for meth.[79]
In 2004 the United States Food and Drug Administration (FDA) issued a ruling prohibiting the sale of dietary supplements containing
ephedra, citing an unreasonable risk of illness or injury.[80] In addition to the FDA ban on sales, laws governing the sale, use, and
possession of ephedra products have been established at the state and local level. If you are considering the use of ephedra, be sure
to check rst whether doing so complies with all national/local laws in your region.
()
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()
(Common misspellings for Ephedrine include ephedrin, ephedirn, ephedirne, ephdrin, ephdra)
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Ephedrine - Scientific Review On Usage, Dosage, Side Effects - Examine

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Ephedrine - Scientific Review On Usage, Dosage, Side Effects - Examine

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16/12/2017 Ephedrine - Scientic Review on Usage, Dosage, Side Effects | Examine.

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All Doses Standardized to Ephedrine HCl

Frequently Asked Questions

Q:Do I need to cycle ephedrine?

Read full answer to "Do I need to cycle ephedrine?" (/nutrition/do-i-need-to-cycle-ephedrine/)

Human E ect Matrix

GRADE LEVEL OF EVIDENCE

Robust research conducted with repeated double-blind clinical trials

Single double-blind study or multiple cohort studies

Uncontrolled or observational studies only

LEVEL OF OUTCOME MAGNITUDE OF EFFECT CONSISTENCY OF RESEARCH RESULTS NOTES

It is thought that most weight lost with ephedrine

Metabolic Rate VERY HIGH

HIGH Ephedrine tends to result in reliable weight loss over time

There may be an acute increase in blood pressure seen with

An increase in heart rate is present following ephedrine

Nasal Congestion VERY HIGH

VERY HIGH An increase in HDL-C has been noted with ingestion of

- A decrease in LDL-C has been noted to be associated with

Ephedrine has been noted to reduce postoperative nausea, but

Studies Excluded from Consideration

1.1 Composition (Ephedra)

1.2 Ephedrine (Ephedrine Alkaloids)

2.1 Digestion and Absorption

4 Fat Mass and Obesity

4.2 Metabolic Rate and Oxygen consumption

4.3 Longterm Human Interventions on Fat Loss

5 Exercise Performance and Skeletal Muscle

5.1 Skeletal Muscle Hypertrophy

5.2 Power Output

5.3 Physical endurance

6 Interactions with Hormones

7.1 Blood Pressure

7.2 Heart Rate and Cardiac Health

7.3 Cardiotoxicity and Overdose

7.4 Lipoproteins and Triglycerides

8.1 ECA stack

9 Safety and Toxicity

9.1 Safety and Toxicity within Recommended Dosage Range

9.2 Case studies

1 Sources and Structure

1.1. Composition (Ephedra)

Ma Huang (Ephedra Sinica), the one sold as a fat burner, contains:

Ephedrine precursor, cathinone (norpseudoephedrine)[13] and derivative ephedroxane.[14]

Proanthocyanidin compounds, and the tannin compounds ellagitannins and gallotannins.[11]

1.2. Ephedrine (Ephedrine Alkaloids)

1R,2S (-)- Ephedrine

1S,2S (+)- Pseudoephedrine

1S,2R (+)- Ephedrine

1R,2R (-)- Pseudoephedrine

2.1. Digestion and Absorption

4 Fat Mass and Obesity

4.2. Metabolic Rate and Oxygen consumption

4.3. Longterm Human Interventions on Fat Loss

5 Exercise Performance and Skeletal Muscle

5.1. Skeletal Muscle Hypertrophy

5.2. Power Output

5.3. Physical endurance