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Lavender (Lavandula angustifolia Miller)

Article  in  Journal of Herbal Pharmacotherapy · February 2004

DOI: 10.1300/J157v04n02_07 · Source: PubMed

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 MONOGRAPH
FROM NATURAL STANDARD

Catherine Ulbricht, PharmD, Column Editor

Lavender (Lavandula angustifolia Miller)

Ethan Basch, MD
Ivo Foppa, MD, PhD
Richard Liebowitz, MD
Jamie Nelson, PharmD
Michael Smith, MRPharmS, ND
David Sollars, MAc, HMC
Catherine Ulbricht, PharmD

Ethan Basch is affiliated with the Natural Standard Research Collaboration. Ivo
Foppa is affiliated with Harvard University. Richard Liebowitz is affiliated with Duke
University. Jamie Nelson is affiliated with the University of Rhode Island. Michael
Smith is affiliated with the Canadian College of Naturopathic Medicine. David Sollars
is affiliated with the New England School of Acupuncture. Catherine Ulbricht is affili-
ated with Massachusetts General Hospital. All are members of Natural Standard Re-
search Collaboration (www.naturalstandard.com).
The information in this monograph is intended for informational purposes only, and
is meant to help users better understand health concerns. Information is based on re-
view of scientific research data, historical practice patterns, and clinical experience.
This information should not be interpreted as specific medical advice. Users should
consult with a qualified healthcare provider for specific questions regarding therapies,
diagnosis and/or health conditions, prior to making therapeutic decisions.
Copyright 2003 Natural Standard Inc. Reprinted with permission.
Journal of Herbal Pharmacotherapy, Vol. 4(2) 2004
http://www.haworthpress.com/web/JHP
Digital Object Identifier: 10.1300/J157v04n02_07 63
64 JOURNAL OF HERBAL PHARMACOTHERAPY

ABSTRACT. An evidence-based systematic review including scien-

tific evidence, expert opinion, folkloric precedent, history, pharmacol-
ogy, kinetics/dynamics, interactions, adverse effects, toxicology, and
dosing. [Article copies available for a fee from The Haworth Document Deliv-
ery Service: 1-800-HAWORTH. E-mail address: <docdelivery@haworthpress.
com> Website: <http://www.HaworthPress.com>]

KEYWORDS. Lavender, Lavendula angustifolia Miller, limonene, perillyl

alcohol, POH

SYNONYMS/COMMON NAMES/RELATED SUBSTANCES

Common lavender, English lavender, garden lavender, Lavandula

burnamii, Lavandula dentate, Lavandula dhofarensis, Lavandula latifolia,
Lavandula officinalis L., Lavandula stoechas, limonene, perillyl alcohol,
pink lavender, POH, true lavender, white lavender.

CLINICAL BOTTOM LINE/EFFECTIVENESS

Brief Background

Lavender is native to the Mediterranean, the Arabian Peninsula, Rus-

sia, and Africa. It has been used cosmetically and medicinally through-
out history. In modern times, lavender is cultivated around the world
and the fragrant oils of its flowers are used in aromatherapy, baked
goods, candles, cosmetics, detergents, jellies, massage oils, perfumes,
powders, shampoo, soaps, and tea. English lavender (L. angustifolia) is
the most common species of lavender used, although other species are in
use, including Lavandula burnamii, L. dentate, L. dhofarensis, L. latifolia,
and L. stoechas.
 Monograph from Natural Standard 65

Many people find lavender aromatherapy to be relaxing, and it has

been reported to have anxiolytic effects in several small, methodologi-
cally flawed trials. Overall, the weight of the evidence suggests a small
positive effect, although additional data from well-designed studies are
required before the evidence can be considered strong.
Lavender aromatherapy is also used as a hypnotic, although there is
insufficient evidence in support of this use.
Small phase I human trials of the lavender constituent perillyl alcohol
(POH) for cancer have suggested safety and tolerability (up to 1200 mg/
m2 four times/day), although efficacy has not been demonstrated.
Scientific Evidence for Common/Studied Uses
Indication Evidence Grade
Anxiety (aromatherapy) B
A
Hypnotic/Sleep (aromatherapy) C B
C
Perineal discomfort following childbirth (bathing) C D
E
Spasmolytic (oral) C
GRADING
Antibiotic (topical) C SYSTEM
LINK
Cancer (oral perillyl alcohol [POH]) C

Historical or Theoretical Uses that Lack Sufficient Evidence

Acne, alopecia, analgesia, angioprotectant, anticolic, anticonvulsant,
antidepressant, antiflatulant, antifungal, anti-inflammatory,1 antimicro-
bial,2 antioxidant,3 antipyretic, antiseptic, anxiety, appetite stimulant,
asthma, balenotherapy (functional circulatory disorders), cholagogue,
choleretic, chronic bronchitis, ciatrizant, cordial, diabetes,4 diuretic,
douche, emmenagogue, exercise recovery, gas, hangovers, hyptension,
infertility, insect repellent, insomnia,5 lice, migraine, non-tubercular
mycobacteria (NTM),6 parasitic infection, psychosis, rheumatism,
Roehmheld’s syndrome, rubefacient, toothache, varicose veins, vomit-
ing.
Expert Opinion and Historic Precedent
Lavender is rich in volatile oils and has been used for centuries both
as a fragrance and medicinal herb. Linen bags containing lavender
flowers were commonly placed under pillows for their alleged soporific
properties.
Lavender is thought by some experts to possess antibacterial proper-
ties. Currently, lavender oil is often used as an aromatherapeutic anxio-
66 JOURNAL OF HERBAL PHARMACOTHERAPY

lytic and hypnotic, including in the hospital setting.7 Infusions of

lavender flowers have been used for similar indications.

Brief Safety Summary

Likely Safe: When consumed in amounts commonly found in foods and

beverages (received Generally Recognized as Safe [GRAS] status for food
use in the United States), or when used in recommended oral/topical doses.
Possibly Unsafe: When used concomitantly with central nervous system
depressants, due to potential additive effects.8,9,10

DOSING TOXICOLOGY

General

Recommended doses are based on those most commonly used in

available trials, or on historical practice. These doses have not necessarily
been shown effective. Anecdotal dosing regimens are based on traditional
health practice patterns and/or expert opinion. With natural products it is
often not clear what the optimal doses are to balance efficacy and safety.
Preparation of products may vary from manufacturer to manufacturer,
and from batch to batch within one manufacturer. Because it is often not
clear what are the active components of a product, standardization may
not be possible, and the clinical effects of different brands may not be
comparable.

Standardization

• Lavender products are not standardized in the United States.

• Each species of lavender has unique chemical constituents and ac-
tivity.
• The flowers are the part of lavender most often used medicinally.

Adult Dosing (18 Years and Older)

Oral

Tea: One to two teaspoons of the herb taken as a tea (based on anecdote
and expert opinion). The tea can be made by steeping 2 U.S. teaspoons (10
grams) of leaves in 250 mL (1 cup) boiling water for 15 minutes.
 Monograph from Natural Standard 67

Oral Perillyl Alcohol (POH): In preliminary (phase I) cancer trials,

doses between 800-1200 mg/m2 four times/day in a 50:50 POH:soybean
oil preparation were tolerated with minimal adverse effects (efficacy has
not been demonstrated).11,12
Inhalation (Aromatherapy)
Aromatherapy: Two to four drops in 2-3 cups boiling water; inhale va-
pors. Aromatherapy can be administered intermittently or daily as needed
(based on anecdote and expert opinion).
Topical/Infusion
Bath Additive: For perianal discomfort after childbirth, 6 drops of laven-
der oil has been studied as a bath additive (no specific brand).13 Those
wishing to use the whole flower may add 1/4 to 1/2 cup of dried laven-
der flowers to hot bath water (based on anecdote and expert opinion).
Massage Therapy: One to four drops per tablespoon of base oil (based
on anecdote and expert opinion).
Pediatric Dosing (Younger Than 18 Years)
Insufficient data available.
Toxicology
There have been rare reports of sensitization after topical use of lav-
ender.14,15
Lavender has been reported to exert ‘narcotic-like’ effects in both an-
imals8,9 and humans.5

PRECAUTIONS/CONTRAINDICATIONS
Allergy
Caution should be exercised in patients with known allergy/hyper-
sensitivity to lavender. Persons with allergy to lavender may experience
mild local skin reactions after topical use of lavender oil.14,16
Adverse Effects
General: In recommended doses, lavender is generally considered to be
well-tolerated, with minimal adverse effects.7,13,17
68 JOURNAL OF HERBAL PHARMACOTHERAPY

Dermatologic: There have been case reports of mild dermatitis follow-

ing the use of topical lavender oil.18 One individual developed an itchy
dermatitis on his face after using lavender oil on his pillow.16 Patch test-
ing subsequently confirmed a positive allergy to lavender. There have been
reports of photosensitization and changes in skin pigmentation after the use
of topical products containing lavender oil.19,14
Neurologic/CNS: Central nervous system depression has rarely been re-
ported with aromatherapy,5,11 and additive narcotic effects have been noted
in rats when taken orally concomitantly with barbiturates or chloral hy-
drate.9,20
Hematologic: Reversible neutropenia has been noted after high oral
doses of perillyl alcohol (POH), a monoterpene constituent of lavender, in
patients with untreatable malignancies (on multiple chemotherapy regi-
mens).11
Gastrointestinal: Nausea, vomiting and anorexia have been reported af-
ter large oral doses of lavender (>5.0 g/day),21,22 and after large doses of the
lavender constituent perillyl alcohol (POH).12

Precautions/Warnings/Contraindications

Avoid in patients with a known allergy/hypersensitivity to lavender,

based on several case reports of dermatitis in patients with lavender al-
lergy.16,19
Use cautiously in patients who are currently taking drugs that depress
the central nervous system, because concomitant use of lavender may
exacerbate sedation.5,9,10

Pregnancy and Lactation

Not recommended due to lack of sufficient data.

Due to its purported properties as an emmenagogue, excessive inter-
nal use should be avoided during pregnancy. However, there is no de-
finitive evidence in this area.

INTERACTIONS

Lavender/Drug Interactions

Sedating Drugs: In rats, concomitant use of lavender and pentobarbital

or chloral hydrate has significantly increased sleeping time and narcotic ef-
 Monograph from Natural Standard 69

fects.9,20 Concurrent use with other sedative or hypnotic agents theoreti-

cally may act in an additive or synergistic fashion.
Anticoagulants, NSAIDs, Anti-Platelet Agents: Lavender contains vary-
ing amounts of coumarins and may therefore theoretically increase the ef-
fect of anticoagulant medications.
Anti-Seizure Medications: Lavender enhances GABA effects and may
therefore intensify the sedative effects of GABA-dependent antiepileptics.
HMG-CoA Reductase Inhibitors, Niacin, Cholesterol Lowering Agents;
Theoretical Positive Interaction: Lavender may act in an additive fashion
with cholesterol-lowering agents: Cineole, a cyclic monoterpene found in
lavender, lowers cholesterol in rats via inhibition of the HMG-CoA en-
zyme; the lavender constituent perillyl alcohol (POH) has been shown to
inhibit the conversion of lathesterol to cholesterol.23,24
Lavender/Herb/Supplement Interactions
Sedating Agents: Lavender has been found to have sedative effects in
animal models, and acts additively with sedatives including pentobarbital
and chloral hydrate.9,20 In theory, it may intensify the effects of other seda-
tive agents such as kava or valerian root.
Anticoagulant Herbs/Supplements: Lavender contains varying amounts
of coumarins and may therefore theoretically increase the effect of antico-
agulant medications.
Lavender/Food Interactions
Insufficient available evidence.
Lavender/Lab Interactions
Low Density Lipoprotein (LDL), Total Cholesterol, High Density Lipo-
protein (HDL): Based on animal studies, oral lavender may act similarly to
HMG-CoA reductase inhibitors and lower total cholesterol/LDL while
raising HDL.23,24

MECHANISM OF ACTION
Pharmacology
Lavender is comprised of over 100 constituents, including linalool,
perillyl alcohol, linalyl acetate, camphor, limonene, tannins, triterpenes,
coumarins, cineole, and flavonoids.
Linalool has been shown to reduce motor activity in mice due to a
70 JOURNAL OF HERBAL PHARMACOTHERAPY

dose-related binding to glutamate, a primary excitatory neurotransmitter

of the central nervous system, and it has been suggested that hypnotic
and anticonvulsant effects of lavender may be due to the potentiation of
the neurotransmitter GABA.25
The mechanism of lavender’s spasmolytic activity has not been fully
elucidated. Gamez et al. studied the antispasmodic effect of L. dentate (a
lavender species) in vitro.26 An observed antagonism of acetylcholine-in-
duced muscle contractions was attributed largely to cineole. Lis-Balchin et
al. observed that the linalool and linalyl acetate in L. angustifolia oil can in-
duce cAMP-mediated relaxation of guinea pig ileum smooth muscle.27 The
authors postulated a cAMP-based mechanism for lavender’s purported
physiological effects on sympathetic nervous system activity.
Components of lavender appear to have cytotoxic properties. Fulton
et al. demonstrated cell proliferating effects of perillyl alcohol (POH)
on smooth muscle cell cultures.28 Both limonene and POH have been
shown to inhibit tumor growth in rats by blocking initiation and by pro-
moting apoptosis.29,30,31 One in vitro study evaluated the effects of POH in
lung carcinogenesis, and described an inhibitory effect on farnesylation, a
step towards activation of the oncogene K-ras.32
The lipid-lowering effect of lavender has been attributed to the con-
stituent cineole, a cyclic monoterpene which lowers cholesterol in rats
via inhibition of the HMG-CoA enzyme.23 The lavender constituent
perillyl alcohol (POH) has been shown to inhibit the conversion of lathesterol
to cholesterol.24
Caffeic acid, a constituent of lavender, has been demonstrated to pos-
sess antioxidant effects in vitro.33
Pharmacodynamics/Kinetics
Topical: Lavender oil is quickly absorbed by the skin. The constituents
linalool and linalyl acetate are detectable in the blood five minutes after
topical application, peak at 19 minutes, and largely disappear from the
blood within 90 minutes.34
Oral: The constituents limonene and perillyl alcohol (POH) are metabo-
lized into perillic acid (PA) and dihydroperillic acid (DHPA). In rats fed a
diet containing POH or limonene, peak levels of PA can be seen at 1-2.5
hours, peak levels of DHPA are noted at 2-3.5 hours, and half-lives for
each metabolite are 1-2 hours.30 POH, PA, and DHPA are detectable in
subjects’ urine following high doses of POH ingestion. Approximately
9% of the total dose can be recovered in the first 24 hours. PA is the ma-
jor metabolite found, with <1% of recovered POH.
 Monograph from Natural Standard 71

The absorption of POH does not appear to be affected by concomi-

tant ingestion of foods.11,12

HISTORY
The name lavender is derived from the Latin lavare, meaning to wash.
In ancient Greece, Persia and Rome, it was used as a perfume in baths and
laundry, and as an antiseptic. Ancient Egyptians created mummification
casts by soaking linen in oil of lavender containing asphalt, then wrapping
the bodies with these and drying them in the sun until the casts were hard.
Lavender has been renowned as a ‘healing agent’ in India and Tibet. In Ti-
betan Buddhist medicine, lavender is still used to treat insanity and psycho-
ses. Today, in Europe and the Americas, lavender is often used as an
anxiolytic and sleep aid.

EVIDENCE TABLE
Condition Study Design Author, N Statistically Quality of Magnitude ARR NNT Comments
Year Significant? Study of Benefit
0-2=poor
3-4=good
5=excellent
Anxiety Not randomized, Saeki, 10 Yes 1 Small NA NA Poor
controlled 2000 description of
methodology;
unclear
blinding or
randomization.
Anxiety Randomized, Dunn, 12 Yes 1 Small NA NA Initial benefit
controlled 1995 2 dissipated
after first
session.
Anxiety Not randomized, Motomura, 42 Yes 0 Large NA NA Small study,
controlled 1998 results unclear
due to lack of
randomization.
Anxiety Case series Itai, 2000 14 Yes NA Large NA NA No significant
difference
compared to
odorless smell.
Hypnotic Case series Hardy, 4 NA NA None NA NA Small series
1995 using
aromatherapy.
Perineal Double-blind, Dale, 63 No 3 None NA NA Subjective
relief randomized, 1994 5 outcome
following controlled measure,
childbirth incomplete
data, no
difference
found.
Tumor Case series Ripple, 18 NA 1 NA NA NA Uncontrolled
regression (phase I clinical 1998 trial using
trial) perillyl alcohol
(POH).
72 JOURNAL OF HERBAL PHARMACOTHERAPY

EVIDENCE DISCUSSION

Anxiety (Aromatherapy)
Summary: In general, the evidence supporting lavender aromatherapy as
an anxiolytic is weak. There are conflicting results from methodologically
flawed studies, with some showing lack of effect. However, overall, the
weight of the evidence suggests a small positive effect in relieving anxiety.
Further study through well-designed randomized trials would strengthen this
case. However, there are inherent difficulties involved with designing blind-
ing or placebo control for study of an olfactory therapy. These difficulties
must be overcome before compelling results can be generated.
Evidence: Saeki et al. attempted to demonstrate that lavender aromatherapy
via footbath produced anxiolytic effects compared to placebo.17 This “be-
fore and after” study, which consisted of 10 subjects, concluded that a hot
footbath with lavender oil is associated with small but significant changes
in autonomic activity. However, the incomplete description of methodol-
ogy and analysis make results difficult to interpret.
Dunn et al. conducted a randomized, single-blind study in 122 inten-
sive care unit patients, allocated to one of three groups: body massage
with grapeseed oil, body massage with lavender oil, or undisturbed
rest.7 Psychological endpoints were assessed using an arbitrary 4-point
scale, and physiological endpoints included blood pressure, heart rate,
and breaths-per-minute. Treatment ranged from one to three 30-minute
sessions, 24 hours apart. All patients received at least one session; 66
patients completed three sessions. After the first session, patients who
had received a massage with lavender oil had significantly less anxiety
than the group who rested. This difference was not maintained in the
following sessions. It is not clear to what extent the lack of dou-
ble-blinding, or the high dropout rate, affected results.
Motomura et al. conducted an experiment in which 42 students were di-
vided into three groups: Group 1 experienced a “stressful condition;” group
2 experienced a “stressful condition” with the addition of lavender odor;
group 3 experienced a “non-stressful condition.” Stress was evaluated
based on a Japanese version of Cox and Mackay’s stress/arousal adjective
checklist. The experiment found that scores in the lavender group were sig-
nificantly lower than the group who was stressed and did not receive laven-
der therapy.35 However, blinding and randomization were not clearly
described.
In a case series consisting of 14 female, chronic renal failure patients
on hemodialysis, Itai et al. evaluated the effect of lavender oil on mood
 Monograph from Natural Standard 73

using the Hamilton rating scale for depression (HAMD) and the Hamil-
ton rating scale for Anxiety (HAMA).36 Compared to natural smell (base-
line), lavender was observed to decrease anxiety as evidenced by the
HAMA scale (P = 0.05). Lavender did not significantly alter patients’
HAMD scores from baseline. When lavender was compared to odorless
conditions, the difference in HAMA and HAMD scores was minimal.
Buckle compared therapeutic benefits of oils from two different spe-
cies of lavender (L. angustifolia and L. burnatti) applied by massage to 28
hospitalized patients.37 A semi-structured interview to collect qualitative,
subjective data was used several days after treatment. The study reported
that L. burnatti had significantly more relaxing effects than its counterpart.
However, further details of statistical analysis or methodology were in-
complete, thus raising question about the results.

Hypnotic/Sleep (Aromatherapy)

Summary: Many experts and patients believe that lavender aromatherapy

is an effective hypnotic. Although preliminary evidence suggests some
hypnotic effects of lavender, there are no randomized trials in the available
literature. Without further study, the current evidence can only be consid-
ered equivocal. However, there are inherent difficulties involved with de-
signing blinding or placebo control for study of an olfactory therapy. These
difficulties must be overcome before compelling results can be generated.
Evidence: Hardy et al. evaluated aromatherapeutic lavender as an alter-
native to conventional hypnotics in four geriatric patients.5 Sleep hours
were monitored during three two-week phases. During phase I, subjects
continued their current hypnotic (temazepam, promazine, chlormethiazole).
Phase II involved a withdrawal and washout period. During phase III, lav-
ender oil was introduced into the patients’ sleeping quarters via an odor dif-
fuser. The results demonstrated that hours asleep were comparable to the
number of hours asleep during phase I of the trial for all four participants.
However, without controls or blinding, results can only be considered pre-
liminary.
Diego et al. demonstrated the effects of three-minute aromatherapy
sessions using a 10% lavender oil concentration on participants’ brain
waves via electroencephalogram (EEG).38 The EEG reading was re-
corded prior, during, and after sessions. Alpha and beta activity were found
to increase after the inhalation of lavender. Notably, increased frontal alpha
and beta activity have been associated with increased drowsiness, which
provides mechanistic supportive evidence for this purported indication.
74 JOURNAL OF HERBAL PHARMACOTHERAPY

Perineal Discomfort Following Childbirth (Baths)

Summary: There is insufficient scientific evidence regarding the use of

lavender oil baths for the relief of postpartum perineal discomfort.
Evidence: Dale and Cornwell examined the effect of lavender oils baths
on perineal discomfort in 635 postpartum women in a randomized trial.13
Subjects were divided into three groups: Group 1 added a natural lavender
oil extract to baths, group 2 added a synthetic lavender oil to baths, and the
third group used an unspecified control substance that had U.S. “Generally
Recognized As Safe” status. The control was reported to be distinguishable
from the other two oils by smell, and in efforts to compensate for this, pa-
tients were informed that the trial was testing “different bath additives.” To
evaluate discomfort, women were asked to complete visual analogue
scales (VAS), a subjective questionnaire used to evaluate the degree of dis-
comfort over the 10 days of the experiment. Data were obtained from
~60% (n = 386) of participants. Although this trial found no significant dif-
ferences in perineal relief between the groups, the large dropout rate and
lack of information about the control substance (which could have been ac-
tive) raise doubts about the validity of results.

Spasmolytic (Oral)

Summary: Preliminary data from animal and in vitro studies indicate a

potential spasmolytic effect of lavender oil inhalation. However, human
evidence is lacking.
Animal Data: A variety of lavender species have demonstrated an abil-
ity to inhibit stimulated muscle contractions in the ileum and conjunctiva of
animal models.26,39,40,27,41

Antibiotic (Topical)

Summary: Preliminary data from in vitro studies suggest that lavender

oils possess antibiotic activity. However, this has not been tested in animal
or human studies, and results cannot be considered clinically relevant.
In Vitro Data: Gabbrielli et al. demonstrated in vitro activity of lavender
oil (L. angustifolia and L. latifolia) against various strains of non-tubercular
Mycobacterium.6 Nelson et al. found documented activity of 2% to
0.12% (v/v) lavender oils against both methicillin-resistant Staphylo-
coccus aureus (MRSA) and vancomycin-resistant enterococci (VRE).2
 Monograph from Natural Standard 75

Cancer (Oral)

Summary: Preliminary data from animal studies suggest an antineoplastic

effect of oral perillyl alcohol (POH) and other monoterpenes found in lav-
ender. Studies have focused on cancers of the pancreas, breast, and intes-
tine. Small phase I studies have been conducted in humans, suggesting
safety and tolerability of POH (up to 1200 mg/m2 four times/day), but effi-
cacy has not been established.
Animal Data: Elegbede et al. and Haag et al. demonstrated regression of
primary mammary tumors in rats after supplementing diets with limonene
and POH (lavender constituents).29,30 Burke et al. documented inhibition of
pancreatic adenocarcinoma growth in hamsters using a similar diet.42
Reddy et al. found a significant chemoprotective effect of oral POH on
carcinogenesis of the large and small intestines in rats.43
Human Evidence: In a phase I clinical trial, Ripple et al. examined
the potential of POH to suppress tumor growth in humans.11 This study
consisted of 18 patients with advanced malignancies of various origins,
refractory to standard therapies. POH was formulated in gelatin cap-
sules containing 250 mg of POH and 250 mg of soybean oil. Prior to re-
ceiving POH, as a washout, patients did not receive hormonal or
immunological therapy for two weeks, or chemotherapy/radiation for
four weeks. Patients were divided into three groups: 800 mg/m2/dose;
1600 mg/m2/dose; or 2400 mg/m2/dose, three times/day. Although no
objective tumor responses were noted, disease stabilization was noted
in several patients for up to six months. POH was generally well toler-
ated, although dose-dependent gastrointestinal side effects (nausea,
early satiety) and fatigue led to withdrawal of one patient from the
study.
In a second case series, the same authors examined the effects of
more frequent administration at slightly lower doses.12 Nineteen patients
with various malignancies, refractory to standard treatment, were treated
at the following doses: 800 mg/m2/dose; 1200 mg/m2/dose; or 1600 mg/
m2/dose, four times/day. The maximum tolerated dose of POH given
continuously four times/day was 1200 mg/m2/dose. Patterns of disease
progression similar to the initial trial were observed at all doses. Al-
though promising, these results must be further evaluated through con-
trolled studies before a recommendation can be made. Nonetheless,
these small studies suggest safety and tolerability of POH at doses up to
1200 mg/m2 four times/day.
76 JOURNAL OF HERBAL PHARMACOTHERAPY

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