by Francis Brinker, N.D.
Copyright 2009
All rights reserved
Last update December 14,
2009
Combining herbal use with
prescribed medication(s) should only be done after consultation with the
prescribing physician and/or the dispensing pharmacist. Information provided in the book and at this
site is not intended to take the place of instructions provided by one’s
doctor, pharmacist or other personal health care provider.
The content on this site is
presented to supplement the information found in the third edition of the
book. By this means the database can be
enlarged, enhanced and updated without the user having to annually purchase a
new printed edition largely containing information already provided in the
previous edition or subscribing to an online updating service. The format for this site is consistent with
that found in the book, so that herbs and appendix categories can be easily
accessed by the same arrangement as in the printed text. The page numbers for
the updates indicate where in the book the associated information can be found,
while additions are identified as "NEW." The added reference
citations begin with 1100. Citations for
lower reference numbers are found in the book. Changes in scientific binomials
and standardized common names used here are now based on the second edition of Herbs
of Commerce (2000).
Since the
information on this site presupposes familiarity with the content in the book,
it must be understood in that context. The content on this site must be
recognized as inadequate without access to what has been published in the 3rd
edition. However, abbreviated versions
of prior referenced statements about the contraindications or the drug
interactions are included at the beginning of an addition to identify the
context of the addition. Listed below are important terms, abbreviations, and
symbols used in the book and/or on this site, followed by a Table of those
herbs and appendix sections to which additions have been made.
Regarding
herbal contraindications, many bridge the empirical vs. speculative
designations, with greater evidence provided by one or the other, though a
combination of factors often contribute. The method of determining such
designations is imprecise, and what is described as a speculative
contraindication for self-prescribing by the general public (the method
employed for this text and web site) may in some cases be more accurately
described as a precaution for an expert prescriber educated in botanical
medicine (as indicated in other texts primarily intended for professional use).
When herbal
influence on drug pharmacokinetics is discussed, the term “bioavailability” is
often used as a short-hand term to describe the total Area Under the
concentration-time Curve (AUC). Though the total time that the drug concentration
is monitored may vary from a few hours to to a few days depending upon the
study, this general term is applied to conveniently indicate that the overall
average circulating serum level of the drug has been significantly altered.
The
following terms are used to describe the different means of determining
botanical effects.
The
categorization of I, II, III and IV is used to rank potential herb-drug
interactions according to their probable pertinence based on the strongest
degree of evidence available.
Where
contradicting data exists for a particular item in any category, this is noted
by an indentation, and the sentence will begin with the word, “However.”
I. human studies –
published research done on healthy individuals
human
clinical studies – published research from therapeutic trials on patients
being treated for a condition
empirical – traditional knowledge or consensus based on
experience from extensive use
human
case reports – published individual responses to using herbal products
human
case series – published responses from several patients using a preparation
of the same herb
II. in animals (types listed) – laboratory
tests using live animals (in vivo)
and various modes of administering the herb or herbal component(s)
III. ex vivo –laboratory interaction
finding on cells, tissue, or organs from animals or humans who were
administered the herbal agent (as contrasted to in vivo when studies are done on the living organisms themselves)
in vitro –laboratory interaction
finding with cell or tissue samples from animals or humans
speculative
– using pharmacological evidence from in
vitro research, animal studies, or human studies to infer probable or
potential interactions or effects in humans
IV. [dubious interactions] shown in brackets with the drugs underlined rather than in bold type are
based on preliminary findings, speculation, inaccurate information, and/or
false assumptions that have been contradicted by established evidence.
Abbreviations
for the various modes of administration are used as follows:
IM (intramuscular) – injected into a
large skeletal muscle
IP (intraperitoneal) – injected into
the peritoneal cavity
IV (intravenous) – injected into a vein
PO (per
os) – by mouth; orally or through a feeding tube; b.i.d. = 2x/day,
t.i.d. = 3x/day
SC (subcutaneous) – injected under the skin
ADDITIONAL
INFORMATION BASED ON THE FOLLOWING IS AVAILABLE FOR THE LISTED HERBS AND
APPENDICES:
+ denotes new contraindication(s) and/or
interaction(s) not previously listed in the book for the herb
^ denotes new herb with contraindication(s) and/or
interaction(s) in body of text or an entirely new appendix section
Ä denotes use of new
standardized common name from second edition of Herbs of Commerce
If none of the above are present in the list below,
elaborations have been made to information already included in the book.
An asterisk (*) in front of an herb’s
scientific name denotes toxic effects from over-consumption of that herb or a
major active component.
Where [CORRECTION:] appears before numbers or
information in ALL CAPS, it denotes correction of an error found in the book.
Introduction +
The following list are those
herbs that are either new or for which updates or new information has been
added.
Agar +
Agave ^
Alfalfa +
American
ginseng +
Andrographis ^
Anise +
Apricot ^
Arnica +
Artichoke +
Ashwagandha +
Asparagus +
Astragalus
Bacopa ^
Barberry +
Basil +
Beebalm ^
Beth root ^
Bilberry
Birch +
Bitter
melon +
Bitter
orange +
Black
chokeberry ^
Black
cohosh +
Black
cumin ^
Black
currant ^
Bladder
kelp ^
Bladderwrack +
Blue cohosh +
Blue
flag ^
Blue
vervain ^
Bloodroot +
Boldo +
Borage
+
Boswellia ^
Bromelain +
Burdock +
Butternut
Cajeput ^
Calendual +
California spikenard ^
Camphor bark +
Caraway ^
Cascara sagrada
Cassia cinnamon + Ä See Cassia
Cat’s claw +
Cayenne
Celandine
+
Celery +
Chamomile,
German +
Ä See Chamomile
Chamomile,
Roman Ä See Roman Chamomile
Chaste
tree +
Chickweed ^
Chicory +
Chinese
cucumber ^
Chinese skullcap ^ Ä
Cinchona +
Cinnamon +
Clove +
Cocoa +
Coffee
Comfrey +
Copaiba ^
Coptis ^
Cordyceps +
Corydalis ^
Cotton +
Couch
grass Ä See Triticum.
Cranberry ^
Cranesbill ^
Crucifers
Cumin ^
Dan
shen
Dandelion +
Devil’s
claw
Dill +
Dog
rose ^
Dong
quai +
Dulse +
Dyer’s
broom +
Eastern
red cedar ^
Eleuthero
Ephedra
Eucalyptus
European pennyroyal ^
European vervain ^
Evening primrose +
False unicorn root ^
Fennel +
Fenugreek +
Feverfew
Flax
Forsythia ^
Fragrant
angelica ^
French
maritime pine ^
Garlic
+
Ginger
+
Ginkgo
Ginseng + Ä See Asian ginseng
Goat’s rue ^
Goldenrod ^ Ä For Solidago virgaurea see European goldenrod.
Goldenseal
+
Gotu
kola +
Grapes ^
Grapefruit +
Guar
gum +
Guarana
Guggul ^
Gurmar + Ä See Gymnema
Hawthorn +
Henna ^
Hops +
Horse chestnut +
Horseradish
+
Horsetail +
Iboga
+
Inmortal
^
Ipecac
+
Jamaica
dogwood +
Job’s
tears ^
Jujube
seeds ^
Kava
+
Konjac
Kudzu +
Kutaki Ä
Lavender Ä See English lavender.
Lemongrass +
Licorice +
Life
root
Lobelia
+
Lomatium ^
Lycium ^
Maca ^
Maitake +
Makandi +
Mangosteen +
Marijuana + See Cannabis.
Marshmallow +
Mate
Meadowsweet +
Milk
thistle +
Muirapuama ^
Mustard
Myrrh +
Nard ^
Neem ^
Nutmeg +
Oat +
Ocotillo ^
Olive +
Orange ^
Oregon grape +
Osha ^
Papain
Passion flower +
Pennyroyal Ä See American pennyroyal.
Peppermint +
Periwinkle Ä See Lesser periwinkle.
Petasites +
Picrorrhiza ^
Plantain Ä For Plantago lanceolata see
English plantain.
Pleurisy root +
Poke ^
Pomegranate +
Prickly ash
Prickly pear
Psoralea ^
Psyllium
Puncture vine ^
Purslance ^
Quassia (Jamaican) ^
Quassia (Surinam) ^
Queen Ann’s lace Ä See Wild carrot
Raspberry +
Red
clover +
Rehmania +
Reishi +
Rhatany ^
Rhodiola ^
Rhubarb,
Chinese Ä See Chinese rhubarb
Royal
sun agaricus ^
Sage +
Schizandra +
Scotch broom
Scouring rush ^
Sea buckthorn ^
Senna +
Sesame ^
Shepherd’s purse +
Shrub aloe ^
Small spikenard ^
Soy +
Spikenard ^
St.
John’s wort
Stevia ^
Stinging
nettles +
Sweet
annie ^
Sweet
clover
Szechuan
lovage ^
Szechuan
pepper ^
Tea +
Tea
tree ^
Thuja +
Thunder
god vine ^
Thyme
+
Tobacco +
Turkey
tail +
Turmeric +
Tylophora ^
Uva
ursi
Valerian
+
Vetiver ^
Watercress +
Wheat ^
Wild
cherry Ä See Black cherry
Wild
lettuce +
Wild
marjoram See Oregano
Wild
yam +
Willow +
Wintergreen ^
Witch
hazel +
Wormwood +
Yarrow +
Yellow dock ^
APPENDIX SECTIONS WITH NEW HERBALS, DATA OR SECTIONS ADDED:
A.2.1 Carrot family
A.4 In Acute Inflammation of the
Urinary Tract
A.4.1 Medicinal Plants Containing Urinary Irritants
A.4.2 Medicinal Plants Containing Soluble Oxalates
A.5 In Gastrointestinal
Irritation
A.5.1 Herbals That Can Upset the GI Tract
A.6
In Hypothyroid Conditions or Euthyroid Goiter
A.6.2
Antigoitrogens
A.7.1 Herbals With Toxic Potential
B.1.1.b.i Selective Precipitation of Alkaloids and
Minerals by Tannins
B.1.3 No Influence on Drug Absorption in Humans ^
B.2 Potentiating Cardiotonic Medicines
B.2.2.b
Potentiation by Kaliuretics and/or Diuretics
B.3 Potentiating Sedative or Tranquilizing
Medicines
B.3.1 Hypnotic and/or
Anxiolytic Drug Enhancement
B.4 Modigying Blood Sugar in Insulin-Dependent
Diabetics
B.5 Modifying the Effects of Anticoagulants
B.7 Modifying Enzyme Activities in Metabolic
Conversions
B.7.1.a Modulation by Phase I &/or Phase II
Enzymes &/or Other Clearance Factors
B.7.1.c Influence on Aryl hydrocarbon Receptor (AhR) ^
B.7.2.a Influence on CYP 1A2 Metabolic Conversion of Substrates
B.7.2.b Influence on CYP 2E1 Metabolic Conversion of Substrates
B.7.2.c Influence on CYP 3A4 Metabolic Conversion of Substrates
B.7.2.d
Influence on CYP 2C9 Metabolic
Conversion of Substrates ^
B.7.2.e
Influence on CYP 2C19
Metabolic Conversion of Substrates ^
B.7.2.f
Influence on CYP 2D6 Metabolic
Conversion of Substrates ^
B.7.3.a Influence on Glutathione S-Transferase
Activity or its Isozyme Levels
B.7.3.b
Influence on Activity and/or Content of UDP-Glucuronosyltransferases
[UGT]
B.7.3.c
Influence on NADPH-Quinone Reductase [QR] (DT-Diaphorase) Activity
and/or Content
B.7.3.d
Influence on Epoxide Hydrolase (Epoxide Hydratase)[EH] Activity
B.7.4.a
Aromatase (CYP19) Conversion of Testosterone to 17b-Estradiol
B.7.4.b 5a-Reductase Conversion of
Testosterone to Dihydrotestosterone
B.7.4.d 11b-Hydroxysteroid
Dehydrogenase type 2 Conversion of Cortisol to Cortisone
B.7.4.e 17b-Hydroxysteroid
Dehydrogenase types 1, 3 or 5 Conversion of Androstenedione to Testosterone
B.7.4.f 17b-Hydroxysteroid
Dehydrogenase type 2 Conversion of Testosterone to Androstenedione or Estradiol
to Estrone ^
B.7.4.g 17b-Hydroxysteroid
Dehydrogenase type 1 Conversion of Estrone to Estradiol ^
B.7.4.h 3b-Hydroxysteroid
Dehydrogenase type 1 or 2 Conversion of DHEA to Androstenedione and/or
Pregnenolone to Progesterone ^
B.7.5 Herbal
Monoamine Oxidase –A &/or –B Inhibitors
C.1 During Pregnancy
C.1.1
Herbals That May Impact the Uterus or Fetal Development
D.1
Drug and Mineral Interactions with Vitamin Supplements
D.1.5 Vitamin B6 (Pyridoxine,
Pyridoxamine, Pyridoxal) / Drug Interactions
D.1.7 Folic Acid / Drug Interactions
D.1.8 Vitamin C (Ascorbic Acid, Ascorbates) / Drug
Interactions
D.1.10.a
Vitamin E-Rich Plant Sources
D.2 Drug and Vitamin Interactions with Mineral
Supplements
D.2.1 Calcium
/ Drug Interactions
D.2.1.a
Calcium-Rich Plant Sources
D.2.2.a
Copper-Rich Plant Sources
D.2.4 Iron (as Ferrous
Sulfate) / Drug Interactions
D.2.4.a Iron-Rich Plant Sources
D.2.5.a Magnesium-Rich Plant Sources
D.2.6.a Manganese-Rich Plant Sources
D.2.7.a Potassium-Rich Plant Sources
E.1.
Complementary Interactions of Herbals with Drugs [formerly Addendum]
E.2. Botanical Aids for Modifying Substance Abuse ^
E.4.
Enhancing
Chemotherapy and Chemoprevention or Reducing the Adverse Effects ^
E.6.
Botanicals and Anti-infectious Agents
1100. – 2639.
Introduction
There are many possible meanings of
the word “herb.” Taken in its broadest medicinal sense, it commonly refers to
all plants and/or plant parts. Traditionally, it has been applied to the
above-ground part of non-woody plants, excluding their roots and/or rhizomes.
The term is used in this text with this intended meaning, to describe the part
of the plant used for many of the botanicals included herein. In the culinary
arts an herb is distinguished from spices as referring primarily to aromatic
leaves, in contrast to seeds, bark, or roots/rhizomes. In all of these cases,
the word is intended to be understood as the whole part of the fresh or dried
plant, characteristically including its fiber content.
For the purposes of understanding
the title of this book in all of its ramifications, the concept of “herb”
incorporates chemically complex derivatives of all plant parts. This extended
application of the term is in consideration of the majority of studies using
only derivatives of the medicinal parts of plants. These extractives include,
for example, juices, teas, tinctures, volatile oils, and other fractions that
are physically or chemically removed from the fresh or dried plant parts. These
preparations are more properly referred to as botanicals or “herbals”, the
terms now employed in the text. Since these commercial derivatives are commonly
consumed, it is important to acknowledge the specific forms used in studies
when this is adequately described in published research.
By extension, major active components of the plants have been used to
help understand the pharmacology of the extracts and whole herbs. Discussion of
isolated phytochemicals should not be taken to imply that the pharmacology of a
commonly used extract or herb is identical to that of a single compound that
these may contain. Rather, the activity of an isolated compound is simply one
contributing factor to the overall effect derived from using the extract or
herb. The same case can be made in regard to a subfraction or even commonly
used extracts, when compared to the whole herb itself. At each level of growing
complexity (from isolate to subfraction to extract to herb) the influence of
the isolate in relation to the overall effect diminishes both in quality and
quantity.
Nevertheless, it remains useful to consider specific pharmacological
research regarding the activity of isolates, subfractions, and extracts, when
considering the effects of the herb itself. For this reason, research data from
all of these forms are used as evidence in this book to help document the
probability of specific outcomes. This remains a useful approach as long as it
is understood that direct application of the findings for a specific
preparation apply only to that preparation and dose; other correlations
necessarily fall short.
The term “bioequivalence” is a relative concept, in that certain
extractives or derivatives of an herb have more or less similarity to one
another, depending on each one’s unique phytochemical content and proportions.
Bioequivalency certainly cannot be assumed to strictly corrlate with an initial
amount of plant material from which many variable preparations can be made.
Though the inherent variability in content and complexity of “similar”
preparations may be unsettling for the scientific purist, it should be no more
uncomfortable than considering the fact that each person who uses a herb or its
extract is also genetically and biochemically unique in their own peculiar
response to the remedy. It is knowledge of the general similarities regarding
pathophysiology, pharmacology and therapeutic responses in conjunction with an
understanding of the individual distinctions between both preparations used and
patients using them that comprise the challenging art of medical practice.
These are facts that must be acknowledged and addressed in each case, to
optimize the safety and efficacy of the intervention. The same relative
significance can be applied to different quantities consumed of the exact same
preparation. While an accepted therapeutic dose and duration can be completely
safe, increasing its consumption in amount and/or length of use beyond its
acknowledged safe limitations can lead to undesirable adverse effects.
Therefore, in addition to characterizing the form used in scientific studies it
is important to describe the dosage used.
In some cases, animal and in vitro evidence can provide either
contradictory or supporting evidence to help assess the likelihood of
interaction report(s) involving botanicals and drugs or in establishing
mechanistic evidence for contraindication rationales.As stand-alone evidence,
laboratory studies with animals (in vivo) and/or with cell cultures (in vitro)
are insufficient to extrapolate the findings to oral dosing in humans. The
reasons for this are many. Animals differ from one another and from humans in
their abilities to digest, absorb, and/or metabolize the many different types of
components found in any complex botanical preparation. Animal studies often
utilize exaggerated doses to produce an effect that is more readily observed or
measure biochemically, but this exposure also may not correlate with typical
human dosage. In many animal studies on botanicals the use of injections helps
to maintain a consistent and reliable dosage, but systemic bioavailability of
the complete phytochemical complex does not accurately represent the partial
systemic exposure that follows digestion and absorption with oral dosing in
humans.
Similar
but distinct problems exists with laboratory studies utilizing cell cultures or
isolated organs. The exposure of living tissues to complex solutions extracted
from plants following intestinal absorption does not involve the same content
and proportion as is found in laboratory conditons where cells and tissues are
exposed to the complete extract. The pre- and postabsorption conversion of
various phytochemicals in the extract, potentially involving both activation
and/or deactivation from digestion and metabolism, does not occur to nearly the
same extent in cell monocultures and the nonreactive in vitro glass
environment. The concentration tested in vitro also often greatly exceed tissue
exposure in vivo. These issues call into question many of the so-called
“mechanisms of actions” that supply the basis for theoretical indications,
contraindications and interactions on which many speculate. In the case of
these in vitro laboratory studies, more may be learned about potential
mechanisms by studying the contribution of isolated components found in the
herbs and/or extracts, so long as the particular isolate has been shown to
absorbed systemically and is bioavailable in the sustained concentrations as
tested in the lab. The only direct application of herb or extract in vitro lab
data might be their local use on superficial tissues, i.e, the skin or mucosa,
or on associated microbial growth on these surfaces.
Contraindications
and Drug Interactions
AGAR p. 27
^ Gelidium spp.
thallus
Drug Interactions
III. + 1)
may inhibit absorption of oral drugs
such as aspirin, digitalis
and other cardiac glycosides, antibiotics,
and anticoagulants if administered
concurrently (speculative)150
AGAVE NEW
^ Agave
americana plant, juice
Contraindications
1) pregnancy
(empirical)2 due to its emmenagogue and abortifacient effects
(empirical)74
ALFALFA p.
27
Medicago sativa
plant
Drug Interactions
I. + 2)
A kidney transplant patient maintained on azathioprine and cyclosporin
for 16 years suffered severe acute rejection after taking alfalfa and black
cohosh (Cimicifuga racemosa) for 6 weeks, though serum cyclosporine levels
were not altered. Anti-T-cell immunoglobulin and steroid helped control
transplant rejection. Immunostimulation through T-cell activition by alfalfa’s
l-canavanine is suspected as contributing to the kidney rejection (PO in human
case report).1553
II. 1)
CORRECTION: increase rate of metabolism of ETHOXYCOUMARIN
in the liver by increasing the activity of hepatic microsomal
mixed-function oxidase reactions (PO in mice)103
III. + 3) The cytotoxic effect of gemcitabine,
a standard drug for pancreatic cancer, on pancreatic cancer cells was inhibited
in the presence of coumestrol and genistein even when used at 2.5 times higher
concentration (in vitro)1681
ALOE p.
29
Aloe vera = Aloe
barbadensis gel (not the dried sap)
Contraindications + 2)
allergic hypersensitivity to aloe preparations such as contact
dermatitis (empirical).1890
+ 3)
pregnancy without professional advice (speculative) due to uterine
stimulant, abortifacient, and/or teratogenic effects (in vitro, PO in
rat study).1890
Drug Interactions
IV. + 1)
Following extensive bleeding in the surgical removal of a large hemangioma,
this effect was attributed in part to a possible interaction between sevoflurane
and the consumption of 4 tablets per day for two weeks of Aloe vera (PO
in human case report). It was not known whether the aloe tablets were a whole
herb product or contained an extract, nor were the tablets analyzed for
constituent or to detect potential adulterants. Sevoflurance inhibits COX
activity and TXA2, impairs platelets, and prolongs bleeding, while
aloe was suspected of contributing by reducing prostaglandin synthesis.1785
This speculation was based on a study of a water extract and successive
fractions with n-hexane, benzene, ethyl acetate, chloroform, acetone, and 96%
ethanol from Aloe vera dried gel. Only the water extract of the gel
reduced PGE2 production (in vitro).1786
ALOES p.
29
*Aloe vera,
Aloe ferox, or Aloe perryi dried leaf latex or sap
(not the gel)
Contraindications
8) Do not take during intestinal obstruction due to stimulation of peristalsis by the
anthroquinones (empirical).4,6,150,401
Causes of obstruction include stenosis and atony.1890
+ 13) allergic hypersensitivity to aloe preparations such as
contact dermatitis (empirical)1890
+ 14)
Do not take if there is known dehydration due to depletion of water and
electrolytes (empirical).1890
Drug Interactions
IV. + 1) Following extensive bleeding in the surgical removal of a
large hemangioma, this effect was attributed in part to a possible interaction
between sevoflurane and the consumption of 4 tablets per day for two
weeks of Aloe vera (PO in human case report). It was not known whether
the aloe tablets were a whole herb product or contained an extract, nor were
the tablets analyzed for constituent or to detect potential adulterants.
Sevoflurance inhibits COX activity and TXA2, impairs platelets, and
prolongs bleeding, while aloe was suspected of contributing by reducing
prostaglandin synthesis.1785 This speculation was based on a study
of a water extract and successive fractions with n-hexane, benzene, ethyl
acetate, chloroform, acetone, and 96% ethanol from Aloe vera dried gel.
Only the water extract of the gel reduced PGE2 production (in
vitro).1786
AMERICAN
GINSENG p.
30
Panax quinquefolius root
Contraindications
1) Estrogenic activity, especially of alcoholic
root extracts, may be present in large part due to zearalenone and its
metabolites from Fusariam fungal contamination (in vitro).1695
In addition estrogen-independent stimulation of human breast cancer cell
proliferation with the alcoholic extract (in vitro)1664
suggests that regular consumption of the root or its alcoholic extracts should
be avoided in those with a history of breast cancer (speculative)
Drug Interactions
I. + 1)
3 grams or more of the powdered root given prior to a glucose challenge reduced
blood sugar levels in seven type 2 diabetics whose condition was being treated
with sulfonylureas or a combination
of these and metformin (PO in human
study).1114
In 12 nondiabetic subjects 3 grams of the dried
cultivated root tended to lower plasma glucose at 90 minutes during a 75-gram
oral GTT, but the same dose of wild root raised blood sugar after 120 minutes
(PO in human study).1713 From 3-9 grams of the ground root improved glucose
tolerance following a 25 gram glucose challenge in 10 nondiabetics (PO in human
study).1685 However, different batches of the root from the same
supplier that differed in ginsenoside ratios were not consistent in reducing
blood sugar of normal subjects under the same experiemental conditions (PO in
human study).1596 Roots grown in Wisconsin have shown wide
variability in total and individual ginsenoside content from those grown in
Illinois.1714
A water extract of the root has been shown to
significantly lower blood sugar, probably due to the activity of several
glycans (IP in mice).1574
An alcoholic extract of the berries at 150 mg/kg daily in
diabetics also lowers fasting blood sugar and improves overall glucose
tolerance while lowering body weight (IP in mice).1704
+ 2)
2 grams of encapsulated powdered root for 3 weeks in healthy subjects
significantly reduced blood levels and anticoagulant effect of warfarin
(PO in human study). The peak INR decreased along with peak plasma warfarin,
compared to placebo.1600
II. + 1)
Hot water extract at 400 mg/100 gm given 10 minutes prior to ethanol delayed the effects of ethanol
on the righting reflex and reduced its plasma levels, probably due to the
additive effect of slowing of gastric emptying by alcohol and American ginseng extract or ginsenosides (PO in mice)1117
+ 2)
the saponin fraction enhanced phenylephrine vasoconstrictor effect (in
vitro)1550
III. 1) Standardized extract synergistically increased suppression
of estrogen-dependent cancerous breast cells when combined with tamoxifen, cytoxan, doxorubicin, taxol
and methotrexate (in vitro).981
Tumor inhibition may be due in part to the
antiangiogenic activity of its predominant ginsenoside Rb1, the opposite effect
associated with Rg1 (in vitro, SC in mice)1686 However, an
alcoholic extract stimulated growth in the MCF-7 human breast cancer cell line
(in vitro), though it showed no estrogenic activity in failing to induce
transactivation of alpha- or beta-estrogen receptors (in vitro) or
increase uterine weight after 4 days (PO in mice).1664
In 3 digoxin immunoassays, an aqueous
American ginseng extract increased the digoxin measurement results for the fluorescence
polarization immunoassay (in vitro). Using the microparticle
enzyme immunoassay, this extract significantly lowered the serum digoxin
measurement (in vitro). No effect was found on the measurement done by
Tina-quant (in vitro).1995
AMERICAN PENNYROYAl
[formerly PENNYROYAL] p. 159
Ä *Hedeoma pulegioides plant
ANDROGRAPHIS NEW
^ Andrographis
paniculata
plant
Contraindications
1) pregnancy due to its abortifacient effects
(empirical),150 antifertility effect in females at high doses (in
mice),777 and fetal damage (in animals)1890
2) gastric hyperacidity such as duodenal ulcers
and esophageal reflux (empirical).1890
Drug Interactions
III. 1) Avoid long-term use with immunosuppressive drugs (speculative)1890 due to the activation of immunocompetent cells by its extract and component andrographolide (in vitro).1967
2) Caution should be used when taking with antiplatelet or anticoagulant medications (speculative),1890 since it inhibits platelet aggregation after consumption by cardiovascular disease patients (ex vivo).404,1890
ANISE p.
31
Pimpinella anisum
seed/fruit
Contraindications
+ 3)
CNS toxicity following consumption the tea, especially in nursing
mothers and/or their breast fed infants (PO in human case reports)1141
+ 4)
pregnancy (speculative)150 probably due to its estrogenic
effects of its essential oil component anethole14 and the antagonism
of testosterone and progesterone by anise seed oil (injected in rats)1312
APRICOT NEW
^ Prunus armeniaca seed
(Ch. xing ren)
Contraindications
1) self prescribing due to potential for adverse
effects from cyanogenic glycosides (speculative)150
2) children due to increased vulnerability to
toxic and lethal effects from cyanogenic glycosides (empirical)150
Drug Interactions
II. + 1) The absorption of sulfasalazine was
increased 2- to 4-fold when taken with apricot extract (PO in rats).2287
ARNICA p.
31
Arnica montana flowers
Contraindications
+ 6) internally by nursing mothers and not
applied topically to the nipple, due to potential toxicity to the infant
(empirical).1890
ARTICHOKE p.
32
Cynara solymus leaves
Contraindications
1) allergic hypersensitivity to artichoke
or other Asteracea [Compositae] family plants (empirical),6,17,401,777,1890
though the likelihood of globe artichoke
preparations producing an allergic response is very low (empirical).1890
A man and a woman who handled artichokes in their
occupations suffered seasonal allergic eruptions and urticaria, respectively,
and tested positive to patch or skin prick tests, especially to the stem,
leaves, and their fuzz (TP in human case reports).1974,1975
2) bile duct obstruction, due to its cholagogue
effect (empirical)6,17,401,777,1890
and its choleretic activity as shown with a single
1.9 gram dose of its 4.5-5:1 strength extract (PO in human study).1270
Drug Interactions
III. 1) It may enhance cholesterol-lowering
agents, due to additive effects (speculative).777
Tablets with 450 mg of a 25-35:1 aqueous extract
reduced total cholesterol, LDL cholesterol, and LDL/HDL ratio (PO in human
clinical study).1271
ASHWAGANDHA p. 33
Withania somnifera
root
Drug Interactions
II. + 2)
After 10 days of using 100 mg/kg of a commercial root extract, tolerance to morphine
analgesia was inhibited, and morphine dependence was blocked (PO in mice
study), suggesting that it could be of use in opiate addiction1277
+ 3)
leucopenia induced by cyclophosphamide was significantly reduced by
ashwagandha methanolic extract (IP in mice). So, the intended cytotoxic
activity of this chemotherapeutic agent and its efficacy in treating cancer may
be diminished (speculative).1583
However, when 4/5 of the
total ashwagandha root extract
was combined with 1/5 Tinospora cordifolia stem extract or the
alkaloid-free polar ashwagandha extract
was given in cyclophosphamide-treated ascitic sarcoma, not only did the
extracts provide myelo- and immuno-protective activity, but the drug’s
antitumor activty was not altered when compared to cyclophosphamide given alone
(PO in mice).2217
Also, 20 mg daily for 5 days of the methanolic
extract was shown to reduce bladder damage caused by cyclophosphamide
metabolites, one of the leading causes of adverse effects from this drug (IP in
mice). Rather than severe inflammation and hemorrhage 4-48 hours after the
drug, when given the extract the bladder morphology was normal, the elevated
serum and urine protein levels were normalized, while the lowered liver and
bladder glutathione levels were enhanced.1279
However, the
discontinuity effects caused by cyclophosphamide on the GI mucous membrane with
bleeding spots in the lower esophagus and upper stomach were not affected by
ashwagandha extract, suggesting the extract’s inability to protect against
general cyclophosphamide cytotoxicity (PO in mice).1278
100 mg/kg root extract given for 15 days with
cyclophosphamide, azathioprin and prednisolone prevented the
myelosuppressive activity of these drugs by increasing the hemoglobin, red
blood cell and platelet counts for all three groups, and the white blood cell
count for the cyclophosphamide and prednisolone groups (PO in mice). The
response was different for azathioprin and prednisolone than with cyclophosphamide
in that it reflected more of a direct response of the immune system to
ashwagandha, rather than indirect modulation or interference with the drug’s
immunosuppressive action.1278
+ 4)
pretreatment with 100 mg/kg extract enhanced the antiepileptic effects of diazepam
and clonazepam when convulsions were induced by lithium-pilocarpine
model (PO in rats)1290
+ 5) Adverse effects such as orofacial dyskinesia and poor memory retention induced by reserpine and associated with brain lipid peroxidation have been reversed dose-dependently by chronic use of ashwagandha root extract (PO in rats).1855
+ 6)
Increased levels of pertussis antibodies were detected after 100 mg/kg of a
water extract was given daily for 15 days after receiving a Diphtheria,
Pertussis, Tetanus [DPT] vaccine (PO in mice). When immunized
animals were challenged on day 14 with intracerebral pertussis, morbidity and
mortality were reduced in those that had been treated with the extract.2006
+ 7)
A decrease in benzo(a)pyrene-induced lung tumor markers AHH, GGT, and LDH in
the serum and lungs by paclitaxel was further decreased when ashwaganha
ethanol extract 400 mg/kg once weekly for 4 weeks was added to paclitaxel
treatment (PO in mice). Likewise, a further reduction of lung glycoprotein
markers was also noted with the combination, compared with use of paclitaxel
alone.2218
+ 8)
Catalepsy induced by haloperidol was reduced dose-dependently when an
ashwagandha water extract was given 30 minutes prior to haloperidol in the
acute study and for 6 days prior in the chronic study (PO in mice). The
reduction in catalepsy was correlated with superoxide dismutase levels in the
brain, indicating that the antioxidant activity of the extract could have contributed
to its effect.2295
III. 1) In 3 digoxin immunoassays, a 60-65% ethanolic
ashwagandha extract increased the digoxin measurement results for the
fluorescence polarization immunoassay (in vitro). Using the
microparticle enzyme immunoassay, this extract significantly lowered the serum
digoxin measurement (in vitro). No effect was found on the measurement
done by Tina-quant (in vitro).1995
asian GINSENG [Formerly GINSENG.] p. 107
Panax ginseng
root
Contraindications
1) high blood
pressure (empirical, human case report)150,361,404,777
However, 200 mg of a ginseng extract standardized to
4% ginsensosides reduced diastolic blood pressure 2 hours after ingestion.1298
2) acute asthma
(empirical)404,777,1308
or other inflammation (empirical)1308
3) acute infections404,777
accompanied by fever (empirical)1308
4) excessive menstruation
or nose bleeds (empirical)777
due to platelet aggregation inhibition by
ginsenoside Rg1 (in vitro)1196 and ginseng
lipophilic fraction (in vitro, ex vivo),
and prolonged time of fibrinogen conversion to fibrin (ex vivo)
following a 25 mg dose of the lipophilic fraction (PO in rats)1194
However, 10 adults taking a
proprietary Asian ginseng product at the manufacturer’s recommended dose for 2
weeks had no increase in coagulation time in ADP and epinephrine assays of
intrinsic and extrinsic platelet function, respectively (ex vivo), but
the product was not analyzed for its phytochemical content.2262
+ 5)
headaches, palpitations or strong pulse, or insomnia since
ginseng can cause these in some people (empirical)1308
+ 6)
anxiety, nervousness or emotional imbalance due to its
enhancement of the sympathetic nervous system (speculative),1308 or
in those with clinical affective disorders such as major depression
who may experience a manic state (PO in human case report)27,560,1461
+ 7)
pregnancy due to possible estrogenic effects (speculative)1308
Estrogenic activity, especially of alcoholic extracts,
may be present in large part due to zearalenone and its metabolites from Fusariam
fungal contamination (in vitro).1695
One study of 88 pregnant women suggested an increase risk
of adverse fetal outcome (PO in human study).1509
Ginsenoside Rb1 at concentrations of 30-50
mcg/ml increased teratogenic effects in whole rat embryos (in vitro),1485
results with uncertain implications for women taking the whole root or complex
extracts in typical doses.
+ 8)
brittle type 1 diabetes (speculative)893 because of the hypoglycemic
effect in diabetic patients (PO in human clinical study),109
probably due to the glycans of ginseng roots known as panaxans (IP in mice)567-569
and/or ginsenoside Rb2 that lowered blood sugar in diabetics (IP in
rats).72
However, the anti-hyperglycemic activity was
not confirmed as a hypoglycemic effect, since doses ranging from 1 to 9 grams
of powdered root in a randomized, multiple-crossover design did not
significantly affect plasma glucose or insulin following an oral glucose
tolerance test (PO in human study). Rather, the 2-hour plasma glucose was
significantly higher in pooled results.1612 Also, effects in 12
nondiabetic subjects on 75-gram oral glucose tolerance test responses to 3
grams of dried root varied according the type of ginseng. The dried whole root
was found to raise plasma glucose, whereas Asian-red ginseng steam-treated root
had no effect (PO in human study).1713 Compound K, the main gut
bacterial metabolite of protopanaxadiols, enhances glucose transport rate,
while the major protopanaxatriol Rg1 inhibits glucose transport across
intestinal cells (in vitro) These act by modulating the sodium/glucose
cotransporter 1 gene expression (in vitro).2043
An alcoholic extract of the berries at 150 mg/kg daily in
diabetics also lowers fasting blood sugar and improves overall glucose
tolerance while lowering body weight and plasma cholesterol levels (IP in
mice). The antihyperglycemic activity, but not the anti-obesity effect, is due
in large part to ginsenoside Re.1705
+ 9)
use at least one week, and definitely in the 24 hours, prior to surgery
due to short term potential for hypoglycemia and long term potential for
decreased coagulation leading to hemorrhage (speculative).1309,1310
The hypoglycemic effect appears to be due to the glycans of ginseng roots known
as panaxans (IP in mice).567-569 Diminished coagulation may be
attributed to panaxynol, ginseng lipophilic fraction, and some ginsenosides’s
antiplatelet activity (in vitro410,565,1194,
1196 and lipophilic fraction ex vivo1194), and
prolonging time of fibrinogen conversion to fibrin by ginsenoside Ro (in
vitro)565 and ginseng lipophilic fraction (ex vivo) following a 25 mg dose of
the lipophilic fraction (PO in rats),1194 and the potent platelet
activating factor antagonism of several ginsenosides (in vitro).718
However, 10 adults taking a
proprietary Asian ginseng product at the manufacturer’s recommended dose for 2
weeks had no increase in coagulation time in ADP and epinephrine assays of
intrinsic and extrinsic platelet function, respectively (ex vivo), but the
product was not analyzed for its phytochemical content.2262
Drug
Interactions
I. 1) Caffeine with
large amounts of “ginseng” led to hypertension, nervousness, diarrhea, skin
eruptions and insomnia in 14 subjects (PO in human case series).108
Caffeine metabolism by CYP 1A2 was not affected when
1.5 gm of ginseng standardized to 5% ginsensosides was consumed daily for 4
weeks. CYP 2D6, 2E1, and 3A4 were also unaffected (PO in human study).1328
3) Phenelzine
produced manic-like symptoms with the use of ginseng (human case reports).26,27
However, the “Natrol High”
product that supposedly contained Asian ginseng in one report26
actually contained the generically- and phytochemically-distinct eleuthero or
“Siberian ginseng” (Eleutherococcus senticosus) as part of a combination
product. Positive identification of ginseng and its causality in the other
report was not established. This interaction was still assessed as possible due
to the evidence in latter report, while the former was described as unevaluable
based upon its inadequate data.1239
+ 5)
When 5.4 gm of red Korean ginseng were taken daily with zidovudine by HIV-1 infected patients
for 4-6 years, it effectively maintained their CD4+ T cell counts and delayed development
of resistance mutations to zidovudine (PO in human clinical study).1335
In addition to zidovudine, red ginseng use with nucleoside reverse
transcriptase inhibitor (NRTI) didanosine lowered resistance
mutations, but not for lamivudine, and no multinucleoside drug resistance
mutations were detected (PO in human clinical study).1336
+ 6)
Following surgical removal of stage III gastric cancer in 42 patients, 4.5
grams daily of red ginseng powder doubled 5-year and overall survival rates and
improved CD3 and CD4 levels compared to placebo, while patients were also given
chemotherapy with 5-fluorouracil and cisplatin (PO in human
clinical study).1382
+ 7)
200 mg daily of the standardized extract G 115 given 4 weeks prior and 8 weeks
after a polyvalent influenza vaccine resulted in significantly fewer
cases of influenza and the common cold during the 8 weeks following vaccination
than in the group receiving placebo. The antibody titers and natural killer
cell activity were also much higher in those receiving the extract, along with
no significant differences in adverse effects (PO in human clinical study).408
+ 8)
200 mg/day of uncharacterized "ginseng" for 18 days inhibited
metabolism of CYP 3A4 substrate nifedipine, as indicated by increased
peak plasma concentration of 29% (PO in humans).1728
However, daily doses for 28
days of 1.5 gm Asian ginseng standardized to 5% ginsenosides failed to alter
the metabolism of CYP 3A4 substrate midazolam in humans (PO in human study).1328
Likewise, 200 mg/day for 14 days of ginseng extract standardized to 4%
ginsenosides failed to alter cortisol metabolism in 20 subjects (PO in human
study).1811
+ 9)
A woman treated for major depression with clomipramine and haloperidol became manic
with the use of 300 mg/day of a ginseng root extract (PO in human case report).1461
Clomipramine is a substrates for CYP 2D6, while
haloperidol is a substrate for CYP 3A4. A daily dose of 1.5 grams of an Asian
ginseng product standardized to 5% ginsenosides inhibited metabolism of the
substrate debrisoquin CYP 2D6 by 7% and an uncharacteried product inhibited CYP
3A4 as shown by increasing the peak plasma concentration of substrate
nifedipine by 29% (PO in human studies),1728,1808 though
standardized ginseng extracts with other 3A4 substrates showed no altered
bioavailability (PO in human studies).1328,1811
10) [Previously III.2.] Warfarin anticoagulant
activity was reduced as the INR fell from 3.1 to 1.4 following several weeks of
taking ginseng extract G 115 capsules 3 times daily (PO in speculative human
case report). Two weeks after the extract was discontinued, the INR returned to
3.3.110
Nonetheless, in a diabetic man with aortic valve
prosthesis, a thrombus interfered with the artificial leaflets valve in
conjunction with a reduction of INR to 1.4 in spite of increasing warfarin
dosage, following use of an undisclosed commercial ginseng product used at an
unreported dose for an indefinite time (PO in human case report).1986
However, a study of 25
ischemic stroke patients given warfarin with or without 1.5 grams/day of an
11:1 aqueous ginseng extract for 2 weeks did not result in any differences in
INR or prothrombin time between the two groups (PO in human clinical study).2326
When 1 gram solid Korean red ginseng aqueous extract daily was given for 6
weeks to patients using warfarin, there were no significant changes in INR
after 3 or 6 weeks, compared to placebo (PO in human clinical trial).2625
Furthermore, an open-label 3-way crossover randomized trial with 12 healthy
subjects found that ginseng extract daily providing 53.6 mg ginsenosides
derived from 3 grams of the root given 7 days before and after a single
warfarin dose does not affect warfarin clearance, INR, or platelet aggregation
(PO in human study).1578 In this study the apparent clearance was
increased by 14%, but this seems unlikely to have clinical significance
(speculative).2016
+ 11)
a randomized, double-blind, crossover trial using Korean ginseng rootlets in
capsules at doses of 2 grams 3 times daily before meals for 12 weeks in 19
patients with well-controlled diabetes type 2 treated with diet plus hypoglycemic
drugs alone or in combination in 14, including sulfonylurea in 10, metformin
in 9, rosiglitazone in 2, and acarbose in 1; this resulted in
reduction in oral glucose tolerance test indices by 8-11% and plasma insulin by
33-38% (PO in human clinical study). It also increased insulin sensitivity
indices by 33% compared to placebo. The rootlets had total ginsenoside
concentration of 1.92% with content of protopanaxadiols Rb1 0.48%, Rc 0.29%,
and Rb2 0.25%, along with protopanaxatriols Rg1 0.51% and Rf 0.23%.2042
Ginseng extract’s anti-hyperglycemic effect was
shown in non-insulin-dependent diabetic patients when 200 mg daily was given
orally for 8 weeks (PO in human clinical study).109 Ginseng extract
G115 at single doses of 200 mg and 400 mg reduced fasting blood glucose levels
in 30 healthy young adults after 60, 90 and 120 minutes (PO in human study).2153
However, the
anti-hyperglycemic activity was not confirmed as a hypoglycemic effect in
healthy subjects, since doses ranging from 1 to 9 grams of powdered root in a
randomized, multiple-crossover design did not significantly affect plasma
glucose or insulin following an oral glucose tolerance test (PO in human
study). Rather, the 2-hour plasma glucose was significantly higher in pooled
results.1612 When given with a 25-gram glucose drink to 27 healthy
subjects, 200 mg of G115 actually raised blood sugar levels after 1 hour but
had no effect after 2 hours, compared to controls (PO in human study).2153
Also, effects on
75-gram oral glucose tolerance test responses in 12 nondiabetic subjects given
3 grams of dried root varied according the type of ginseng. The dried whole
root was found to raise plasma glucose, whereas Asian-red ginseng steam-treated
root had no effect (PO in human study).1713 Compound K, the main gut
bacterial metabolite of protopanaxadiols, enhances glucose transport rate,
while the major protopanaxatriol Rg1 inhibits glucose transport across
intestinal cells (in vitro) These act by modulating the sodium/glucose
cotransporter 1 gene expression (in vitro).2043
II. + 3)
Extract G115 increased intestinal clearance of the active metabolite albendazole sulfoxide (IV in rats)1711
+ 4) An acidic polysaccharide fraction of red ginseng, derived from the marc following 85% ethanol extraction, combined with paclitaxel increased life span with transplanted sarcoma 180 by 29-43% at 25 mg/kg and reduced B16 melanoma tumor weight by 76% at 100 mg/kg, compared to the results from using paclitaxel alone (IP in mice)1721
+ 5)
The use of the 5 grams/day of the root as a decoction for 30 days along with doxorubicin
(adriamycin) given by intraperitoneal injection over a 2-week period
reduced the physical and biochemical signs of heart failure associated with the
drug (PO in rats).2257
III. + 1) Insulin dosage may need adjusting (speculative) because of ginseng extract’s hypoglycemic effect in diabetic patients (PO in human clinical study).109
Effects in 12 nondiabetic subjects on 75-gram oral
glucose tolerance test responses to 3 grams of dried root varied according the type of
ginseng and the protopanaxadiol to protopanaxatriol ratio. The dried whole root
was found to raise plasma glucose, whereas Asian-red ginseng steam-treated root
had no effect (PO in human study). The Asian-red protopanaxadiol content and
ratio were greater.1713
A randomized study found that while 6 grams Korean red
ginseng root body and water extract were ineffective in reducing glycemia from
a 50-gram glucose tolerance test, the rootlets were effective (PO in human
study). A dose of 2 grams of rootlets was found to be equally effective, and
the ginsenoside Rb1 was identified as the sole predictor of effects on
postprandial glucose.1977
However, another study with 27 young healthy
subjects showed that the extract G115 at single 200 mg doses lowered fasting
blood sugar from 60-120 minutes compared to placebo, but when given with a
drink containing 25 grams of glucose it raised blood glucose levels more than
when glucose was given alone (PO in human study).2018
An ethanolic extract of ginseng berries that differed in
ginsenoside proportions had an even greater anti-hyperglycemic and anti-obesity
effects than the root extract (IP in mice).1597 The alcoholic
extract of the berries at 150 mg/kg daily in diabetics also lowers fasting
blood sugar and improves overall glucose tolerance while lowering body weight
and plasma cholesterol levels (IP in mice). The antihyperglycemic activity, but
not the anti-obesity effect, is due in large part to ginsenoside Re.1705
2) [See IV. 2)]
+ The
synergistic cytotoxic effect of the chemotherapy drug mitomycin C
combined with ginseng component panaxytriol was shown on gastric carcinoma MK-1
cells (in vitro).1712
3) [Formerly IV. 1)] Using 5 digoxin
immunoassays on 2 liquid Asian ginseng extracts and 1 capsule, one liquid
increased the digoxin concentration results only for the fluorescence
polarization immunoassay (in vitro, ex vivo with rats, ex vivo with
humans). Using the microparticle enzyme immunoassay, the liquid extract
significantly lowered the serum digoxin measurement (ex vivo with humans).1352,1995
IV. 1) [See III. 3]
ASPARAGUS p.
34
Asparagus racemosus root
Drug
Interactions
II. + 1)
Increased levels of pertussis antibodies were detected after 100 mg/kg of a
water extract was given daily for 15 days after receiving a Diphtheria,
Pertussis, Tetanus [DPT] vaccine (PO in mice). When immunized
animals were challenged on day 14 with intracerebral pertussis, morbidity and
mortality were reduced in those that had been treated with the extract.2006
ASTRAGALUS p.
34
Astragalus
membranaceus root
Contraindications
+ 2)
allergic hypersensitiviy or autoimmune conditions, since they may
be aggravated due to immunostimulating polysaccharides (speculative).409
+ 3)
following organ transplantation due to immunostimulating polysaccharides
(speculative).409
Drug Interactions
I. 1) The effects of recombinant interferon-a1
were therapeutically enhanced with an astragalus preparation that improved the
outcome in chronic viral cervicitis associated with human papillomavirus type
16 and herpes simplex virus type 2 (human clinical study).2359
+ 2) A meta-analysis compiled
34 randomized trials that combined astragalus herbal formulas with chemotherapy
regimens based on cisplatin for non-small-cell lung cancer in 2,815
patients. The data showed that chemotherapy plus oral astragalus formulas such
as Jin Fu Kang, or Ai Di Zhu She Ye injections containing astragalus used 8
studies, improved outcomes versus chemotherapy alone (PO or IV in human
clinical studies). Seven studies (529 patients) showed reduced risk of death
after 6 months, twelve (940 patients) after 12 months, nine (768 patients)
after 24 months, and six (556 patients) after 36 months. One of the studies
reducing this risk from 12-36 months used astragalus alone, rather than in a
formula. Tumor response rate favored the combination with herbs in 29 of 30
studies reporting this data, including two with astragalus alone. Karnofsky
performance status was stabilized or improved in one study with astragalus
alone, two studies with Jin Fu Kang, four studies with Ai Di Zhu She Ye, and
five studies with other astragalus formulas, totaling 1,095 patients.1851
Astragalus decoction enhanced immune function by increasing proliferation of
spleen cells, increasing B cell IgG production, enhanced induction of cytoxic T
cells, and increased macrophage cytokine production of IL-6 and TNF (in
vitro).1852
II. 2) The hydroalcoholic extract induced Th cells and enhanced
antibody response following use of cyclophosphamide
(IP in mice).599
A partially purified fraction completely reversed
immunosuppression induced by cyclophosphamide (IV in rats).1504
Another fraction of the water extract of the roots
was shown after 6 days to increase proliferation of colony-forming
unit-fibroblast proliferation and improve bone marrow stromal cell survival,
its production of IL-6, and expression of mRNA and bcl-2 protein, which helps
promote blood cell formation after cyclophosphamide myelosuppression (IP in
mice).2212
So, if cyclophosphamide is being used for treatment of lymphomas or leukemias or to prevent graft rejection, concurrent use of astragalus could have an undesirable antagonistic effect to the immunosuppression.
BACOPA new
^ Bacopa monniera =
Herpestis monniera whole plant
(Brahmi; Ind.: Brahmi Patra)
Drug Interactions
II. 1) Both cold aqueous infusion and 95%
alcoholic extract potentiated sleep induced by pentobarbital,
though the water extract was much more active (IP in rats)1291
2) Dried alcoholic extract at 40
mg/kg prevented increased lipid peroxidation and decreased antioxidant enzymes
in liver caused by morphine
when the two were given concurrently (PO in rats).1661 In addition,
prior exposure of intestinal ileum to the alcoholic extract before exposure to
morphine reduced the subsequent naloxone-induced contraction of the ileal
tissue (in vitro), suggesting a possible use in reducing morphine
withdrawal symptoms.1662
3) After using phenytoin for 7 days cognitive deficit demonstrated in
a passive avoidance task was reversed by 40 mg/kg dried alcoholic extract given
concurrently for the next 7 days (PO in mice), suggesting possible use to
prevent this adverse drug effect. Acquisition and retention of memory were also
improved, and phenytoin's anticonvulsant activity was not affected.1663
BARBERRY p.
35
Contraindications
+ 9)
Do not use in nursing mothers without professional advice (speculative), since berberine is passed
through the breast milk to the infant1890 and displacement by
berberine of bilirubin from serum albumen which may lead to kernicterus (IP in
rats).1092
Drug
Interactions
I. + 3)
Berberine 1.2 grams daily, given as tablets to 79 congestive heart failure
patients on ACE inhibitors along with digoxin in 76, nitrates
in 71, and diuretics / spironolactone in 77, significantly
increased left ventricular ejection fraction and exercise capacity, improved
dyspnea-fatigue index, and reduced frequency of ventricular premature complexes
compared with 77 patients using only comparable conventional medications. The
mortality of the berberine group decreased significantly as well, and there
were no apparent side effects (PO in human clinical study).1457 In
56 congestive heart failure patients on loop diuretics and ACE inhibitors, including
51 using digoxin and 46 on nitrates, the significant increases in left
ventricular ejection fraction and decreases in ventricular premature beats from
baseline from 1.2 grams of berberine daily was also significant better when
plasma berberine concentrations were higher versus lower than 0.11 mg/L (PO in
human clinical study).2639
+ 4)
Berberine at 0.6 grams daily for 3 months increased previously stabilized cyclosporin
A trough blood concentrations by 90% in 52 renal transplant patients,
and when given for 12 days to 6 transplant patients increased the cyclosporine
bioavailability by 35% (PO in human clinical study), likely by inhibition of
CYP 3A4 (speculative)2281 or by increased efflux by inducing
P-glycoprotein (in vitro).1046
+ 5) The combination of 500 mg berberine 3 times
daily for 3 months in 43 patients with poorly-controlled type 2 diabetes
together with one or more of their regular oral hypoglycemic medications
including sulfonylureas in 28, metformin in 20 acarbose in
15, and/or insulin in 10 resulted in lower fasting and postprandial
blood sugar from week 1 through week 12 (PO in human clinical study). Fasting
plasma insulin was also lowered by 28% and an index of insulin resistance by
45% of those on medications, while total cholesterol and LDL were likewise
reduced. In 31 newly diagnosed type 2 diabetics to whom 15 were given the same
dose of berberine and 16 used 500 mg metformin 3 times daily, berberine’s
hypoglycemic effect was similar to that of metformin on fasting and
postprandial blood glucose, as well as reducing glycosylated hemoglobin and
plasma triglycerides (PO in human clinical study). Transient gastrointestinal
adverse effects were experienced by 35% of the patients, or 20 in total.2315
II. 1) The antitumor constituent berbamine (20 mg/kg once daily
for 7 days) significantly enhanced antitumor activity of cyclophosphamide against Walker tumor (IP in rats).398
When the alkaloid component berberine was given once
or twice at doses of 50, 100, or 200 mg/kg before cyclophosphamide injection,
it significantly reduced the chemotherapy adverse effect of bladder hemorrhage
in a dose-dependent manner (IP in rats).2570
2) Berberine administered prior to pentobarbital increased the induced sleeping time (IP in mice)1032
A single 4 mg/kg dose of berberine prolonged pentobarbital sleeping time and increased strychnine toxicity (PO in rats)1215
+ 3) Pre-treatment with 4 mg/kg berberine prevented a rise in
serum levels of liver enzymes from excessive acetaminophen, suggesting
protection from its toxic effects (PO in rats). Use of this dose three times
every six hours following a toxic dose of acetominophen reduced liver damage.1215
III. 3) Berberine increased efflux of rhodamine 123 and paclitaxel by inducing P-glycoprotein and thereby reducing the retention and concentration of these drugs in human hepatoma and digestive tract cancer cells, respectively (in vitro)1045,1046
+ 4)
Studies in human liver-derived cells with berberine was found to have an
additive effect with lovastatin by increasing LDL receptor mRNA
expression (in vitro). This statin did not reduce this effect of
berberine, indicating a different mechanism of action (in vitro). In 63
high-cholesterol subjects taking 1.0 grams berberine HCl daily for 3 months,
serum cholesterol was reduced 18%, LDL cholestreol 20%, and triglycerides 28%,
compared to those using placebo (PO in human study). In the 32 who were taking
no other medication or herbs, cholesterol was reduced 29%, LDL cholesterol 25%,
and triglycerides 35%. HDL cholesterol was unaffected, and berberine was well
tolerated. Berberine was found to have a dose-dependent cholesterol-lowering
effect (in hamsters).1656
+ 5)
Do not combine with phenylbutazone or other drugs that displace protein
binding of bilirubin (speculative),1890 since displacement by
berberine of bilirubin from serum albumen which can lead to kernicterus (IP in
rats).1092
BASIL p.
37
Ocimum basilicum plant
Drug Interactions
III. + 1)
Alkaline aqueous extracts of basil were shown to potentiate insulin
activity in glucose metabolism (in vitro).1464
BEEBALM NEW
^ Monarda spp. plant
(Oswego tea, mountain balm/ wild begamot; horsemint;
spotted beebalm)
Contraindications
1) pregnancy due to the emmenagogue and uterine
stimulant activity (empirical)150
BETH
ROOT NEW
^ Trillium erectum root
(birth root, purple trillium, wakerobin)
Contraindications
1) pregnancy due to emmenagogue activity
(empirical)150
2) stomach or intestinal irritation due to its
irritant properties (empirical)150
BILBERRY p.
38
Vaccinium myrtillus
fruit
Drug
Interactions
II. 1) CORRECTION: anti-ulcer activity demonstrated by its 25%
ANTHOCYANIDIN extract was shown by one of its aglycone components (PO in rats).624
III. 1) Warfarin and antiplatelet drugs may be enhanced at
high doses (speculative).777,1890
CORRECTION: The prostaglandin modulation by the
anthocyanosides enhances antiaggregatory processes (in vitro;1084,1086 EX VIVO AFTER PO in rats,684,1086). A daily dose of 480 mg
of an extract containing anthocyanosides (equivalent to 120 mg daily of
anthocyanidins) led to decreased platelet aggregation after 30 days that
decreased further after 60 days (EX VIVO AFTER PO in humans).1085
On the other hand bilberry anthocyanins tended to
reduce retinal hemorrhage due to anticoagulant therapy (in humans) and the
extract reduced post-surgical bleeding complications (empirical).1316
BIRCH p.
38
Betula pendula =
Betula alba leaves or bark
Drug
Interactions
I. + 1)
Warfarin potentiation was determined with 11 patients who concurrently used
ointment containing methyl salicylate, the primary component of birch bark oil.
All of the patients had unusually high INRs after extensive topical use of the
ointment, based on patient history and salicylate blood levels. One had GI
bleeding, 2 were bruising, and 3 had other bleeding events (topically in human
case reports).1392 Several other cases with the same etiology
resulted in significant bleeding problems requiring plasma infusion or
temporary cessation of warfarin intake in 2 cases. A similar case with simply
an elevated INR of 12.2 occurred after applying a low-dose methyl salicylate
gel to both knees for 8 days (topically in human case reports).714,1393,1394
Another case of local application to arthritic knees for two weeks increased
the INR to 6.1 and resulted in multiple bruising.1426 Still another
warfarin case had bleeding and a doubled prothrombin time after using large
amounts of methyl salicylate over arthritic joints (topical in case reports).1427
The methyl salicylate may affect vitamin K metabolism or displace warfarin from
protein binding sites (speculative).1394
BITTER MELON p.
39
Momordica charantia
fruit and its juice
Contraindications
+ 2) Brittle type
1 diabetes (speculative)893
due to hypoglycemic effects in normal and diabetic animals (PO in rats)746-749
and in healthy and diabetic humans when using the cooked fruit, juice or
extract (PO in human studies)34,35,745
Drug
Interactions
II. + 1)
A combination of 500 mg/kg daily each of bitter melon dried juice and an
Ayurvedic preparation of zinc (Jasad Bhasma) reduced fasting blood sugar and
increased the hypoglycemic effect of 250 and 500 mg/kg tolbutamide (PO
in rabbits)1544
However, in a study with
type 2 diabetics using oral hypoglycemic drugs who were given 2 capsules
of fruit and seed extract 3 times daily, no change in glycosylated hemoglobin
or fasting blood sugar was seen after 3 months when compared to placebo (PO in
human clinical study).2275
BITTER ORANGE p.
40
Citrus aurantium fruit, peel, or juice
(Port.: laranja-amarga, laranja-azeda,
laranja-cavalo; Ch.: zhi shi; Jap.: kijitsu; Kor.: chisil)
Contraindications
+ 4)
Avoid juice in severe high blood pressure, rapid heart rate, and
narrow-angle glaucoma due to its content of the adrenergic synephrine
(speculative).1421 A single 900 mg dose of a dried fruit extract
standardized to 6% synephrine significantly raised systolic and diastolic blood pressures and heart
rate (PO in human study).1867
However, in other tests with
the dried fruit extract standardized to 6% synephrine, a single dose of 450 mg
did not raise blood pressure (PO in human study).1866 Also, 8 oz. did not affect blood
pressure or heart rate in normal subjects (PO in human study)1421
Drug
Interactions
II. + 1)
Essential oil from the peel at 0.5-1.0 gm/kg increased the sleeping time
induced by pentobarbital (PO in mice).1626
+ 2)
In a crossover study 200 ml of decoction of 20 gm of the fruit increased the
maximum concentration of cyclosporine by 64% and resulted in acute
toxicity in 1 of 5 subjects (PO in swine).2028 Enhanced absorption
of cyclosporine may occur due to the inhibition of CYP 3A4, as shown by a 40%
reduction following consumption of 8 oz. of the juice (PO in human study).1031
However, an uncharacterized
bitter orange product lacking the CYP3A4-inducing compound
6,7-dihydroxybergamottin failed to alter bioavailability of 3A4 substrate midazolam
in 12 subjects after 4 weeks (PO in human study).1589
III. + 1) Use of the juice with monoamine
oxidase inhibitors (MAOIs) should be avoided (speculative) due to
its content of the synephrine (speculative), even though 8 oz. did not cause
adrenergic cardiovascular effects in normal subjects (PO in human study)1421
+ 2)
Use of the juice with drug substrates of CYP3A4 may lead to their
enhanced absorption due to the reduction of this isozyme by 40% following
consumption of 8 oz. of the juice (PO in human study).1031
However, an uncharacterized
bitter orange product lacking the CYP 3A4-inducing compound
6,7-dihydroxybergamottin failed to alter bioavailability of 3A4 substrate
midazolam in 12 subjects after 4 weeks (PO in human study).1589
+ 3)
Consumption of the juice with decongestant cold preparations (presumably
containing pseudoephedrine, an alkaloid similar to synephrine in the juice)
should be avoided (speculative).1421
BLACK CHERRY [formerly WILD
CHERRY] p. 198
Ä *Prunus serotina bark
BLACK COHOSH p.
40
*Actaea racemosa = Cimicifuga
racemosa roots/rhizome
Contraindications
1) Avoid in pregnancy during the first trimester2
due to its emmenagogue possible uterine stimulating
effect (speculative).2141
However, only low-level
evidence is available that indicates the need to use it with caution and
rigorous high-quality studies with humans are needed to better determine its
safety in pregnancy.2141
2) Black cohosh
preparations are inappropriate for use with nursing mothers150,777,1890
due to its possible hormonal effects (speculative).2141
However, only low-level
evidence is available that indicates the need to use it with caution and
rigorous high-quality studies with humans are needed to better determine its
safety in lactation.2141
3) estrogen-dependent
tumors including some breast cancer
due to potential estrogenic activity (speculative).777
However, black cohosh and
its ethanolic and isopropenolic extracts were found to significantly reduce
breast cancer risk a case-control study involving 949 breast cancer cases and
1524 controls, whether cancers were of estrogen receptor-postitive or -negative
status (PO in human study).2114 In 61 menopausal women taking 80 mg
daily of black cohosh extract containing 2.4% 23-epi-27-deoxyactein, including
45 who used the extract the full 24 weeks, no significant effect on estrogenic
markers in the serum or on cellular mophology in nipple aspirate fluid was
detected (PO in human clinical study).2494 In addition, animals with transplanted
breast cancer and with their ovaries removed were given either synthetic
estrogen (mestranol) positive control, two different doses of an isopropanolic
extract of black cohosh, or the vehicle negative control daily for 6 weeks.
Only those receiving mestranol had enhanced cancer growth at the end of the
study (PO in rats).1383
Also, the isopropanolic extract inhibited cell proliferation in a human breast adenocarcinoma test system (MCF-7) and inhibited estrogen-induced growth of this system (in vitro).1384 The liquid ethanolic extract failed to induce proliferation of the MCF-7 human breast cancer cell line or transactivation of either human alpha- or beta-receptor (in vitro) or increased uterine weight after 4 days (PO in mice).1664 Both the isopropanolic and ethanolic extracts were shown to dose-dependently inhibit growth and induce apoptosis of both estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB231 breast cancer cells (in vitro). The effective concentrations were lower for the isopropanolic extract.1719 Unlike tamoxifen that stimulates estrogen endometrial adenocarcinoma tumor growth, the isopropanolic extract did not increase this growth or metastasis to lymph nodes or lungs in rats when given alone or combined with tamoxifen (PO in rats).1697 Black cohosh as a 40% 2-propanol extract binds to serotonin receptors of the hypothalamus (in vitro), which, rather than any estrogenic activity, may explain its reduction of hot flashes (speculative).2031 The black cohosh 40% isopropanolic extract at 40 mg per day for 12 weeks was shown to have no effect on estrogen concentrations or luteinizing hormone [LH] pulsatility in postmenopausal women (PO in human clinical study). Nonetheless, with naloxone blockade it did suppress LH pulsatility especially during sleep, and its m-opioid receptor binding ranged from 10-61% across brain regions involved with emotional and cognitive functioning.2495
+ 4)
Signs or symptoms indicative of liver dysfunction such as tiredness,
loss of appetite, yellowing of skin or eyes, dark urine, or severe upper
stomach pain with nausea and vomiting after using black cohosh products are
reasons for its discontinuation and avoidance in these individuals (empirical),
due to its association with nearly 3 dozen hepatotoxicity cases in Europe plus 8 published
case reports.1901
Fulminant liver failure in two women in their 50s
followed use of 500-1000 mg/day of black cohosh root for 5-8 months (PO in
human case reports). Both had high bilirubin, aminotransferases, Alk Phos, and
INR, when other probable causes were screened out.1902,1903 One of
the women drank 2 glasses of wine daily as a probable contributing factor; she
had fatigue, weight loss, and upper right abdominal tenderness. Two weeks after
her exam she developed encephalopathy and died from hemorrhage during
transplantation surgery on day 39. Both autoimmune and drug-induced liver
damage were deemed probable after analysis.1902 The other had
jaundice, dark urine and light stools; 1 week after prednisone treatment for
possible autoimmune hepatitis, her aminotransferase levels improved but INR
increased. She developed encephalopathy from the acute hepatitis and underwent
a successful liver transplantation. Temporal association with long-term black
cohosh use prior to this acute episode was the only evidence implicating it as
a causative factor.1903
A 57 year-old woman taking 6 other medications for
over 2 years used black cohosh tablets of unknown brand or dose for 1 week prior to developing
fatigue and lethargy; she saw a doctor 2 weeks later (PO in human case
report).Her anti-nuclear antibody titer and liver biopsy suggested autoimmune
hepatitis. Symptoms resolved in two weeks after withdrawing black cohosh and
tapering steroids. Liver function tests were normal at nine weeks. After 4 months symptoms and signs
recurred, but steroid treatment had rapid success.1909
However, problems with these
reports include a lack of analytical verification of the product contents, insufficient
exclusion of other potential causes, and an implausible proposed mechanism.1905,1906
An assessment by the European Medicines Agency concluded that, of 42 patients
suspected of severe hepatotoxicity related to black cohosh use, only 16 were
sufficiently documented and in only 4 ot these was the causality possible or
probable.1901 A diagnostic algorithm applied to these 4 patients
that utilized conventional causality assessment factors allowed an objective
analysis of the data to show that 1 patient was not assessable and the other 3
were unrelated to drug use, including black cohosh. In 2 cases the steroid
therapy possibly augmented the hepatotoxicity that was finally established as
herpetic hepatitis, leading to transplantation is both cases and the death of
one.2490 The steroid therapy employed in these cases was effective
only in one that was finally diagnosed as autoimmune hepatitis.1909
In a 12-month study of 22 peri- or postmenopausal women using a 128 mg daily of
a dry extract made with a 75% ethanol solvent and standardized to7.3 mg
triterpene glycosides, no elevation of liver function tests for ALP, ALT, or
AST showed significant elevation compaired to 22 similar women in the placebo
group. (PO in human clinical study).2596
Other cases associated with hepatotoxic effects did
not document such high or prolonged dosage. A 47 year-old woman who used a
black cohosh product for one week developed jaundice and elevated
aminotransferases, but fibrosis from her liver biopsy is indicative of months of
hepatotoxin exposure. She required a liver transplant after two weeks (PO in
human case report). Another hepatotoxicity case with a 43-year-old woman involved use of a
multi-herb preparation (skullcap, valerian, black cohosh, passionflower, dong
quai, hops, oat, chasteberry) with potential adulterants (PO in human case report).1904
Hepatotoxicity associated with black
cohosh fluid extract in a 52-year-old women with jaundice from acute liver
failure showed low serum albumin and high serum bilirubin, Alk Phos, ALT, and
GGT, along with an elevated INR of 3.0. She had taken a mixture of fluid
extracts for 3 months but had ceased their use 4 weeks prior. A week after
examiniation she developed hepatic encephalopathy and herpato-renal failure,
requiring a liver transplantation.1908
However, in the latter case
the 200 ml bottles containing the combination of 1:1 fluid extracts that she
used had 80 ml of ground ivy (Nepeta hederacea) but only 20 ml of black
cohosh.1907 The ground ivy’s pulegone, a well recognized hepatotoxin,
was the most likely cause of liver failure in this case.1908 In a review of the total
69 known distinct hepatotoxicity cases from the European Medicines Agency [36 cases], other
published case reports [11 cases], and others reported in a USP study [22
cases], an updated structured quantitiative scale for causality found that 68
had an excluded, unlikely, unrelated, or unassessable causality for black
cohosh; the only 1 possibly case with causality was complicated by multiple
confounding factors (case series review).2597
Drug Interactions
I. + 1) Use
of 50 mg black cohosh extract daily along with 150 mg of soy extract containing
40% isoflavones (60 mg daily) and 100 mg dong quai extract daily for 24 weeks
by 49 menstrual migraine patients significantly reduced the number of doses of triptans and analgesics after
20-24 weeks compared to placebo (PO in human clinical study)1422
+ 2)
Solid black cohosh extract obtained with 58% ethanol (CR BNO 1055),
corresponding to 20 mg of the root, was given by randomization for one year
with 20 mg tamoxifen in daily oral doses with premenopausal breast
cancer survivors (PO in human clinical study). About 74% of those using only
tamoxifen had severe hot flushes, compared with only 24% of those combining it
with the extract. Nearly half of the tamoxifen plus extract group were free of
hot flushes, the most frequent adverse effect of tamoxifen.1655
Alone, both the hydroethanolic and hydropropanolic extracts of the
rhizome inhibited cell proliferation in a human breast adenocarcinoma test
system (MCF-7) and inhibited estrogen-induced growth of this system (in
vitro).1384,1556 The isopropanolic extract alone significantly
inhibited estrogen-deprived cell growth and with tamoxifen further enhanced
inhibition of the breast adenocarcinoma proliferation (in vitro).1384
Unlike tamoxifen that stimulates estrogen endometrial adenocarcinoma tumor
growth, the isopropanolic extract did not increase this growth or metastasis to
lymph nodes or lungs in rats when given alone or combined with tamoxifen (PO in
rats).1697 Black cohosh as a 40%
2-propanol extract binds to serotonin receptors of the hypothalamus (in
vitro), which, rather than any estrogenic activity, may explain its
reduction of hot flashes (speculative).2031
When tested for estrogen-dependent gene
transcription in two types of estrogen alpha-receptor cells, the isopropanolic
extract was shown to be both non-estrogenic and anti-estrogenic (in vitro).
The ethanolic extract activity differed in terms of active extract
concentration, and in one of the alpha-receptor cell assays the ethanolic
extract, though non-estrogenic, was not anti-estrogenic (in vitro).1556
III.
1) [FORMER: See IV. 1) ]
+ Increased
cytotoxicity of doxorubicin was noted only when EMT6 nonestrogen-dependent
mouse breast cancer cells were exposed to a concentration representing 2.5
times or more of the recommended dose of a commercial 50% ethanolic liquid
extract standardized to 3% triterpene glycosides (in vitro). Two
different commercial hydroalcoholic liquid extracts had similar, though less
potent, cytotoxicity-enhancing effects after exposure to the 3 extracts at 100
times the concentration expected from the recommended black cohosh extract dose
(in vitro). At this high concentration a less potent effect of enhancing
doxetaxel cytoxicity was found with the initial extract, while the same
extract and dose reduced the cytoxicity of cisplatin (in vitro).
No interactive effects were found with 4-hydroperoxy-cyclophosphamide or
radiation even at the high extract dose (in vitro).1736
IV. [formerly III. 1) ] 1) Estrogen
replacement therapy may lead to estrogen excess due to phytoestrogen content of
black cohosh (speculative)893
However, when the 40%
isopropanolic extract given to perimenopausal and postmenopausal women in daily
doses derived from 39 mg or 127.3 mg of the dried root were used to assess
estrogenic activity, the lack of changes in vaginal cells indicated a
nonestrogenic effect. Likewise, no significant changes in serum hormone levels
relevant to sexual function were noted (PO in human study).1558 A
dried 58% aqueous/ethanolic extract in daily doses corresponding to 40 mg of
the rhizome was compared to 0.6 mg of conjugated estrogens and placebo in a study
with 62 menopausal women. The extract was as beneficial as the estrogens for
menopausal symptoms and on serum markers of bone metabolism. While the
estrogens and extract increased vaginal cell growth similarly, only the
estrogens increased uterine endometrial thickness. Black cohosh hydroalcoholic
extract therefore has demonstrated selective estrogen receptor modulator (SERM)
activity for bones and the vagina without affecting the uterus (PO in human
study).1559 Black cohosh contains SERM compounds that primarily
interact with the estrogen beta-receptors and affect hypothalamus, bone, liver,
brain, and arteries, but the components did not interact with estrogen
alpha-receptors of the uterus (in rats).1557 The liquid ethanolic
extract failed to induce proliferation of the MCF-7 human breast cancer cell
line or transactivation of either human alpha- or beta-receptor (in vitro)
or increased uterine weight after 4 days (PO in mice).1664 When
tested for estrogen-dependent gene transcription in two types of estrogen
alpha-receptor cells, the isopropanolic extract was shown to be both
non-estrogenic and anti-estrogenic (in vitro). The ethanolic extract
activity differed in terms of active extract concentration, and in one of the
alpha-receptor cell assays the ethanolic extract, though non-estrogenic, was
not anti-estrogenic (in vitro).1556 Black cohosh as a 40%
2-propanol extract binds to serotonin receptors of the hypothalamus (in
vitro), which, rather than any estrogenic activity, may explain its
reduction of hot flashes (speculative).2031 The black cohosh 40%
isopropanolic extract at 40 mg per day for 12 weeks was shown to have no effect
on estrogen concentrations or luteinizing hormone [LH] pulsatility in
postmenopausal women (PO in human clinical study). Nonetheless, with naloxone
blockade it did suppress LH pulsatility especially during sleep, and its m-opioid receptor binding
ranged from 10-61% across brain regions involved with emotional and cognitive
functioning.2495
BLACK
CUMIN NEW
^ Nigella sativa seed
Drug Interactions
I. 1) Chemical war victims from inhalation of mustard gas
reliant on inhaled and oral salbutamol and corticosteroids
required less of these drugs except for the inhaled corticosteroids after 2
months of taking an aqueous extract of black cumin than controls who did not,
yet the respiratory symptoms/wheezing and pulmonary function of those using the
black cumin extract was still significantly better than controls (PO in human
clinical study).2489
II. 1) Nephrotoxicity from cisplatin was ameliorated by
the main active seed oil component thymoquinone when it was given 5 days before
and after the chemotherapy drug at 4 and 8 mg/kg daily (PO in rats and mice,
respectively). The antitumor activity of cisplatin for Ehrlich ascites
carcinoma was enhance by thymoquinone at 8 mg/kg daily (PO in mice).2615
BLACK
CURRANT NEW
^ Ribes nigrum seed oil
[Due to their content of gamma linolenic acid (GLA),
the oil from black currant seeds is similar in activity to borage seed oil and
evening primrose oil. See EVENING PRIMROSE.]
Drug Interactions
I. 1) Rheumatoid arthritis patients using corticosteroids &/or
NSAIDs added 10.5 gm black currant seed oil containing 2 gm GLA (20
subjects) or placebo soybean oil (14 subjects) for 6 months. Those treated at
the end had significantly improved joint tenderness count and tenderness score
with no adverse effects; 2 cases of nausea occurred in the placebo group. Four
patients in the treatment group and 11 receiving placebo were also maintained
on steady doses of second-line anti-rheumatic drugs, particularly methotrexate,
hydroxychloroquine, or gold salts (PO in human clinical study).1399
2) Faster clinical response to tamoxifen was achieved when gamma linolenic acid as found in black
currant seed oil was given to 38 patients with estrogen-dependent breast cancer
(PO in human clinical study).589
III. 1) Due to a decrease in plasma heparin-neutralizing activity
and platelet aggregation inhibition associated with prostaglandin PGE1
that is formed from metabolism of dihomo-gamma-linolenic acid (PO in human
study),681,693 a component formed from GLA in black currant seed
oil, heparin may be potentiated (speculation)
BLACK
PEPPER p.
41
Piper nigrum
fruit
I. 1) Phenytoin was more rapidly
and more completely absorbed and eliminated more slowly in 5 males when taken
with 20 mg of the component piperine (PO in human study).205
A single 20 mg dose of piperine in 2
groups of 10 men receiving 300 mg or 400 mg daily of phenytoin increased mean
plasma drug concentration and bioavailability (PO in human study).1943
+ 4)
Piperine dose of 20 mg increased serum concentrations of curcumin after
0.25-1.0 hours and increased bioavailability by 2000% (PO in human study).1533
Piperine content of black pepper
ranges from about 5-7%.1586
II. + 5)
Increased anti-nociceptive and anti-inflammatory activity from nimesulide
was achieved when 100 mg was combined with 60 mg piperine from black pepper (PO
in mice). This was apparently due to reduced metabolic breakdown of nimesulide.1821
+ 6)
Decreased absorption and anti-inflammatory effect of diclofenac sodium
was observed when it was combined with trikatu, a 1:1:1 mixture of black pepper, long
pepper and ginger (PO in rabbits and rats).2003 Since the drug was
mixed with the herbs in solution prior to administration, the interaction may
have been chemical in nature, rather than biological (speculative).
+ 7)
Reduced absorption, peak concentration, and bioavailability of isoniazid
resulted for 4 hours when it was given together with 500 mg/kg trikatu, a 1:1:1
mixture of dried fruits of black pepper, long pepper and dried rhizomes of
ginger providing 10 mg/kg of the alkaloid piperine (PO in rabbits). This may be
due to a decrease in gastric emptying time (speculative).2005
+ 8)
Increased absorption and peak concentration of indomethicin after 4
hours was achieved when it was given together with 500 mg/kg trikatu, a 1:1:1
mixture of dried fruits of black pepper, long pepper and dried rhizomes of
ginger (PO in rabbits). The pharmacokinetic effect may have been due to an
increased GI blood flow (speculative), but was not due to change in
indomethicin metabolism.2004
III. + 3) Increased membrane transport of the drugs
digoxin and cyclosporine (in vitro) by piperine inhibition
of P-glycoprotein
may lead to increased bioavailability.1820
+ 4) Reduced metabolism of verapamil by piperine inhibition of CYP3A4 (in vitro) may lead to increased bioavailability.1820 Bisalkaloid components called dipiperamides A, B, and C inhibit CYP3A4 metabolism of nifedipine and act much more potently than piperine (in vitro).1822
BLADDER
KELP p.
43
Nereocystis
luetkeana thallus
Contraindications
+ 4)
large amounts during pregnancy due to potential development of infantile
goiter (empirical)150
BLADDERWRACK p.
43
Fucus vesiculosus
thallus
Drug Interactions
III. 1) Interactions may occur with thyroid replacement medication
like thyroxine or hyperthyroid drugs like carbimazole (speculative) due to its
natural iodine content.1890
2) Do not combine with iodine-containing drugs like amiodarone
or bneziodarone, since there is a greater risk of causing
iodine-induce thyrotoxicosis with these drugs (speculative).1890
BLOODROOT p. 44
*Sanguinaria
canadensis rhizome
Contraindications
+ 3)
hiatal hernia, esophageal varices, stomach ulcer or peptic ulcer
due to aggravation and/or potential hemorrhage from emetic effect if bloodroot
is taken in excessive doses (speculative)150
Drug Interactions
III. + 1) Do not take large doses after recent
consumption of central nervous system stimulants, due to the emetic
action potentially inducing convulsions (speculative).150
+ 2)
Do not take large doses after recent consumption of central nervous system sedatives,
due to the emetic action potentially inducing aspiration pneumonitis
(speculative).150
BLUE COHOSH
*Caulophyllum
thalictroides root
Contraindications
. 1) pregnancy prior
to labor, due to its emmenagogue and abortifacient effects (empirical)2,6,,7,10,74,150
and potential embryotoxic and teratogenic effects
from its extracts and alkaloids (in animals).2,1890
. + 2)
Not to be used by fertile women trying to conceive or nursing mothers
(speculative), due to the potential for teratogenicity in the embryos or
toxicity in the infants, respectively.1890
BLUE FLAG NEW
^ *Iris
versicolor, Iris virginica roots/rhizome
(flag lily, iris liver lily, poison flag, snake
lily, sweet flag, water flag, wild iris; Fr.: fleur-de-lis)
Contraindications
1) pregnancy
(speculative)150 due to its potential toxicity (empirical)2,150
Drug
Interactions
III. 1) Do not take large doses after recent consumption of central
nervous system stimulants, due to the emetic action potentially inducing
convulsions (speculative).150
2)
Do not take large doses after recent consumption of central nervous system sedatives,
due to the emetic action potentially inducing aspiration pneumonitis (speculative).150
BLUE VERVAIN NEW
^ Verbena
hastata
plant
(American vervain, false vervain, Indian hyssop,
purvain, Simpler’s joy, traveler’s joy, vervain, wild hyssop)
Contraindications
1) pregnancy
(speculative)2,150 due to its emmenagogue effect in early pregnancy
(empirical)2
BOLDO p.
45
Peumus boldus leaves
Contraindications
+ 8)
pregnancy or with nursing mothers due to possible toxic effects
in the fetus from boldine (PO in rats) or in infants from the essential oil
components, respectively.1890
+ 9)
Avoid prolonged use (speculative), due to possible toxic effects from
the essential oil components.1890
Drug Interactions
+ 1)
A woman stabilized on warfarin developed an elevated INR after several
weeks of using a capsule of fenugreek before meals and 10 drops of boldo
extract after meals. Her INR returned to the normal range after stopping the
herbal products but became elevated again after resuming their use (PO in human
case study). It may be that warfarin metabolism was reduced or the serum
protein bond of warfarin was modified (speculative).1489
BORAGE p.
46
*Borago officinalis
plant
BORAGE SEED OIL
[Borage seed oil does not contain toxic
pyrrolizidine alkaloids6,150 but has separate effects and interactions
due to its gamma linolenic acid (GLA) content similar to black currant seed oil
and evening primrose oil. See EVENING PRIMROSE.]
Drug Interactions
I. 1) In a 6-month randomized, double-blind,
placebo-controlled (RPCDB) trial with 37 rheumatoid arthritis (RA) patients,
7.2 ml borage seed oil (1.4 gm GLA) or cottonseed oil placebo was given daily
in addition to stable doses of NSAIDs and corticosteroids. Those
receiving GLA had significant reductions in number of tender joints (36%),
tender joint score (45%), swollen joint count (28%), and swollen joint score
(41%). The placebo group was unchanged or grew worse (PO in human clinical
study).1401 In a second RPCDB trial using daily placebo sunflower
seed oil or 2.8 gm GLA derived from borage seed oil, 56 RA patients on stable
amounts of NSAIDs, corticosteroids and second-line anti-rheumatic drugs
received the GLA for the first six months and/or the second six months. After
the first half year, 14 of 22 in the GLA group had at least a 25% improvement
in the four measures, while 4 of 19 using placebo improved this much. When all
received GLA in the second half year, 16 of 21 in the original GLA group had
this degree of response over baseline, while the placebo/GLA group also
improved. Three months after the end of the trial, the GLA group had a smaller
increase in 3 of the 4 measures (PO in human clinical study).1402
III. 1) Due to a decrease in plasma heparin-neutralizing activity
and platelet aggregation inhibition associated with prostaglandin PGE1
that is formed from metabolism of dihomo-gamma-linolenic acid (PO in human
study),681,693 a component formed from GLA in borage seed oil, heparin
may be potentiated (speculation)
BROMELAIN p.
47
Ananas comosus extract
from fruit, stem
Contraindications
1) allergic
hypersensitivity to bromelain (empirical)17
A worker who handled bromelain for 10 years
developed rhinitis and asthma that could be induced by both 0.03 mg of inhaled
bromelain and 190 grams of ingested pineapple (human case report).
Cross-reactivity with bromelain by skin and RAST tests occurred with 5 of 6
workers sensitized to airborne papain, and 2 of the 6 had immediate asthmatic
reactions (human clinical study).1275 Cross-sensitivity shown by
RAST inhibition suggested bromelain, papain, wheat flour, rye flour, grass
pollen and birch pollen possess more or less similar or identical antigenically
active regions (in vitro),1276 corresponding to positive skin
tests to bromelain in 2 of 60 asthmatics and positive RAST tests to bromelain
in 8 of 60 asthmatics not exposed to airborne sources of this protease (in
vitro).1275
2) bile duct obstruction6,17,401,777
due to its choleretic activity as shown with a
single 1.9 gram dose of its 4.5-5:1 strength extract (PO in human study)1270
Drug
Interactions
I. 1) Bromelain at 20 mg/kg increased cerebrospinal fluid
levels of penicillin injected intramuscularly 4 hours later (per
duodenum in rabbits).1111
3) potentiates bleeding with anticoagulants (PO in case report), [CORRECTION]31
probably due to inhibition of platelet aggregation
shown with 30 mg/kg (IV in rats)1110, increased fibrinolytic
activity shown with 25 mg/kg (enterally in rats),1110 and increased
prothrombin time shown with 5 mg/kg (PO in rabbits)1110
However, following doses of
40 mg four times daily for one week the coagulation and bleeding times were not
changed, and the prothrombin time was only slightly increased (PO in human
study).1253
4) increases blister fluid concentration of tetracycline in 18 males (PO in human
study)1112
+ 5)
In a randomized, placebo-controlled, double blind trial following episiotomy
for childbirth, 160 patients required aspirin or aspirin with codeine
or propoxyphene HCl for the pain; half received an additional 2
tablets of bromelain (50,000 RU/tablet) 4 times daily for 3 days, beginning 4
hours after delivery. For the bromelain group the responses were considered
good or excellent in 90%, compared to 44% of these responses for the placebo
group, a highly significant difference. While 75%-78% of each group received
asprin or aspirin/propoxyphene, 14% more in the placebo group received the
aspirin/codeine (PO in human clinical study).1405
However, in treating
osteoarthritis of the knee, a randomized, double-blind controlled trial found
that the 14 patients using bromelain as an adjuvant with conventional and/or
alternative medications had not better outcomes based on symptom scores than 17
who used placebo (PO in human clinical trials). Those who recently or currently
used corticosteroids were excluded from this trial.2152 Also, in a
case of combining with NSAID use for rheumatoid arthritis, a 76-year-old woman
developed ecchymosis on her forearms when she used bromelain with naproxen
(PO in human case report).2126
6) In another placebo-controlled, double-blind study
59 patients were given 2 tablets of bromelain 4 times daily for 2 days prior to
cataract surgery, and for the 5 days following. In addition to local cortisone
for all, those on bromelain and the 52 placebo patients also
received oral aspirin and propoxyphene for pain as needed. On the seventh
postoperative day there was significant reduction of lid edema, conjunctival
hyperemia, and conjunctival edema in the bromelain group compared to placebo.
Operative complications included mild hemorrhage in 13 bromelain patients and 6
placebo patients (PO in human clinical trial).1406
II. + 1)
increased concentration of the antibiotic cefazolin
in bronchial secretions when given at 100 mg/kg (PO in rats)1110
+ 2)
increases blood and urine levels of the antibiotic ethambutol (in rabbits)1112
+ 3)
increases duration of sleeping time when given prior to pentobarbital (IP in mice)1112
III. 1) may enhance cholesterol-lowering
agents (speculative).777
Tablets with 450 mg of a 25-35:1 aqueous extract
reduced total cholesterol, LDL cholesterol, and LDL/HDL ratio (PO in human
clinical study)1271
BUCHU p.
48
*Agathosma betulina
= Barosma betulina leaves
Contraindications
4) nursing mothers (speculative), since the
essential oil may pass through the breast milk to the infant with unforeseen
consequences.1890
BURDOCK p.
50
Arctium lappa
root
Contraindications
1) allergic
hypersensitivity to the root (human case reports).662
Some even suggest avoiding if there is known
hypersensitivity to other Compositae family plants (speculative).1890
Drug Interactions
II. + 1)
Freeze-dried water extract of burdock root at 300 mg/kg decreased SGOT, SGPT,
and malondialdehyde levels caused by liver damage from acetaminophen.
The decrease in glutathione and cytochrome P450 in the liver caused by
acetaminophen was reduced by burdock extract (PO in mice)1404 The freeze-dried decoction of
burdock at 100 mg/kg reduces edema from injected carrageenan (SC in rats) and
decreases liver toxicity of CCl4 at this dose (IP in rats). This
extract has radical scavenging activity (in vitro).1407
BUTCHER’S BROOM NEW
^ Ruscus
aculeatus roots and rhizome
(box holly)
Contraindications
1) broken skin or ulcerated skin, due to
the irritant effect of the saponins (speculative).1890
BUTTERNUT NEW
^ *Juglans
cinerea
bark
(lemon walnut, oil nut, white walnut)
Contraindications
1) pregnancy (speculative) since large doses may
cause a cathartic action150
CAJEPUT NEW
^ Melaleuca
leucodendron = Melaleuca cajeputi leaf oil
(white tea tree, broad-leaved tea tree, paper-barked tea tree, swamp tea tree, white-wood)
Drug
Interactions
I. 1) Component 1,8-cineole (eucalyptol) induces hepatic
microsomal mixed-function oxidase enzyme induction (in rats), resulting in
increased clearance of aminopyrine with
aerosol inhalation of eucalyptol 10 min. daily for 10 days (human study).28
II. 1) Pentobarbital,
zoxazolamine, and amphetamine given
24 hours after an aerosol exposure to 1,8-cineole for 2-10 min/day for 4 days
were effective for a reduced length of time (in rats).28
cALENDULA p.52
Calendula
officinalis flowers
Contraindications
+ 2) allergic hypersensitivity to calendula or
allergies to other members of the Asteraceae family (empirical).1890
CALIFORNIA
POPPY p.52
Eschscholtzia californica
herb
Contraindications
+ 2)
nursing mothers (speculative) without professional advice.1890
CALIFORNIA SPIKENARD NEW
^ Aralia
californica rhizome and roots
Contraindications
1) pregnancy (speculative)150 probably due to its
similarity to the related species and known emmenagogues Aralia nudicaulis
and A.racemosa, known as small spikenard and spikenard, respectively
(empirical)1125
CAMPHOR
BARK p.
53
Cinnamomum camphora = Laurus camphora bark
oil
Contraindications
5) epilepsy (empirical), since its rapid
absorption through the skin and mucus membranes in small doses can result in
CNS overstimulation and seizures (empirical).400
6) during fever (empirical),400 due to
potential CNS toxicity (empirical).2
*Cannabis
sativa leaves and tops
Contraindications
2) Avoid in those with a history of schizophrenia, since
psychotic symptoms may be induced with consumption (empirical).2,627,629
Cannabis use increases the risk of incidence of
psychosic symptoms in the young, stronger effects in those predisposed to
psychosis, and a poor prognosis for those with established psychotic disorder
(human study).1372,1737
3) Heavy, prolonged
use
may cause psychological dependance and physical
withdrawal (human studies)1198 and increased risk of depressive
symptoms including consideration of suicide and experiencing loss of ordinary
pleasure (human study).1229
+ 6) Daily heavy use due to reversible cognitive deficits detectable for at least 7 days after quitting (PO in human study),1197 as well as impairments in memory and attention (human study)1272 and decrements even after 28 days abstinence in neurocognitive performance (human study)1146
Drug
Interactions
I. 2) Vomiting induced by chemotherapy
including cyclophosphamide, doxorubicin, cisplatin, procarbazine,
methotrexate, dacarbazine and streptozocin
was relieved by cannabis in 78% of the patients (inhaled in human clinical
study).1078
One incident of lethal ischemic stroke was
associated with cisplatin-based chemotherapy and cannabis inhalation (human
case report). Ischemic strokes have occurred at least 15 times with cisplatin
use alone and a few times following cannabis inhalation.1346
CARAWAY NEW
^ Carum
carvi seeds
Contraindications
1)
allergic hypersensitivity to similar
plants in carrot (Apiaceae) family (speculative)10
CASCARA SAGRADa p.
53
*Frangula purshiana = Rhamnus purshiana aged bark [NOTE: new
scientific name]
CASSIA [formerly
CASSIA CINNAMON] p.
55
Cinnamomum cassia
= Cinnamomum aromaticum bark [See also Cinnamon.]
1) large doses in pregnancy150,401
due to potential hepatotoxicity of its extremely
high coumarin content (speculative)2231,2248
Drug
Interactions
I. + 1)
In 60 men and women with type 2 diabetes using sulpholylureas such as glibenclamide,
when either 1, 3, or 6 grams of cassia cinnamon or placebos was given daily for
40 days, all three cassia doses reduced fasting glucose along with trigyceride,
LDL cholesterol, and total cholesterol (PO in human clinical study).1592
A 9:1 aqueous extract
at a dose of 336 mg/day for 4 months significantly reduced serum glucose in
type 2 diabetics with poor glycemic control, though 77% were already taking
non-insulin oral hypoglycemics including sulphonylureas, metformin,
glinides, glitazones, and their combinations (PO in human clinical study).1900
One gram daily of cassia powder randomized to type 2 diabetics with blood sugar
poorly controlled by oral hypoglycemics and/or insulin had a significant
reduction in hemoglobin A1C after 90 days compared to controls (PO in human clinical study).2603
However, in a study
involving 25 postmenopausal women with type 2 diabetes, all but 4 of whom were
taking metformin, sulphonylureas and/or thiazolidinediones, 1.5 grams
daily of cassia cinnamon taken for 6 weeks had no effect on fasting blood sugar
or lipids or insulin sensitivity or glucose tolerance (PO in human clinical
study). This disparate result may have been due to use of a different
geographic source of cassia, since the bioactive components have not been
identified to establish an effective profile.2139 Similarly, 60
patients in a randomized, double-blind trial were given 500 mg encapsulated
cassia powder or placebo twice daily for 3 months while ¾ were also taking
metformin and over 1/3 were using thiazoledinedione (PO in human clinical
study). No reduction in fasting glucose, insulin levels or glycosylated
hemoglobin were found.2237
Cassia cinnamon powder given to 7 healthy males at a
dose of 5 grams, either with or 12 hours prior to an oral glucose tolerance
test, resulted in a reduction of total plasma glucose and improved insulin
sensitivity (PO in human study).2567 Taken with a meal, 6 grams of cassia cinnamon
lowered postprandial glucose and slowed gastric emptying in 14 healthy subjects
(PO in human study).2294
However, in 15 healthy
subjects, a single dose of 1 or 3 grams of cassia cinnamon failed to
significantly alter postprandial blood glucose, glucose-dependent
insulinotropic polypeptide or ghrelin response, gastric emptying, or satiety,
though 3 grams did significantly lower changes in glucagon-like peptide 1
response and maximum concentration, the insulin response at 60 minutes, and
total serum insulin for 120 minutes postprandially (PO in human study).2531
III. + 2)
Alkaline aqueous extracts of cassia cinnamon were show to greatly potentiate insulin
activity (in vitro).1464 This is likely due to enhanced
insulin signaling in skeletal muscle as shown with freeze-dried cassia hot
water extract (PO in rats).1762
However, in a
placebo-controlled study with 72 type 1 diabetes adolescents, after consuming a
1-gram dose of cinnamon powder daily for 90 days no differences were found in
total daily insulin intake, number of hypoglycemic episodes, glycated
hemoglobin (A1C), or change in A1C between the cinnamon and placebo groups (PO
in human clinical study). Unfortunately, the authors did not characterize the
type of cinnamon (Cinnamomum spp.) by species name.2108 Giving 3 grams Cassia cinnamon with rice
pudding significantly lowered the insulin response at 60 minutes, and total
serum insulin for 120 minutes postprandially (PO in human study).2531
Cassia bark aqueous extract increased insulin
release from insulin-secreting cells in a dose-dependent manner by 144-182% (in
vitro). The extract and the bark significantly increased plasma insulin in
animals, the bark for 1-2 hours and the extract for 1-4 hours. Cassia cinnamon
bark and extract were more effective than cinnamon (C. zeylanicum)
extract (PO in rats). Only after glucose consumption did the extract reduce
blood glucose (PO in rats).1763 The bark reportedly lowers blood
sugar in normal animals due to cinnamaldehyde effects (PO in animal studies).319 Moreover, water-soluble polyphenol polymers
of A type doubly linked procyanidin oligomers of catechins and/or epicatechins
increased insulin-dependent glucose metabolism 20-fold (in vitro).1659
+ 3)
Essential oil from cassia with its strong antifungal effect against Candida
albicans potentiated amphotericin B by reducing the required
concentration to inhibit candida (in vitro).1856
CAT’S CLAW p. 57
Uncaria tomentosa bark
Contraindications
2) Avoid in pregnancy
(empirical)701,1487,1890 and in women attempting conception
(empirical),1890
due to traditional use as a contraceptive
(empirical)150,1890 and the increased risk of fetal malformation or
damage (PO in mice).1890
Drug
Interactions
I. + 1)
Water soluble extract with 8-10% active carboy alkyl esters but free of
oxindole alkaloids given in 350 mg tablets twice daily enhanced immune response
to 23 valent pneumococcal vaccine by elevating lymphocyte/neutrophil
ratios in blood and reducing decay in 12 serotype antibody titers at 5 months
with no adverse effects (PO in human study)1240
+ 2)
60 mg aqueous-acid extract of root with pentacyclic oxindole alkaloids (14.7
mg/g)used for a year or 28 weeks with 40 rheumatoid arthritis patients on sulfasalazine
or hydroxychloroquine treatment for at least 6 months previously showed
a reduced number of painful and swollen joints compared to baseline. In the
first 24-week (placebo) phase the extract group had fewer painful joints than
the placebo group. The steroid prednisolone was used by 38% of the participants; use of NSAIDs
was also allowed.1321
II. + 1)
Intestinal ulceration by indomethacin
was reduced by aqueous extract of cat’s claw (PO in rats).597
This same concentration of cat’s claw decoction in
drinking water given for 3 days prior to a toxic dose of indomethacin (20
mg/kg) caused a protective effect that greatly reduced the extent of erosion to
the stomach lining (PO in rats). Anti-inflammatory and anti-oxidant effects of
this cat’s claw bark extract were both demonstrated as well (in vitro).1389
The protective effect against indomethacin-induced stomach damage was due to
its suppression of NF-kB activation (PO in rats).1784
+ 2)
Avoid use with antihypertensives, since its rhynchophylline
alkaloids may lower blood pressure further (speculative)1487
III. + 3) Use of preparations standardized to pentacyclic
oxindole alkaloids concurrently with immunosuppressants should be
avoided to prevent antagonistic effects (speculative).1890
CAYENNE p.
57
Drug
Interactions
I. 1) 20 gm of powdered chili (containing 9.56 mg capsaicin, a concentration of 478 ppm) reduced gastric mucosal damage from aspirin (PO in human study).211
At 10-30 mg/kg capsaicin aggravated the damage
caused by aspirin (PO in rats).1120
II. 3) Prevention of ethanol/acid-induced ulcers was shown by giving 3-30 mg/kg of capsaicin (PO in rats).522
Dilute capsaicin at 0.1 mcg/kg protected the stomach
from mucosal damage by ethanol. At 10-30 mg/kg capsaicin aggravated the damage
caused by ethanol (PO in rats).1120
CELANDINE p.
59
*Chelidonium
majus root and plant
Contraindications
+ 9) Idiosyncratic hepatotoxic reaction after using celandine,
since mild to severe acute hepatitis occurred in 10 patients following its
consumption (PO in human case reports).
These cases were independent of dose and commercial preparation (5
different manufacturers of celandine products, including of two herbal
combinations) and had long and variable latent periods (1-9 months). Recovery
was complete 2-6 months after discontinuation of celandine, but hepatitis
recurred in the one patient who re-introduced it after release from the
hospital.1142 These observations implicate celandine involvement in
a case of hepatotoxicity in a patient who used a different herbal combination
containing celandine (PO in human case report).1143
+ 10) nursing mothers,
and only preparations of the leaves may be used, but after first receiving
professional advice due to the potential for causing liver problems
(speculative)1890
+ 11) prolonged use (speculative), due
to its potential toxicity (empirical)1890
Drug Interactions
III. + 1)
Chelerythrine, a major alkaloid component, enhanced the retention of rhodamine
123 in human breast cells by inhibiting its efflux mediated by
P-glycoprotein (in vitro)1034
2) May aggravate hepatotoxic reactions to anesthetics, steroids,
estrogen, or chlorpromazine (speculative), due to its own liver stimulant
and toxic effects (empirical)1890
CELERY p.
60
Apium
graveolens seeds (fruit) or stalks
Contraindications
+ 5)
Not to be used by nursing mothers without professional advice
(speculative).1890
Drug Interactions
I. + 2)
Compared to a basal diet with no vegetables, after eating for 6 days a diet
with the umbelliferous vegetables 110 gm (0.75 cup) frozen carrots, 100 gm (1.25 cup)
fresh grated parsnips, 50 gm (0.5 cup) celery, 5 gm (3 Tbs) parsley and 0.5 gm
(1 tsp) dill daily, 36 subjects had a significantly decreased rate of caffeine
metabolism (PO in human study)1634
+ 3)
Use of celery seed reduced serum concentrations of thyroxine in two
patients (PO in human case reports)1890
CHAMOMILE [formerly CHAMOMILE, GERMAN] p. 61
Matricaria recutita =
Matricaria chamomilla plant or flowers
Contraindications
3) allergic hypersensitivity (human case reports,
human clinical studies)4,663,666
An enema containing an
oily extract of chamomile flowers given during labor resulted in an
anaphylactic response and cesarean delivery with severe asphyxia in the newborn
which died the following day (human case report)1144 In 14 patients
allergic to either chamomile or spices and weeds and with a positive skin-prick
test to chamomile, 10 had a history of immediate-type reaction to chamomile, 11
were sensitized to mugwort and 8 to birch tree pollen based on RAST, while 4
showed IgE binding to high molecular weight chamomile protein allergens (in
vitro).1740 A man developed acute eczema on his forearms and
hands after washing and applying compresses of chamomile and Roman chamomile
tea (topically in human case report). In patch tests he was shown to be
sensitive to both of the teas and their mix, a Roman chamomile extract, yarrow,
tansy, and feverfew extracts, and a sesquiterpene lactone mix. The chamomile
sesquiterpene lactone desacetyl matricarin likely contributed to his reaction.1742
Drug Interactions
I. + 1) Non-heme iron absorption is reduced with consumption of the tea prepared with 3 grams per cup (PO in human study) likely due to its flavonoid content1246
+ 2) From 10-15 drops of a flower extract in 4
oz of water and used as a thorough mouth rinse 3 times daily prevented and/or
effectively treated oral mucositis from systemic chemotherapy in 78
cancer patients treated with L-asparginase, cisplatin, cyclophosphamide,
cytosine arabinoside, daunorubicin, doxorubicin, 5-fluorouracil,
methotrexate, and/or vincristine (TP in human clinical study). It
also prevented oral mucositis in 19 of 20 head and neck cancer patients treated
locally with radiation.2541
Oral ulcers and mucositis from overdose of
methotrexate resolved within 2 weeks following use of 20 ml of a 1:125
chamomile infusion used as a gargle 4 times daily (local in human case report).1803
3) [Formerly IV.1).] One woman on warfarin
had pelvic ecchymoses and increased INR of 7.9 from 3.6 five days earlier,
after drinking several cups daily of chamomile made with a teaspoon of dried
leaves and applying a lotion containing a chamomile preparation (PO in human
case report).1876
However, such a response
could also have occurred if she drank grapefruit juice with here co-medication
amiodarone, though she denied in general any change in her diet in the prior
days.1876
Chamomile has been iden