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3. Hypericum, Drug Interactions, and Liver Effects by Paul Bergner
4. Materia Medica Classics: William Bloyer on Ginger, with commentary
and review
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HYPERICUM, DRUG INTERACTIONS, AND LIVER EFFECTS
by Paul Bergner
Two articles published in the February 14 issue of The Lancet have
identified potentially serious interactions between concentrated extracts
of St Johnswort (Hypericum perforatum) and several drugs used in AIDS and
organ transplant patients. Hypericum apparently increases the activity
of the liver enzymes that metabolize and inactivate the drugs, lowering
effective blood levels. In the case of the AIDS drug indinavir, hypericum
standardized extracts at a dose of 300 mg three times a day lowered blood
levels by 57-82%, rendering it therapeutically ineffective. In two patient
with heart transplants, hypericum extracts in the same dosage reduced
circulating levels of the anti-rejection drug cyclosporin to the point
that both patients began to reject the transplanted heart. Hypericum had
reduced circulating cyclosporin levels to approximately 50-50% of their
pre-hypericum levels within two weeks.
The specific enzyme system whose activity was increased in the test
subjects is the CYP3A, part of the p450 microsomal enzyme system, responsible
for Phase I detoxification in the liver and also present in intestinal
and kidney cells. The CYP3A subfamily is the most abundant group of p450
enzymes in the liver. Many drugs are mainly metabolized by the CYP3A
enzymes, as are many fat soluble hormones, including estrogens and cortisol.
Thus hypericum could have similar actions to those reported with many drugs.
Depending on whether the drugs are metabolized to their active form or
inactive forms by the enzymes, simultaneous consumption of hypericum extracts
may either increased of decrease blood levels. Consequences could range
from innocuous to fatal depending on the nature of the drug and how critical
the drug dose is to the patient’s health. For the two drugs reported in
Lancet present a strong hazard for patient injury because of the critical
nature of the drugs, the widespread promotion of concentrated extracts
of hypericum for depression, and because depression frequently accompanies
AIDS and organ transplantation. The reports should prompt modern
herbalist to use caution in prescribing hypericum for depression in patient
receiving simultaneous pharmaceutical drug prescriptions.
Table
Some drugs metabolized by the CYP3A enzyme system
aldrin, carbamazepine, corticosteroids cyclosporine, erythromycin,
indinavir, lidocaine, lovastatin, methadone, midazolam, nefedipine,
quinidine,
Endogenous hormones metabolized by the CYP3A enzyme system
estradiol, estriol, testosterone, cortisol
More drugs which are most likely to have some interaction with
St Johnswort can be found online at
http://www.dml.georgetown.edu/depts/pharmacology/davetab.html
Herbs in the last column, labeled 3A4,5,7 may be affected by St. Johnswort
which could either increase or decrease their effectiveness.
The reports may also explain some traditional uses of hypericum. Older
texts in European herbalism describe hypericum as a liver herb. Sebastian
Kneipp; My Water Cure, for instance, states: “This medicinal herb has a
particular influence on the liver; its tea is an excellent remedy for it.”
Andrew Chevallier’s contemporary Encyclopedia of Medicinal Plants states
that hypericum is a cholagogue and tonic for the liver and gallbladder.
The liver effects of hypericum are hardly taught today, with the herbs
antidepressant effects taking the spotlight after clinical trials and intensive
marketing of the herb for that reason. Liver effect and antidepressant
effects may in fact be related. In traditional Greek/Arabic medicine, as
well as in traditional Chinese medicine, some forms of depression are considered
as arising from impaired function of the liver, and the same CPY3A system
that hypericum stimulates is responsible for clearing cortisol from the
system. Elevated cortisol, the adrenal stress hormone, is associated with
depression.
The CPY3A system is also responsible for clearing estrogen from the
system, and the recent findings may explain the traditional use of hypericum
for female complaints associated with hyperestrogenism. Finley Ellingwood,
MD classified hypericum as a “sedative especially useful in the diseases
of women” in the 1919 version of his materia medica. More recently, Malcolm
Stuart said of hypericum in his Encyclopedia of Herbs and Herbalism that
“Certainly when taken internally, the herb stimulates both gastric and
bile secretions, and is effective for irregular menstruation.”
Chevallier, Andrew. The Encyclopedia of Medicinal Plants. New York:
DK Publishing, 1996
Ellingwood, Finley. American materia Medica, Therapeutics and Pharmacognosy.
Portland, Oregon: Eclectic Medical Publications, 1983 [Reprint of 1919
original]
Kneipp, Sebastian. My Water Cure. 62nd Edition [translation reprint].
Pomeroy Washington: Health Research, 1972
Piscitelli, SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J. Indinavir
concentrations and St John's wort. Lancet 355(9203)
Ruschitzka F, Meier PJ, Turina M, Lüscher TF, Noll G. Acute heart
transplant rejection due to Saint John's wort Acute heart transplant rejection
due to Saint John's wort. Lancet 355(9203)
Stuart, Malcolm [editor]. The Encyclopedia of Herbs and Herbalism.
New York: Grosset and Dunlap, 1979
GINGER -- ZINGIBER OFFICINALIS
by William E. Bloyer
We continue our reprint of excerpts of the comments on materia medica of Professor William Bloyer of the Eclectic Institute in Cincinnati, in the 1898 volume of the Eclectic Medical Journal.
This remedy is so common that many of our text books do not deign
to mention it; however, it is an excellent remedy and should have a place
beside the capsicum bottle on the shelf of every dispensary.
It is classified as a stimulant, carminative, diaphoretic, errhine,
sialagogue, rubefacient, etc. It is pungent, aromatic - grateful
to the taste. The dose is from five to twenty drops, well diluted.
It is better to give it in hot water, as it is more prompt, and requires
less of it. A saturated tincture is made by covering the fresh root
with full strength alcohol is efficient and cheap. The root should
be fresh - the fresher the greater its power - the old is inert.
Judging others by ourselves, which is said to be righteous judgment,
we believe this remedy is a neglected one. Many times is could be
given with, or in alteration with, other remedies to advantage, when it
is not done. We get into habits of prescribing certain lines of remedies
and relying upon them. If ginger is not within your line, add it
now. It is a stimulant to the digestive tract, and, after all, everything
depends upon digestion and assimilation. This tract is to the body
what the firebox is to the engine - not enough fire and fuel, not enough
steam, not enough food and absorption, not enough blood, or life.
It promotes digestion by stimulation; it removes or prevents flatulence,
thereby relieving or overcoming spasm and colic.
In some cases of fever, where there is a diminished salivary
secretion, together with borborigmus, colicky pains, etc., ginger, though
a stimulant, affords quick relief. (A stimulant is not always contra-indicated
by fever.) The gratefulness and warmth to the mouth reflexly stimulates
salivary secretion and relieves the dryness of the mouth. In such
cases the addition of a little specific sanguinaria or lobelia is wise.
They assist in promoting the secretions and in reducing high temperature,
etc.
In atonic dyspepsia and enfeebled states of the alimentary tract,
with specific nux vomica, ignatia, etc., or with so-called bitter tonics
if you prefer them, ginger is an excellent remedy.
In diarrhoea, in dysentery, in cholera morbus, with nausea and
vomiting, with cold extremities and surface of the body, don’t forget ginger.
In recent cold, due to a checked perspiration, ginger, either the tincture
given in hot water, or the infusion, together with hot water bottles, hot
foot or body baths, promptly relieves. We have seen it given in teaspoonful
doses of the fresh powder, stirred in a teacup of cold water, drank at
once and patient go to bed - get up relieved - cured. Its sudorific
and stimulant action makes ginger a valuable for suddenly suppressed menstruation
due to cold. It can be given freely alone or with other remedies.
Ginger should always be at hand when cramps, colic, diarrhoea,
etc., due to the ingestion of unripe or stale fruits, hot weather, etc.,
prevail. It can be added to other remedies to promote warmth and
to give flavor. It will add to the usefulness and pleasantness of
both bitter tonics and purgatives. It relieves or prevents the griping
of the latter.
Powdered ginger is very active, therefore an essential part of
the old-fashioned but useful spice plaster
Bloyer, W.E., Zingiber. Eclectic Medical Journal. 1896; 56(7): 342-343
Commentary.
Ginger has recently attracted the attention of modern science because
of its potential anti-inflammatory and antiemetic actions. Bloyer describes
these uses above. In the first paragraph, however, Bloyer describes
a therapeutically useful property that will likely never be studied by
scientific medicine – “warming” properties and stimulation of peripheral
circulation.
Stimulation of the circulation was a mainstay of Thompsonian, Physio-medicalist,
and Eclectic herbal medicine in the nineteenth and early twentieth centuries.
This action in various herbs has also been used in traditional medical
systems such as Greek-Arabic, Ayurvedic, and traditional Chinese medicine.
The clinical use of circulatory stimulants requires a system of assessment
that identifies patterns of constitutional or environmentally induced “coldness.”
Cold and/or pale hands, feet, or face, sensation of chilliness, desire
for warm drinks or food, aversion to cold drinks or food, aversion to environmental
cold or wind, desire for extra layers of clothing or bedding, etc. Many
other symptoms may accompany this milieu of poor circulation, such as headache,
muscle aches, poor digestion, or delayed menstruation, and any number of
conditions which originated with or are exacerbated by exposure to cold.
Among the Thompsonian herbalists, cayenne (Capsicum spp.) was the premier
circulatory stimulant, and Samuel Thomson himself was largely responsible
for the initiation of the import of that herb in large quantities from
the West Indies in the early nineteenth century. Thomsonians used
ginger in an identical manner to cayenne, and considered it more appropriate
than cayenne as a stimulant for children, the elderly, and
those overly weakened by disease.
Ginger might be used alone, or more often as an important addition
to a formula in cold individuals. As Bloyer point out, it makes a useful
addition to digestive bitters. It might counteract the “cold” properties
of such bitters in cold individuals. Ginger acts as a digestive stimulant
on its own, probably through increasing circulation to the gastric and
intestinal mucosa, and might even take the place of digestive bitters in
some individuals.
Anti-inflammatory activity
Scientific interest in zingiber was aroused during the 1980s and early
1990s based on traditional herbal usage for arthritis and migraine (Srivastava
and Mustafa, 1989 and 1992; Mustafa and Srivastava, 1990). Authors speculated
that activity was due to inhibition of the enzyme cyclo-oxygenase, with
an action similar to aspirin. Note that Bloyer describes fever-lowering
properties for ginger. Inhibition of cyclo-oxygenase, as well as modification
of other mediators of inflammation has been demonstrated with the use of
ginger or its constituents in animal trials .
(Chang et. al.; Guh et. al.; Mascolo et. al.; Suekawa et. al.).
Blood thinning properties
Other investigators have examined whether ginger has significant blood
thinning properties, which might be predicted from an aspirin-like pharmacology.
In vitro research shows that gingerol, a constituent of ginger, has blood-thinning
properties (Guh et al). Bordia et al found that doses of 4 grams of ginger
powder daily for three months did not alter various measurement of blood
coagulation in humans, while a single dose of 10 grams of the powder reduced
platelet aggregation. Jansen et al, however, found that 15 gram doses of
ginger for two weeks had no anti-thrombotic effect in humans.
Anti-emetic properties
Bloyer also describes anti-emetic properties for ginger. Recent clinical
trials have confirmed this for nausea for a variety of causes including
seasickness (Grontved et all, 1988), motion sickness (Holtmann et al),
post anesthesia nausea (Bone et al; Phillips et al), morning sickness in
pregnancy (Fischer-Rasmussen et al), and chemotherapy (Meyer et al).
Cautions in pregnancy
Bloyers also notes an emmenagogue effect, and the clinical question
arises about the appropriateness of the use of ginger as anti-emetic in
early pregnancy. Some contemporary herbalists forego its use in pregnancy
for this reason (Geller), and reference works on traditional Chinese herbalism
list caution on the use of higher doses (3-9 grams) of dried ginger root
in pregnancy (Bensky and Gamble; Ni). The United States Food and Drug Administration
places doses of ginger at 5 grams or less per day in the “generally regarded
as safe” category. The clinical trial of dried ginger powder in morning
sickness found it to be effective in doses of 250 mg, taken four times
a day in capsules, for a daily dose of 1 gram, significantly below the
traditional Chinese dose. The outcome of that trial, although better than
placebo, was not that good clinically -- about a third of the women thought
the milk sugar placebo was more effective than the ginger. Another method
of delivery, such as a tea, or even stirring the ginger from the capsules
into warm water before drinking, or increasing frequency of the dose, could
improve results. Note that Chinese sources already cited list no contraindication
in pregnancy for fresh ginger root, which is considered in that system
to be less heating and more supeificially-acting than the dried root, while
those sources describe an antiemetic effect for fresh root as well as dry.
In practice, for the treatment of morning sickness, a tea of the fresh
root might be taken by sips as needed to allay nausea might be the safest
method.
References
Bensky, D. and Gamble, A. Chinese Herbal Medicine: Materia Medica. Seattle, Washington: Eastland Press, 1986.
Bone ME, Wilkinson DJ, Young JR, McNeil J, Charlton S. Ginger root--a
new antiemetic. The effect of ginger root on postoperative nausea and vomiting
after major gynaecological surgery. Anaesthesia 1990 Aug;45(8):669-71
Bordia A, Verma SK, Srivastava KC. Effect of ginger (Zingiber officinale
Rosc.) and fenugreek (Trigonella foenumgraecum L.) on blood lipids, blood
sugar and platelet aggregation in patients with coronary artery disease.
Prostaglandins Leukot Essent Fatty Acids 1997 May;56(5):379-84
Chang CP, Chang JY, Wang FY, Chang JG. The effect of Chinese medicinal herb Zingiberis rhizoma extract on cytokine secretion by human peripheral blood mononuclear cells. J Ethnopharmacol 1995 Aug 11;48(1):13-9
Fischer-Rasmussen W, Kjaer SK, Dahl C, Asping U. Ginger treatment of hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol 1991 Jan 4;38(1):19-24
Geller, C.A. Personal Communication. 1992
Grontved A, Brask T, Kambskard J, Hentzer E. Ginger root against seasickness.
A controlled trial on the open sea. Acta Otolaryngol (Stockh) 1988 Jan-Feb;105(1-2):45-9
Guh JH, Ko FN, Jong TT, Teng CM. Antiplatelet effect of gingerol isolated from Zingiber officinale. J Pharm Pharmacol 1995 Apr;47(4):329-32
Holtmann S, Clarke AH, Scherer H, Hohn M. The anti-motion sickness mechanism of ginger. A comparative study with placebo and dimenhydrinate. Acta Otolaryngol (Stockh) 1989 Sep-Oct;108(3-4):168-74
Janssen PL, Meyboom S, van Staveren WA, de Vegt F, Katan MB. Consumption of ginger (Zingiber officinale roscoe) does not affect ex vivo platelet thromboxane production in humans. Eur J Clin Nutr 1996 Nov;50(11):772-4
Mascolo N, Jain R, Jain SC, Capasso F. Ethnopharmacologic investigation of ginger (Zingiber officinale). J Ethnopharmacol 1989 Nov;27(1-2):129-40
Meyer K, Schwartz J, Crater D, Keyes B. Zingiber officinale (ginger) used to prevent 8-Mop associated nausea. Dermatol Nurs 1995 Aug;7(4):242-4
Mustafa T, Srivastava KC. Ginger (Zingiber officinale) in migraine headache. J Ethnopharmacol 1990 Jul;29(3):267-73
Ni, M. Chinese Herbology Made Easy. Los Angeles: College of Tao and Traditional Chinese Healing, 1986
Phillips S, Ruggier R, Hutchinson SE. Zingiber officinale (ginger)--an antiemetic for day case surgery. Anaesthesia 1993 Aug;48(8):715-7
Srivastava KC, Mustafa T. Ginger (Zingiber officinale) and rheumatic disorders. Med Hypotheses 1989 May;29(1):25-8
Srivastava KC, Mustafa T. Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders. Med Hypotheses 1992 Dec;39(4):342-8
Suekawa M, Ishige A, Yuasa K, Sudo K, Aburada M, Hosoya E. Pharmacological
studies on ginger. I. Pharmacological actions of pungent constitutents,
(6)-gingerol and (6)-shogaol. J Pharmacobiodyn 1984 Nov;7(11):836-48