Modern Phytotherapist

Transcription

Volume
2
No
3 1996
Modern Phytotherapist
c MEDIHERB 1996
FOR PROFESSIONAL USE ONLY. NOT FOR PUBLIC DISTRIBUTION
Endangered Herbs - Seeking Out
Alternatives
BY KERRY BONE
The wildcrafted herbs Golden Seal (Hydrastis canadensis),
False Unicorn (Helonias luteum) and Echinacea angustifolia
root, all from the USA, are becoming increasingly more
expensive and difficult to obtain. While Golden Seal and
False Unicorn are nearing endangered status, there is no
solid evidence that this status also applies to Echinacea
angustifolia. In addition, it is fortunate for Echinacea
users that cultivated E. purpurea root is readily available,
and that cultivated E. angustifolia root is becoming
increasingly so. Nonetheless, the price of E. angustifolia will
continue to rise until such time that large quantities are
available from growers.
The purpose of this article is to examine possible alternatives
to the use of Golden Seal and False Unicorn. This makes
economic as well as ecological sense. To date there have been
few serious attempts to cultivate these plants commercially.
No doubt, there may be circumstances when only Golden
Seal or False Unicorn will give the desired clinical benefit.
However, if serious consideration is given to prescribing
alternative herbs, then the use of these rare plants can be
appropriately minimized.
Contents
Endangered Herbs Seeking Out Alternatives
1
Editorial: Herbal Safety
2
Potential Hepatotoxicity
in Patients Receiving Herbal
Medicine in a Clinical Setting
- A Preliminary Report
6
Evening Primrose Oil
20
Integrating Western and
Eastern Herbal Medicine:
A Clinical Perspective
31
continued page 3 ➔
1 Modern Phytotherapist
Case History of Chronic
Lymphocytic Leukaemia
38
Editorial
Editorial
Herbal Safety
More than 100 deaths from liver problems had been
linked to 13 antibiotics and other drugs used
between 1972 and March 1996, the Adverse Drug
Reactions Advisory Committee said yesterday. The
committee said that although some of the 13 drugs
could save lives, doctors should take care in
prescribing them. (our emphasis)
The safety of a medicine can never be considered
in isolation from its efficacy. This is known as
risk-benefit assessment. Such an assessment is
qualitative not quantitative, (in other words, the
division of a number for risk by a number for
efficacy is never actually performed) and hence
always involves some element of subjectivity. For a
drug which is life-saving, a greater safety risk is
acceptable when it is used in that context. This is
the reason dangerous therapeutic drugs are
tolerated by the regulators and perhaps explains
the mild response of the committee quoted in the
newspaper article above.
This understated article is extraordinary in many
respects, including the title. In particular, natural
therapists and phytotherapists may be surprised at
the mild response from the committee over drugs
which are consistently causing loss of life due to
hepatotoxicity. The use of several herbs has been
banned on only the slightest association of
hepatotoxicity eg, Symphytum, Tussilago and
Eupatorium cannabinum.
A major problem in the assessment of many
herbal medicines is the lack of hard data
supporting their efficacy. Hence, in the eyes of the
authorities the benefit is zero, so any risk is
unacceptable. One positive development in this
area is that the Australian government now
accepts well-established traditional use as
evidence for efficacy. This is possibly a first for the
English-speaking world.
When it comes to concerns about safety, why are
herbs treated so differently from drugs? The same
article would have elicited horrified headlines if it
was about herbal medicines. This is a complex
issue which has many aspects. The German
government takes the attitude that herbs, being
natural medicines, must be completely safe.
Hence, even the slightest doubt about safety is
unacceptable. But is it reasonable to expect
absolute safety for medicinal plants?
Nonetheless, the fact remains that in order to
protect the status of herbal medicines,
information about efficacy is required
as well as safety.
brief article appeared on
page 2 of the Brisbane Courier-Mail on
Wednesday, May 15 1996:
T
HE FOLLOWING
Fatal Curatives
Our view is that professional herb users have an
obligation to be well versed in these topics and be
capable of making a case against adverse publicity.
A series of seminars presented by MediHerb has
recently addressed these issues, dealing with the
accumulation of safety and efficacy data on
Editors: Kerry Bone and Nicholas Burgess
Managing Editor: Michelle Morgan
P.O. Box 713, Warwick, Queensland, 4370, Australia.
Telephone: +61 7 4661 0700 Facsimile: +61 7 4661 0788
email: [email protected]
web site: www.mediherb.com.au
Contents copyright © MediHerb Pty Ltd 1996
For professional use only. Not for Public Distribution.
Clinical
professional herb use. This should
provide additional information, allowing a
proactive approach to promoting and defending
herbal medicine to patients, the general public
and legislators.
One stigma in particular which has been attached
to herbal medicines in the scientific literature is
that of hepatotoxicity. This edition contains a
preliminary report on the effect on liver function
of western herbal medicine prescribed in a clinical
setting. To date, no adverse effects attributable to
herbal therapy have been observed, giving further
credence to the commonly held view by
phytotherapists that, used properly, herbal
medicine is safer medicine.
Endangered Herbs - Seeking Out Alternatives…
continued from page 1
Golden Seal
Golden Seal is a slow-growing deciduous perennial
from the Ranunculaceae family which likes a moist,
rich soil and plenty of shade. It is most plentiful in
the Ozarks, the Appalachians and upper and middle
Mississippi and Ohio River Valleys.1 In Canada,
Golden Seal is indigenous to the extreme southwest
peninsula of Ontario.1 It was originally cultivated in
Oregon and Washington at the turn of the century,
and can be found in small patches in the forests of
these two states.1 Although Golden Seal is being
cultivated commercially, its requirements for shade
and a rich soil make it expensive to grow. Moreover,
it is only harvested after 3 to 4 years. Because of
these difficulties, cultivated Golden Seal only
satisfies a small part of the ever-increasing demand
for this herb.
The principle active components in Golden Seal are
isoquinoline alkaloids, mainly 2 to 4% hydrastine
and 3 to 4% berberine.2 Berberine gives Golden Seal
its golden yellow colour.
Many modern uses of Golden Seal relate to its
berberine content. Berberine has the following
pharmacological properties:
• mydriatic,3 increases lachrymal secretion3
• antibacterial,4,5 antifungal,6 antiprotozoal7 - 10
• antidiarrhoeal11,12
• antiarrhythmic,13 cardiotonic14
• cytotoxic15 - 18
• increases bilirubin excretion,19 choleretic3
Berberine has successfully been used in clinical trials
for gastroenteritis,20 diarrhoea caused by Escherichia
coli,21 duodenal ulcer associated with Helicobacter
pylori,22 trachoma (topically),23,24 giardiasis,25,26 hepatic
cirrhosis,27 non-insulin-dependent diabetes28 and
primary or secondary thrombocytopaenia.29 It is also
a useful therapeutic agent in intestinal dysbiosis of
any nature.
Berberine is also found in species of Berberis, eg
Indian Barberry (Berberis aristata) and Barberry
(B. vulgaris). So these species can be successfully
substituted for Golden Seal for any of the above
therapeutic uses. For best clinical results, use a highstrength preparation of Berberis with a known
berberine content, eg 15 mg per mL.
False Unicorn
Like Golden Seal, False Unicorn is a slow-growing
deciduous perennial which can be encountered in
moist woods, bogs and meadows throughout most of
Modern Phytotherapist 3
Clinical
0.4% steroidal saponins. Compare this to 2.0%
found in a Wild Yam (Dioscorea) 1:2 extract and
1.8% in Beth Root (Trillium) 1:2. Either there are
other components in False Unicorn which
substantially contribute to its activity, or the steroidal
saponins in False Unicorn are particularly active.
Perhaps False Unicorn is over-rated?
the eastern USA. However, unlike Golden Seal it is a
member of the Lilaceae (Lily) family and is a hardy
plant, and thrives in a rock garden, sun or shade.1
Despite this, there appear to have been few attempts
to grow False Unicorn Root commercially.
Like many members of the Lily family, False Unicorn
contains steroidal saponins. These have not been
well-defined chemically, although one has been
named chamaelirin which is a glycoside of
diosgenin.1 There have been no recent
phytochemical studies on False Unicorn, so it is
difficult to suggest to substitute from a consideration
of active constituents.
Further to this, I recently developed a method for
measuring (without characterising) the steroidal
saponins in False Unicorn. In a 1:2 extract we found
Substitutes for False Unicorn can be based on its
therapeutic applications. The most notable
substitutes on this basis are Black Cohosh
(Cimicifuga racemosa) and Wild Yam. In addition,
herbs containing steroidal saponins such as Beth
Root and Sarsaparilla could be suitable (Beth Root is
also not abundant in the wild, but is cheaper and
more available than False Unicorn). Some
practitioners might feel that Beth Root is mainly
indicated as an uterine antihaemorrhagic. However,
its steroidal saponin content indicates that Beth Root
could have many similar uses to Wild Yam. Likewise,
it is inadvisable to regard Sarsaparilla just as a "male"
herb. Bulgarian research has shown that a herbal
preparation containing steroidal saponins called
Tribestan works equally well in male and females
to promote fertility.30 (The saponins in Wild Yam
and Beth Root are chemically very close to
those in Tribestan).
Wild Yam and False Unicorn are often prescribed
together. In this case it is worthwhile to try replacing
the False Unicorn with an additional quantity of
Wild Yam.
Black Cohosh might prove to be a valuable substitute
for False Unicorn, especially for the treatment of
problems associated with menopause. It is widely
used in Germany for this problem and
pharmacological studies (in women) have suggested
that it may act by decreasing LH.31 Clinical studies
have also demonstrated a significant benefit (for
example see MediHerb Professional Monitor No. 16).
Clinical
REFERENCES
1
Veninga, L and Zaricor, B R: Goldenseal/Etc, Ruca Publications,
Santa Cruz (1978)
2
British Herbal Medicine Association: British Herbal Compendium,
Volume 1, Dorset (1992)
3
Simeon, S et al: Plantes méd phytothér 23, 202 (1989)
4
Pepljnjak, S and Petricic, J: Pharmazie 47, 307 (1992)
5
Sun, D et al: Antimicrob Agents Chemother 32, 1274 (1988)
6
Mahajan, V M et al: Sabouraudia 20, 79 (1982)
7
Vennerstrom, J L and Klayman D L: J Med Chem 31, 1084 (1988)
8
Ahuja, A et al: Ind J Pub Health 37, 29 (1993)
9
Ghosh, A K et al: Ind J Med Res 78, 407 (1983)
10
Dutta, N K et al: J Ind Med Assoc 50, 349 (1968)
11
Takase, H et al: Nippon Yakurigaku Zasshi 102, 101 (1993)
12
Khin, M U: J Diarrhoeal Dis Res 10, 201 (1992)
13
Hua, Z and Wang, X L: Yao Hseuh Hseuh Pao 29, 576 (1994)
14
Wang, Y X et al: J Cardiovasc Pharmacol 23, 716 (1994)
15
Pasqual, M S et al: Mutation Res 286, 243 (1993)
16
Chi, C W et al: Life Sci 54, 2099 (1994)
17
Kumazawa, Y et al: Int J Immunopharm 6, 587 (1984)
18
Kuo, C L et al: Cancer Letters 93, 193 (1995)
19
Chan, M Y: Compar Med East West 5, 161 (1977)
20
Sharda, D C: J Ind Med Assoc 54, 22 (1970)
21
Rabbani, G H et al: J Infect Dis 155, 979 (1987)
22
Hu, F L: Chung-Hua I Hsueh Tsa Chih 73, 217 253 (1993)
23
Babba, O P et al: Ind J Med Res 76, 83 (182)
24
Mohan, M et al: Ind J Ophthal 30, 69 (1982)
25
Choudhry, V P et al: Ind Pediat 9, 143 (1972)
26
Gupte, S: Am J Dis Child 129, 866 (1975)
27
Watanabe, A et al: Acta Med Okayama 36, 277 (1982)
28
Ni, Y et al: Chin J Integr Med 8, 707 (1988)
29
Purohit, S K et al: Ind J Pub Health 26, 34 (1982)
30
Zarkova, S: Tribestan: Experimental and Clinical Investigations, Chemical
Pharmaceutical Research Institute, Sofia (Undated)
31
Düker, E et al: Planta Medica 57, 420 (1991)
Mr Kerry Bone
B.Sc (Hons), Dip Phyto, MNHAA, MNIMH
Kerry Bone was an experienced research and
industrial chemist before studying herbal
medicine full-time in the UK where he
graduated and joined the National Institute of
Medical Herbalists. He is currently a practising
herbalist, and Technical Manager of MediHerb.
Mr Bone’s technical articles, such as the
MediHerb Professinal Review, are regularly
published in Australia and overseas. His standing
as an expert herbalist was acknowledged by his
appointment to the Traditional Medicines
Evaluation Committee of the Therapeutic
Goods Administration. He has more than
10 years experience in herbal practice.
Clinical
Potential Hepatotoxicity in Patients
Receiving Herbal Medicine in a Clinical
Setting - A Preliminary Report
BY DAVID MCLEOD, KERRY BONE AND MICHELLE MORGAN.
Table of Contents
Introduction
Documented Cases of Suspected Hepatotoxicity of Herbal Remedies
• London Survey
• Germander (Teucrium chamaedrys)
• Chaparral (Larrea tridentata)
• Comfrey (Symphytum officinale) and Pyrrolizidine Alkaloids
• Traditional Chinese Herbal Remedies
• Other Herbal Remedies
Clinical Trial
• Method
• Patient Characteristics Before Treatment
• Patient Exclusions from Statistical Analysis
Results and Discussion
•Comparison of Second Test to Baseline
•Area Under the Curve (AUC) Change from Baseline
•Individual Analysis of Patients with High Serum Values Whilst on Treatment
•Individual Analysis of Patients Excluded from Statistical Analysis with Special Causes
Conclusion
References
Appendix
6
6
7
7
7
8
8
8
9
9
9
10
11
11
11
12
15
16
16
17
Introduction
substitution or contamination of the herbal product,
or an inappropriate dosage regime.
There is a perception amongst the medical
community that herbal medicines are a likely cause
of hepatotoxicity. One recent study advised doctors
to strongly suspect herbal medicines in cases of
unexplained hepatitis.1 This perception probably
began with the discovery that a number of
commonly used herbs contain traces of pyrrolizidine
alkaloids, which are known hepatotoxins. Since then,
cases of herbal hepatotoxicity have been regularly
reported in the scientific literature.
The purpose of this study is to determine the
likelihood that herbal medicines, prescribed in a
clinical setting, might cause liver damage. Our
preliminary report on 84 patients begins with a
review of some of the documented cases of
hepatotoxicity attributed to herbal medicine.
In many cases the association between herbal
treatment and hepatotoxicity is tenuous. In others,
the hepatotoxicity may have resulted from
Documented Cases of
Suspected Hepatotoxicity of
Herbal Remedies
In the following cases, other factors including alcohol,
drugs, hepatitis of viral or autoimmune origin, and
Clinical
previous history of biliary disease were generally ruled
out as the cause of the hepatotoxicity.
London Survey
The National Poisons Unit, London conducted a
survey to investigate the frequency and severity of
adverse effects from exposure to traditional
medicines and food supplements reported to the
Unit from 1983 to 1991.2 Of 5563 cases, a link was
identified between exposure to traditional medicines
or food supplements in 49 cases. Contributing
factors included patients taking larger doses than
those recommended in the belief of an increased
therapeutic effect, poor labelling, deliberate or
accidental contamination with heavy metals and
access of children under 5 years to inappropriate
doses of vitamins.
Adverse effects included thyrotoxicosis from Kelp
tablets, drowsiness from herbal tranquillizers
containing Valerian and Passiflora, and severe
bronchospasm from ingestion of royal jelly.
Four cases of liver toxicity were reported and
believed to be due to long term ingestion
of herbal medicines:
•
•
•
•
A herbal tranquillizer ostensibly containing
Skullcap (Scutellaria lateriflora), Valerian
(Valeriana officinalis), Hops (Humulus lupulus)
and Gentian (Gentiana lutea) caused hepatitis.
A product ostensibly containing Skullcap and
Broom (Cytisus scoparius) caused jaundice.
Babchi seeds (Psoralea corylifolia) and Umarda
tree bark taken to treat vitiligo caused hepatitis.
Chinese herbs used for treatment of eczema
reputedly caused hepatitis on first exposure
(taken for 3 to 5 months) and acute liver failure
leading to death after the second exposure (taken
over 2 to 3 weeks). This herbal mixture contained
Cocculus trilobus, Dictamnus dasycarpus,
Eurysolen gracilis, Glycyrrhiza spp, Lophatherum
spp, Paeonia spp, Potentilla spp and Rehmannia
glutinosa. The herbal mixture did not contain
pyrrolizidine alkaloids or aflatoxins.3
Germander (Teucrium chamaedrys)
Two women developed severe acute hepatocellular
liver injury within 1 to 2 months of treatment with
Germander (Teucrium chamaedrys) for weight loss.
The patients recovered after discontinuing the herbal
preparation. Involuntary rechallenge in one patient
resulted in reappearance of symptoms of liver injury.4
Reports of 26 cases of cytolytic hepatitis and several
additional cases (including one case of fatal
fulminant hepatitis) prompted the French health
authorities to ban all preparations containing
Germander in May, 1992.5
In seven patients who developed hepatitis after
Germander consumption, jaundice disappeared
within 8 weeks of discontinuing the herb and
complete recovery was achieved in 1.5 to 6 months.
In three cases, readministration of Germander
resulted in recurrence of hepatitis.6
A sixty-eight year old woman died from hepatic
failure after consuming Germander tablets for weight
loss. (Three tablets per day containing 150 mg
Germander for 2 weeks, and 6 months later at the
same dosage for 1 to 2 weeks).7
Chaparral (Larrea tridentata)
A thirty-three year old woman developed subacute
hepatic necrosis after several months of ingestion of
Chaparral leaf (Larrea tridentata). Symptoms first
appeared 3 months after she began taking 15 tablets
per day. She reduced the tablets herself to one tablet
per day and her health improved. She increased the
dose and one month later was admitted to
hospital. The Chaparral was discontinued and her
liver recovered.8
A sixty year old woman ingested Chaparral (together
with Garlic powder, Nettle and Chickweed) for 10
months and developed severe hepatitis which
progressed to end-stage liver failure requiring liver
Clinical
transplantation. Three weeks prior to admission into
hospital the patient had increased her intake from 1
to 2 capsules per day to six. Jaundice occurred 2
weeks later. The patient was also taking Diltiazem
which was dismissed as a possible cause based on the
clinical and histologic presentation. It is believed that
the patient developed subclinical hepatotoxicity from
chronic use of Chaparral and when she increased the
dose, acute liver injury was superimposed on chronic
liver disease resulting in fulminant hepatic failure.9, 10
Comfrey (Symphytum officinale) and
Pyrrolizidine Alkaloids
Refer also to the Appendix
Pyrrolizidine alkaloids (PAs) are found in over 300
species of plants, including plants of the genus:
Heliotropium, Crotalaria, Senecio and Symphytum.11
Venocclusive liver disease (characterized by vein
blocking) was extensively observed in Jamaica due to
the consumption of Senecio or Crotalaria spp as a
bush tea. Similar outbreaks of liver disease were also
observed in areas of Africa, South and North
America. In 1975, an outbreak of liver poisoning
occurred in Afghanistan in which 1630 of 7200
inhabitants were affected, due to ingestion of PAs
from Heliotropium spp in contaminated bread.
Similarly, 67 people in India were affected by cereal
contaminated by the seeds of a plant of the
Crotalaria spp. Several cases of venocclusive disease
from ingestion of PAs from herbal teas and Comfrey
leaf have been reported. In one case a woman died
from hepatic venocclusive disease after ingestion over
2 years of small amounts of PAs in Maté
(Ilex paraguariensis).12
Portal hypertension associated with obliteration of
the smaller hepatic veins occurred after ingestion
of a dietary supplement containing Comfrey and
pepsin. 85 mg of PA had been consumed over a six
month period.12
A twenty-three year old man who died of
venocclusive disease is reputed to have consumed
Comfrey (4 to 5 leaves every day for 1 to 2 weeks)
prior to illness.13
Traditional Chinese Herbal Remedies
A fifty-one year old man with psoriasis developed
abnormal liver function tests after consuming a
Chinese herbal preparation over 8 weeks. After
discontinuing the herbs, the liver enzymes returned
to normal.14
Two women suffered acute hepatic illness after
ingestion of a traditional Chinese herbal preparation.
A preparation containing Dictamnus dasycarpus,
Paeonia suffruticosa, Rehmannia glutinosa, Hedyotis
diffusa, Sophora subprostrata, Gentiana scabra, Smilax
glabra and Paris polyphylla had been taken daily for 2
months to treat psoriasis. The mixture was not
contaminated by fungi or heavy metals. The other
patient had been treating her severe eczema for six
months with a mixture containing Dictamnus
dasycarpus, Paeonia suffruticosa, Schisandra chinensis,
Angelica sinensis, Bupleurum chinensis, Phellodendron
chinense, Tribulus terrestris, Schizonepeta tenuifolia
and Saposhnikovia divaricata. Liver function in both
patients returned to normal within several months of
ceasing the herbal mixtures.15
Hepatitis occurred in seven patients who had taken
Jin Bu Huan Anodyne tablets (Lycopodium
serratum). The tablets were analysed and found to
contain the alkaloid l-tetrahydropalmatine and no
contaminants. All patients had taken appropriate
doses of the herbal preparation. Reuse of the tablets
by two patients caused abrupt recurrence of the
hepatitis. Liver function returned to normal some
time after discontinuation of the tablets. There are
other reports of adverse effects associated with
ingestion of these tablets, including further cases of
hepatitis and three children who experienced CNS
and respiratory depression with bradycardia after
unintentional overdosage. Tetrahydropalmatine is
also present in Stephania and Corydalis spp.16
Four patients treated with the herbal medicine
syo-saiko-to (containing Bupleurum spp.) exhibited
acute drug-induced liver injury after one and a half
to three months. All patients showed a rise in
aminotransferases after readministration or
challenge test. Acute liver injury was verified by
histological investigation. Cholestasis was observed
in two patients.17
Other Herbal Remedies
A patient developed serious liver and pulmonary
disease over a six month period while taking three
types of herbal medicines: BFC, Bowel Tonic and
Nervine. Each herbal preparation was taken as 0.5
teaspoon three times a day for 6 days a week. Along
with seven other herbs, Comfrey root (6 parts in 27)
and Skullcap (1 part in 27) were present in the BFC.
After discontinuing the herbs, the patient's condition
improved over six months, with liver function tests
Clinical
and chest X-ray returning to normal
after 4 months.18
A forty-nine year old woman presented with liver
damage (diagnosed by liver function tests and
biopsy) on two separate occasions, 2 years apart,
after taking a herbal preparation containing Kelp,
Motherwort, Skullcap and Mistletoe (Viscum album).
The Mistletoe was the suspected cause
of the hepatitis.19, 20
Four women sustained liver damage after taking
herbal medicines (Kalms, Neurelax) sold in health
food stores for relieving stress. In three of the four
cases the onset of liver damage occurred rapidly after
the herbal medicine was used. These preparations
contain Valerian, Asafoetida (Ferula foetida), Hops
and Gentian. Prior to October 1984, Kalms
contained Skullcap. However, an investigation of
herbal medicines available in the UK discovered
Skullcap available from wholesalers was not a
Scutellaria spp.21 In fact, a species of Teucrium
(T. canadense) is often substituted for Skullcap, and
was probably the cause of hepatotoxicity for
formulations reportedly containing Skullcap, such as
those described in the above three paragraphs.
A twenty-six year old woman developed hepatitis
after ingestion of ten times the recommended dose of
Senna (Cassia spp: 20 g Senna leaf per week initially,
increased with Senna pod extract containing 100 mg
sennoside B). Her liver function tests improved
within a week of discontinuing the herb, and
deteriorated when she took it again 2 months later.
Liver tests returned to normal some time after
discontinuing the laxatives.20, 22
Despite these cases, herbal hepatotoxicity may be a
rare event. It is estimated that 200 tons of Chaparral
have been consumed over the last 20 years in the
USA,23 yet only a few cases of liver damage associated
with Chaparral consumption have been reported.
However, these papers have stimulated the
perception in some quarters that herbal medicines
present a likely risk to the optimum functioning of
the liver. In order to test this hypothesis, we felt that
it would be useful to monitor the liver health of
patients receiving long-term herbal therapy.
Clinical Trial
This clinical trial has been undertaken in order to
assess the possible extent to which herbal medicine
in a clinical setting might contribute to liver toxicity.
This is a preliminary report. The study began two
years ago. Patients from a normal herbal practice
agreed to have liver function tests performed during
the course of their herbal treatment. A liver function
test was performed by the practitioner after the first
consultation and subsequently at about 3-monthly
intervals. Patients who had already been taking
herbal medicines were not included in the trial. To
date eighty-four patients have had at least two tests
performed, some have as many as 5 sets of test
results. Records were made of the orthodox drugs,
herbal medications, nonherbal supplements and
alcohol consumed by these patients. Serum GOT,
GPT and GGT were analysed. Included in the
Appendix is a useful description of Liver Function
tests and their interpretation as an assessment of
hepatotoxicity.
Method
The liver function tests were performed on a
Reflotron blood biochemistry analyser (Boehringer
Mannheim). The practitioner (David McLeod) is
trained and authorised to use the machine. Prior
to the commencement of the trial the Reflotron
was professionally serviced and indicated a good
calibration.
New reagent strips were used and quality control
tests were randomly performed throughout the trial.
Lithium heparin-coated glass capillary tubes that
measure a calibrated volume were filled with
patient's blood. The blood sample is then placed on
the reagent test strip and inserted into the machine.
The Reflotron warms the blood to a predetermined
temperature and measures the amount of liver
enzyme in the blood. A measurement of liver enzyme
is reported in units of U/L.
Patient Characteristics Before
Treatment
Of the eighty-four patients participating in the trial
so far, sixty (71%) are women and twenty-four
(29%) are men. The median age of participants was
30 to 40 years (range: 19 to 85 years). Four patients
(5%) were defined as heavy smokers (20 or more
cigarettes per day), the other 80 patients (95%) were
non-smokers or ex-smokers. Refer to Appendix for
discussion of smoking and effect on Liver Function
tests. In general the patients' diets were satisfactory
(all food groups were represented and some fruit and
vegetables consumed).
Clinical
Patients presented with a variety
of disorders including:
•
female reproductive tract disorders
(endometriosis, infertility, dysmenorrhoea, PMT,
menopausal symptoms, ovarian cysts, fibroids).
• nervous system disorders (anxiety, depression,
obsessive compulsive disorder, manic
depression, stress).
• gastrointestinal disorders (poor digestion,
abdominal pain, constipation, gastritis, Crohn's
disease, irritable bowel syndrome, diverticulitis,
Gilbert's syndrome, polyp on gallbladder,
jaundice, sclerosing cholangitis).
• immune system disorders (chronic viral and
bacterial infections, depleted immunity, chronic
fatigue syndrome, chronic glandular fever, cancer,
lymphoblastic leukaemia).
• inflammatory conditions (arthritis,
osteoarthritis, rheumatoid arthritis).
• respiratory tract disorders (hayfever, sinusitis,
asthma, bronchitis).
• skin disorders (eczema, acne, psoriasis,
skin allergies).
• cardiovascular disorders
(hypertension, tachycardia).
• miscellaneous: exhaustion, headaches, migraine,
growth on thyroid, hyperthyroidism,
hypothyroidism, leg discomfort, obesity,
Hashimoto's disease, sarcoidosis.
The range of herbs prescribed was broad, as would
be expected given the variety of disorders and the
large group of individuals:
•
•
•
•
•
•
•
•
immune stimulants and suppressants: Echinacea,
Picrorrhiza, Tylophora, Hemidesmus, Stephania,
Astragalus, Pau d'Arco, Cat's Claw.
mucous membrane trophorestoratives and
demulcents: Golden Seal, Licorice.
hepatic trophorestoratives and protectives: St
Mary's Thistle, Schisandra, Bupleurum, Globe
Artichoke.
bitters and aromatics: Gentian, Cinnamon,
Peppermint, Agrimony, Angelica.
laxatives: Butternut, Cascara sagrada, Fringe Tree.
specifics for the digestive system: Coleus, Greater
Celandine, Malabar Tamarind.
demulcents: Chickweed, Slippery Elm,
Marshmallow.
reproductive tract herbs: Dong Quai, Shepherd's
Purse, Black Cohosh, Blue Cohosh, Wild Yam,
Black Haw, Pulsatilla, Chaste Tree, False Unicorn
Root, Wild Yam, Squaw Vine, Saw Palmetto,
Damiana, Sage, Paeonia.
• nervous system tonics and adaptogens: St John's
Wort, Withania, Siberian Ginseng, Korean
Ginseng (Panax), Rehmannia.
• nervines: Valerian, Skullcap, Betony, Lavender,
Zizyphus, Kava, Polygonum.
• antimicrobial: Garlic, Barberry, Propolis (which
is not technically a herb).
• anti-inflammatory and anti-allergic herbs:
Devil's Claw, White Poplar, Guaiacum, Willow
Bark, Feverfew, Chamomile, Fenugreek, Celery
Seed, Baical Skullcap, Albizzia.
• urinary tract herbs: Horsetail, Dandelion leaf.
• respiratory tract herbs: White Horehound,
Elecampane, Mullein, Baptisia, Grindelia,
Pleurisy Root, Poke Root, Eyebright,
Horseradish, Adhatoda.
• cardiovascular system herbs: Hawthorn, Dan
Shen, Mistletoe, Thuja, Ginkgo, Sweet Clover.
• circulatory stimulants: Ginger, Prickly Ash.
• diaphoretics: Yarrow, Elder, Boneset.
• lymphatics and endocrine system herbs:
Calendula, Bugleweed, Bladderwrack, Gymnema.
• depuratives: Nettle, Burdock, Blue Flag, Yellow
Dock, Figwort, Sarsaparilla, Oregon Grape,
Clivers, Red Clover.
• miscellaneous: Pinellia, Atractylodes, Gotu Kola,
Codonopsis, Lomatium.
Herbs cited in the above literature as demonstrating
suspected hepatotoxicity such as Valerian, Skullcap,
Mistletoe, Stephania and Corydalis were prescribed
to patients in this trial. Due to legal constraints or
practitioner choice Comfrey, Coltsfoot, Germander
and Chaparral were not used.
Patient Exclusions from Statistical
Analysis
Of the eighty-four patients included in this trial,
three patients can be validly excluded from the
statistical analysis because of confounding factors:
one patient (male) has sclerosing cholangitis and
Crohn's disease, two patients (one female, one male)
have been taking methotrexate as chemotherapy for
lymphoblastic leukaemia and for rheumatoid
arthritis, respectively. Refer to Appendix and Table 5.
The following statistical analysis was conducted on
the results of liver function tests for the remaining
eighty-one patients.
Clinical
Serum Test
Normal Range (U/L)
GGT (Female)
7 to 32
11.6
5.0
23.9
GGT (Male)
11 to 50
23.0
6.8
82.0
-
14.7
5.0
82.0
GOT
< 40
23.5
3.2
43.0
GPT
< 40
20.5
9.5
68.0
GGT (All)
Average (U/L)
Minimum (U/L)
Maximum (U/L)
Table 1: Liver Function Baseline.
Results and Discussion
The average value of each serum enzyme for patients
before herbal treatment is provided in Table 1,
together with the minimum and maximum values.
The normal range indicates serum values which are
considered normal for a healthy individual.
Comparison of Second Test to
Baseline
The serum values obtained before treatment
were used as a baseline for comparison with
subsequent tests.
•
•
•
•
The mean difference from the baseline indicates
the average difference between the second test
and the baseline.
A positive change from baseline indicates an
increase in the serum value.
The data appeared to be normally distributed,
hence a one-sample t-test was conducted.
A 95% confidence interval was chosen. This
means that there is a 95% chance that the true
population mean change from baseline falls
within the required range of a sample mean.
More exactly, in a statistical sense, this confidence
interval means that if a series of identical studies
Serum Test
were carried out repeatedly on different samples
from the same population, then, in the long run,
95% of these confidence intervals would include
the population difference between means.24
• A t-test enables us to conclude whether there
is a significant difference between the means of
the tests and the baseline (indicated by the twosided p-value).
Results for comparison of the second test to baseline
are summarised in Table 2. Small increases in serum
GGT for female patients, GOT and GPT were
observed on average, however these changes were not
statistically significant, as indicated by the p-values.
(p<0.05 (significant), p<0.01 (highly significant)).
Area Under the Curve (AUC)
Change from Baseline
The AUC change from baseline allows all available
data on each subject to be utilized. In other words
third, fourth and even fifth tests where available, can
be included in the statistical analysis. In this case the
period between each test was used in the calculation
to take the time frame of the tests into consideration.
The results in Table 3 indicate that over the
treatment period patients receiving herbal treatment
showed minor, but not statistically significant,
increases in serum liver enzymes.
Normal
Baseline
Mean difference
95% Confidence Significance
Range (U/L) Average (U/L) from baseline (U/L) Interval
(p-value)
GGT (Female)
7 to 32
11.6
0.2
- 0.7 to 1.1
0.71
GGT (Male)
11 to 50
23.0
-2.4
- 6.4 to - 0.6
0.24
-
14.7
-0.5
- 1.8 to 0.8
0.40
GOT
< 40
23.5
1.2
- 0.4 to 2.8
0.16
GPT
< 40
20.5
1.2
- 0.9 to 3.3
0.27
GGT (All)
Table 2: Liver Function Baseline compared to Second Test.
Clinical
Serum Test
Normal
Baseline
Mean difference
95% Confidence Significance
Range (U/L) Average (U/L) from baseline (U/L) Interval
(p-value)
GGT (Female)
7 to 32
11.6
0.2
- 0.3 to 0.8
0.43
GGT (Male)
11 to 50
23.0
0.7
- 2.9 to 4.3
0.71
-
14.7
0.3
- 0.7 to 1.3
0.51
GOT
< 40
23.5
0.6
- 0.5 to 1.7
0.26
GPT
< 40
20.5
0.8
- 0.5 to 1.8
0.23
GGT (All)
Table 3: Liver Function AUC (baseline compared to all tests).
Individual Analysis of Patients
with High Serum Values Whilst
on Treatment
A high serum value is defined as a value above the
normal range. Consistent elevations in one or more
of the enzymes consistently over the time of herbal
treatment would indicate a potential hepatotoxic
reaction. Hence all patients with serum enzyme
values above the normal range are considered more
closely below.
Patients with high serum values are indicated in
Table 4. Individual serum enzymes marked with an
asterisk (*) contain high values (ie. serum values
higher than the normal range (U/L): GGT (female):
7 to 32; GGT (male): 11 to 50; GOT: <40; GPT: <40).
The full set of serum enzyme results are included for
completeness. Patients who started with a value out
of the normal range which then decreased over the
course of treatment are not included in this
particular analysis.
Individual histories for these patients are indicated
below. Refer to Appendix for brief explanation of
nutritional supplements. The herbs listed were used at
some stage throughout the treatment period.
Standard dosage of herbs is defined here as 5 to 7 mL
three times per day.
Patient 4: This male patient presented in a rundown
condition with a chronic cough (and would
occasionally vomit with excess phlegm). The patient
received the following herbs in standard dosage over
13 months: Echinacea, Golden Seal, Withania,
Elecampane, Eyebright, Licorice, Baical Skullcap,
Bupleurum, Astragalus, Siberian Ginseng and
Bilberry. The patient was also taking C.S.T. and
Kellamin supplements and no other medication. The
patient does not smoke, however his alcohol
consumption ranged from nothing to excessive binge
drinking. Excessive alcohol had been consumed 10
days prior to the second liver function test. The
patient's elevation in serum enzyme levels was most
likely caused by alcohol consumption, especially
since the serum levels of GGT and GPT were
consistently high, including the baseline values.
Patient 10: This male patient presented with
infertility (a low sperm count) and a chronic cough.
The patient received the following herbs in standard
dosage over 6 to 7 months: Echinacea, Picrorrhiza,
Elecampane, St Mary's Thistle, Licorice, Astragalus,
White Horehound and St John's Wort. He was also
taking zinc and vitamin C powder and no other
medication. This patient is a heavy smoker
consuming about 35 cigarettes, including cigars, per
day. The patient's alcohol consumption consisted of
up to 6 to 8 rums and 2 large beers daily. His
elevation in serum enzyme levels was most likely
caused by alcohol consumption, especially since the
baseline readings for GGT and GPT were high. The
smoking may also have contributed to the elevations.
Patient 11: This female patient presented with
infertility, endometriosis and was recovering from
Ross River virus and periods of depression. The
patient received the following herbs in standard
dosage over 12 months: Echinacea, Picrorrhiza,
Licorice, Withania, Astragalus, St John's Wort, Poke
Root, Blue Cohosh, Golden Seal, Ginger, Peppermint,
Chaste Tree, Burdock and Siberian Ginseng. The
patient was also taking Evening Primrose Oil, a
multivitamin and vitamin C. Other medication
included the antidepressant Prozac (fluoxetine). The
patient does not smoke and her alcohol consumption
was low. Some adverse reactions have been observed
with the use of Prozac, usually rash or allergic
reactions. Clinical findings reported in association
with rash include mild transaminase elevation with
other symptoms. Prozac should be avoided in those
Clinical
Patient No.
4 (male)
10 (male)
11 (female)
16 (female)
36 (female)
40 (male)
44 (female)
61 (male)
62 (male)
74 (female)
76 (female)
Serum enzyme Baseline
GGT*
GOT
GPT*
GGT*
GOT
GPT*
GGT
GOT
GPT*
GGT
GOT*
GPT
GGT
GOT
GPT*
GGT*
GOT*
GPT*
GGT
GOT
GPT*
GGT*
GOT
GPT*
GGT
GOT
GPT*
GGT*
GOT
GPT*
GGT
GOT
GPT*
Second test
Third test
58.2
32.4
44.4
49.6
21.7
33.1
13.4
29.3
43.7
11.4
43
39.4
15.3
29.4
35.3
28.9
29.8
31.8
13
25.5
30.8
51.3
30.9
35.6
26.8
29.5
51.9
33.7
26.1
46.5
15.7
39.3
41.4
52
24.3
39.5
75.2
32.6
33.8
13.5
31.8
46.5
10.2
33.9
22.6
14.8
37.7
42.9
23.9
27.5
28.3
11
24
17
61.2
39
75.9
47.5
23.5
46.5
82
34.3
47
20.5
29.4
25.9
10.7
21.8
15.8
7.5
21.2
12.9
44.2
35.7
24.1
12.3
25.8
26.8
60.1
42.7
68
18.5
25.3
25.9
23.9
22.8
32.9
6.8
24.3
12.9
27.4
20
19.5
8.4
25.8
17.3
Fourth test
Fifth test
45.1
28.1
41
11.1
31.2
22.9
145
33.8
48.8
27.4
39.9
69.5
140
44.7
57.9
13
36.5
35.6
25.5
25.2
33.3
Table 4: Liver Function test results for patients in the analysis outside of the normal range with
subsequent levels high or fluctuating.
with hepatic impairment.25 Only one of the
transaminase enzymes was elevated. This may
represent a mild elevation in a liver enzyme due to
herbal treatment. Further tests over time might
reveal whether this is a significant response.
menopausal symptoms, occasional tachycardia and
anxiety. She received the following herbs in standard
dosage over 12 months: Echinacea, Picrorrhiza,
Withania, St John's Wort, Poke Root, Black Cohosh,
Chaste Tree, False Unicorn Root, Hawthorn, Valerian,
Kava, Elder, Calendula and Yarrow. The patient was
also taking Evening Primrose Oil, Cardian and S.A.D.
The patient was also receiving Hormone
Replacement Therapy (HRT), oestrogen and
progesterone which she discontinued after the first
visit and did not restart. The patient does not smoke
and her alcohol consumption was low. GOT
increased in the first test after treatment and then
Clinical
dropped and stabilized within normal range. GPT
followed a similar pattern. Liver function tests may
be affected by oestrogenic compounds, such as oral
contraceptives and those administered in HRT,25
although there is suggestion of the need for
reconsideration of the listed contraindications
depending on the specific compound used in HRT.26
This may have been an isolated idiosyncratic
reaction. The patient is clearly now stable on her
herbal treatment.
obsessive compulsive disorder, depression and had
undergone a hysterectomy some 15 years earlier. The
patient received the following herbs in standard
dosage over 7 months: Withania, St John's Wort,
Kava, Zizyphus, Sage, Lavender and Schisandra. The
patient was also taking Inkephalon and no other
medication. The patient does not drink alcohol or
smoke. GOT and GPT levels were elevated after
herbal treatment began, with GOT elevated out of
the normal range. This may represent a mild
elevation in liver enzymes due to herbal treatment.
Patient 40: This male patient suffered from
sarcoidosis (which was diagnosed subsequent to the
first consultation), mild hypertension and a history
of sinusitis. The patient received the following herbs
in standard dosage over 18 months: Echinacea,
Picrorrhiza, Licorice, Golden Seal, Gotu Kola, White
Horehound, Angelica, Hemidesmus, Elecampane,
Adhatoda, Grindelia, Dan Shen, Horsetail, Pau
d'Arco, Schisandra and St Mary's Thistle. (St Mary's
Thistle alcoholic extract was replaced with silymarin
tablets after a baseline liver function test was
obtained). The patient was also taking vitamin C,
magnesium, coenzyme Q and LM1 tablets at various
stages throughout treatment. Other medication
included Tenormin (a beta-adrenergic blocker),
which was later changed to Norvasc (calcium
channel blocker) and Prinivil (antihypertensive). The
patient does not smoke. The patient's alcohol
consumption was low, only having an occasional
drink which ceased after commencement of herbal
treatment. Calcium channel blockers can cause
transient elevations in serum GOT and GPT.27 The
elevation in serum enzyme values may have been due
to the disease process: sarcoidosis. Refer to Sarcoidosis
in the Appendix.
sinusitis, menopausal symptoms (in particular hot
flushes) and was taking antibiotics every two
months. The patient received the following herbs in
standard dosage over 15 months: Echinacea,
Picrorrhiza, Black Cohosh, Golden Seal, False
Unicorn Root, Sage, Hawthorn, Zizyphus, Eyebright,
Baical Skullcap, Angelica, Prickly Ash, Elecampane,
Calendula and Elder. The patient was also taking
C.S.T. and no other medication. The patient was on a
special, healthy diet, does not smoke and her alcohol
consumption was low. GPT rose out of normal range
at the fourth test and decreased again by the fifth
test. This trend was also observed in GGT and GOT
although not rising above the normal range. This
may have been an isolated idiosyncratic reaction.
diverticulitis, bowel haemorrhage, abdominal
bloating and pain. The patient received the following
herbs in standard dosage over 12 months: Licorice,
Slippery Elm, Cramp Bark, Agrimony, Barberry,
Peppermint, Ginger, Skullcap, Valerian, Devil's Claw,
Siberian Ginseng and Yarrow. The patient was also
taking Azeopangen, Bifidus (culture), vitamins and
no other medication. The patient does not smoke,
however his alcohol consumption was described as
moderate (spirits) with occasional binge drinking,
and a history of heavy drinking. The baseline liver
function test was taken not long after Christmas and
may have been affected by holiday drinking. This
patient's serum enzyme levels were raised at baseline
and are likely to be caused by the history and extent
of alcohol consumption.
Patient 62: This male patient presented with a
history of repeated colds and influenza. The patient
12 months: Licorice, Echinacea, Astragalus,
Calendula, Elecampane, Siberian Ginseng,
Schisandra and Angelica. The patient was also taking
a multivitamin and vitamin C and no other
medication. The patient does not smoke and his
alcohol consumption was low. The patient had
received the first hepatitis B vaccination prior to the
baseline liver function test which was abnormally
high. GPT was raised after herbal treatment but was
only slighly higher than the baseline value. This
result was not observed in the other enzymes and
further tests may be required to arrive at a
conclusion. There is evidence to suggest that GOT
and GPT values remain in the normal range after
vaccination against hepatitis A and B.28-33
chronic fatigue syndrome and premenstrual
syndrome with a history that included Ross River
virus, glandular fever, emotional stress and a
Clinical
Patient No.
45 (male)
51 (female)
77 (male)
Serum enzyme
GGT*
GOT*
GPT*
GGT
GOT*
GPT*
GGT
GOT*
GPT*
Baseline
557
59.8
69.9
15.3
23.8
36.6
17.5
22
30.0
Second test
817
96.5
145
10.7
34.9
51.7
20.5
63.8
148
Third test
Fourth test
15.5
21.4
32.6
11.4
40.7
99.2
Tables 5: Liver Function test results for patients excluded from the analysis due to special causes.
suspected nervous breakdown. Since that time the
patient had given birth, she felt her health had
improved and had gained weight. Her blood pressure
reading was 90/60. The patient received the following
herbs in standard dosage over 9 months: Echinacea,
Angelica, Korean Ginseng (Panax), Siberian Ginseng,
Lomatium, Calendula, Licorice, Malabar Tamarind,
Peppermint, Ginger and Valerian (Mexican). The
patient was also taking magnesium, vitamins,
evening primrose oil and Kellamin. Other
medication included the contraceptive pill. The
patient does not drink alcohol or smoke. GGT and
GPT values were raised in the second test but
stabilized in the third and fourth to within the
normal range. Lomatium was excluded from the
herbal formula after the second liver function test
but reintroduced after the third test. The
contraceptive pill is metabolized in the liver and may
have exerted an effect. Some combined oral
contraceptive agents may cause elevation in GOT
and GPT.25 Alternatively, this may have been an
isolated idiosyncratic reaction.
chronic sinusitis, hayfever, multiple allergies,
occasional psoriasis and lymph gland enlargement
and had received desensitization injections. The
patient had undergone a hysterectomy two to three
years prior, due to severe endometriosis. The patient
6 months: Echinacea, Licorice, Ginger, Golden Seal,
Eyebright, Bayberry, Schisandra, Fenugreek and
Skullcap. The patient was also taking vitamins A, B,
C, E and C.S.T., Garlic, and Evening Primrose Oil.
Other medication included HRT and an
antihistamine. The patient does not smoke and her
alcohol consumption was low. GGT and GPT values
were raised in the second test, with GPT out of
normal range, but stabilized in the third test. Liver
function tests may be affected by oestrogenic
compounds, similar to oral contraceptives and those
administered in HRT.25 Alternatively, this may have
been an isolated idiosyncratic reaction.
Individual Analysis of Patients
Excluded from Statistical Analysis
with Special Causes
Individual histories and characteristics of the three
patients that were validly excluded from the
statistical analysis are outlined below. Refer to Table 5
for the Liver Function test results for these patients.
Patient 45: This male patient presented with Crohn's
disease, asthma, depression and sclerosing
cholangitis. The patient received the following herbs
in standard dosage over 4 to 5 months: Licorice,
Schisandra, St Mary's Thistle, St John's Wort,
Withania, Chamomile, Siberian Ginseng, Ginger,
Korean Ginseng (Panax), Astragalus and Slippery
Elm. (St Mary's Thistle was administered as
silymarin tablets). Other medication included
Prozac, Pulmacort, Bricanyl, Augmentin and
Dipentum. The patient does not smoke and his
alcohol consumption was low. As indicated above,
the elevation in serum enzymes was likely to be
caused by the disease process: sclerosing cholangitis.
Note that serum levels were already significantly
elevated at the baseline.
Patient 51: This female patient presented with acute
lymphoblastic leukaemia. The patient received the
following herbs in standard dosage and a second
formula at 12 mL twice daily over 12 months:
Licorice, St Mary's Thistle, Withania, Siberian
Ginseng, Ginkgo, Astragalus, Echinacea, Picrorrhiza,
Clinical
Codonopsis, Clivers, Bupleurum, Rehmannia,
Pau d'Arco, Cat's Claw and Slippery Elm. (St Mary's
Thistle was administered as silymarin tablets).
The patient was also taking vitamins A, B, C, E;
Azeopangen, beetroot powder and a mild laxative
formula. Other medication included cortisone,
antibiotics, methotrexate (chemotherapy began just
after the baseline reading was taken), asparaginase,
vincristine, norethisterone, dexamethasone,
mercaptopurine (began treatment prior to the fourth
test) and Zantac (for nausea). The patient had a
small stroke after the first days of radiation around
the time of the third test. The patient does not drink
alcohol or smoke. As indicated above, the elevation
in serum enzymes was probably caused by the
chemotherapy (methotrexate and possibly other
drugs). In particular, elevation of GOT and GPT but
not GGT is characteristic of methotrexate
hepatotoxicity.25 The patient's doctor stopped the
methotrexate treatment 5 months after the time of
the last liver function test, but the patient has since
restarted the methotrexate due to a relapse.
rheumatoid arthritis in which all joints were affected
and had hip replacements; was exhausted, depressed,
had poor libido, was suffering from gastric reflux and
had undergone a cholecystectomy earlier. The patient
3 to 4 months: Licorice (high glycyrrhizin), Devil's
Claw, Siberian Ginseng, Stephania, Murraya,
Hawthorn and Picrorrhiza. The patient was also
taking calcium, glucosamine, eicosapentaenoic acid
and docosahexaenoic acid (omega-3 series essential
fatty acids). Other medication included Aropax,
Indocid, prednisone, Tenormin, methotrexate. The
patient had been taking methotrexate when the
baseline was taken (it is not known for how long).
The elevation of GOT and GPT but not GGT in the
second test was characteristic of methotrexate
hepatotoxicity,25 and the patient's doctor reduced the
dosage of methotrexate. The patient does not smoke
and his alcohol consumption was low. An adverse
drug-herb interaction may have occurred between
the methotrexate and the herbal treatment.
Conclusion
The results of the liver function tests for this group
of patients suggest that herbal medicine in a clinical
setting is unlikely to cause a significant and
consistent elevation of serum enzymes. There were
no significant changes in mean serum values during
herbal treatment. The trial is continuing and will
hopefully provide results for 200 patients receiving
herbal treatment for up to one year.
Based on the results for individual patients with
serum enzyme levels outside the normal range, three
patients out of eighty-one (patients 11, 36, 62)
demonstrated an unexplained rise in serum enzyme
levels over time. These changes were minor, but an
association with herbal treatment cannot be
conclusively ruled out. However, on the basis of
results thus far, it can be concluded that the practice
of herbal medicine is unlikely to cause
hepatotoxicity. Patients taking hepatotoxic drugs and
also receiving herbal treatment should be monitored
for potential negative drug-herb interactions. These
may be caused by changes in the pharmacokinetics
of the drug, rather than additive hepatotoxic effects.
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Martin, F.M. and Braasch, J.W.: Current Prob Surg 29, 133 (1992)
38
Ong, J.C. et al: Aust & NZ J Med 24, 149 (1994)
39
Fennerty, M.B.: Postgrad Med 94, 81 (1993)
40
Kremer, J.M. et al: Arth & Rheum 37, 316 (1994)
41
Brass, E.P.: Cleveland Clin J Med 60, 466 (1993)
42
Schnabel, A. et al: Rheumatol Internat 14, 33 (1994)
43
Carvallo, A. et al: Rev Med Chile 121, 777 (1993)
44
Phillips, C.A. et al: J Rheumatol 19, 229 (1992)
Appendix
Pyrrolizidine Alkaloids
Smoking
A small study of male alcoholics has indicated
tobacco-smoking alcoholics have more elevated GOT
and alkaline phosphatase levels (with GOT/GPT
ratio greater) than non-smoking alcoholics,
suggesting a more pronounced hepatic aggression.36
Sclerosing Cholangitis
Primary sclerosing cholangitis is a disorder
characterized by a progressive, inflammatory,
sclerosing, and obliterative process affecting the bile
ducts. The lesion may appear as an isolated entity or
may occur in association with inflammatory bowel
disease, especially ulcerative colitis, or with
fibrosclerosis syndromes.35
Pyrrolizidine alkaloids are made from two fused fivemembered rings with a common nitrogen in
position 4 which is called a 'necine base'. PAs with
saturated necine bases are nontoxic (such as those
found in Arnica montana and Echinacea spp). For a
PA to be toxic, several conditions need to be satisfied,
including a double bond between the 1 and 2
position (unsaturation). PAs are metabolized in the
liver to compounds which cause liver cell necrosis.
Oxidative reactions catalyzed by oxidases and
cytochromes lead to toxic pyrrole-like intermediates.
These highly reactive metabolites are bound by the
liver, resulting in hepatotoxicity.9
Abnormal liver function tests are observed in
patients with sclerosing cholangitis. Liver
transplantation is the definitive treatment.37
Yearly liver function tests are recommended for
children with inflammatory bowel disease, and if
abnormal, the possibility of sclerosing cholangitis
should be considered.38
Liver Function Tests
Hepatic adverse reactions from methotrexate
treatment include an increase in GOT, GPT, alkaline
phosphatase, serum bilirubin; liver dysfunction and
fatty liver.25
Liver function tests are used to assist in the diagnosis
and management of a variety of disorders and
diseases of the liver and gallbladder. 'Liver function
test' refers to a number of possible tests performed to
assess how well the liver is functioning. A variety of
biological parameters (including enzymes, drug
metabolites, bilirubin, bile acid, protein) are analysed
from the blood of the patient. They are static tests
that do not indicate the eventual outcome of the
disease since they are unable to identify the
functional reserve of the liver.34 For this reason, liver
function tests are usually performed over a period of
time to assess the effectiveness of the liver function
in response to treatment and/or removal of toxins
such as alcohol, drugs or pollutants. Transaminases
(or aminotransferases: GOT, GPT) are the enzymes
most often used as markers to indicate hepatocellular
injury.34 Table 6 outlines the characteristics of the
enzymes most commonly analysed for liver
metabolism disorders and suspected hepatotoxicity.
Methotrexate
Methotrexate is an antineoplastic and antiinflammatory drug with immunosuppressant
properties. It is an antirheumatic folic acid
antagonist and a dermatologic agent.
Methotrexate can cause hepatotoxicity and needs to
be used cautiously, usually by reviewing Liver
Function tests regularly.39,40 Methotrexate can cause
hepatic fibrosis during chronic use, but the liver
injury is poorly reflected by plasma transaminase
concentrations.41
One hundred and eighty-five patients with active
rheumatoid arthritis participated in a prospective
non-blind trial over 12 months. The objective was to
assess the rate of side-effects and dose-limiting
toxicity in those receiving 15 or 25 mg/week of
methotrexate. 39% of patients on the lower dose of
the drug demonstrated a tendency towards higher
levels of liver enzyme elevations, 47% for those on
the higher dose.42
Clinical
glutamic-oxaloacetic transaminase (GOT) also known as aspartate aminotransferase (AST)
•
•
•
•
catalyzes the transfer of the amino group of glutamic acid to oxaloacetic acid, forming α-ketoglutaric
acid and aspartic acid.
present in many tissues, including heart, skeletal muscle, kidney and the brain and is thus somewhat
less specific as an indicator of liver function.
normal range: < 40 U/L
important in diagnosis of liver disease and myocardial infarction.
glutamic-pyruvic transaminase (GPT) also known as alanine aminotransferase (ALT)
•
•
•
•
catalyzes the transfer of the amino group of glutamic acid to pyruvic acid, forming α-ketoglutaric acid
and L-alanine.
found primarily in the liver, hence is a more specific indicator of liver function.
normal range: < 40 U/L
important in diagnosis of hepatocellular injury.
Levels of GOT and GPT
•
•
can be elevated in nonhepatic diseases, such as myocardial infarction and skeletal muscle disorders.
very high levels indicate extensive hepatic necrosis; high levels indicate mild acute viral hepatitis,
chronic liver diseases.
• in severe alcoholic hepatitis only modest increases in GOT and GPT (usually < 5.0 ukat/L = 60 U/L) are
commonly observed.
• in general GOT and GPT levels parallel each other (ie GOT/GPT ≈ 1), with the following exceptions:
alcoholic hepatitis: GOT/GPT >2 (resulting from a reduction in hepatic GPT due to a deficiency in the
cofactor pyridoxine-5-phosphate); fatty liver associated with pregnancy: GOT/GPT >1.
However, absolute levels of aminotransferases correlate poorly with the severity of liver injury, so levels are
usually analysed over time.
gamma-glutamyltranspeptidase (GGT)
•
•
catalyzes the transfer of the gamma-glutamyl group from peptides (eg glutathione) to other amino acids.
plays a role in amino acid transport.
Levels of GGT
•
•
GGT correlates with alkaline phosphatase levels in liver disease, and is the most sensitive indicator of
biliary tract disease. However, elevations of GGT are nonspecific and may be associated with other
disorders.
GGT may be increased by agents which induce microsomal enzymes. It has been suggested as a
potential marker of alcoholism, however the overall lack of specificity has limited its clinical usefulness.
Table 6: Enzymes commonly analysed as part of Liver Function test35.
The toxicity of methotrexate in low doses (7.5 mg
per week) was prospectively assessed over 2 years in
21 patients with rheumatoid arthritis using gold or
penicillamine treatment. An increase in serum
transaminases, rising to less than twice the normal
value was observed in 75% of patients over the
treatment period, although there were no changes in
liver histology.43 (Gold and penicillamine have been
associated with rare cases of hepatic toxicity also).41
Severe liver diseases may occur in patients with RA
treated with low doses of methotrexate.44
Clinical
Sarcoidosis
Sarcoidosis is a chronic, multisystem disorder
characterized in affected organs by an accumulation
of T lymphocytes and mononuclear phagocytes,
noncaseating epithelioid granulomas, and
derangements of the normal tissue architecture.
Sarcoidosis is characterized at the sites of disease by
exaggerated T helper lymphocyte immune processes.
The organ most frequently affected is the lung.
Although liver biopsy reveals liver involvement in 60
to 90 percent of cases, liver dysfunction is usually not
important clinically. Approximately 20 to 30 percent
have hepatomegaly and/or biochemical evidence of
liver involvement. Usually these changes reflect a
cholestatic pattern and include an elevated alkaline
phosphatase level; the bilirubin and
aminotransferases are only mildly elevated, and
jaundice is rare.35
Nutritional Supplements
Azeopangen tablets: A digestive enzyme preparation
containing pancreatin.
C.S.T.: A formula indicated for sinus, hayfever and
catarrhal states, which contains garlic, beta-carotene,
papain and pancreatin.
Cardian tablets: A formula for the cardiovascular
system, which contains magnesium, potassium and
supporting vitamins and minerals.
Mr David McLeod
DMH, BAc, ND, MNHAA
David McLeod was previously the Chairman and
Head of the Brisbane College of Natural
Therapies and is currently the President of the
Board of Directors of the National Herbalists
Association of Australia. He operates a busy
clinic in Brisbane and has qualifications in
Traditional Chinese Medicine and Western
Herbal Medicine. David has lectured on
herbal medicine extensively, both in Australia
and overseas.
Ms Michelle Morgan
B.Sc
Michelle Morgan has a Bachelor of Science
degree majoring in Chemistry from the
University of Queensland (1987) and worked in
the scientific field for many years. She also has
expertise in Quality Assurance, working for over
3 years in building products manufacture.
Michelle currently works for MediHerb as
Assistant Technical Manager where she is
responsible for technical writing and research
Michelle is also studying to become a herbalist.
Glucosamine tablets: A formula used for the
treatment of arthritis, which contains glucosamine
and supporting vitamins and minerals.
Inkephalin tablets: A formula indicated for pain and
depression, which contains dl-phenylalanine and
Kellamin: A general multivitamin and mineral
formula.
LM1 tablets: A formula indicated for liver
detoxification and as a liver corrective, which
contains choline, methionine, taurine and
S.A.D. tablets: A formula indicated for depression
and anxiety, which contains l-glutamine,
l-tryptophan and supporting vitamins and minerals.
(This product is no longer available in this form as
tryptophan is a restricted substance).
Clinical
Evening Primrose Oil
BY MICHELLE MORGAN
Editorial Comment
In this article the author has covered in great
depth this widely available and very popular
product. The analysis of the research is invaluable
for those who wish to have a more "in depth"
understanding of EPO.
•
•
•
The article provides detailed information about:
•
•
•
•
•
•
anti-inflammatory effects: applicable to
rheumatoid arthritis where EPO can reduce
stiffness and pain and increase mobility.
possible uses in ulcerative colitis.
dermatitis and psoriasis where it will improve
the dryness, scaling and severity of the disease
(despite some conflicting data!).
its beneficial effect in the treatment
of allergies.
usefulness in alcohol withdrawal and in
treating the effects of alcoholism.
beneficial effects in the symptoms of premenstrual syndrome (including mastalgia).
Common Name: Evening primrose
Part Used: Fixed oil from the seed
of Oenothera biennis.
Family: Onagraceae
Oenothera biennis grows 1 to 2 metres in height, with
handsome, bright yellow flowers. It was imported
and carried all over Europe about 200 years ago from
North America, and is today commonly found in
waste places, sandy areas and on railway
embankments. Since the flowers first open in the
evening and remain wide open throughout the
following day, it became known as the evening
primrose. The seeds were recommended as a coffee
substitute in wartime and have an aromatic flavour
reminiscent of poppy seed oil.1
Active Constituents
The seeds of Oenothera biennis contain 15 to 20%
fixed oil that contains essential fatty acids (EFA):
65% linoleic acid (LA) and 8 to 10% gamma20 Modern Phytotherapist
•
•
reducing the symptoms of endometriosis.
improving calcium absorption and increasing
bone calcium to help in osteoporosis,
especially in combination with fish oil.
cardiovascular disease, where EPO is an
effective treatment for raising HDL, lowering
triglycerides, lowering LDL and lowering total
cholesterol, thus being a major factor in
reducing the risk of cardiovascular disease.
It has also been shown to be effective in
the treatment of hypertension, including
reducing the risk of hypertension and
eclampsia in pregnancy.
diabetes, where EPO is beneficial in assisting
to prevent peripheral neuropathy. The drug
has NHS approval in England for this
application.
EPO may also be helpful in the treatment of
some nervous system disorders, for example
dementia and possibly schizophrenia.
linolenic acid (GLA).2,3 Refer to Figure 1 below.
Essential Fatty Acids
Essential fatty acids (EFAs) are nutrients which
cannot be manufactured within the body and must
be supplied by the diet. EFAs play a role in the
structure of cell membranes, helping to ensure their
fluidity and flexibility and modulate the behaviour of
membrane-bound proteins. They are precursors of
the so-called eicosanoids (prostaglandins,
leukotrienes and thromboxanes) which function in
platelet aggregation and inflammatory processes and
act as intra- and intercellular mediators.
EFAs are classified as polyunsaturated fatty acids
since they contain two or more double bonds. There
are two types of EFA: the omega-6 series (n-6 series)
which is derived from linoleic acid (LA) and the
omega-3 series (n-3 series) which is derived from
alpha-linolenic acid (ALA). These are so named
because of the position of the double bond nearest to
Clinical
EFA Metabolism
Within the body LA and ALA are metabolized by a
series of alternating desaturations and elongations.
Refer to Figure 3.
Figure 1: Gamma-Linolenic Acid (GLA).
Figure 2: Position of first double bond in GLA
(n-6 series).
n-6 series
n-3 series
LA (linoleic acid)
ALA (alpha - linolenic acid)
DGLA (and GLA) are precursors of the one-series of
prostaglandins (eg prostaglandin E1 which is a
vasodilator, inhibits platelet aggregation, is antiinflammatory and inhibits phospholipase A2).
Phospholipase A2 breaks down cellular membranes
and releases arachidonic acid. Arachidonic acid,
although required for normal cellular function under
certain conditions becomes the precursor of prothrombic, vasoconstrictor and pro-inflammatory
metabolites (eg prostaglandin E2).
Although GLA has been found in higher
concentrations from other sources including borage
oil, blackcurrant oil and fungal lipids, they do not
appear to be as clinically effective as EPO.4 These oils
contain n-3 fatty acids as well as the n-6 series.
Refer to the Appendix (after References)
for Abbreviations.
Pharmacology
GLA (gamma-linolenic acid)
Prostaglandin Metabolism and
General Anti-inflammatory Activity
DGLA (dihomogammalinolenic acid)
AA (arachidonic acid
EPA (eicosapentaenoic acid)
•
DHA (docosahexaenoic acid)
Figure 3: The metabolism of essential fatty acids on the
n-3 and n-6 series.
the methyl (-CH3) end of the molecule. In the n-3
series this double bond is between the third and
fourth carbon atoms, in the n-6 series it is between
the sixth and seventh carbon atoms (refer to Figure 2
above). A proper balance of n-6 and n-3 fatty acids is
required in the diet.
In EFAs all the double bonds are in the cis
configuration (trans fatty acids are believed to have
adverse cardiovascular effects). In the cis
configuration the atoms are on the same side of the
double bond, in the trans the atoms are on opposite
sides of the double bond. The cis molecules are less
stable than the trans, and polyunsaturated cis fatty
acids are quite vulnerable to oxidation.
•
•
GLA and DGLA have been shown to inhibit
inflammation and excessive immune reactivity in
vitro, and in vivo: eg adjuvant arthritis,
experimental allergic encephalomyelitis,
autoimmune disease, salmonella-associated
arthritis and urate-induced inflammation.5-12
EPO raised gastric mucosal prostaglandin
synthesis in humans, but not in rats.13,14 EPO,
however protected rats but not humans against
aspirin-induced damage.13,15
Four different doses of GLA in the form or either
borage oil or EPO were fed to rats over 6 weeks.
In the test group, DGLA and GLA levels
increased dose-dependently in liver, red blood
cell and aorta phospholipids. The arachidonic
acid/DGLA ratio in tissues decreased with
increasing intake of GLA. There was no
significant difference in the uptake of GLA
between the two groups. The dose of GLA
did not influence PGE2 production in
stimulated aortic rings and TxB2 levels in serum,
although an increase in PGE1 occurred in the
stimulated aorta.16
Clinical
Bone Metabolism
•
•
GLA and EPA were orally administered to
different groups of rats in several ratios.
Intestinal calcium absorption, calcium balance
and bone calcium all increased significantly
in the 3:1 (GLA:EPA) ratio group, compared
to controls.17
Several different ratios of GLA and EPA were
administered to young rats, as a mixture of EPO
and fish oil. Bone calcium content increased
significantly in the group receiving the high
GLA:EPA diet compared to controls receiving LA
and ALA.18
•
•
Diabetes
•
•
Several studies have indicated that treatment
with GLA can prevent or reverse diabetic
neuropathy in animals. This is achieved without
changing the sorbitol or other polyol levels in
peripheral nerves, and without having any effect
on the control of blood sugar.19-24
Short term biochemical changes have been
noted from GLA treatment in diabetic patients.
GLA tended to normalize the platelet fatty
acid composition, reduced total cholesterol
and apolipoprotein B, and inhibited
platelet aggregation.25-28
Male and Female
Reproductive Function
•
•
In a placebo-controlled trial during the
reproductive period, male and female blue foxes
were fed either a standard diet or one
supplemented with EPO, zinc sulphate and
vitamin E. A tendency for a increased litter size
in the treatment group was found, mainly as an
effect of male treatment.29
Control male minks were mated with control and
test female minks and test males were mated with
control and test females. For those males
supplemented with EPO, there was a tendency
for a reduced rate of stillborns and loss of life
during the first 21 days of life. EPO did not affect
reproductive performance in females, but there
was a tendency for lower weight losses during
lactation.30
Cytotoxic Effects
•
The cytotoxicity of GLA and other fatty acids
containing 2, 4, 5, and 6 double bonds were
examined on human breast cancer cells in vitro.
GLA and arachidonate with 3 and 4 double
bonds were the most cytotoxic fatty acids
compared to acids with 6 double bonds which
•
were the least effective. The effectiveness of a
given fatty acid in killing cancer cells correlated
with the extent of lipid peroxidation of the added
fatty acid in the cells.31
GLA, AA and EPA were highly effective in killing
human breast, lung, and prostate tumour cells in
vitro, while leaving normal cells viable.32 GLA, AA
and EPA enhanced free radical generation in
tumour cells but not in normal cells in vitro.33
GLA suppressed the rate of proliferation of
malignant cell lines in vitro. A further study
indicated that LA, GLA, AA, EPA, ALA, DHA,
PGE1 and PGA1 suppressed the rate of cell
proliferation in human osteogenic sarcoma
cells in vitro. At high concentrations total
suppression of colony formation and cell
proliferation occurred.34
The growth of human breast carcinoma
xenografts were studied in mice treated with
dietary supplements of EPO and fish oil and
compared to controls. Animals in the treatment
group developed tumours which were
significantly smaller than controls.35
Hypotensive Effects
•
•
•
•
•
Vegetable oils including sunflower oil, linseed oil,
and EPO enhanced the hypotensive effect of
antihypertensive drugs (dihydralazine, clonidine
and captopril) in rats under experimental
conditions.36
Hypertension induced in rats was reversed by the
addition of DGLA at 5.0% of dietary energy.37
The effect of salt-loading on blood pressure (BP)
development and its modification by dietary n-3
and n-6 fatty acids was studied in the borderline
hypertensive rat. EPO abolished the pressor
response, reducing BP below control levels.38
GLA supplementation reduced cardiovascular
responses to chronic stress in normal and
borderline hypertensive rats.39, 40
GLA did not demonstrate antihypertensive
activity in experimental hypertension in rabbits.41
Other Effects
•
•
Treatment of pregnant rats with ethanol and
EPO led to a significant reduction in the
embryopathic activity of ethanol.42
EPO had a favourable effect on progression of
renal failure in rats.43 A diet containing EPO and
fish oil favourably altered renal phospholipids,
eicosanoid synthesis and plasma lipids in
experimental nephrotic rats.44 EPO had a
favourable effect on experimental autoimmune
glomerulonephritis in rats.45
Clinical
Toxicology
High doses of 5 to 10 mL/kg/day administered to
several animals exhibited no toxic effects or
carcinogenicity.46
Atopic Dermatitis, Psoriasis
•
Veterinary Studies
Dermatitis
•
•
•
•
Eleven cats with papulocrustous dermatitis
randomly received either EPO or sunflower oil
for 12 weeks. Cats in both groups improved
during the period of treatment and the
concentration of LA in erythrocyte phospholipid
increased in the cats fed EPO. Six weeks after the
treatment was withdrawn, the cats fed EPO had
deteriorated less than those fed sunflower oil.47
Fourteen cats with crusting dermatoses were
treated with various combinations of EPO and
fish oil. The cutaneous symptoms improved in
those treated with either EPO alone or in
combination with fish oil. The subsequent
administration of a combination of the two oils
resulted in a resolution of the dermatosis.48
A significant effect was observed on erythema in
dogs with non-seasonal atopic dermatitis. They
were treated with EPO in a double blind placebocontrolled crossover study. Plasma LA levels were
significantly higher and AA levels increased
significantly for the EPO group, both in the first
and second phases of the study. There was also a
significant treatment effect in the second phase.49
A randomized double blind parallel study over
eight weeks assessed the effects of olive oil in a
group of 21 atopic dogs whose symptoms were
previously well controlled by supplementation
with EPO and fish oil. 80% of dogs that switched
to olive oil treatment deteriorated despite a
significant reduction in plasma concentration of
DGLA, a precursor of potentially antiinflammatory mediators. Of the dogs that
remained on EPO/fish oil only 18%
demonstrated deterioration.50
Clinical Studies
Clinical trials have shown benefits in diabetic
neuropathy, hypertension, mastalgia, PMS, osteoporosis
and dementia. Mixed results have been obtained in
trials for atopic eczema and dermatitis; rheumatoid
arthritis, ulcerative colitis, diabetic lipid metabolism
and alcoholism. The benefits of EPO therapy are
disputed in schizophrenia and cancer. No benefit was
observed in the treatment of menopausal hot flushes.
•
•
•
•
•
Extensive randomised double blind placebocontrolled trials in which GLA was provided to
patients with atopic eczema have demonstrated
highly significant improvement in all features of
the disease, especially in itch.51-57 Placebocontrolled parallel trials over many years
indicated marked improvement in inflammation,
dryness, scaling and overall severity compared
to controls. However, there is still conflicting
evidence in trials based on a crossover
design alone.58
GLA reduces the requirement for topical steroids
(by about 70%), and other medications such as
oral steroids, antihistamines and antibiotics.4,51
Skin roughness can also be significantly
reduced.59,60 Some patients with atopic eczema
have however demonstrated little or no response
to GLA treatment. Investigations using a mixture
of 80% EPO and 20% fish oil have given better
results than EPO alone.4
A double blind placebo-controlled study
conducted on children with atopic dermatitis
found a significant improvement in the overall
severity of the condition in children treated with
GLA, independent of the occurrence of
IgE-mediated allergy. GLA treatment increased
the amount of n-6 fatty acids in red blood cell
membranes, particularly in those treated with the
highest dose. Also a significant increase in DGLA
occurred in the high dose group.61
In a double blind placebo-controlled parallel
trial, patients with atopic dermatitis were
randomized to receive EPO, EPO plus fish oil or
placebo for 16 weeks. 102 patients completed the
trial and no improvement was demonstrated by
the EFA treatment.62
A double blind parallel trial of a combination of
EPO and fish oil in the treatment of 37 patients
with chronic stable plaque psoriasis was
undertaken. There was no significant
improvement in clinical severity of psoriasis or
change in transepidermal water loss.63
Thirty-seven patients with infantile seborrhoeic
dermatitis were treated topically with borage oil
(24% GLA) and compared to twenty-five healthy
children without skin disorders. Patients were
completely free from all skin symptoms within 3
to 4 weeks. The significant differences in
transepidermal water loss that existed between
patients before treatment and controls were not
found after the GLA treatment.64
Clinical
Female Reproductive System
Disorders
Diabetes (NIDDM, IDDM, and Diabetic
Neuropathy)
•
Diabetic neuropathy is a common complication of
diabetes, in which many peripheral nerve fibres
degenerate. In England EPO/GLA is an approved
treatment for diabetic neuropathy on the National
Health Scheme.
•
•
•
•
In open and placebo-controlled studies, GLA has
demonstrated better activity than placebo in the
treatment of PMS and mastalgia.65-73 Physical and
psychological symptoms of PMS were
significantly improved with GLA treatment,
albeit slightly compared to placebo. A dramatic
improvement was observed in a study in women
with atopic eczema whose symptoms are
exacerbated premenstrually. In a placebocontrolled study in forty women with
premenstrual irritable bowel syndrome,
significant improvement was observed in 50% of
patients taking GLA, compared to controls.4
Over many years at the Cardiff Mastalgia Clinic,
patients with cyclical and non-cyclical mastalgia
have received a variety of drug treatments.
Danazol was found to be the most effective drug,
with bromocriptine and EPO having equivalent
efficacy. Patients taking EPO reported fewer
adverse events.74
A randomised double blind placebo-controlled
study investigated the efficacy of GLA in the
treatment of menopausal hot flushes and
sweating.35 women suffering hot flushes at least
three times a day received either four capsules of
500 mg EPO plus 10 mg vitamin E or a placebo
twice a day for 6 months. The only significant
improvement for women taking GLA was a
reduction in the maximum number of night
time flushes (p<0.05). Overall there was no
benefit over placebo in treating menopausal
flushing.75
In a placebo-controlled study, women suffering
from endometriosis were given concentrated
GLA and EPA or placebo. 90% of those in the
treatment group reported relief of symptoms
compared to 10% of those in the placebo group.4
In a partially double blinded placebo-controlled
clinical trial, a combination of EPO and fish oil,
magnesium oxide or a placebo were administered
to pregnant women for 6 months. 21% of the
women had personal or family histories of
hypertension. Those taking the EPO and fish oil
had significantly lower incidence of oedema
(13%) compared to the control group (29%)
(p=0.004). Significantly fewer women developed
hypertension in the group receiving magnesium
oxide. Three cases of eclampsia occurred, all in
the control group.76
•
•
•
•
The effects of EPO and fish oil on glucose and
lipid metabolism, prostaglandin levels and body
composition were studied in patients with noninsulin-dependent diabetes. Patients in the
treatment group received 4 g EPO, 2.4 g fish oil
and 200 mg vitamin E (as preservative) per day
for 4 weeks. Fasting plasma glucose,
haemoglobin, total cholesterol, body weight and
body fat did not differ significantly from the
control group. However, the oil treatments
improved abnormal lipid and thromboxane A2
metabolism.77
In a double blind placebo-controlled study,
eleven children with IDDM received either EPO
(45 mg GLA) or placebo capsules for 8 months.
Patients took 2 capsules per day for 4 months
and then 4 capsules per day for a further 4
months. At the dosage of 4 capsules per day,
DGLA levels increased and PGE2 levels decreased
significantly in the EPO group compared to
controls (p<0.01). Fatty acid, PGE2, PGF2α levels
were unchanged during the earlier period.78
In randomized double blind placebo-controlled
parallel trials conducted over seven centres in the
UK and Finland, one hundred and eleven
patients with mild diabetic neuropathy received
GLA (480 mg/day) or placebo over 1 year and
were assessed by standard tests. A significant
favourable change was noted in the treatment
group for thirteen of the sixteen parameters
investigated, demonstrating a beneficial effect on
the course of mild diabetic neuropathy. Sex, age,
diabetes type, age of onset or duration of
diabetes did not significantly effect the result.
The treatment was however more effective in
relatively well-controlled than in poorlycontrolled diabetic patients.79 Patients could
continue in the trial for a further 12 months and
all those who participated received GLA
(unknowingly). Improvement continued over
this period.80
Twenty-two patients with distal diabetic
polyneuropathy who participated in a double
Clinical
blind, placebo-controlled study received either
360 mg GLA per day or placebo capsules for 6
months. Patients in the treatment group showed
significant improvement in the symptoms of
distal diabetic polyneuropathy.81
•
Arthritis
A review of the clinical trials marked with asterisks
(**) has noted the limited applicability of their
results. Overall these studies were not well controlled
(olive oil may itself produce beneficial results and
may not be the best choice of placebo and the effect
of vitamin E has not been completely ascertained).
The trials did not run for long enough (at least 6
months is required to assess symptomatic
improvement, longer than one year for diseasemodifying potential). The concomitant use of
medications was not standardized (some of the drugs
may have influenced the patients' subjective
assessment) and abrupt discontinuation of NSAIDs
may have aggravated patients' symptoms early on,
thus masking the effect of GLA. The most
appropriate statistical tests were not conducted and
drop-out rates were high.82
•
•
•
In a randomized double blind placebo-controlled
24-week trial, thirty-seven patients with
rheumatoid arthritis and active synovitis received
1.4 g/day GLA or placebo. Treatment with GLA
resulted in significant reduction in the signs and
symptoms of disease activity (p< 0.05) compared
to the placebo group which showed no change or
worsened.83 But refer to Adverse Effects Section.
**In a placebo-controlled clinical trial, 18
patients with rheumatoid arthritis received
20 mL/day of EPO (1500 mg GLA/day) or olive
oil for 12 weeks. Plasma levels of PGE2 decreased
and TxB2 increased in both treatment groups,
but no significant improvement in laboratory
findings or clinical signs occurred in either
group.84
**In an open trial, GLA (360 mg/day) and
cofactors (zinc, niacin, vitamins C and B6) were
administered to patients with rheumatoid
arthritis, whose NSAIDs had been abruptly
terminated. The symptoms or biochemical
parameters of arthritis did not improve, but one
measure of inflammation (skin reactivity to UV
light) showed improvement. Only two of the
seventeen patients deteriorated. Although not
demonstrated statistically, three patients reported
subjective improvement during treatment.85
•
•
**In a double blind placebo-controlled clinical
trial, forty-nine rheumatoid arthritis patients
were treated with EPO (540 mg GLA/day), EPO
plus fish oil (240 mg GLA + 450 mg EPA/day) or
placebo, over a period of 12 months. Significant
improvement was demonstrated in subjective
symptoms and a significant reduction in NSAID
therapy for those receiving EPO and EPO plus
fish oil, compared to placebo. After this
treatment period, placebo was given to all
patients for a following 3 months. After 3
months of placebo, the condition of those
originally receiving the EPO/fish oil treatment
had relapsed. Despite the changes in subjective
assessment of symptoms and NSAID use
throughout the treatment EPO did not alter any
of the biochemical indicators of the disease.86
**Forty patients with rheumatoid arthritis and
upper gastrointestinal lesions due to NSAIDs
took part in a double blind placebo-controlled
study over a six month period. Patients received
either 6 g/day EPO or 6 g/day of olive oil. Three
patients in each group reduced their dose of
NSAIDs. A significant reduction in morning
stiffness occurred in the EPO group at 3 months.
A significant reduction in pain and articular
index occurred at 6 months for those taking
olive oil.87
In a double blind placebo-controlled trial, 38
patients with psoriatic arthritis received a
combination of EPO and fish oil daily for 9
months. All patients then received placebo
capsules for a further 3 months. At the third
month of the study, patients reduced their intake
of NSAIDs and maintained the decrease,
symptoms permitting. All measures of skin and
joint symptoms were unchanged by the
treatment. The requirement for NSAIDs was
unchanged for both the treatment and placebo
groups. However, a rise in serum TxB2 was
observed in the treatment group during the
placebo phase. In addition, a decrease in LTB4
production occurred during the treatment phase
followed by a marked rise during the placebo
phase. Although these biochemical results can be
interpreted as an anti-inflammatory effect, the
authors concluded that there is no evidence that
EFAs act as disease-modifying agents.88
Clinical
Schizophrenia
•
•
•
•
Studies in groups of schizophrenics from
England, Ireland, Scotland, Japan and the USA
have indicated a lowering of linoleic acid in
patients' plasma phospholipids, with variation in
other EFAs.89-91 In one study, the n-6 EFA levels
were significantly reduced, whereas the n-3 EFA
were elevated in comparison to controls.89
Treatment of neuroleptic-resistant schizophrenics
with EFAs and penicillin in an attempt to
increase synthesis of the one-series
prostaglandins had a therapeutic effect in six
severely ill patients.92
In a randomized single blind placebo-controlled
trial, twenty-one inpatients with a schizophrenic
illness resistant to neuroleptic drug treatments
received either neuroleptic medication and
DGLA, placebo and DGLA, or two placebo
medications. No marked treatment effects were
noticed on ratings of the patients' behaviour or
symptomatology, although some positive clinical
effects were noted in dyskinetic patients.93
In a double blind placebo-controlled crossover
trial, thirty-seven psychiatric patients,
predominantly schizophrenics with tardive
dyskinesia (abnormal involuntary movements)
received capsules containing EPO over 16 weeks.
A further thirty-seven people in two groups, a
psychiatric control group and a normal control
group, were given a placebo. Although EFA
supplementation did not produce improvement
in abnormal movement measurements, there was
significant improvement in mental state,
schizophrenic symptoms and memory. In the
open phase at the end of the trial, addition of
cofactors (zinc, niacin and vitamins C and B6) to
EPO treatment produced an increase in n-3 and
n-6 EFA incorporation into red cell membranes.
During this phase marked and significant clinical
improvements in memory, schizophrenic
symptoms and abnormal movement were
observed in comparison to placebo or EPO
only treatment.94-96
•
•
•
Cancer Therapy
•
•
Cardiovascular Effects
•
In an open clinical trial, twelve hyperlipidaemic
patients received 3 g/day GLA for 4 months. After
treatment, plasma triglyceride levels were
decreased by 48% (p<0.001), HDL-cholesterol
levels increased by 22% (p<0.01), and total
cholesterol and LDL-cholesterol levels were
significantly decreased. Experimentally-induced
platelet aggregation and serum TxB2 levels
decreased, with a significant increase in bleeding
time. In a parallel study in rats, vascular
prostacyclin (PGI2) production was enhanced by
the supplementation.97
In a double blind placebo-controlled crossover
study, 25 non-obese patients with uncomplicated
essential hypertension received placebo for 4
weeks followed by EPO plus fish oil or sunflower
seed and linseed oil for 12 weeks. The mean
systolic blood pressure of patients receiving
EPO plus fish oil was significantly lowered after
8 and 12 weeks, while those receiving
sunflower/linseed oil had no significant
reduction of blood pressure.98
GLA lowers blood pressure in pregnant
women.4,99-101 In an open placebo-controlled
clinical trial, 10 pregnant and 10 non-pregnant
women received 3 g/day LA, 32 mg/day GLA and
co-factors for prostaglandin synthesis (such as
magnesium and zinc) for a week. Their pressor
response to an infusion of three doses of
angiotensin II was then compared to pregnant
and non-pregnant controls who had not been
given supplements. Diastolic pressor response to
angiotensin II was significantly less after
treatment, especially in the pregnant women.99
twenty-one patients with Raynaud's
phenomenon received a two week course of
placebo, after which eleven received EPO for 8
weeks and ten received placebo. Patients
receiving EPO experienced significant
improvement in symptoms, but there was no
change in blood flow despite changes in platelet
behaviour and TxB2 levels.4,102
EPO and vitamin C given to 6 patients with
primary liver cell cancer demonstrated some
clinical improvement and reduction in tumour
size (3 patients). One patient demonstrated
marked reduction of liver and tumour size and
liver damage.34
In an open clinical trial GLA was administered
by intra-cerebral injection (1 mg/day for 10 days)
to 15 patients with malignant gliomas. The
cerebral gliomas regressed, as evidenced by
computer tomography, and patients' survival was
increased by 1.5 to 2 years.103
Osteoporosis
•
In a clinical trial conducted in old people's
homes, forty women with confirmed
osteoporosis were divided into 4 groups and
received either fish oil, EPO, fish oil plus EPO, or
olive oil (control) over sixteen weeks. Serum
alkaline phosphatase levels dropped in both the
Clinical
fish oil and the combined oil groups indicating
an increase in bone mineral density. Osteocalcin
levels, an indicator or bone growth, rose in the
fish oil group and more significantly in the
combined oil group. Although the EPO had
no effect on its own, it increased the effect of
the fish oil on the bone formation markers,
probably due to a more balanced plasma fatty
acid profile.104
Other Effects
•
•
•
•
In a randomized placebo-controlled study, 43
patients with stable ulcerative colitis received
either EPO, fish oil or olive oil (placebo) for 6
months in addition to their usual medication.
Alteration of cell membrane fatty acids was
observed for those taking EPO and fish oil
compared to the control group. Although there
was no difference in stool frequency, rectal
bleeding, disease relapse, sigmoidoscopic
appearance or rectal histology in the three
groups, EPO significantly improved stool
consistency compared to fish oil and placebo at 6
months, and this difference was maintained 3
months after treatment was discontinued
(p<0.05).105
In a double blind placebo-controlled study, sixtythree patients with post-viral fatigue syndrome
received a preparation containing EPO (80%)
and fish oil (20%) or a placebo (8 x 500 mg
capsules per day) over a 3-month period. At the
end of the trial 85% of patients in the treatment
group compared to 17% in the control group
assessed themselves as improved (p<0.0001).
Improvements occurred in every symptom and a
normalization of essential fatty acid levels in red
blood cell membranes was observed in the
treatment group.4,106
In a double blind placebo-controlled clinical
trial, the effect of EPO supplementation to
alcoholics was investigated. In the early weeks of
withdrawal from alcohol, EPO significantly
reduced the severity of the withdrawal syndrome
and improved liver function. Relapse rates over 6
and 12 months did not improve. However, in
those who did not relapse, several parameters of
cerebral function (such as memory and visual
motor coordination) improved significantly with
EPO treatment.4
Analyses of blood samples from patients with
dementia have shown reduced EFA for
Alzheimer's disease and in particular, multiinfarct dementia. In a placebo-controlled trial,
patients with Alzheimer's disease received EPO
or placebo. Highly significant improvements
•
•
occurred on several tests of cerebral function for
the treatment group compared to controls.4
eighty-nine renal transplantation patients
received either EPO or placebo, together with
standard immunosuppressive medication. Graft
survival was significantly better in the EPO
group compared to controls during the first 3 to
4 months post-transplant, but not significantly
different at 6 months.107
A rare case of multiple mucoceles within the oral
cavity responded entirely to systemic GLA
treatment. The condition recurred several
months following discontinuation of treatment.
GLA may have exerted an effect on minor
salivary gland composition and/or viscosity.108
Adverse Effects
General
The most common adverse effects to be reported in
trials using GLA for the treatment of the above
conditions is headache and mild nausea. (These
adverse effects are however less severe than those
caused by orthodox drugs, particularly those used to
treat rheumatoid arthritis).82
Arachidonate Buildup
The potential risk of arachidonate buildup associated
with long-term use of GLA in the treatment of
rheumatoid arthritis has been recently raised. Several
tests have shown GLA administration to increase
arachidonate levels: 2.0 g per day of GLA given to
Clinical
previously obese women increased the arachidonate
content of their serum phospholipids. With
prolonged administration of GLA over more than a
year, arachidonate will accumulate in tissue thus
possibly counteracting early therapeutic effects of
GLA. Tissue buildup of arachidonate might promote
subsequent inflammation, thrombosis and
immunosuppression. Symptoms may rebound in
patients after discontinuation of GLA.109 Worsening
of synovitis in several patients has been recorded
after withdrawal of GLA treatment. The authors of
this study considered this to be due to absence of the
anti-inflammatory effects of the EFA, however they
agree caution should be exercised.110
Epilepsy
In recent years there has been concern for the use of
EPO in patients with a history of epilepsy.
Originally this concern arose from trials in patients
with schizophrenia who were being treated
concomitantly with anti-schizophrenic drugs
(phenothiazines and related compounds). Episodes
of epilepsy were reported, but no definite link to
EPO treatment has been established, rather the
nature of the mental illness and side effects of the
orthodox medication are the likely cause. Similar
events were reported in patients not taking EPO.4
There has been a report of the occurrence of
epileptic seizures after ingestion of EPO in a drugstabilized epileptic dog.111
There have, however, been no reports of an epileptic
attack being associated with EPO preparations other
than in patients taking epiloprogenic (epilepsy
enhancing) drugs.112 Perhaps in response to these
trials in patients with schizophrenia, the British
Epilepsy Association warns those with epilepsy to
avoid EPO because of a possible lowering of the
threshold for seizures.111,112 Currently the reported
position of Australian doctors is that EPO should be
avoided in patients with a history of epilepsy.113,114
This position is probably excessively cautious.
Actions
Anti-inflammatory, antiallergic, hypotensive, corrects
n-6 EFA deficiency.
Medicinal Uses
Evening primrose oil is licensed in the UK for
symptomatic relief of atopic eczema and
premenstrual or non-cyclical mastalgia.115
•
•
•
•
•
•
•
•
•
•
Inflammatory disorders: atopic eczema,
dermatitis, psoriasis, rheumatoid arthritis,
ulcerative colitis.
Premenstrual syndrome and disorders
exacerbated premenstrually such as atopic
eczema and irritable bowel syndrome; mastalgia,
endometriosis.
Diabetic neuropathy.
Bone metabolism disorders, osteoporosis.
Hyperlipidaemia.
Hypertension.
Alcohol withdrawal and the effects of alcoholism.
Post-viral fatigue.
Impaired fatty acid metabolism, n-6
EFA deficiency.
Dementia; adjunct to orthodox medication
for schizophrenia.
Cautions and Contraindications
EPO may have potential to instigate undiagnosed
temporal lobe epilepsy, especially in those receiving
phenothiazines.114
Dosage
Oils like EPO are difficult to preserve as they can
easily be oxidized and go rancid, so it is best
administered with a preservative, protected from
oxygen in soft gelatin capsules.
Low to medium dosage should be used for
conditions such as atopic dermatitis, mastalgia and
post viral fatigue syndrome: 250 to 500 mg GLA per
day (approximately 2.6 to 5.2 g per day of EPO).
Medium to high doses can be used for conditions
such as diabetes, alcoholism, inflammatory disorders
(including arthritis, ulcerative colitis) or
cardiovascular disorders (hyperlipidaemia,
hypertension): 0.4 to 2.0 g GLA per day
(approximately 4.2 to 21.0 g per day of EPO). A
suitable dose to begin treatment for RA is 500 to
600 mg GLA per day (approximately 5.2 to 6.3 g per
day of EPO).
EPO can be applied topically to skin lesions.
Clinical
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Appendix
Abbreviations
AA: arachidonic acid
ALA: alpha-linolenic acid
CHD: coronary heart disease
DHA: docosahexaenoic acid
DGLA: dihomogamma-linolenic acid
EFA: essential fatty acid
EPA: eicoapentaenoic acid
EPO: evening primrose oil
GLA: gamma-linolenic acid
HDL: high-density lipoprotein
IDDM: insulin-dependent diabetes mellitus
LA: linoleic acid
LDL: low-density lipoprotein
LTB4: leukotriene B4
n-3 EFA: omega-3 essential fatty acid
n-6 EFA: omega-6 essential fatty acid
NIDDM: non-insulin-dependent diabetes
NSAID: non steroidal antiinflammatory drug
PGE1: prostaglandin E1
PGE2: prostaglandin E2
PGF2α: prostaglandin F2α
PGI2: prostaglandin I2
PMS: premenstrual syndrome
TxB2: thromboxane B2
Therapeutic Philosophy
Intergrating Western and Eastern
Herbal Medicine: A Clinical Perspective
BY MUHAMMAD SALIM KHAN
DHom, DO, MGO, MRH, Dlr
This article was first published in the Bristish journal: Vis Medicatrix Naturae, Summer 1995.
Editorial Comment
Western herbalists looking to rediscover the
historical and philosophical roots of their
therapeutic system should look no further than
Unani or Tibb. This living tradition is based on
the medical system of the ancient Greeks. In fact
the name Unani (used on the Indian
subcontinent) means "Ionian" or "Greek". Tibb is
based on the humoral theory developed by the
Hippocratic school and further refined by Galen.
The Tibb physician with the most far-reaching
impact in the Islamic and western worlds was
Avicenna, who was best known for his work The
Canon of Medicine, which contained about one
million words.
With the humoral theory there are four humours
in the human body: blood, phlegm, black bile and
yellow bile. According to Galen, illness meant a
disruption of the harmony of the humours, and
the balance had to be re-established by treatment.
Therefore, this was a highly evolved system of
matching a treatment to the constitution and
circumstances of the individual patient. (Source:
Unani Medicine of the Subcontinent by Claudia
Liebeskind in Oriental Medicine: An Illustrated
Guide to the Asian Arts of Healing, Serindia
Publications, 10 Parkfield, London SW15 6NH,
1995. General editors: Jan Van Alphen & Anthony
Aris. Text available from Chinaherb Co. Sydney.)
Salim Khan is in private practice as an osteopath
and medical herbalist in Leicester. He is Chairman
of the UK Tibbi Practitioners Association and
is a member of the General Council and
Register of Consultant Herbalists and the
Guild of Osteopaths.
Introduction
The Current Situation
The last two decades have seen a renaissance of
alternative and complementary therapies throughout
the world. There is a plethora of books and courses
on different therapies. However, when examined
closely, most of these books are a mixture of ancient
teachings taken out of context and mixed with some
aspect of modern scientific discovery. There is an
absence of integration and wholeness. One of the
hallmarks of natural medicine and health care was
balance, wholeness and unity. Herbal medicine is the
oldest and most widely used form of medicine in the
world today. However, herbal medicine as practised
today, particularly in the West and especially in
Britain and America suffers from a lack of consistent
and comprehensive framework or paradigm. This
article is intended to explore ways that integration
and unity can be realised, at various levels of our
work, our organisations and ourselves.
The Mesnavi of Jalal-ud-din Rumi, a classic work of
wisdom, contains a story called 'The Disagreements
as to the Description and Shape of an Elephant'. It
runs as follows:
"The elephant was in a dark house. Some people had
brought it for exhibition. To see it, many people were
going, every one, into that darkness and, as seeing it
with the eye was impossible, each one was feeling in the
dark with the palm of his hand. The hand of one fell
on the trunk: He said 'This creature is like a water
pipe'. The hand of another touched its ear; to him it
appeared to be like a fan. Another handled its leg and
said. 'I found the elephant shape to be like a pillar'.
Another laid his hand on the back- he said: 'Truly this
elephant is like a throne.' Similarly when anyone heard
a description of the elephant, he understood it only
concerning the part he had touched. Because of the
diverse place of view, their statements differed: one
man entitled it 'Dal', another 'Alif '. If there had been a
candle in each one's hand the difference would have
gone out of their words".
The eye of sense perception is only like the palm of
the hand: the palm has not the power to reach the
whole of the elephant.
The genius of Rumi has penetrated to the centre of
the problem of knowledge. Each hand, as it were,
fumbles over some part of the elephant, each
proclaiming what they have discovered, and none
able to relate the part to the whole. The invention of
instruments that render the senses a thousand or
more times more acute does not reduce the
difficulties: if anything it increases them. Because of
the minute examination one is unable to listen to
what is being said at the other end of the elephant.
Even if it was possible to spare the time to study
different disciplines or specialities, the search for
knowledge has become so intense, so much data and
so many observations have been accumulated, that
no person can ever hope to know all that others have
recorded. The prospect of synthesising so much data
seems to be an impossible task. It would seem that
the very existence of an elephant has been forgotten.
Consequently, the efforts are solely upon the
compilation of vast catalogues of observation
on the trunk, legs, or the tail, depending on one's
area of interest.
This is the unsatisfactory state in which the whole
body of knowledge finds itself. It is equally true of
medical science: medicine studies the human being,
who is an indivisible whole of such enormous
complexity that it is impossible to grasp the truth.
Modern medical science, therefore, has taken the
body to pieces in order to study each piece separately.
The modern physician, called upon to deal with a
sick human being, is confronted with a truly
formidable task. What renders this task so difficult is
that the physician is unaware of what a normal
human being is, still less a sick one. He or she has
acquaintance with the organs of a human being and
has an idea how they work, but of the reality or
nature of the human being is woefully ignorant.
Since the Renaissance in European society, the
fundamental conceptions of the creation of life and
the human being have developed on mechanistic and
materialistic lines to the exclusion of any higher
values. In general, this view of the world has created
fundamental problems - both technological and
psychological - which have pushed humanity to the
edge of an abyss.
As Capra says in The Turning Point:
"At the beginning of the last two decades of our
century, we find ourselves in a state of profound,
world-wide crisis. It is a complex, multi-dimensional
crisis whose facets touch every aspects of our lives - our
health and our livelihood, the quality of our
environment and our social relationships, our economy,
technology and politics. It is a crisis of intellectual,
moral and spiritual dimensions of a scale and urgency
unprecedented in recorded human history. For the first
time we have to face the real threat of extinction of the
human race and all life on this planet."
It is in this context that herbal medicine can help to
restore balance and order, specifically in health and
well-being. Any comprehensive tradition of medicine
has a network of interdependent ideas and practices
through which the origin, understanding, treatment
and prevention of illness and the maintenance of
health are explained. Thus in reality there are close
and intimately inseparable relations between the
conception of a human being and health and disease.
When we examine herbal medicine it can be divided
into the systems of the West, and the systems of the
Orient/East. The western systems of herbal medicine
are: the naturopathic herbalists, the allopathic
school, the planetary herbalists and physiomedicalism. It is interesting to note that Samuel
Thompson, founder of physio-medicalism, wrote:
"I found that all animal bodies were formed of four
elements. The earth and water constitute the solid, and
air and fire, or heat, are the cause of life and motion;
that cold or lessening of power of heat is the cause of all
disease. That to restore heat to its natural state was the
only way that health could be produced, and that, after
restoring the natural heat, by clearing the system of all
obstructions and causing a natural perspiration, the
stomach would digest the food taken into it, and the
heat of nature be enabled to hold her supremacy".
The oriental systems can be divided into three
main groups: traditional Chinese medicine (TCM),
traditional Indian medicine (Ayurveda and
Siddha) and traditional Persian/Middle
Eastern medicine (Tibb).
The need for integration and unity, and the practice,
of herbal medicine can be expressed at various levels:
(1) Individual: where integration and unity is an
inherent human need,
(2) Professional level: where it is essential for
•
•
•
•
•
•
clear communication
the establishment of areas of agreement
diagnostic purposes
therapeutic purposes
research and development
legal protection.
The Transcultural Principles of
Herbal Medicine
In order to establish clear unity we may explicitly
agree to core principles that we share irrespective of
our training or school. I call these transcultural
principles. These are:
•
•
•
•
organisation of the cosmos are concerned with
complex energies. This understanding of the universe
also extends to other organisms including human
beings. This framework is developed by creating a
spectrum for measuring the qualities of heat, cold,
moisture and dryness (see Table 1). These four
primary qualities (khawas) are used as qualitative
dimensions of measurement, hot and cold being
active and moist and dry passive. This concept is
further developed to yield four basic universal
symbols of the primary elements. The macrocosm,
the cosmos and its miniature - human being - is the
resultant interplay of these four elements which are
united in unvarying patterns.
Vis medicatrix naturae - the healing power of
nature, which regulates, protects and heals.
Energy - the chi of Chinese, the prana of Indian
and the quwa of Middle Eastern medicine.
Wholeness and the unity of the individual.
The micro-macro principle - that each being is a
complete biological miniature universe.
The Integrated Perspective and
its Clinical Application
Energies and Elements
The transcultural principles provide us with a
perspective that can be useful in clinical practice. Of
course each tradition uses its own jargon to express
this and Tibb is no exception.
The elements (arkan) are the simple constituents of
minerals, plants and animals. Throughout the
classical civilisations of China, the Middle East, India
and Greece, the concept of elements has been used to
explain and understand nature's most complex
processes, including health and disease. Tibb as a
living and dynamic tradition of medicine and health
care shares with classical societies the idea of
elements. However, owing to its own unique
historical and social contexts, it has its own
particular emphasis, which will be the focus
of this article.
The manifestation of existence by being is a result of
polarisation of material prima into energy (qawa).
From the Tibbi perspective, the highest levels of
Table 1: The Polarisation of Khawas into Four Basic
Qualities
This understanding of qualities and the elements is
an intricate and subtle idea that requires the
transcending of gross materialism. The elements can
be perceived as components, dynamic qualities,
primary forms or different phases of a cycle.
However, in all these aspects, the elements represent
dynamic aspects of the phenomena of life,
originating from one creative source.
The Four Elements
(Refer to Table 2)
Earth
Earth is an element normally situated at the centre of
all existence. In its nature it is at rest and all other
elements naturally tend towards it, however great a
distance away they might be. This is because of its
intrinsic weight. Earth is cold and dry. In the scheme
of creation, it serves the purpose of rendering things
firm, stable, lasting and heavy. It is by means of the
earthly element that other parts are fixed and held
together into a compacted form. Thus it is because
of earth that the outward form is maintained. The
vibration rate of the earth is slow. It is passive and
receptive in nature like the female principle in
creation.
Water
Water is a simple substance whose position in nature
is exterior to the orbit of the earth and interior to
that of air. This is because of its relative density. It is
cold and moist. The purpose of water in the scheme
of creation lies in the fact that it lends itself to
dispersion. Water provides, in the construction of
things, the possibility of being moulded and shaped
without permanency. Water being moist allows
shapes to be readily fashioned. Water is the source of
life as well as being essential to life.
Air
Air is a simple substance, occupying the position
above the sphere of water and beneath that of fire.
This is because of its relative lightness. Air is hot and
moist. In nature, in the process of creation, its
purpose is to rarefy and render things finer, lighter
and more delicate.
primary qualities residing within the elements.
Temperament as defined above is a synthesis of
physical, emotional, intellectual and spiritual aspects
of an individual. It is a dynamic statuesque to each
individual. Every being is endowed with the most
suitable temperament for the purpose and
conditions of its creation. Human beings possess the
most suitable temperaments for the conditions of
life. Temperament is the inherent predisposition to
respond and react along qualitatively predetermined
characteristic patterns. Temperamental differences
are the differences of response patterns to identical
situations. Each individual reacts and responds
according to an innate psycho-emotional pattern,
which he or she shares with others as well as it being
unique to himself or herself.
The Origins of Temperament
The temperament of each individual is unique, due
to inborn strength and weakness of various forces. It
is liable to temporary changes due to psycho-social
factors such as emotions, occupation, food and
ecological factors such as climate (see Table 3).
According to Tibb, each part of the human body has
been assigned a characteristic temperament. Thus
each specific organ has a hot, cold, moist or dry
temperament suitable for its structural and
functional requirements (see Table 4).
Fire
Fire is a simple substance, occupying a position in
nature higher than that of the other three elements.
Fire is hot and dry. The part fire plays in the creation
of things is that it matures, refines and intermingles
with all things. Its penetrative power enables it to
permeate the substance of air. It thus subdues the
coldness of earth and water and enables their
integration into various compounds.
Earth
heaviness, stability, firmness
Water
dispersion, maleability
Air
refraction, lightness
Fire
maturation, integration, rising
Table 2. The Elements and Subtle Processes.
Temperament
The temperament is that dynamic quality that results
from mutual action and interactions of the four
Table 3: The Spectrum of Temperaments of the
Whole Person.
The Humours
Akhlat is the biological application and extension of
the elements. There are four primary fluids
(al-akhlaat al-arbah) sometimes referred to as
daughters of the elements (banat al-arkan).
Hot Organs
Cold Organs
Moist Organs
Dry Organs
(In Descending Order)
1) Vital force
1) Phlegm
1) Phlegm
1) Hair
2) Heart
2) Hair
2) Blood
2) Bone
3) Blood
3) Bones
3) Oil
3) Cartilage
4) Liver
4) Cartilage
4) Fat
4) Ligaments
5) Flesh
5) Ligaments
5) Brain
5) Tendons
6) Muscles
6) Tendons
6) Spinal cord
6) Membranes
7) Spleen
7) Membranes
7) Breasts
7) Arteries
8) Kidneys
8) Nerves
8) Testicles
8) Veins
9) Breasts
9) Spinal cord
9) Lungs
9) Motor nerves
10) Testicles
10) Brain
10) Liver
10) Heart
11) Muscular coats of arteries
11) Fat
11) Spleen
11) Sensory nerves
12) Muscular coats of veins
12) Oil of body
12) Kidneys
12) Skin
13) Skin
13) Skin
13) Muscles
14) Skin
Table 4: The Spectrum of Temperaments of Specific Organs.
There are two types of fluid: normal and abnormal.
Normal fluids are capable of being assimilated and
integrated into tissue or energy, whilst abnormal
fluids are unsuitable for assimilation and can be a
source of imbalance and ill-health. There are four
primary fluids in their normal state which are
responsible for the physiological, morphological and
energy requirements of the body. Food begins to be
changed and modified as soon as it comes into
contact with the lining of the mouth. Saliva also
promotes digestion due to its innate activity. Within
the stomach, digestion changes food into chyme, a
juice-like fluid. Chyme is absorbed through the
stomach and small intestine into the liver. The liver
works rapidly with the chyme, maturing it and
converting it into the four primary fluids. The main
characteristics of the primary fluids are given below.
Blood
Normal blood (dum) is connected to the element air,
being hot and moist in nature. The associated organs
are the lungs, blood and liver. Blood is active in
childhood, spring and between three and nine in the
morning. Normal blood is red, sweet and without
smell. Blood possesses an attractive force. Its
function is to provide nutrition to the organs and
tissues. Abnormal blood can result from cold and
heat, mixture with other fluids, dietary
mismanagement or emotional imbalance.
Phlegm
Normal phlegm (bulghum) is sweet, associated with
the element water, and cold and moist in nature. It is
dominant in old age, winter and during the night
from nine p.m. to three a.m. The related organs are
the kidneys, the bladder and the brain, although it
moves freely in the blood and joints. It possesses an
expulsive force. Phlegm is different from the other
fluids in that it can be converted into blood when
necessary. It moistens the organs and joints to
prevent dryness caused by excess friction and heat.
There are several varieties of abnormal phlegm and
their main causal factors are lack of heat, working in
water for long periods, and an excess of phlegmproducing foods such as milk and cheese.
Bile
Normal bile (safra) is yellow bile, corresponding to
the element fire, being hot and dry in nature. It is
active in youth, summer, and between nine a.m. and
three p.m. Bile is light in weight and yellow in colour.
Bile is taken into the gall bladder and the blood.
The heart and the gall bladder are the associated
organs. The yellow bile that is taken into the blood
makes the blood light and thin for easy passage
through the capillaries. Yellow bile that enters the gall
bladder serves that organ and activates the intestines
and rectum for defecation by peristaltic movements.
Abnormal yellow bile can be caused by its mixture
with other fluids or because of a change of
temperament. The causative factors can be excess
heat, hot or sweet and greasy food.
Black Bile
Sauda - as the Arabic word indicates - is black bile
and is the sediment of normal blood. Black bile
corresponds to the element earth, being cold and dry
in nature and possessing a retentive force. Its taste is
midway between sweetness and astringency. Black
bile is associated with middle age and autumn and is
active between three and nine p.m. daily. The
associated organs are the spleen, stomach and bones.
Black bile is taken from the liver into the spleen and
the blood. The bile that enters the blood is necessary
for the nutrition of organs such as the bones. Within
the blood itself, black bile makes it thick. The bile
that enters the spleen is used by the spleen for
nutrition and to purify the rest of the body of its
excrementitious material, and part of it is sent to the
stomach. It renders the stomach firm, active and
induces hunger by its acidity. Abnormal black bile
can be caused by excess heat or cold inefficiency of
the spleen, dietary indiscretions such as food
containing thick, dry ingredients, and negative
emotional conditions. There are several varieties of
abnormal black bile that are a source of ill health,
particularly mental-emotional diseases.
From these basic characteristics of the primary fluids
we can begin to understand the relationship between
the various factors. This simple and clear
relationship begins to form a coherent picture
indicating how closely and intimately interwoven are
the relationships between diet, seasons, health and
well-being.
Assessment and Evaluation
Assessment of Temperament
The temperament (synthesis) of an individual is
assessed against that of a balanced person under
normal conditions. Since the skin, specifically the
skin of the terminal phalanges, is the most balanced,
touch has been adopted as the most suitable means
of assessment. However, in practice all five senses are
used to arrive at a proper assessment. Practical
clinical training and experience primes the
practitioner to make professional judgements. The
ten primary indicators for the assessment of innate
temperament are:
i) Physique.
ii) Complexion.
iii) Hair.
iv) Muscularity and adiposity.
v) Feel of the body.
vi) Functional condition of the organs.
vii) Excretions.
vii) Receptivity of organs.
ix) Sleep and wakefulness.
x) Psychological aspects.
Principles Employed to Restore
Balance
Having arrived at an assessment of the whole
person's constitution and temperament as well as
specific organs, we are now able to understand the
qualitative nature of various interventions. Different
interventions have their own energetic qualities too.
In order to maintain or restore lost balance within an
organ or the person as a whole, we need to match the
intervention to the imbalance (see Table 5). The
principles behind treatment are: a) to conserve and
maintain balance if the individual mizaj is in a state
of equilibrium (this is achieved through the like or
similar principle) and b) to restore balance when
lost, through application of the contrary principle.
Conclusion
From this brief paper, it should be clear how almost
all aspects of lifestyle and interventions - be they
dietary, naturopathic, herbal or psychological become amenable to systematic understanding. This
understanding can be used with the patient to help
him/her toward health and well-being. The universal
idea and fact is that disease and disorder are, in
reality, a manifestation of moving away, violation or
deviation from natural laws.
Stimuli that
Promote Heat
Cooling Stimuli
Moistening
Stimuli
Drying Stimuli
1) Moderate quantity
of food.
1) Excessive activity
(as it causes dispersion
of internal innate heat).
1) Rest.
1) Activity.
2) Moderate quantity 2) Excessive repose (which
2) Sleep.
of physical exertion.
induces cold because of
lessening of innate heat).
2) Wakefulness.
3) Moderate amount
of mental activity.
3) Excess of food and drink.
3) Retention.
3) Excessive
evacuations.
4) Moderate use
of hot baths.
4) Excessive worry.
4) Elimination of drying
matters or activities.
4) Sexual intercourse.
5) Moderate amount
of massage.
5) Extreme reduction
of food.
5) Excess of food.
5) Inadequate food.
6) Vigorous exercise
6) Excessive joy or pleasure.
over a short period.
6) Drinks of moist quality.
6) Foods of dry type.
7) Hot types of food
and drink.
7) Cold types of food
and drink.
7) Foods of moist quality.
7) Medicines of
dry type.
8) Hot types
of medicines.
8) Cold occupations.
8) Medicines of
moist quality.
8) Repeated
emotional
outbursts.
9) Hot types
of occupations.
9) Cold types of medicine.
9) Activities that lead to an
increase of moisture
(eg. bathing after meals).
9) Drying applications
by salt baths.
10) Dry cupping
(not wet type).
10) Cold applications which
increase moisture.
10) Exposure to cold.
11) Hot applications
of plasters.
11) Applications which
moderately liquefy the
body secretions.
11) Excessively hot
applications that
lead to excessive
dissipation of
moisture.
12) Moderate amount
of wakefulness.
12) Moderate degree
of pleasure.
13) Moderate amount
of sleep.
14) Moderate amount
of pleasurable activity.
15) Anger.
16) Mild, not severe,
anxiety or worry.
17) Increased density
of the skin.
Table 5: Energetic Qualities of Interventions.
Clinical
Case History of Chronic
Lymphocytic Leukaemia
BY DAVID MCLEOD
Introduction
Case History
The leukaemias are a diverse group of bone marrow
malignancies. In general, the acute leukaemias are
potentially curable with standard combination
chemotherapy but the chronic leukaemias, despite a
more prolonged, indolent course, are incurable.1
Male patient aged 68 years. First presentation
October 1993. Diagnosis confirmed in August 1993
from a bone marrow test.
In a review of 119 patients, older age, a low
haemoglobin, low platelet count, and the presence of
lymphadenopathy and fever at presentation
correlated adversely with survival. Overall, forty
patients died as a consequence of chronic
lymphocytic leukaemia or from disease-related
causes, 34/40 dying of infection.2 Twenty-one
patients developed second cancers. It was concluded
that new approaches are urgently needed.
Symptoms included: lymph gland enlargement in
groin, axilla and neck; severe reactions to insect bites
(ants), which took several months to heal.
Splenomegaly was also present. The disease was in
the very early stages, so no medical treatment was
offered. A haematologist would monitor blood tests
every three months. However, this was a patient
likely to have a poor prognosis.2 A blood test in
February 1993 showed the white blood cell count
was 11.8. (Normal range 4.0 to 10.5). In August 1993
the white cell count was 13.2.
I prescribed the following formula:
Herbal Formula
Withania (Withania somnifera)
1:2
40 mL
Culvers root (Leptandra virginica)
1:2
15 mL
Angelica (Angelica archangelica)
1:2
10 mL
Red Clover (Trifolium pratense)
1:2
15 mL
Poke Root (Phytolacca decandra)
1:5
5 mL
Licorice (Glycyrrhiza glabra)
1:1
15 mL
100 mL
Dose: 5 mL t.d.s.
Also Echinacea angustifolia root 1:2 5 mL three
times a day.
Additional treatment included a vitamin and
antioxidant formula (BACE); vitamin C (18 g daily,
self prescribed), vitamin E (1500 iu daily), Garlic
(1 raw clove daily), daily exercise (a half hour walk),
and relaxation.
Clinical
Over the next 18 months various formulas were
prescribed which contained selections from the
above herbs and Bupleurum, Eleutherococcus
(Siberian Ginseng), Galium aparine (Clivers),
Calendula, Tanacetum parthenium (Feverfew),
Viscum album (Mistletoe), Stachys betonica (Wood
Betony) and Astragalus. Some of these herbs were
used to treat recurrent headaches.
Outcome
Treatment is ongoing. But by June 1994 the patient's
white blood cell count was normalized and this has
been maintained ever since at about 7.0 to 8.5.
Platelet count (previously high) became normal in
November 1994 and has been normal ever since. The
patient remains well and in relatively good health.
The Echinacea was maintained throughout.
Treatment settled at the following formula, together
with the Echinacea as given above:
Herbal Formula
Withania (Withania somnifera)
1:2
40 mL
Siberian Ginseng
(Eleutherococcus senticosus)
1:2
25 mL
Astragalus (Astragalus
membranaceus)
1:2
25 mL
Feverfew (Tanacetum parthenium)
1:5
10 mL
100 mL
Dose: 5 mL t.d.s.
The additional treatment described above was
maintained throughout.

Modern Phytotherapist

Transcription

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