Herb standardization

- a benign quality marker

or a destroyer of phytochemical synergy?

Elizabeth M Williamson
Professor of Pharmacy and Director of Practice

University of Reading

UK delegate to the group of experts (phytochemistry) of the European Pharmacopoeia and

member of the expert advisory group on herbal and complementary medicines to the
British Pharmacopoeia
 Types of herbal extract
• Infusions (teas) – often ‘home made’ by patient
• Decoctions (made by boiling), fluid extracts and
tinctures (made with ethanol and water) – often
prepared by herbalist
• Essential oils, steam distilled, expressed or solvent
extracted – usually commercial
• Unstandardized extracts – home made or commercial
• Standardized (or ‘normalized’ according to the
European Pharmacopoeia) extracts: includes
‘quantified’ and ‘purified’ extracts – commercial
 General quality control issues
• If you grow your own herbs, you know the
quality!
• If you buy them in, the following may present a
problem:
– Identity of plant – mistaken identity or substitution
– General quality of the plant – depends on climate,
processing (drying) etc
– Contamination with organic or inorganic material
– Spoilage by insect pests or moulds
– Content of active constituents – a reasonable range
• These are measures of basic quality – and no
more than you would expect of food!
 Identification of the plant species

• Whole plant organs – relatively easy to

identify
• Cut herbs – difficult to identify
• Final product – almost impossible to identify!
 The European Pharmacopoeia
• ALL THE PREVIOUS TYPES OF PREPARATION
CAN BE QUALITY CONTROLLED – e.g. using the
methods and standards of the European
Pharmacopoeia (Ph. Eur.)
• Objectives: to provide quality standards for
medicinal substances important for public health
in Europe – for all kinds of drugs, including
herbals
• Scope: covers of all types of herbal preparations,
from the fresh or dried plant material to the
different types of extract, for purity and quality –
not safety or efficacy
• Not many extract monographs yet available, but
are a priority
 Pharmacopoeial monographs
• Identity of plant or extract: microscopy and thin-layer
chromatography
• Phytochemical content of plant or extract: assay either
colorimetrically or by HPLC.
• Limits chosen reflect a range found on a normal, good quality
sample: data taken from literature, industry (importers, growers
as well as manufacturers) and academia
• Test for foreign organic matter (other plant species, unwanted
parts of a plant) – e.g. heavy metals or radioactivity from a
polluted environment, pesticide residues
• – some are very toxic (e.g. Aspergillus niger, which produces
aflatoxins), bacteria (e.g. Salmonella, E. coli)
• Presence of microbial, heavy metal etc contamination
• Approach is pragmatic, and from a public safety point of view - it
DOES NOT FAVOUR industry, although their batch data is used
and some of their analytical methods
 Definition of standardization
‘the establishment of reproducible
quality by comparing a product with
established reference substances and
by defining minimum and sometimes
maximum concentrations of one or
more compounds or groups of
compounds’

NB: CRITERIA FOR STANDARDIZATION

based on what is normal for a good quality
product – hence the European term
‘NORMALIZATION’
 What is (and isn’t) standardization?
IT DOES INCLUDE: IT DOES NOT
• Combining batches to INCLUDE:
give a consistent • The production of
product ‘artificial’ extracts
• Removing unwanted • The addition of isolated
constituents (e.g. fats, substances, whether of
proteins, sugars) to natural or synthetic
give a more origin – ‘spiking’
concentrated product: • The addition of
e.g. soya isoflavones anything not normally
• Removing toxic found in the plant
constituents to give a if this occurs, it is
safer product: FRAUD
e.g. butterbur
 Types of Standardized Extract
• Type A: (Truly) standardized to active constituents
– senna, standardized to anthraquinones 5.5-8.0%
– belladonna, standardized to alkaloids (as hyoscyamine)
0.95-1.05%
• Type B: ‘quantified’ – standardized to constituents that
contribute to activity
– St John’s wort, standardized to hypericin 0.1-0.4%
– Ginkgo biloba, standardized to both flavonoids 16-26%
and terpene lactones (ginkgolides) 5-7%
• Type C: standardized to lead compounds of unknown
pharmacological relevance, which serve as quality
markers
– Artichoke, standardized to 2-5% cynarin
– Valerian, standardized to 0.8-1% valerenic acid
 Purified or refined extracts
• Involve a further process of purification, for example
removal or minimisation of toxic ingredients:
Removal of ginkgolic acids from Ginkgo biloba

• There will soon be two monographs in the Ph.Eur, one

for the normal standardized extract, and one for the
purified extract

• Concentration of anthocyanins in bilberry extract:

Contains 32.4-39.6% anthocyanins, and less than 1.0%
free anthocyanidins
 Why standardize?
• For reproducibility in any herb
• For more potent herbs
• For patients to purchase and self-medicate
• For enabling a dose regime to be defined
• For use in clinical studies (otherwise data
considered anecdotal only)
• If a preparation is to be marketed as a
medicinal product
• For compliance with Pharmacopoeial
standards - for quality assurance
 Do you get what you pay for?

Ginkgo Biloba 1,250mg Ginkyo 50mg (30 Tabs)

60 for £1.95 Price: £9.95 Inc VAT
360 for £4.95

no way of knowing!
 When not to standardize

• When visiting a qualified herbal practitioner

– these are individually made for the patient,
and the practitioner knows exactly what they
are and where they have come from
• When preparing a fresh herbal tea
• When no standard is available to measure
• If you don’t want to……
 Myths about standardization 1.

‘Poor extracts can be spiked with an

active constituent to make them look
better’
………..so let’s look at Ginkgo biloba
and Hypericum perforatum
 Ginkgolide B
• Tocris catalogue no 1657
• Cost: £149.00 for 50 mg
 Hypericin
• Tocris catalogue no 1520
• Cost: £45.00 for 1 mg
 Myths about standardization 2.
‘the majority of advocates of standardization consist
of academics and medical doctors who have little
personal or clinical experience with herbs’
(Dr M Tierra, Founding member of the American Herbalists
Guild….. is he an academic or a medical doctor?!)

………so don’t herbal practitioners care about the

quality of the products they buy? Do they make
everything themselves?
Don’t they care what’s in them? Don’t they believe
that the healing qualities of a herb depends on it’s
composition and therefore quality?
 Silybum marianum analysis comparing flavonoid and phenolic
acid profiles of a commercial tincture with one made by a
herbalist
COMMERCIAL TINCTURE Retention Time FRESH TINCTURE
5.51 & 5.80 Caffeic acid derivative
8.41 Caffeic acid derivative
8.83 & 8.90 p-coumaric acid derivative
p-coumaric acid 10.78
Ferulic acid 11.48 Ferulic acid
11.7 p- coumaric acid
12.9 Caffeic acid derivative
13.8 Flavanone
Flavanone 14.1 Flavanone
14.8 Flavanone
15.5 Flavanol glycoside
16.6 p-coumaric acid derivative
16.9 Flavanone
17.8 Flavanone
18.8 p-coumaric acid derivative
p-coumaric acid derivative 19.1 p-coumaric acid derivative
 Fresh v commercial tincture
Fresh tincture Commercial tincture
• Herbalist took the • Previous product was NOT
plant and made the standardized
tincture • Contains a much narrower range of
• The analytical profile actives
shows an excellent • Suggests decomposition of many
range of antioxidants derivatives to parent compound
• Standardization in this • A good standardization would ensure
case is unnecessary! derivatives were chosen, not the
parent compound (e.g. senna is
always standardized to the glycosides,
never the parent compound, and the
assay ensures this)
 Myths about standardization 3.
‘the majority of advocates of standardization ….. Are researchers
whose work is funded by the companies that manufacture the
standardized extracts used in their clinical trials’
M Tierra, Founding member of the American Herbalists Guild
Comment:
• Quite true, such researchers do advocate using standardized
extracts, since clinical trials are very expensive and funding
difficult to come by
• The value of clinical trial results depends on reproducibility and
statistics. If you can’t say exactly what you gave the patient, and
the dose that you gave, then the data is not reproducible,
unreliable, unacceptable for publication and you may as well not
bother doing them.
• You won’t get ethics approval anyway…………..
Why are herbalists against standardization?

• If compulsory, would prevent them

making their own products (tinctures,
ointments etc)
• Restriction of professional freedom

• True, but they are never going to be

made compulsory for practitioners

• Misunderstanding as to what they are?

 Why are herbalists shouldn’t be against
standardization!
• Good clinical trial results enhance the status
and perception of herbal medicine and of
herbalists
• Conversely, bad publicity damages everyone
involved in herbalism
• If you can’t make the preparation yourself,
you need to be confident that the product
you are using is safe - and will be effective
• Standardized products are never going to be
made compulsory for practitioners – and it is
only possible for certain herbs where the
actives are well known
Some other standardized extracts
• ‘It is of the greatest importance that the
blend should never vary from this
standard, which customers will have come
to expect…..the second aim is, therefore,
to achieve consistency’ ‘Whisky web: the art of
blending’

• ‘Non-vintage champagne is a blend of

several different years' wine. Because of
this, the character of non-vintage
champagne is very consistent year after
year’ ’www.finewine.com’
 Conclusion
• Standardization is just another tool for quality
control
• In preparations standardized to Pharmacopoeial
monographs, the analysis will also have been
performed – and this will show that the range of
constituents is still there!
• Therefore, there is no logical reason why
standardization should ‘destroy’ synergy – quite
the opposite, it should preserve it
• However: it is quite easy for any manufacturer to
say that their product is standardized……….