Herb Standardisation - Liz Williamson

8/14/2019 Herb Standardisation - Liz Williamson

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Herb standardization

- a benign quality marker

or a destroyer of phytochemical synergy?

Elizabeth M WilliamsonProfessor of Pharmacy and Director of Practice

University of Reading

UK delegate to the group of experts (phytochemistry) of the European Pharmacopoeia andmember of the expert advisory group on herbal and complementary medicines to theBritish Pharmacopoeia
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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 solventextracted usually commercial

Unstandardized extracts home made or commercial

Standardized (or normalized according to the

European Pharmacopoeia) extracts: includesquantified and purified extracts commercial


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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!


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Identification of the plant species

Whole plant organs relatively easy to

identify Cut herbs difficult to identify

Final product almost impossible to identify!


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The European Pharmacopoeia

ALL THE PREVIOUS TYPES OF PREPARATION

CAN BE QUALITY CONTROLLED e.g. using themethods and standards of the European

Pharmacopoeia (Ph. Eur.)

Objectives: to provide quality standards for

medicinal substances important for public healthin Europe for all kinds of drugs, including

herbals

Scope: covers of all types of herbal preparations,

from the fresh or dried plant material to thedifferent types of extract, for purity and quality

not safety or efficacy

Not many extract monographs yet available, but

are a priority


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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


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Definition of standardization

the establishment of reproduciblequality by comparing a product withestablished reference substances andby defining minimum and sometimes

maximum concentrations of one ormore compounds or groups ofcompounds

NB: CRITERIA FOR STANDARDIZATIONbased on what is normal for a good qualityproduct hence the European termNORMALIZATION


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What is (and isnt) standardization?

IT DOES INCLUDE: Combining batches to

give a consistentproduct

Removing unwantedconstituents (e.g. fats,proteins, sugars) togive a moreconcentrated product:e.g. soya isoflavones

Removing toxicconstituents to give asafer product:

e.g. butterbur

IT DOES NOTINCLUDE: The production of

artificial extracts

The addition of isolatedsubstances, whether ofnatural or syntheticorigin spiking

The addition of

anything not normallyfound in the plant

if this occurs, it isFRAUD


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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 thatcontribute to activity

St Johns 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 unknownpharmacological relevance, which serve as qualitymarkers

Artichoke, standardized to 2-5% cynarin

Valerian, standardized to 0.8-1% valerenic acid


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Purified or refined extracts

Involve a further process of purification, for exampleremoval or minimisation of toxic ingredients:

Removal of ginkgolic acids from Ginkgo biloba

There will soon be two monographs in the Ph.Eur, onefor the normal standardized extract, and one for thepurified extract

Concentration of anthocyanins in bilberry extract:

Contains 32.4-39.6% anthocyanins, and less than 1.0%free anthocyanidins


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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


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Do you get what you pay for?

no way of knowing!

Ginkyo 50mg (30 Tabs)Price: 9.95 Inc VAT

Ginkgo Biloba 1,250mg60 for1.95

360 for4.95
http://www.healthydirect.co.uk/product/Deep+Vein+Thrombosis/0111.htmhttp://www.healthydirect.co.uk/product/Deep+Vein+Thrombosis/0111.htmhttp://www.healthydirect.co.uk/product/Deep+Vein+Thrombosis/0111.htmhttp://www.healthydirect.co.uk/product/Deep+Vein+Thrombosis/0111.htmhttp://www.healthydirect.co.uk/product/Deep+Vein+Thrombosis/0111.htmhttp://www.healthydirect.co.uk/product/Deep+Vein+Thrombosis/0111.htm


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When notto 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 dont want to


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Myths about standardization 1.

Poor extracts can be spiked with an

active constituent to make them look

better..so lets look at Ginkgo biloba

and Hypericum perforatum


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Ginkgolide B

Tocris catalogue no 1657

Cost: 149.00 for 50 mg


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Hypericin

Tocris catalogue no 1520

Cost: 45.00 for 1 mg


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the majority of advocates of standardization consistof academics and medical doctors who have littlepersonal or clinical experience with herbs(Dr M Tierra, Founding member of the American HerbalistsGuild.. is he an academic or a medical doctor?!)

so dont herbal practitioners care about thequality of the products they buy? Do they makeeverythingthemselves?

Dont they care whats in them? Dont they believethat the healing qualities of a herb depends on itscomposition and therefore quality?

Silybum marianum analysis comparing flavonoid and phenolic


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Silybum marianum analysis comparing flavonoid and phenolic

acid profiles of a commercial tincture with one made by a

herbalist

p-coumaric acid derivative19.1p-coumaric acid derivative

p-coumaric acid derivative18.8

Flavanone17.8

Flavanone16.9

p-coumaric acid derivative16.6Flavanol glycoside15.5

Flavanone14.8

Flavanone14.1Flavanone

Flavanone13.8

Caffeic acid derivative12.9p- coumaric acid11.7

Ferulic acid11.48Ferulic acid

10.78p-coumaric acid

p-coumaric acid derivative8.83 & 8.90

Caffeic acid derivative8.41

Caffeic acid derivative5.51 & 5.80

FRESH TINCTURERetention TimeCOMMERCIAL TINCTURE


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Fresh v commercial tincture

Commercial tincture Previous product was NOT

standardized

Contains a much narrower range of

actives

Suggests decomposition of manyderivatives to parent compound

A goodstandardization would ensure

derivatives were chosen, notthe

parent compound (e.g. senna is

always standardized to the glycosides,never the parent compound, and the

assay ensures this)

Fresh tincture Herbalist took the

plant and made the

tincture

The analytical profile

shows an excellentrange of antioxidants

Standardization in this

case is unnecessary!


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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 standardizedextracts, 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 cant 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 wont get ethics approval anyway..


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Why are herbalists againststandardization?

If compulsory, would prevent themmaking 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?


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Why are herbalists shouldntbe against

standardization!

Good clinical trial results enhance the statusand perception of herbal medicine and ofherbalists

Conversely, bad publicity damages everyoneinvolved in herbalism

If you cant make the preparation yourself,you need to be confident that the productyou are using is safe - and will be effective

Standardized products are never going to bemade compulsory for practitioners and it isonly possible for certain herbs where the

actives are well known


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Some other standardized extracts

It is of the greatest importance that theblend should never vary from this

standard, which customers will have come

to expect..the second aim is, therefore,

to achieve consistencyWhisky web: the art ofblending

Non-vintage champagne is a blend of

several different years' wine. Because ofthis, the character of non-vintage

champagne is very consistent year after

yearwww.finewine.com


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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 ofconstituents 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.

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Herb Standardisation - Liz Williamson