The MediHerb 'Quantified Activity' Program
The MediHerb Quantified Activity (QA) program aims to establish meaningful quality guidelines for the manufacture of herbal extracts. It is a system for ensuring the production of consistent quality extracts with guaranteed minimum levels of active constituents.
To date, MediHerb has quantified the activity of over 70 herbs through this program. To our knowledge such a program has never been undertaken in Australia, nor has it been matched anywhere in the world.
The constituents chosen as ‘quality indicators’ are carefully selected under the guidance of Kerry Bone and represent the most up-to-date scientific knowledge available.
The process of developing Quantified Activity extracts is complex and involves many steps. However, once the constituents are selected and the quantified activity levels are set, the main focus is to ensure the supply of consistent quality raw material and the retention of the constituents throughout the manufacturing process.
It is important to point out that Quantified Activity extracts are not purified single constituent extracts nor have they been manipulated in any way by non-traditional processes. They are whole galenical extracts of carefully selected whole herbs, manufactured using the MediHerb 1:2 Cold Percolation process, and still contain the complex range of active constituents from the raw herb. In other words, quantified activity extracts are mainly achieved by the testing and selection of high quality, carefully dried raw materials.
The Echinacea QA Story
Echinacea is MediHerb’s first quality story and a good example to explain the Quantified Activity program.
When MediHerb first started manufacturing in 1986 there was confusion in the global herbal industry over what constituted authentic Echinacea. Echinacea angustifolia and E. purpurea were routinely being substituted by unsuspecting manufacturers with another herb, Parthenium integrifolium. The substitution was made possible due to the uncanny physical similarity of the roots of Parthenium and especially Echinacea purpurea.
The solution implemented by MediHerb to guarantee supply of authentic Echinacea led to the development of the “Quantified Activity” program which exposed the Parthenium/Echinacea substitution and helped establish MediHerb’s credibility in the herbal industry.
The earliest methods employed by MediHerb to assess herb quality and identity relied on a trained herbalist checking the herb’s physical appearance, colour, odour and taste. Taste was of particular importance because of the insight it gave into the herb’s chemistry.
Traditionally, the test for Echinacea quality was the ability of the root to cause an intense tingling sensation in the mouth when chewed. The substitution of Parthenium integrifolium for Echinacea was successful only if appearance was checked and taste was not. When chewed, Parthenium root did not cause any tingling sensation in the mouth. The components which cause the tingling sensation from Echinacea are called alkylamides. So, one very simple solution was to taste the roots!
As MediHerb developed more sophisticated analyses, thin layer chromatography (TLC) was adopted which allowed the gross aspects of Echinacea’s chemistry or its “chemical finger-print” to be compared to a certified reference sample from the correct species. However, TLC mainly demonstrates if a compound is present, but not its quantity.
MediHerb understood that alkylamides were important for the efficacy of Echinacea and began to investigate methods to quantify the alkylamides along with other important compounds such as cichoric acid. At the time there was no published test methodology for alkylamides and the process of developing the high performance liquid chromatography (HPLC) methodology took MediHerb a number of years.
Once armed with the HPLC methodology for identifying quality in terms of alkylamide content, MediHerb worked with Echinacea growers to determine appropriate growing conditions and handling parameters to ensure optimum retention of the alkylamides. Internally, MediHerb established protocols to ensure optimum retention and stability of alkylamides during all phases of the production process; from receipt of the raw material to completion of the finished product. Alkylamides are very delicate compounds and are easily damaged or lost during processing, hence developing these protocols took many years to conclude.
From these exacting analyses MediHerb was able to establish our standard for acceptance of Echinacea raw material based on alkylamide content. The task then was to work with herb growers to ensure that we were able to consistently source the herb according to our specification. Using our validated 1:2 Cold Percolation process we could then be confident that we would always extract a known amount of alkylamides along with all the other active compounds in every batch. Thus ensuring a consistent quality product with “Quantified Activity”, every batch, every time.
The research into Echinacea continues today and our most recent efforts are aimed at further improving quality and efficacy, and understanding how Echinacea works.
Quantified Activity and Standardization
At times, we receive an herb that has higher levels than our minimum specification, so you as the clinician receive that higher level of activity. We never dilute to meet a minimum specification. Herein lies the difference between Quantified Activity and standardisation. With standardization, extracts with an active level that exceeds the specified standard would then be diluted to fall within that standard.
For more information on standardization see the MediHerb Professional Library
With the MediHerb Quantified Activity program, we have linked together all of the possible parameters that can affect product and extract quality and can guarantee that a high quality, efficacious extract will be produced every time.
Standardized Extracts: A Balanced Perspective
In those cases where there is strong clinical data supporting the use of a particular standardized extract, MediHerb has adopted that standard and dosage approach for its tablet products. A good example is Ginkgo biloba.
There is considerable controversy and misinformation over the use of standardized extracts. Many of these are in fact full spectrum galencial extracts, made by traditional extraction with ethanol and water, which are merely produced to a consistent quality marker (or markers). No adulteration of the extract has taken place and isolated phytochemicals have not been added to the extract. Good examples of these are Devil’s Claw, St John’s Wort and Horsechestnut. In addition, MediHerb’s extensive quality control procedures are capable of detecting adulterated or “spiked” extracts. Such extracts are never used in MediHerb products.
For more information on this complex topic see Kerry Bone’s articles:
Modern Phytotherapist Vol 6, No 1 & 2 in the Professional Library
Phytoequivalence is a concept that was developed in Germany in the mid-1990s, and means that one herbal extract matches, or is equivalent to, another herbal extract, more specifically to one of the clinically-proven extracts. It is somewhat of a misnomer as phytoequivalence really means chemical equivalence, ie that the two extracts have the same chemical profile. But it was also intended to mean more than that. Extracts that are phytoequivalent should be able to demonstrate the same pharmacological or physiological activity when ingested by humans. This is however difficult to demonstrate (for example, it could be done by showing the similarity of the levels of marker compounds (or their derivatives) in the bloodstream of humans after oral doses of the two products). A marker compound is a characteristic compound used to represent the quality standard for a standardized extract – it is often, but, not necessarily, one of the pharmacologically active compounds.
Phytoequivalence = extracts that are physiologically equivalent
At the very least a match of the chemical profile, such as a chromatographic fingerprint, which outlines the full chemical spectrum of the extract is required. Comparison with the reference (clinically-proven) extract should indicate the presence of all major constituents, and the same levels of marker compounds and similar levels of all other measurable constituents. It is important to realize that phytoequivalence is not demonstrated by just comparing the level of only one or two marker compounds.
Obtaining a good chromatographic fingerprint (usually by high performance liquid chromatography (HPLC)) for investigating phytoequivalence for a herb depends on several factors:
- A good extraction method to obtain almost all the pharmaceutically active compounds
- A chromatogram with good separation
- A representative concentration profile of the bioactive components detected by a proper detector
Bulgarian clinical trials have shown that Tribulus herb (aerial parts) extract rich in protodioscin enhances libido and fertility and alleviates menopausal symptoms. If a Tribulus product is made from the root or fruit of the plant, or is sourced from anywhere else other than Eastern Europe, it will probably contain low levels of protodioscin and so will be quite different to the clinically-proven Bulgarian standardized extract.
This is despite what might be claimed on the label for such products because often inferior methods of analysis have been used to measure the furostanol saponins (which includes the marker compound, protodioscin), such as gravimetric or colorimetric techniques. The phytoequivalence and quality of Tribulus products is best assessed by HPLC.
Phytoequivalence = demonstrated similarity of all phytochemical constituents (all constituents present and at the right concentration)
In a paper published in 2004, researchers from China compared 18 fingerprints of Ginkgo biloba extracts purchased from pharmaceutical stores, companies and collected from producing areas of China. All of these samples were supposed to meet the standard for flavonoids measured by ultraviolet spectroscopy. Standardized extract of Ginkgo from Europe was the clinically-proven extract used as the reference for phytoequivalence. The samples looked similar in the HPLC chromatograms, however further statistical analysis of this data indicated problems with three samples. A peak in two samples around the retention time of 10 minutes was much higher than the peak in the standardized Ginkgo extract, and was found to be the flavonoid rutin which had been added (in order to meet the old, UV spectroscopy standard). Inferior clinical results might well have been obtained using these non-phytoequivalent extracts.
MediHerb goes to great lengths using sophisticated analytical methodology to ensure that products such as standardised Ginkgo 2:1 standardized liquid extract, Ginkgo Forte, Tribulus and Saligesic tablets are phytoequivalent to the clinically-trialed products.