MH Enhance Quality Assurance
MediHerb’s renowned commitment to quality, safety and efficacy extends across the MH Enhance range of nutritional products. First and foremost, the practitioner can be assured that the MediHerb Quality Assurance Manager defines the requirements of laboratory testing required for each product and personally authorises the release for sale. Independent TGA certified laboratories that have expertise in nutritional assays conduct the analysis of the products. Should the products for some reason not meet our exacting quality standards, they are rejected just as the MediHerb herbal products are.
Safety in the Formulation
Safety is high on the agenda when it comes to MH Enhance product formulation. Any ingredient that is considered for inclusion in a particular product must go through a thorough assessment of its safety and toxicology. From this perspective, we assess how much of this nutrient is found in the food supply, and the appropriate forms and amounts used in any scientific research on that ingredient. Strict standards are also predetermined to ensure only quality materials from reputable sources are used and that there is adequate data available on its stability.
Synergy and Efficacy
In formulating the MH Enhance products our team of naturopaths and nutritional experts consider the requirements of practitioners in the clinical setting. We know from our own experience that practitioners need products that meet a genuine health need and also work quickly to resolve the issue. As part of this process we consider the modern patient who may have an established nutrient deficiency or a diet that may be devoid in certain nutrients. We also look at the most prevalent health conditions and diseases occurring today.
Our goal is to combine a synergistic blend of nutrients into a product to address a specific health issue, such as cardiovascular health, improved blood glucose control, or enhanced bone and joint health. Our focus on inclusion of synergistic nutrients means that the MH Enhance products may not seem to have the highest levels of individual single nutrients within a product, but it will have all the right cofactors to ensure maximum absorption and effect. This philosophy requires MediHerb to research and then translate credible scientific evidence into nutritional products that work.
Inclusion of herbs can also be found in the MH Enhance products where we feel the herb may add further therapeutic benefit to the synergistic blend of nutrients. These are of course at efficacious dosages and are the same quality MediHerb herbal extracts you find in our full herbal range of products.
The MediHerb mission for the MH Enhance products is to provide safe, efficacious, bioavailable nutritional products that will support modern health needs. For the patient, this means they can have the utmost confidence in knowing that the product they are taking contains what is exactly on the label, uses the best forms and combinations of nutrients to have the desired effect and the product quality is guaranteed by MediHerb.
The Science of Botanicals: The MediHerb Research Laboratory
At MediHerb we are extremely fortunate to have an outstanding team of people in Research and Development and Quality Control: over 12 scientists including three chemistry PhDs, a biochemistry PhD, three herbalists, three chemists two nutritionists and a pharmacist. Together the team has diverse industry experience in food and herbal products, university research, drug analysis in hospitals, pharmaceuticals, quality assurance, technical writing and clinical nutrition.
The MediHerb Research Laboratory has a strong association with the University of Queensland. The University is ranked as one of the top three research universities in Australia and has a strong focus on biotechnology and medical research.
Thin layer chromatography plays an important role in herb
The high performance liquid chromatography (HPLC) and
mass spectrometry (MS) equipment is essential for the
analysis of herbal materials.
MediHerb Research Objectives
The research group at MediHerb is committed to the development of efficacious herbal therapies. This involves three major areas of focus, which are all interconnected:
It is by combining phytochemical, biochemical, clinical, and traditional herbal knowledge that MediHerb can continue to produce high quality products, which meet the changing needs of the market.
- Formulation of efficacious herbal solutions to meet
- Validating the efficacy of herbal formulas by clinical
trials and in vitro research
- Researching the phytochemistry of medicinal plants.
The MediHerb Research Laboratory is well equipped with gas chromatographs (GC), thin layer chromatography (TLC), ultra-violet-visible (UV-Vis) spectrophotometers, high performance thin layer chromatography (HPTLC), and high performance liquid chromatographs (HPLC). The HPLCs are equipped with photo diode array (PDA), evaporative light scattering detectors (ELSD) and sophisticated mass spectrometer (MS) detectors. Access to nuclear magnetic resonance (NMR) and infra-red (IR) spectrometers, polarimeters, gas chromatographs with mass spectrometer detection, and HPLC with MS/MS capabilities is available on campus.
The Research and Development team works closely with herbalists and naturopaths within the company and with a board of leading Australian and international herbalists on product development. This ensures that MediHerb has taken the best of science, traditional knowledge and current clinical knowledge to make the most efficacious herbal and nutritional solutions relevant to your clinical practice.
New Product Development Process
MediHerb has implemented a rigorous new product development process, which ensures that the appropriate steps are undertaken when investigating the introduction of a new product into our product line.
By reviewing all the relevant information available regarding the therapeutic outcome, we are seeking to develop a short list of key herbs and nutrients which are then subjected to closer analysis.
This involves detailed examination of the:
- Clinical outcomes
- Phytochemistry/Biological activity
- Analytical methodology
- Continuity of supply
- Economic sustainability
- Synergy of the final formula
- Cost to the patient, and
- Practicality of final dose formulation
Once the prototype formulation is agreed upon, MediHerb may undertake a controlled human trial to prove the efficacy and safety of the product. This may either be a full clinical trial or may be an open trial in conjunction with our experienced clinicians (feedback trial). Products with well documented evidence of traditional use are often subjected to the feedback trial. For more novel formulations that do not have significant traditional use, a full clinical trial evaluation may be performed.
Clinical Trials at MediHerb
MediHerb invests significantly into the future of herbal medicine and our profession by funding clinical trials. MediHerb has a reputation for its extensive depth of scientific knowledge and is often approached by research groups to collaborate on projects investigating herbal therapies. MediHerb assesses each of these requests closely and applies stringent criteria to assess viability. The trial must fit with MediHerb’s philosophy of superior quality, innovative, and holistic herbal solutions, and must be conducted at a reputable research establishment. MediHerb does not fund or involve itself with research that utilises animals as human models.
The MediHerb Echinacea Research Story
Traditional usage of herbal medicines is always fundamental to MediHerb in how we utilise herbs but also poses questions for further modern research investigation. One such example of this is Echinacea. The root of Echinacea angustifolia is extremely large and is somewhat difficult to extract from the earth, despite this, it is the only part and species of Echinacea that was used by the Native Americans and the Eclectics. In particular, the Eclectics defined good quality root “as imparting a persistent tingling sensation” which is a clear reference to the alkylamide levels as a quality indicator (Felter & Lloyd 1983 (1905)). The Eclectics used a high ethanol content for extraction (which is very efficient for the extraction of alkylamides) and typically prescribed from 1 to 5 g/day of dried E. angustifolia root (in liquid form) (Felter 1983 (1905)).
In Europe during the 1930s the German herbalist Madaus used E. purpurea as he was more successful at growing this species. His interest in homoeopathy led him to use a preparation made of the fresh tops of the E. purpurea plant. This remains the most popular form of Echinacea in Germany today and contains very low levels of alkylamides.
There has been much debate centred upon the identity of the agents within Echinacea which are responsible for the immunological effects. MediHerb chose to quantify the levels of alkylamides in its Echinacea Premium products over 5 years ago. Consequently, MediHerb has gathered a wealth of information on the levels of alkylamides and caffeic acid derivatives in the various plant parts and preparations with which it deals.
In 1999 Dr Anna McIntosh from the National College of Naturopathic Medicine, Portland, Oregon used MediHerb Echinacea Premium liquid as part of a placebo-controlled, double-blind, clinical trial as a preventative for upper respiratory infections. This positive clinical trial showed that Echinacea Premium was effective in reducing the incidence of colds and flu by up to 70%.
MediHerb Echinacea Actives Project 2004
In 2003, MediHerb committed to a large research project with the primary question to be answered:
The project was divided into four parts:
- Predict which compounds are likely to be absorbed by using the Caco-2 model
- Determine which compounds have immune modulating effect
- Confirm bioavailability by undertaking a human pharmacokinetic study
- Examine physiological effects on the human immune system
The Caco-2 Intestinal Absorption Model
Caco-2 monolayers are used to identify compounds with good passive absorption from the digestive tract and added to this was the complex mixture of phytochemicals from Echinacea Premium. The following key findings were made:
- All the alkylamides were transported across the monolayer, with the actual extent varying depending upon the structural differences between the alkylamides
- The major alkylamide was very well transported (70% transported after 90 minutes) as had been reported by the Bauer group (Bauer 1999)
- The caffeic acid derivatives found in Echinacea Premium were all very poorly transported
- Cinnamic acid, a potential metabolite of the caffeic acid derivatives was well transported
- No synergistic effects of absorption were found, with the pure alkylamides being transported to the same extent as in the parent Echinacea extract
This work has recently been published by Matthias et al in the Journal of Clinical Pharmacy and Therapeutics, 2004; 29: 7-13.
Immune Modulating Effects
The key findings of these studies were that:
- Echinacea did not activate the immune system in the absence of other immunological stimuli
- Alkylamides and cichoric acid all decreased NFκB levels in stimulated cells
- Cichoric acid and the mixtures of alkylamides from Echinacea Premium all decreased TNFα production in stimulated cells
- Echinacea alkylamide mixtures and a 2-ene alkylamide decreased nitric oxide production in stimulated cells
This modulation of the immune response allows the body’s natural immune system to operate more efficiently than is possible in a system exhibiting dysfunction. In other words, to date it appears that the alkylamides have an immune modulating effect and recent research by Bauer and Gertsch have implicated the cannabinoid receptors.
Pharmacokinetics of the Echinacea Preparation Following Ingestion
The pharmacokinetics of Echinacea Premium were established in a human trial and the primary findings were:
- No caffeic acid conjugates were found (i.e. cichoric acid and echinacoside)
- No degradation products of the caffeic acid conjugates were found
- Alkylamides were the only phytochemicals from Echinacea which were identified in the human plasma samples
- The alkylamides showed typical absorption profiles as have been reported for oral drug preparations
- After about six hours most of the alkylamides had been metabolised or excreted. This is consistent with the recommended dosing regime of one tablet three times per day
Physiological Effects of Echinacea Premium in Humans
To further understand the effects of Echinacea Premium in humans, a small study was undertaken to investigate the effects on heat shock proteins and whole blood parameters. A small number of patients were dosed with Echinacea Premium tablets for two weeks, with these physiological parameters measured at the beginning and the end of the trial. Positive trends were evident for the heat shock protein level (hsp70) and the white cell counts. Further work is planned to further evaluate these effects in a much larger study.
The Importance of Liver Metabolism
Only alkylamides were found in human plasma after ingestion of Echinacea Premium tablets, but the levels were quite variable and first pass liver metabolism was suspected as influencing this observation. The 2,4-diene alkylamides were found to be rapidly degraded by human liver microsomes, in contrast the 2-ene alkylamides were much more slowly degraded. More interestingly, it was discovered that the 2-ene alkylamide, undeca-2E-ene-8,10-diynoic acid isobutylamide, actually slowed down the rate of 2,4-diene alkylamide degradation. The protective effect of this major alkylamide is a highly novel finding and it was deduced that only relatively small proportions of this compound will result in a product with enhanced bioavailability. (A patent has been applied for to protect this very important finding.)
This is the first work that supports the traditional use of Echinacea angustifolia root preparations, since the 2-ene alkylamides are not found in Echinacea purpurea.
The Echinacea Premium products combine the more potent but expensive, Echinacea angustifolia root extract, with the more economical, Echinacea purpurea, while still maintaining the ideal ratio of the protective 2-ene alkylamide (in terms of liver metabolism) to the more prevalent 2,4-dienes.
- Only alkylamides are transported in the Caco-2 intestinal absorption model
- Alkylamides have immune modulating effects in in-vitro models
- Pharmacokinetics: Only alkylamides are found in human plasma after ingestion of Echinacea Premium
- Echinacea Premium increased heat shock protein and white blood cell counts
- 2-ene alkylamides (only found in Echinacea angustifolia root) have been shown to protect 2,4-diene alkylamides, indicating that a mixture of E. angustifolia root and E. purpurea root is necessary for an efficacious product
The Story Continues
Further research is underway or planned in collaboration with Australian and European scientists:
- A human clinical trial of Echinacea Premium at the University of Wisconsin (due for completion in 2007)
- Evaluation of the pharmacokinetics of the liquid oral preparation of Echinacea Premium against the oral tablet preparation in collaboration with the University of New England
- Evaluation of the mechanism of immune effects in preparation in collaboration with the University of New England and Southern Cross University
- Collaboration with researchers at Swiss Federal Institute of Technology and the University of Graz to further investigate the cannabinoid receptor findings
Links to Echinacea Scientific Posters:
In vitro activity of alkylamides and ethanolic extracts from Echinacea
Permeability studies of alkylamides and caffeic acid conjugates
from Echinacea using a Caco-2 cell monolayer model
Pharmacokinetics of alkylamides and caffeic acid conjugates from Echinacea
NIH/MediHerb Echinacea Clinical Trial
Our research collaborations extend to the United States where we have a large scale National Institutes of Health (NIH) funded project to examine the efficacy of MediHerb’s Echinacea Premium tablets for the alleviation of the common cold. This project is a double-blind, placebo-controlled trial among the patients of the Verona Family Medicine Clinic, USA. This valuable trial will provide further evidence of efficacy that has already been demonstrated by a three-arm trial completed at the National College of Naturopathic Medicine in 1998. This earlier trial compared Echinacea Premium (standardised for alkylamides) to an adaptogen formula containing Korean Ginseng, Withania and Astragalus, and placebo in the prevention of winter colds over a three month period (MacIntosh et al.,1999). Those taking Echinacea Premium had a statistically significant (p = 0.03) decrease in winter infections when compared to placebo. The placebo group averaged an infection rate of 10% whereas the Echinacea group infection rate dropped to 2% at day 70. Ex vivo evidence of the efficacy of MediHerb Echinacea Premium for boosting immune function has also been obtained by researchers at the Royal Melbourne Institute of Technology (Francis et al., 2000).
NIH/MediHerb Bacopa Clinical Trial
Another NIH funded trial is to investigate the use of Brahmi (Bacopa monnieri) for cognitive enhancement in an aging population in collaboration with the Oregon Health & Science University. The principal investigator in this project, Dr Carlo Calabrese, approached MediHerb to supply a phytochemically characterised product and matching placebo for use in the trial.
For more information on the National Institutes of Health (NIH) see www.nih.gov.
MediHerb has also donated herbal medicines and matching placebos for other clinical trials. We are able to offer a uniquely integrated service to trial investigators: research-driven product quality and manufacturing; pharmaceutical standard GMP; packaged products with blinding completed and all relevant documentation. Some of these trials include:
- Valerian Complex for sleep problems in older adults (Royal Melbourne Institute of Technology)
- Formulated product for ADHD (Royal Melbourne Institute of Technology)
- Horsechestnut for venous leg ulcers (University of South Australia)
- Cognition enhancement in healthy students (University of Tasmania)
- Formulated product for menopause (Royal Melbourne Institute of Technology)
- Mexican Valerian for sleep difficulties in children with intellectual deficits (Royal Melbourne Institute of Technology) (Francis A, Dempster R. Phytomedicine 2002: 9(4): 273-279)
Clinical Feedback Trials
Clinical feedback trials involve our practitioners in the development and validation of new products prior to launch. By working together we are able to gather valid clinical data in a timely and cost-effective manner. Feedback trials were completed for Saligesic (a highly potent Willow Bark product for the relief of lower back pain) and Cramplex (a formulated product for the immediate relief of dysmenorrhoea) prior to their launch. The data generated from these trials is depicted in the graphs and clearly demonstrates their efficacy.
Understanding the complexities of the phytochemicals within herbs is fundamental to quality and efficacy. Once these are defined and identified through extensive laboratory analysis, quality assurance procedures can be established to ensure that the same premium quality raw material is consistently used.
A complicating factor of phytochemical analysis is the concept of marker and active compounds:
- a marker is a characteristic phytochemical found in a herb plant that is chosen to represent a quality standard
- an active is a phytochemical that is important for a given therapeutic effect of a herb
A marker compound may or may not be responsible for any therapeutic efficacy of the herb. A vast amount of phytochemical data has been compiled on various plant species from around the world, but there is a relative scarcity of data relating to the identification of active constituents. This is partly due to the often observed finding that the therapeutic action of a herb is due to the synergy of multiple phytochemicals, rather than just one isolated component.
MediHerb, in conjunction with the University of Queensland, is currently involved in a research project investigating the phytochemical profile of poorly-defined medicinal plants. This ground-breaking research has already provided some interesting data on widely used herbs whose phytochemical profile has previously been poorly understood, for example:
- A unique steriodal saponin has been identified in Chamaelirium luteum (False Unicorn) that is not found in any other medicinal herb. This unique phytochemical could be the key to False Unicorn’s therapeutic effect
- Investigation into the affect of bleaching Paeonia lactiflora (Paeonia) roots (as done in Traditional Chinese Medicine) has shown that the active constituent Paeoniflorin, is modified into another compound. The action of this new compound is unclear. Work is continuing to discover if its effect is therapeutic or otherwise
- Work is currently underway to characterise the saponins present in Dioscorea villosa (Wild Yam) as the information currently available comes from out-dated scientific literature
A project investigating the phytochemical characterisation of herbs with anthelmintic activity was conducted in conjunction with the Chemistry Department of the University of Queensland and the Department of Primary Industries. This project involved a PhD student and a Post-Doctoral researcher and targeted the identification of herbs with high anthelmintic activity and the constituents of those herbs responsible for this activity. The results of this research led to the reformulation of MediHerb’s Wormwood Complex tablets.
It is now considered to be a requirement for publication of clinical trials that the phytochemical constituents of the formulation be known and they must be included in the submission. Variations in phytochemical constituents is believed to be responsible for the varied clinical results obtained in many trials. A recent analysis of garlic trials (Lawson et al, 2001) has linked the efficacy of garlic formulations to those containing a high level of allicin release. However, in many early trials this information was not provided, either because it was not available or was proprietary.
Research programs on the growing and post harvest handling of herbs have been undertaken at a range of academic institutions, most with the support of the Australian Government under the Rural Industries Research and Development Corporation (RIRDC) grant scheme. These projects look at the importance of varietal selection, soil and climatic conditions, harvest time, post-harvest drying methods and storage in herb quality and efficacy. Projects under the RIRDC scheme have included three-year PhD research grants for the optimisation of Echinacea purpurea (in conjunction with the University of Newcastle), a study of Matricaria recutita (Chamomile) at the University of Tasmania, and examination of Valeriana officinalis (Valerian) at the University of Newcastle. Another project has recently been completed in collaboration with the Research Institute of Agroecology in Slovakia, investigating the optimal growth conditions for Tribulus terrestris (Tribulus).
Many smaller projects have centred on the optimisation of other herbs within the MediHerb range. One such example is Cynara scolymus (Globe Artichoke). Globe Artichoke contains a mixture of caffeoylquinic acids and flavonoids that contribute to its clinical effect. These were found to be quite variable in the raw materials sourced by MediHerb. A research project was initiated to investigate the causes of the variability, looking at varietal differences, geographical effects, harvest parameters, and post-harvest handling. It was found that by optimising the post-harvest handling of the Globe Artichoke leaves it was possible to increase the level of desirable phytochemicals by a factor of six.
By optimising the post-harvest handling of Globe Artichoke the levels of phytochemicals were increased by a factor of six.
Quality through Pharmaceutical Good Manufacturing Practice
In many countries including Australia, Japan and Europe, it is required that herbal products are manufactured according to the pharmaceutical code of ‘Good Manufacturing Practice’ (GMP). This is a quality assurance program that ensures:
- Validated equipment and processes
- Documented processes and systems
- Detailed records of each stage of manufacturing of each and every batch of product
- Control of the manufacturing environment, air and water
- Control of manufacturing materials, via quarantine, segregation and reconciliation
- Stability testing of goods offered for sale
- Documentation of customer complaints
Quality in the Laboratory – Good Laboratory Practice
The MediHerb laboratories are legally required to comply with the Australian standards of Good Laboratory Practice (GLP) under the Therapeutic Goods Act. GLP means adherence to strict criteria such as:
- Test method reliability: validation and control
- Instrument calibration and maintenance programs
- Reagent and standard quality control
- Authorised materials and product specifications
- Quality, integrity and authenticity of data
In Australia, herbal and nutritional products are regulated by the Therapeutic Goods Administration (TGA), part of the Federal Government. This is the same body and standard applied to pharmaceutical manufacturing. The TGA conducts regular audits of MediHerb’s manufacturing facility to ensure GMP compliance. In practice, however, herbal manufacturing under GMP is more complex than for conventional drugs because of the extra complexity conferred by the varying constituents present in the herb’s biological matrix. Compliance with GMP and TGA requirements further underscores our own dedication to making the most superior quality products.
Click Here for MediHerb's TGA Manufacturing Licence
At MediHerb our world-leading understanding of all these quality issues ensures that the practitioner ALWAYS receives superior quality efficacious clinical solutions.
That’s the guarantee of the MediHerb Philosophy.