HerbalEGram: Volume 12, Issue 4, April 2015

The recent removal of St. John’s wort (Hypericum perforatum) products from the Amazon.co.uk website is prompting debate in the United Kingdom herbal industry on what to do about unlicensed herbal products and how to protect UK consumers from products that may be unsafe or of deficient or otherwise unacceptable quality, while not placing an undue regulatory burden on companies.

The debate surfaced in March after 107 products were removed from the site by the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) for making unauthorized claims or being inappropriately labeled. While some industry groups believe that the agency overstepped by pulling products that were not making medicinal claims, herbal industry leaders agree the primary concern was one of safety.

The general position, according to MHRA media officer James McCreadie, is that the agency acted in accordance with procedures set out in its guidance, which requires that medicinal products hold a product license based on standards for safety, quality, and efficacy (email, March 27, 2015). While MHRA would not comment on specific products, McCreadie noted that consideration of claims being made “goes well beyond the information that is put on the packaging and can also extend to information on webpages and personal testimonies.”

The Traditional Herbal Registration (THR) scheme is a simplified procedure, he added, which enables certain medicinal products to be registered based on quality, safety, and evidence of their traditional use. “Products registered under the THR scheme are intended for minor conditions suitable for self-medication,” McCreadie said.

Under the European Traditional Herbal Medicinal Products Directive, products with this designation must meet quality and safety specifications and are required to include comprehensive safety and drug interaction information with the product. The registration process takes time and can cost as much as $200,000 per product,¹ depending on how much existing data a company has on its product. Unlicensed products do not adhere to these requirements.

“I think the only reason that the St. John’s wort was targeted was on the grounds of consumer safety,” said Dick Middleton, PhD, MGPhC, chairman of the British Herbal Medicine Association (BHMA), the UK’s leading trade association for the medicinal herb industry (email, March 20, 2015). “St John’s wort is a very useful herb for treating mood disorders and has a wide clinical research base,” he explained. “I believe that MHRA was concerned that consumers were not being empowered safely to choose to take St. John’s wort because of a lack of reliable consumer information and lack of quality assurance. This is clear because MHRA has registered many St. John’s wort products as traditional herbal medicines.”

Several St. John’s wort extracts have been well-studied for the primary use of addressing mild-to-moderate depression;¹ a 2008 meta-analysis of randomized controlled clinical trials documented their general efficacy and safety, reporting no serious adverse side effects.² Drug interactions have been a dominant area of concern, although some experts suggest that clinical evidence does not support this conclusion. That said, there is general agreement among clinicians and scientists that St. John’s wort extracts with a high hypreforin content have an herb-drug interaction profile that needs to be considered before use. Such extracts have been shown to influence drug metabolizing enzymes and drug transporter proteins that may lead to reduced therapeutic activity for certain drugs, including antidepressants, immunosuppressants, anti-coagulants, statins, oral contraceptives, and anti-cancer drugs.³


Finding a middle ground

The current cause of confusion in the UK comes from the two different market classifications for herbal products. Registered herbal medicines are used to treat, prevent, or cure specific medical conditions, while “botanicals” (as they are referred to in the UK) are used for general health and wellness and may not be advertised as medical treatments. Middleton agrees that there needs to be a place for both categories on the market. However, he said, the difficulty is that there is “no adequate control over the quality of botanicals, and this is illustrated time and again by studies that demonstrate lack of provenance and quality of these products.”

A case in point, Middleton noted, was the recent study of 40 rhodiola (Rhodiola rosea) root products purchased from UK websites and tested for ingredient identification. Eight products were found to be either the wrong species (R. crenulata) or adulterated with other species. “The traditional herbal medicines tested were all correct and had the highest rosavin content of all the samples,” he said. Rosavins are thought to be primary active constituents in R. rosea, but they are absent in R. crenulata, which makes them an ideal chemical marker to distinguish the authentic species from the adulterant. “So this is extremely relevant to the consumer and whether the product would work for them,” Middleton emphasized.

In Europe, he continued, “the EU through EFSA [the European Food Safety Authority] needs to assess and issue health claims for botanicals, whilst at the same time putting a scheme in place that ensures appropriate quality standards for such products. Easy words—very difficult to implement!”

These same concerns were echoed by Simon Mills, secretary of the European Scientific Cooperative on Phytotherapy (ESCOP), a consortium of European medicinal plant research experts and related parties with expertise in medicinal plant research. “Botanicals are not yet generally recommendable as their quality is found to be so variable,” Mills said (email, March 23, 2015). “We hope that standards we have worked so hard to establish for Traditional Herbal Medicinal Products can be a mark for the food supplement sector to emulate. We see initiatives like [the ABC-AHP-NCNPR] Botanical Adulteration Program, and indeed the FDA GMPs [Good Manufacturing Practices], as significant examples of what could be possible for the botanical sector over here.”

Although it may be too early to say, there has been little, if any, backlash in the herbal products market since the St. John’s wort products were removed. “The sector is always concerned about bad publicity,” Middleton said, “particularly as the majority of the sector is striving to manufacture high quality products.”

The other ongoing issue is that UK consumers can still purchase unlicensed herbal products on websites other than Amazon.co.uk. For MHRA, the effort will continue, according to McCreadie, who said the MHRA took action last year to close down more than 1,600 websites illegally advertising and selling medicines in the UK. “We continually look at sites selling inappropriately and will also take action where sites are brought to our attention,” he said.

There is also some speculation as to which, if any, other herbal products might be on MHRA’s radar. Black cohosh (Actaea racemosa) could be of concern, noted Middleton, due to previous quality issues and isolated hepatotoxicity reports. “There is ongoing, unresolved debate as to whether hepatotoxicity reports have been related to Black Cohosh, or could even possibly be related to adulteration with similar species,” he said.

Although manufacturers are not lining up to do battle over the regulatory classifications, it is clear, according to Mills, that THR is too demanding for some companies’ bottom lines. But, he noted, those companies “are pragmatically adapting their product ranges to the new horizons of EFSA — wherever they may be,” he said. “Some of us believe that much is being lost here, but actually our main common goal is to get a clear quality mark in the market. And this is where [groups] like BHMA can lead.”

—Karen Raterman

References

1. Herbal medicinal products. Eurocam website. Available at: http://cam-europe.eu/herbal-medicinal-products.php. Accessed April 2, 2015.
   
   
2. Blumenthal M. Clinical Overview: St. John’s wort (Hypericum perforatum L.). The ABC Clinical Guide to Herbs. Austin, TX: American Botanical Council. 2003:303-316.
   
   
3. Linde K, Berner MM, Kriston L. St John’s wort for major depression. Cochrane Database Syst Rev. 2008;(4):CD000448.
   
   
4. Gardner Z, McGuffin M. Hypericum perforatum L. Botanical Safety Handbook, 2nd ed. American Herbal Products Association. Boca Raton, FL: CRC Press. 2013:449-459.