Monday, January 25, 2016

What is in Traditional Chinese Medicines — a network analysis

I used to work for the New South Wales Institute of Technology, which in the late 1980s mutated into the University of Technology Sydney (UTS). During this process it acquired an organization called the College of Traditional Chinese Medicine. This group was placed in the Faculty of Science, for lack of anywhere else to put it.

These people had little contact with the rest of the faculty, and I don't recall ever meeting any of them. Indeed, their work was not really based on Western science. These days, the UTS College of Traditional Chinese Medicine offers a Bachelor of Health Science in Traditional Chinese Medicine, although they are most obvious in the UTS Chinese Herbal Medicine Clinic, which is also nominally still part of the Faculty of Science.

The presence of Traditional Chinese Medicine (TCM) in an Australian university setting is relevant to today's blog post, because Australia seems to be one of the few places to have shown any interest in connecting TCM and Western science. Indeed, there is also a Uniclinic of Traditional Chinese Medicine within the School of Science and Health at Western Sydney University. Most of the interest in studying TCMs has otherwise been confined to Asia (see Dennis Normile. 2003. The new face of Traditional Chinese Medicine. Science 299: 188-190).

Recently, a group of Australian researchers decided to have a look at the content of some of the TCMs available in their country:
Megan L. Coghlan, Garth Maker, Elly Crighton, James Haile, Dáithí C. Murray, Nicole E. White, Roger W. Byard, Matthew I. Bellgard, Ian Mullaney, Robert Trengove, Richard J.N. Allcock, Christine Nash, Claire Hoban, Kevin Jarrett, Ross Edwards, Ian F. Musgrave & Michael Bunce (2015) Combined DNA, toxicological and heavy metal analyses provides an auditing toolkit to improve pharmacovigilance of traditional Chinese medicine (TCM). Nature Scientific Reports 5: 17475.
Some of these TCMs (12 out of 26) are registered for use with the Therapeutic Goods Administration, which regulates their use within Australia, while the other TCMs are not (which technically means that they should not have been commercially available). However, there is little in the way of pharmacovigilance of herbal medicines anywhere in the world.

All of the products were comprehensively audited for their biological (via next generation DNA sequencing), toxicological (LC-MS analysis) and heavy metal (arsenic, cadmium and lead, via SF-ICP-MS analysis) contents. For the latter two analyses the amount of material detected was also quantified.

As usual, we can use a phylogenetic network to visualize these data, which I have done using a neighbor-net network on the presence-absence data. The result is shown in the figure. TCMs that are closely connected in the network are similar to each other based on their detected contents, and those that are further apart are progressively more different from each other. The registered products are highlighted in red.

There is wide variation among the products. The seven most divergent TCMs in the network are all unregistered, with the remaining seven being more similar to the registered TCMs. Only two TCMs (TCM10 and TCM17) have no discrepancies between the detected contents and what was declared (either to the regulatory agency, or to the consumer in the form of an ingredients list).

The authors summarize this situation:
Genetic analysis revealed that 50% of samples contained DNA of undeclared plant or animal taxa, including an endangered species of Panthera (snow leopard). In 50% of the TCMs, an undeclared pharmaceutical agent was detected including warfarin, dexamethasone, diclofenac, cyproheptadine and paracetamol. Mass spectrometry revealed heavy metals including arsenic, lead and cadmium, one with a level of arsenic >10 times the acceptable limit.
This study presents genetic, toxicological, and heavy metal data that should be of serious concern to regulatory agencies, medical professionals and the public who choose to adopt TCM as a treatment option. Of the 26 TCMs investigated, all but two can be classified as non-compliant on the grounds of DNA, toxicology and heavy metals, or a combination thereof. In total, 92% were deemed non-compliant with some medicines posing a serious health risk.
Such findings are not only of concern to the consumer, but also flag the need for detailed auditing of herbal preparations prior to evaluation in clinical trials.

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