A team of scientists from Singapore and Taiwan have discovered a decisive link between traditional Chinese herbal remedies and liver cancer. More specifically, it was the presence of one such chemical called “aristolochic acid” (AA), a known carcinogenic – found in various herbal remedies – which puts the largely Asian population at an increased risk of developing liver cancer.

Aristolochic acid, the deadly toxic

The multinational team of researchers, led by Professor Steven Rozen from Duke-NUS Medical School, Professor Teh Bin Tean from the National Cancer Centre Singapore, Professor Alex Chang from the John Hopkins Medicine Singapore and Professor Hsieh Sen-Yung from Chang Gung Memorial Hospital in Taiwan, discovered the link by comparing the mutational signatures of AA and liver cancer cases in Taiwan.

Mutational signatures are patterns of changes in the DNA which lead to cancer. By sequencing the DNA of liver cancers, the team obtained the mutational signature for comparative analysis against AA-related mutations. By doing so, they discovered that over 75% of the cases of liver cancer were related to AA-related mutations.

"Although we knew that there was exposure to AA in Taiwan, we were very surprised to find such a high proportion of liver cancer sufferers had exposure to AA," remarked Professor Hsieh.

While AA is a known carcinogen, previously implicated in kidney failure and urinary tract cancers, this is the first time a link between AA and liver cancer has been determined. What’s more, AA is a natural compound commonly found in Aristolochia and Asarum plants. These plants which are often used in traditional herbal remedies for the purposed of weight loss and slimming.

Affected countries

Proportions of examined liver cancers with AA mutations in various regions. Photo credit: Duke-NUS Medical School/EurekAlert
Proportions of examined liver cancers with AA mutations in various regions. Photo credit: Duke-NUS Medical School/EurekAlert

Since its initial link to kidney and urinary tract cancer was discovered, AA-containing products have been banned in various countries. In Europe, Aa has been officially banned since 2001. Singapore has banned AA since 2004 with an enforcement leading to a recall of a batch of AA-containing products in 2014.

In China and Taiwan, some herbs containing AA have been banned since 2003; nonetheless, some AA-containing herbs are still allowed in China. The lack of an outright ban in China or Taiwan makes it easier for manufacturers to continue making AA-containing herbal remedies and harder for consumers to knowingly avoid them.

Most of the affected patients came from Asian countries, with Taiwan and China having the highest percentages of AA-related cancer cases. Other Asian countries such as Japan and South Korea revealed to be affected too; but, to a lesser extent. Nevertheless, the countries affected were not limited to Asian countries with AA-related cancer cases reported in France, Spain, North American and the United Kingdom.

Loose regulations

Despite the decade long ban, the rates of AA-associated cancers have not fallen in recent years. Much of these are due to the loose regulations where AA herbs can still be found easily online. Moreover, some herbal remedies contain AA as part of the formulation, but, are not stated due to improper labelling or understanding.

The US Food and Drug Administration (FDA) has issued warnings about herbs containing AA. But for many, the warning has seemingly fallen on deaf ears, largely due to the lack of public awareness and enforcement. To make matters worse, the sale of AA-containing herbal remedies is also allowed – granted they are labelled appropriately and no health claims are made. In many Asian countries, AA-containing products and herbs have been banned for over a decade. Yet, AA-containing products and herbs are still widely available in the market. Citing its recent link to the development of liver cancer, Professor Alex Chang, from the research team, noted that “public education and awareness are very important for avoiding exposure”. MIMS

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