Summary Safety Review - Green tea extract-containing natural health products - Assessing the potential risk of liver injury (hepatotoxicity)

November 15, 2017 update: December 12, 2017

Product

Green tea extract-containing natural health products

Potential Safety Issue

Liver injury (hepatotoxicity)

Key Messages

• Green tea extract-containing natural health products are authorized for sale in Canada for a variety of uses, including to help in weight management (along with diet and exercise) and as a source of antioxidants for the maintenance of good health. The vast majority of those who consume green tea, in any form, do so without harm.
• Health Canada reviewed the potential risk of liver injury (hepatotoxicity) associated with green tea extract because of ongoing reports of serious liver injury worldwide, including a recent report in Canada.
• Health Canada's review concluded that there may be a link between the use of green tea extract and a risk of rare and unpredictable liver injury. While this risk is already identified in Health Canada's Green Tea Extracts monograph, Health Canada's review found that cases of liver injury continue to be reported in Canada and worldwide, and that Canadian safety information could be stronger.
• As a result, Health Canada will strengthen the current cautionary risk statement in Health Canada's Green Tea Extracts monograph to include the following:
  • "If you have a liver disorder, consult a health care practitioner prior to use. Stop use if you develop symptoms of liver trouble such as yellowing of the skin/eyes (jaundice), stomach pain, dark urine, sweating, nausea, unusual tiredness and/or loss of appetite and consult a health care practitioner"; and
  • "Rare, unpredictable cases of liver injury associated with green tea extract-containing products have been reported (in Canada and internationally)
• The safety review also recommended that green tea extract products be used by adults only. The Green Tea Extracts monograph was updated in August 2017 to include a subpopulation "Adults (18 years and older)".
• As a precautionary measure, Health Canada is requesting product licence holders of natural health products containing green tea extract as a medicinal ingredient and are intended for children and adolescents, to either remove the green tea extract from the product, or revise the label to indicate that the product is for adults (18 years and older) only.
  • Health Canada will continue to monitor any new information to determine whether additional risk mitigation measures are required, including, for example, limiting the amount of green tea extract's main antioxidant, epigallocatechin gallate (EGCG), in products. In the meantime, the Department is asking companies to confirm the quantity of EGCG in their products to inform any future additional actions.
• An Information Update  and a Health Product Risk Communication will be published to give the Canadian public and healthcare professionals more details about this risk.

Overview

Health Canada reviewed the potential risk of liver injury with green tea extract-containing natural health products because of ongoing reports of serious liver injury worldwide, including a recent report in Canada. More information regarding this recent case was published in Health Canada's Health Product InfoWatch in 2016. Health Canada's Green Tea Extracts monograph published in 2008 includes the following risk information:

• A statement about the risk of liver injury: "consult a healthcare practitioner prior to use if you have a liver disorder or if you develop symptoms of liver trouble (such as abdominal pain, dark urine or jaundice)"; and
• a direction to "take with food".

Use in Canada

• Green tea extract is a medicinal ingredient found in natural health products authorized for sale in Canada for a variety of uses, including to help in weight management (along with diet and exercise) and as a source of antioxidants (a substance that may prevent or delay some types of cell damage) for the maintenance of good health. Most of these products are not authorized for use by individuals under 18 years of age, including those authorized to help in weight management, and they are not recommended for use by individuals with liver problems.
• The main antioxidant in green tea is EGCG. Green tea extract-containing natural health products are available in different dosage forms such as capsules tablets, powders and liquids for oral administration (to be taken by mouth).
• There are currently over 2,500 licensed natural health products containing green tea extract as a medicinal ingredient in Canada; over 550 of these products have a claim related to weight management (in combination with diet and exercise).
• Unlike natural health products, green tea consumed as a beverage or other food product typically contains less EGCG than the amounts found in green tea extract-containing natural health products, on a per serving basis. The vast majority of those who consume green tea, in any form, do so without harm. 

Safety Review Findings

• At the time of the review, Health Canada had received 11 Canadian cases (between 2006 to 2016) of suspected liver injury associated with the use of products containing green tea extract.^{Footnote 1} Of these 11 cases, only 2 had enough information to be fully assessed. It was determined in these 2 cases that the liver injury was potentially related to the use of green tea extract-containing products.
• A search in the World Health Organization Adverse Drug Reaction Database found 89 international reports of liver injury associated with the use of green tea-containing products; however, none of these reports had enough information for a more in-depth assessment by Health Canada.
• The safety review also looked at published international information of liver injury with the use of green tea extract, including the United States Pharmacopeia's (USP) 2008 safety review of green tea extract where 34 reports of liver injury involving green tea extract products were found. Since 2008, there have been another 19 published international case reports of liver injury regarding the use of green tea extract-containing products that were identified as part of Health Canada's assessment. In the majority of these reports, stopping the use of the product, along with medical attention in hospital, was the first line of treatment and resolved the presenting signs and symptoms of liver injury. However, 1 patient developed a more serious disease (i.e.,chronic liver fibrosis) and 2 patients required a liver transplant.
• Cases of serious liver injury with green tea extract-containing products continue to be reported worldwide. However, they are rare and unpredictable events where the underlying reasons why liver injury happens are not well understood. Previous safety data has suggested that taking green tea extract-containing products with food can reduce the risk of side effects. This is already reflected in Health Canada's Green Tea Extracts monograph, which instructs to "take with food." 

Conclusions and Actions

• Health Canada's review concluded that there may be a link between green tea extract-containing natural health products and the risk of liver injury. While this risk is already identified in Health Canada's Green Tea Extracts monograph, Health Canada's review found that cases of liver injury continue to be reported in Canada and worldwide, and that Canadian safety information could be stronger.
• Health Canada is strengthening the safety information and will ask that manufacturers make the changes to green tea extract-containing natural health products. This will include information that rare and unpredictable, but potentially serious, cases of liver injury have been reported with green tea extract-containing product use and to stop using these products if certain symptoms or signs of potential liver injury happen (e.g., nausea, vomiting, abdominal pain, yellowing of the skin/eyes, dark urine, sweating, unusual tiredness and/or loss of appetite).
• The safety review also recommended that green tea extract products be used by adults only. The Green Tea Extracts monograph was updated in August 2017 to include a subpopulation "Adults (18 years and older)".
• As a precautionary measure, Health Canada is requesting product licence holders of natural health products containing green tea extract as a medicinal ingredient and are intended for children and adolescents, to either remove the green tea extract from the product, or revise the label to indicate that the product is for adults (18 years and older) only.
• Health Canada will continue to monitor any new information to determine whether additional risk mitigation measures are required, including, for example, limiting the amount of green tea extract's main antioxidant, epigallocatechin gallate (EGCG), in products. In the meantime, the Department is asking companies to confirm the quantity of EGCG in their products to inform any future additional actions.
• An Information Update  and a Health Product Risk Communication will be published to better inform the Canadian public and healthcare professionals about this risk.
• Health Canada will continue to monitor safety information involving green tea extract-containing products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified.

Additional Information

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of green tea extract both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.