Isoflavones in food supplements for post-menopausal women: no evidence of harm

A comprehensive review of the available scientific evidence has revealed no indication that isoflavones at levels typically found in food supplements cause harm to post-menopausal women. Isoflavones are naturally occurring substances which are found, among other sources, in soy, red clover and kudzu root. Their extracts are often used as ingredients in nutritional supplements.

Dr Alicja Mortensen, Chair of the EFSA expert Panel on Food Additives (ANS), which carried out the assessment, stated: “The evidence reviewed does not suggest there are harmful effects on the three organs considered for this assessment – mammary gland, uterus and thyroid gland. We considered studies testing doses of isoflavones that are typically found in food supplements targeted at menopausal women in the EU.

“These conclusions were drawn on the basis of data collected on post-menopausal women and are supported by the results from animal studies.”

Dr Mortensen stressed, however, that “these are limited to the doses and duration of intakes investigated in these studies that range from three months to just under a year for those products available on the market in Europe”.

EFSA’s experts also attempted to assess the possible risks for women during the transition period to menopause and for menopausal women with a history or family history of cancer. They found, however, that there is no data to assess the safety of these substances for these groups of women.

In line with EFSA’s new “Promoting Methods for Evidence Use” approach, the ANS Panel captured the strategy for performing this risk assessment in a protocol that documents all the steps taken in reaching its final conclusions. This was the first EFSA opinion to pilot this new way of working, which enhances the robustness and transparency of the scientific process.

Prof Ursula Gundert-Remy, an ANS Panel Member and Chair of the Panel’s working group on isoflavones, said: “Defining a protocol before the start of the assessment helped us a lot to clarify the scope of our review and the information needs upfront. The focus was exclusively on the possible health effects on the uterus, thyroid gland and mammary gland specifically in peri- and post-menopausal women.

“For example, this made it clear that we would exclude all studies on men or data related to the use of soy formula in infants. It was also clear that information about the possible benefits of isoflavone-based food supplements was outside the scope of this assessment.”

Food contact materials: building on scientific developments

EFSA’s experts recommend refining the safety assessment of substances used in food contact materials, including the introduction of a more comprehensive approach to estimate consumer exposure, particularly for infants and toddlers. In the future, EFSA intends to update the Guidance on data requirements for the evaluation of these substances.

“This opinion reflects both advances in science and our experience over the last decade in applying existing EU guidelines,” said Dr Laurence Castle, a member of EFSA’s expert Panel on Food Contact Materials (CEF) and chair of the working group that developed the opinion.

Dr Castle stated that the scientific opinion “presents recent scientific developments that impact on the estimation of consumer exposure to substances migrating from food contact materials, the tiered approach to their safety assessment, toxicological data requirements and consideration of the migration of non-intentionally added substances (NIAS)”.

The next step in this process is for the European Commission to discuss with authorities in Member States the implications of these refinements for risk management. The Commission will then advise EFSA on the necessary levels of protection for consumers. EFSA will use the Commission’s advice to develop Guidance on data requirements for applications for the safety assessment of substances in food contact materials.

Among the opinion’s findings and key proposals are:

•      Identification and evaluation of all substances that migrate should focus more on the finished materials and articles, including the manufacturing process used, rather than concentrating on the substances used.

•      To better estimate consumer exposure EFSA’s experts propose setting four default food categories driven by infants’ and toddlers’ food consumption, that are approximately 9, 5, 3 and 1.2 times higher than the current default for consumption (i.e. 17 grams/kilogram of body weight per day). Using these default categories would give a higher level of protection for consumers, particularly for infants and toddlers.

•      The amount of toxicity data needed should be related to the expected human exposure. The CEF Panel proposes three threshold levels of human exposure, namely 1.5, 30 and 80 micrograms/kilogram of body weight per day, as triggers for the requirement for additional toxicity data. This applies in principle to all migrating substances, i.e. both intentionally and non-intentionally added substances (including oligomers).

•      Genotoxicity testing for substances used in food contact materials should be mandatory even if their migration into food leads to a low exposure. Alternative methods to animal testing could have increased importance for the safety assessment of NIAS.

The CEF Panel experts considered stakeholder feedback from a public consultation whilst finalising their opinion and refined some aspects. They included an additional food consumption category and clarified how to combine information on food consumption with information on migration of chemicals into food, to estimate consumer exposure. They also clarified the need to take account of other sources of exposure to these substances and introduced an additional tier in the toxicological data requirements.