The debate on the health benefits—and risks—of concentrated isoflavones from soy products, red clover and kudzu (phytoestrogens) goes on. Fermented soy products have been used for years, most notably in the East, to help women manage menopausal symptoms including hot flushes. As more research has been carried out, some of it showing very clear beneficial effects, more supplements containing concentrated phytoestrogens have come onto the market, including in the EU.

In 2007, the German government’s risk assessment advisors at the Federal Institute for Risk Assessment (Bundesinstitut für Risikobewertung [BfR]) published its “not without risk” opinion that cast a shadow over the safety of these supplements. The BfR was suggesting that the risk of breast and uterine cancers along with thyroid complications may be increased among those choosing to use these supplements based on isolated, high dose isoflavones.

EFSA: the game changer?

Last week, an opinion from the NDA panel of the European Food Safety Authority (EFSA), itself a response to the worrisome BfR opinion, added some serious weight to the debate. It concluded there was “no evidence of harm” from these supplements. EFSA’s view has impact because it is legally the highest authority on food safety in Europe, its powers overriding those of the BfR or any other national authority on food safety. And, contrast to so many opinions affecting supplements in the past, the EFSA opinion isn’t bad news. In fact, it’s good news for this category of supplements and the women who rely on them.

Empirical evidence: fermented soy

For years, especially in the East where a high proportion of the population is lactose intolerant, fermented soy products rich in isoflavones have been traditionally sought after as ‘medicinal foods’ because of their perceived health benefits, especially in reducing symptoms of the menopause and improving bone density in post-menopausal women. Women consuming fermented soy products like miso, tempeh and natto might consume up to 100 mg of isoflavones per day. The average Caucasian European consumes just 2 mg.

From traditional use to clinical trials and supplements

Positive results from scientific studies then fuelled a rash of more supplements in Western countries. More importantly, women who chose isoflavone supplements also generally chose to avoid Hormone Replacement Therapy (HRT), the most common prescription for menopausal symptoms prescribed by conventionally-trained medical doctors. Therefore it’s not difficult to understand that there could be a motive for a regulator to be pushed by drug companies to try to lock out supplements that reduce sales of HRT.

Most isoflavone supplements attempt to mimic the intakes from food in the East and these have been the subject of numerous studies, and it’s these typical levels of isoflavone exposure (35-150 mg/day) that EFSA considered in its review and opinion.

The BfR perspective

The BfR is notoriously geared to over-egging the risks of foods, micronutrients and other elements of our diet that we know to be important for health. In some cases, the Institute is so hyper-cautionary over risk that it comes up with views that end up severely limit consumer free choice and ability to self-care. An example of this is the maximum recommended level of vitamin B12, being a mere 9 mcg/day, when there is no properly substantiated evidence of harm from the vitamin at any dosage, other than an indirect effect of masking pernicious anaemia. And then, that’s usually only at extremely high milligram levels.

The BfR, it should be said, is also no fan of supplements. This is likely the main driver for its beef against concentrated, isolated isoflavones from soy or red clover, which was consolidated in its expert opinion of 2007. The type and amount of individual isoflavones varies with each of the plant sources, and there’s by far the least data available for kudzu, with most being from the soy forms.

Black mark, BfR

In our view, the BfR opinion is a particularly bad piece of scientific work. It recognises that acute adverse effects from concentrated soy isoflavones have been identified, and these are likely acute allergic reactions, unsurprising given that soy is a major food allergen. Let’s not forget that some of these effects may be more pronounced because the soy in many supplements is not fermented. In addition, soy crops have undergone considerable changes as a result of plant breeding in recent years and especially since the development of GM crops. Many of the concentrated products may originate from the USA but because they contain less than 0.9% GMO material, GMO labelling, even in the EU, is not required. Some may be contaminated with these protein fractions, although this is difficult to establish.

The BfR’s primary concern is in any event not these acute, allergic reactions, but the possibility of other effects being linked to the oestrogenic activity of isoflavones in high doses and therefore their long-term effects. Here, the BfR finds itself using largely speculative evidence for possible risks for oestrogen-dependent forms of breast cancer, as well as uterine cancers, other uterus-related conditions, and adverse effects on thyroid function.

Where BfR really goes wrong, is that it juxtaposes this largely speculative evidence of potential harm, with its failure to find (and it didn’t try very hard) sufficient evidence of benefit. It therefore chose to look at benefit from a much more limited perspective than risk. Let’s remember, the BfR’s remit in its opinion was actually not to do a benefit assessment at all, simply a risk assessment. Our view is that if it was given a remit to do a risk/benefit analysis, it should look at benefit with the same degree of rigour that it uses to evaluate risk. This faux-pas—both scientifically, and politically—is where the BfR goes badly off-piste. It’s also not the first time either.

Your turn, EFSA

On the basis of the BfR’s concerns, EFSA was handed the job of evaluating concentrated isoflavones, from a risk perspective. It evaluated 43 human studies and 62 animal ones. It attempted to assess a maximum safe level of intake. Had EFSA followed suit with BfR’s views about risk, its opinion could have easily spelled disaster for tens of thousands of women who choose natural phytoestrogen supplements over HRT.

Soy isoflavones inhibit thyroid peroxidase (TPO) and therefore have the potential to suppressthyroid hormone (T4) secretion, especially in cases of iodine deficiency. Ensuring women maintain adequate iodine in their diets and from supplements, along with other nutrients, is therefore key.

Some evidence of breast tumour growth, interference with thyroid hormone metabolism and various uterine effects is discussed in EFSA’s opinion, although human data for the majority of these potential adverse effects shown in vitro (tissue culture, cell lines, etc) or in animal studies are very limited or conflicting.

With a new NDA panel signing off the opinion last week, it could have been all over for this category of supplements, with the European Commission passing emergency measures to force the withdrawal of concentrated isoflavone supplements from the EU market.

Well, it wasn’t to be. At least for now.