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Letters to the Editor
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Alternative therapies
Soy foods and their medicinal uses
From Dr M. A. Stockham, MRPharmS
The article on soy isoflavones (PDF 200K) by Nima Kotecha and Brian Lockwood
(PJ,
15 October, p483) highlights an inconsistency of standards between foods and
medicines with respect to medical claims. In my view, if foods are to be used
for medicinal purposes the same rigorous standards on quality, efficacy and
safety should be applied as they are for medicines.
The section on safety in the article could lead one to believe that phytoestrogens
and genistein are rather benign compounds, when they are used for acute conditions,
maybe, apart from gastro-intestinal irritation. But they are far from being
benign on continuous treatment. Endocrine disturbances, due to the compounds
acting as agonists or partial agonists on most oestrogen receptors are well
documented. Many oestrogens also interact with “non hormonal” binding
sites with quite surprising consequences. There are papers describing suppression
of the thyroid, immune system, and sperm production. DNA breakages have been
associated with phytoestrogen treatment and there are reports of increased
incidence of leukaemia, breast and colon cancer. Infertility, growth and disturbance
of pregnancy have also been described.
Have we not learnt the lessons from stilboestrol (diethylstilbestrol), which
was withdrawn when it was discovered that 20 years after treating pregnant
mothers there was a significant increase in vaginal cancer in their daughters?
Do not some of us wonder why we now have an epidemic of breast, prostate and
colon cancer, all organs which have oestrogen binding sites. Tumour induction
by the natural sex steroids in hormone replacement therapy products, such
as estradiol, are probably attributable to multiple risk factors. Estradiol,
estrone and estriol appear to be intrinsically safe at replacement levels
but the non- physiological phytoestrogenic compounds of the genistein type
carry the same di-aryl structure as stilboestrol and furthermore have a potentially
reactive hydroxy-ketone or ketone function in the structure: a recipe for
DNA binding and damage.
I also note that certain dietary isoflavone supplements have been given “generally
recognised as safe” approval in the US for incorporation into nutrition
bars and yoghurts. It has been calculated that up to 100mg of phytoestrogen
could, unwittingly, be consumed on a daily basis. Thus the article could lead
to individuals taking large amounts of estrogenic compounds over and above
this daily challenge without, in my view, an adequate safety analysis.
Having directed a research project in the field of phyto-estrogens and synthetic
analogues while in the pharmaceutical industry, I could not give a positive
approval for the medicinal use of soy-based products. On current evidence
the prospect for serious long-term dangers far outweigh the potential clinical
benefit. If it is not current practice, I would argue that soy products should
be quality controlled for isoflavone content and limits applied to prevent
oestrogen overload in the general population.
Mike Stockham
Saffron Walden, Essex
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BRIAN LOCKWOOD, author of the article, responds:
This letter contains
a number of pertinent points to address.
Mike Stockham holds a perfectly valid point of view concerning standards
for foods used for medical purposes. However, the nature of foods
and their promotion,
allows members of the public to purchase the product and to exceed normal
safe levels. Soy and its derived products are a staple foodstuff of
a number of
far eastern Asian diets, and constituent isoflavones are routinely consumed
at levels of up to 200mg daily by large populations. Soy formula milk and
soy protein are widely consumed in the US, with the agreement of the
Food and Drug
Administration to use health claims. Pharmaceutical companies may claim that
there is unfair competition in the area of complementary medicines and nutraceutical
supplements, but the balance has to some extent been redressed over the past
few years by these companies buying many of the suppliers of these products.
This article was written for pharmacists with the aim being to alert them
to the claimed benefits of soy for menopausal symptoms, but also include
discussion
concerning side effects. The majority of reported adverse effects have been
found in animal experimentation, usually using unnaturally high dosage levels.1–3 An in-depth review of adverse effects of soy products and isoflavones has been
published previously, but the detail was considered to be outside the scope
of this article.4 Minimal toxicity has been reported after treating postmenopausal
women with up to 16 mg/kg genistein daily for 30 days.5 In our view the article
gives a balanced view of the benefits and adverse effects.
Specific points have been raised concerning the history of stilboestrol,
but there is only slight structural similarity to soy isoflavones, and no
evidence
to suggest that they may act similarly. As with all flavonoids that are widespread
food components, these isoflavones can theoretically form free radicals,
and as such have potential to cause damage to DNA.
Many nutraceuticals have the “generally recognised as safe” status
in the US, and many are incorporated into functional foods and pharmaceutical
dosage forms. There will always be the risk that individual consumers will
take excessive levels, but the large companies involved in their supply will
have made a safety analysis, based upon both normal and abnormal usage. This
article has simply reviewed the published literature in the area, and reported
the levels of isoflavones used in a number of trials. Quality control of nutraceuticals,
including soy isoflavones, have been reported in the literature, and recently
reviewed; unfortunately the general quality is poor.6 However monographs are
being written, and consumer organisations and regulatory authorities are applying
pressure for improvement in standards.
References
1. Faqi AS, Johnson WD, Morrissey RL, McCormick DL. Reproductive toxicity
assessment of chronic dietary exposure to soy isoflavones in male rats.
Reproductive
Toxicology 2004;18:605–611
2. Misra RR, Hursting SD, Perkins SN, Sathyamoorthy N, Mirsalis JC, Riccio
ES, et al. Genotoxicity and carcinogenicity studies of soy isoflavones. International
Journal of Toxicology 2002;21:277–285
3. Doerge DR, Sheehan DM. Goitrogenic and estrogenic activity of soy isoflavones.
Environmental Health Perspectives Supplements 2002;110:349–353
4. Davies E, Greenacre D, Lockwood GB. Adverse effects and toxicity of nutraceuticals.
Reviews in Food and Nutrition Toxicity 2005;3:165–195
5. Bloedon LT, Jeffcoat AR, Lopaczynski W, Schell MJ, Black TM, Dix KJ, et
al. Safety and pharmacokinetics of purified soy isoflavones: Single-dose
administration to postmenopausal women. American Journal of Clinical Nutrition
2002;76:1126–1137
6. Lockwood GB. Nutraceutical supplements. In: Swarbrick J, Boylan JC, editors.
Encyclopedia of Pharmaceutical Technology. New York: Marcel Dekker, Inc,
2005;1–23. |
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