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Possible shortcomings of fertility study

In a much-publicized paper recently published in the journal Fertility and Sterility, researchers at Loma Linda University reported that high doses of a number of popular herbs had adverse effects on hamster oocytes (eggs) and oocyte penetration by sperm in an in vitro laboratory experiment [Ondrizek et al., 1999]. Herbs tested were St. John's wort (Hypericum perforatum L., Clusiaceae), echinacea (Echinacea purpurea L. [Moench], Asteraceae), ginkgo (Ginkgo biloba L., Ginkgoaceae), and saw palmetto (Serenoa repens [Bartr.] Small, Arecaceae). All of the herbs except saw palmetto were reported to "damage reproductive cells" at high concentrations.

Buried deep within the article is one sentence in which the authors acknowledge the limitation of their research by suggesting, "The possibility of a lack of physiologic effect in vivo [in a living animal] should be considered." This type of extremely preliminary testing is never considered conclusive evidence, and if offered as evidence by supporters of herbal products, would be considered "junk science." Nonetheless, the journal Fertility and Sterility chose not only to publish the study, but also to issue a press release bringing the exaggerated results into the public spotlight. The resulting articles by The New York Times and many other newspapers misled the public into believing that a substantial adverse effect of the herbs had been discovered through credible research.

In the study, saw palmetto, echinacea, ginkgo, and St. John's wort extracts were tested in two concentrations to evaluate their effects on hamster eggs stripped of the protective coating called the zona pellucida. The hamster eggs were incubated with the herb extracts for one hour and then tested to find out whether fertilization would still occur. The results showed that saw palmetto had no effect on fertilization and that a significant effect was seen with St. John's wort, ginkgo, and echinacea only at high concentrations. In addition, exposure to high concentrations of St. John's wort and echinacea was reported to reduce sperm viability, and, in the case of St. John's wort, to cause sperm mutation.

There are numerous problems with this type of testing. First, in living animals, there is no evidence that the compounds in the extracts used either enter the bloodstream or ever come in contact with egg cells. Even if the extract were 100 percent absorbed (which it is not) and if it remained unchanged by the liver (which it does not), and if 100 percent of what was absorbed reached the ovaries and the testes (which is unknown, but unlikely) the "low concentration" is still too high by a factor of six-fold. The researchers used a dilution of 1/1,000 of the standard dose of each supplement, and suspended this amount in one milliliter of medium. This is a simple and clear mathematical error. The average blood volume of a human body is around 6,000 milliliters. Hence the dilution should have been 1/6,000 of the dose instead of 1/1,000.

Even if the researchers had used a correct dosage, they have no way of knowing which parts of the body are reached by what compounds in an extract. Many common substances will cause damage to isolated cells in petri dishes. The elaborate digestive and detoxification functions of the stomach, intestines, and liver produce dramatic differences between what is consumed and what eventually enters the bloodstream. The results of this test, namely that this concentration of certain herb extracts reduced the fertilization of hamster eggs, falls far short of the evidence necessary to conclude there is any effect in living organisms, and is much less than that required to put out a general caution to "infertile couples" about the potential effects of the herbs in questions.

In conclusion, among many other possible study shortcomings, the Loma Linda researchers appear to have miscalculated dosages and used an inappropriate assay to reach sweeping, unsupportable conclusions about the effects on fertility of several popular herbal dietary supplements.

Rob McCaleb, HRF

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[Ondrizek RR, Chan PJ, Patton WC, et al. An alternative medicine study of herbal effects on the penetration of zona-free hamster oocytes and the integrity of sperm deoxyribonucleic acid. Fertility and Sterility 1999; 71(3): 517-522.]


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