Neural tube defects and herbal medicines containing lead: A possible relationship

doi:10.1016/j.mehy.2008.10.010

Medical Hypotheses

Volume 72, Issue 3, March 2009, Pages 285-287

https://doi.org/10.1016/j.mehy.2008.10.010 Get rights and content

Summary

Neural tube defects (NTDs) are the most common cause of potentially preventable congenital malformations in the human fetus. Even with the universal folate supplementation the incidence of NTDs remain higher is developing world than the industrialized countries. We think that lead, a component of many herbal medicines taken during pregnancy for generalized well being of mother and fetus may have a role to play. Lead, a bivalent ion, competes with zinc for crossing into the gut wall and hence slowly decreases the zinc stores in the body and replaces them with lead. As zinc is required at many steps in the absorption and synthesis of biologically active folate moiety, this state of zinc deficiency leads to lack of folate in the metabolically active cells. Hence, the DNA repair and nucleic acid biosynthesis are largely affected in the rapidly dividing embryo leading to NTDs and other abnormalities. We suggest that the marketing of the herbal medicines should be regulated and scientific studies should be carried out on them in order to know their potential effects.

Introduction

Neural tube defects (NTDs) are one of the most common causes of congenital malformations in the human fetus. Their incidence is higher in some parts of the world than others, for example in India it ranges from 3.9 to 8.8 per 1000 births and in China it ranges from 4 to 10 per 1000 births [1], [2] as compared to most developed countries where it is ranges from 2 to 4 per 1000 births [3]. Despite universal folate supplementation during pregnancy in these countries, rate of NTDs still remains higher than Western world. Many environmental and genetic factors can be potentially held accountable for the higher incidence of NTDs in India and China. However, many environmental factors that cause NTDs still remain unknown. Some studies in the past have linked lead to NTDs in humans, but a definite mechanism and substantial data are still lacking [4], [5], [6]. We explored the role of herbal medicines containing lead in causing NTDs and propose a supporting hypothesis.

Section snippets

Use of herbal medicines containing lead in pregnancy

In India, nearly 50% of pregnant women take herbal medicines at some point in their pregnancy [7]. Apart from the active ingredients, herbal medicines contain other pharmacological active substances or heavy metals, such as lead, cadmium and mercury [8], [9], which may have harmful effects on human pregnancy. However, the manufacturers of herbal medicines as well as literature provide no record of potential malformations and/or abortions they may cause in humans. Animal studies have

Evaluation of the hypothesis

Ethically it would not be possible to do a prospective study on pregnant women to corroborate the hypothesis. On the other hand, an animal model with pregnant female using a double blind, randomized controlled study may potentially evaluate this hypothesis, with one group of pregnant mice receiving herbal medicines containing lead and other receiving placebo. A prospective follow-up of zinc, folate, and lead levels both in the mother and offsprings with correlation to incidence of congenital

Discussion

Of all the classes of chemical compounds, metals have the greatest potential for embryotoxicity and teratogenicity [31]. Studies in the past have consistently shown teratogenic potential of lead, cadmium, arsenic, and mercury [24], [28], [31]. We recommend that herbal products containing high concentrations of lead, arsenic, cadmium and mercury should be strongly discouraged in pregnant women due to their possible direct and indirect (through anti-folate mechanism) teratogenic and toxic

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Effect of exposure to trace elements in the soil on the prevalence of neural tube defects in a high-risk area of China
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Our objective is to build a model that explains the association between the exposure to trace elements in the soil and the risk of neural tube defects.
We built a function with different parameters to describe the effects of trace elements on neural tube defects. The association between neural tube defects and trace element levels was transformed into an optimization problem using the maximum likelihood method.
Tin, lead, nickel, iron, copper, and aluminum had typical layered effects (dosage effects) on the prevalence of neural tube defects. Arsenic, selenium, zinc, strontium, and vanadium had no effect, and molybdenum had one threshold value that affected the prevalence of birth defects.
As an exploratory research work, our model can be used to determine the direction of the effect of the trace element content of cultivated soil on the risk of neural tube defects, which shows the clues by the dosage effect of their toxicological characteristics. Based on our findings, future biogeochemical research should focus on the direct effects of trace elements on human health.
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This chapter discusses a large number of popular and widely used nutraceutical ingredients, which have been researched and reviewed by the worldwide scientific community. Chromium (III) may have beneficial effects in the regulation of insulin action, metabolic syndrome and cardiovascular disease. Chromium (III) picolinate (CrPic) has gained much attention as a safe supplement that reportedly promotes fat loss and muscle enhancement in humans. Niacin-bound chromium (III) complex (NBC) attenuate insulin resistance and lowering plasma cholesterol levels, increasing cardioprotective potential and lean body mass. Ginger has been used as an herbal medicine to treat a wide range of ailments. Genistein and related phytoestrogens are best known as chemopreventive agents for a variety of human diseases and cancers, these are found in wide variety of plants. Resveratrol is a natural polyphenol found in grapes and other plants. The inhibitory actions of resveratrol analogs on steroidogenesis in Leydig cells indicate novel mechanisms of action of these compounds, which may be of potential therapeutic interest, where suppression of androgen action is needed. Green tea have anticancer properties, repeated intake of green tea extract may aggravate cyclophosphamide-induced body weight loss and malformations of fetuses by modulating CYP2B and CYP3A. Berberine is found in some herbal teas and health-related products. Likewise ginseng, boswellia serrata, hyaluronic acid, St. John's wort, pomegranate fruit extract, lutein, d-ribose, echinacea, omega-3 and omega-6 fatty acids, and curcumin are widely used nutraceutical ingredients. In future, more human studies, broad spectrum safety and toxicological studies and long-term evaluations are required for human consumption without causing any adverse events.
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¹: These authors contributed equally to this work.

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Neural tube defects and herbal medicines containing lead: A possible relationship

Summary

Introduction

Section snippets

Use of herbal medicines containing lead in pregnancy

Evaluation of the hypothesis

Discussion

Lancet

Am J Clin Nutr

Semin Perinatol

Am J Obstet Gynecol

J Nutr

Mol Cell Neurosci

J Nutr

Prevalence of neural tube defects in economically and socially deprived area of China

Childs Nerv Syst

Looking for causes of neural tube defects: where does the environment fit in?

Environ Health Perspect

Fetal anomalies resulting from maternal bullet-related plumbism

J Trauma