Vol. 25 No. 2
March-April 2003

Natural and Synthetic Substances Related to Human Health (IUPAC Technical Report)

by J. G. Topliss, A. M. Clark, E. Ernst, C. D. Hufford, G. A. R. Johnston, J. M. Rimoldi, and B. J. Weimann

Pure and Applied Chemistry,
Vol. 74, No. 10, pp. 1975—1985 (2002)

There is a widespread belief on the part of the general public that natural substances are inherently superior to synthetic substances with regard to efficacy and safety in matters related to human health. This question is examined by reviewing the therapeutic use of drugs and herbal medicine preparations, the role of vitamins and nutrients, and the effects of toxic substances.

Substances produced in nature exhibit a variety of properties with respect to their effects on human health. These effects range from controlling regulatory processes essential for human life, serving as nutrients, acting as medicinal agents to cure or alleviate disease (either as single substances or mixtures as in herbal preparations), to producing extreme toxicity. Many have both favorable and unfavorable effects, often dose dependent. Even some vitamins can have untoward effects at very high doses, and the most potent natural toxin of all, botulinum, is used as a drug in minute doses to treat some conditions involving involuntary muscle contractions.

Natural substances originate from a wide variety of living organisms and serve different purposes. In addition to those that serve essential roles in human life, such as vitamins and nutrients, some are noxious and act as defense mechanisms against predators, while others paralyze prey. Yet others may have no obvious purpose but are metabolic end products that may possess all manner of properties from useful to harmful. These include genistein, widely distributed in plants, which in animal tests can disrupt endocrine function, and the botulinum toxins. Herbal products used as medicinal agents may have both harmful and beneficial effects in humans, and have not been subjected to the same rigorous standards of efficacy, safety, and purity accorded single chemical entities approved as drugs by regulatory agencies. The chemical structures of natural products are diverse and complex. Natural products provided the earliest medicinal agents–both complex mixtures from botanical preparations and single drug substances–long before synthetic organic chemistry developed to the stage where it could be an important route to new drugs. Natural products continue to be important today as sources of new drugs.

Synthetic substances, produced by chemical synthesis from basic chemical building blocks and utilized for a variety of purposes, have proliferated over the last half century as synthetic methodology and production technology have developed to highly sophisticated levels. Modern drug research is now predominantly based on substances produced by chemical synthesis, which involves the use of computer- aided drug design, combinatorial libraries, and structural optimization of lead compounds of both natural and synthetic origin to maximize the benefitrisk ratio. However, the discovery of bioactive natural products, which serve as leads for new drugs, remains an important drug discovery strategy. On the other hand, herbal products, for better or worse, remain essentially as the plant produced them: complex multicomponent mixtures that are often not well characterized or understood. Greater understanding will only be achieved as rigorous and well-designed scientific studies are conducted to examine the properties of these products that are consumed by millions of people each year.

The introduction and use of synthetic substances for various industrial purposes, in addition to impurities arising from industrial processes, have resulted in exposure to toxicity risk. Of course, a high level of toxicity is the intended purpose of a nerve gas. Pesticides can be toxic to humans, and dioxins are toxic substances, products of combustion, which can be generated through natural events such as forest fires or industrial processes. DDT, PCBs, and phthalate plasticizers are synthetic substances that pose risks as disruptors of endocrine function.

Another type of substance is a natural one that has been modified by a chemical synthesis process to a semisynthetic derivative in order to improve its properties. Examples include the numerous antibiotic semisynthetic penicillin and cephalosporin drugs and vitamin derivatives that improve stability. Natural substances that are also available in an identical molecular form by synthesis, represent another distinct category. A typical example is vitamin C, which is produced commercially by synthesis, and the synthetic substance is referred to as a nature-identical vitamin.

In conclusion, from the examples presented in this article, it is clear that natural and synthetic substances have a similar overall range of properties with regard to efficacy and safety, in terms of their impact on human health. The actions of individual substances are determined by their molecular structures and dose, not whether they are of natural or synthetic origin.

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2002/7410/7410x1957.html