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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. 19751985 (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 agentsboth complex mixtures from botanical
preparations and single drug substanceslong 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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