The radical assault on our health

January 16, 1998

FREE RADICALS AND OXIDATIVE STRESS: ENVIRONMENT, DRUGS AND FOOD ADDITIVES.Edited by C. Rice-Evans, B. Halliwell and G. G. Lunt. Portland Press 6pp, Pounds 65.00. ISSN 0067 8694.

FREE RADICALS IN BRAIN PHYSIOLOGY AND DISORDERS. Edited by L. Packer, M. Hiramatsu and T. Yoshikawa. Academic Press, 474pp, Pounds 75.00. ISBN 0 12 543444 6.

FREE RADICALS: A PRACTICAL APPROACH. Edited by N. A. Punchard and F. J. Kelley. Oxford University Press, 310pp, Pounds 29.95 Pounds 60.00. ISBN 0 19 963559 5 and 63560 9.

Farmer and others recognised that food rancidity was brought about by oxidation of unsaturated fats in food by free radicals as early as 1943. Harman in 1956 first proposed that accumulation of free radical damage to unsaturated functional fats in animals underlies the ageing process. This idea has been greatly expanded so that a great many degenerative diseases not specifically of old age are also now suggested as having a free radical cause. The list is impressive: Alzheimer's, Parkinson's, epilepsy, damage following re-perfusion of blood to the brain after a stroke and a host of less notorious diseases.

A conference at Sussex University in December 1994 provided the papers recorded by C. Rice-Evans et al. This brought together leading medical scientists and food technologists whose approaches to free radicals and how to deal with them had been intellectually dislocated for far too long. This book is therefore imperative study material for the new Food Safety Committee. K. Davies's paper outlines "The paradox of life"; oxygen as a necessity and oxygen as a poison. "Peroxidised membranes and lipid oxidation products represent a constant threat to aerobic cells." There are several different homeostatic mechanisms for repair of membranes, but in disease and old age these may be compromised. This and the following chapters examine the sources of potentially damaging free radicals and anti-oxidant strategies in food and food packaging contrasted with those in living tissues.

Sources of damaging radicals include radiation, chelating agents, chemical and environmental pollutants such as nitrogen dioxide and the combined ingredients in the exhausts of diesel vehicles and not least the side-effects of "therapeutic" drugs. Anti-oxidants include vitamin E, vitamin C, carotene, dietary polyphenols; also those particularly mineral elements necessary for the functioning of free radical scavenging enzymes and polyamines. These elements are copper, zinc, manganese and selenium.

Addis and others from leading American medical schools provide a final contribution, which says less directly about free radicals and whose content, one suspects, may also have been the least familiar to most of the other participants. They address the problem of the consumption in diet of a combination of fats, including in particular those containing trans fatty acids that may make us particularly prone to disease and decay from free radical oxidation. Unlike proteins, which are rebuilt in the body from amino acid building blocks, our body fats, both in fatty deposits and in the structural phospholipids of all membranes, depend to substantial extent on the fats that we eat - and we have not got it right yet.

In the food industry, anti-oxidant chemicals are widely used to extend shelflife by avoiding oxidative damage to food itself or its packaging. While doing that job well and apparently safely in the light of that industry's conventional safety testing, anti-oxidants may yet pass on unexpected problems to consumers.

The chelating agent ethylene diamine tetracetic acid (EDTA) is one these. (It is widely used in vegetable canning in North America). Three papers draw attention to its hazard. Singh and others from Kings College, London, while considering suggested therapeutic use of iron chelators, warn of their potential side-effects. EDTA is unable fully to wrap around iron it chelates so that it is present in solution as a free radical generator in the form of a complex with water. Hippeli and Elstner also draw attention to the fact that the chelator EDTA strongly enhances oxidative processes in vivo. Erikkson and Na from the Danish food industry discuss antioxidant agents used to protect raw materials and processed foods. Chelating agents such as EDTA (called sequestering agents in food technology) are widely used to chelate metallic ions which would otherwise cause problems in appearance or stability. Their table of the large number of common additives used, omits EDTA, despite its mention in the text, which may suggest that the Danish food industry (or the editors?) appreciated its particular hazards.

Kuar and Barry Halliwell recall that early work on OH free radicals was mainly done by radiation chemists. Dodd and others from the Patterson Institute of Cancer Research, Manchester point out that free radicals that can be developed in bone by radiation are so very stable and long lived as to be able to be used in archaeology for dating purposes by using electron spin resonance. They do not add the corollary that radurisation of bone meal might thus be capable of generating large quantities of stable free radicals.

Gerald Scott from Aston University's chemical engineering department discusses anti-oxidants in food packaging: They may become harmful by doing their job in protecting the packaging from the food. "Anti-oxidants and stabilisers have to undergo a rigorous toxicity testing regime before they are licensed as food contact additive. However, in commercial practice, the potentially toxic derived transformation products formed in the package during its manufacture have generally not been tested at all." Is this still true?

The second book is a Festschrift in honour of Akitane Mori on his retirement from the department of neurosciences in Okayama University and a long and fruitful association with the University of California at Berkeley.

It is a measure of the regionalisation of science, that for such a remarkable conference as was put together by Packer in 1995 in Tokyo on such an important topic, there was not a single British contributor among 106, although most other European countries were substantially represented.

Mori's contributions have been concerned with the aetiology of epilepsy, and in particular with convulsant activity of guanidino compounds produced by OH free radicals reacting with creatinine. His interests, over many years, have sparked off a great many other investigations of the effects of free radicals in other abnormal conditions. Space does not allow much individual discussion of the 34 chapters of this splendid book.

On behalf of the World Health Organisation, to which Packer has been a consultant, Prilpko states in chapter 31 that by 1991, 23 conditions were recognised as having free radical involvement: these include Parkinson's disease, Alzheimer's disease, epilepsy, multiple sclerosis, alcoholism, schizophrenia, dementia, the cocaine syndrome, Aids/HIV, Tardif dyskinesia,"shock", and damage consequential on stroke or other head trauma. Ageing as a less specific condition is not included in the WHO list although Harman's free radical theory of ageing proposed as long ago as 1960 is fully supported, and in details extended, by so much work from then until now. Because of the high social costs of so many free radical-associated disorders it was WHO's view that there was urgent need greatly to strengthen neuroscience and to find ways to combat free radical damage by drug therapy. It is regrettable that Prilpko did not also suggest the need to try to reduce susceptibility to free radical damage through diet or by reducing pollutants. That I suppose would have trespassed on the functions of other organs of the United Nations? Or is it a matter of blind spots being the most lethal disease of all?

Halliwell's work here in Britain which is discussed in chapter 32 by Mori with three co-authors from Berkeley, provides perhaps the closest cross-reference between these two books. Halliwell has pointed out that the particular enrichment of the central nervous system in unsaturated lipids and non-haem iron creates a particularly sensitive environment for free radical oxidative damage.

Between these covers can be found up-to-date (as at August 1995) and thorough accounts from some of the foremost workers on free radical damage.They address the ways through which such damage is mediated biochemically and in cell biology in relation to brain disorders included above.

Overlooked however in both these books are Michael Crawford's crucial and pioneering studies begun long ago in Africa on the two contrasting sets of essential fatty acids depending on the omega-6 and omega-3 configurations of unsaturation. Brain membrane lipids are very special in requiring much higher ratios of omega-3 to omega-6 than other organs and for their great chain elongation and further de-saturation. Trans fatty acids in diet may accentuate the problem of their dietary mismatch. Anybody wishing to develop down that line should read for a start Neurobiology of Essential Fatty Acids (1992), edited by Nicolas Bazan and others, being Advances in Experimental Medicine and Biology, Vol. 318. It never ceases to astonish me how paths diverge in science, but rarely converge again.

That volume, from a conference held in Queensland, has led not just to a veritable revolution in thinking about nutrition and health in Australia but to a trade of formidable size between Canada and Australia in linseed. The curious may wish to find out why. (With British summer fields changing from yellower (oil seed rape low in omega-3) to bluer (linseed high in omega-3) suggests that perhaps our food and feed industries are not so far behind after all in appreciating the niceties (and nastities?) of dietary fats.) The third book of my trilogy is a scientific cookbook of the most useful sort. Gone are the days when delving among the materials and methods sections of published papers, or, more primitively still, starting from scratch and even inventing one's own equipment, was the way to get started in a new line of research. It is now protocols, like recipes, that are followed. Only the occasional cook need work innovatively. Good data can be procured without new technology. Using well-established protocols makes for better comparability of data.

The very reasonable concerns over food and health at the end of the millennium will inevitably call for more and better research focused around free radical damage. Thus the recent book Free Radicals: A Practical Approach will greatly assist any laboratory wishing to enter the fray in what must be one of the most exciting areas of medicine, nutritional science and food technology. It has to be said that the introductory sections to each chapter are in themselves small masterpieces of explanation of the states of the arts for which the protocols are relevant. Thus this book will be not just a laboratory manual but should be a bestseller in the student market.

Colin L. A. Leakey, an independent biologist, was a visiting professor in the department of pharmacy, University of Strathclyde, and lectures on man,food diet.

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