167 Molecular and Cellular Biochemistry 208: 167–168, 2000. © 2000 Kluwer Academic Publishers. Printed in the Netherlands. Vanadium and diabetes. What about vanadium toxicity?: A reply John H. McNeill Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada Received 24 March 1999; accepted 6 August 1999 Controversies and viewpoints Dr. Domingo has expressed concern that in our article, Poucheret et al. [1], we have not touched on the subject of potential vanadium toxicity. He refers to our article as a ‘review’ and implies that we have deliberately avoided discussing toxicity. In fact, as is clearly stated at the front of the issue of the journal, the article is the written form of a paper presented at the 2nd World Conference of the International Society for Molecular Nutrition and Therapy held August 20–27, 1997 in Winnipeg, Canada. We were invited to speak on Vanadium and Diabetes and therefore the article con- centrated on this topic although antihypertensive effects of vanadium and its potential effects on bone were also discussed. We are well aware of the literature on vanadium toxicity and have published a number of articles from our laboratory on the topic [2–7] as well as a book chapter [8]. All chemicals have toxicity at the right concentration and vanadium is not an exception. The question is, can vanadium produce potentially promising therapeutic effects at doses that produce no toxicity or limited toxicity? We believe that our own work and the published findings of others support a positive answer to that question. For example, we have given vanadyl sulfate to control and STZ diabetic rats in doses that controlled blood glucose in diabetic animals for a 1-year period, a very long time in the life of the rat. No biochemical, histological or functional changes due to the vanadium were noted [2–4]. The cellular pathology and secondary complications of diabetes were however prevented or reduced by the vanadium treatment in these studies [2–5, 7]. In all studies where it has been measured, vanadium has been shown to accumulate in some tissues [8]. We disagree that this is necessarily a toxic effect. The accumulation must result in a pathological change in order to be so classified. Another element, fluoride, also accumulates in bones and teeth but has a positive effect at the lower end of the accumulation curve. In our paper [1], we did describe ex- periments that showed no effect on vanadium accumulation on bone structure. Dr. Domingo agrees with us that in the human studies the major side effect is gastrointestinal problems, we in turn agree with him that the studies to-date have been for limited periods of time. In a chronic disease such as diabetes it is important to know what the long-term effects of chronically administered vanadium will be. Since human studies have only recently begun these data are currently not available but undoubtedly will be available in the next few years. Nevertheless there is no need to panic about vanadium toxicity! In North American, vanadium is consumed as a supplement in doses approaching those used in the published clinical studies. It is encouraging that no toxicity has yet been reported. Dr. Domingo goes on to list a number of other toxicities, including death that have been reported in the literature following oral vanadium administration to animals. As he is well aware, and as Srivastiva [9], whom he quotes, has commented, a significant amount of ‘vanadium toxicity’ that was reported in the early animal studies was due to dehydration. Some animals refused to drink the vanadium solutions. With STZ rats, failure to drink for one day can produce death. It is now known that stopping the vanadium treatment for a brief period (days) and then restarting it at a lower vanadium concentration in the drinking water solves the problem. Dr. Domingo comments on the mutagenic and carcinogenic potential of vanadium. His own statement is that vanadium is weakly mutagenic and that carcinogenicity has not been ruled out. Another way of stating this is that there is as yet no Address for offprints: J.H. McNeill, Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, B.C. V6T 1Z3, Canada