Ivan House

Toxicological Problems Resulting from Exposure to Traditional Remedies and Food Supplements

SummaryThe National Poisons Unit, London, carried out a pilot survey to investigate the frequency and severity of adverse effects/toxicity from exposure to traditional medicines and food supplements reported to the Unit. Enquiries related to suspected poisoning events were reviewed retrospectively from January 1983 to March 1989, and prospectively in 1991. Further information about cases identified by the prospective review was obtained, when appropriate, by follow-up questionnaire, clinical consultation by a consultant toxicologist, toxicological analyses of samples from patients and from products, and botanical identification of dried plant material.In total, 5536 enquiries were identified. Symptoms were reported in 657 (12%) of these. There was a large number of reports of accidental ingestion of vitamin preparations by children under 5 years. Appropriate assessment was possible in only relatively few cases, due to insufficient documentation, and poor labelling of certain products.A probable link between exposure and adverse effects was identified in 42 cases, and was highly probable in two. Heavy metal poisoning resulting from use of contaminated traditional remedies was confirmed in 5 cases. There was evidence that some patients took excessive doses of food supplements, without realising that this might result in toxic effects.The results of this pilot study suggest that there is a need for further surveillance to provide an appropriate risk assessment of food supplements and herbal remedies, improved quality control and labelling of these products, and increased awareness of their potential hazard.

Heavy metal poisoning from Ayurvedic traditional medicines: an emerging problem?

The use of Ayurvedic medicines is common in both adults and children and is increasing in many areas of the world. This paper will discuss the risks of heavy metal poisoning associated with the use of Ayurvedic medicines and illustrate this with some cases managed by the authors. Many Ayurvedic medicines contain heavy metals, including lead, mercury and arsenic, and there have been numerous reports of clinically significant heavy metal poisoning related to their use. However, there have been few studies that allow quantification of the incidence of this problem. There is limited regulation of these products in most areas of the world. Recent European legislation may help to improve safety of products bought in shops, but it is likely to have a relatively limited overall impact as it will not cover personal imports or products prescribed by traditional medicine practitioners. There is an urgent need for studies to quantify the frequency and potential risk of heavy metal poisoning from Ayurvedic medicines and for culturally appropriate education to inform the public of the potential for toxicity associated with these products.

Copper:caeruloplasmin ratio

Investigation of copper status can be a diagnostic challenge. The non-caeruloplasmin-bound copper (NCC) has deficiencies; accordingly, the copper:caeruloplasmin ratio has been suggested as an alternative index of copper status. A reference interval for this index was derived. In addition to making the interpretation of copper easier, the copper:caeruloplasmin ratio should also enable adjustment for relatively high caeruloplasmin concentrations without recourse to producing gender- and age-derived intervals. The copper:caeruloplasmin ratio has weaknesses similar to those identified for NCC in that immunological methods used for caeruloplasmin can cross react with apocaeruloplasmin and there is no standardised method for caeruloplasmin. Caeruloplasmin assays also have uncertainty from precision, bias and specificity and, accordingly, method-related differences may have a large effect on the copper:caeruloplasmin ratio in a manner similar to the NCC.

Severe iatrogenic bismuth poisoning with bismuth iodoform paraffin paste treated with DMPS chelation

Background. Bismuth iodoform paraffin paste (BIPP) is used for the packing of wound and surgical cavities. Features of both bismuth and iodoform toxicities have been associated with the use of BIPP, but there are no previous reports of 2,3-dimercaptopropane-1-sulphonate (DMPS) chelation therapy for bismuth poisoning secondary to its use. Case Report. A 67-year-old man presented with a pelvic tumor requiring extensive surgical resection. BIPP packing was required post-operatively for surgical wound breakdown. A few days after insertion, the patient developed neurological features of bismuth toxicity (blood and urine bismuth concentrations were 340 μg/L and 2800 μg/L, respectively), which was treated with removal of the BIPP packing and DMPS chelation [27 days of intravenous DMPS (5 mg/kg 4 times daily for 5 days, 5 mg/kg three times daily for 5 days followed by 5 mg/kg twice a day for 17 days) followed by 24 days of oral DMPS (200 mg three times a day for 10 days, followed 200 mg twice daily for 14 days)]. This resulted in improvement in his symptoms and a decline in his pre-chelation bismuth concentration of 480 μg/L to 5 μg/L following chelation. There were no adverse effects during chelation. Conclusions. DMPS chelation appears to be a potentially effective chelating agent in bismuth toxicity.

Adjusting copper concentrations for caeruloplasmin levels in routine clinical practice

Background: An investigation on copper metabolism usually includes the measurement of serum levels of copper and caeruloplasmin. Using these levels, some laboratories derive levels of non-caeruloplasmin-bound copper (NCC); however, a considerable number of patients may show negative values, which is not physiologically possible. Aim: To derive an equation for adjusted copper in a manner similar to that widely accepted for adjusted calcium. Methods: A linear regression equation for the relationship between caeruloplasmin and copper was used: [copper] (μmol/l) = 0.052×[caeruloplasmin] (mg/l). An equation for copper adjusted for caeruloplasmin was derived using this equation and the reference interval of 10–25 μmol/l for copper. Results: The derived equation was [adjusted copper] (μmol/l) = [total copper] (μmol/l)+0.052×[caeruloplasmin] (mg/l)+17.5 (μmol/l). The adjusted copper concentrations on the 2.5th and 97.5th centiles were 12.7 and 21.5 μmol/l, respectively, with the population having a gaussian distribution. The relationship between NCC and the adjusted copper concentrations is linear and independent of caeruloplasmin concentration. Conclusion: Calculation of copper adjusted for caeruloplasmin uses the same variables as those for NCC. Accordingly, the problems that are caused by the lack of specificity of caeruloplasmin immunoassays are the same as those identified for NCC. This calculation, however, overcomes the negative values that are found in a considerable minority of patients with NCC, as well as age and sex differences in the caeruloplasmin reference interval. As the concept is already familiar to non-laboratory healthcare professionals in the form of calcium adjusted for albumin, this method is potentially less confusing than that for NCC.

Should all patients with unexplained anaemia be screened for chronic lead poisoning

The global prevalence of lead poisoning is declining. However, the prevalence of lead poisoning in patients with either microcytic or normocytic anaemia is unknown. Blood samples from anaemic patients residing in south-east London without an obvious cause for anaemia had their blood lead concentration (BLC) analysed.A batch of 988 samples was analysed for BLC using atomic absorption spectroscopy. Median haemoglobin was 10.3 g/dL (range: 4.2–10.9) in females, 10.6 g/dL (range: 5.2–11.4) in males and 10.7 g/dL (range: 6.7–10.9) in children. Median BLC was 2.63 μg/dL (0.21–24.0 μg/dL; 95th centile 7.54 μg/dL). Fifteen samples (1.5%) had a BLC>10.0 μg/dL, five samples (1%)>15.0 μg/dL and one sample (0.1%)>20.0 μg/L. In the 106 children, median BLC was 2.34 μg/dL (0.5–14.5 μg/dL; 95th centile 6.12 μg/ dL). Only one child (14.5 μg/L) had a BLC>10.0 μg/dL. There was a poor correlation between haemoglobin and BLC (r2=0.08).Routine screening for lead poisoning cannot be justified in all patients with unexplained anaemia, unless there is a history or clinical features to suggest lead toxicity. Additionally, we have shown that in this former high-risk area for lead exposure, there is a low point prevalence of significant lead poisoning, even in an anaemic population.

Very low plasma copper levels do not automatically imply severe copper deficiency

Copper is an essential co-factor for many enzymes, including cytochromes. The vast majority of plasma copper is transported bound to caeruloplasmin; the rest is bound to albumin, transcuprein and copper-aminoacid complexes. Copperhomeostasis is controlled by the liver, which synthesizes the copper storage/ transport protein apocaeruloplasmin, which forms caeruloplasmin on the addition of copper . Low plasma copper concentrations occur in patients with primary copper de¢ciency (Menke’s disease, non-Wilsonian copper movement disorder) or excess copper syndromes (Wilson’s disease), or secondary to disorders such as nephrotic syndrome, remitting acute leukaemia, some childhood iron de¢ciency anaemias or Kwashiorkor. Oliver et al. described two cases of very low plasma copper concentrations, and concluded that these were as a result of severe copper de¢ciency despite adequate daily copper intake. Both of these patients were given approximately 12% more copper, and the plasma copper concentrations remained more or less unchanged approximately 50 days later. After more than 50 further days, one of the patients eventually achieved a ‘satisfactory’ plasma copper concentration, while the other remained eiectively unchanged. However, the changes in the plasma copper concentrations for both patients seem to be strongly associated with the changes in caeruloplasmin concentrations throughout this period. This is in keeping with plasma copper concentrations being dependent on the production of its transport protein apocaeruloplasmin. The relationship between caeruloplasmin and copper has a correlation coe⁄cient of approximately 0.92, and, as a result, the caeruloplasmin concentration should always be kept in mindwhen interpreting plasma copper concentrations. Low plasma caeruloplasmin concentrations are more likely to result from issues relating to protein metabolism than from copper de¢ciency in these patients. Accordingly, the low plasma copper concentrations described are more likely to have been secondary to the low caeruloplasmin concentrations, and, if the latter increased, the total plasma copper concentration also increased. Thus, the real lesson from these two cases is that very low copper concentrations are not necessarily due to copper de¢ciency, and that it is essential to interpret low plasma copper concentrations in the light of the respective caeruloplasmin concentrations.