Selenium against arsenic toxicity and skin lesions

Spallholz, Julian

Abstract

An 800-person, 48-week, randomized, double-blinded, placebo-controlled Phase III clinical intervention trial to assess the efficacy of dietary selenium supplements in reducing arsenic body load and in arresting the growth of cancer-associated skin lesions. Background: Arsenicosis in children and adults is characterized by 1) melanosis on hands and trunk, 2) palmar-plantar hyperkeratosis, 3) basal and squamous cell carcinomas, and 4) various internal carcinomas. Mouse-, rat- and rabbit-model studies have demonstrated selenium's ability to mediate arsenic excretion through the formation of Se/As/GSH complexes and its ability quench arsenic radical oxidative species through the GPx pathway. A 2002, randomized, double-blind, placebo-controlled study among 82 Chinese villagers found reduced arsenic body load and melanosis in selenium-treated patients vs. placebo controls. Relevance; Bangladesh and West Bengal are suffering from an arsenicosis epidemic in which 5 million people are exposed to arsenic in drinking water > 300ug/L. The authors are collaborating with UNICEF to assess selenium's ability to counteract arsenic toxicity, with the potential of including selenium in nationwide nutrition programs. Proposal; To supplement the diet of 800 children and adults from arsenic-contaminated villages of Pabna District, Bangladesh, with either 200/150 ug selenite/day or placebo/day for 48 weeks. Endpoints; Primary/Confirmatory: Arsenic content of hair (As(CH3)2) and fingernail (Total As), sampled every 16 weeks and determined by HPLC-HG-AFS and NAA. Secondary/Exploratory: Progression or arrested progression of 1) palmar-plantar keratosis 2) melanosis of the upper trunk, assessed from controlled, randomized, blinded high-res, photographs by a panel of 5 dermatologists. Four quadrants of the patients' upper trunks will also be photographed by the DermLite epiluminescence digital dermascope and analyzed by the CVIPTools pigmented lesion analysis software package. Tertiary/Exploratory: Se content of hair and nails, measured alongside As by HG-AFS and NAA. To correct for individual exposure and metabolic variation, each individual will be compared to their baseline (t = 0 weeks'). Hypothesis; Ingestion of selenite supplements will result in a statistically significant decrease in body arsenic content. Anticipated Results: A 35% or greater reduction in body arsenic load in treatment versus placebo will be considered successful for presentation to UNICEF, USAID, and the Governments of India and Bangladesh.