The aetiology of Kashin-Beck disease (KBD) remains elusive. Four factors have been convincingly associated with the disease: selenium deficiency, iodine deficiency, grain contamination with mycotoxin-producing fungi, and water pollution with organic material and fulvic acid. The most credible studies from a scientific standpoint, i.e. randomised placebo controlled trials and observational cohort studies have either not been conducted or did not provide unequivocal demonstration in favour of any of these hypotheses. Many studies such as case-control, cross-sectional, "before-after", and even more so, ecological studies have been conducted. They merely produced weak evidence and fail to support any single factor to the exclusion of the others. The most scientifically sound studies have included animal models, laboratory experiments and pathology studies; however, these have only provided indirect evidence. Although none of the competing theories prevails when they are compared using a predefined and standard set of causality criteria (temporality, strength of the association, biological gradient, experimental evidence, biological plausibility, coherence, specificity and analogy), none should be discounted. This is an indication that a comprehensive and unifying theory is most likely to be multifactorial. Because the ultimate goal of those who are compelled by the challenge of KBD is to prevent its occurrence, a perfect understanding of its mechanisms is not indispensable for action. Well-conducted randomised intervention should be the priority of researchers as well as public health professionals to demonstrate what works and what does not.
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