Causal association biologic plausibility

Criteria similar to those listed by Adams (2003) are used to establish causality and are derivatives of Koch s postulates and Hume s criteria. The list includes (1) strength of association, (2) consistency of association, (3) specificity of association, (4) time order or temporality, (5) biological gradient over space and time, (6) experimental evidence available, and (7) biological plausibility. In many instances, especially at a regional scale and over long periods of time, meeting the requirements for each of these criteria can be difficult. 

A review of 69 published and unpublished case reports of black cohosh-associated hepatotoxicity indicated that there was an excluded, unlikely, unrelated, or unassess-able causality for black cohosh in 68 of 69 cases and "little, if any, supportive evidence for a significant hepatotoxic risk of black cohosh" (Teschke et al. 2009). Although one animal study on black cohosh rhizome has identified a biologically plausible mechanism of hepatotoxicity at high dose levels (Liide et al. 2007), no changes in liver enzyme levels have been observed in several human studies (Bai et al. 2007 Nasr and Nafeh 2009 Osmers et al. 2005 van Breemen et al. 2009). Healthcare practitioners and consumers should be aware of the possible association between products containing black cohosh and hepatotoxicity. 

Although the observational studies suggested modest associations of homocysteine with risk of vascular disease that were biologically plausible, such studies could not establish if these associations were causal. The randomized trials assessed the effectiveness of dietary supplementation with B vitamins to lower homocysteine levels on risk of cardiovascular morbidity and mortality. The initial trials were designed in the mid-1990s before the results of the Homocysteine Studies Collaboration meta-analysis (Homocysteine Studies Collaboration 2002) were reported in 2002. Consequently, few of the individual trials had sufficient statistical power to confirm or refute the 10% difference in... 

---