Comprehensive and mechanistically focused dose-time response relationships are reported infrequently in the biomedical literature. Significant attempts have been made to identify such studies with the intention of better understanding the nature of the dose response in the low-dose zone and to identify underlying adaptive mechanisms when cells are stressed [1,2]. Boron is one such substance that has been the object of a broad spectrum of robust dose response investigations, along with complementary mechanistic features. These investigations have addressed a wide range of experimental models, diverse organ systems, and endpoints. What has been most strikingly shown in these studies was the very common, even dominating, series of observations that boron, an essential element in plants and animals, typically acts via an hormetic biphasic dose-response relationship, showing a stimulatory response at low doses, while being inhibitory and/or toxic at higher doses. Of particular interest is that many of the reported investigations were conducted with whole animals with 5–11 doses being employed, situations that are infrequently encountered in the biomedical literature.

The present paper provides the first integrated assessment of the occurrence of hormetic biphasic effects of boron in animal models, including both in vitro and in vivo studies, their mechanistic foundations and their clinical and the public health implications. Despite the fact that hormetic dose responses dominate the boron dose response experimentation, the concept of hormesis failed to be cited in the published papers, missing opportunities to link these findings with the broader and supportive hormetic literature within other areas of biomedical research. This glaring omission is actually rather common as has readily been pointed out in a series of papers on multiple types of stem cells [[3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]] and wound healing, dealing with keratinocytes [16] fibroblasts [17] and platelet enriched plasma [18]. Consequently, a brief overview of the concept of hormesis is provided after the introduction to better orient researchers to the hormesis dose response concept.