title: The nutrient-toxin dosage continuum in human evolution and modern health.
abstract: Recent findings support the long-recognized principle that nutritive and toxic effects of an ingested material depend not only on its nature but very much on its quantity. The well known observation that essential nutrients can be toxic at high dosages suggests that the same reversal of effect may be true of many substances that could be beneficial but not essential at low dosages (the phenomenon of hormesis). This has been demonstrated for many well known toxins. We suggest a mathematical model that describes these dosage effects as an expected result of the evolution of human metabolic and dietary adaptations for maximizing benefits and minimizing costs of the ingestion or other intake of any substance. Evolved mechanisms for achieving benefits may be unrelated to those for reducing costs. These evolutionary considerations suggest important consequences demonstrable by experimental or epidemiological studies. They also suggest ways in which our evolved dietary adaptations may be currently maladaptive, and individual development of taste preferences poorly calibrated by early experience in modern environments. The apparent reality of hormesis raises the possibility of counterproductive effects of current dosage recommendations and limits for nutrients and pollutants. We propose that some conceptual and factual problems are urgently in need of resolution. Fundamental to evolutionary biology is the tendency for organisms to become increasingly adapted to those environments to which they are most commonly exposed (Parsons 1990).
authors.affiliation: Department of Public Health, Cornell University Medical College, New York, New York 10021, USA. LIG2002@MAIL.MED.CORNELL.EDU
authors.forename: L M
authors.initials: LM
authors.lastname: Gerber
authors.forename: G C
authors.initials: GC
authors.lastname: Williams
authors.forename: S J
authors.initials: SJ
authors.lastname: Gray
mesh_terms: D000222:Adaptation, Physiological; D005075:Biological Evolution; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000494:pharmacology*; D006801:Humans; D009752:Nutritional Status; D011634:Public Health; D013649:Taste; D014118:Toxins, Biological / Q000494:pharmacology*
chemical_list: D004785:Environmental Pollutants; D014118:Toxins, Biological