Methylxanthines and Human Health: Epidemiological and Experimental Evidence

  • Marie-Soleil Beaudoin
  • Terry E. GrahamEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 200)


When considering methylxanthines and human health, it must be recognized that in many countries most caffeine is consumed as coffee. This is further confounded by the fact that coffee contains many bioactive substances in addition to caffeine; it is rich in phenols (quinides, chlorogenic acid, and lactones) and also has diterpenes (fatty acid esters), potassium, niacin, magnesium, and the vitamin B3 precursor trigonelline. There is a paradox as consumption of either caffeine or caffeinated coffee results in a marked insulin resistance and yet habitual coffee consumption has repeatedly been reported to markedly reduce the risk for type 2 diabetes. There is strong evidence that caffeine reduces insulin sensitivity in skeletal muscle and this may be due to a combination of direct antagonism of A1 receptors and indirectly β-adrenergic stimulation as a result of increased sympathetic activity. Caffeine may also induce reduced hepatic glucose output. With the exception of bone mineral, there is little evidence that caffeine impacts negatively on other health issues. Coffee does not increase the risk of cardiovascular diseases or cancers and there is some evidence suggesting a positive relationship for the former and for some cancers, particularly hepatic cancer.


Caffeine Coffee Insulin resistance Type 2 diabetes Adenosine Cardiovascular disease 



Area under the curve


Cyclic AMP


Chlorogenic acid


Central nervous system


Cardiovascular disease


Cytochrome P450 1A2


Free fatty acid


Glucose-dependent insulinotropic polypeptide


Glucagon-like peptide-1


Insulin sensitivity index


Oral glucose tolerance test


Sympathetic nervous system


Type 2 diabetes



The work by the authors was supported by the Natural Science and Engineering Research Council of Canada (NSERC). M.-S.B. received an Ontario Graduate Scholarship.


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© Springer Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of Human Health and Nutritional SciencesUniversity of GuelphGuelphCanada

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