The mechanisms underlying caffeine’s acute effects and withdrawal symptoms are not entirely understood. The purpose was to determine whether these effects or symptoms co-exist in clusters, and whether they are associated with polymorphisms in β1- and β2-adrenoceptors. Subjects (n=1271) were from the Toronto Nutrigenomics and Health Study. The acute effects and withdrawal symptoms clustered into 4 and 6 factors, respectively. Subjects with the ADRβ2 Gly16Arg Gly/Arg genotype were more likely than Gly allele homozygotes to report “fatigue” withdrawal symptoms. Among >200 mg/d caffeine consumers, ADRβ2 Gly allele carriers had a greater risk, compared to Arg allele homozygotes, of reporting ‘flu-like somatic’ withdrawal symptoms. Among subjects with the CYP1A2 -163 A>C A/A genotype and 100-200 mg/d caffeine consumers, ADRβ1 Arg389Gly Gly allele carriers had a greater risk, compared to Arg allele homozygotes, of reporting “dysphoric mood” withdrawal symptoms. The findings suggest that β1- and β2- adrenoceptors play a role in caffeine withdrawal.

The mechanisms underlying caffeine’s acute effects and withdrawal symptoms are not entirely understood. The purpose was to determine whether these effects or symptoms co-exist in clusters, and whether they are associated with polymorphisms in β1- and β2-adrenoceptors. Subjects (n=1271) were from the Toronto Nutrigenomics and Health Study. The acute effects and withdrawal symptoms clustered into 4 and 6 factors, respectively. Subjects with the ADRβ2 Gly16Arg Gly/Arg genotype were more likely than Gly allele homozygotes to report “fatigue” withdrawal symptoms. Among >200 mg/d caffeine consumers, ADRβ2 Gly allele carriers had a greater risk, compared to Arg allele homozygotes, of reporting ‘flu-like somatic’ withdrawal symptoms. Among subjects with the CYP1A2 -163 A>C A/A genotype and 100-200 mg/d caffeine consumers, ADRβ1 Arg389Gly Gly allele carriers had a greater risk, compared to Arg allele homozygotes, of reporting “dysphoric mood” withdrawal symptoms. The findings suggest that β1- and β2- adrenoceptors play a role in caffeine withdrawal.