Cocoa may inhibit adenosine receptors modulating the blood brain barrier at the neurovascular unit improving cognition and white matter integrity.
Steven RBrenner, Physician retired., St. Louis University Dept. Neurology and PsychiatrySBren20979@aol.com
None
Submitted November 05, 2013
Sorond et al. discuss neurovascular coupling in response to cocoa in older people. [1] The effect of cocoa may be mediated by theobromine, the primary alkaloid in cocoa. The effects may be similar to caffeine, since theobromine is one of the primary demethylated metabolites of caffeine. In humans, the other metabolites are paraxanthine and theophylline. [2] Caffeine and theobromine both activate adenosine receptors in a similar manner. Adenosine receptor signaling modulates blood-brain barrier (BBB) permeability. [3] Activation of the A1 or A2A Adenosine receptor results in increased BBB permeability. [3]
Caffeine protects against disruptions of the BBB in animal models of Alzheimer and Parkinson disease, most likely through blocking cell surface adenosine receptors in endothelial cells, inhibiting cAMP phosphodiesterase activity, and affecting release of calcium from intracellular stores. [4] Mild cognitive impairment patients with plasma caffeine levels above 1200 ng/ml did not progress to dementia in the following two to four years of follow up, while some patients with lower levels did convert to dementia. [5]
Theobromine may inhibit adenosine receptors at the neurovascular unit, thus improving cognition and the integrity of the BBB in the cerebral white matter.
1.FA Sorond, SHurwitz, DH Salat, DN Greve, NDL Fisher. Neurovascular coupling, cerebral white matter interegrity, and response to cocoa in older people. Neurology 2013;81: 904-909 Published online Aug7, 2013, doi: 10.1212/WNL.0b013e3182a351aa.
2. A Lelo, DJ Birkett, RA Robson, JO Miners. Comparative
pharamacokinetics of caffeine and its
primary demethylated metabolites, paraxanthine theobromine and theophylline. Clin Pharmacol Ther. 1986; 39: 54-59.
3. AJ Carman, JH Mills, A Krenz, DG Kim, MS Bynoe, Adenosine receptor signaling modulates permeability of the blood-brain barrier. J Neurosci.
2011; 31: 13272-13280. Doi: 10.10.1523/JNEUROSCI.3337-11.2011.
4. X Chen, O Ghribi, JD Geiger. Caffeine protects against disruptions of the blood-brain barrier in animal models of Alzheimer's and Parkinson's disease. J Alzheimers Dis. 2010; 20(Suppl 1): @127-S141. Doi: 10.3233/JAD- 2010-1376.
5. C Cao, DA Loewenstein, X Lin, C Zhang, L Wang, R Duara, Y Wu et al. High Blood caffeine levels in MCI linked to lack of progression to dementia. J Alzheimer Dis. 2012; 30: 559-572. Doi: 10.3233/JAD-2012- 111781.
For disclosures, please contact the editorial office at journal@neurology.org.
Sorond et al. discuss neurovascular coupling in response to cocoa in older people. [1] The effect of cocoa may be mediated by theobromine, the primary alkaloid in cocoa. The effects may be similar to caffeine, since theobromine is one of the primary demethylated metabolites of caffeine. In humans, the other metabolites are paraxanthine and theophylline. [2] Caffeine and theobromine both activate adenosine receptors in a similar manner. Adenosine receptor signaling modulates blood-brain barrier (BBB) permeability. [3] Activation of the A1 or A2A Adenosine receptor results in increased BBB permeability. [3] Caffeine protects against disruptions of the BBB in animal models of Alzheimer and Parkinson disease, most likely through blocking cell surface adenosine receptors in endothelial cells, inhibiting cAMP phosphodiesterase activity, and affecting release of calcium from intracellular stores. [4] Mild cognitive impairment patients with plasma caffeine levels above 1200 ng/ml did not progress to dementia in the following two to four years of follow up, while some patients with lower levels did convert to dementia. [5]
Theobromine may inhibit adenosine receptors at the neurovascular unit, thus improving cognition and the integrity of the BBB in the cerebral white matter.
1.FA Sorond, SHurwitz, DH Salat, DN Greve, NDL Fisher. Neurovascular coupling, cerebral white matter interegrity, and response to cocoa in older people. Neurology 2013;81: 904-909 Published online Aug7, 2013, doi: 10.1212/WNL.0b013e3182a351aa.
2. A Lelo, DJ Birkett, RA Robson, JO Miners. Comparative pharamacokinetics of caffeine and its primary demethylated metabolites, paraxanthine theobromine and theophylline. Clin Pharmacol Ther. 1986; 39: 54-59.
3. AJ Carman, JH Mills, A Krenz, DG Kim, MS Bynoe, Adenosine receptor signaling modulates permeability of the blood-brain barrier. J Neurosci. 2011; 31: 13272-13280. Doi: 10.10.1523/JNEUROSCI.3337-11.2011.
4. X Chen, O Ghribi, JD Geiger. Caffeine protects against disruptions of the blood-brain barrier in animal models of Alzheimer's and Parkinson's disease. J Alzheimers Dis. 2010; 20(Suppl 1): @127-S141. Doi: 10.3233/JAD- 2010-1376.
5. C Cao, DA Loewenstein, X Lin, C Zhang, L Wang, R Duara, Y Wu et al. High Blood caffeine levels in MCI linked to lack of progression to dementia. J Alzheimer Dis. 2012; 30: 559-572. Doi: 10.3233/JAD-2012- 111781.
For disclosures, please contact the editorial office at journal@neurology.org.