Caffeine and Inflammation - Especially Neuroinflammation

Since I missed our discussion last week I wanted to create a more in-depth post and this block of discussion has provided me an opportunity to talk about a pet theory of mine. Years ago I stumbled past a folk remedy book about recovering from sports injuries that talked about avoiding caffeine. At roughly the same time, I read an article in Outside magazine that suggested a link between caffeine and post-injury pain reduction. (I couldn’t find online references for either, sorry about that.)

My own antecdotal evidence suggested that caffeine actually slowed recovery after a major injury, but it wasn't until I found several papers on the subject that I realized the issue was one of Ca2+ mobilization and that caffeine interferes with bone remodeling and repair in the early stages [1,2.] I also wonder if there is a link between caffeine modulating inflammatory responses and lesser phagocytosis of damaged tissue resulting in prolonged tissue recovery times. I've been unable to locate any hard research on this. Either way, I think I can make a strong case that caffeine has positive effects with regard to CNS inflammation and generally negative effects with regard to peripheral inflammation.

Caffeine exerts its effects on inflammation by antagonistically binding adenosine receptors (Especially A1 and A2A, but others with lesser affinity.) This has several consequences downstream from the CNS, as well as within the CNS. In brain, caffeine antagonism of A1 and A2A receptors blocks the activity of adenosine, which acts to reduce the exocytosis of glutamate. Glutamate plays a central role in neuro-inflammation and studies that sought to modulate its release showed protective effects for diseases including Parkinson’s, Dimentia, and Alzheimer’s [3,4,5,6.] This activity also serves to excite neural cells resulting in a signal being received by the pituitary implying that some sort of “fight or flight” situation must be unfolding; it, in turn, tells the adrenal glands to begin releasing epinephrine. Epinephrine has serious consequences on inflammation, as those who have taken Neuroendocrine Physiology will probably remember. Among other things, it inhibits leukocyte vascular adhesion, reverses stimulus for TNF-alpha production, and increases IL-6 production. All of which would have demonstrable consequences for peripheral inflammation.

The reason I bring this up now is that some of the most promising research regarding caffeine and inflammation modulation seems to be centered around its possible neuro-protective effects. Indeed, plenty of research has been done on caffeine in relation to diabetes and other inflammatory disorders to little current avail. The current state of research for caffeine and Alzheimer’s, for example, suggests that caffeine may not just play a preventative role but might also function as a useful therapy [5.] Additionally, several studies have noted an improvement in motor symptoms and a slowing of disease course in Parkinson’s when patients are regular caffeine users, including the study referenced here [4.] Since caffeine is such a part of many American’s daily lives and it seems to have a definable place in control of neuro-inflammation, I wanted to make sure it got mentioned. Thanks for reading!

1. 1. Lu, Pin-Zhen (May 2008.) “Caffeine Induces Cell Death via Activation of Apoptotic Signal and Inactivation of Survival Signal in Human Osteoblasts.” Int J Mol Sci. 2008 May; 9(5): 698–718. PMC2635715.
2. 2. Duarte, PM (August 2009.) “The effects of caffeine administration on the early stage of bone healing and bone density: A histometric study in rats.” Arch Oral Biol. 2009 Aug;54(8):717-22. PMC19482261.
3. 3. Brothers, Holly M (August 2010.) “Caffeine attenuates lipopolysaccharide-induced neuroinflammation.” Neurosci Lett. 2010 August 16; 480(2): 97–100. PMC2905864.
4. 4. Ross, GW (2001.) “Current evidence for neuroprotective effects of nicotine and caffeine against Parkinson's disease.” Drugs Aging. 2001;18(11):797-806. PMC11772120.
5. 5. Marques, S (2011.) “Modulating Alzheimer's disease through caffeine: a putative link to epigenetics.” J Alzheimers Dis. 2011;24 Suppl 2:161-71. PMC21427489
6. 6. Gelber, RP (2011.) “Coffee intake in midlife and risk of dementia and its neuropathologic correlates.” J Alzheimers Dis. 2011;23(4):607-15. PMC21157028.