Coffee is said to increase cortisol. Caffeine is said to increase anxiety. I need to reduce both but I drink coffee daily for its neuro protective benefits. Can I finally say goodbye to coffee and replicate these benefits via a different means?
I’m revisiting this subject because I’m really tired of having to drink coffee. I have experimented with just adding a spoonful of coffee grounds to a little yogurt and gulped it down to get it over with. Maybe that conveys even more benefits than drinking it? Or maybe my liver will cry out for help if I keep this up.
“ Most of its effects are attributed to caffeine by the antagonism of adenosine receptors in the central nervous system; however, other coffee constituents like chlorogenic acids have also shown much promise in therapeutic value. Existing research considers coffee to have great potential, but additional studies are still needed to clarify the mechanisms and actual causal relationships in certain neuropathologies. “
“National Health and Nutrition Examination Survey (NHANES), which was conducted by Centers for Disease Control and Prevention (CDC), that coffee, caffeinated coffee, and caffeine were associated with cognitive performance while decaffeinated coffee was not [30].” -boohoo. I did not want to read that. I was hoping to eliminate caffeine.
“A study in mice demonstrated neuroprotection on 1-methyl-4-phenyl-1,2,3,6 tetra-hydropyridine (MPTP) model of PD by virtue of A2AR activity [44]. The local antioxidant property of CGAs aids in neurogenesis and together with pyrogallol, trigonelline, catechol, 5-hydroxytryptamides, and N-methylpyridinium exhibits similar effects by increasing calcium signaling and dopamine release in the central nervous system [13,41]. Another explanation is that coffee raises the number of bifidobacteria that are associated with mitigating local inflammatory response, diminishing procarcinogenic processes and lower misfolding rates of α-synuclein in the enteric nervous system, therefore reducing the risk of PD by decreasing dissemination of the protein to the brain [45]. There are very few studies that have looked into this avenue and require further investigation to better understand the mechanism. It is of note that the strongest association among all neurodegenerative diseases has been indicated in caffeine consumption with PD incidence [46”
* 3 cups a day for the greatest benefit! Oh no!
ncbi.nlm.nih.gov/pmc/articl...
From Science of Parkinson’s 2020
Oh Simon, you are so good. I thank you.
“For a long time it was been reported that coffee may be able to reduce the risk of developing Parkinson’s, but the mechansim by which this association could be occurring has remained elusive.
Now researchers from South Korea have discovered a biological pathway that could help to explain the protective association.
It involves a protein called PARP and a chemical called chlorogenic acid.”
“Numerous preclinical studies have suggested that the neuroprotective effect may be a result of caffeine (click here for a review on this topic), but a clinical trial found that 6–18 months of caffeine “did not provide clinically important improvement of motor manifestations of Parkinson’s” (Click here to read more about this).
And this has left the research field wondering what particular component(s) of coffee could be having the potential neuroprotective effect on Parkinson’s.”
Aha! Maybe I don’t have to ingest caffeine! Reading on to determine (hopefully)
PARP! A study in Korea states that it is the activity of PARP that confers the Neuroprotective benefits of coffee. How?
“RECAP #2: PARP (or Poly (ADP-ribose) polymerase) is a protein involved in detecting DNA damage and initiating a repair response.
It achieves this by binding to damaged DNA regions and beginning to synthesise chains of poly-ADP ribose (or PAR). But if this process becomes unregulated and too much PAR begins to build up, it can lead to a form of cell death called Parthanatos.” (Which is similar to apoptosis / programmed cell death)
“But what is apparent is that inhibiting PARP appears to be neuroprotective in models of neurological conditions.”
Okay, how do we inhibit PARP? Is that what coffee is doing? How can it be replicated and maybe even improved?
“Research groups have also found that inhibition of PARP reduces levels of the Parkinson’s associated protein alpha synuclein (Click here to read more about this).”
I AM NOW ON A MISSION TO INHIBIT PARP!
“ Poly (ADP-ribose) drives pathologic alpha-synuclein neurodegeneration in Parkinson’s disease” 2018
“By treating neurons grown in cell culture with preformed alpha synuclein fibrils, the researchers noted an increase in levels of both PARP and PAR, as well as an increase in cell death. When they treated these cells with PARP inhibitors, they found that the levels of PARP, PAR, and cell death all dropped dramatically.”
Mouse study: when mice were treated with a PARP inhibitor, in the presence of AS, dopamine neurons did not die. When not treated with a PARP inhibitor , dopamine neurons did die.
Wait…..
Now he is saying it’s PAR not PARP 🙄 would have been nice to just go directly to the point seeing as this is science and not a novel.
“On top of this result, exposing both normal cells and cells with no PARP to increased levels of PAR resulted in increased aggregation of alpha synuclein – which suggested to the researchers that it is PAR and not PARP that directly increases levels of alpha synuclein aggregation. By treating the cells with PARP inhibitors, the levels of PAR were also significantly reduced, which in turn resulted in less alpha synuclein aggregation.”
SUMMARY : (sort of)
“Alpha synuclein is killing cells by activating PARP (via the parthanatos cell death pathway)
PARP activation leads to increased levels of PAR which accelerate alpha synuclein aggregation (a feed-forward cycle)
PAR levels are increased in the brains of people with Parkinson’s
Given all of these results, the investigators suggested that clinically available PARP inhibitors should be considered for clinical testing in Parkinson’s”
Okay, so we are back to PARP inhibitors being a worthwhile target to seek out.
“Inhibiting PARP appears to be neuroprotective in models of neurological conditions, including Parkinson’s.
By blocking PARP, researchers have demonstrated the rescue of both neurotoxin and alpha synuclein models of Parkinson’s.”
“, the investigators found that liquiritigenin induced increases in RNF146 levels were able to protect the dopamine neurons (and this effect was associated with reducing levels of PAR):”
Okay? Can we supplement with liquiritigenin? No. Now what?
“also noticed that another agent in their drug screen – chlorogenic acid – exhibited the same properties (reducing PARP activity) and so they decided to investigate this in follow up research, which is the report we are reviewing today.”
CHLOROGENIC ACID - note to self, inhibits PARP and is found in coffee.
“administration of chlorogenic acid reduced the behavioural issues associated with this alpha synuclein model and protected the mice from dopamine neurodegeneration.”
Looking forward to the conclusion.
“The mechanism by which this neuroprotective effect may be occurring is unknown – there are a lot of chemicals in coffee. Recently, however, researchers in South Korea have highlighted one active component of coffee – chlorogenic acid – and an interesting mechanism of action (inhibition of PARP) that could help to explain the beneficial effect of coffee.”
Okay, at present I have concluded it’s best to keep drinking coffee (darn) and 3 cups is optimum (big darn!) BUT, how else can we get CHLOROGENIC ACID since that is quite clearly beneficial?
LL-37, a natural antimicrobial molecule present in the brain and gut, Suppresses Alpha-synuclein Clumping in Parkinson’s
Coffee and Parkinson's disease. The incredible effects of this drink.
Feedback from a PD research scientist in the department of Clinical Neuroscience at the University of Cambridge (UK), on PASADENA Trial...
