Friday Hope: Caffeine: Blood-Brain Barrier Protection and SARS-CoV-2 Therapeutic Properties

Caffeine's ability to protect the Blood-Brain Barrier also offers protection against neurodegenerative diseases, such as Alzheimer's and Parkinson's.

Schematic diagram of the proposed antiviral mechanisms of caffeine against SARS-CoV-2. Caffeine can inhibit the production of TNF-α and the expression of the inflammasome NLRP3 and its activity by the MAPK/NF-κβ pathway, decreasing the production of IL-1β and IL-18. Caffeine also inhibits viral entrance by blocking the RBD and ACE2 complex formation. Caffeine also inhibits 3CLpro, a protease required to release two polypeptides that are necessary for viral transcription and replication. TNF-α, tumor necrosis factor alpha; NF-κβ, nuclear factor kappa beta; ACE2, angiotensin-converting enzyme 2; NLRP3, inflammasome NOD-like receptor 3; IL-6, interleukin 6; IL-1β, interleukin 1 beta; IL-18, interleukin 18; MAPK, mitogen-activated protein

Given the recent study showing that SARS-CoV-2 disrupts the Blood-Brain Barrier (BBB), I stated that I would search for therapeutics which help to protect the BBB and ward against neurodegenerative diseases. I found one such therapeutic which not only helps to protect the BBB, but is also useful against SARS-CoV-2. This is none other than Caffeine.

CAFFEINE AND ALZHEIMER'S (AD)

Caffeine has the abliity to protect against the development of AD on a number of fronts. One is protecting the integrity of the BBB.

Recent epidemiological and experimental studies indicate that caffeine, when administered chronically, has beneficial effects against a number of acute and chronic neurological disorders including stroke, AD, and PD. For AD, the protective effects of caffeine have been observed in humans as well as in animal models of this neurodegenerative disorder. Epidemiologically, chronic ingestion of caffeine conferred protective effects against AD and a retrospective study showed that caffeine intake is associated with a significantly lower risk for AD. Prospective studies confirmed the above findings by showing that chronic caffeine intake improved memory and cognitive function in normal aged individuals as well as in AD patients. Subsequently, experimental studies conducted using animal models of AD noted that caffeine improved cognitive abilities, reduced Aβ production, and stabilized BBB integrity. Thus, caffeine and drugs like caffeine might be part of any regimen intended to prevent, delay, and/or treat AD.

CAFFEINE AND PARKINSON'S (PD)

Additionally, the Adenosine-blocking, BBB protecting aspect of Caffeine may also treat Parkinsonian symptoms.

For PD, it was reported some 35 years ago that caffeine through blocking adenosine receptor activation could ameliorate parkinsonian symptoms. Subsequent retrospective, prospective, and epidemiologic studies demonstrated that caffeine when administered chronically decreased the risk of developing PD. Experimental studies confirmed and extended the epidemiological findings by showing that caffeine was neuroprotective against the loss of dopaminergic neurons that occurs in the substantial nigra of MPTP-treated mice. Thus, current evidence strongly suggests that caffeine is a promising agent in the prevention and/or treatment of PD.

Caffeine protects against disruptions of the blood-brain barrier in animal models of Alzheimer’s and Parkinson’s disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086010/

CAFFEINE AND SARS-CoV-2

Now we arrive at how Caffeine is also a useful therapeutic in treating COVID. There are many mechanisms by which Caffeine accomplishes this.

Antiviral

Notably, caffeine has also been observed to inhibit viral RNA synthesis and viral protein synthesis by some virus species such as the Newcastle disease virus, influenza virus, poliovirus, herpes simplex virus type 1 (HSV-1), human immunodeficiency virus (HIV), vaccinia virus, and polyomavirus. In particular, an in vitro study showed that caffeine was able to inhibit the replication of the hepatitis C virus.

Blocking Spike and ACE2

From the data generated in MDs, the IE between caffeine and RBD–ACE2 complexes was calculated, showing a strong interaction with 6LZG. The results show that caffeine is especially efficient at interacting with 6LZG, thus blocking the formation of the RBD–ACE2 complex.

Immunomodulatory

Among the many possible benefits caffeine might indirectly have in the infection caused by SARS-CoV-2, a strong emphasis should be made in the immunomodulatory effects it possesses. The application of a bolus of caffeine at a dose of 6 mg/kg produces an increase in the total lymphocyte and CD8+ lymphocyte count. Exposure of human cells to high and prolonged concentrations of caffeine has been shown to promote NK cell activity [69,70]. NK cells and lymphocytes are among the first cells activated against a viral threat and play a crucial role in the pathophysiology of COVID-19 infection.

Possible Beneficial Actions of Caffeine in SARS-CoV-2
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196824/

That daily cup (pot??!!) of Joe that you enjoy may be helping you far more than you know. Of course, Caffeine consumption is not for everyone and there are some individuals who have negative reactions to it. The above is a work of medical research, and not medical advice. Always consult your Primary Care Provider before using any supplements or drugs.

As for myself, I have been a lifelong coffee fanatic. I drink a ten cup pot almost every day. I'm not advocating for this level of consumption, I just happen to find fine coffee to be - drinkable art!

Please have a safe, joyous and blessed Holiday weekend here in the States. As always, thank you for your support, readership and dialog.