Caffeine May Protect Against Parkinson’s Due to LRRK2 Mutations

Caffeinated drinks like coffee may help to protect people from Parkinson’s disease caused by mutations in the LRRK2 gene, much as research suggests it does in preventing sporadic, or non-familial, forms of this disease, a study reported.

The study, “Association of caffeine and related analytes with resistance to Parkinson’s disease among LRRK2 mutation carriers: A metabolomic study,” was published in the journal Neurology.

“These results are promising and encourage future research exploring caffeine and caffeine-related therapies to lessen the chance that people with this gene develop Parkinson’s,” Grace Crotty, MD, a neurologist with Massachusetts General Hospital and the study’s first author, said in a press release.

Mutations in the LRRK2 gene are one of most common genetic causes of familial Parkinson’s. However, not all people with LRRK2 mutations go on to develop the disease.

The LRRK2 protein that this gene is responsible for producing plays an important role in cellular metabolism, such as autophagy (the cell’s recycling and waste-disposal system), and the mitochondrial activity that provides energy to cells.

Increasing evidence suggests that caffeine, or coffee consumption, may lower the risk of developing Parkinson’s and other neurodegenerative diseases.

A team of researchers at Massachusetts General Hospital investigated the association between Parkinson’s disease and coffee consumption in 368 people taking part in the LRRK2 Cohort Consortium (LCC), an assembly of study participants with and without Parkinson’s who carry mutations in the LRRK2 gene. LCC is coordinated and funded by the Michael J. Fox Foundation.

The study included 188 Parkinson’s patients: 118 with a LRRK2 mutation (mean age, 63.9) and 70 without these mutations (mean age, 64.4).

Also enrolled were 180 healthy people serving as controls: 115 carrying an LRRK2 mutation (mean age, 61) and 65 non-carriers (mean age, 63).

Researchers assessed differences among the four groups, and interactions between LRRK2 gene and Parkinson’s disease status using statistical models adjusted for age, sex, and study group.

Levels of caffeine and caffeine metabolites (byproducts produced in the body) in both blood samples and cerebrospinal fluid (CSF) — the clear, colorless liquid that fills and surrounds the brain and spinal cord — were also evaluated, with fasting times before samples were taken similar among all four groups.

Additionally, 212 study participants answered questionnaires regarding their daily caffeine consumption, including information on consuming caffeinated drinks such as coffee, black tea, green tea, and soda.

Results showed that the blood concentration of caffeine was significantly lower in Parkinson’s patients than in controls, especially among LRRK2 mutation carriers.

Among those with gene mutations, Parkinson’s patients had a 76% lower concentration of caffeine in their blood than did this healthy control group. Patients with a normal gene copy had a 31% lower concentration of caffeine in their blood compared to their respective control group.

Blood plasma levels of caffeine metabolites were also significantly lower in patients with LRRK2 gene mutations than in patients without these mutations: paraxanthine (66% vs. 21%), theophylline (67% vs. 21%), 1- methylxanthine (62% vs. 14%), and trigonelline, a marker of coffee consumption, (63% vs 15%).

CSF samples were available for 68 of those with analyzed blood samples. Among LRKK2 mutation carriers, both CSF and blood caffeine levels were significantly lower in the Parkinson’s group that in healthy mutation carriers (by 74% and 76%, respectively). In contrast, among non-mutation carriers, blood caffeine levels were 24% higher in Parkinson’s patients while those of the CSF were 23% lower when compared with healthy controls.

Caffeine consumption was also significantly lesser in LRRK2 mutation carriers with Parkinson’s (41% fewer daily milligrams of caffeine) than in mutation carriers without the disease.

“We don’t know yet whether people who are predisposed to Parkinson’s may tend to avoid drinking coffee or if some mutation carriers drink a lot of coffee and benefit from its neuroprotective effects,” Crotty said.

Researchers noted several limitations to their study’s finding, including the fact that it looked at people at one point in time, and did not address the effect of caffeine over time on risk for Parkinson’s and disease progression.

Although this study further supports an association, the researchers believe it is not yet possible to say definitively that caffeine consumption lowers the risk of Parkinson’s.