Summary: For carriers of the Parkinson’s related LRRK2 gene, coffee consumption can help lower the risk of developing symptoms of the disease.
Even for people with a gene mutation tied to Parkinson’s disease, coffee consumption may be associated with a lower risk of actually developing the disease, according to a new study published in the September 30, 2020, online issue of 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,” said study author Grace Crotty, M.D., of Massachusetts General Hospital in Boston and a member of the American Academy of Neurology. “It’s also possible that caffeine levels in the blood could be used as a biomarker to help identify which people with this gene will develop the disease, assuming caffeine levels remain relatively stable.”
Earlier studies have shown that coffee consumption may protect against the development of Parkinson’s disease in people who have no genetic risk factors for the disease. This study looked at people with a genetic mutation that increases the risk of Parkinson’s. The mutation is in a gene called LRRK2 for leucine-rich repeat kinase 2. But having the abnormal gene does not guarantee that people will develop the disease, so researchers are hoping to identify other genetic or environmental factors that affect whether people develop the disease.
The study compared 188 people who had Parkinson’s disease to 180 people who did not have the disease; both groups had people with the LRRK2 gene mutation and those without it. Researchers looked at the amount of caffeine in the blood, as well as other chemicals that are produced as caffeine is metabolized in the body, and how it varied among the groups. A total of 212 of the participants also completed questionnaires about how much caffeine they consumed each day.
Among people carrying the LRRK2 gene mutation, those who had Parkinson’s had a 76% lower concentration of caffeine in their blood than those who did not have Parkinson’s. People with Parkinson’s with a normal copy of the gene had a 31% lower concentration of caffeine in their blood than non-carriers without Parkinson’s.
Carriers of the gene mutation who had Parkinson’s also had lower consumption of caffeine in their diet. The gene carriers with Parkinson’s consumed 41% less caffeine per day than the people who did not have Parkinson’s, both with and without the gene mutation.
“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.
Crotty noted that the study looked at people at one point in time, so it does not help researchers understand any effect caffeine has over time on the risk for Parkinson’s or how it may affect the disease’s progression. It also does not prove that caffeine consumption directly causes a lower risk of Parkinson’s; it only shows an association.
Funding: The study was supported by the Michael J. Fox Foundation for Parkinson’s Research, Farmer Family Foundation Initiative for Parkinson’s Disease Research, Jane & Alan Batkin Research Fellowship, Edmond J. Safra Fellowship in Movement Disorders and the National Institutes of Health. Several study authors are employees of Denali Therapeutics, which is developing a drug that would target LRRK2 gene function.
Association of caffeine and related analytes with resistance to Parkinson’s disease among LRRK2 mutation carriers: A metabolomic study
Objective: To identify markers of resistance to developing Parkinson’s disease (PD) among LRRK2 mutation (LRRK2+) carriers, we carried out metabolomic profiling in individuals with PD and unaffected controls (UC), with and without the LRRK2 mutation.
Methods: Plasma from 368 PD and UC subjects in the LRRK2 Cohort Consortium (LCC), comprising 118 LRRK2+/PD+, 115 LRRK2+/UC, 70 LRRK2-/PD+ and 65 LRRK2-/UC, and CSF available from 68 of them were analyzed by liquid chromatography with mass spectrometry. For 282 analytes quantified in plasma and CSF, we assessed differences among the four groups and interactions between LRRK2 and PD status, using ANCOVA models adjusted by age, study site cohort, and sex, with p-value corrections for multiple comparisons.
Results: Plasma caffeine concentration was lower in PD vs. UC subjects (p<0.001), more so among LRRK2+ carriers (by 76%) than among LRRK2- subjects (by 31%), with significant interaction between LRRK2 and PD status (p=0.005). Similar results were found for caffeine metabolites (paraxanthine, theophylline, 1-methylxanthine) and a non-xanthine marker of coffee consumption (trigonelline) in plasma, and in the subset of corresponding CSF samples. Dietary caffeine was also lower in LRRK2+/PD+ compared to LRRK2+/UC with significant interaction effect with the LRRK2+ mutation (p <0.001).
Conclusions: Metabolomic analyses of the LCC samples identified caffeine, its demethylation metabolites, and trigonelline as prominent markers of resistance to PD linked to pathogenic LRRK2 mutations, more so than to idiopathic PD. As these analytes are known both as correlates of coffee consumption and as neuroprotectants in animal PD models, the findings may reflect their avoidance by those predisposed to develop PD or their protective effects among LRRK2 mutation carriers.