Table 2.
Summary of the clinical studies that show the neuroprotective effects of caffeine in PD patients and prospective studies that highlight the direct correlation between the consumption of caffeine and the low risk of PD.
| Title Study | Type Study | Patients | Age | Outcome | Results | Ref. |
|---|---|---|---|---|---|---|
| Caffeine for Motor Manifestations of Parkinson’s Disease (NCT01190735) | Complete phase 2 clinical study | 28 | aged 18 years and older | The aim of the study was to evaluate the tolerability and efficacy of the treatment at increasing doses of caffeine (100–200–300–500 mg). | NA | - |
| Caffeine for Excessive Daytime Somnolence in Parkinson’s Disease (NCT00459420) | Double-blind controlled phase 2/3 complete study | 58 | aged 18 years and older | The study evaluated the effects of caffeine in idiopathic PD patients treated daily with caffeine (100 mg) and for the following 3 weeks with caffeine (200 mg). | Caffeine treatment led to a reduction in the ESS score and the improvement of the Clinical Global Impression of Change outcomes and UPDRS. | [112] |
| Caffeine as a Therapy for Parkinson’s Disease (NCT01738178) | Complete phase 3 clinical study | 121 | aged 45–70 years | The aim of the study was to evaluate the effects of caffeine (200 mg) in idiopathic PD patients. | Caffeine did not improve motor parkinsonism, while it led to a slight improvement in sleepiness. Patients taking for long-time caffeine had a slight increase in dyskinesia and a worsening in cognitive tests. | [113] |
| Prospective study of caffeine consumption and risk of Parkinson’s disease in men and women | Prospective cohort study | 10 men and 16 women |
aged 40–75 years and aged 30–55 years | The study assessed the relationship between caffeine consumption with PD risk. | Moderate coffee consumption reduced the PD risk more in men than women. | [17] |
| Coffee Consumption, Gender, and Parkinson’s Disease Mortality in the Cancer Prevention Study II Cohort: The Modifying Effects of Estrogen | Cohort study | 909 men and 340 women | average aged 57 years men and aged 56 years women | The aim of the study was to evaluate the relationship between caffeine consumption and mortality rate for PD. | Caffeine consumption associated with smoking and alcohol led to a decrease in PD risk and a reduction in the rate of mortality. | [114] |
| Caffeine and Risk of Parkinson’s Disease in a Large Cohort of Men and Women | Prospective study | 197 men and 120 women | mean age 75 years men and 74 women | The study evaluated the relationship between caffeine consumption and PD risk. | Caffeine consumption reduced the risk of PD onset in both sexes. | [115] |
| Associations of Lower Caffeine Intake and Plasma Urate Levels with Idiopathic Parkinson’s Disease in the Harvard Biomarkers Study | Case-control study | 566 | average age 67 years | The aim of the study was to assess the effects of caffeine consumption and PD risk. | Caffeine consumption was associated with a lower risk of onset of idiopathic PD in the sex-independent way. | [116] |
| Association of Coffee and Caffeine Intake with the Risk of Parkinson Disease | Cohort study | 8004 | aged 45–68 years | The study assessed the relationship between caffeine consumption and PD risk. | The habitual caffeine consumers showed PD risk to be 5 times lower compared to non-coffee consumers. | [15] |
| Risk Factors for Parkinson’s Disease: The Leisure World Cohort Study | Case-control study | 395 | mean ages 75 years | The aim of the study was to evaluate the effects on caffeine consumption, as well as smoking and other risk factors related to PD risk. | Coffee consumption and smoking led to a reduction in the PD risk. | [117] |
| Coffee and tea consumption and the risk of Parkinson’s disease | Cohort study | 200 | aged 25–64 years | The study assessed the relationship between caffeine consumption and PD risk. | The higher caffeine consumption reduces the PD risk, especially in the 25–49 age range. | [118] |
| Prospective Study of Coffee Consumption and Risk of Parkinson’s Disease | Prospective Study | 101 | aged 50–79 years | The aim of the study was to analyze coffee consumption on the incidence of PD. | The daily consumers of coffee showed a lower risk of PD onset compared to non-coffee drinkers. | [16] |
| Differential Effects of Black Versus Green Tea on Risk of Parkinson’s Disease in the Singapore Chinese Health Study | Cohort study | 157 | aged 45–74 years | The study evaluated the relationship between caffeine consumption and PD risk. | The habitual coffee consumers or black tea, but not of green tea showed a low risk of developing PD. | [119] |
| A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson’s disease | Meta-analysis study | 18,605 | NA | The aim of the study was to assess coffee consumption and PD risk. | The daily coffee consumers showed a low PD risk compared to non-consumers. | [120] |
| Dietary and Lifestyle Variables in Relation to Incidence of Parkinson’s Disease in Greece | Cohort study | 118 | aged 20–86 years | The aim of the study was to examine the relationship between caffeine and eating habits as well as lifestyle and PD risk. | Caffeine consumption was associated with a lower risk of PD. | [121] |
| Caffeine Intake, Smoking, and Risk of Parkinson Disease in Men and Women | Cohort study | 318,260 | aged 50–71 years | The study was to evaluate the relationship between caffeine intake and PD risk. | Caffeine intake reduced the risk of PD onset independently by gender. | [122] |
NA: not available; ESS: Epworth Sleepiness Scale; UPDRS: Unified Parkinson’s Disease Rating Scale; HC: healthy controls; PD: Parkinson’s Disease.