GRAPHICAL ABSTRACT

INTRODUCTION

The history of the Muslim world spans approximately 1,400 years, with more than two billion Muslims worldwide, making Islam the second-largest religion globally [1,2]. A significant proportion of Muslims actively practice their faith, including observing the traditions of Ramadan. Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting approximately 2 in 100 individuals over the age of 60, with an estimated 30 million people living with this condition worldwide [3]. Among these individuals, 91% in the Middle East and North Africa (MENA) region, 89% in Central Asia, 40% in Southeast Asia, 30% in Sub-Saharan Africa, 25% in Asia, 6% in Europe, and 1% in the Americas identify as Muslim [4].

The prevalence of PD in the MENA region has increased over the last 30 years and is currently estimated to be approximately 82.6 cases per 100,000 people. In 2019, the disease burden, measured in disability-adjusted life years, was found to be higher in females than in males, with males showing lower rates across almost all age groups [5]. Notably, a slight increase in PD burden was associated with higher socioeconomic development index levels. Factors contributing to this rising prevalence include an aging population, environmental changes such as increased air pollution, and shifts in dietary habits and lifestyles. Additionally, among females, those with anemia or higher education levels have been identified as more vulnerable to developing PD [6].

The global population with PD is expected to increase by 40% by 2040. Ramadan, the holy month of fasting in Islam, occurs in the ninth month of the lunar calendar and shifts approximately 11 days each year [7]. Fasting during this month is one of the Five Pillars of Islam and is mandatory for all adult Muslims. Participants abstain from food and drink from sunrise to sunset, typically eating two meals: Suhoor before dawn and Iftar at sunset [8]. While those who are ill are exempt from fasting, some choose to observe it regardless of health risks due to their strong faith and emotional connection to the month [9].

The enduring benefits of fasting during Ramadan for those seeking a healthier lifestyle include potential advantages such as weight loss and the cessation of unhealthy habits such as smoking [10]. However, several unmet needs remain concerning the potential adverse health effects of fasting in vulnerable individuals, such as those with unstable PD, where fasting may negatively impact both motor and nonmotor symptoms [11]. Fasting can significantly impact individuals with medical conditions because of dehydration, metabolic changes, and delays in medication intake; this is particularly evident in diabetes, where fasting can heighten the risk of complications such as diabetic ketoacidosis, hypoglycemia, dehydration, and other metabolic issues. While the effects of fasting on those with PD are not yet clearly understood, it is likely that many Muslims with PD could be similarly affected [12].

Physiological changes during Ramadan fasting

Fasting can significantly influence blood glucose levels and increase morning leptin production, largely because of changes in meal timing and the body’s circadian rhythms [13,14]. These hormonal and metabolic shifts are vital for regulating energy and the response to food. Intermittent fasting, in particular, has been shown to increase insulin sensitivity and improve glucose metabolism [15,16]. The increase in morning leptin levels after fasting suggests that the body is adapting to a reduced eating schedule [17]. Meal timing plays a critical role; for example, delaying the start of eating can increase blood glucose levels [18,19]. Adjusting mealtimes can affect glucose responses and other metabolic functions. 20,21 Additionally, circadian rhythms impact the production of hormones such as leptin and influence how the body reacts to food intake [22,23].

Management of Parkinson’s disease

Replenishing dopamine is essential for managing PD, with levodopa being the most effective treatment. Patients typically take levodopa 3–4 times daily, but as the disease progresses, some may need up to 10–12 doses, often in combination with other medications [24]. Additional strategies for symptom control can include the use of dopamine agonists, catechol-O-methyltransferase (COMT) inhibitors, and various other formulations. Alternative delivery methods, such as transdermal patches, are also used to enhance treatment adherence and effectiveness. These doses are often calculated based on levodopa equivalent doses (LED) [25].

What happens if patients stop or delay taking Parkinson’s medications suddenly during fasting?

Abrupt cessation of anti-Parkinson’s medications can sometimes trigger or resemble a catatonic state, where the patient becomes completely frozen, rigid, and unable to move; this may evolve into an akinetic crisis, characterized by severe dehydration, fever, rhabdomyolysis, and other potentially detrimental consequences, such as malignant hyperthermia [26,27], especially in fasting individuals or in warm climates. Additionally, abrupt withdrawal from dopamine agonists may cause dopamine agonist withdrawal syndrome, which affects up to 19% of patients with symptoms such as anxiety, irritability, fatigue [28] (Figure 1).

Continuous objective monitoring using wearable sensors and its role in Parkinson’s disease

The Parkinson’s KinetiGraph (PKG) is a wrist-worn device that objectively monitors the motor symptoms of PD at home [29]. It generates several scores, such as the bradykinesia score, dyskinesia score, percentage tremor time, and percentage time immobile, providing a thorough assessment of motor function that complements traditional clinical evaluations [30,31]. The PKG also tracks sleep quality, daytime sleepiness, inactivity, and tremors, making it a comprehensive tool for managing PD [32,33].

Hypothesis

Fasting due to Ramadan and a lack of fluid intake lead to deterioration in overall motor status, deterioration in motor fluctuation status, deterioration in nonmotor fluctuation status, worsening sleep quality due to worse early morning akinesia, worsening and fluctuating neuropsychiatric states, worse mobility, and an increased risk of falls and fractures in frail subjects.

Objectives

We address the above hypotheses by using the following enablers: the Ramadan Regime (twice a day Regime); Hoehn and Yahr Scale (HY) and the Unified PD Rating Scale (UPDRS) for motor state; the PD Non-Motor Symptoms Questionnaire (NMSQ) and Non-Motor Symptoms Scale (NMSS) for the assessment of global nonmotor state; the Hospital Anxiety and Depression Scale (HADS), Panic Disorder Severity Scale (PDSS), and Parkinson’s Disease Questionnaire (PDQ-8) for the assessment of sleep, anxiety, depression, and quality of life; and the PKG 24-hour ×4-week home monitoring for early morning offs (EMOs), overall motor state, bradykinesia, dyskinesia, tremor, and sleep score.

MATERIALS & METHODS

Study design

This four-week longitudinal observational cohort study was conducted at King’s College Hospital Dubai, UAE, from February 20, 2025, to April 1, 2025. Patients were recruited from the Movement Disorder Service at King’s College Hospital Dubai, with additional participation from Saudi German Hospital, UAE, and Bahrain Specialty Hospital, Bahrain; EMC hospitals Jakarta, Indonesia; and Parkinson’s Research Alliance India affiliated hospitals, India. Patients were invited to a baseline visit one week prior to Ramadan (February 20–27) for initial assessments. Following the baseline visit, patients were instructed to wear the PKG wrist-worn device on their symptom-dominant side for four continuous weeks during Ramadan. A prepaid envelope was provided for patients to return the device to the hospital, where it was reviewed by a neurologist within 24 hours of receipt. The implementation of any changes was assessed during the entire holy month (4 weeks) of the fasting period, with a follow-up one week after Ramadan.

Study population

Our study included 75 patients diagnosed with idiopathic PD as defined by the UK PD Brain Bank criteria [34]. All participants were 40 years or older and met the eligibility criteria for PKG use, including unstable PD management, wearing-off phenomena, nocturnal akinesia, dyskinesia, motor fluctuations, nonmotor fluctuations, and sleep disturbances. The exclusion criteria included significant comorbid neurological or psychiatric disorders, patients who were unwilling or unable to provide informed consent, and those with diabetes or cardiovascular conditions. Patients with idiopathic PD who wanted to fast during the holy month of Ramadan were enrolled and allocated into two groups based on their personal choice regarding medication adherence during Ramadan. The Ramadan Regime group (n=50) agreed to follow a customized twice-daily Parkinson’s medication (Ramadan regime) schedule tailored to accommodate fasting hours. The Nontreatment group (n=25) chose to cease all Parkinson’s medications during fasting for religious reasons (patient’s personal preference). Both groups were assessed at two time points: baseline (pre-Ramadan) and post-Ramadan (at the end of the fasting period). Demographic, clinical, and wearable sensor data were collected at both time points (Table 1). Participants were required to be able to wear the PKG watch for seven consecutive days before Ramadan and again during the entire holy month of fasting (4 weeks). Patients were excluded if they were unable to comply with the study protocol or withdrew before completing the 7-day watch data collection.

Ethical consideration

Participants underwent neurological and specific PD assessments administered by health care professionals. The study was approved by the Dubai Scientific, Research and Ethics Committee (DSREC-03/2025_14). Furthermore, the study was performed in accordance with the ongoing UK portfolio adopted for the NILS longitudinal cohort study at the National Parkinson’s Centre of Excellence at King’s College Hospital in London, Dubai, in accordance with the General Data Protection Regulation (GDPR UAE) endorsed by the UAE Parkinson’s expert group.

Data collection

The clinical parameters included demographic data (nationality, age, weight), disease data (disease duration, disease subtype, LED equivalent staging, UPDRS-III, and dyskinesia), and nonmotor symptoms (sleep [Epworth Sleepiness Scale], PDSS, fatigue [Parkinson’s Fatigue Scale 16; PFS-16], and quality of life [PDQ-8]).

PKG 24-hour recordings for seven days were conducted prior to fasting (baseline), and PKG 24-hour recordings for 4 weeks were conducted during the entire holy month of fasting for patients who chose the Ramadan Regime (RR), as well as for non-Ramadan regime (NRR) patients (fasting but not taking medication, because of religious beliefs; PKG scores: bradykinesia score, dyskinesia score, tremor score, EMO, sleep score).

Participant stratification

Group 1 comprised patients on RR (n=50), and group 2 comprised Ramadan fasters in the Nontreatment group (NRR) who were not taking Parkinson’s medications (n=25).

Ramadan regime (medication adjustments during fasting)

The levodopa equivalent daily dose (LEDD) is calculated based on the updated standardized LED conversion [25] twice a day, at the start of the fasting period (Suhoor) and at the end of the fasting period (Iftar); participants’ medications are switched to an equivalent dosage of either prolonged-release or extended-release oral levodopa or subcutaneous levodopa, intrajejunal levodopa, prolonged-release or extended-release dopamine agonists, or a transdermal dopamine patch [35,36]. Studies have shown that the immediate-release form of a dopamine agonist can be safely switched overnight to the equivalent extended-release form or by adding a COMT inhibitor to controlled-release levodopa preparations. Some studies have demonstrated the safety of switching from immediate-release preparations to controlled-release formulations [37,38].

For LEDD, a Mann–Whitney U test revealed significantly higher baseline doses in the Ramadan Regime group (median=735 mg, interquartile range [IQR]=500–900) than in the Nontreatment group (median=500 mg, IQR=400–600) (U=272.5, z=-4.01, p<0.001). A Wilcoxon signed-rank test further indicated that LED significantly decreased post-Ramadan in the Ramadan Regime group (z=-6.22, p<0.001).

Data analysis

All the statistical analyses were performed using SPSS Statistics version 28.0 (IBM Corp.), with the level of statistical significance set at p<0.05. Descriptive statistics were calculated to summarize demographic and clinical characteristics. Continuous variables are reported as the mean±standard deviation and median with IQR, whereas categorical variables are expressed as frequencies and percentages. Normality was assessed using the Shapiro–Wilk test, supplemented by visual inspection of histograms and Q–Q plots. Between-group comparisons were conducted using the Mann–Whitney U test for continuous variables and the chi-square test for categorical data. To evaluate the diagnostic performance of the selected postintervention variables, receiver operating characteristic (ROC) curve analysis was performed. Area under the curve values were computed with corresponding 95% confidence intervals to assess sensitivity and specificity.

RESULTS

Our study involved 75 fasting patients with PD, who were divided into a Nontreatment group (25 participants) and a Ramadan Regime group (50 participants) (Table 1). There were no significant differences in the sex distribution, disease subtype, age, or disease duration between the two groups. The median age was 67 years for the Nontreatment group and 69 years for the Ramadan group, while the median disease duration was 6 years for both groups. A Mann–Whitney U test was conducted to evaluate weight differences between the groups, revealing no significant difference in weight between the Nontreatment and Ramadan Regime groups (U=495.5, p=0.144). This finding may suggest that during the holy month, patients tend to break their fast with traditional high-calorie foods, such as sweets and other high-protein and high-carbohydrate meals. However, our study revealed significant changes in motor function (measured by the UPDRS-III) in the two groups: the Nontreatment group experienced worsening (z=-4.41, p<0.001), whereas the Ramadan Regime group showed improvement (z=-2.68, p=0.007); thus, therapy-related complications (UPDRS-IV) significantly differed (U=379.5, z=-2.81, p=0.005) (Table 2). The Ramadan Regime group improved significantly (z=-4.19, p<0.001), whereas the Nontreatment group did not significantly change (z=-1.89, p=0.058). For nonmotor symptoms (NMSQ), there was no significant difference at baseline (U=590.0, z=-0.64, p=0.674), but the post-Ramadan results revealed a significant difference (U=13.0, z=-6.99, p<0.001), with the Nontreatment group worsening and the Ramadan Regime group improving. Compared with the treatment group, the nontreatment group experienced notable excessive daytime sleepiness (EDS) scores, and sleep quality, as assessed by the PDSS and fatigue scores (PFS-16), significantly decreased in the Nontreatment group but remained stable in the Ramadan Regime group. Wilcoxon tests indicated significant changes within both groups. At baseline, the quality of life (PDQ-8) scores were similar for both groups, with a median of 16.0. After Ramadan, the Nontreatment group had a significant decrease in quality of life (median=22.0), whereas the Ramadan Regime group had improved quality of life (median=14.0); this resulted in a significant difference between the two groups. The Ramadan Regime group—who adhered to a customized twice-daily Parkinson’s medication schedule—demonstrated either significant improvement or clinical stability across these same domains. Therapy-related complications such as dyskinesias (UPDRS-IV) decreased significantly only in the Ramadan Regime group, while no significant change was observed in the Nontreatment group. These findings suggest that maintaining a modified Parkinson’s treatment schedule during Ramadan fasting may effectively reduce symptom burden and support overall functional health and well-being in observant fasting Muslim patients with PD.

The changes in the PDQ-8 scores, reflecting quality of life before and after Ramadan fasting, are shown in Figure 2. The Nontreatment group demonstrated a clear deterioration in quality of life following Ramadan, with a noticeable upward shift in the median and interquartile range of scores. In contrast, participants in the Ramadan Regime group showed significant improvement postintervention, with decreasing PDQ-8 scores indicating better quality of life (Figure 2). This difference suggests that cessation of Parkinson’s medication during fasting is associated with worsening patient-reported outcomes, whereas a structured, twice-daily treatment regime may offer protective benefits.The changes in the PDQ-8 scores, reflecting quality of life before and after Ramadan fasting, are shown in Figure 2. The Nontreatment group demonstrated a clear deterioration in quality of life following Ramadan, with a noticeable upward shift in the median and interquartile range of scores. In contrast, participants in the Ramadan Regime group showed significant improvement postintervention, with decreasing PDQ-8 scores indicating better quality of life (Figure 2). This difference suggests that cessation of Parkinson’s medication during fasting is associated with worsening patient-reported outcomes, whereas a structured, twice-daily treatment regime may offer protective benefits.

Post-Ramadan changes in PKG sleep/immobility scores are shown in Figure 3. The scores of the Nontreatment group substantially increased, indicating disrupted sleep or prolonged immobility during the fasting period. In contrast, participants in the Ramadan Regime group demonstrated a marked decrease in PKG sleep/immobility scores, reflecting improved sleep continuity or reduced immobility overnight, and these objective sensor-based findings align with patient-reported outcomes, underscoring the value of continued medication in preserving sleep quality during Ramadan fasting (Table 3).

DISCUSSION

To our knowledge, this is the first study to address the potential effects of prolonged fasting in Muslim patients with idiopathic PD who fasted, especially during the holy month of Ramadan.

Our study allowed patients to make choices based on their real-life circumstances, respecting their religious beliefs. Among 75 patients, 50 chose the “Ramadan regime,” which does not indicate an inability to tolerate drug withdrawal, contrary to suggestions from the editor. The comparator group chose not to take medications during fasting for religious reasons and accepted the risk of worsening their condition, as the “Ramadan regime” for PD had not been previously tested. This decision was considered natural, and using convenience comparator groups is standard in such studies. Among the 75 participants, 50 were studied for motor and nonmotor outcomes of fasting during Ramadan using a customized twice-daily Parkinson’s medication schedule (RR), whereas 25 did not receive any treatment during fasting because of religious beliefs (NRR). Both groups were matched for age, sex, median age, and disease duration, although the RR group had a higher overall motor stage (HY stage) than the NRR group did. Key findings indicate that the NRR group experienced a significant decline in motor status (UPDRS-III) and motor fluctuation status (UPDRS-IV) at the end of the Ramadan period, whereas the RR group experienced significant improvements in these scores. Our study revealed that self-reported NMSQ scores worsened significantly in the NRR group but improved in the responding RR group. The deterioration in the NRR group was attributed to increases in EDS and fatigue, along with worsening overall sleep scores. Quality of life, measured by the PDQ-8, decreased in the NRR group but improved in the RR group. Additionally, compared with the baseline, the RR group experienced a significant reduction in levodopa equivalence doses, highlighting the effectiveness of transitioning to transdermal or nonoral medication options for dose optimization.

Data from Parkinson’s PKG recordings complement our clinical findings that the NRR group experienced a decline in motor scores and worse bradykinesia after Ramadan, whereas the RR group showed significant improvement. Additionally, notable nocturnal worsening of both motor and nonmotor symptoms, including EMO, was detected in the NRR group. The PKG-based sleep scores corroborated these findings, with significantly poorer scores in the NRR group than in the RR group. Our study included a significant number of patients who chose to follow this regime, and a comparison group was also established, with a particular focus on those who experienced “wearing off” symptoms while primarily on levodopa treatment. Patients with PD often find the “wearing off” effect to be particularly challenging. The varied symptoms and progression of PD underscore the need to identify its subtypes. In this study, PD patients were classified into motor and nonmotor subtypes. The results indicated that even within a small sample, there was a notable decline in motor function, increased nonmotor symptom burden—particularly fatigue and sleep issues—and overall quality of life in the nonmotor subtype group. Additionally, for the first time, these clinically measured outcomes were corroborated by data from validated wearable sensors. The effect on motor outcomes is of great interest. Both the RR and NRR groups were matched in terms of disease duration, but the HY stage was higher in the RR group. However, the NRR group showed a worsening motor state after Ramadan, as indicated by the UPDRS-III scores and supported by PKG bradykinesia scores. Our a priori assumption was that nonmotor symptoms would worsen after Ramadan fasting, and our data confirm that the NMSQ measures nonmotor symptom burden using the self-completed 30-item questionnaire and that the nonmotor symptom burden worsened significantly in the NRR but improved in the RR.

In the EmPark study by Metta et al. [39], we reported that Emirati Muslim PD patients have a moderate PD burden and that the nonmotor symptom profile is dominated by sleep, fatigue, mood and sexual dysfunction [40]. What might be the overall clinical implications of this study? A 2020 estimation suggested that approximately 1.9 billion people are identified as Muslims worldwide, which represents approximately 25% of the global population. Considering the prevalence of PD, this would mean that a very large number of Muslim PD patients would be affected by the effects of Ramadan fasting, as noted in our study. The proposed customized Ramadan regime of treatment therefore has clinical implications for all such Muslim PD patients who may be fasting during Ramadan worldwide and not just in the Emirates. We propose a practical, step-by-step guide named the Ramadan Regime (Figure 4) designed to customize and optimize Parkinson’s medication schedules to align with fasting hours. This approach is simple, effective, and feasible for use in resource-limited settings or even in countries with limited resources. Therefore, we recommend that this regime be included in treatment pathways and guidelines for managing Parkinson’s disease during extended fasting periods.

Strengths and limitations of the study

While some may view the sample size of this study as small, we contend that it is important for a pioneering investigation of this nature. The diversity of the participants, the stringent protocols followed, and the inclusion of biomarker data, such as information from wearable sensors, contributed to the robustness of our findings. Participants were carefully selected based on strict criteria, and this study is not just a narrative observational analysis; it incorporates detailed clinical data along with wearable sensor data collected at two key time points. Specifically, participants wore the PKG watch for one week prior to Ramadan and throughout the fasting month; those who did not adhere to the protocol or who withdrew before completing the data collection were excluded from the analysis. Furthermore, we noted significant dropouts in the Nontreatment group due to severe adverse effects from the cessation of Parkinson’s medications.

Conclusion

This study demonstrated that, compared with those who discontinued treatment, Muslim patients with PD who fasted during Ramadan and who adhered to a customized twice-daily medication regime experienced more favorable clinical outcomes. Participants who followed the Ramadan Regime maintained motor stability; reported fewer nonmotor symptoms; and reported improvements in fatigue, sleep quality, and overall quality of life. Objective data from wearable sensors supported these findings, showing reduced bradykinesia and improved sleep mobility in the treatment group. Conversely, patients who abstained from all medications experienced notable worsening in both clinical and sensor-based measures, including the emergence of early morning motor symptoms. Additionally, ROC analysis confirmed that post-Ramadan quality of life, PKG bradykinesia, and PKG sleep scores were highly effective in distinguishing between the two groups, highlighting the utility of these outcomes as robust indicators of treatment status. Together, these findings support the clinical benefit of adapting Parkinson’s medication schedules during Ramadan to preserve patient well-being and functional health.

Notes

Conflicts of Interest

The authors have no financial conflicts of interest.

Funding Statement

None

Acknowledgments

The authors thank the Parkinson’s Centre of Excellence King’s Dubai team (Therese Masagnay, Clarissa Sangilan, Alex Rizos, Bassem Khalil, GKC UK, and PD patients participated in this study. Furthermore, the authors thank King’s College Parkinson’s Centre of Excellence London UK Research and Clinical team for their support.

Author Contributions

Conceptualization: Vinod Metta. Data curation: Haidar Dafsari. Formal analysis: Vinod Metta, Kallol Ray Chaudhuri. Investigation: Mohamed Elmahdy, Bassam Darwish. Methodology: Hani T. S. Benamer, Tom Loney. Project administration: Hasna Hussain, Afsal Nalarekttil. Resources: Huzaifa Ibrahim, Mishal Abu Al-Melh, Guy Chung-Faye, Bushra Alblooshi, Shaikha Almazrouei, Mohamed Al Mheiri, Rukmini Mridula, Sai Sampath Kumar, Vinay Goyal, Karolina Popławska-Domaszewicz, Cristian Falup Pecurariu, Prashanth Kukle, Jacob Chacko. Supervision: Kallol Ray Chaudhuri, Rupam Borgohain, Rajinder K. Dhamija. Writing—original draft: Vinod Metta. Writing—review & editing: all authors.

Figure 1.

Potential consequences of abrupt stoppage of dopamine replacement therapy (DRT) may occur during Ramadan fasting in Parkinson’s disease patients.

Figure 2.

Box plot of quality of life (PDQ-8) scores before and after Ramadan. PDQ-8 scores are presented by groups and time points. Higher scores indicate worse quality of life. PDQ-8, Parkinson’s Disease Questionnaire; NT, nontreatment group; RR, Ramadan Regime group.

Figure 3.

Box plot of PKG sleep/immobility score (PKG-SS) before and after Ramadan. PKG-SS scores are presented by group and time. Higher scores indicate poorer sleep quality or increased immobility. PKG, Parkinson’s KinetiGraph; NT, nontreatment group; RR, Ramadan Regime group.

Figure 4.

Managing Parkinson’s disease during Ramadan fasting (Ramadan Regime). DD, daily dose; COMT, catechol-O-methyltransferase; PD, Parkinson’s disease; MAO-B, monoamine oxidase B; LEDD, levodopa equivalent daily dose.

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