Mediterranean Diet Effects on Parkinson's Disease

PD is a progressive neurodegenerative disorder marked by both motor and non-motor symptoms, leading to reduced quality of life and increased economic burden for patients and caregivers. Prior to diagnosis, patients often experience a prodromal phase characterized by symptoms such as anosmia, constipation, and sleep disturbances. PD is the second most common neurodegenerative disease globally and the fastest-growing, with an increasing prevalence since 1990.

The disease is linked to the buildup of α-synuclein in Lewy bodies within the brain and neuroinflammation caused by microglial activation. This process results in the degeneration of dopaminergic neurons in the substantia nigra, which is central to PD pathology. Recent research has highlighted the role of immune dysfunction in PD, with alterations observed in adaptive and innate immune responses. A reduction in specific T cells (e.g., CD4+ T cells, Th2, Th17, and T regulatory cells) and a shift towards a pro-inflammatory Th1 response have been associated with neuronal damage in PD. Moreover, aberrant α-synuclein may trigger an adaptive immune response, highlighting the relevance of the immune system as a potential therapeutic target.

Gut and nasal microbiota also appear to play a role in PD. Alterations in the gut microbiome, including changes in short-chain fatty acid-producing bacteria, have been observed in PD patients. Notably, increases in Lactobacillus, Akkermansia, and Bifidobacterium have been reported in the gut, while the Lachnospiraceae family and Faecalibacterium genus are reduced.

Moreover, although still unconfirmed, nasal microbiota may contribute to neurodegeneration by traveling through the olfactory and trigeminal pathways, possibly initiating or exacerbating brain inflammation.

Evidence suggests that specific dietary patterns may influence PD risk and progression. Foods like dairy are associated with an increased risk of PD, while coffee, nicotine-containing vegetables (e.g., peppers and tomatoes), and high consumption of vegetables, nuts, and fish may reduce symptomatology.

The MD, a plant-based diet rich in vegetables, fruits, whole grains, and healthy fats like olive oil, has been linked to numerous health benefits, including improved cognitive function, cardiovascular health, and a reduced risk of developing PD.

Studies show that a high-fiber diet can positively impact α-synuclein aggregation and microglial activation. Adherence to the MD may lower PD risk by up to 26%, slow disease progression, and improve both motor and non-motor symptoms. In contrast to pharmacological treatments, the MD has minimal side effects and could address several unmet needs in PD management, particularly in slowing disease progression and reducing comorbidities such as dementia.

This six-month randomized controlled trial aims to explore whether strict adherence to the MD can stabilize or slow the progression of motor and non-motor symptoms in PD patients. It will also investigate the impact of the MD on the immune system, gut and nasal microbiota, and fecal metabolomics, making it the first trial to assess these factors together. The study's primary goal is to determine the benefits of MD adherence on symptom management while also exploring correlations between immune function, microbiota composition, fecal and urinary metabolomics, and diet adherence levels.

Inclusion criteria

• PD diagnosis according to international guidelines;
• Age between 40 and 85 years;
• Naive to medication or with a stable dosage of anti-Parkinson's therapy for at least two weeks;
• Hoehn & Yahr stage ≤3;
• Normal independent feeding;
• Ability to complete informed consent;
• Willingness to maintain the usual diet in the period between T0 and T1;
• Willingness to maintain the usual diet if randomized to the control group in the T1-T2 period;
• Willingness to make changes in their diet to follow a Mediterranean diet if randomized to the intervention group in the T1-T2 period;
• Willingness to fill out questionnaires;
• Willingness to provide blood samples during the study collection periods;
• Willingness to provide stool samples during the study collection periods;
• Willingness to fast (without food or drink except water, tea or coffee) at least 12 hours before each sample collection;
• Willingness to discontinue taking supplements, probiotics, herbal or high- dose vitamins or minerals that could impact inflammation during the period between T0 and T1 and for the duration of the study protocol;
• No medical and/or social conditions that could interfere with participation in a six-month interventional study.

Exclusion criteria

• Atypical or secondary parkinsonism;
• Underweight (<18.5);
• Obesity (BMI>30);
• Pregnancy or suspected pregnancy;
• Normal assisted nutrition;
• Enteral nutrition;
• Chronic autoimmune diseases;
• Chronic use of immunosuppressive drugs in the past year;
• Chronic use of cytotoxic cancer drugs in the past year;
• Major abdominal surgeries;
• Concurrent participation in other interventional studies;
• Intentional change in diet after PD diagnosis.