From the Guidelines
To avoid dopaminergic downregulation in patients with Parkinson's disease, advising them to take levodopa medications at least 30 minutes before meals and recommending a protein-redistribution dietary regimen is crucial. This approach maximizes levodopa absorption and efficacy, as levodopa competes with dietary large neutral amino acids for intestinal absorption and transport across the blood-brain barrier 1. The protein-redistribution dietary regimen involves consuming a low-protein breakfast and lunch, and having a second course with no quantitative restrictions on protein only at dinner. This regimen has been shown to improve motor function and disability, and increase the duration of the "ON" state in patients with motor fluctuations 1.
Key considerations for implementing this regimen include:
- Monitoring patients actively to avoid potential complications such as weight loss, micronutrient deficits, hunger before dinner, and dyskinesias 1
- Setting daily protein requirements to 0.8-1.0 g/kg of body weight 1
- Balancing potential benefits with clinical conditions, such as comorbidities and frailty status, particularly in very old patients with Parkinson's disease 1
- Avoiding strict low-protein diets, as there is no evidence supporting this dietary regimen 1
- Managing other gastrointestinal problems, such as delayed gastric emptying and constipation, which can impair levodopa efficacy 1.
By following this protein-redistribution dietary regimen and taking levodopa medications at least 30 minutes before meals, patients with Parkinson's disease can help avoid dopaminergic downregulation and optimize their treatment outcomes.
From the Research
Dopaminergic Downregulation
To avoid dopaminergic downregulation, several strategies can be considered:
- Using dopamine agonists, which can be used alone before the introduction of levodopa or as an adjunct to levodopa 2
- Adding a peripherally-acting COMT inhibitor or an MAO-B inhibitor to levodopa, which can reduce motor fluctuations in patients with advanced disease 2
- Using MAO-B inhibitors as initial levodopa-sparing therapy, which was found to be at least as effective as dopamine agonists 3
- Considering the use of rasagiline as an add-on to dopamine agonists, which was found to provide statistically significant improvement in total UPDRS scores 4
Mechanisms of Downregulation
The down-regulation of dopamine D2 receptors is likely related to the long-term and intermittent administration of dopaminergic treatments rather than to disease progression 5
- Complete withdrawal of dopaminergic drugs can reverse this down-regulation 5
- An up-regulation of putaminal dopamine D2 receptors can be demonstrated in late-stage PD after dopaminergic drug withdrawal 5
Treatment Options
The choice of treatment should be based on the individual patient's needs and response to therapy:
- Dopamine agonists, such as pramipexole, ropinirole, and rotigotine, can be effective as monotherapy or in combination with levodopa 6
- MAO-B inhibitors, such as selegiline and rasagiline, can be effective as monotherapy or in combination with levodopa 6
- Levodopa, combined with carbidopa, is still the most effective treatment for symptoms of Parkinson's disease 2