What Is NAD⁺ and Why It Matters in Parkinson’s Disease
NAD⁺ (nicotinamide adenine dinucleotide) is a coenzyme essential for energy metabolism, mitochondrial health, and cellular repair. In Parkinson’s disease (PD), where neurons that produce dopamine slowly die off, energy dysfunction and oxidative stress are major drivers. NAD⁺ levels naturally decline with age and are often found to be lower in patients with neurodegenerative diseases, including PD.
Boosting NAD⁺—either through direct supplementation (like NADH or NAD⁺) or precursors (like NR or NMN)—may potentially help protect these vulnerable brain cells.
How NAD⁺ Might Protect Dopamine-Producing Neurons
Mitochondrial Support
NAD⁺ is a key component of the mitochondrial energy cycle. In PD, mitochondrial dysfunction is common. Studies show that increasing NAD⁺ may restore ATP production and improve the survival of energy-stressed neurons.Reduction of Oxidative Stress
NADH and NADPH help neutralize harmful reactive oxygen species (ROS). By reducing oxidative stress, NAD⁺ may shield neurons from damage.Inflammation Control
NAD⁺ supports sirtuins—enzymes that help reduce inflammation and promote healthy aging. In PD, lowering neuroinflammation may slow disease progression.Proteostasis and Autophagy
NAD⁺ is involved in activating pathways that clear damaged proteins and organelles, a process crucial for neuron health.
Animal and Lab Studies: A Strong Foundation
A 2018 study in fly and iPSC-derived neuron models showed that NR (a NAD⁺ precursor) restored mitochondrial function and reduced neuron loss in PD-like conditions.
Zebrafish and mouse models treated with NR showed reduced endoplasmic reticulum (ER) stress, improved movement, and higher NAD⁺ levels in brain tissues.
In rotenone and MPTP toxin models (common in PD research), NADH supplementation preserved motor function and dopaminergic neuron density.
Some studies observed better energy metabolism and increased activity of antioxidant enzymes like superoxide dismutase and catalase following NADH or NR treatment.
These findings demonstrate NAD⁺’s ability to protect brain cells under PD-like stress in lab settings—but what about humans?
Human Studies and Randomized Controlled Trials
NADPARK Trial (2022)
Design: Phase I randomized trial of NR (1000 mg/day for 30 days) in early-stage PD patients.
Findings: Significant increase in brain NAD⁺ levels, improvement in brain metabolism, and reduction in inflammatory markers.
Limitations: Short duration, and clinical improvements were mild.
NR-SAFE Trial (2023)
Design: 4-week randomized, double-blind safety trial of high-dose NR (3000 mg/day).
Findings: Safe and well-tolerated. Boosted NAD⁺ levels by ~5x. Some improvement in motor scores (MDS-UPDRS), but result may have been influenced by timing of medications.
Significance: Demonstrated high-dose NR is safe and has measurable biological effects.
Older NADH Trials (1990s)
One small open-label trial reported symptom improvements in 80% of PD patients using 5–10 mg/day of oral NADH.
A small RCT (n=15) showed modest improvements in motor function after 4 weeks.
However, a 1994 double-blind study using IV and IM NADH found no statistically significant difference between treatment and placebo.
The NOPARK Trial – Currently Underway
Design: Phase II/III trial with over 400 early-stage PD patients.
Intervention: 1000 mg/day of NR for 12 months.
Goal: Determine if NAD⁺ can slow clinical progression of Parkinson’s disease.
Status: Ongoing, with results expected in 2025.
This is the most rigorous test to date and will help determine whether NAD⁺ therapy offers more than just theoretical benefit.
Limitations and Open Questions
Most clinical trials have been short-term and focused on biomarkers, not long-term symptom slowing.
Some animal studies suggest prolonged NAD⁺ supplementation could reduce dopamine production in certain conditions—so dosing and patient selection matter.
High-dose NR may affect methylation pathways and homocysteine levels—though studies show this effect is mild and likely manageable.
In short: boosting NAD⁺ shows promise, but we still need more long-term human data before it can be considered a treatment or preventative.
Final Thoughts: Where We Stand
Boosting NAD⁺ may one day offer a new approach to slowing or preventing Parkinson’s disease—but it’s not ready for prime time just yet. The scientific rationale is strong, animal studies are encouraging, and early human trials show safety and biological effects. If the NOPARK trial confirms real-world benefits, NAD⁺ supplementation may become a useful tool in Parkinson’s prevention or management.
Until then, it’s a promising but still experimental strategy—worth watching, and maybe worth discussing with your doctor if you’re interested in neuroprotective therapies.
Interested in Exploring NAD+ Therapy?
If you’d like to learn more about how NAD+ supplementation may support your health, visit our NAD+ IV therapy page.
Ready to schedule an appointment? Book online or contact us today—we’re happy to answer your questions and help you get started.
Disclaimer: The information in this blog post is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the guidance of a qualified health professional with any questions you may have regarding a medical condition.
Share This Post On Social Media:
References
Brakedal B, et al. (2022). The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson’s disease. Cell Metabolism, 34(3): 396–407.e6
Berven H, et al. (2023). NR-SAFE: a randomized, double-blind safety trial of high-dose nicotinamide riboside in Parkinson’s disease. Nature Communications, 14: 7793
Schöndorf DC, et al. (2018). Nicotinamide riboside rescues mitochondrial defects in models of Parkinson’s disease. Cell Reports, 23(10): 2976–2988
Lu L, et al. (2014). Nicotinamide mononucleotide improves energy activity and survival rate in an in vitro Parkinson’s model. Exp Ther Med, 8(3): 943–950
Birkmayer W, et al. (1989). NADH improves the disability of parkinsonian patients. J Neural Transm, 1(4): 297–302
Birkmayer JGD, et al. (1993). NADH—comparison of oral and parenteral application in Parkinson’s disease. Acta Neurol Scand, 87(Suppl. 146): 32–35
Pérez-Mato M, et al. (2021). NAD+ metabolism and aging in Parkinson’s disease. Mechanisms of Ageing and Development, 196: 111485
