NAD-boosting treatment shows no Parkinson’s benefit in yearlong trial

A major clinical trial involving 410 people with early Parkinson’s disease has found no clinical benefit from nicotinamide riboside (NR), a compound that increases cellular levels of nicotinamide adenine dinucleotide (NAD). The findings are published in JAMA.

The NOPARK trial was led by professor Charalampos Tzoulis at Haukeland University Hospital and the University of Bergen. Participants at 11 Norwegian centers were randomly assigned to receive either NR or placebo for one year. Neither the participants nor the study teams knew who received which treatment.

Disease severity was measured using the MDS-UPDRS scale, on which a higher score indicates more pronounced symptoms. After 52 weeks, participants who received NR had worsened by an average of 2.45 points, while the placebo group remained essentially unchanged. The adjusted difference was 2.72 points in favor of placebo.

The difference was statistically significant, but modest and below the commonly used threshold for a clinically important difference. These findings show that NR provided no clinical benefit in early Parkinson’s disease, with outcomes on average slightly worse than with placebo.

Brain imaging showed no evidence that NR either slowed or accelerated changes in the brain’s dopamine system. The overall occurrence of adverse events was similar in the two groups.

“We had a strong biological rationale for testing this treatment, and earlier, smaller clinical studies had produced encouraging findings. NR clearly increased NAD metabolism, but this did not translate into clinical improvement. Our results therefore do not support NR as a treatment to slow Parkinson’s disease,” says professor and study director Tzoulis.

Why the treatment was tested

NAD is essential for cellular energy metabolism and several other vital processes, including DNA repair and regulation of inflammation. Preclinical studies and small clinical trials had suggested that increasing NAD levels might protect nerve cells affected by Parkinson’s disease. NOPARK was designed to test that possibility in a large, rigorous phase 3 trial. Participants received 500 mg of NR twice daily or matching placebo for one year.

Advice for people with Parkinson’s disease

Based on these findings, the researchers do not recommend that people with Parkinson’s disease use NR or other NAD-boosting supplements outside controlled clinical studies. The findings do not, however, rule out the possibility that NAD-boosting treatments could be beneficial in other diseases. Effects may differ between conditions and need to be evaluated separately in appropriately controlled clinical trials.

“We are deeply grateful to the participants and their families for their trust, time and commitment. Although the results were not what we had hoped for, their contribution has answered an important medical question and provided valuable guidance for future research. We also thank our colleagues at all 11 centers, whose dedication made this national study possible,” says professor Tzoulis.

The research team will now continue to analyze the data to better understand the biological mechanisms behind the findings and to explore whether different groups of patients may have responded differently to the treatment. These analyses may help guide future research and the development of new treatment strategies.

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Gaby Clark

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Robert Egan

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