We are the first group to demonstrate chronic vitamin B3 (niacin and niacinamide) deficiency in individuals with Parkinson's disease (PD). Niacin and niacinamide are the source of NAD which supplies energy and DNA repair to every cell in the body. PD patients frequently report symptoms which we believe are related to the vitamin deficiency, including daytime fatigue, sleep dysfunction and low-level mood. In addition, niacin but not niacinamide acts on GPR109A, an anti-inflammatory receptor. We are also the first group to show elevated GPR109A levels in the white blood cells (macrophages) and substantia nigra of PD patients, providing additional evidence of the consequences of chronic niacin deficiency in PD. In this exploratory trial, we propose to provide over-the-counter nutritional supplementation to test the hypothesis that correcting the deficiency via niacin's dual actions (energy supply and anti-inflammation) will improve symptom outcomes and reduce inflammation better than niacinamide.
Aim 1. To determine whether niacin supplementation will reduce inflammation and improve the symptoms of PD patients better than niacinamide.
Aim 2. To determine whether macrophage polarization and mitochondrial boost will reflect niacin and niacinamide supplementation independently. We will accomplish these aims with a two-arm double blind, randomized, fixed-dose, parallel niacinamide- controlled intention-to-treat 18-month pre-post prospective cohort design with mid-point assessment. The primary endpoint of this trial will be a decrease in the severity of motor symptoms as assessed by the Unified Parkinson's Disease Rating Scale Motor Section (UPDRS III). Secondary endpoints include wearable- technology measurements to document improvements in balance control and cognitive functions including nightsleep and executive control, as well as increased glycolysis and decreased GPR109A levels.

Public Health Relevance

Parkinson?s disease (PD) is a devastating progressive neurological condition. We are the first group to demonstrate chronic vitamin B3 deficiency in individuals with PD. Niacin and niacinamide, two common versions of vitamin B3, are the sources of energy and DNA repair for all cells in the body. Low B3 levels can produce some of the symptoms commonly reported among PD individuals, namely daytime fatigue, nightsleep disorder and mood changes. Niacin but not niacinamide binds to GPR109A to reduce inflammation. Neuroinflammation is central in PD pathology. We observed up-regulation of this receptor in the substantia nigra and white blood cells (WBCs) of PD patients. We hypothesize that the dual actions of niacin supplementation to correct the vitamin deficiency will produce better outcomes than niacinamide.

National Institute of Health (NIH)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRD1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Charlie Norwood VA Medical Center
United States
Zip Code