Nicotinamide Exacerbates Motor Symptoms of Parkinson’s Disease in Mice

Nicotinamide Exacerbates Motor Symptoms of Parkinson’s Disease in Mice

A form of vitamin B3 can promote degeneration of nerve cells linked to Parkinson’s disease and exacerbate disease manifestations in mice, a study reveals.

Despite the benefits of the compound demonstrated in previous studies, these new contrasting findings suggest that its mechanism of action is complex and not specific for therapeutic effectiveness in Parkinson’s disease.

The study, “The Histone Deacetylase Inhibitor Nicotinamide Exacerbates Neurodegeneration in the Lactacystin Rat Model of Parkinson’s Disease” was published in the Journal of Neurochemistry.

Nicotinamide, also known as niacinamide or nicotinic amide, is a derivate of vitamin B3 found in various foods including beef, chicken, pork, fish, peanuts, and mushrooms, among others.

It is the precursor of an important metabolic compound called NAD+ that is essential for cells to produce the energy they need to function normally. Besides this, nicotinamide also is known to act as an inhibitor of enzymes called HDACs. These enzymes are responsible for regulating the genes that are available to produce active proteins and those that are silenced and inactive, through a process called epigenetics.

In Parkinson’s, both cellular energy production mechanisms and epigenetic processes are deregulated. Given that, nicotinamide could hold therapeutic potential for this disease by providing dual-protective activity.

A previous study has shown that treatment with nicotinamide could improve energy production by supporting the formation of new mitochondria — small cellular organelles that provide energy and are known as cells’ “powerhouses.” The study also showed that the treatment could prevent the loss of motor function in a fly model of Parkinson’s disease.

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To further explore nicotinamide’s potential, researchers treated rats with induced Parkinson’s disease for 28 days. The disease was chemically induced by injection of lactacystin in one side of the substantia nigra — the brain area affected most by the disease — promoting the accumulation of altered and toxic proteins, mimicking what occurs in human disease.

Contrary to what researchers expected, nicotinamide treatment enhanced the death of brain cells and structural brain changes. Also, animals treated with a nicotinamide showed increased rate of motor decline and development of behavioral deficits compared to untreated animals.

Despite these negative effects, analysis of the genetic landscape of these animals’ brain tissue revealed that nicotinamide treatment increased the expression of several neuroprotective genes. However, this potentially positive effect failed to increase neuroprotection; rather, it exacerbated neurodegeneration. (Gene expression is the process by which information in a gene is synthesized to create a working product, like a protein.)

“These findings highlight the importance of inhibitor specificity” to achieve therapeutic effectiveness in Parkinson’s disease, researchers wrote.

In addition, the team believes these results demonstrate “the contrasting effects” of nicotinamide in cell survival in different animal models of the disease.


  1. James Casterton says:

    I was diagnosed with Parkinson’s Disease in May, 2018. In June, I was happy to learn of the study suggesting nicotinamide riboside was neuroprotective. I have been taking TruNiagen daily since then.

    Are you now referring to a form of nicotinamide other than nicotinamide riboside? I hope so…

    • Alice Melão says:

      Dear James, nicotinamide and nicotinamide riboside are different molecules, although they contribute for the same molecular process for the production of energy. Yet they may contribute differently to other mechanisms, which may help explain the contrasting result of the studies. A lot is yet to be discovered and you should always be cautious on the medicines you take, discussing it with your physician.

    • GFC says:

      University hospital in Augusta Ga. did a phase 3 study and was supposed to do to start a larger study on riboside. For some reason all the info on this is now missing from the internet. Has anyone got any info on this?

  2. Luca says:

    So the two studies are based on two different molecules ? the one with the fruit fly model and this one ? ( the previous beeing based on nicotinamide riboside , and this one on nicotinamide ) If this is the case you should clarify a little. I’m in the same situation as Mr. Casterton….Thank you for letting us know…

  3. GFC says:

    University Hospital in Augusta Ga. did a phase 3 study on Riboside. They also were to start further studies, but for some reason the 1st study and all info has been deleted from the internet. Curious to hear from anyone who has any info on this.

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