Nicotinamide is a form of vitamin B3 that scientists are looking at as a potential treatment for Alzheimer’s disease. They believe nicotinamide may have neuroprotective effects, meaning it may help protect brain cells from Alzheimer’s damage.

How nicotinamide works

The precise cause of Alzheimer’s is unknown, but it is characterized by the death of brain cells. The disease is associated with abnormal accumulation of two proteins in the brain: beta amyloid and tau. These proteins form clumps that cause brain cell dysfunction. Beta amyloid clumps are called plaques and tau clumps tangles.

In addition to harmful protein accumulation, Alzheimer’s is associated with dysfunctional mitochondria in brain cells. Mitochondria are structures in the cell that produce its energy. Without functional mitochondria, a cell will die.

Mitochondrial dysfunction and protein accumulation may be related because a coenzyme called nicotinamide adenine dinucleotide (NAD)(+) plays a role in both. A coenzyme is a molecule that helps enzymes drive a chemical reaction.

Nicotinamide is a precursor of (NAD)(+), which means cells can use a chemical reaction to turn nicotinamide into (NAD)(+). (NAD)(+) is a crucial component of the chemical reaction that mitochondria use to produce energy. It is also involved in the chemical process that produces beta amyloid.

A study in mice showed that dietary supplements of nicotinamide can increase the amount of (NAD)(+) in the brain, reduce the production of beta amyloid, and slow the decline of patients’ cognitive function. Another study in mice suggested that nicotinamide may help reduce a form of tau protein involved in tangle formation in the brain.

Some researchers also think nicotinamide can help protect mitochondria by activating their response to stress, allowing them to defend themselves better against the effects of Alzheimer’s. Their work showed that nicotinamide increased worms’ health and lifespan. And it led to similar improvements in human brain cells in a lab.

While nicotinamide has shown promise as an Alzheimer’s treatment, the research it is still in its very early stages.

Nicotinamide in clinical trials

Researchers conducted a Phase 1/2 clinical trial (NCT00580931) of nicotinamide’s safety as an Alzheimer’s treatment. Participants received either nicotinamide or a placebo for six months. The research team assessed them every six weeks using the Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog). The trial was completed in 2014 but no results have been published.

A Phase 2 clinical trial (NCT03061474) of nicotinamide is in the recruitment stage. Researchers are seeking participants ages 50 and over with mild cognitive impairment due to Alzheimer’s.

Participants will either be given nicotinamide or placebo tablets twice a day for 12 months. Researchers will then measure levels of tau protein in the cerebrospinal fluid that surrounds their brain and spinal cord. Depending on the results, the treatment may be extended 12 months.

Researchers are recruiting an estimated 48 participants in California. Results are expected in February 2019.


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