A form of vitamin B3 named nicotinamide prevents transgenic mice from getting Alzheimer’s pathology. But will it work in humans?

If humans were like transgenic mice, than a miracle cure for Alzheimer’s disease has been found. Nicotinamide (also called niacinamide) works to decrease levels of phosphorylated tau which one of the key neuropathological hallmarks of Alzheimer’s disease. Tau is involved in the formation of mircotubules which can be thought of as the train tracks (or key transportation system) along the length of the cell. Without it, both intra- and extracellular communication can’t occur. It also increases the stability of this transportation system via other mechanisms, and works to increase p25, a protein which has been linked to improved learning and memory.

The transgenic mice that were used had 2 of the most important key pathological hallmarks of Alzheimer’s disease (Abeta plaques and tangles) and memory loss as well which begins at 4 months in these mice. Thus scientist Kim Green and colleagues fed the mice pharmacological doses of nicotinamide in their drinking water at age 4 month until they were 8 months old. They found that the mice did just as well in many measures in the Morris Water Maze (used to test memory) as normal control mice. Much of the typical neuropathology expected in the mice never appeared.

So does nioctinamide show promise for preventing or reversing Alzheimer’s in humans? No and yes.

Because of disappointing outcomes from previous human trials with other substances in those with Alzheimer’s, current trials are targeting early stages of the disease to prevent further decline. Thus, like the mice who were just at the beginning stages of showing pathology when the experiment began, Green who is starting a phase 2 trial at UC Irvine is looking for patients who are in the early stages of the disease.

While vitamin B3 is easily found in meat, fish, beans, potatoes and cereals, equivalent doses for humans would be far more than what we’d normally get in our diet. Investigators are starting a phase 2 trial in humans at UC Irvine, and will be giving subjects 1,500 mg twice a day. Normally a multivitamin only contains 10mg, and the standard recommended daily dose is 16mg for men and 14mg for women. Doses at pharmacological levels could induce liver toxicity and other side effects, and more information on safety will be available with the completion of phase 2 and 3 clinical trials.

However, there is an observational prospective study conducted by Martha. C. Morris at Rush University that shows in their Chicago population of 3718 subjects that those who consumed more niacin (a precursor to nicotinamide) over a 5.5 yr period had substantially less cognitive decline. This same study showed in a smaller subset that those who consumed more niacin also had a 70% lower risk of Alzheimer’s disease.

So while a reversal of Alzheimer’s disease is unlikely, nicotinamide or niacin shows great promise of slowing the cognitive decline associated with the disease, and or decreasing the risk of the disease. While it’s too early to take pharmacologic doses of vitamin B3, you might want to keep your eye on your B3 intake, and to stay tuned for more news in the future with regards to this vitamin.

For more information:

http://www.sciencedaily.com/releases/2008/11/081104180926.htm

http://www.alzforum.org/new/detail.asp?id=1962

http://www.npr.org/templates/story/story.php?storyId=96747179

References:

Green KN, Steffan JS, Martinez-Coria H, SunX, Schreiber SS, Thompson LM, LaFerla FM. Nicotinamide Restores Cognition in Alzheimer’s Disease Transgenic Mice Via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau. Journal of Neuroscience. 2008 Nov 28(45):11500-11510.

Morris MC, Evans DA, Bienias JL, Scherr PA, Tangney CC, Hebert LE, Bennett DA, Wilson RS, Aggarwal N. Dietary niacin and the risk of incident Alzheimer’s disease and of cognitive decline. J Neurol Neurosurg Psychiatry. 2004 Aug;75(8):1093-9.