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- Niacinamide -


General Information:

Names: Niacinamide, nicotinamide
Wikipedia entry:

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Observations:

Niacinamide / nicotinamide

See also Tau Busters, B-complex Vitamins, Niacinamide Riboside

Wikipedia entry:

Nicotinamide, also known as niacinamide and nicotinic acid amide, is the amide of nicotinic acid (vitamin B3 / niacin). Nicotinamide is a water-soluble vitamin and is part of the vitamin B group. Nicotinic acid, also known as niacin, is converted to nicotinamide in vivo, and, though the two are identical in their vitamin functions, nicotinamide does not have the same pharmacologic and toxic effects of niacin, which occur incidental to niacin's conversion. Thus nicotinamide does not reduce cholesterol or cause flushing,[1] although nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults. In cells, niacin is incorporated into nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), although the pathways for nicotinamide and nicotinic acid are very similar. NAD+ and NADP+ are coenzymes in a wide variety of enzymatic oxidation-reduction reactions...
http://en.wikipedia.org/wiki/Niacinamide


Here is a thread about
niacinamide on the Alz.org forum. It is from early November of 2008:
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/3931050033

Apparently, nicotinamide combats the tau protein problem common to so many of these neurodegenerative diseases. Also known as "niacinamide", it appears to be readily available from health food stores. The dosing given to the mice was 200 mg/kg/day in their drinking water. I don't know if this number is for the mass of the water, or the body weight of the mice. "The mice received the equivalence of about 2 g of nicotinamide for humans." Several supplement suppliers make 500mg capsules or tablets. This would mean one would have to take 4 of these per day. Not so bad.

Here are the article cited in the thread:

First, a Google search:
http://news.google.com/news?hl=en&tab=in&ned=us&q=vitamin+b3&btnG=Search+News

Vitamin Holds Promise for Alzheimer's Disease
Treatment cured memory problems in mice, researchers found
U.S. News and World Report
Posted November 5, 2008
http://health.usnews.com/articles/health/healthday/2008/11/05/vitamin-holds-promise-for-alzheimers-disease.html



The abstract for the niacinamide study:

Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau

Kim N. Green,1 Joan S. Steffan,2 Hilda Martinez-Coria,1 Xuemin Sun,3 Steven S. Schreiber,3,5 Leslie Michels Thompson,1,2,4 and Frank M.
LaFerla1

Departments of 1Neurobiology and Behavior, 2Psychiatry and Human Behavior, 3Neurology, 4Biological Chemistry, and 5Anatomy and Neurobiology, University of California, Irvine, Irvine, California 92697-4545

"Memory loss is the signature feature of Alzheimer's disease, and therapies that prevent or delay its onset are urgently needed. Effective preventive strategies likely offer the greatest and most widespread benefits. Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance memory and synaptic plasticity. We evaluated the efficacy of nicotinamide, a competitive inhibitor of the sirtuins or class III NAD+-dependent HDACs in 3xTg-AD mice, and found that it restored cognitive deficits associated with pathology. Nicotinamide selectively reduces a specific phospho-species of tau (Thr231) that is associated with microtubule depolymerization, in a manner similar to inhibition of SirT1. Nicotinamide also dramatically increased acetylated {alpha}-tubulin, a primary substrate of SirT2, and MAP2c, both of which are linked to increased microtubule stability. Reduced phosphoThr231-tau was related to a reduction of monoubiquitin-conjugated tau, suggesting that this posttranslationally modified form of tau may be rapidly degraded. Overexpression of a Thr231-phospho-mimic tau in vitro increased clearance and decreased accumulation of tau compared with wild-type tau. These preclinical findings suggest that oral nicotinamide may represent a safe treatment for AD and other tauopathies, and that phosphorylation of tau at Thr231 may regulate tau stability.
http://www.jneurosci.org/cgi/content/abstract/28/45/11500


Nicotinamide Restores Cognition in Alzheimer's Disease Reduces Alzheimer's tau lesions and memory loss in mice
By Will Block Life Enhancement

"At the end of the trial, the AD mice performed as well in memory testing as healthy mice, a remarkable result strongly suggesting that nicotinamide had protected their brains from memory loss, and restored memory that would have been lost. “Cognitively, they were cured,” first author of the study, Dr. Kim Green said. “They performed as if they’d never developed the disease.”3 “The vitamin completely prevented cognitive decline associated with the disease, bringing them back to the level they’d be at if they didn’t have the pathology,” said Dr. Green. “It actually improved behavior in non-demented animals too.”4 Meaning that healthy mice fed nicotinamide outperformed mice on a normal diet. “This suggests that not only is it good for Alzheimer’s disease, but if normal people take it, some aspects of their memory might improve,” said Dr. Frank LaFerla, the lead author of the study..."

"Nicotinamide is a water soluble member of the B vitamin group. Also known as niacinamide, nicotinamide is the amide of nicotinic acid (vitamin B3), also known as niacin. In vivo, niacin is converted to nicotinamide and although the two are identical in their vitamin functions, nicotinamide does not have the same pharmacologic effects of niacin, which may affect the liver negatively in some individuals. Unlike niacin, nicotinamide does not reduce cholesterol or cause flushing. In cells, niacin forms the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Although the pathways for nicotinamide and nicotinic acid are very similar. NAD+ and NADP+ are coenzymes in a wide variety of enzymatic oxidation-reduction reactions..."

"In their search for just what was going on, nicotinamide did not affect levels of the protein beta amyloid, which clumps in the brain to form plaques, the second type of Alzheimer’s lesion. Given this lack of effect on beta amyloid levels, the researchers figured the compound must be improving cognition through some other mechanism. Upon analyzing protein extracts from whole brain samples of treated and control AD mice, they found a 20 percent reduction in levels of tau in the nicotinamide-treated animals. They saw no differences at several tau sites typically phosphorylated in AD mice at the end of eight months, but a whopping 60 percent reduction in Thr231-phospho-tau—a particular species of tau that has been reported to interfere with microtubule polymerization and is a commonly used biomarker for AD—in the nicotinamide group compared with vehicle. “It’s incredibly dramatic,” Green told the Alzheimer’s Research Forum. “This thing [a biomarker for AD] is just wiped from the brain very specifically...”5

References

   1. Wang SS. When Alzheimer’s hits at 40. New York Times, Nov. 14, 2008.
   2. Green KN, Steffan JS, Martinez-Coria H, Sun X, 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. J Neurosci 2008 Nov 5;28(45):11500-10.
   3. Dotinga R. Vitamin holds promise for Alzheimer’s disease. Healthday Nov. 5, 2008.
   4. Sample I. Vitamin pill that may slow Alzheimer’s goes on trial. The Guardian, Nov. 05 2008.
   5. Anon. Alzheimer’s Research Forum. Nov. 8, 2008.
http://www.life-enhancement.com/article_template.asp?ID=2049


Understanding neurofibrillary tangles (image)
http://www.life-enhancement.com/images/LEM0901tangles_large.jpg

Vitamin B3 Reduces Alzheimer's Symptoms, Lesions: Clinical Trial On Nicotinamide Effect In Alzheimer's Patients

ScienceDaily (Nov. 5, 2008) — An over-the-counter vitamin in high doses prevented memory loss in mice with Alzheimer's disease, and UC Irvine scientists now are conducting a clinical trial to determine its effect in humans. Nicotinamide, a form of vitamin B3, lowered levels of a protein called phosphorylated tau that leads to the development of tangles, one of two brain lesions associated with Alzheimer's disease. The vitamin also strengthened scaffolding along which information travels in brain cells, helping to keep neurons alive and further preventing symptoms in mice genetically wired to develop Alzheimer's. "Nicotinamide has a very robust effect on neurons," said Kim Green, UCI scientist and lead author of the study. "Nicotinamide prevents loss of cognition in mice with Alzheimer's disease, and the beauty of it is we already are moving forward with a clinical trial."...
http://www.sciencedaily.com/releases/2008/11/081104180926.htm

Nicotinamide-induced mitophagy: An event mediated by high NAD+/NADH ratio and SIRT1 activation.
http://www.ncbi.nlm.nih.gov/pubmed/22493485




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Updated: July 2, 2012
Inception: July 2, 2012