An article in the November 5, 2008 issue of the Journal of Neuroscience revealed the discovery of researchers at the University of California, Irvine of a protective effect of nicotinamide, otherwise known as niacinamide (a form of vitamin B3), against memory loss in mice bred to develop a condition that mimics human Alzheimer’s disease. Nicotinamide is a member of a group of compounds known as histone deacetylase (HDAC) inhibitors, which have been shown to enhance memory. The compounds have been demonstrated to exert a protective effect on the central nervous system in rodent models of Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis (ALS).
For the current research, Kim Green, Frank LaFerla and their associates used mice bred to develop brain deposits of amyloid beta as well as phosphorylated tau protein, which forms neurofibrillary tangles that occur in human Alzheimer’s disease patients. The team added nicotinamide daily to the drinking water of four-month-old Alzheimer’s mice and normal mice, while other groups of mice received untreated water for four months. Cognition testing to evaluate short term and long term memory in areas of the brain affected by Alzheimer’s disease was conducted at the beginning and end of the study.
The team found lower levels of phosphorylated tau in the brains of the Alzheimer’s mice that received nicotinamide, as well as an increase in proteins that strengthen the brain’s microtubules along which information travels within the brain’s cells. "Microtubules are like highways inside cells,” Dr Green explained. “What we're doing with nicotinamide is making a wider, more stable highway. In Alzheimer's disease, this highway breaks down. We are preventing that from happening."
While untreated Alzheimer’s mice demonstrated memory loss by the end of the experiment, those that received nicotinamide performed at the same level as the normal mice. Even in normal mice that received nicotinamide, cognition was slightly enhanced. "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," noted Dr LaFerla, who is a professor of neurobiology and behavior at UC Irvine.
"Nicotinamide has a very robust effect on neurons," Dr Green added. "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."
“The results presented here suggest that nicotinamide has a potential as a novel, safe and inexpensive Alzheimer’s disease therapy, either alone or in combination with amyloid beta-lowering therapies,” Dr Green and colleagues conclude.
Neurofibrillary tangles, which are made of a protein called tau, are bundles of twisted filaments found within neurons. Tau is normally responsible for helping cells to function correctly; it delivers various substances throughout the cell. In people who have Alzheimer’s disease, tau becomes abnormally shaped and twists into pairs of helical filaments that gather in tangles. Because of the tangles, the neurons lose their ability to function, and the neurons eventually die. No one knows why this happens but there are probably several overlapping causes of Alzheimer’s disease.
There are many choices of both drugs and nutritional supplements available for patients with Alzheimer's disease. In light of new evidence that oxidative stress and inflammation are central to Alzheimer’s disease, people at risk of Alzheimer’s (or those who have early dementia) are advised to take supplements that reduce inflammation and oxidative damage. These include:
Curcumin—900 to 1800 milligrams (mg) daily
EPA/DHA—1400 mg daily of EPA and 1000 mg daily of DHA
Vitamin E—400 international units (IU) daily (with 200 mg of gamma-tocopherol)
Vitamin C—1 to 3 grams daily
Ginkgo biloba—120 mg daily
Acetyl-L-carnitine arginate—750 to 2000 mg daily
CoQ10—100 to 600 mg daily
N-acetylcysteine—600 mg daily
Aged garlic—1200 mg daily
Vinpocetine—15 to 20 mg daily
Green tea extract (93 percent polyphenols)—725 mg daily
B vitamins—A full complement of B vitamins (including folate, vitamin B6, and vitamin B12) to lower homocysteine. Specific suggested doses include 1000 micrograms (mcg) of vitamin B12, 250 mg of vitamin B6, and 800 mcg of folic acid.
Niacin—Up to 800 mg daily. Start slowly and take with food to avoid flushing.
Melatonin—1 to 3 mg each night
DHEA—15 to 75 mg daily. Have blood tested in 3 to 6 weeks to determine optimal dose.
Huperzine—50 mcg up to four times per week
Blueberry extract—500 to 2000 mg daily. If you eat blueberries, you don’t need to take this much blueberry extract.
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