Vitamin B3 and Alzheimers Disease

9/11/2008 4:37PM

Vitamin B3 and Alzheimers Disease

Nicotinamide is a form of Vitamin B3. This is a promising study because this compound was found to target a key and early initiator of amyloid plaque formation in the brain. That process is tau phosphorylation which is implicated in many neurodegenerative conditions. Nicotinamide can be purchased as supplement and is generally safe but at very high doses can be toxic.

The Science Daily news release is available here.



The Journal of Neuroscience, November 5, 2008, 28(45):11500-11510; doi:10.1523/JNEUROSCI.3203-08.2008
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
Correspondence should be addressed to Frank M. LaFerla, Department of Neurobiology and Behavior, University of California, Irvine, 1109 Gillespie Neuroscience Building, Irvine, CA 92697-4545. Email: laferla@uci.edu
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 -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.

SAM-e can be Dangerous

SAM-e is being widely promoted as a "natural antidepressant". Quite by accident I recently stumbled upon some data which indicated that sustained use of SAM-e is potentially very dangerous.

SAM-e is S-adenosylmethionine. Part of its known actions is to act as a methyl donor. If you are using SAM-e you must make sure your vitamin B levels are adequate. The use of SAM-e has been associated with hyperhomocysteinemia, excess SAM-e is associated with Parkinson's Disease like disorders, excess methyl donation is a risk factor for some cancers, and the hyperhomocysteinemia that can arise from unwise use of SAM-e can induce atherosclerosis. It has also been found that in the brains of schizophrenic patients there is an over expression of SAM-e. Excessive SAM-e also induces oxidative stress and lipid peroxidation.

If you are taking S-adenosylmethionine be absolutely certain you have a very good intake of the B vitamin group, particularly folate, and you have a good antioxidant intake as well.

NEVER take SAM-e in conjunction with any antidepressants, "natural" or otherwise. It is probably advisable that before taking SAM-e you should have your homocysteine levels checked. If these levels are high then do not take it and immediately boost your intake of B vitamins and folate.

If you are using SAM-e for depression you might want to consider an "unnatural antidepressant" prescribed by your doctor. Antidepressant drugs are amongst the most widely prescribed drugs and have been subject to extensive trials and analysis. They have an excellent safety profile but it can take quite some experimentation to find the antidepressant that works for you. As recent studies have indicated the efficacy of antidepressants appears contingent on the induction of neurogenesis. This is probably a downstream effect from antidepressant use. At present I am taking an antidepressant. No, I'm not depressed, I just prefer the occasional dosing of an antidepressant because the one I am using has a number of favourable qualities.

Ideally if you are suffering from depression you should first try strategies that do not require taking anything. Check your diet, get some regular exercise, spend time with positive people, stabilise your sleep patterns if need be, get out in the sun occasionally(yes, sunshine, probably via circadian regulation and vitamin D, can give a slight boost to serotonin levels), and find ways to reduce your stress levels.

A brief overview of SAM-e is available at Wikipedia.