Thursday November 6 2008
A vitamin pill could slow the progression of Alzheimer’s disease, according to media reports today. The Guardian said that animals studies found that nicotinamide, a form of vitamin B3, protected the animals from memory loss associated with a condition similar to Alzheimer’s.
But the dose used in the study - on mice - would be high if given at an equivalent level in humans, far higher than levels of the vitamin found in food or in vitamin supplements.
Vitamin B3, also known as niacin or nicotinic acid, can be found in low doses in foods such as meat, poultry, fish, nuts, beans and also in cereals and potatoes. It can also be obtained in vitamin supplements.
A human trial giving equivalent doses would have to use 2g of the vitamin a day. The Food Standards Agency advises that taking 500mg or less of nicotinamide supplements a day is unlikely to cause any harm, but that there is insufficient data to establish a safe upper level. The Guardian reports that serious side-effects, including liver damage, have been seen in doses of 10g or more.
At present, there is not enough evidence to advise taking vitamin B3 to treat Alzheimer’s.
Where did the story come from?
Dr Kim Green and colleagues from Neuroscience Departments at the University of California carried out the research. The study was published in the peer-reviewed: Journal of Neuroscience. Financial support for the research was provided by national research bodies and charities.
What kind of scientific study was this?
This was an animal study in mice that had been genetically engineered to have a condition with similar features to Alzheimer’s disease. The researchers wanted to see if nicotinamide had any effect on the short and long-term memories of these mice.
The researchers say that there are enzymes that add or remove the chemical “acetyl” group from proteins and influence many of the complex processes that occur within cells. These enzymes are linked to neurodegenerative diseases such as Alzheimer’s and have been extensively studied in previous experiments on yeasts and mice.
Nicotinamide is known to impair the function of one group of these enzymes: histone deacetylases (HDACs). Other chemicals that do this have been shown to improve some neurodegenerative conditions in flies and mice, and the researchers wanted to see if nicotinamide would have a similar effect in the mouse model of Alzheimer’s disease.
To investigate this, the researchers added the vitamin to the mice’s drinking water for a four month period. They tested the short-term and long-term memory of the mice over time with a water-maze and some object-recognition tasks. After the memory experiments the researchers tested the protein content within the brains using a range of methods.
Of interest to the researchers was the tau protein, which in Alzheimer’s disease builds up in the brain and can lead to the development of tangles, one of two brain lesions associated with the condition. The researchers also looked at the protein “scaffolding” within the nerves as this is thought to help keep neurons alive and help nerve signals to travel along the nerves.
What were the results of the study?
The researchers say that the mice’s cognitive abilities, demonstrated by their ability to get out of the water maze, was improved in the nicotinamide treated mice compared to untreated mice. The nicotinamide also selectively lowered the level of a particular form of the tau protein (the phosphorylated tau protein) and strengthened the 'scaffolding' along which information travels in brain cells.
What interpretations did the researchers draw from these results?
The researchers say that the findings suggest that “oral nicotinamide may represent a safe treatment for Alzheimer’s disease” and that phosphorylation of the tau protein may regulate tau stability. This would help keep neurons alive and prevent further memory loss in the mice genetically wired to develop Alzheimer's.
What does the NHS Knowledge Service make of this study?
In the long-term, this research could have important implications for the treatment of Alzheimer’s. However, this is still early research and it is unknown if nicotinamide will have the same effect in humans as it does in mice. There could be differences in the way that the chemical is absorbed, metabolised, travels to the brain or acts within cells. There are also issues with getting the dose correct and in ensuring that there are no other adverse effects in humans. Further research to determine this could take years to complete.
Reportedly, nicotinamide is currently being tested in treating other degenerative neurological conditions in humans. This could mean that some of its effects in humans may be known sooner than if it had only been tested in animals. However, many vitamins have been tested for dementia in humans (see Cochrane reviews) without any obvious signs of success.
Sir Muir Gray adds...
There is no evidence yet to start on any of the B vitamins.
Links to the headlines
Vitamin B supplement could slow Alzheimer's disease. Daily Mail, November 06 2008
Vitamin pill that may slow Alzheimer's goes on trial. The Guardian, November 06 2008
Vitamin 'may be Alzheimer's aid'. BBC News, November 06 2008
Vitamin B supplements could prevent Alzheimer's memory loss. The Daily Telegraph, November 06 2008
Links to the science
Green KN, Steffan JS, Martinez-Coria H, et al. Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau. J Neurosci 2008; 28: 11500-11510
Malouf R, Grimley Evans J. Vitamin B6 for cognition. Cochrane Database Syst Rev 2003, Issue 4
Isaac MGEKN, Quinn R, Tabet N. Vitamin E for Alzheimer's disease and mild cognitive impairment. Cochrane Database Syst Rev 2008, Issue 3
Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev 2008, Issue 4
Malouf R, Areosa Sastre A. Vitamin B12 for cognition. Cochrane Database Syst Rev 2003, Issue 3
Rodríguez JL, Qizilbash N, López-Arrieta J. Thiamine for Alzheimer's disease. Cochrane Database Syst Rev 2001, Issue 2