The study, published in Nutrition Reviews, assesses previous research and clinical trials that have attempted to use nutritional modification to aid brain functioning, suggesting that certain compounds may bring about physiological and cognitive benefits for the brain.
“The rates at which brain neurons form new dendritic spines and then synapses depend upon brain levels of three limiting compounds – uridine, DHA, and choline … Hence, oral administration of these compounds can increase brain phosphatide levels,” explained the reviewers, led by Dr Richard Wurtman, Professor of Neuropharmacology at the Massachusetts Institute of Technology (MIT), USA – who also works as aconsultant for Danone (US name Donnon) Nutricia.
They added that administration of such compounds over several weeks “can enhance cognitive functions and neurotransmitter release in experimental animals,” whilst their administration to patients with mild Alzheimer's disease “significantly improved memory in a clinical trial involving about 220 subjects.”
The researchers explained that diseases of aging, such as Alzheimer's disease, decrease the number of synapses thereby impairing cognition and “ultimately compromising most brain functions.”
Loss of function is generally thought to result from the toxic effects of amyloid-beta and its aggregates on synapses, and their precursors’ dendritic spines. However, no treatment strategy has been found to increase the number of synapses in brains of Alzheimer patients.
“An extensive and often frustrating search has been pursued for several decades to find a treatment that might block amyloid-beta formation, aggregation, or toxic effects or perhaps remove the amyloid-beta using a monoclonal antibody,” said Wurtman and colleagues.
They explained that synapses are made up of a special membrane, made up of phosphatide lipids and a specific set of proteins – known as the ‘synaptic membrane’.
Previous research has shown that treating animals with three particular phosphatide precursors present in the blood and formed within the body (uridine and choline) or derived from foods (choline and omega-3 fatty acids) can have beneficial effect:
“It increases brain phosphatides, synaptic proteins, neurite outgrowth, and the formation of dendritic spines,” said the reviewers.
They noted that the treatment also “enhances cognition and the release of some brain neurotransmitters in the animals.”
Prof Wurtman and his colleagues explained that the brains of patients with Alzheimer's disease are deficient in choline and DHA, which leads to a selective decreases in numbers of P2Y2 receptors, dendritic spines, and synapses.
Previous studies have suggested that when animals treated for several weeks with uridine, choline, and the omega-3 fatty acid docosahexaenoic acid (DHA), the quantities of synaptic membrane synthesized from these compounds increase significantly – both in whole brain and per brain cell.
The researchers noted that treatments which raise blood DHA levels rapidly have been found to increase its uptake into and retention by brain cells; they explained that dietary omega-3’s, such as DHA, are “preferentially incorporated into brain.”
Wurtman and co-workers also noted that administering a uridine-DHA-choline mixture has been found to improve cognition and increase dendritic spine number synaptic membrane levels.
They said that therefore seems reasonable “to explore whether this treatment might also improve cognition in impaired patients with Alzheimer's disease.”
A previous clinical trial (Scheltens et al - Alzheimer's & Dementia; Volume 4) involving subjects with mild Alzheimer's disease examined the effects of a cocktail of phospholipids, proteins and nutrients, on a delayed verbal memory task and the item-modified Alzheimer's Disease Assessment Scale. The study found that the group receiving the mixture had “a significant benefit”
“This proof-of-concept study was interpreted as demonstrating that giving a drink that contains DHA, uridine, choline, and other nutrients for 12 weeks can improve memory in mild and very mild Alzheimer's disease, and that further studies now in progress are justified,” said the reviewers.
Source: Nutrition Reviews
Volume 68, Issue Supplement s2, pages S88–S101, doi: 10.1111/j.1753-4887.2010.00344.x
“Nutritional modifiers of aging brain function: use of uridine and other phosphatide precursors to increase formation of brain synapses”
Authors: R.J Wurtman, M. Cansev, T. Sakamoto, I. Ulus