The most important nutrient for the brain is fat, and not just because the brain is made of fat but because of what the fat does. In particular, brain cell membranes control the entrance and exit of material to and from each cell. Increasing the permeability of cell membranes speeds neuronal transmission.
Brain cell membranes also become rigid with age. Thus, nutrients that can maintain membrane fluidity show particular promise in maintaining healthy cognitive function.
Phosphatidylserine (PS) has a fluidising effect on brain cell membranes, which speeds signal transmission among neurons. Research has demonstrated that PS can improve learning, memory, concentration and attention in older people with evidence of memory impairment.1 However, PS has been historically derived from bovine cortex, and when bovine spongiform encephalopathy, or mad cow disease, emerged in 1991, research into this phospholipid cratered. In the later 1990s, a form of PS derived from soy was developed, which was shown to be safe in a study of 120 elderly subjects at doses up to 600mg/day.2
Despite a positive safety profile, and some studies noting equivalent results whether from bovine-sourced or soy-sourced — compared with egg-sourced PS3 — results from studies using soy-derived PS have been equivocal.4,5 More research is needed to adequately discern whether soy-sourced PS can be as beneficial as bovine-sourced, or whether organic cows fed a strictly vegetation diet could be a satisfactory source. In addition, krill oil-sourced phospholipids are coming on the market, and this unique source also needs further research on its efficacy.
Citicoline, a form of the B vitamin choline, is used by the brain to repair brain cell membranes and also helps restore membrane phospholipids. In a recent study, conducted on 11 healthy young subjects at Harvard Medical School in 2004, oral citicoline supplements were able to cross the blood-brain barrier to raise brain choline levels within a few hours following oral intake.13 Also known as CDP-Choline, it has been studied because of its ability to inhibit phospholipid degradation.6 Brain cells are able to turn citicoline into phosphatidylcholine (PC), and citicoline also helps replenish the brain's content of PS.7
One double-blind, placebo-controlled, randomised study at the Massachusetts Institute of Technology tracked 95 subjects between 50 and 85 years old who took 1g/day citicoline for three months. Citicoline improved delayed recall on logical memory, but only for those with relatively inefficient memories. In a crossover follow-up with 32 of the subjects who took 2g/day for two additional months, the higher dosage was associated with improved immediate and delayed logical memory, which may be a precursor of dementia.8
Another human clinical trial found that citicoline possesses memory-enhancing activity in free recall tests (but not in recognition tests) at doses ranging from 300-1,000mg/day.9
Also of note, oral citicoline was associated with an increase in levels of brain phosphodiesters, including a phospholipid derivative called glycerophosphocholine, or alpha-GPC.10
Alpha-GPC is one of the hotter ingredients being integrated into brain-health formulations today. It is a precursor to the neurotransmitter acetylcholine and the membrane constituent PC, and can increase the rate of phospholipid synthesis.11
Animal studies demonstrate increased choline metabolites in the brain following oral administration. Several reports differ as to whether similar increases are observable in human subjects.12
Studies have investigated its efficacy for cognitive disorders including stroke and Alzheimer's. An Italian multicentre clinical trial on 2,044 patients suffering from recent stroke were supplied alpha-GPC in doses of 1,000mg/day for 28 days and 400mg/day for five ensuing months. The trial confirmed the therapeutic role of alpha-GPC on the cognitive recovery of patients based on four measurement scales, three of which reached statistical significance.14
A randomised, controlled clinical trial that compared alpha-GPC to acetyl-L-carnitine among 126 patients with mild to moderate Alzheimer's found significant improvements in most neuropsychological parameters in both groups, as well as tolerability, though the alpha-GPC group fared slightly better.15
Acetyl-L-carnitine is the acetyl derivative of L-carnitine. The L-carnitine pool in the body consists of nonesterified L-carnitine and many acylcarnitine esters. Of these esters, acetyl-L-carnitine is quantitatively and functionally the most significant. The importance of L-carnitine and its ester derivatives in fatty acid metabolism in such tissues as myocardial and skeletal muscle is well established, but their function in nervous tissue, which is mainly dependent on glucose for energy production, is still unknown. L-carnitine as a precursor of acetyl-L-carnitine is of considerable interest because of its capacity to counteract several physiological and pathological phenomena typical of brain ageing processes.
An imbalance of changes caused by increased production of free radicals and decreased functional efficiency of the antioxidant system has been suggested to be one of the primary factors that contribute to the ageing process.16 Administration of L-carnitine to old rats for up to 21 days reversed the age-associated changes in lipid peroxidation and restored both enzymatic and nonenzymatic antioxidants in various brain regions in a duration-dependent manner.17 Results suggest that the neuroprotective effect on the brains of old rats was achieved by the elevation of antioxidants with L-carnitine.
Further animal studies suggest that L-carnitine supplementation can improve brain function and learning ability.18,19 A study with elderly people revealed that L-carnitine resulted in significantly improved mental status compared with the placebo group.20
Green tea polyphenolic constituent epigallocatechin-3-gallate (EGCG) has new animal research to buttress its claim that it blocks the initial process that leads to Alzheimer's disease. The key event leading to Alzheimer's appears to be the formation of a peptide known as beta-amyloid, which clusters into senile plaques on the blood vessels and on the outside surface of neurons of the brain — which ultimately leads to the killing of neurons. The peptide is created by enzyme clipping of the normal neuron membrane protein known as amyloid precursor protein, which is thought to be a natural neuroprotective agent.21
An in vitro and mice study published in the Sept. 21 issue of the Journal of Neuroscience found that EGCG decreases production of the beta-amyloid protein.22 After treating Alzheimer's mice for several months with daily injections of pure EGCG, the researchers observed a 54 per cent decrease of plaque.
Of note, the researchers found that other flavonoids in green tea actually oppose EGCG's ability to prevent the build-up of beta-amyloid plaque, which means that drinking green tea may not have any effect. The researchers noted that humans would need at least 1,500mg/day EGCG to approximate the injection dosage that benefited the Alzheimer's mice, and that that amount would be safe and well tolerated. However, the difference of oral vs injection may also be of import.
This study follows earlier research findings that the neuronal toxicity of beta-amyloid is mediated through free radicals, which can be attenuated by antioxidants such as EGCG.23
EGCG is also thought to work via its role in amyloid precursor protein secretion, which protects against toxicity induced by beta-amyloid. An Israeli lab study found EGCG leads to a six-fold increase in release of the amyloid precursor protein.24
In a related area, the red wine constituent resveratrol has also been shown to lower the levels of secreted and intracellular beta-amyloid peptides, apparently by promoting intracellular degradation of the senile peptide.25 This gives this natural compound potential therapeutic value against Alzheimer's disease.
Of note to product developers looking to introduce functional brain-health products is a new study presented at the US-based Alzheimer's Association's first conference on the prevention of dementia (in the summer of 2005). A research team presented findings with 1,800 elderly people who were dementia-free at the start of the nine-year study. Those who drank fruit or vegetable juices at least three times per week had a 75 per cent reduced risk of the disease, compared with those who drank these juices less than once a week.
The results could lead to a new avenue of delivery system for cognitive enhancement product offerings.26
Over-the-horizon drinks target mood enhancement
Vitamin-fortified waters and probiotic-infused dairy drinks may be leading the functional beverages category today, but some product developers are looking to concoct drinks that address not so much brain health as brain modification.
"We call them 'euphorics,'" says Liquid Underground president Chip Marsland. "Functional drinks can address a lot of things; there's a whole market for relaxation beverages."
He says they are looking into neurotransmission stimulants, relaxants, alkaloids, SSRIs and more. This represents an extension of the functional beverages category — drinks that do not have to be necessarily healthy, just as long as they have an immediate effect on consumers. Their first launch is planned for the New Zealand market.
"Successful companies will make things that you can feel," says Marsland. "When was the last time you felt your cholesterol being lowered?"
Already, companies are putting niacin into energy drinks, which give consumers the telltale niacin "flush."
"Coffee would not be the beverage it is today if it didn't have that element in it that did something for the consumer," says Tim Avila, president of Systems Bioscience in California.
He says relaxation ingredients worthy of exploration include L-theanine, relora, magnolia, kava and valerian.
"I can see a Red Bull equivalent, only to make you chill out," Avila says. "It's just around the corner, just a matter of who comes out with the best product and how they promote it."
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