Choline Alfoscerate

• The ability of the brain to take in necessary raw materials.
• The loss of balance in key cholinergic enzymes.
• The loss of choinergic neurons.

Choline alfoscerate (al-FOSS-er-ate), or alpha-glycerylphosphorylcholine (GPC), is a phospholipid - a complex fatty substance containing phosphorus, like phosphatidylserine and phosphatidylcholine - and is an important building block in the construction of nerve cell membranes. After completing an analysis of thirteen published clinical trials, involving over 4000 patients, a group of Italian scientists concluded that "The stated therapeutic usefulness of Choline Alfoscerate in the relief of cognitive symptoms, such as memory and attention impairment, differentiates [it] from cholinergic precursors used in former clinical trials", such as choline, lecithin, or phosphatidylcholine. The reason, as evidence now suggests, is that the effects of this versatile nutrient extend well beyond its role as a mere choline source: choline alfoscerate supports the restoration of a whole spectrum of youthful cholinergic functions.

Weak Link 1: Decreased Choline Uptake
Choline alfoscerate is a rapidly absorbed source of choline, which easily enters the brain. GPC raises free plasma choline more rapidly than other uncharged choline precursors. Because it is a phospholipid - the same sort of material of which the brain and Blood-Brain Barrier (BBB) are made - Choline Alfoscerate does not carry the electrical charge of regular choline, and so freely crosses the blood-brain barrier. The choline from Choline Alfoscerate is incorporated into brain phospholipids within 24 hours of absorption.

Weak Link 2: Enzyme Imbalances
The brain makes acetylcholine using an enzyme known as choline acetyltransferase. As we get older, ChAT activity goes down, while the activity of enzymes that break down chat goes up. As a result, aging brains make less acetylcholine from the choline available to them, while they tear acetylcholine down more quickly. Animal studies suggest that Choline Alfoscerate may also improve the levels of ChAT.

Weak Link 3: Brain Drain
This is perhaps the most serious issue facing the aging brain: the cholinergic neurons of the brain simply wither away with age. The number of neurons declines, and those neurons that remain literally shrink, becoming less well-connected to the rest of the brain. This decay is made all the worse by the fact that the ability of the surviving cholinergic neurons to release and respond to ACh is also impaired with age!

There are two main reasons for this loss of function. First, the composition of the nerve cell membrane is altered with age, becoming less flexible and responsive. This makes it harder for the neuron which is sending the signal to release the ACh messenger, and harder for the receiving neuron to pick it up. Choline alfoscerate restores membrane and fluidity responsiveness, both because having more Choline Alfoscerate in the membrane directly makes the membrane more fluid, and perhaps because Choline Alfoscerate inhibits an enzyme (lysophospholipase) that breaks down some brain phospholipids.

Second, some of the receptors to which ACh is designed to bind - the "mailbox" to which they are addressed - also decline with age. This is especially true of the muscarinic-type-1 (M1) receptors - the ones involved in higher mental function. While most other cholinergic receptors remain plentiful throughout life. Fortunately, Choline Alfoscerate selectively restores the number of memory-specific cholinergic receptors.

Even more incredibly, animal studies show that Choline Alfoscerate actually increases the number of cholinergic neurons as well. In addition, Choline Alfoscerate may reverse the atrophy of existing cholinergic neurons, since studies show that Choline Alfoscerate increases the number of receptors for nerve growth factor (NGF). Supplying NGF to old monkeys clearly reverses cholinergic neuron atrophy, restoring the number and size of these neurons to more youthful levels.

Controlled Trials: It Works
In one controlled trial in victims of vascular dementia, greater improvements on several measures of cognitive function were seen amongst those patients treated with Choline Alfoscerate than in those given another choline precursor. The differences were statistically significant, and both patients and physicians rated the results with GPC more satisfactory.

Another controlled trial in Alzheimer's disease compared Choline Alfoscerate to acetyl-L-carnitine (ALCAR), a nutrient already proven to slow the progression of AD in younger patients. Most behavioral and mental function test results showed improvement in the Choline Alfoscerate group - and the improvements were greater than those seen in the ALCAR group.

Yet another trial monitored the progress of 2044 patients who were being treated with Choline Alfoscerate after recent strokes or transient ischemic attacks (TIAs - sometimes called "mini-strokes"). Statistically significant improvements were seen on several scales of cognitive performance, such that the Mini Mental State (MMS) score was found to be within the normal range, Chrichton Rating Scale (CRS) decreased by a significant 4.3 points, and the Global Deterioration Scale scores indicated "no cognitive decline" or "forgetfulness" rather than clinical mental impairment.

There is also a hint that Choline Alfoscerate may prove of use in Parkinson's disease (PD). PD is characterized by reductions in the production of the neurotransmitter dopamine in an area of the brain called the substantia nigra. This leads to a loss of motor control, typically manifesting in facial ticks or tremors, dry mouth, and a "masklike" facial expression. In laboratory animals, measures of dopaminergic activity were enhanced by GPC treatment.

The Growth Hormone (hGH) Connection
In addition to is exciting potential for supporting the healthy functioning of the brain, Choline Alfoscerate may provide us with part of the key to reversing some of the more visible symptoms of the aging body. For some time, research has been focusing in on the age-related loss of human growth homone (hGH, or somatotropin) as a major source of the symptoms of aging. hGH helps keep our bones strong, our immune systems vigorous, our wound-healing abilities optimal. It builds muscle and burns fat. Its levels are high in our youth, when all of these functions are at their peak, and their decline follows the decline in many aspects of youthful function. As experiments by Dr. Daniel Rudman and others have shown, administration of hGH to aging humans can bring about changes in body composition which are "equivalent in magnitude to the changes incurred during 10-20 years of aging."

It may surprise you to learn that older brains make just as much hGH as younger ones. It's the release of those growth hormone stores that goes down with age. The body's release of hGH is controlled by two brain messengers: growth-hormone releasing hormone (GHRH), which acts like the "accelerator" for growth hormone secretion, and somatostatin, which takes the role of the "brakes." The loss of hGH release with age is mostly caused by too much somatostatin: in effect, the aging brain is always "riding the brakes." Where does Choline Alfoscerate fit into this picture? Importantly, the cholinergic system can significantly curb the activity of somatostatin. Indeed, the slow loss of cholinergic tone is a big part of the reason why growth hormone release goes down with age. So it's no surprise that Choline Alfoscerate has only very mild effects on hGH levels in young, healthy athletes when taken by itself: after all, their cholinergic systems are in their prime, and so their somatostatin levels are kept under control. But older bodies are different: with lower cholinergic activity, somatostatin levels become excessive, and hGH release is impaired. As you'd expect, then, GPC significantly boosts hGH release in older folk, and does so dramatically when used in combination with stimulation by GHRH.

When younger (average age 32) men and women took Choline Alfoscerate alone, they showed almost no improvement in hGH release; yet older men and women experienced a significant increase in growth hormone. More impressively, when the two groups took GPC in combination with a GHRH stimulus, the young men's hGH levels increased by 36% more than they did after the GHRH alone; but the same Choline Alfoscerate/GHRH combination tripled older peoples' hGH compared to the GHRH-only treatment (see Figure 1). Taking Choline Alfoscerate in combination with hGH releasers that directly stimulate hGH or GHRH, such as niacin (as in "flushless" niacin (inositol hexanicotinate - not niacinamide!), glutamine, or glycine - may thus provide the same potent synergistic effect seen with GHRH itself.