BRAIN HEALTH - THE CITICOLINE CONNECTION

If you want to prevent age-related cognitive decline and keep serious memory loss at bay, you need to "feed" your brain what it needs to function at its best. Citicoline (CDP-choline; cytidine 5'-diphospho-choline) is a nucleotide (a building block of DNA) found in every cell in the body. It plays a key role in the creation of cell membranes. Citicoline triggers the production of the neurotransmitter acetylcholine, and modu-lates transmission of other neurotransmitters dopamine and norepineph-rine. It may also help protect and regenerate brain tissue. Recent studies show that increasing citicoline levels through nutritional supplements, may help prevent premature cognitive decline.

One of citicoline's most important effects in the brain may be its abil-ity to increase production of adenosine triphosphate (ATP) in the frontal lobe. ATP provides energy to the mitrochondria of each cell. Not only is this energy vital for cellular activity, increasing its production may help reduce memory problems and the mental fatigue associated with age.

A study conducted at the Brain Imaging Center at McLean Hospital in Belmont, Massachusetts, used the latest brain scanning technology to monitor brain activity in people taking supplemental citicoline. After supplementing for six weeks, the participants showed increased levels of specific markers for ATP in a frontal lobe region of their brains. Citicoline's positive effects on the brain persisted long after supplementation stopped, suggesting that the supplement may have a cumulative ability to repair and maintain neuron function.

Unlocking The Power of The Mind

How well does citicoline work? A growing number of clinical trials on healthy adults with mild forgetfulness show that citicoline improves both immediate and delayed recall of words and objects. Other research shows that citicoline supplements benefit brain function in seniors with cog-nitive impairment. Specifically, citicoline improves short and long-term memory, attention span and perceptual-motor capacity. Supplementing with citicoline can also help seniors remember words and phrases. During a double-blind placebo-controlled trial of 95 volunteers between the ages of 50 and 85, those taking 2,000 mg of supplemental citicoline daily for two months significantly improved their verbal memory compared to the volunteers taking a placebo.

Citicoline has also been used successfully to treat degenerative brain diseases like Alzheimer's. In an analysis of 12 clinical trials conducted by the Cochrane Collaboration, researchers found citicoline improved brain function in older people suffering from chronic brain diseases. The researchers concluded that citicoline provided modest and consistent improvements of memory and behavior in patients with Vascular Cog-nitive Impairment and Dementia. While more longer-term studies are needed, these findings are particularly exciting because there are currently very few treatments for dementia.

Future Possibilities

Because citicoline readily crosses the blood-brain barrier and reaches the central nervous system, some researchers are beginning to examine this nutrient as a potential therapy for addiction. Experiments show that citicoline raises both norepinephrine (adrenaline) and dopamine levels, and therefore may reduce cravings experienced by people addicted to cocaine. In a 12-week placebo-controlled study of 44 bipolar patients with a history of cocaine dependency, those taking a citicoline supple-ment every day used cocaine less often than the control group. They also performed better in tests measuring how well they remembered learned facts. To the extent that drugs commonly abused including heroin and other opiates, alcohol, cocaine, amphetamines and nicotine activate and regulate dopamine, boosting dopamine levels naturally could help reduce the desire for these drugs.

Citicoline may also be a viable treatment for those with head injuries. In a clinical trial of 216 patients who had suffered moderate to severe head trauma, citicoline accelerated the cognitive recovery from post-traumatic coma, helping the patients walk better and earlier, and shortening their hospital stay.

A pure and natural brand of citicoline is CognizinR, manufactured by Kyowa Hakko Bio Co. Ltd., a leading global ingredient and pharmaceuti-cal manufacturer. Cognizin is the only brand that has been scientifically studied to be safe and effective for use in foods and dietary supplements to improve brain chemistry and function.

Smart Brain Supplements

Cognition and memory can be enhanced by a variety of herbs and nutri-ents that increase blood flow, support antioxidant levels in the brain and protect it from inflammation. Following are some of the most promising and effective.


Acetyl-L-Carnitine: Similar to the amino acid L-carnitine, acetyl-L-carnitine can protect the brain from neurotoxicity and oxygen depriva-tion. It also preserves the energy-producing mitochondria in brain cells. It appears to be effective in treating mild cognitive impairment, as well as early stages of Alzheimer's. One clinical trial of 334 Alzheimer's patients at Stanford University School of Medicine discovered that acetyl-L-carnitine slowed the progression of the disease, especially among younger participants.

People without cognitive problems or memory loss can also benefit from acetyl-L-carnitine. During one recent study of 96 people over the age of 70, Italian researchers found that those taking acetyl-L-carnitine had less mental and physical fatigue. The supplement group also experienced a boost in cognition.

Beyond Cognition

Citicoline's cognition support benefits are enough to recommend it to everyone as they age, however, because it supports proper func-tioning of neurons, this remarkable nutrient may also improve other conditions caused by neurological dysfunction. The most promising potential use of citicoline may be in the treatment of stroke.

A groundbreaking trial recently showed that patients given citico-line within 24 hours of an ischemic stroke (ischemic means due to restriction of blood supply) recovered consciousness faster and had a higher probability of overcoming motor deficit than those who were not given the nutrient. In a meta-analysis of four different clini-cal trials involving more than 1,600 stroke patients, approximately 25 percent of the patients given 2,000 mg, 1000 mg, or 500 mg of citicoline within 24 hours of their stroke, recovered completely within three months. Subjects who took the highest dose of citico-line had a recovery rate of nearly 28 percent compared to just 20 percent among the control group taking a placebo.

Studies suggest that citicoline can also benefit vision. Glaucoma, for instance, is most commonly the result of a buildup of pressure from the fluid in the eye (intraocular pressure). This pressure can damage the optic nerve, which transmits images to the brain. In an open trial, 36 patients with glaucoma were given one gram of citicoline daily for ten days. The researchers concluded that citi-coline had a positive effect on optic nerve damage by increaing the flow of nutrients to nerves affected by the disease. In another study of seniors with mild to severe glaucoma, high doses of citico-line improved vision and retinal function in those who had the most common form of the disease. Supplemental citicoline has few side effects and a strong record of safety, allowing patients to take high doses on a long-term basis.

Citicoline has been shown to improve vision as well as neurological function.

Citicoline's capacity to increase dopamine levels is the key to its use in improving vision. Dopamine is the main neurotransmitter in the retina and it is a chemical messenger for light adaptation in the eye helping sharpen the contrast between light and dark. Cell sur-vival and eye growth also depend on dopamine.

A lack of dopamine in the retina can also cause amblyopia, or "lazy eye." People suffering from amblyopia experience dimness or blurring of their eyesight in one eye, which is otherwise healthy, due to a fault in the transmission of signals to the brain. Eventually, amblyopia can cause blindness, but citicoline may offer hope. Italian researchers have performed several trials in patients with amblyo-pia, confirming that citicoline significantly improves both the symp-toms of the "lazy eye" and neurological function. As a result, people with amblyopia regain much of their visual acuity.

Alpha-Lipoic Acid (ALA): ALA is an antioxidant that has been researched as a treatment for Alzheimer's and Parkinson's diseases. Both fat- and water-soluble, ALA travels throughout the body and may protect cells by enhancing other detoxifying agents such as glutathione, which serves as an antioxidant in brain tissues. ALA also contributes to meta-bolic functions that affect the brain, including glucose metabolism. It is so effective that studies show it can halt the oxidative damage that occurs as our brains age. ALA also has the ability to recycle vitamins C & E, increas-ing their effectiveness.

Additionally, there is preliminary evidence that combining alpha-lipoic-acid with acetyl-L-carnitine provides enhanced antioxidant, anti-inflammatory and metabolic regulation in the brain, which, in turn, improves cognition.

B Vitamins: There is some evidence that this family of vitamins particularly folic acid and vitamin B6 helps guard against age-related memory loss and dementia. Folic acid, with the aid of B6 and B12, may support memory by moderating homocysteine an amino acid found naturally in the body that, in high amounts, is considered a significant risk factor for heart disease, Alzheimer's disease and dementia.

In a study of more than 1,200 people, French researchers found that those with homocysteine levels higher than 15 ?mol/L had a risk of cognitive decline three times greater than people with lower levels, below 10 ?mol/L. Another study of 818 volunteers between ages 50 and 75 found that those who took high levels of folic acid 800 mcg over the course of three years had less age-related memory loss than people taking a placebo.

Evidence from clinical trials suggests that both folic acid and citico-line ameliorate the cognitive decline associated with aging. Folic acid, by itself, lowers circulating concentrations of homocysteine, while citicoline improves memory by helping maintain neuronal membranes. It also influ-ences acetylcholine production and regulates the transmission of dopamine and norepinephrine. However, the cognitive effects of taking folic acid and citicoline together have never been studied. Given their complementary mechanisms, a combination of folic acid and citicoline is likely to have a synergistic effect on memory and executive brain functions.

Fish Oil. This is an excellent source of the omega-3 fatty acid docosa-hexaenoic acid (DHA), an essential fatty acid in the brain, necessary for neural integrity and function. In double-blind, randomized, controlled trials, accelerated cognitive decline and mild cognitive impairment were found to be related to lower tissue levels of DHA and another omega-3 fatty acid EPA, also found in fish oils. Supplementation with fish oil, how-ever, improved cognitive function.

In one study conducted at Tufts University, low dietary intakes and plasma concentrations of DHA were associated with low risk of dementia and Alzheimer's disease. Among the large group of elderly Americans who took part in the nine-year Framingham Heart Study, those with the high-est blood levels of DHA were about half as likely to develop dementia and had a 39 percent lower risk of developing Alzheimer's disease than those with the lowest DHA levels.

Ginkgo Biloba: Perhaps the most well known memory-enhancing herb, ginkgo biloba boosts blood flow in the brain, destroys free radicals and pro-tects brain cells from premature death. There is also some evidence that this Ayurvedic herb modulates dopamine levels in some neural regions. One study of 262 adults found that those taking 180 mg of ginkgo for six weeks scored better on memory tests than those taking a placebo. Smaller trials show that ginkgo can also improve attention span and mental flexibility.

Huperzine A: Used to treat dementia and memory loss, huperzine A (HupA) inhibits acetylcholinest-erase, an enzyme that degrades the neurotransmitter acetylcholine in the brain. HupA also lowers oxi-dative stress and reduces the death of brain cells caused by exposure to toxins.

In one double-blind trial, 50 patients with Alzheimer's disease were treated with 200 mcg of HupA for eight weeks. The patients were evaluated with an array of psychologi-cal and physiological tests to determine their mental and physical health before and after treatment. About 58 percent of the patients treated with HupA showed improvements in their memory, as well as in cognitive and behavioral functions. These results were significantly better than those seen in the placebo group. Other research shows that HupA can improve learning performance. Best of all, this natural memory-enhancer passes through the blood-brain barrier, so it works quickly and stays active for hours without adverse side effects.

Phosphatidylserine (PS): PS is an essential fatty acid that makes up part of every cell membrane in the body. In the brain, it helps cells effec-tively communicate with each other.
A number of double-blind trials have validated the ability of supple-mental plant-derived PS to improve memory, learning, concentration, word recall and mood in both middle-aged and elderly subjects suffering from age-related cognitive dysfunction. In one study, 425 elderly volun-teers were given either 300 mg of PS or a placebo for six months. Research-ers measured cognitive function at the end of the trial and found that the subjects in the treatment group had significantly higher memory and learning scores than those taking the placebo.

 Turmeric: This curry spice is an excellent source of curcumin, a potent anti-inflammatory that reduces oxidative damage in the brain. Recent studies suggest that curcumin may also inhibit the formation and accumu-lation of amyloid plaque. Turmeric bolsters brain-derived neurotrophic factor (BDNF), a signaling molecule involved in mood. In the Singapore National Mental Health Survey of the Elderly, which involved more than 1,000 people, researchers found that those who ate the most curcumin-rich curry had a significantly lower risk of cognitive impairment than those who rarely consumed it.

Vinpocetine: This extract from the seeds of the periwinkle plant rap-idly passes through the blood-brain barrier where it increases circulation. There is also some evidence that vinpocetine can protect brain cells from the damage induced by excitotoxins such as glutamate.

One double-blind study divided 42 patients with chronic cerebral dys-function into two groups. One group received 10 mg of vinpocetine three times a day for 30 days, followed by 5 mg three times daily for 60 days. The other group received a placebo. By the end of the trial, the patients on vinpocetine scored consistently better in all evaluations of the effective-ness of treatment.

Because vinpocetine increases cerebral blood flow, it may also help stroke victims. A meta-analysis of international clinical trials showed a sig-nificant improvement in cognitive achievement in chronic stroke patients after oral therapy with vinpocetine.