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05-01-2015

Centrophenoxine stimulates the brain and combats ageing

Memory Centrophenoxine, also known as Meclofenoxate, was developed in 1959 and has been widely used for more than 30 years for age-related brain disorders and memory impairment. Centrophenoxine stimulates glucose and oxygen uptake in the brain which is essential for energy generation as well as carbon dioxide production. It removes the accumulation of potassium and lipofuscin. The transfer of potassium and sodium across membranes is vital for good cellular communication but can be impeded by lipofuscin. Centrophenoxine is very effective at treating problems associated with damage to the brain from ageing, stroke, drugs or chemicals including excess alcohol consumption. It also protects against environmental chemicals.

Centrophenoxine comprises two biochemicals: diethylaminoethanol (DMAE) and parachlorophenoxyacetate (pCPA). DMAE is a natural ingredient found in foods such as fish, and is also a metabolite of choline which is naturally present in humans. pCPA is a synthetic ingredient similar to various plant hormones known as ‘auxins’. Both are powerful antioxidants that can protect the brain from free radical damage. pCPA is also an analogue of pyroglutamic acid (PCA) which is naturally present in the brain.
The therapeutic benefits of centrophenoxine have been observed notably in cases of cerebral atrophy, brain injury, post-apoplectic state (following a stroke), chronic alcoholism and barbiturate poisoning.

Clinically-demonstrated effects

In clinical studies on patients with symptoms such as confusion, psychosomatic asthenia (extreme weakness), disturbances of memory or intellectual concentration, significant progress was seen after only a few weeks’ treatment.
In European scientific literature, a marked improvement in symptoms including fatigue, irritability, confusion or memory loss was reported in geriatric patients treated with centrophenoxine.

Two small pilot studies of patients with tardive dyskinesia, a neurological disorder characterized by abnormal involuntary movements of the mouth, tongue, jaw, neck or extremities, normally caused by use of anti-psychotic drugs, showed a significant reduction in these symptoms in almost two-thirds of patients following treatment with centrophenoxine.
Regular intake of centrophenoxine can prevent mental deterioration. It improves memory performance both in healthy individuals and in those with dementia.

In a double-blind study of 50 elderly patients with medium-level dementia, centrophenoxine produced significantly greater memory stimulation than a placebo. It also led to improvements in general health status.

In a double-blind study of geriatric subjects, centrophenoxine was found to increase the brain’s ability to transfer new information into secondary memory. Alongside this enhanced memory function was an improvement in the ability to carry out everyday activities. Patients spoke in terms of ‘increased alertness’ and ‘feelings of well-being’ when describing the treatment’s benefits.

Boosts brain energy

Centrophenoxine has a stimulant effect on the brain. It enhances the brain’s uptake of glucose and oxygen as well as carbon dioxide production, so increasing ATP generation.

Demonstration of centrophenoxine's ability to boost the resistance of cerebral cells in rats, mice and rabbits to various forms of oxygen deprivation, including cyanide intoxication, reduction in atmospheric pressure and oxygen pressure in breathed air, provides confirmation that it operates through the enhancement of alternative pathways of glucose metabolism.

Using electroencephalograms (EEGs), scientists observed in rats a sustained increase in brain metabolic activity even under hypoxic conditions (low brain oxygen). Other experiments on rats showed that centrophenoxine increased electrical cortical activity by almost 40% in both adult and elderly animals. Since brain electrical activity is a reflection of brain metabolic activity, this is further confirmation of centrophenoxine’s neuro-energising effect.

A superior cholinergic agent

DMAE, the main constituent of centrophenoxine, is converted into choline by the liver with the addition of a methyl group (CH3); it thus provides DMAE and choline to the brain. A vitamin B-like substance, choline is both obtained from the diet and produced by the body. Essential for optimal brain function, it is used to produce other biochemical substances such as acetylcholine, a key neurotransmitter for memory, learning and intellectual concentration. It also provides the basis for the production of phosphatidylcholine and sphingomyelin, two essential cell membrane constituents.

Although the body does make choline, significant amounts come from dietary sources such as liver, meat and eggs. However, vegetarian diets or those high in processed foods provide little choline, and inadequate choline intake is incompatible with good health.

Between meals, choline blood levels in humans typically range from 8 to 12 micromoles. Choline flows both ways across the blood-brain barrier: from the brain towards the blood when blood levels are less than 14 micromoles and vice versa when they are 14 micromoles or more.

Under fasting conditions, such as in between meals, when the flow is from the brain to the blood, choline is derived (in order to make acetylcholine) from auto-cannibalism of membrane phospholipids. Choline insufficiency can sometimes lead to permanent auto-cannibalisation, membrane damage and cell death.

What’s more, a number of studies have linked long-term auto-cannibalisation of choline to the development of Alzheimer’s disease.

Consuming choline-rich foods or supplementing with choline lecithin, DMAE or centrophenoxine can increase choline plasma levels to 30 micromoles or more, resulting in higher levels of choline and acetylcholine in the brain.

Choline supplements such as choline chloride or choline bitartrate have poor availability with up to 60% often destroyed by intestinal bacteria.

Centrophenoxine is an ideal source of blood and brain choline for several reasons. Firstly, DMAE is not digested by intestinal bacteria and is quickly and easily converted by the liver into choline in line with the body’s requirements. The DMAE provided to neurons by centrophenoxine inhibits the enzyme choline dehydrogenase, thus preventing choline from becoming irreversibly oxidised into betaine and maintaining higher blood and brain levels of choline than would otherwise be possible. Lastly, DMAE crosses the blood-brain barrier much more easily.

Thus centrophenoxine is probably the most effective way of raising blood and brain levels of choline and acetylcholine. At the same time, it protects neurons from the risks of choline auto-cannibalisation.

A powerful antioxidant

Imre Zs-Nagy, a leading authority on centrophenoxine, believes it is the substance’s antioxidant effects which make it so valuable for brain health. He maintains it is more effective at delivering DMAE into the brain than DMAE itself.
Once inside brain cells, DMAE is converted into phosphatidyl choline. Phosphatidyl DMAE is similarly incorporated into nerve cell membranes, and around 40% persists in this form for more than 24 hours in place of choline. Unlike phosphatidyl choline, phosphatidyl DMAE is a powerful free radical scavenger, and is particularly effective at quenching the hydroxyl radical.

Various experiments have been conducted on the damaging effects of hydroxyl radicals on nerve cells and proteins as well as on the benefits of centrophenoxine/phophatidyl DMAE in combatting such damage. Iron overload in cerebrospinal fluid, for example, is extremely dangerous because it encourages the formation of hydroxyl radicals. At lower doses, it has been found to accelerate ageing in young rats. Research shows pre-treatment with centrophenoxine provides significant protection to rat synaptic membranes against this type of iron overload.

In a comparison of membrane proteins from 2, 12 and 24 month old rats, researchers observed an increase in high molecular weight proteins and a decrease in low molecular weight proteins. This was the result of increased cross-linking of proteins due to the hydroxyl radical attacks that occur over a lifetime. Two months’ centrophenoxine treatment reversed this phenomenon in the elderly rats, because of the incorporation of phosphatidyl DMAE into neuronal membranes which reduced the cross-linking of proteins. In effect, the centrophenoxine rejuvenated the aged rats’ synaptic membranes.

When young, adult and elderly rats were treated with centrophenoxine for 40 days, a significant increase in neuronal membrane fluidization was observed in all three groups.

Neuronal membranes generally become less fluid and more rigid with age because of hydroxyl radical-induced damage and protein cross-linking. Decreased fluidity of neuronal membranes impairs their ability to conduct electrical impulses. Since fluidity decreases as membrane lipid peroxidation caused by hydroxyl radicals increases, these results were seen as further evidence of centrophenoxine’s anti-hydroxyl radical and brain cell-rejuvenating effects. 

For two months, researchers gave centrophenoxine to rats aged 1.5, 13 and 26 months. They had already noted in the 26-month old rats a significant reduction (50%) in total RNA and messenger RNA production. They found the centrophenoxine significantly increased RNA synthesis in these rats - to levels approaching those of the 13-month old rats.

RNA (derived from DNA in the cell nucleus) enables cells to receive “instructions” from their nuclear genes and to replace worn-out or hydroxyl radical-damaged proteins with new proteins. Centrophenoxine counteracts the decrease in brain RNA and protein production generally seen with age.

Maintaining consistently high levels of phosphatidyl DMAE in neuronal cell membranes by regularly supplementing with centrophenoxine may represent an effective strategy both for combatting brain ageing and repairing or regenerating hydroxyl radical-damaged cell membranes, even in the later stages of life.

Removes lipofuscin

Some of the first data to emerge from animal studies showed centrophenoxine to be highly effective at reducing levels of lipofuscin, a residue of membrane fragments, damaged proteins and fatty acids that accumulates in cells over a lifetime. Lipofuscin was found to occupy up to 30% of the volume of the cells of elderly animals. As more and more lipofuscin accumulates, cells become less able to function properly and can quickly die once a critical volume is reached. Lipofuscin is sometimes called ‘age pigment’, appearing as brown marks on some parts of the body - on the face (ageing spots) and on the hands which the French refer to as ‘fleurs de cimetière’ (cemetery flowers).

It has been shown in healthy, elderly animals that prolonged administration of centrophenoxine leads to significant reductions in lipofuscin.

A considerable decrease in lipofuscin was observed in mice following six weeks’ treatment with centrophenoxine. In a study on elderly rats, lipofuscin levels in various regions of the brain fell by between 25% and 42% after eight weeks’ treatment. In rats aged 6, 9 and 12 months, six weeks’ treatment resulted in a decrease in lipofuscin and an increase in antioxidant enzymes in the cerebellar cortex. The life expectancy of the centrophenoxine-treated animals was much longer than that of untreated rats. This study is the only one to scientifically demonstrate that taking centrophenoxine extends lifespan in animals. Animal and human studies have shown that low levels of lipofuscin are correlated with healthy cell function and high levels with poor cellular health.

Memory and learning capacity was restored to youthful levels in elderly animals whose lipofuscin levels had been reduced by centrophenoxine.

It has been suggested that centrophenoxine’s beneficial effects on mental function in people with dementia may be partly due to its scientifically-demonstrated potential for reducing lipofuscin volume in nerve cells. Many researchers believe its benefits are also due to improvements in cell metabolism.


Centrophenoxine: effects on aging mammalian brain, Nandy K, 1978, J Am Ger Soc 26, 74-81.
A survey of the available data on a new nootropic drug, Zs-Nagy et al., 1994, BCE-001 Ann NY Acad sci 717, 102-14.
Centrophenoxine increases the rate of total and mRNA synthesis in brain cortex of old rats: an explanation of its action in terms of the membrane hypothesis of aging. Zs-Nagy et al., 1984, Exp Gerontal Geriatr 9, 17-30.
The differential effects of meclofenoxate on memory loss in the elderly, Marcer D et al, 1977, Age and ageing 6, 123-31.6
Age-related change in the multiple unit activity of the rat brain parietal cortex and the effect of centrophenoxine, Roy D. et al, 1988, Exp Gerontal 23, 161-74.
Choline: an important nutrient in brain development, liver function and carcinogenesis, Zeisel S, 1992,J Am Coll Nut 1, 478-81.
Choline, an essential nutrient for humans, Zeisel, S et al., FASEB J 5, 2093-98.
Alterations in the molecular weight distribution of proteins in rat brain synaptosomes during aging and centrophenoxine treatment of old rats, Nagy K et al. 1984, Mech Age dev 28, 171-176.
Fluidising effects of centrophenoxine in vitro on brain and liver membranes from different age groups of mice. Wood et al. 1986, Life Sci 39, 2089-95.
Effects of centrophenoxine on lipofuchsine pigment in the nervous system of old rats, Riga S et al.1974, Brain Res 72, 265-275.
Effects of centrophenoxine on body composition and some biochemical parameters of demented elderly people. Fulop T Jr et al., 1990, Arch Gerontal Geriatr 10, 239-51.
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Eliminates liposfuscin and fights cerebral ageing

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