Centrophenoxine was developed in 1959 and since then it has been used by numerous people to enhance cognitive performance. Centrophenoxine is primarily touted for its memory-boosting properties as well as being beneficial for those suffering from age-degenerative brain disorders such as Alzheimer’s and Parkinson’s. Some believe it can improve overall brain function and even help you live longer.
There is evidence that centrophenoxine can help improve neurotransmitter function, remove cellular waste, improve brain energy, and even impact mRNA synthesis.
Also known as Lucidril or Meclofenoxate (brand names), centrophenoxine is available as a dietary supplement usually consumed in powder or tablet form.
What Is Centrophenoxine?
Centrophenoxine is made up of two other biochemicals:
- Fimethyl-aminoethanol (DMAE): DMAE is an amine naturally found in the brain, albeit in small amounts.
- Parachlorphenoxyacetic acid (PCPA): PCPA is a synthetic auxin. Auxins are plant hormones that stimulate growth.
DMAE by itself is not easily absorbed, however, when it is combined with PCPA to produce centrophenoxine it is much more bioavailable and better transported to the brain. Hence although DMAE is sold by itself, to maximize the benefits, you are better off consuming it as centrophenoxine.
Animal studies have proven this discrepancy; researchers found DMAE to be half as potent as centrophenoxine when it comes to elevating choline levels. Additionally, the combination also appears to boost acetylcholine (more on this soon).
DMAE is found naturally in fatty fish such as sardines, salmon and anchovies. This is part of the reason old wives’ tales refer to fish as ‘brain food’.
How Does It Work
There are a number of mechanisms that have been explored in animal studies to account for the cognitive and anti-aging benefits of centrophenoxine.
Centrophenoxine As A “Neuro-Energizer”
Researchers have labeled Centrophenoxine as a neuro-energizer due to its ability to enhance alternative pathways of glucose metabolism, the way in which cells convert glucose into energy they can use. The more energy the brain has, the better it can perform. Studies have found that centrophenoxine can stimulate glucose uptake and oxygen consumption in vitro (brain slices) and in vivo (living organisms) (1).
Another study found that centrophenoxine increased the brain electrical activity in aged mice as further evidence of its neuro-energizer properties (2).
Centrophenoxine And Acetylcholine
Centrophenoxine is a cholinergic compound. Other cholinergic compounds include acetylcholine, which is a main neurotransmitter in the human brain. Acetylcholine is important for a number of cognitive functions including learning, memory formation, attention and motivation.
Choline is a precursor to the important Acetylcholine. The body can make some choline, however, the majority is consumed via food such as eggs, meat and spinach. Highly processed ‘junk-foods’ are typically low in choline. Due to the western diet many people may be low in choline, which can be harmful to health. Supplementing with centrophenoxine is a very efficient way of elevating choline levels because of its improved bioavailability compared to other options.
Rat studies have indicated that centrophenoxine supplementation can significantly elevate choline levels in the central nervous system. Moreover, these elevated choline levels were accompanied by elevated acetylcholine in the hippocampus (3). The hippocampus is located in the brain and is an area associated with memory, mainly long-term memory.
As centrophenoxine induces alterations of the CNS metabolism, it is likely to exert its effects partially by increasing the levels of acetylcholine in the brain
Centrophenoxine Protects Cells From Oxidative Damage
This mechanism has multiple benefits by its modulation of age-related oxidative damage and oxidative damage due to toxin exposure.
Anti-Aging Effects By Combating Oxidative Stress
Free radicals are byproducts of oxygen metabolism, the process by which cells obtain energy. Cells in the brain have high-energy requirements and undergo high rates of oxygen consumption. This free radical damage is presumed to be responsible for the degenerative effects of ageing on the brain. With amounting evidence that free radical-induced oxidative damage plays a role in degenerative diseases such as Alzheimer’s, it’s something to be minimized if possible (4).
Supplementing with an antioxidant that works as a ‘free radical scavenger’ could be one way to combat the harmful effects of oxygen metabolism. Animal studies have shown that supplementing with centrophenoxine is effective in increasing the activity of antioxidant compounds in the brain, and so it might be beneficial for an aging brain (5).
Fights Buildup Of Toxins In The Brain
Aluminum is widely known to be a neurotoxin that could cause neurodegeneration. Aluminum is also associated with Alzheimer’s disease, Parkinson’s disease and multiple sclerosis (6).
The main factors of aluminum exposure in humans are the environment, occupational and dietary (through food, food additives, contamination through utensils). Aluminum affects > 200 biological reactions, including many in the brain, and can alter gene expression (6).
It’s no doubt that excessive aluminum exposure can be harmful, and for some occupations and lifestyles reducing contact is tricky or not achievable. An animal study explored how administration of centrophenoxine could reverse aluminum-induced alteration of chemical reactions in the brain. The rats that were administered aluminum had significantly decreased levels of reduced glutathione, an antioxidant especially important for cellular defense against aluminum toxicity. However, those who were then treated with centrophenoxine for 6 weeks had a significant improvement in these levels. Interestingly, those who were just administered centrophenoxine alone also had an increase in reduced glutathione levels (7).
These findings indicate that centrophenoxine may prevent aluminum-induced cellular damage by improving the levels of reduced glutathione and hence it has antioxidant potential.
Helps Age-Related Decline Thorough Moderation Of Lipofuscin Concentration
Lipofuscin are yellow-brown pigment granules, mainly composed of lipid but also containing sugars and heavy metal waste like aluminum. They appear to be the result of unsaturated fatty acid oxidation and their concentration increases with age.
Sometimes referred to as ‘cellular trash’ or ‘age pigments’ they accumulate in important areas of the body including the liver, kidneys and adrenals, heart and of course the brain. Accumulation of lipofuscin is thought to be a result of an imbalance in formation and dispersal mechanisms.
There is evidence that these granules are a driver for neurodegenerative disorders such as Alzheimer’s Disease and Parkinson’s (8).
Multiple nootropics appear to reduce the accumulation of lipofuscin in the brain tissue, including centrophenoxine.
Animal studies have shown that treatment with centrophenoxine is correlated a reduction of neuronal lipofuscin pigment in both the cerebral cortex and the hippocampus in older mice (16-24 months in mice age). When the memory and learning of the mice was tested, by making them go through a maze, those who had been treated with centrophenoxine learned faster than those who hadn’t (9) (10).
Centrophenoxine And Genes – Increases mRNA Synthesis
RNA is an important molecule; it carries information on protein sequence from the DNA to the other parts of our cells where proteins are made. Simply put- DNA holds our information and mRNA carries it.
Age is associated with a decline of mRNA production. With age, mRNA is susceptible to oxidative damage, which ultimately results in diminishing levels of protein synthesis, cell damage/death (11).
One study measured mRNA synthesis in the brain of female rates by radioisotope technique. Compared to 1.5 and 13-month old rats the older group (26 months) had a considerable decrease in the synthesis rate of mRNA. However, this decline was reversed with centrophenoxine supplementation. The synthesis rates in the older rats were restored to almost that of the adult ones (12).
This is another example of how the antioxidant properties of centrophenoxine are beneficial in the brain.
Pre-Clinical Studies
Animal behavioral studies have shown potential for Centrophenoxine to improve memory, particularly in aged brains.
In one-study female mice ages 11-12 months (old in mice years) were given centrophenoxine for 3 months and their learning and memory tested using a T-maze. They compared the number of trials to complete the maze between 20 treated mice, 20 untreated mice the same age and 20 younger untreated mice. The mice that received the treatment learned the maze with significantly fewer trials than those who didn’t receive the treatment (13).
Other studies have shown that centrophenoxine improves learning and memory in those with memory impairment (14).
Centrophenoxine may even help those who have suffered a stroke. A study used rats with chronic cerebral hypoperfusion induced deficits. It sounds complicated, however it just refers to one of the major consequences of a stroke. It is associated with cognitive impairment, and in rats this is exhibited by a longer time to escape a Morris water maze. The rat’s memory was improved by administration of centrophenoxine, alongside a number of other measurable benefits such as returning pro-inflammatory mediators to their normal levels and reducing neuronal damage (15).
This indicates that centrophenoxine may not only be useful for those who have suffered a stroke, but also for those with cerebrovascular type dementia.
Both centrophenoxine and DMAE have been found to increase the lifespan of mice from somewhere between 30-50% (16).
Human Clinical Evidence For Centrophenoxine
So there is amounting pre-clinical evidence on how centrophenoxine can produce physiological changes in the central nervous system and mechanisms for its benefit to cognitive function. However, is this shown in clinical evidence? Do human trials show benefits?
Centrophenoxine For Anti-Aging
As mentioned above, we know the potential for centrophenoxine to combat age-related decline due to its lipofuscin clearing and free radical scavenging properties.
One double-blinded, randomized controlled trial looked at 9 months of centrophenoxine treatment in 74 elderly people. Those who received the centrophenoxine therapy performed better than the placebo group in the measure of delayed free-recall. This is the process of moving new memories into the long-term memory bank. However 5 other measures of memory were also compared, and none of these 5 had any significant improvement in the centrophenoxine group compared to the control (17).
Centrophenoxine For Relieving The Symptoms Of ADHD
In the 70s a trial was conducted using DMAE (main component of centrophenoxine to treat ADHD in children) (18).
74 children with learning problems and hyperactivity were included in this double-blinded, placebo-controlled trial. After 3 months the researchers found that DMAE improved the performance of children with behavioral disorders.
As most applications of centrophenoxine are geared towards the elderly, it’s worth noting that its benefits also extend to younger individuals.
Centrophenoxine For Neurodegenerative Diseases
A double-blinded clinical trial in Hungary included 50 participants, all-suffering from dementia with an average age of 77 years. The intervention group was administered 2g of centrophenoxine (a relatively high dose). Centrophenoxine was found to rehydrate the intracellular mass, which is consistent with the ‘free radical scavenger’ hypothesis. Further proving that centrophenoxine is a powerful antioxidant (19).
Another study looked at the use to two nootropics for the treatment of senile Alzheimer type dementia. It included 63 people around 70 years of age, all suffering from mild to moderate dementia. They were treated with one of two nootropics (one being centrophenoxine). Each individual’s results after 3 months were compared to their baseline results however it was not placebo controlled.
Both nootropic treatments showed a significant improvement over baseline. Measurements improved included attention, concentration, memory, performance IQ and full IQ; moreover, the deterioration index (assessment for dementia decline) was diminished.
Although this study did not include a placebo, it still provides evidence for the use of centrophenoxine in improving the cognitive function of those with dementia (20).
How To Take Centrophenoxine
Centrophenoxine comes as a powder and capsule, usually capsules are 200 – 400 mg. A typical therapeutic dose used in clinical trials is 600 – 2000 mg/day
It is usually taken in higher doses for lipofuscin clearance, hence if taking to reverse signs of aging, high doses for a shorter period (such as a month) is the norm. Otherwise, as a general cognitive enhancer, more moderate doses for a longer period of time are utilized.
Studies have shown that the lipofuscin clearance properties are generally only effective in older brains; hence for younger individuals a smaller dose should suffice.
Many centrophenoxine users report that they feel discomfort if they don’t take it with food (in particular heartburn), it may also absorb better or faster if taken with a meal.
Like other nootropic compounds, it’s also a good idea to start with a low dose and increase gradually as individuals can have different resistance levels. Likewise splitting the dose between morning and midday is another way to ease into it. Taking it late at night should be avoided as it may disrupt sleeping patterns.
Taking too much centrophenoxine or a long period of time can result in a buildup of acetylcholine and result in associated unpleasant side effects. To avoid this, cycling doses is recommended, usually one 5 days on 2 days off.
Stacking of nootropic compounds is done to augment their benefits. Stacking of centrophenoxine is usually done with Racetams, such as Oiracetam, Aniracetam and Piracetam. For example, centrophenoxine can be the source of choline that is required by Piracetam. Headaches associated with Piracetam due to low choline levels might be minimized with this stack.
What Does It Feel Like?
Most nootropic users take centrophenoxine in the morning for a brain boost in order to improve memory. Most reviews on amazon include comments on its ability to relieve forgetfulness, improve recall and a number mention relief from ‘senior moments’.
A number of reviews mention depression, usually reported within the first few weeks of taking it and going away on when stopping usage.
Another recurring comment is people remarking on its effectiveness straight away, feeling less forgetful even after the first dose.
Possible Side Effects
The most common side effects of taking centrophenoxine include:
- Stomach discomfort
- Body odor
- Drowsiness
- Confusion
- Increased blood pressure
- Moderate depression
- Heartburn
- Irritability
If taking centrophenoxine you should be aware of its potential depressive properties and stop taking it straight away if you suspect your mental health is suffering.
Centrophenoxine should also be avoided entirely in those who suffer from epilepsy, bipolar disorder and major depression as too much acetylcholine can worsen these conditions
Centrophenoxine is also a teratogen, an agent that can cause birth defects. Hence, women who are pregnant or trying to become pregnant should avoid it entirely.
In a Chinese 24 male volunteers were given a 200 mg dose of centrophenoxine in the form of a tablet for one week followed by 200 mg in a capsule, with a washout period of one-week in-between. Although this was just a small study, no adverse effects were reported and it was deemed to be tolerable (21).
Summary
Centrophenoxine is one of the oldest used Nootropics; it exhibits its benefits via a number of mechanisms extensively explored in animal models. This list includes centrophenoxine boosting neurotransmitter function, removing cellular waste, improving brain energy, and impacting mRNA synthesis.
If you are looking to boost your memory, recall things more easily and generally feel sharper, then adding centrophenoxine to your nootropic stack could be an option you consider. As with any new nootropic, increase the dose gradually and be aware of any harmful side effects you could be susceptible to.
If you are interested in reversing or preventing age-related cognitive decline centrophenoxine could also be for you. Lipofuscin clearance usually requires a larger dose so take this into account.
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