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Nootropics II: Cholinergics For Your Mind and Muscle

Kevin Kuhn: Classified Nutrition

In the first article about Nootropics, we covered the major players in the Racetam family of brain-boosting ingredients.  Only time will show us the bigger picture with regard to which of the 20+ racetam ingredients works best for brain performance.  Time will also shed light on other nootropic compounds, like those in the Cholinergic category.

Cholinergic research and interest is gaining steam because of the potential for these compounds to increase both physical performance by directly affecting muscle contraction and mental performance by directly affecting processes related to learning.  Cholinergic ingredients are further broken down into two main categories depending on whether they produce choline (which is then used to produce acetylcholine) or they have direct effects on the enzymes involved in converting choline to acetylcholine or preventing the degradation of acetylcholine back to choline.  To determine if getting your hands on some cholinergics is worth the stress on your wallet, you have to look at each ingredient separately.

The main cholinergic ingredients used in supplements today include Alpha-GPC, CDP-Choline, DMAE, Centrophenoxine, Huperzine-A, and Curcumin.


Alpha-GPC, which is probably the most well-known of the cholinergic compounds, is perhaps the most pharmacologically active in this family, and is therefore perhaps the most efficient way to supplement for increases in brain acetylcholine levels.  While choline can be ingested on its own to increase the choline concentration in the brain, absorption is enhanced when choline is combined with another molecule, as is the case with Alpha-GPC and CDP-Choline.

The unique aspect of Alpha-GPC is that the GP (glycerphosphate) part of the molecule has the effect of promoting and assisting with proper cell wall structure while the C (choline) part of the molecule provides the substrate for conversion to acetylcholine.  Though it is the most well known, there are very few studies related to its actual effects on cognition and athletic performance.  Though the dose for potential cognitive benefit seems to be around 1200 mg, a pilot study using 600 mg of Alpha-GPC before exercise showed a 14% increase in Bench Throw power.  A 600 mg dose was also shown to acutely increase the levels of circulating growth hormone.  Personally, I don’t put very much weight into a single study, so I would hold off until more studies are conducted that show more evidence for brain and/or performance enhancing effects.

Nootropics II:  Cholinergics For Your Mind and Muscle

“Alpha-GPC is perhaps the most efficient way to supplement for increases in brain acetylcholine levels.” 


CDP-Choline is a nootropic that delivers choline and uridine to the brain.  Like other cholinergics, this choline is used to synthesize acetylcholine, while the uridine assists with cognitive function by increasing cellular membrane synthesis.  Though it is about equally as potent as Alpha-GPC, CDP-Choline is seen more as a cognitive supplement with less impact on physical performance.  The effective dose of CDP-Choline is goal-dependent, as some of the cognitive effects (improved attention and memory) are more apparent at a low dose while other effects are not seen until higher doses have been ingested.


DMAE, which is one methyl group away from being a choline molecule, is thought to affect mental performance by scrubbing away at beta-amyloid, which is “age pigment” that builds up on neural tissue over time and causes a decline in normal cognitive function.  DMAE also affects neural performance by delivering choline substrate for conversion to acetylcholine.  Due to evidence that shows DMAE can protect nerve cells by attaching to them and acting as an antioxidant, it has been used primarily for preventing cognitive decline, with very little evidence to support any physical performance benefits.  Also noteworthy is that DMAE supplementation does have potential for increasing risk of birth defects, and is therefore not recommended for women who are of childbearing age.


Centrophenoxine is a compound that combines an absorption enhancer with DMAE.  Similarly to CDP-Choline, the dose of Centrophenoxine is directly related to specific outcomes.  If the goal is to reverse beta-amyloid buildup in order to prevent signs of aging, high doses of Centrophenoxine are taken for a month while a low dose taken consistently is used as a general neuro-protector or neuro-enhancer.  Unique to Centrophenoxine is that long-term benefits may be possible from just a single month or cycle at a high dose.  Due to the DMAE in Centrophenoxine, it is also not advised for women of childbearing age due to the potential for birth defects.


Huperzine-A is a very unique ingredient that is extracted from the Huperziceae family of herbs.  It works differently than the previously mentioned cholinergics in that it does not increase acetylcholine levels by delivering choline to the brain.  Instead, it works as an inhibitor of the enzyme acetylcholinesterase, which is responsible for breaking down acetylcholine.  It therefore passively increases acetylcholine within the brain by preventing the amount that is naturally broken down.

Though the exact dosage and cycle length is still not established, a typical dose and cycle of Huperzine-A is 50-200 micrograms per day for 2-4 weeks because of its long half-life and lingering effects even after supplementation has stopped.  It is growing in popularity as a cholinergic because of the fewer negative side effects in comparison to the acetylcholine-boosting cholinergic supplements and because of the potential neuro-protective (defending against glutamate, aging pigment, and oxidative stress) and neurogenic (proliferating nerve stem cells in the hippocampus) effects.


Last, but not least, Curcumin has been found to have some profound effects on the mind and body primarily through reducing inflammation.  Curcumin, which is the yellow pigment that gives the spice Turmeric its color, has been shown to be helpful at reducing risk of cardiac issues, reducing the risk of diabetes, treatment and prevention of some types of cancer, and as a means to prevent cognitive decline.  The main mechanism by which it can potentially boost cognition or at least prevent the normal decline in cognitive function is through protection against glutamate toxicity, promoting synaptic plasticity, and removing markers of stress.

Curcumin has a very low bioavailability rating, so ingesting it with peperine (black pepper extract) is necessary to maximize the potential nootropic effects.  When combined with peperine or some other absorption enhancer, the typical dosage rages between 80 mg up to 500 mg.  Personally, I feel the most comfortable recommending Curcumin, in comparison to the other discussed ingredients, because of the numerous ways it benefits the body and the amount of data that shows it to be both safe and effective.


There is so much potential for brain-boosting supplements to change the way we train, compete, and recover, but there is still much research, especially human trials, that must be conducted before we can see the whole nootropic picture.  Some of these cholinergic ingredients show great promise, but we don’t have all the evidence yet, so be sure you know as much as possible about these ingredients before adding them to your supplement regime.

When in doubt about a specific ingredient, a great place to start is examine.com.  There seems to be a clear consensus that cholinergic ingredients will have a future because of the established effects that increased levels of acetylcholine within the brain can have on increasing muscle contraction speed and power as well as the direct effects that acetylcholine has on memory formation and learning.  Athletes of all types are always looking to get that little extra out of their body, and cholinergic compounds may be the supplement that really boosts the connection between your mind and muscle.

About Kevin Kuhn

Kevin KuhnKevin Kuhn, M.S.Ed., CSCS, MFS is a Kinesiologist and Sport Nutrition Coach in Dallas, Texas, as well as the Vice President of Research and Development for Classified Nutrition (ClassifiedNutrition.com).  Before moving to Dallas in 2012, Kevin was the head strength & conditioning coach for the Indiana Invaders professional running club in Indianapolis, Indiana.  Kevin specializes in athletic performance with great interest and experience in running-specific strength & conditioning, corrective exercise, and exercise and sport nutrition.  Kevin has been certified by the National Strength & Conditioning Association as a Certified Strength and Conditioning Specialist (CSCS) and as a Master Fitness Specialist by the Cooper Institute.

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