Alpha GPC: The Neuroplasticity Hack
It is especially useful to our brains in the synthesis and release process of the neurotransmitter acetylcholine by neurons.
Choline, a water-soluble nutrient, is essentially one step removed from the real nootropic, Acetylcholine, for which it is a chemical precursor. Choline itself cannot travel across the blood-brain barrier to become Acetylcholine (which we’ll refer to from now on as ACh), bitrate Choline is somewhat more effective in crossing it and Alpha GPC freely moves from the bloodstream into the brain.
This article is mostly going to focus on decoding what the human studies are saying about Choline supplementation and how this squares up with the anecdotal experiences of Biohackers online.
Scientific Research
There are over 400 results on Pubmed for human research in just the past 5 years specifically for Alpha GPC and 10 notable human clinical trials have been conducted on Choline supplementation in humans.
Why Biohackers need Choline
Choline and Alpha GPC is a favorite of responsible Biohackers because it balances out the brain chemistry that results from the heightened baselines of other neurotransmitters, particularly Dopamine and Serotonin, resulting from taking the Racetams and other Nootropics.
Any fairly vocal Biohacker is accustomed to hearing this general criticism…
You shouldn’t take things that unbalance your brain chemistry or use up your neurotransmitters because you don’t know what that’s going to do long term…
My response is that everything in our environment — from a stressful day at the office or a decadent dessert we eat at a party to watching a scary movie — imbalances our brain chemistry.
Supplementing choline precursors is just a very direct way of rebalancing it. Also, our mind and body are a master self-regulator, humans thrive and survive in a vastly different spectrum of environments, if I take an excess of a particular cognitive enhancer the body will flush it out or just store it as fat.
It’s a good idea to supplement Choline if you are taking Piracetam or other Racetam nootropics which increases the rate at which your brain uses ACh. Otherwise, racetams can cause headaches.
Acetylcholine — a Neurotransmitter of Many Talents
ACh works in both the peripheral nervous system and the central nervous system. The peripheral nervous system is what we think of as the system that pervades our entire body so our muscles can get instructions from our brain, the central nervous system consists of our brain, spinal cord, and to an extent our auditory, olfactory, and visual sensory systems in the head.
It’s a communicator between our mind and muscles, so it affects everything from athletic performance to coordination. For this reason, everyone from professional gamers to autosports drivers take it to give them a competitive edge. Its functions include:
- It delivers instructions to cardiac muscle fibers.
- Its release in the hippocampus is essential to learning and the formation of new memories.
- Levels of ACh in the cortex are linked to responsiveness to audio and visual stimuli.
Are You Acetylcholine Dominant?
Ben Greenfield explains in his exhaustive manifesto Boundless…
If you’re acetylcholine dominant, you are tuned in to your senses, highly creative, and open to new ideas. You make the best of any situation, no matter how bad it may be. You can stick to the same workout program for a long time because you can sink your teeth into routines, but you are also flexible, creative, and spontaneous. You enjoy activities involving words, ideas, and communication — many artists and actors are acetylcholine dominant. You can handle high intensity and high volume, but your body needs more rest to recover. You are extremely social, charismatic, and charming, and you highly value relationships. You love adventure and travel and are constantly learning new skills and information…
Does this sound like you?
I am quite notably inclined toward acetylcholine dominance. So what has worked best for me? Since acetylcholine is a neurotransmitter that is synthesized in the brain using choline, acetylcholine-dominant people burn through their choline stores faster than normal, so consuming more choline from the diet and from supplements is important. In addition to eating a diet high in healthy, choline-rich sources of fat, such as eggs, nuts, cold-pressed oils, and avocados, I have found it helpful to take 4 g or more of fish oil per day and the nootropic supplement Qualia, which contains a host of choline precursors and derivatives.
If you’re choline dominant get more of the stuff in your system — especially on the days when you’re taking a lot of Nootropics to blow through a major project!
Mechanisms of Action
- It’s an essential cog in the lipid metabolite synthesis process, which results in the manufacture of ACh.
- For the efficient transport/transmission function of the ACh system.
- It provides membrane fluidity to cells throughout the body, a lack of which results in membrane rigidity. In this respect, it’s a factor in aging and cell death.
Antioxidant
It combats free radicals in the cells, that are introduced by stress and environmental pollutants, another important aging factor.
Alpha GPC
Glyceryl Phosphoryl Choline is the most bioavailable form of choline you can supplement regularly. It’s an important part in both the genesis of ACh, as a building block of the neurotransmitter and in optimizing the ongoing effectiveness of the overall system. If the ACh system were a car, Cholinergics are oil.
It is my preferred ACh precursor because it’s the closest to the actual neurotransmitter. It’s a little more expensive but my mind, especially my memory and capacity to learn fast, is my moneymaker so I prefer the most bioavailable form.
CDP Choline
Is also known as Citicoline, has been the subject of numerous clinical trials and is a promising Nootropic. CDP Choline is less bioavailable but has more downstream Nootropic effects.
The very knowledgable biohacker Ryan Michael Ballow succinctly characterized the difference between Alpha GPC and CDP Choline.
- CDP Choline — Is less bioavailable, releasing less Choline in the brain. CDP Choline is more stimulating. Enhances verbal intelligence more, giving you greater access to your vocabulary.
- Alpha GPC — Induces more Choline and gives you more human growth hormone. Alpha GPC enhances working memory more. Probably better for cognition demanding tasks.
So Alpha GPC is more of a quintessential smart drug, whereas CDP choline is more of a stimulant.
A randomized, double-blind, placebo-controlled trial was completed in 2017 totaling 50 depressed patients, it found that 200 milligrams of CDP Choline made a difference after 2 to 6 weeks:
Citicoline has been used for vascular accidents and has been effective in cognitive rehabilitation. It has been used successfully to reduce craving in patients with substance abuse disorder and for mood management of bipolar disorder… Significantly greater improvement was observed in the [Hamilton Depression Rating Scale] scores of the citicoline group compared with the placebo group from baseline…
A 2017 study found that it helps mercury-induced mitochondrial damage and renal dysfunction.
Another recent double-blind and placebo-controlled study of 66 Iranians found that in combination with another drug risperidone it effectively treats Schizophrenia:
The citicoline group demonstrated significantly greater improvement in negative scores… Citicoline add-on therapy to risperidone can effectively improve the primary negative symptoms of patients with schizophrenia.
Neuroplasticity Agent
This is the capacity of our minds to adapt to novelty — learning Portuguese, studying philosophy, or starting a martial art — and thrive. Personal development of any significance requires that the gears of the mechanisms of Neuroplasticity are well greased.
A 2009 paper Alternative medicine review stated [Alpha GPC] is neuroprotective and supports neuroplasticity via nerve growth factor receptors.
ACh plays an especially important role in the formation of new long term memories; Focusing effect of acetylcholine on neuroplasticity in the human motor cortex, a 2007 German study of 12 healthy human subjects, includes some great insights…
Cholinergic neuromodulation is pivotal for arousal, attention, and cognitive processes…
The German study went on to say that…
…it has been hypothesized that ACh enhances the signal-to-noise ratio of input processing… These findings are in line with a cholinergic focusing effect that optimizes the detection of relevant signals during information processing in humans.
This finding is great news for overwhelmed lifehackers, entrepreneurs, professionals and students, who face the continual challenge of distraction. The healthy Germans in the study got better at focusing on the important information due to the long term excitability that ACh facilitates. It’s been well said that we live finite lives in an age of infinite distraction; the screens that are rarely further than an arm’s reach away from us are constantly socially engineering us to ignore our actual goals and instead get stuck in the quicksand of digital amusement. Nootropics like this are a potent tool for getting unstuck.
Anti-Memory Loss Agent
Forgot your keys? Walked into a room of your house and can’t remember what you are supposed to be doing there? Opened a browser tab and forgot what you are working on? Or is the name of someone you met just a week ago ‘on the tip of your tongue’?
- A University of London study of over 7000 civil servants, demonstrated that age-related memory decline can start in your 40's.
- A University of Perugia review of the data of 13 clinical trials, totaling over 4000 human participants, identified it as an effective therapy for memory loss, as indicated by memory tasks. A placebo-controlled study in the review found that after 3 months those treated increased memory function by 15.6% while those on the placebo declined by 8%.
Athletic Performance Enhancer
Interestingly this same Nootropic that maintains the minds of the aging and protects the cognition of those afflicted by stroke also provides a quantifiable advantage to top-performing physical specimens; from MMA fighters and bodybuilders to collegiate athletes and endurance sports aficionados.
2004 paper published in Powerlifting USA Magazine, illuminates a few crucial considerations for athletes:
Thomas Incledon, president of Human Performance Specialists, a sports pharmaceutical consulting firm, cites acetylcholine and associated neural co-factors as the next generation of ergogenics: “Increasing acetylcholine and neurotransmitter enhancers will be one of the next phases. When you increase acetylcholine, you are able to activate more muscle fiber, which, in turn, lowers the relative intensity of a workout [by increasing the amount of weight that can be lifted].”
“How does one simultaneously increase motor unit recruitment, increase muscle fiber stimulation, and decrease muscle fiber fatigue? Understanding the role and optimization of acetylcholine is the key to bridging the “power gap” and actualizing true genetic strength potential.”
A 2012 Japanese study stated
…These findings suggest that a single dose of GPC increases growth hormone secretion and hepatic fat oxidation, with concomitant increases in choline levels, in young adults.
In another double-blind study of 7 human males, the subjects improved their power output by 14% 90 minutes after supplementing 600 milligrams. To quote the study:
These data indicate that a single 600 mg dose of [Alpha GPC], when administered 90 minutes prior to resistance exercise, increases post-exercise serum [growth hormone] and peak bench press force.
Cognition Enhancer
A self-experimenter on Longecity reported:
“I suffer from cognitive delays (tests indicate I function roughly at a third of the cognitive speed of most people), major depressive mood disorder, and chronic fatigue… I find that this also has a calming effect, but it leaves my mind razor sharp.”
To quote a 2013 Italian paper
In a number of clinical studies, alpha-GPC demonstrated benefit in patients with cognitive dysfunction. In light of the limited therapeutical results obtained in the past decades by the use of cholinesterase inhibitors in dementia, and of the relevance of their side effects in long-lasting therapies…
Vs Alzheimer’s
To quote a 6-month double-blind study of 261 human subjects afflicted with mild to moderate Alzheimer’s:
In this multicenter, double-blind, randomized, placebo-controlled trial, patients affected by mild to moderate dementia of the Alzheimer type were treated… Statistically significant differences were observed between treatments after 90 and 180 days…
…on a variety of scales that are used to measure the severity of cognitive decline as a result of supplementing 1200 milligrams (split into three doses daily) for 6 months.
A recent human study from Georg-August-University, Germany stated:
Loss or dysregulation of cholinergic inputs leads to cognitive impairments like those manifested in Alzheimer’s disease. Such dysfunction can be at least partially restored by an increase of [ACh].
In a population study done in Hordaland, Norway of 46 to 74 year-olds choline blood levels were found to be inversely correlated with anxiety symptoms. Choline is used as a treatment for bipolar disorder, alcoholism and Alzheimer’s disease.
Sleep
A University of Barcelona, Neurology Department paper noted that Choline supplementation improved sleep as measured by the Pittsburgh Sleep Quality Index (PSQI).
Lucid Dreaming
An Alpha GPC supplement called Galantamine is particularly popular amongst lucid dreaming aficionados. The popular anecdotal experience reported by lucid dreamers is that they get the most lucidity bang for their cholinergic buck by doing Alpha GPC a few hours into their nightly sleep cycle, yes this means they wake up in the middle of the night to take pills, which while not ideal for sleep isn’t so big of a problem if they are waking up anyways to write in a dream journal (see my Evernote lifehack for this).
Vs Stroke
Or mini-stroke (known in dorky medical jargon as a transient ischemic attack) sufferers should strongly consider supplementing 1200 milligrams daily.
Integrated Brain Restoration after Ischemic Stroke, a 2009 paper University of California, Berkeley stated:
Brain injury from ischemic stroke can be devastating, but full brain restoration is feasible… [Alpha GPC] has been administered to almost 3,000 stroke patients in five stroke trials. Brain plasticity underpins the function-driven brain restoration that can occur following stroke.
A 2017 in vitro Canadian study identified Choline and B Vitamins as pharmacological promoters of neuroplasticity:
The first objective assessed the impact of folate deficiency prior to ischemic damage followed by B-vitamins and choline supplementation… Within the perilesional cortex, we show enhanced proliferation, neuroplasticity and anti-oxidant activity in mice fed the [choline-rich] supplemented diet.
Pregnancy
Choline is very important during pregnancy, rat experiments support the theory that healthy levels of Choline during pregnancy are essential to the long-term memory capacity of the baby.
Prenatal Vitamin
In terms of pregnancy, perhaps the most important thing about eggs is the choline found in the yolk. Choline is an essential nutrient that is known to be an integral part of a baby’s brain development. It also guards against birth defects. The National Academy of Sciences suggests 450 milligrams of choline per day for pregnant women and 550 milligrams per day for breast-feeding mothers. A pregnant woman can get almost half of the minimum daily choline she needs — 250 milligrams — from two eggs, but we recommend exceeding minimum recommendations by a large margin because our goal is to optimize health, not simply to prevent malnutrition.
The Better Baby Book by Dave Asprey
Dietary Sources
In nature, we find Choline in high amounts in
- Beef liver (5oz has +400 milligrams of Choline)
- Atlantic cod
- Salmon
- Pastured eggs (One egg yolk contains 115 milligrams of Choline)
- Grass-fed raw dairy
If you have a highly optimized, all-organic diet you’re probably in good shape, however Choline deficiency is common (90% of the general population by some estimations) and supplementation is a good idea, especially if you are taking other smart drugs that affect the ACh system.
Sources
Science.Bio sells pharmaceutical-grade powdered Alpha GPC and Pure Nootropics offers capsuled Cholinergics; both Alpha GPC and CDP Choline, these products are COA-verified for purity.
Alpha GPC, consumed in powder form is clumpy and has a mostly boring taste but is frequently described as sweet. It’s a suspicious-looking white powder that you really would want to keep out of sight of TSA agents, border guards, or highway patrol officers.
Veteran biohackers respect choline for the brainpower it unleashes when properly stack with other Nootropic ingredients that it shares synergies with — to simplify this you may just want to take in a multi-vitamin Nootropic stack, like Qualia or capsuled Alpha GPC + Uridine.
Downloadable Alpha GPC?
You may be interested in taking it as an infoceutical — a non-pharmacological, side-effect-free version of the supplement that takes advantage of the phenomenon of water memory — which is imprinted on water via quantum collocation and electromagnetism using this device…
Infocueticals typically have 1/3 or half the effect of the actual medicine being imprinted. If you’re skeptical of Infopathy that’s understandable, it’s a game-changing application of a little-known scientific phenomenon. But I’d urge you to evaluate the scientific evidence (presented in my biohacker review) that downloadable medicine is no longer science fiction…
Experiential
The important thing to understand is that more Choline is not always better. Excess Choline can result in Choline blues, where you feel a bit tranquilized and slow, which might not be what you want from your Nootropics.
“I find myself typing faster and getting more done when I’m on ACh [precursor supplement]”
Reported a now infamous Biohacker in Nicaragua.
Socializing Effects
One self-experimenter reported its effects on socially induced nervousness:
“Also it’s like social anxiety is suddenly disappearing. I’m not antisocial, but I normally have to force myself to greet others. For the last two weeks I have been casually going up and talking to people I normally avoided.”
Dosage & Usage
For a boost in brainpower 500mg daily + normal dietary intake.
It turns out that choline is beneficial for everyone. In adults, choline is key to cell function (especially neural function), liver metabolism, and disease prevention. For example, a 2008 study linked high choline intake with a 24 percent lower rate of breast cancer. Women over nineteen need 425 milligrams every day, and men over nineteen need 550 milligrams. Research has found that only one in ten Americans gets enough choline every day. (p. 72)
More than 3500 milligrams daily can lead to diarrhea, low blood pressure, and a fishy odor.
Cofactors
For cognitive enhancement in healthy Biohackers, Alpha GPC is rarely consumed on its own. Racetams, especially Piracetam, are a popular combination. The Longecity.org crowdsourced recommended Piracetam-Choline ratio is 4:1
Alpha GPC is potent stuff so the ratio recommended is pretty asymmetrical; for 4–6 grams of Piracetam, you would want to take 500 milligrams, an 8:1 ratio.
Other Cofactors…
A lot of Nootropics promote the release of ACh but do not provide the building blocks for it, so it’s a good idea to add choline if you are supplementing…
ALCAR and Phosphatidylserine are named in a 2005 paper out of the University of California, Berkeley as Mitochondrial cofactors of choline:
The trophic nutrients acetyl L-carnitine (ALCAR), glycerophosphocholine (GPC), and phosphatidylserine (PS) provide mitochondrial support and conserve growth factor receptors; all three improved cognition in double-blind trials.
Ampakines, particularly Aniracetam is a biohacker favorite, the popular dosage is 1500 milligrams Aniracetam to 500 milligrams Alpha GPC, a 3:1 ratio.
B Vitamins, are involved in the conversion of Choline into ACh, especially B5 (Pantothenic Acid).
Side Effects
In a human study of 44 participants, the researchers concluded:
The trial confirms… and the low percentage of adverse events confirms its excellent tolerability.
Based upon my reading of hundreds of forum threads, Reddit posts, and user testimonials, it seems to me that a higher percentage than usual of users report adverse effects of headaches, irritability, and general moodiness either immediately or a few days after adding Alpha GPC to their supplemental regimen.
The ACh system in the body is very complicated, supplementing it with such a bioavailable source is not conducive to everyone’s constitution. The informed recommendation seems to be; if you aren’t feeling great on Alpha-GPC switch to a different source of choline, CDP choline, choline bitrate, or Centrophenoxine.
