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The Best Acetylcholine Supplements

The Top 9 Evidence-Based Supplements for Learning, Memory, and Deeper Sleep

Acetylcholine was the first of the major neurotransmitters discovered. Involved with liver and cardiovascular health, it receives attention for its role in muscular control, and sleep cycle regulation, specifically REM or deep sleep, learning, and memory.

Embracing its role in cognition enhancing for learning and memory, acetylcholine supplements remain top-rated supplements along with racetams in nootropics and biohacking community. Liver dysfunction, atherosclerosis, cellular structure degradation, and neurodegenerative diseases are believed to be linked to choline (vitamin b4), deficiency, which, along with Acetyl-CoA, produce acetylcholine.

Acetylcholine is the chief neurotransmitter involved in the regulation of the parasympathetic nervous system, also referred to as the “rest and digest system.” Recent research is beginning to evaluate the role of acetylcholine dysfunction in mood and anxiety disorders.

Choline is a primary methyl donor for Methionine S-Adenosine (SAMe), which is involved in over 50 functions. Choline regulates homocysteine ​​levels within energy metabolism, DNA methylation for detoxification, and the creation of neurotransmitters. We have linked low levels of choline to muscular damage and non-alcoholic fatty liver disease.

The building blocks for cell membranes, phospholipids, are made from phosphatidylcholine. Healthy functioning cell membranes promote the maintenance of effective cell function, communication, and acetylcholine.

As high functioning acetylcholine is recognized and understood for its role in memory, learning, and concentration, we invariably associate low acetylcholine levels with cognitive disorders in the case of Alzheimer’s disease. Finally, we believe acetylcholine imbalance is involved with neurological disorder seen as Parkinson’s disease.

There are two types of acetylcholine receptors; muscarinic and nicotinic. Trending in the news is the study of the protective role of nicotinic acetylcholine receptors against the coronavirus, COVID-19 infection, and how it interacts with the ACE2 enzyme of the renin-angiotensin system in protection of the central nervous and cardiovascular system.

What are the Top 9 Evidence-Based Acetylcholine Supplements?

#1 Alpha-GPC

Alpha-GPC, the choline pro-drug, also known as Alpha-glycerophosphocholine, is the strongest confirmed effective choline source. It remains one of the most popular nootropics.

The clinical data on the effects of Alpha-GPC on cognition remain very strong, as we find this supplement in use as a part of many “stacks” both in the nootropics community and even outside of it. The user reviews rate it as stronger and often more stimulating than its often referenced counterpart, CDP-Choline (Citicoline).

#2 CDP-Choline (Citicoline)

While CDP-Choline, also called (Citicoline), does not have as strong clinical support as does Alpha-GPC, it is still the prodrug for both choline and cytidine. As cytidine converts to uridine, this appears to be a potential bonus “two-in-one” supplement benefit. CDP-Choline, for the mechanism of easy and rapid conversion into these two compounds, is rated like Alpha-GPC, an effective choline source.

#3 Krill Oil or Vegan Algae Oil

Proven for serotonin and dopamine synthesis, emerging studies show phospholipid-based omega-3’s in the form of either krill or algal oil may be superior to the triglyceride-based cod liver or fish oil omega-3’s, because of the differences in structural form. Phospholipids offer more bioavailability and efficiency for absorption, as every cell membrane in the human body comprises phospholipids.

In this form, they are much more shelf-stable along with lower heavy metal exposure than fish oil, allowing for lower dosages to be used. While we need more human studies, initial studies are very promising.

While past studies show general support for omega-3’s in the form of fish oil, we theorize that krill or algal phospholipid is the superior form in absorption and can be used instead. The studied dosage has been anywhere from 1 to 4 grams.

Recent evidence concludes phospholipids are effective choline sources, as phosphatidylcholine is a phospholipid attached to a choline particle that easily crosses the blood-brain barrier. Newer studies are evaluating the benefits of phospholipids on the endocannabinoid system.

#4 Creatine

Solid evidence exists for the use of creatine supplements to increase phosphocreatine stores in the brain to improve symptoms of depression. Regarding cognition, we have linked creatine to targeted activity on the acetylcholine receptors. We also believe creatine increases mitochondrial function and dopamine levels.

Some nootropics users are now combining creatine with d-ribose, another mitochondria booster, and cardioprotective supplement. We theorize creatine improves cognition, not only through an increase in energy but likewise via neuroprotection.

More and more evidence continues to emerge supporting creatine for use as much more than just a popular workout supplement. Finally, creatine appears to be a nutrient of deficiency and supplement focus for vegans, as do females generally showing more benefit for supplementation. Studies typically have used 5 grams for daily dosages.

#5 Uridine

Uridine, or Uridine Monophosphate or Uridine 5‘-monophosphate increases synapse formation and neuronal plasticity, which could help support the brain. Recently we have discovered Uridine to increase brain membrane, phospholipid precursors.

Additionally, uridine is also thought to be involved in neuro-protection, as we use it as a popular supplement to support the brain from neurotransmitter toxicity.

#6 Huperzine A

Huperzine A may carry a similar mechanism as Alzheimer’s disease medications such as donepezil, rivastigmine, tacrine, and galantamine, which act on the acetylcholine system of the brain. Huperzine A is a long-acting compound that delivers fewer side effects and even possibly superior overall effects.

The weakness for use we see in some user reports with this compound being too long-acting and too strong.

#7 Curcumin

Curcumin is the primary active polyphenol compound in turmeric that gives it its bright yellow color. Several curcumin studies have been recently released, as we believe it to carry its effect through potent antioxidant and anti-inflammatory mechanisms.

While researchers have questioned the low bioavailability of curcumin, one study has shown it in the form of BCM-95 to be effective for serotonin-related depression indications. Other areas of curcumin research involve its effect on dopamine, BDNF, working memory, NMDA, glutamate, attention, mood, and cortisol.

Finally, as more and more studies continue to emerge on bioavailable curcumin, it has been found to increase acetylcholine levels.

#8 Black Seed Oil

Black seed oil (Nigella Sativa), one of the world’s oldest plants native to South Asia, has been used for an array of indications, and has been affectionately been referred to as, “the cure for all diseases except for death.” While black seed oil, also known as black cumin oil, has lacked studies, recently it has been used with great success in the opioid community to assist in recovery, and as well has been used both anecdotally and now supported in human studies for raising acetylcholine, GABA, and serotonin levels.

We have attributed the believed mechanism for this anxiolytic and inhibitory effect to thymoquinone, its most important phytochemical compound.

#9 Centrophenoxine

We have found Centrophenoxine to be an effective cholinergic compound with a DMAE (dimethylaminoethanol) enhancing effect. They say DMAE is what Alpha-GPC is to choline.

Traditionally sold under the brand name Lucidril, Centrophenoxine can be purchased online or over the counter. Notably effective for removal of waste product buildup in the brain, it can be effective in reversing the signs of aging, when taken in high doses for a period of a month.

When taken chronically at lower doses, it can act as a neuroprotective agent and neural enhancer.

Top 9 Notables

Acetyl-L-carnitine (ALCAR), American ginseng (Cereboost), bacopa monnieri, galantamine, Gotu kola, noopept, pterostilbene, phosphatidylcholine, phosphatidylserine.

Essential Cofactors

Calcium, Choline, Copper, Docosahexaenoic Acid (DHA), Iodine, Iron, Magnesium, Vitamin B1 (Thiamin), Vitamin B2 (Riboflavin), Vitamin B3 (Niacinamide), Vitamin B5 (Pantothenic Acid), Vitamin B6 Pyridoxal-5-Phosphate (P5P), Vitamin B7 (Biotin), Methylated Vitamin B9 (Folate), Methylated Vitamin B12, Omega -3 and Omega-6 PUFAs, Selenium, Vitamin C (Ascorbic Acid), Vitamin D3, Vitamin E, Zinc.


Nicotine, Choline.


Anticholinergics, Antihistamines.


Acetyl-CoA + Choline = Choline Acetyltransferase => Acetylcholine.

Acetylcholine Receptors

Muscarinic, Nicotinic.


Acetyl-CoA, Choline.


Adrographis, Apigenin, Ashwagandha, Asian Ginseng, BPC-157, Berberine, Bromantane, Butyric Acid, COQ10, Cacao, Caffeine, Cannabidiol (CBD), Carvacrol, Catalpol, Chocolate, Choline Bitartrate, Cinnamon, Clary Sage, Cocoa, Coca Leaf, Cod Liver Oil, Creatine, DHA, DMAE, Danshen, EGCG, Eleuthero (Siberian Ginseng), Epimedium, Fenugreek, Fish Oil, Fo-Ti, Ginger, Ginkgo Biloba, Grape Seed Extract, Green Tea, Hibiscus, Holy Basil, Inositol, Iron, Kratom, Korean Ginseng (Panax Ginseng), L-Dopa, Tryptophan, Lavender, Lemon Balm, Licorice, Lithium Orotate, Luteolin, Maca, Magnolia Bark, Matcha Tea, Melatonin, Methionine S-Adenosine (SAMe), Mucuna Pruriens, Muira Puama, NAC, Niacin (Vitamin B3), Niacinamide (Vitamin B3), Nicotine, Noni, Oil of Oregano, Oregano, Oleamide, PQQ, Phenibut, Pregnenolone, Probiotics, Protein, Purple Passion Flower, Pramiracetam, Propolis, Quercetin, Rhodiola Rosea, Reishi, Resistant Starch, Resveratrol, Rosemary, Shilajit, Soy Lecithin, Sumac, Rosemary, Saffron, Schisandra, St. John’s Wort, THC, Trimethylglycine (TMG), Tulsi, Ubiquinol, Taurine, Valerian, White Oolong Tea.

Your Friend in Health,

Mark Stein



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