Choline Supplementation and Stacking Guide
Choline is one of the most popular nootropic ingredients on the market. There are multiple sources and types of choline, but their overall purpose as nootropics is to increase acetylcholine (a neurotransmitter) levels in the brain. Choline is naturally found in many foods, including eggs and beef and chicken liver, but additional choline supplementation, especially with a “premium” choline source can provide nootropic effects .
The two most common “premium” choline sources are CDP-Choline (also known as citicoline and/or cytidine 5’-diphosphocholine) and Alpha-GPC (also known as Alpha-glycerophosphocholine). Both CDP-choline and Alpha-GPC have numerous studies demonstrating that they can improve various aspects of cognition, making them the go-to choline sources for nootropic stacks. Some nootropic effects of choline supplementation include enhanced attention, processing speed, working memory, verbal learning, and executive function . 250mg is an effective dose for CDP-choline, although some studies use upwards of 500mg . As for Alpha-GPC, 200mg appears to be an effective minimum dose, while studies noting increased power output and growth hormone tend to use higher doses of around 600mg [4–5].
The third common choline source is choline bitartrate, which can be considered a “budget” form of choline, as it is less costly than CDP-choline and Alpha-GPC, but does not seem to possess quite the same level of nootropic effects, and requires a larger dose, which can limit its use in capped products. With that said, a proper dose of choline bitartrate can still provide some nootropic effects, and may also have other benefits as well. An effective dose of choline bitartrate is 2000mg (2g); this dose of choline bitartrate provides similar choline content to 5 hardboiled eggs . The main issue with products that use choline bitartrate is that they simply do not use enough; while 200–300mg of CDP-choline or Alpha-GPC is sufficient, you need approximately 10 times that amount of choline bitartrate to be truly effective. However, most consumers are not aware of the vastly different doses required for these choline sources, or even of the differences between these choline sources, making it very easy for a company to get away with severely under-dosing choline bitartrate and still having a label that looks good to the majority of consumers.
Choline Bitartrate: 2000mg (2g)
Choline and AChE Inhibitors (increasing acetylcholine from two angles)
While choline sources (mentioned above) increase acetylcholine levels, AChE (acetylcholinesterase) inhibitors work by stopping an enzyme from breaking acetylcholine down, which effectively leads to higher concentrations of acetylcholine. By stacking, or combining, a choline source with an AChE inhibitor, you can optimize your acetylcholine levels by increasing them in two ways, both by directly increasing acetylcholine levels (choline source) and by preventing the existing acetylcholine from being broken down (AChE inhibitors).
The most common AChE inhibitor is huperzine-A, with galantamine being another effective option. Both huperzine and galantamine have been shown to be able to acutely inhibit AChE in healthy adults, with 100–200mcg of huperzine or 4–8mg galantamine being effective doses, with some research showing huperzine to be able to inhibit AChE to a slightly greater degree and reach maximal inhibiting activity quicker than galantamine, although both are certainly effective as AChE inhibitors .
Another promising and effective, although less widely known AChE inhibitor is sage (salvia officinalis or salvia lavendulaefolia). Sage extract has been shown to possess potent AChE inhibiting activity in healthy adults, and there are also numerous studies showing it can acutely improve various aspects of cognition and mental performance, including increased/improved alertness, immediate word recall calmness and contentedness, and accuracy as well as decreased mental fatigue [7–11]. Effective doses of sage vary depending on the extract (officinalis or lavendulaefolia, essential oil or powdered extract, etc.) but doses of 25–50 microliters of essential oil and at least 300mg of sage powder/extract have been used with promising results in studies.
Sage Extract: 300mg
Choline and Racetams (Synergistic Nootropics)
We’ve already covered that pairing a choline source with an AChE inhibitor can maximize acetylcholine levels, but you can take things one step further by adding a racetam to your choline source. Racetams are a class of nootropics that, while some of them have existed for a long time, have been gaining a great deal of popularity recently. Piracetam is the original and most researched racetam. While it is most often used and studies for its effects on cognitive decline and/or impairment, it has also been shown to have effects on health adults, including decreased EEG complexity (indicating increased cooperativity of brain processes) and improved verbal learning. Both of the studies on healthy subjects used a dose of 2.4g, with one study using a single 2.4g dose and the other splitting the 2.4g into three doses of 800mg [12–13]. Where things really get interesting though is when you combine a choline source and a racetam.
While most of the research demonstrating synergy used rodent subjects, they still show a great deal of promise, and there is a lot of anecdotal reports of the combination having profound effects among nootropic supplement users. One study found that neither the equivalent dose (for a 70kg human) of 1.12g choline was unable to improve performance on a passive avoidance test, and the equivalent of 1.12g piracetam resulted only in slight improvements, but the combination of the two resulted in several times greater improvements than piracetam alone. Additionally, rats given twice the dose (equivalent of 2.24g) of either choline or piracetam alone still did not enhance performance nearly as well as the combination of the 1.12g equivalent doses of the combination of choline and piracetam. Additionally, while there were acute effects, continued use (1 week) was superior to acute use . Additionally, the combination of CDP-Choline and piracetam in doses that are too low to be effective alone were able to enhance retention when combined, suggesting synergy between the two nootropics .
Another option is Noopept, a dipeptide conjugate/analogue of piracetam that is often described as a “new and improved” or “buffed up” alternative to piracetam that is effective at much smaller doses than piracetam. Limited human research comparing the two has found 20mg Noopept to be more effective than 1.2g piracetam in recovery of brain damage . Additionally, Japanese research suggests that Noopept can be used for rapid adaptation to hot and cold climates, and that it can also improve physical work capacity in the heat .
Don’t Forget About Caffeine
Caffeine is a common component in many nootropic stacks, and for good reason; it is one of the most researched and proven ingredients known to man and has many benefits from increased energy and reduced fatigue to improved power output. What most people do not know however, is that caffeine has the ability to increase choline’s ability to release acetylcholine . In simple terms, this means that caffeine potentiates the effects and strength of choline. Another benefits of caffeine that isn’t widely known is that it is an AChE inhibitor . With these benefits in mind, it is clear to see why caffeine is such a beloved ingredient, and why it is such a useful component in many nootropic stacks.
For more information on the benefits of caffeine, along with helpful information on how to dose it and what to stack it with to maximize its benefits, stay tuned for our upcoming caffeine supplementation guide!
Recap: Dosing and Stacking Guide
Premium choline source. Effective for nootropic purposes.
Premium choline source. Likely preferred source for power output and/or GH release.
Choline Bitartrate (2000mg)
Budget-friendly choline source that still has some nootropic effects.
Effective AChE inhibitor, reaches peak inhibition quickly.
Effective AChE inhibitor, reaches peak inhibition slightly slower than huperzine.
Sage (25–50microliters essential oil or 300mg+ of extract)
Effective AChE inhibitor with numerous studies showing acute nootropic effects.
The “original” racetam. Effective in humans, demonstrated synergy with choline in animal studies.
Dipeptide conjugate/analogue of piracetam that is effective in much smaller doses than piracetam. Limited research suggests it may be more effective than piracetam.
Caffeine (dose according to tolerance and desired stimulation, typically 100–300mg)
Tried and true; good old caffeine. Included here for its ability to potentiate choline.
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