Choline Acetyl Sources of Benefits, Side Effects and Types

Choline Acetyl – Which are the most faithful helpers of brain activity? Cholinergics – Sources of Acetylcholine Benefits, Side Effects, and Types

The functioning of the brain and the entire nervous system is a complex process involving dozens of neurotransmitters, each of which has a specific action. The use of such substances as dietary supplements is not new, and they have long been the subject of scientific activity. Against the backdrop of modern brain and nervous system stress, let us ask ourselves: do we need neurotransmitters? What would it be like if we could memorize more, concentrate, think faster, be in a good mood? The answer can be given by the “first” among neurotransmitters – acetylcholine.

What is acetylcholine and how does it work?

Acetylcholine was first discovered in 1914 by British scientist Sir Henry Hallett Dale, who studied the substance’s effects on heart function but did not classify it as a neurotransmitter. The German Otto Loewy did, making acetylcholine the first neurotransmitter discovered by science.

Acetylcholine is an organic cation that acts as a neurotransmitter at choline synapses in the central and peripheral nervous system. It is also one of the neurotransmitters in the autonomic nervous system, occupying an important role in the sympathetic and parasympathetic parts, and is the only neurotransmitter used in the motor part of the somatic nervous system. It in turn is responsible for volitional control of the body and is part of the peripheral nervous system.

Acetylcholine is important to both the central and peripheral nervous systems. In the peripheral nervous system, it is associated with muscle activation due to the large concentration of acetylcholine receptors in skeletal muscle fibres. It improves contractions not only of skeletal muscles but also of cardiac muscles.

In the central nervous system, acetylcholine forms a neurotransmitter system that is called cholinergic and has an anti-excitatory effect. Its involvement in the central nervous system is associated with waking from sleep, sleep quality, retention of focus, memory, brain activity in general, decision making and controlling movements.

What are the sources of acetylcholine?

Sources of Choline Acetyl are a distinct category of nootropics (neurostimulants) that encompass different groups of substances.

In the first place are the precursors of acetylcholine. These are compounds that, after several enzymatic reactions, are converted to acetylcholine, some of which contain choline in their formulas. Some of the most popular precursors are:

  • Choline bitartrate;
  • DMAE (Dimethylaminoethanol);
  • Alpha-GPC (L-Alpha Glycerylphosphorylcholine);
  • CDP-Choline (Cytidine 5-diphosphocholine).

Second are substances that play the role of cofactors in the formation of acetylcholine. Cofactors are helper molecules that accelerate or stimulate biochemical transformations in the body, in this case the formation of acetylcholine. Popular cofactors of acetylcholine are:

  • Acetyl Carnitine;
  • Vitamin B5 (Pantothenic Acid).

The third group of substances involved in acetylcholine synthesis are inhibitors of the enzyme acetylcholinesterase, which is involved in the breakdown of acetylcholine. By inhibiting the enzyme, levels of the neurotransmitter are increased. Such inhibitors are:

  • Huperzine A (from Huperzia serrata);
  • Rosemary;
  • Cannabis.

Another group of substances that would increase acetylcholine levels are its agonists. The agonists bind to the receptors on the cells and get the same response. They often mimic the action of acetylcholine. Popular agonists are:

  • Nicotine.

Proven and potential benefits in humans

The benefits of most sources of acetylcholine can be multifaceted and not directly related to acetylcholine synthesis and effects on brain activity, so we will limit ourselves to benefits related to the cholinergic system and effects on the nervous system.

  • Proven inhibitory effect of huperzine A on the enzyme acetylcholinesterase, therefore increasing acetylcholine levels. There is a great deal of interest in the effects of huperzine A on neurodegenerative diseases and Alzheimer’s disease in particular. Several studies have shown a positive effect with huperzine A intake, with one large study involving 474 participants aged between 50 and 90 years taking 300 to 500 mcg of huperzine A daily for 8 to 24 weeks. The results noted improvement on the Mini-Mental State and Daily Living Scale. Results from other tests also showed improvement in cognitive parameters and quality of life, but no changes in disease status;
  • Acetylcholine precursors have also shown potential benefits in the treatment of Alzheimer’s disease. While DMAE did not demonstrate positive results in human studies, Alpha-GPC and CDP-Choline exhibited positive effects. In human tests, CDP-Choline dramatically improved minimental status and other cognitive functions, as well as improving cerebrovascular function. Choline bitartrate taken in high doses also shows an effect, but it is limited to certain cognitive functions such as concentration and recognition;
  • Acetyl L-carnitine has been used successfully in mild cognitive impairment and mild Alzheimer’s, as well as in the early stages of the disease. Studies have covered periods of 3 to 12 months using doses of 2 to 3 grams daily. Improvements were noted in all clinical parameters and psychometric tests. Acetyl L-carnitine did not successfully slow disease progression in patients over 65 years of age, but in younger inidiates it demonstrated a slowing;
  • Huperzine A improves memory and learning ability;
  • DMAE use demonstrates mood improvement;
  • Potential benefits of DMAE in children suffering from hyperactivity or attention deficit. So far, there are no definitive results from laboratory tests;
  • Alpha-GPC demonstrated rapid mental recovery in 71% of patients who suffered cerebral ischemic attacks. Mini mental status improved dramatically, with no residual brain slowing and memory loss;
  • An Italian study compared the action of acetyl L-carnitine and Alpha-GPC in individuals suffering from Alzheimer’s type dementia. Alpha-GPC showed serious improvement in all neurophysiological parameters, with acetyl L-carnitine also giving positive results, but not as pronounced. Acetyl L-carnitine acts in dementia mainly in terms of short-term memory;
  • CDP-Choline acts positively in recovery from stroke due to its effects on pro-inflammatory cytokines. This effect may also show benefits in other diseases of the central nervous system;
  • Choline bitartrate has an effect on people suffering from bipolar disorder (abrupt mood change);
  • Acetyl L-carnitine, unlike some of the other precursors, successfully crosses the brain barrier, having neuroprotective and antioxidant properties. Studies suggest that it is also one of the strongest precursors of Choline Acetyl ;
  • Acetyl L-carnitine successfully improves mood. In the elderly, it has noted positive effects in suppressing depressive states.

Proven and potential benefits in animals

  • Studies in rats have shown positive results in the effects of huperzine A on neurotrophy and nerve growth factor stimulation, which would also have benefits in neurodegenerative diseases;
  • In rats, huperzine A acts as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, which protects the brain from damage by glutamate;
  • DMAE increases the survival span of old rats by 11% to 50%;
  • A comparative study between choline and DMAE in mice shows that DMAE reaches and stays in the brain for a longer period of time, while choline increases lipid choline levels more. There are also studies that deny the ability of DMAE to form Choline Acetyl, all of which are on animals;
  • When Alpha-GPC was used on rats, the precursor demonstrated not only an increase in acetylcholine levels, but also the ability to cross the brain barrier as well as increase the activity of choline itself, which would have benefits in aging and cholinergic deficiency;
  • When used by rats, Alpha-GPC showed a restorative effect in scopolamine-induced amnesia. The effect is long lasting and is associated with effects on Choline Acetyl;
  • Pantothenic acid and ethanol intake by rats affects Choline Acetyl synthesis. High ethanol intake results in vitamin B5 deficiency, which in turn slows acetylcholine synthesis. This leads to the conclusion that insufficient levels of pantothenic acid may influence Choline Acetyl levels;
  • In rats, CDP-Choline improves brain dysfunction in cerebral ischemia. This is due in part to restoration of cerebral glucose metabolism;
  • In rats, the effect of CDP-Choline was observed after induced brain injuries, with the substance demonstrating not only an increase in acetylcholine, but also an improvement of all cognitive processes and a positive impact on cholinergic system-dependent neurobehavioral deficits;
  • Choline bitartrate shortens the time to thought activity in male and female rats;
  • In rats, acetyl L-carnitine alters brain energy sources by increasing utilization of lipid fractions and ketone bodies;
  • The combination of acetyl L-carnitine and R-alpha lipoic acid improves memory in adult rats by protecting RNA and DNA damage from oxidant stress. The result is most noticeable when the two substances are combined;
  • Acetyl L-carnitine stimulates nerve growth factor binding as well as improves brain functions in late age-related neuronal deficits.

Side effects of individual sources?

Most of the acetylcholine sources do not present with acute side effects, but some may demonstrate moderate ones. For example, nausea grading to vomiting, stomach discomfort, severe overexcitement including difficulty falling asleep may be noted with initial acetyl L-carnitine intake. These effects do not occur in all individuals, are often dose-dependent, and resolve relatively quickly.

In some individuals, acetyl L-carnitine may cause palpitations and high blood pressure, and is not recommended for people who have suffered a heart attack. Despite its action as a mood enhancer, effects such as depression and anxiety may occur with long-term use.

Acetyl L-carnitine intake also increases the release of free radicals due to accelerated metabolism, so combining it with antioxidants is recommended.

No acute side effects are noted with most acetylcholine precursors. Studies have shown no side effects from Huperzine A, Choline Bitartrate, and CDP-Choline, making them completely safe to use.

On the other hand, the use of DMAE exhibited adverse effects in some patients during the studies, which were expressed as drowsiness, slowed reactions, confusion, and a slight increase in blood pressure. However, DMAE is considered a safe supplement.

In one study of Alpha-GPC, high doses in the range of 1000 mg resulted in side effects such as palpitations, nausea and vomiting, insomnia, and headaches. Side effects were noted in 2.14% of subjects, with only 0.7% discontinuing intake.

What should we not combine acetylcholine sources with?

Combining choline sources with anticholinergic agents is not recommended. Anticholinergics are drugs that block the impulses in the parasympathetic nerve responsible for binding acetylcholine to its receptor in nerve cells.

Anticholinergic agents can be divided into antimuscarinic and anticotinic, the latter acting as neuromuscular and ganglionic blockers.

Most of these drugs are prescribed by prescription, so their use should always be after consultation with a physician. Anticholinergics can also be natural substances such as the alkaloids found in most plants of the Cartophaceae (Solanaceae) family.

Recommended doses for Choline Acetyl

There is no universal dose that applies to all sources. Supplementation should be approached individually in each case. Our recommendation is to strictly follow the manufacturers’ instructions.

Higher doses per daily intake are normal for Choline Acetyl precursors, and these usually vary.

Recommended doses for Choline Acetyl are:

  • DMAE (250 mg – 1 to 3 times a day);
  • Alpha-GPC (300-600 mg – 1 to 2 times daily);
  • Choline Bitartrate (500-1000 mg – 1 to 3 times daily).

More specific is the intake of other sources of acetylcholine.For example, huperzine A shows the positive results and lack of side effects when taken 400 mcg – 1 to 2 times a day.

Acetyl L-carnitine can be taken up to 2000 mg daily. Some studies show that for medical purposes there is no difference in results when using 2000 and 3000 mg daily intake of acetyl L-carnitine.

In which supplements can we find acetylcholine sources?

Most sources of acetylcholine can be found on the market. Some of the aforementioned, such as cannabis and nicotine are not available at supplement stands.

There are also numerous medicinal sources, most notably acetylcholinesterase inhibitors and acetylcholine agonists, which are not covered in the article, but are also widely available in the pharmacy network. Such are donepezil, galantamine, tacrine, neostigmine, etc.

Among dietary supplements, acetylcholine precursors are particularly popular. In the range of almost every brand of health food supplements can be found choline bitartrate, Alpha-GPC, DMAE, pantothenic acid, acetyl L-carnitine. Acetyl L-carnitine is also found in the ranges of sports supplement manufacturers, almost always as a pure powder or capsule product.

Very often sources of Choline Acetyl are used in complex formulas, which can be divided into two types – brain stimulants and sports pre-workout formulas.

Brain stimulators avoid stimulants and rely more on nervous system enhancers. These are formulas that are suitable for intense work, learning, concentration needs.

Very often sources of acetylcholine such as huperzine A, acetyl L-carnitine, choline bitartrate and DMAE are used in sports formulas for pre-workout stimulation due to their properties to improve mood, focus, mental strength and in part to acetylcholine’s functions related to muscle contractions.

Learn more

Sources used