Acetylcholine transmission in the central nervous system plays a vital role in cognitive function, specifically in attention and memory. That’s why increasing acetylcholine can be an effective way to support focus, memory, speed of thought, and overall mental clarity.
The entire cortex and the hippocampus receive cholinergic inputs from the basal forebrain, a structure responsible for cognitive awareness and alertness [1]. Acetylcholine, in effect, is the mediator of communication between important brain structures.
Impaired cholinergic neurotransmission, either due to low levels of Acetylcholine or poorly functioning cholinergic neurons, has been implicated in the cognitive decline associated with aging. Furthermore, even just slightly increasing Acetylcholine levels can enhance working memory and focus [2, 3]. Maximum Mind boosts Acetylcholine in two ways: by increasing Acetylcholine availability with a proprietary alpha GPC, citicoline, and uridine Matrix and by preventing its degradation with huperzine A.
“Lack of Direction, Not Lack of Time, Is the Problem. We All Have Twenty-Four-Hour Days.”
―Zig Ziglar
What Are Nootropics?
“The only difference between the master and the novice is that the master has failed more times than the novice has tried.”
―Stephen McCranie
First things first, what are nootropics? Corneliu Giurgea, a Romanian neuroscientist, coined the term nootropic (pronounced new-tropic) in 1972. He believed that smart drugs should be invented and made widely available for the purpose of enhancing the general population’s brain health and increasing human intelligence.
According to Dr Giurgea’s findings, nootropics enhance cognition, memory, alertness, concentration, creativity, and attention. They became known as cognitive enhancers, substances that amplify the way the brain’s many cognitive functions operate and how we process information.
Simply put, cognitive enhancers (or nootropics or smart drugs) are prescription or off-the-counter drugs or supplements that enhance cognition. Some nootropics contribute to brain health while others can be quite dangerous.
Since Marco’s Grounds only works with safe and natural compounds in their purest forms, for most of our discussions we will restrain ourselves to natural nootropics that increase cognition safely.
How Maximum Mind Boosts Acetylcholine
“Focusing is about saying No.”
―Steve Jobs
The choline precursors matrix of Alpha-GPC, Citicoline, and Uridine increases acetylcholine levels to enhance cognition from 3 different neural pathways.
Alpha-GPC for Increasing Acetylcholine
L-alpha glycerylphosphorylcholine (alpha GPC) is a phospholipid metabolite that resides in the neuronal membrane. During times of low Acetylcholine, membrane metabolites can be used to synthesize Acetylcholine. Alpha GPC allows the passing of fatty acids through the membrane and can be used to directly synthesize Acetylcholine in the neuron [4]. Furthermore, alpha GPC provides membrane fluidity, allowing flexibility and changes in the neuron’s shape. The low density of alpha GPC in the membrane can cause rigidity, leading to decreased neuronal functionality.
Alpha GPC supplements have been shown to directly cross the blood-brain barrier and be incorporated into the cell membrane. The compound can be utilized directly to synthesize choline in the neuron, which subsequently increases the biosynthesis of acetylcholine [5]. In animal studies investigating the effects of alpha GPC, elevated concentrations of acetylcholine were found in both the frontal cortex and hippocampus following alpha GPC supplementation. These findings were correlated with significant improvement in working memory and attention tasks [6].
Read more about alpha GPC on the Marco’s Grounds Deep Dive or dig deeper into the benefits of alpha GPC here.
Uridine for Increasing Acetylcholine
Uridine is one of the 5 standard nucleosides; the others are adenosine, cytidine, guanosine, and thymidine. These compounds are the building blocks of the main information carrier molecules in the body (DNA and RNA) and play a central role in cellular metabolism. ATP – the “A” standing for adenosine – is known for its role in carrying packets of chemical energy needed for cellular functions. Uridine plays a similar role in two non-ATP high-energy molecules used in a subset of metabolic reactions.
Uridine is needed for UTP (made from uridine instead of adenosine) as an activator of substrates in some specific metabolic reactions. Uridine can also be converted into cytidine and support CTP. In this role, it is used for the synthesis of the glycerophospholipids (including phosphatidylcholine in the Kennedy pathway) needed for healthy cell membranes throughout the body and in the brain. And uridine may support different neuroregulatory processes and neurotransmitters. Uridine also crosses the blood-brain barrier [7–12]. These structural and functional roles have led to it being used as a nootropic.
Supplemental uridine dramatically increased the number of neurites per cell and neurite branching, according to a study published in Neuroscience [13].
Enhanced neurite outgrowth and branching are strongly associated with improved cognition.
Read more about uridine on the Marco’s Grounds Deep Dive or dig deeper into the benefits of uridine here.
Citicoline for Increasing Acetylcholine
Citicoline is a compound made up of choline and cytidine with neuroprotective as well as cognition increasing effects. Citicoline decreases age-related memory impairment and cognitive decline and enhances attention, learning and memory.
After ingestion, CDP choline originates choline and cytidine, the latter then being converted into uridine too for a synergistic effect. Both choline and uridine are neuroprotective. Choline is a nicotinic acetylcholine receptor agonist that increases the production of acetylcholine, adrenalin, and noradrenaline and increases dopamine release by acting on dopamine transporters [14-17]. Further, choline also increases phosphatidylcholine production in the brain – an important component of cell membranes [17]. Supplementation with citicoline has been shown to help maintain neuronal membrane integrity and reduce neuronal death [17, 18]
Note: there’s an effective dose of citicoline as Cognizin® in each dose of Maximum Mind.
Read more about citicoline on the Marco’s Grounds Deep Dive and about the benefits of citicoline for brain power here.
Huperzine A for Increasing Acetylcholine
Huperzine potentiates acetylcholine by inhibiting degradation. Huperzine A is a well-described, competitive and reversible inhibitor of acetylcholinesterase, the enzyme responsible for degrading endogenous acetylcholine [19]. When compared to pharmacological acetylcholine inhibitors, such as tacrine or donepezil, Huperzine A has been shown to have a higher binding affinity and preferentially inhibits a sub-type of acetylcholinesterase found predominately in mammalian brains [20]. This inhibition leads to elevated acetylcholine levels in the synaptic cleft, where acetylcholine is released and subsequently binds to target receptors.
Huperzine A enhances memory and cognitive performance as shown by more than ten large-scale, double-blind, placebo-controlled clinical trials from the past two decades supporting the significant increase in working memory and global cognition with huperzine A supplementation [21]. Both patient and non-patient studies have evaluated the effects of huperzine A. A 1999 study examined 68 adolescents given either Huperzine A or a placebo. Those who received a huperzine A supplement showed significant improvement in their memory quotient and performance on the Weschler memory scale [22].
These studies have provided a framework to initiate clinical trials using Huperzine A to treat memory impairments. The efficacy of huperzine A against age-related degenerative conditions and trauma-related memory impairments, such as the recently documented brain injuries in ex-NFL players in the United States, is currently being investigated [22].
Read more about huperzine A on the Marco’s Grounds Deep Dive or read more about the benefits of huperzine A here.
Finishing Thoughts
“If you believe it’ll work out, you’ll see opportunities. If you don’t believe it’ll work out, you’ll see obstacles.”
―Wayne Dyer
Maximum Mind can boost acetylcholine with combined supplements. Maximum Mind includes both a precursor matrix to acetylcholine production and a potent acetylcholinesterase inhibitor to prevent acetylcholine breakdown. In other words, Maximum Mind provides both the building blocks for the increase of acetylcholine neurotransmitters and potentiates the amount remaining after release by inhibiting its breakdown.
Numerous peer-reviewed scientific studies support the cognitive benefits of Marco’s Grounds Focus Matrix (alpha GPC, citicoline and uridine) and huperzine A on an individual level. Combining these potent extracts into Maximum Mind provides a Quadro channel to support peak cognitive function in healthy adults.
Why not experience the benefits of increasing acetylcholine in their purest and most bioavailable form with Maximum Mind?
Literature
- Amenta F, Tayebati SK: Pathways of acetylcholine synthesis, transport, and release as targets for the treatment of adult-onset cognitive dysfunction. Curr Med Chem 2008, 15:488-498.
- Furey ML, Pietrini P, Haxby JV: Cholinergic enhancement and increased selectivity of perceptual processing during working memory. Science 2000, 290:2315-2319.
- Parnetti L, Amenta F, Gallai V: Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data. Mech Ageing Dev 2001, 122:2041-2055.
- Tayebati SK, Tomassoni D, Di Stefano A, Sozio P, Cerasa LS, Amenta F: Effect of choline-containing phospholipids on brain cholinergic transporters in the rat. J Neurol Sci, 302:49-57.
- Amenta F, Tayebati SK, Vitali D, Di Tullio MA: Association with the cholinergic precursor choline alphoscerate and the cholinesterase inhibitor rivastigmine: an approach for enhancing cholinergic neurotransmission. Mech Ageing Dev 2006, 127:173-179.
- Sigala S, Imperato A, Rizzonelli P, Casolini P, Missale C, Spano P: L-alpha-glycerylphosphorylcholine antagonizes scopolamine-induced amnesia and enhances hippocampal cholinergic transmission in the rat. Eur J Pharmacol 1992, 211:351-358.
- Cansev, M., Watkins, C. J., van der Beek, E. M., & Wurtman, R. J. (2005). Oral uridine-5′-monophosphate (UMP) increases brain CDP-choline levels. Brain research, 1058(1-2), 101-108.
- Gibellini, F., & Smith, T. K. (2010). The Kennedy pathway—de novo synthesis of phosphatidylethanolamine and phosphatidylcholine. IUBMB life, 62(6), 414-428.
- Weiss, G. B. (1995). Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline. Life sciences, 56(9), 637-660.
- Richardson, U. I., Watkins, C. J., Pierre, C., Ulus, I. H., & Wurtman, R. J. (2003). Stimulation of CDP-choline synthesis by uridine or cytidine. Brain Research, 971(2), 161-167.
- Ulus, I. H., Mauron, C., & Krzysztof, J. (1989). Choline increases acetylcholine release and protects against the. Brain Research, 484, 217-227.
- Cornford, E. M., & Oldendorf, W. H. (1975). Independent blood-brain barrier transport systems for nucleic acid precursors. Biochimica et Biophysica Acta (BBA)-Biomembranes, 394(2), 211-219.
- Pooler, A. M., Guez, D. H., Benedictus, R., & Wurtman, R. J. (2005). Uridine enhances neurite outgrowth in nerve growth factor-differentiated pheochromocytoma cells. Neuroscience, 134(1), 207-214.
- Weiss, G. B. (1995). Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline. Life sciences, 56(9), 637-660.
- Levin, E. D. (2013). Complex relationships of nicotinic receptor actions and cognitive functions. Biochemical pharmacology, 86(8), 1145-1152.
- Khosrow Tayebati, S., Tomassoni, D., Ejike Nwankwo, I., Di Stefano, A., Sozio, P., Serafina Cerasa, L., & Amenta, F. (2013). Modulation of monoaminergic transporters by choline-containing phospholipids. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders), 12(1), 94-103.
- Fagone, P., & Jackowski, S. (2013). Phosphatidylcholine and the CDP–choline cycle. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 1831(3), 523-532.
- Dempsey, R. J., & Rao, V. L. R. (2003). Cytidinediphosphocholine treatment to decrease traumatic brain injury-induced hippocampal neuronal death, cortical contusion volume, and neurological dysfunction. Journal of neurosurgery, 98(4), 867-873.
- Li WM, Kan KK, Carlier PR, Pang YP, Han YF: East meets West in the search for Alzheimer’s therapeutics – novel dimeric inhibitors from tacrine and huperzine A. Curr Alzheimer Res 2007, 4:386-396.
- Cheng DH, Tang XC: Comparative studies of huperzine A, E2020, and tacrine on behavior and cholinesterase activities. Pharmacol Biochem Behav 1998, 60:377-386.
- Ha GT, Wong RK, Zhang Y: Huperzine a potential treatment of Alzheimer’s disease: an assessment on chemistry, pharmacology, and clinical studies. Chem Biodivers, 8:1189-1204.
- Sun QQ, Xu SS, Pan JL, Guo HM, Cao WQ: Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students. Zhongguo Yao Li Xue Bao 1999, 20:601-603.
