Daily stressors (not to mention general aging) can be difficult and demanding on both our bodies and brains. Between the two, surveys have shown that Americans fear reduced brain function (57%) even more than they fear physical decline (43%) [1]. To combat that slow-down of our physical and mental capacities, we can commit to focus on both physical and mental health through exercise, mental wellness practice, and nutrition.

Although your brain is less than 2% of your body weight, it uses about 20% of your body’s daily energy intake, so it needs high-quality nutrition to function well. Poor nutritional choices, and not providing your brain with the specific nutrients it needs to thrive, can result in scattered thinking, or worse. Luckily, we now know that certain nutrients have been shown to be very good at supporting your brain cells, cognition, and memory. Metabolic Maintenance now provides a few of them combined at optimal levels in a potent and powerful nutritional formula called Brain Cell Support™ .

What is Citicoline?

Citicoline (short for cytidine-5′-diphosphocholine) is a choline donor with a variety of cognitive-enhancing, neuroprotective, and neuroregenerative properties. It is a naturally occurring chemical in the body and brain. Citicoline is involved in the biosynthesis of brain phospholipids and neurotransmitters acetylcholine, norepinephrine and dopamine. Citicoline also boosts energy metabolism in the frontal cortex by increasing ATP, reducing oxidative stress, and promoting a normal inflammatory response. Therefore, citicoline plays roles in both the physical health and the function of the brain, which is why citicoline has been the focus of extensive research related to neurodegenerative diseases [2,3]. 

Data from a number of studies have contributed to unveiling the pathways that lead to benefits of citicoline. For example, citicoline’s targeted action for increasing brain phospholipid synthesis has been demonstrated to act through the following pathway. Citicoline is absorbed as a combination of its hydrolyzed products, uridine, and choline. Once crossing the blood-brain barrier, neurons convert uridine and recombine it with choline to become citicoline in the brain. From that point, citicoline moves into the metabolic pathway of phosphatidylcholine production and is incorporated into brain membrane lipids, protecting brain cells, and counteracting neuron inefficiency [4]. This mechanism is not only functional for combating neurodegenerative disorders; citicoline has also been shown to support memory, attention, and behavior in mentally healthy older adults as well [5-8]. 

Studies have demonstrated citicoline may also help to maintain optimal visual function through a similar mechanism. As we age, some people begin to lose the retinal ganglion cells of the eye. Citicoline may protect the longevity of retinal ganglia through the promotion of phospholipid synthesis, protecting these eye cells much as it does for cells in the brain [9].

What is Cognizin®?

Cognizin® is a well-researched, branded form of citicoline that can provide the nutrition the brain needs to stay sharp and focused [5]. Cognizin® brand citicoline, specifically, has been shown to increase cellular synthesis and brain energy in middle-aged adults, as evidenced by increased levels of metabolites, phosphoethanolamine, and ATP, respectively, when compared to placebo [6].

Cognizin® has also been suggested to help with focus, motor speed, and attention [7,8].

What Else Does Metabolic Maintenance’s Brain Cell Support Contain?

Although Cognizin® is clearly a powerful nutrient, Brain Cell Support formula is so much more than citicoline. Brain Cell Support assists brain structure and function by providing precursors of neurotransmitters, necessary building blocks for neurons, cofactors for energy production, and neuroprotective antioxidants. Hyla Cass, M.D., designed this formula to be one of the most potent combinations of nutrients and plant extracts available to support your memory, mood, and ability to focus. 

Brain Cell support combines Cognizin® with acetyl L-carnitine (which is superior to L-carnitine in terms of neural support). Citicoline and acetyl L-carnitine both support energy production in the brain, specifically in the frontal cortex. It also contains dimethylaminoethanol (DMAE), phosphatidylserine, and the brain supporting botanicals ginkgo biloba and gotu kola. 

There are some synergistic relationships between the nutrients as well. For example, DMAE crosses the blood-brain barrier and is a precursor to choline, which may increase levels of the memory neurotransmitter acetylcholine, and also acts as a precursor for more citicoline

How Do The Other Ingredients Support My Brain?

Acetyl-L-Carnitine provides the acetyl component for acetylcholine, the primary neurotransmitter involved in learning and memory. The L-carnitine portion transports fatty acids across the mitochondrial membrane for cellular energy production. Acetyl-L-carnitine supplementation has been shown to have positive effects on memory, attention, and concentration. It may also help to reduce both physical and mental fatigue in the elderly, by contributing to improved cognitive status and physical functions [10].

Acetyl-L-carnitine is more easily absorbed from the gut, and more readily crosses the blood-brain barrier than carnitine. Furthermore, carnitine levels are known to decrease significantly as we age [11]. There is some evidence to show that acetyl-L-carnitine supplementation, alone, could be associated with improved cognitive function of individuals experiencing cognitive decline . There are also implications for a beneficial contribution by acetyl-L-carnitine to a balanced, more positive mood in non-Alzheimer’s patients [11].

The mechanism of action for this effect is still under consideration, but is likely due to a boost in mitochondrial activity in the brain, or an increase in the availability of acetyl groups for the synthesis of the neurotransmitter, acetylcholine. Acetylcholine is responsible for both relaying messages back-and-forth between brain cells and between brain and muscles, controlling body movements. 

Acetylcholine levels are known to decrease in many forms of dementia, and most treatments target this latter mechanism [11]. Acetylcholinesterase inhibitors (AChEIs), which are often prescribed as a first-line treatment for Alzheimer’s disease, work by slowing the metabolism of acetylcholine to increase its availability in the brain [12]. Unfortunately, AChEIs are also associated with various adverse side effects [12]. Supplemental nutrients and/or herbal medicines offer alternative pathways to increase the availability of acetylcholine, without contributing to additional consequences. 

DMAE crosses the blood-brain barrier and is a precursor for choline, which also contributes to acetylcholine production, again, a necessary neurotransmitter for mental sharpness and physical movement [13]. DMAE has shown positive results in studies involving a variety of cognitive and disruptive disorders, including attention-deficit hyperactivity disorder (ADHD) and memory studies [13]. DMAE may also aid in the ability to concentrate, recall memories (especially short-term memories), focus, maintain mental clarity, and improve sleep patterns in otherwise healthy adults [13].

Phosphatidylserine (PS) is a phospholipid; a fatty substance that covers and protects every cell in the body. In terms of the brain, it is essential for healthy nerve cell membranes, and the transmission of messages between cells [14]. 

Our nerve cells typically deteriorate as we age, partially due to a natural decline in PS levels [14]. Unfortunately, this deterioration also impairs neurotransmission and can affect our ability to learn, remember, and stay alert [14]. Phosphatidylserine supplementation may help to slow age-related memory loss. In a 2010 study, it was reported that elderly people with relatively low memory scores and mild cognitive impairment at the start of the study experienced a significant improvement in memory after six months of supplementation with PS, compared to those who took a placebo [14].

Phosphatidylserine may also play a role in helping to regulate mood in those experiencing mood disorders, as well as attention span, and impulse control in those diagnosed with ADHD [14].

Ginkgo biloba extract comes from the leaves of the ginkgo biloba tree (also known as the maidenhair tree). Although it has been used historically to target a very wide range of ailments, from low libedo to bladder infections, the strongest scientific evidence supports the action of this herbal extract as a powerful antioxidant. Ginkgo has been studied extensively for its ability to slow cognitive decline and improve memory. Ginkgo extract contains high levels of flavonoids and terpenoids, antioxidants that provide protection against oxidative damage to cells, including brain cells, potentially preventing the progression of tissue degeneration in patients with dementia [15,16]. 

Ginkgo is also known for supporting normal tone and elasticity of blood vessels, and a healthy flow of blood to the brain [16]. This effect is due to its contribution to balancing prostacyclin and thromboxane A2 levels, resulting in improved vasoregulation [16]. The beneficial effects of ginkgo biloba leaf extract that have been measured in patients with Alzheimer’s Disease might also be due to the inhibition of toxicity and cell death induced by beta-amyloid peptides [16].

Centella asiatica, commonly known as gotu kola or asiatic pennywort, is similar to ginkgo biloba in its long history of use in traditional medicine, and its role in the increase of peripheral blood flow. Additionally, gotu kola has been shown to promote neuronal growth [17]. Gotu kola contains several active ingredients, the most important group being the pentacyclic triterpenes, including asiaticoside, madecassoside, asiatic acid, and madecassic acid [12].

Gotu kola consumption has been associated with improvements in self-reported alertness (after 2 months of supplementation), reductions in self-reported anger (within one hour of ingestion), reduced anxiety, increased calmness, improved working memory, attention span and concentration ability, information processing speed, and memory capacity [12]. Most of these connections are likely related to the proposed mechanism of action for gotu kola’s role in anxiety. This effect has been attributed to one of gotu kola’s active components, asiatic acid, which is a compound that triggers the regulation of the calming neurotransmitter, gamma-aminobutyric acid (GABA) [18]. The asiatic acid in gotu kola affects the absorption of GABA by the brain, so may contribute to relief from anxiety, while negating sedative effects and other adverse reactions to traditional GABA agonist drugs such as Ambien (zolpidem) and barbiturates. It may also contribute to balancing mood, improving sleep, and reducing chronic fatigue [18].Gotu kola is also similar to ginkgo in its potency of antioxidant effects, and ability to neutralize many of the free radicals that cause damage to cells at the molecular level [18]. These same properties may provide protection against stomach ulcers and certain destructive cellular mutations [18].

References

1. Hakko, Kyowa. “Most Americans Fear Mental vs. Physical Decline,” Wakefield Research. May 2014. 
2. Alvarez, X. Anton, et al. “Citicoline improves memory performance in elderly subjects.” Methods and findings in experimental and clinical pharmacology 19.3 (1997): 201-210.
3. Killgore, William DS, et al. “Citicoline affects appetite and cortico‐limbic responses to images of high‐calorie foods.” International Journal of Eating Disorders 43.1 (2010): 6-13.
4. Kamiya, Toshi. “The Eyes Are The Windows To The Brain — Citicoline May Promote Optimal Visual Function”. Cognizin Website. June 2018. https://cognizin.com/en/articles/the-eyes-are-the-windows-to-the-brain-citicoline-may-promote-optimal-visual-function 
5. Cognizin. “Nourish the Brain to Help Cultivate a Calm Mind”. Cognizin Website. June 2018. https://cognizin.com/en/articles/cognizin-article-mindful-magazine-blog
6. Silveri, M. M., et al. “Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy.” NMR in Biomedicine: An International Journal Devoted to the Development and Application of Magnetic Resonance In vivo 21.10 (2008): 1066-1075.
7. McGlade, Erin, et al. “Improved attentional performance following citicoline administration in healthy adult women.” Food and Nutrition Sciences 3.06 (2012): 769.
8. Yurgelun-Todd, D. “The effect of citicoline supplementation on motor speed and attention in adolescent males.” Journal of Attention Disorders(2015): 1557-1246.
9. Parisi, Vincenzo, et al. “Treatment with citicoline eye drops enhances retinal function and neural conduction along the visual pathways in open angle glaucoma.” Graefe’s Archive for Clinical and Experimental Ophthalmology 253.8 (2015): 1327-1340.
10. Malaguarnera, Michele, et al. “Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue.” Archives of gerontology and geriatrics 46.2 (2008): 181-190.
11. Mendelson, Scott D. “NUTRITIONAL SUPPLEMENTS AND METABOLIC SYNDROME”. Metabolic Syndrome and Psychiatric Illness, 2008.
12. Puttarak, Panupong, et al. “Effects of Centella asiatica (L.) Urb. on cognitive function and mood related outcomes: A Systematic Review and Meta-analysis.” Scientific reports 7.1 (2017): 10646.
13. Laifer, Stephen. “DMAE: The Smart Supplement.” Life Extension Magazine November 2004. https://www.lifeextension.com/magazine/2004/11/aas/Page-01
14. Wong, Cathy. “The Health Benefits of Phosphatidylserine”. Very Well Mind Website. Updated June 18, 2019. https://www.verywellmind.com/the-benefits-of-phosphatidylserine-89496
15. Nordqvist, Joseph. “Health Benefits of Gingko Biloba”. Medical News Today. December 18, 2017. https://www.medicalnewstoday.com/articles/263105.php 
16. Popa, Andeea. “Ginkgo Biloba and Memory”. Cleveland Clinic Center for Continuing Education. 5:5 (September/October 2002) https://www.clevelandclinicmeded.com/medicalpubs/pharmacy/sepoct02/ginkgo.htm
17. Puttarak, Panupong, et al. “Effects of Centella asiatica (L.) Urb. on cognitive function and mood related outcomes: A Systematic Review and Meta-analysis.” Scientific reports 7.1 (2017): 10646.
18. Wong, Cathy. “The Health Benefits of Gotu Kola: Asian herb may improve circulation, mood, and wound healing”. Very Well Health Website. Feb 22, 2019. https://www.verywellhealth.com/the-benefits-of-gotu-kola-89566