Share this post
Cutting edge science for cognitive enhancement
We’re not getting older, we’re getting better. There has been an astonishing increase in average life expectancy over the last hundred years, according to the National Institute on Aging. Today, over 40 countries boast a life expectancy of 80 years or more. The 85-and-over population is projected to increase over 350% by 2050, and the global number of centenarians is projected to rise by a remarkable tenfold by 2050.
Not only are we living longer, but our intelligence is steadily rising. On measures of “fluid” intelligence—basic problem solving—every generation has had an increase of 15 IQ points.  According to Harvard’s Steven Pinker, this has been demonstrated in 30 countries. 
It’s great news that we’re smarter and living longer lives. But that means there is a high premium on maintaining a cognitive edge—one that lasts for our entire lifespan. Science is now discovering novel nutraceuticals that can replenish and protect brain function.
Targeted nutraceuticals can boost our brainpower, sharpen our memory, lift our mood, heighten our awareness, and protect our neural circuitry from the slow deterioration that aging might otherwise bring.
“Research over the past five years has provided exciting evidence for the influence of dietary factors on specific molecular systems and mechanisms that maintain mental function,” writes Dr. Fernando Gomez-Pinilla, a UCLA professor who analyzed over 160 studies on how food affects the brain. Targeted nutraceuticals can boost our brainpower, sharpen our memory, lift our mood, heighten our awareness, and protect our neural circuitry from the slow deterioration that aging might otherwise bring.
Food ingredients impact multiple brain processes by regulating neurotransmitter pathways, synaptic transmission, membrane fluidity, and signal-transduction pathways, according to Gomez-Pinilla. He states, “The slow and imperceptible cognitive decay that characterizes normal aging is within the range-of-action of brain foods, such that successful aging is an achievable goal for dietary therapies.”
What follows is a look at the latest science on potent and effective new brain foods—mind nourishing nutrients—and the mechanisms by which those molecules work.
Lipids: the brain’s restorative nutrients
Lipids are the liquid gold of your brain: about 60% of your brain tissue is composed of fats that keep cell walls flexible and fluid, yet structurally sound. , Brain cells are especially rich in a lipid called phosphatidylcholine (PC), which your body synthesizes from a substance called citicoline (cytidine 5′-diphosphocholine). Your body makes citicoline from the essential, water-soluble nutrient choline.
Citicoline is a potent brain-enriching nutrient, vital to healthy brain metabolism.
It turns out that citicoline is a potent brain-enriching nutrient, vital to healthy brain metabolism. Since 1956, when it was first successfully synthesized, citicoline has been the subject of nearly a thousand peer reviewed studies, 380 of these in humans. Citicoline is a precursor not only to PC, but also to sphingomyelin (found in high concentrations in the membranes of nerve cells) and cardiolipin (found almost exclusively in the mitochondrial inner membrane).
Citicoline is also a building block for the neurotransmitter acetylcholine, which helps us learn and remember. In addition, citicoline is a precursor to betaine, a nutrient that helps protect against heart, brain, liver, and vascular diseases by acting as a methyl donor (methylation is a profoundly important biological process.) In sum, an impressive range of studies have found citicoline to be neuroprotective.,
In the brain, an oral dose of citicoline is biologically transformed into restorative lipids that are then incorporated into cell membranes. Citicoline increases phospholipids in the frontal lobes of the brain, which regulate motor function, problem solving, spontaneity, memory, language, judgment, impulse control, and social and sexual behavior., It is non-toxic and well tolerated. ,
Citicoline helps enhance production of neurotransmitters like acetylcholine and dopamine, which are essential for memory, learning, and problem solving. It preserves the structural and functional integrity of brain cells, and has been shown to enhance cognition, counteract the deposition of beta-amyloid in Alzheimer’s disease, reverse the effects of brain injury, and improve early stage cognitive loss associated with dementia. It also boosts verbal memory, learning, and attention in healthy individuals.
Citicoline nourishes neurons
There is tantalizing evidence that citicoline may help stave off mild deficits in memory associated with aging. We know that as the brain ages, energy metabolism decreases and lipid metabolism changes. The activity and amounts of dopamine, acetylcholine, and important hormones declines. Age-related changes in phospholipid metabolism and mitochondrial function also occur., Citicoline seems to offset these declines by increasing phospholipid uptake in the brain.
In animal studies, 500 mg/kg daily of citicoline for 27 months starting with three-month-old mice, and for up to 90 days in year-old mice, led to significant increases in phosphatidylcholine production and availability., And in healthy older humans, supplementation with 500 mg per day of citicoline for six weeks stimulated phosphatidylcholine synthesis in the brain, as shown by magnetic resonance spectroscopy, a brain scanning technique.
Memory is the bedrock of the self: without it we cannot know who we were, are, or will be. Conditions like Alzheimer’s disease (AD) and vascular dementia invisibly, inexorably destroy the “self” from within, progressively impairing the ability to think, recognize, learn, and remember. Over five million Americans currently suffer the ravages of AD, according to the National Institutes of Health.
Even more adults—up to 20% of those over 65—suffer from mild cognitive impairment, defined as problems with memory, language, or other mental functions that do not yet drastically interfere with daily living. A study of over 21,000 adults over 50 found that 20% report memory issues.
Citicoline has been demonstrated to help the aging brain. It improves learning, memory, motor skills, and coordination in both animal and human studies.
Citicoline has been demonstrated to help the aging brain. It improves learning, memory, motor skills, and coordination in both animal and human studies., It turns back the hands of time for aged rats, such that they perform as well as young rats in navigating mazes. In animal studies it counteracts the deposition of beta-amyloid, which is correlated with the degree of neurodegeneration in AD, improving memory retention. These results hint that citicoline might make a significant contribution to delaying or even reversing the cognitive decline associated with aging.
Citicoline has been shown to improve logical memory, both immediate and delayed (logical memory requires an understanding of the information learned). In a randomized, double-blind, placebo controlled study, 95 volunteers aged 50 to 85 years old were screened for dementia, memory disorders, and other neurological problems, and from this group, a subgroup of 32 individuals with relatively inefficient memory (though without significant cognitive impairment) was identified. In the initial part of the study, which lasted for three months, all subjects took either placebo or 1000 mg of citicoline per day. Supplementation of citicoline was shown to improve delayed recall on logical memory only in the subjects with relatively inefficient memories. This subgroup then took placebo or citicoline, at a dose 2000 mg per day, in a double-blind cross-over design, for two months each. Supplementation of the higher dosage of citicoline was linked with improved logical memory, both immediate and delayed. Another study of 84 elderly individuals with demonstrated memory loss found that citicoline at 1000 mg a day improved “acquisition efficiency” (how quickly and efficiently new information is absorbed and retained), while placebo did not.
Citicoline also may improve mild vascular cognitive impairment resulting from impaired blood flow to the brain. In an open-label multicenter study of 349 elderly Italians (with an average age of approximately 80), participants were offered 500 mg of citicoline twice daily, or no treatment at all, for a period of nine months. Twenty-one patients with suspected AD were excluded from the study and 15 dropped out, while two were lost to non-treatment related death, leaving 265 patients in the treatment group, and 84 in the control group. In the treatment group, the Mini Mental State Examination (MMSE) scores remained virtually unchanged through the study, while those who were untreated declined over the nine months of the study.
Tune up your healthy brain
Citicoline facilitates learning and memory in healthy individuals, young and old. Citicoline has been shown to boost attention in healthy, middle-aged women. Sixty adult women ages 40 to 60 received either citicoline (250 or 500 mg) or placebo daily for 28 days. Tests measuring attention were given at the outset and conclusion of the study. The citicoline-supplemented groups made significantly fewer errors than the placebo group. “Citicoline administration improves attention not only in clinical populations but also in healthy female adults,” conclude the researchers. “Citicoline supplementation [may] ameliorate cognitive deficits associated with healthy aging.”
Citicoline also improves cognitive function in healthy youth. A 2015 study on adolescent males found that citicoline improved attention and psychomotor speed (grace, speed, skill in physical tasks), and reduced impulsivity compared to placebo. In the 28-day double-blind study, teenage males received 250 or 500 mg of citicoline per day or a placebo. “The current study,” the researchers conclude, “demonstrates measurable effects in human populations using a relatively small dose of citicoline.”
Mint flavored memory
The vibrant green leaves of spearmint (Mentha spicata) give off a fresh, invigorating fragrance that makes a tasty tea and an aromatic garnish in salads and sauces. Spearmint is packed with vitamins, antioxidants, and polyphenols.
Not all spearmints are created equal, however. A new strain of spearmint developed through selective-breeding techniques (not GMO) is unusually high in a potent water-soluble antioxidant called rosmarinic acid (RA), which may boost your brain power—including attention, concentration, spatial and verbal memory., Rosmarinic acid has been shown to possess neuroprotective effects in different models of neuroinflammation and neurodegeneration, as well as chemical-induced neurotoxicity and oxidative stress.
Research on 29 different species of herbs, including rosemary, found that mint species had the highest amount of RA, and spearmint was the highest of all, up to 58 mg/g of RA. However, a novel, specially bred spearmint strain contains over 100 mg/g of RA.
Several clinical studies have shown that high-RA spearmint extract boosts attention, concentration and memory.
Several clinical studies have shown that high-RA spearmint extract boosts attention, concentration and memory. The first, a small 2015 pilot study, assessed healthy, adult men and women, aged 50 to 70, who took 900 mg of high-RA spearmint extract for 30 days. There was a significant improvement in attention and concentration from the baseline scores, as assessed by a battery of cognitive tests. Similar effects were seen in a larger placebo-controlled study of 142 healthy men and women (18 to 50 years of age). There also were improvements in reactive agility (the ability to react to a stimulus quickly and efficiently, at high speed) in this population, reported in a separate publication.
Finally, men and women with age-associated mild memory impairment benefitted from high-RA spearmint extract. For 90 days, 90 healthy men and women 50 to 70 years of age, with age-associated memory impairment but no dementia, took two capsules of either placebo or high-RA spearmint per day with breakfast, providing a daily total of zero, 600, or 900 mg of the spearmint extract. Not only did the individuals who received the 900 mg daily dose exhibit significant improvements of spatial working memory and quality of working memory (the ability to remember and use relevant information while in the middle of an activity) compared to placebo, they also had significant improvements in their ability to fall asleep.
Supplemental citicoline and high-RA spearmint extract may help stave off mild deficits in memory associated with aging and improve cognitive performance in adults of all ages. In Part 2 of this post we’ll discuss three more ingredients with proven results: coffee cherry, lion’s mane, and ginseng.Click here to see References
 National Institute on Aging. Global Health and Aging [Internet]. Bethesda (MD): U S Department of Health and Human Services; 2017 [cited 29 Jul 2019]. Available from: https://www.nia.nih.gov/sites/default/files/2017-06/global_health_aging.pdf
 Graham C, Plucker J. The Flynn Effect [Internet]. Baltimore (MD): Johns Hopkins University; 2001-2002 [cited 29 Jul 2019]. Available from: http://www.intelltheory.com/flynneffect.shtml
 Pinker S. The Better Angels of our Nature. New York (NY): Viking; 2011.
 Gomez-Pinilla F. Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci. 2008 Jul;9(7):568-78.
 Chang CY, et al. Essential fatty acids and human brain. Acta Neurol Taiwan. 2009 Dec;18(4):231-41.
 Küllenberg D, et al. Health effects of dietary phospholipids. Lipids Health Dis. 2012;11:3.
 Jambou R, et al. Citicoline (CDP-choline): what role in the treatment of complications of infectious diseases. Int J Biochem Cell Biol. 2009;41(7):1467-70.
 Conant R, Schauss AG. Therapeutic applications of citicoline for stroke and cognitive dysfunction in the elderly: a review of the literature. Altern Med Rev. 2004;9(1):17-31.
 Qureshi I, Endres JR. Citicoline: a novel therapeutic agent with neuroprotective, neuromodulatory, and neuroregenerative properties. Nat Med J. 2010; 2(6):11-25.
 Alvarez-Sabin J, et al. The role of citicoline in neuroprotection and neurorepair in ischemic stroke. Brain Sci. 2013 Sep 23;3(3):1395-414.
 Agut J, et al. Radioactivity incorporation into different cerebral phospholipids after oral administration of 14C methyl CDP-choline. Arzneimittel-Forschung. 1983;33(7A):1048-50.
 Babb SM, et al. Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study. Psychopharmacology (Berl). 2002;161(3):248-54.
 Silveri MM, et al. Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy. NMR Biomed. 2008;21(10):1066-75.
 Grieb P. Neuroprotective properties of citicoline: facts, doubts and unresolved issues. CNS Drugs. 2014 Mar;28(3):185-93.
 Schauss AG, et al. Single- and repeated-dose oral toxicity studies of citicoline free-base (choline cytidine 5′-pyrophosphate) in Sprague-Dawley rats. Int J Toxicol. 2009;28:479-87.
 Fioravanti M, Yanagi M. Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. Cochrane Database Syst Rev. 2004;(2):CD000269.
 Wang J, et al. Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment. Acta Pharmacol Sin. 2009;30:879-88.
 Whiley L, et al. Evidence of altered phosphatidylcholine metabolism in Alzheimer’s disease. Neurobiol Aging. 2014 Feb;35(2):271-8.
 Li D, et al. Longitudinal association between phosphatidylcholines, neuroimaging measures of Alzheimer’s disease pathophysiology, and cognition in the Mayo Clinic Study of Aging. Neurobiol Aging. 2019 Jul;79:43-9.
 Lopez G-Coviella I, et al. Effects of orally administered cytidine 5′-diphosphate choline on brain phosopholipid content. J Nutr Biochem. 1992;3:313-5.
 Wang CS, Lee RK. Choline plus cytidine stimulate phospholipid production, and the expression and secretion of amyloid precursor protein in rat PC12 cells. Neurosci Lett. 2000 Mar 31;283(1):25-8.
 National Institute on Aging. Alzheimer’s Disease Fact Sheet [Internet]. Bethesda (MD): U S Department of Health and Human Services; 2019 [cited 29 Jul 2019]. Available from: https://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-fact-sheet
 Langa KM, Levine DA. The diagnosis and management of mild cognitive impairment: a clinical review. JAMA. 2014 Dec 17;312(23):2551-61.
 Gallo V, et al. Serum perfluoroalkyl acids concentrations and memory impairment in a large cross-sectional study. BMJ Open. 2013 Jun 1;3(6):e002414.
 Weiss GB. Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline. Life Sci. 1995;56(9):637-60.
 Drago F, et al. Effects of cytidine-diphosphocholine on acetylcholine-mediated behaviors in the rat. Brain Res Bull. 1993;31(5):485-9.
 Alvarez XA, et al. Citicoline protects hippocampal neurons against apoptosis induced by brain beta-amyloid deposits plus cerebral hypoperfusion in rats. Methods Find Exp Clin Pharmacol. 1999;21:535-40.
 Teather LA, Wurtman RJ. Dietary cytidine (5′)-diphosphocholine supplementation protects against development of memory deficits in aging rats. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27(4):711-7.
 Spiers PA, et al. Citicoline improves verbal memory in aging. Arch Neurol 1996:53:441-8.
 Agnoli A, et al. Therapeutic approach to senile memory impairment: a double blind clinical trial with CDP choline. In: Wurtman RJ, Corkin S. Growden JH, eds. Alzheimer’s Disease: Proceedings of the Fifth Meeting of the International Study Group on the Pharmacology of Memory Disorders Associated with Aging. Boston (MA): Birkhauser; 1989:649-54.
 Cotroneo AM, et al. Effectiveness and safety of citicoline in mild vascular cognitive impairment: the IDEALE study. Clin Interv Aging. 2013;8:131-7.
 McGlade E, et al. Improved attentional performance following citicoline administration in healthy adult women. Food Nutr Sci. 2012;3(6):769-73.
 McGlade E, et al. The effect of citicoline supplementation on motor speed and attention in adolescent males. J Atten Disord. 2019 Jan;23(2):121-34.
 Cirlini M, et al. Phenolic and volatile composition of a dry spearmint (Mentha spicata L.) extract. Molecules. 2016;21(8):1007.
 Alankar S. A review on peppermint oil. Asian J Pharm Clin Res. 2009;2:187-94.
 Braidy N. Neuroprotective effects of rosmarinic acid on ciguatoxin in primary human neurons. Neurotox Res. 2014;25:226-34.
 Nabavi SF, et al. The cellular protective effects of rosmarinic acid: from bench to bedside. Curr Neurovasc Res. 2015;12(1):98-105.
 Shekarchi M, et al. Comparative study of rosmarinic acid content in some plants of Labiatae family. Pharmacognosy Mag. 2012 Jan;8(29):37.
 Narasimhamoorthy B, et al. Differences in the chemotype of two native spearmint clonal lines selected for rosmarinic acid accumulation in comparison to commercially grown native spearmint. Industrial Crops Prod. 2015 Jan 1;63:87-91.
 Nieman KM, et al. Tolerance, bioavailability, and potential cognitive health implications of a distinct aqueous spearmint extract. Funct Foods Health Dis. 2015 May 30;5(5):165-87.
 Falcone PH, et al. The attention-enhancing effects of spearmint extract supplementation in healthy men and women: a randomized, double-blind, placebo-controlled, parallel trial. Nutr Res. 2019 Apr;64:24-38.
 Falcone PH, et al. Efficacy of a nootropic spearmint extract on reactive agility: a randomized, double-blind, placebo-controlled, parallel trial. J Int Soc Sports Nutr. 2018 Dec 12;15(1):58.
 Herrlinger KA, et al. Spearmint extract improves working memory in men and women with age-associated memory impairment. J Altern Complement Med. 2018 Jan;24(1):37-47.
Share this post
The Forgotten Man: Male Infertility and Its Causes
Can antioxidants improve male fertility? Infertility affects one in six couples, and it can be a devastating experience for those who wish to conceive. Half of all infertility cases are due to male factors,,, yet men have been largely forgotten when it comes to the treatment of infertility., With the development of assisted reproductive…
Molecular Hydrogen: An Adjunctive Therapy for Conventional Cancer Care?
Evidence suggests this unconventional antioxidant can help mitigate radiation side effects We’ve delved into many of the basics pertaining to hydrogen (H2): what it is, its history of use, and various means of delivering it to the body. We also have discussed how it acts as a selective antioxidant and an anti-inflammatory, and as…
Live Long and Prosper
How a great diet can add years to your life Do you want to live to be 90 or 100? Thanks to advances in medical science, that goal is increasingly within reach. Most of us don’t want to live longer, however, if we are going to be burdened by the diseases of aging –…
Taking a Month Off Alcohol: What Will a Month Booze-Free Do for You?
A trend growing in popularity takes center stage, with clinical studies backing its benefits Perhaps you’ve seen it proudly announced on social media, “I’m going a month booze-free,” by a friend or acquaintance. Or maybe it has infiltrated your sphere because of news stories on outlets such as NPR, the BBC, Fortune, or the…
Molecular Hydrogen as a Neuroprotectant
A potential new treatment for neurodegenerative diseases Neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), Alzheimer’s disease (AD), and Huntington’s disease (HD), among others, are often associated with oxidative stress and neuroinflammation., In each of these diseases, there are similarities in the role of genetics, neurotransmitters, accumulation of toxic proteins, membrane…
Protecting Yourself from the Damaging Effects of Air Pollution
How to keep your cells healthy in the face of particulate matter pollution in the air The more populated our world becomes, the more the by-products of development, consumerism, and transportation become an issue. Many of the effects are obvious: we can’t avoid seeing supermarkets popping up where there once were trees, new shiny…