Choline is an essential dietary nutrient that is involved in a number of metabolic processes in the body.1Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline National Academies Press (US); 1998
While its physical benefits involve improved detox and overall cellular function, the biggest payoff is seen in its mental health benefits.
Choline is one of the most important dietary nutrients for optimal brain health.
Not only is it a precursor to one of the most important neurotransmitters, acetylcholine, it is also a methyl-donor.
This means that choline can influence genes turning on and off, thus influencing how your body reacts to certain environmental stimuli.
Including adequate amounts of choline to your diet dietary choline can have a profound effect on your mental health.
What Is Choline
Choline is an essential nutrient that is native to the body in small amounts.
Your body produces choline in the liver in the form of phosphatidylcholine.
The amount of endogenous choline produced, however, is not enough for most humans to thrive which makes it essential to get from food.2Hollenbeck CB. An introduction to the nutrition and metabolism of choline. Cent Nerv Syst Agents Med Chem. 2012
In the body, choline is metabolized into four main pathways.
These pathways include acetylcholine, trimethylamine (TMA), betaine, and phospholipids.
These four pathways influence many different functions of your body including brain health, detox, cellular health, and gene expressions.3Alejandra M. Wiedeman, Susan I. Barr, Timothy J. Green, Zhaoming Xu, Sheila M. Innis,† and David D. Kitts. Dietary Choline Intake: Current State of Knowledge Across the Life Cycle Nutrients. 2018
What Does Choline Do
Choline metabolism serves a number of different biological functions.
It is required for the synthesis of the phospholipids in cell membranes, methyl group metabolism, and cholinergic neurotransmission.4Zeisel SH, Blusztajn JK.Choline and human nutrition JAnnu Rev Nutr. 1994
Choline and Methylation
One of choline’s major purposes is to oxidize into betaine and subsequently SAM-e which has a direct effect on epigenetic regulation of gene expression.5ALuka Z, Mudd SH, Wagner C. Glycine N-methyltransferase and regulation of S-adenosylmethionine levels. J Biol Chem. 2009
Once choline is oxidized into betaine it will eventually be used for the conversion of homocysteine to methionine.6Steven H. Zeisel, M.D., Ph.D.corresponding author and Kerry-Ann da Costa, Ph.D. Choline: An Essential Nutrient for Public Health Nutr Rev. 2009
This conversion is important as homocysteine can be very inflammatory in the body. The build-up of homocysteine in the body has been tied to heart disease and neurodegenerative diseases like Alzheimer’s disease.7Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, Wilson PW, Wolf PA.. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002
The epigenetic process of methylation can dictate so much of the way our body responds to environmental stimuli.8Pajares MA, Pérez-Sala D. Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism? Cell Mol Life Sci. 2006
Choline and Neuroprotection
Adequate concentrations of choline have demonstrated the ability to preserve neurons, brain volume, and neuronal transmissions.9Eliasz Engelhardt, Denise Madeira Moreira, and Jerson Laks. Vascular dementia and the cholinergic pathways Dement Neuropsychol. 2007
Choline has also shown effective at supporting the aging brain.10Meck WH, Williams CL, Cermak JM, Blusztajn JK. Developmental periods of choline sensitivity provide an ontogenetic mechanism for regulating memory capacity and age-related dementia. Front Integr Neurosci. 2008
This includes its positive effects on protecting the brain from the onset of dementia and Alzheimer’s as mentioned above.
It has also shown an inverse relationship to seizures,11Wong-Goodrich SJ, Mellott TJ, Glenn MJ, Blusztajn JK, Williams CL. Prenatal choline supplementation attenuates neuropathological response to status epilepticus in the adult rat hippocampus.Neurobiol Dis. 2008 stroke,12Jadavji NM, Emmerson JT, MacFarlane AJ, Willmore WG, Smith PD. B-vitamin and choline supplementation increases neuroplasticity and recovery after stroke. Neurobiol Dis. 2017 and ischemia13Borges AA, El-Batah PN, Yamashita LF, Santana Ados S, Lopes AC, Freymuller-Haapalainen E, Coimbra CG, Sinigaglia-Coimbra R. Neuroprotective effect of oral choline administration after global brain ischemia in rats. Nutr Neurosci. 2015 .
Choline Protects The Liver
It also plays a major role in facilitating cholesterol transport.
Choline deficiencies have been tied to a number of liver dysfunctions15Al Rajabi A, Castro GS, da Silva RP, Nelson RC, Thiesen A, Vannucchi H, Vine DF, Proctor SD, Field CJ, Curtis JM, Jacobs RL. Choline supplementation protects against liver damage by normalizing cholesterol metabolism in Pemt/Ldlr knockout mice fed a high-fat diet. J Nutr. 2014 including:
- Non-alcoholic fatty liver disease
- Raised triglycerides
- Altered cholesterol metabolism
- Increased oxidative stress
Each of these issues can also directly affect other functions in the body including weight gain, impaired detox, and mental health and wellness.16Paul Carrier,* Marilyne Debette-Gratien, Murielle Girard, Jérémie Jacques, Philippe Nubukpo, and Véronique Loustaud-Ratti. Liver Illness and Psychiatric Patients Hepat Mon. 2016
Choline deficiency can be highly individual. Different people may experience different choline deficiency symptoms depending on their bio-individuality.
While the liver does produce a low amount
These symptoms include:
- Birth Defects17Shaw GM, Carmichael SL, Yang W, Selvin S, Schaffer DM. Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am J Epidemiol. 2004
- Fatty Liver18Zeisel SH, Da Costa KA, Franklin PD, Alexander EA, Lamont JT, Sheard NF, Beiser A. Choline, an essential nutrient for humans. FASEB J. 1991
- Neurodevelopment and Cognition Alterations19Leermakers ET, Moreira EM, Kiefte-de Jong JC, Darweesh SK, Visser T, Voortman T, Bautista PK, Chowdhury R, Gorman D, Bramer WM, Felix JF, Franco OH. Effects of choline on health across the life course: a systematic review. Nutr Rev. 2015
- Cardiovascular Disease (CVD)20Yu D, Shu XO, Xiang YB, Li H, Yang G, Gao YT, Zheng W, Zhang X. Higher dietary choline intake is associated with lower risk of nonalcoholic fatty liver in normal-weight Chinese women.J Nutr. 2014
- Cancer21Xu X, Gammon MD, Zeisel SH, Lee YL, Wetmur JG, Teitelbaum SL, Bradshaw PT, Neugut AI, Santella RM, Chen J. Choline metabolism and risk of breast cancer in a population-based study. FASEB J. 2008
Needless to say, getting enough dietary choline can be the difference between a happy healthy life and an endless battling of health conditions.
Choline For Memory and Learning
In light of all its physical benefits, one of the biggest payoffs of dietary choline is its brain-boosting effects.
Over the years, choline has demonstrated an uncanny ability to be an essential nutrient for optimal mental performance.
For example, choline can be an effective nutrient for improving memory and learning functions in the brain.22Michael E. Hasselmo. The Role of Acetylcholine in Learning and Memory Curr Opin Neurobiol
Along with improving memory, choline has been shown to halt memory decline.23Meck WH, Williams CL, Cermak JM, Blusztajn JK. Developmental periods of choline sensitivity provide an ontogenetic mechanism for regulating memory capacity and age-related dementia. Front Integr Neurosci. 2008
In fact, the degree of cognitive impairment in individuals with Alzheimer’s disease is closely correlated with the loss of basal forebrain cholinergic neurons.
These cholinergic neurons are highly influential to cortical structures involved in memory and executive function.24Croxson PL, Kyriazis DA, Baxter MG. Cholinergic modulation of a specific memory function of prefrontal cortex.Nat Neurosci. 2011
Higher amounts of acetylcholine in the brain have shown to keep the cholinergic system active.
Keeping the cholinergic system active has the dual benefit of increased memory and learning capabilities while lowering neurodegeneration and the onset of dementia and Alzheimer’s.25Furey ML, Pietrini P, Haxby JV.. Cholinergic enhancement and increased selectivity of perceptual processing during working memory. Science. 2000
Choline, BDNF and Neuroplasticity
Neuroplasticity refers to the brain’s ability to modify, change, and adapt both structure and function throughout life and in response to experience.26Patrice Voss, Maryse E. Thomas, J. Miguel Cisneros-Franco, and Étienne de Villers-Sidani. Dynamic Brains and the Changing Rules of Neuroplasticity: Implications for Learning and Recovery Front Psychol. 2017
Essentially it is your brain’s ability to adapt, grow, and get stronger. This is a crucially important aspect of optimal cognitive function.
In fact, being able to adapt and learn the necessary skills is at the heart of human evolution!
Choline and the entire cholinergic system plays an influential role in this important cognitive task.
Choline has shown to be effective at raising BDNF levels in the brain and improving neuroplasticity.27PRERANA J. KEERTHI AND NAFISA M. JADAVJI. B-Vitamin and Choline Supplementation Changes the Ischemic Brain Neurobiol Dis. 2017
Brain-derived neurotrophic factor (BDNF) is one of the neurotrophic factors that stimulates and controls the growth of new neurons from neural stem cells (neurogenesis). This is crucial in your brain’s ability to learn and evolve.28Siresha Bathina and Undurti N. Das. Brain-derived neurotrophic factor and its clinical implications Arch Med Sci. 2015
BDNF is also neuroprotective as it has been shown to lower inflammatory cytokines while raising anti-inflammatory cytokines.
It is also effective at lowering neurotoxicity induced by glutamate and overall neuroinflammation.
Choline For Anxiety and Depression
While choline can be a powerful nutrient for memory and learning, less is known of its influence in mood disorders like anxiety and depression.
There is evidence of increased dietary choline effectively lowering anxiety.29Bjelland I, Tell GS, Vollset SE, Konstantinova S, Ueland PM., Choline in anxiety and depression: the Hordaland Health Study. Am J Clin Nutr. 2009
While the evidence for improving instances of depression is less conclusive.30Riley CA, Renshaw PF. Brain choline in major depression: A review of the literature. Psychiatry Res Neuroimaging. 2018
There have been both positive and negative outcomes when using choline as a treatment for depression.
However, the conversation of choline being ineffective as a depression treatment involves more nuance.
For example, it may not be the amount of choline that is the issue as much as it may be the brain’s ability to properly metabolize choline that determines the level of depression.31Frank P MacMaster* and Vivek Kusumakar. Choline in Pediatric Depression Mcgill J Med. 2006
While results can be highly individual, the evidence for choline as a treatment for mood disorders is inconsistent and not recommended.
Choline, Focus, and ADHD
Another brain-boosting effect of choline is it’s potential to increase your ability to focus.
We know that the modulation of the medial prefrontal cortex (mPFC) by acetylcholine (ACh) is critical for attention.32Passetti F, Dalley JW, O’Connell MT, Everitt BJ, Robbins TW. Increased acetylcholine release in the rat medial prefrontal cortex during performance of a visual attentional task. JEur J Neurosci. 2000
This may be due to the stimulation of the nicotinic subclass of acetylcholine receptor (nAChR) within the mPFC and its attentional performance under conditions of high attentional demand.33Hahn B, Shoaib M, Stolerman IP. Involvement of the prefrontal cortex but not the dorsal hippocampus in the attention-enhancing effects of nicotine in rats. Psychopharmacology (Berl). 2003
Studies that measure acetylcholine release by means other than increasing dietary choline also show greater engaged attention and response accuracy.34McGaughy J, Sarter M. Behavioral vigilance in rats: task validation and effects of age, amphetamine, and benzodiazepine receptor ligands.Psychopharmacology (Berl). 1995
There is also evidence of choline deficiencies in ADHD.35Brett A. English, Maureen K. Hahn, Ian R. Gizer, Michelle Mazei-Robison, Angela Steele, Daniel M. Kurnik, Mark A. Stein, Irwin D. Waldman, and Randy D. Blakely. Choline transporter gene variation is associated with attention-deficit hyperactivity disorder J Neurodev Disord. 2009
While there is not too much direct evidence linking dietary choline to improvements in ADHD, you can deduce from the available data that it may be a useful nutrient.
Choline For Addiction and Recovery
Addictive disorders are a significant public health concern with a 14.6% lifetime prevalence rate in the U.S.36Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication.
, Arch Gen Psychiatry. 2005
In fact, over 20% of all deaths in the United States can be attributed to substance abuse.
Citicoline has shown promise in being a useful nootropic in the fight against addiction.
There is some evidence that citicoline may decrease the initiation and maintenance of drug use, as well as increase treatment adherence and relapse prevention.37Nicholas D. Wignall, M.A. and E. Sherwood Brown, M.D., PhD. Citicoline in Addictive Disorders: A Review of the Literature, Am J Drug Alcohol Abuse. 2014
There is also evidence that citicoline may help rehab and protect the brain against the neurotoxic load that comes from substance abuse.38D’Orlando KJ, Sandage BW Jr. Citicoline (CDP-choline): mechanisms of action and effects in ischemic brain injury., Neurol Res. 1995
Choline and Perinatal Brain Development
Choline is important during the perinatal period, especially for spinal cord and brain development represented by the high rate of transfer of choline across the placenta.39Steven H. Zeisel. Choline: Critical Role During Fetal Development and Dietary Requirements in Adults Annu Rev Nutr. 2006
High choline concentrations in the brain and spinal cord are important for neural tube closure and brain development.
In fact, women in the lowest quartile for daily choline intake had a 4-fold greater risk of having a baby with a neural tube defect versus women in the highest quartile.40Shaw GM, Carmichael SL, Yang W, Selvin S, Schaffer DM. Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am J Epidemiol. 2004
Choline in a mother’s diet can have a direct effect on a child’s memory, learning, and overall cognitive abilities.41Zeisel SH. The fetal origins of memory: the role of dietary choline in optimal brain development. J Pediatr. 2006
These effects may be due to choline’s influence on DNA methylation, altered gene expression, and associated changes in stem cell proliferation and differentiation
Choline Food Sources
While most plant foods contain some choline, animal foods are the most reliable way to get choline in the more bioavailable form of phosphatidylcholine.
The best food sources of dietary phosphatidylcholine include:42Zeisel SH, Mar MH, Howe JC, Holden JM. Concentrations of choline-containing compounds and betaine in common foods. J Nutr. 2003
- Beef liver
- Chicken liver
- Pork Sausage
- Pork Loin
Supplementing With Choline
Supplementing of choline can be an effective way to meet your body’s daily choline needs, especially if you follow a plant-based or calorie restricting diet.
Choline supplements come in a number of different forms and can be used for different purposes. Below are some examples of popular choline supplements.
Phosphatidylcholine is the most bioavailable source of choline you can supplement with as it can raise serum levels of choline over 12 times higher than other sources of choline.43Hirsch MJ, Growdon JH, Wurtman RJ. Relations between dietary choline or lecithin intake, serum choline levels, and various metabolic indices. Metabolism. 1978
You can find phosphatidylcholine as the most abundant phospholipid in all mammalian cell membranes which tells you how crucial it is to proper cellular function.
In the brain, phosphatidylcholine increases the biosynthesis of the neurotransmitter acetylcholine (ACh.).
As mentioned above phosphatidylcholine also plays an important role in liver nutrient metabolism and lipid transport.
Of all the forms of choline, phosphatidylcholine will give you the best results for liver and metabolic functions.
Citicoline, also known as CDP-Choline is another form of choline that is native to the body.
It can act as a precursor to phosphatidylcholine and helps boost overall choline in the body.
Unlike other forms of choline, citicoline is also a source of cytidine which breaks down to uridine which can function as another powerful nootropic.
In contrast to phosphatidylcholine, citicoline has shown to be a cleaner, less toxic version of phosphatidylcholine as it is less prone to conversion to triethylamine and TMAO.44Kamil Synoradzki and Paweł Grieb Citicoline: A Superior Form of Choline? Nutrients. 2019
l-Alpha-glycerylphosphorylcholine also known as Alpha-GPC is a natural endogenously produced choline derivative and acetylcholine precursor in the brain.45Tuboly E, Gáspár R, Ibor MO, Gömöri K, Kiss B, Strifler G, Hartmann P, Ferdinandy P, Bartekova M, Boros M, Görbe A. L-Alpha-glycerylphosphorylcholine can be cytoprotective or cytotoxic in neonatal rat cardiac myocytes: a double-edged sword phenomenon. Mol Cell Biochem. 2019
Compared to other sources of choline, Alpha-GPC can be used exclusively for nootropic effects as it quickly crosses the blood brain barrier.
Alpha GPC has shown to be effective in boosting overall cognition and supporting neuroprotection.46Lee SH, Choi BY, Kim JH, Kho AR, Sohn M, Song HK, Choi HC, Suh SW. Late treatment with choline alfoscerate (l-alpha glycerylphosphorylcholine, α-GPC) increases hippocampal neurogenesis and provides protection against seizure-induced neuronal death and cognitive impairment. Brain Res. 2017
Of all the forms of choline, choline bitartrate may have the least effective cognitive enhancing qualities.
While it does contain enough choline to raise choline levels in the blood, studies have shown that the choline bitartrate does not effectively enhance cognition to the level of the other forms of choline.47D. P. Lippelt, S. van der Kint, K. van Herk, and M. Naber No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults PLoS One. 2016
For as much good as choline does in the body and the brain there may be an upper limit for some people.
Increased choline levels have been associated with several neurodegenerative conditions including multiple sclerosis and adrenoleukodystrophy.48Tetsuhito Murata Hirohiko Kimura Masao Omori Hirotsugu Kado Hirotaka Kosaka Tetsuya Iidaka Harumi Itoh Yuji Wada MRI white matter hyperintensities, 1H‐MR spectroscopy and cognitive function in geriatric depression: a comparison of early-and late‐onset cases International Journal of Geriatric Psychiatry. 2001
Some research has demonstrated that excess choline consumption may be tied to increases in neurological disorders49Zeisel SH Is maternal diet supplementation beneficial? Optimal development of infant depends on mother’s diet. Am J Clin Nutr. 2009 and even cancer.50Richman EL, Kenfield SA, Stampfer MJ, Giovannucci EL, Zeisel SH, Willett WC, Chan JM.Choline intake and risk of lethal prostate cancer: incidence and survival. Am J Clin Nutr. 2012
Considering all of choline’s mental health benefits mentioned above, along with it’s demonstrated anti-cancer benefits;51Xu X, Gammon MD, Zeisel SH, Lee YL, Wetmur JG, Teitelbaum SL, Bradshaw PT, Neugut AI, Santella RM, Chen J.Choline metabolism and risk of breast cancer in a population-based study. Department of Community and Preventive Medicine, Mt. Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. 200852Cho E, Willett WC, Colditz GA, Fuchs CS, Wu K, Chan AT, Zeisel SH, Giovannucci EL.Dietary choline and betaine and the risk of distal colorectal adenoma in women. J Natl Cancer Inst. 2007 53Zhou RF, Chen XL, Zhou ZG, Zhang YJ, Lan QY, Liao GC, Chen YM, Zhu HL. Higher dietary intakes of choline and betaine are associated with a lower risk of primary liver cancer: a case-control study. 2017 more research is needed to confirm this phenomenon.
Excessive amounts of choline have been associated with body odor, sweating, salivation, hypotension, and hepatotoxicity in humans54Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Hardcopy Version at National Academies Press. 1998
Specifically, body odor, sweating, salivation was seen at doses that are orders of magnitude greater than the estimated intake from food of choline chloride at 150 and 220 mg/kg of body weight/day for 2 to 6 weeks.
Hypotension was seen at oral administration of 10 g/day of choline chloride (which is equivalent to 7.5 g [72 mmol] of choline alone)
As this article demonstrates choline is an essential nutrient in the diet.
While it is found in many common foods, it may be necessary to supplement it as well to get adequate amounts in the body.
If you are looking to improve cognitive function, especially memory, learning, and focus, choline supplementation can do you wonders.
Like any other nutrient, it’s important to know what you need it for and what goal you are trying to accomplish.
Experimenting is important too. That is easy with choline as it does have a very safe profile and is non-toxic unless taken in incredibly high amounts.