Choline is a vital nutrient playing a crucial role in three major pathways - acetylcholine synthesis, methyl donation via betaine, and phosphatidylcholine synthesis. [1] The body synthesizes acetylcholine, a key neurotransmitter found throughout the central nervous system, from acetyl coenzyme A and choline. [2] Acetylcholine is an important methyl donor used in numerous metabolic processes and to metabolize lipids. [3]
Choline also oxides into betaine and methylates homocysteine into methionine. [1] Methionine is used to add methyl groups to and modify the function of DNA, RNA, and protein. [1]
Choline's role in phosphatidylcholine synthesis ensures the maintenance of cell membrane structural integrity and signaling function. [4] Choline's importance goes beyond general health and well-being; it ensures your body functions, period.
The negative effects of consuming a choline-deficient diet can manifest in as quickly as three weeks. Complications from a low choline diet include liver dysfunction and damage, DNA damage, white blood cell death, muscle damage, increased cardiovascular risk, and neurodegeneration. [5][6][7]
Those at high risk for choline deficiency include developing infants, pregnant or lactating women, those with long-term liver damage, and IV-fed individuals. [8] While choline deficiency is rare in the general population, it's becoming increasingly common in individuals following strict diets (e.g. vegetarians, vegans, allergy-based) that limit or eliminate the intake of meat, milk, and eggs.
This article discusses recommended dosage, use, types, benefits, and frequently asked questions around choline
Choline Recommended Dosages and Use
The recommended dosage of choline depends on your age, gender, and whether you're pregnant or lactating. The Institute of Medicine's recommended adequate intake is 550mg/day for a 70kg body weight, or about 8mg/kg. [1] Outside of the bodyweight dosage recommendation the Institute of Medicine recommends higher intakes for women that are pregnant or lactating as well as those with genetic variations that increase dietary methyl requirements. [7]
The U.S. Department of Agriculture offers a list with the choline content of over 630 plant and animal-based foods. The top six choline-rich foods, per 100g serving, are beef liver (418mg), chicken liver (290mg), eggs (251mg), wheat germ (152mg), bacon (125mg), and dried soybeans (116mg). [9] Only two foods in the top six aren't animal-based; this speaks to the importance of choline supplementation for those on strict diets.
For those looking to supplement their dietary intake of choline, start with 50-100mg of choline and increase to a once-daily dose of 250-500mg. [10] It can be consumed at any time of the day and with or without food.
Choline is found in pre-workouts, multivitamins, general health products, and nootropic blends. it's worth noting that choline in supplement form is almost always bonded with one or more other compounds. For example, 100mg of choline bitartrate will not provide you with 100mg of pure choline. Specific concentrations of choline in its various forms will be discussed in the next section.
You do not need to cycle off this compound as it's naturally found in food and used in the human body for critical functions. While you may not notice acute effects from choline, chronic consumption offers a number of key health benefits discussed later in the article.
Forms of Choline
The three most popular forms of orally ingested choline are choline bitartrate, alpha-GPC, and CDP-choline. Other forms include choline chloride, choline citrate, hydroxide, and choline-O-sulfate. [3] This article will focus on the three most popular forms.
Choline bitartrate is the most popular form of choline due to high choline concentration (41% weight) and low cost. While it is the least expensive form it does come with one major drawback - it doesn't consistently increase choline concentrations in the brain. [11] This means it may not be the best choice for those using choline-depleting nootropics. However it still offers numerous other benefits discussed in the next section of the article.
Alpha-glycerophosphocholine, also known as alpha-GPC, is a more expensive form of choline but offers a high choline concentration (40% by weight) and is absorbed by both the brain and body. [11] A small study on eight male subjects found that a single 1,000mg dose of alpha-GPC significantly increased choline levels and growth hormone 60 minutes post-ingestion as well as increased free fatty acid blood levels and liver fat cell oxidation 120 minutes post-ingestion. [12]
Adequate choline intake positively affects learning and memory, psychological state, liver function, cardiovascular health, inflammation, cancer risk, and exercise endurance.
These findings suggest alpha-GPC to be a highly absorbed choline form that also increases growth hormone levels and fat burning. Over 2,000 patients who suffered a full stroke or mini-stroke consumed 1,000mg of alpha-GPC daily for 28 days following by 400mg/day 5 months thereafter.
71% of patients experienced significant cognitive recovery with tests indicating "no cognitive decline" or "forgetfulness" post-stroke. [13] While many readers may not have had the traumatic experience of a stroke, these findings suggest alpha-GPC can prevent or even reverse cognition decline and neurodegeneration.
Cytidine diphosphate-choline, also known as CDP-choline or citicoline, increases growth hormone levels, decrease prolactin levels, improve attention, mnemonic, and behavioral capabilities. [14][15] CDP-choline is also wide used to improve post-stroke recovery in 70+ countries, promote sciatic nerve regeneration in rats, decrease the effects of a traumatic brain injury in humans, and improve the memory of people with dementia. [16][17][18][19]
Unlike choline bitartrate, CDP-choline increases choline concentrations in both the brain and body. CDP-Choline has a relatively low choline concentration (18.5% by weight) so dosages of 500-2,000mg are used in human trials to evaluate effectiveness. [11][20] CDP-choline is one of the most expensive but also one of the most readily absorbed and effective forms of choline. Regardless of which choline type you use, ensure it comes from a reliable supplier; if you choose a bulk supplier then ensure you have a high-precision scale to measure the appropriate dosage.
A Deeper Look at Choline Benefits
Adequate choline intake positively affects learning and memory, psychological state, liver function, cardiovascular health, inflammation, cancer risk, and exercise endurance. Choline is most commonly highlighted as a critical nutrient for pregnant and lactating women as it plays a key role in the normal growth and development of the brain and cognitive processes in babies. [21] In fact, women who don't eat sufficient choline have 4 times the risk of having a baby with brain, spine, or spinal cord defects. [7]
Adequate choline intake is required during crucial growth and developmental periods of infants and children. Choline also strongly impacts the psychological state of adults. A study of 5,918 males and females ages 46-49 and 70-74 found an inverse relationship between anxiety levels and choline consumption; those in the lowest 20% of choline consumption had the highest anxiety level, which decreased when choline intake increased. [22] If you've been feeling stressed and down recently then consider your choline intake as it may be playing a role.
Choline has a profound impact on liver function for those that do and do not drink alcohol. Alcohol negatively impacts the natural metabolism of choline. [23] Increased choline consumption helps ensure alcohol doesn't force your body in to a choline-deprived state. When healthy adult subjects consumed a choline-insufficient diet, 77% of males and 80% of postmenopausal females showed signs of fatty liver and muscle damage which was reversed when they consumed a choline-rich diet. [7]
Choline also plays a critical role in very low-density lipoprotein (VLDL) secretion and liver fat oxidation. [24] VLDL build-up can lead to plaque buildup in the arteries which causes numerous cardiovascular risk and complications.
From the cardiovascular health standpoint, choline protects against cardiac hypertrophy, the process by which the heart muscle thickens and decreases the sizes of the heart chambers. [25] Cardiac hypertrophy is commonly caused by high blood pressure, a condition affecting millions of people across the globe. Choline not only protects against cardiovascular risk but also decreases key inflammatory markers.
Those with the highest choline and betaine intake had the lowest concentrations of C-reactive protein, an indicator of cardiovascular risk, homocysteine, interleukin-6, and tumor necrosis factor. [7] If you're looking to minimize inflammation and keep your heart healthy ensure choline is a staple in your diet and supplement regimen.
An analysis of 1,508 patients with breast cancer and 1,556 control patients found an inverse relation between choline intake and breast cancer risk; those in the highest 20% of choline consumption (>455.8mg/day) had a reduced breast cancer risk compared to the lowest 20%. [5] This research also emphasized the important adequate methionine and betaine consumption.
When choline is depleted during intense physical exercise, it may fall below normal levels and negatively impact exercise endurance. [26] To maximize exercise endurance you should consume choline immediately prior to, during, or immediately post-workout. This will minimize the likelihood and duration of your body?s functioning in a choline-deficient state.
Failure to consume enough choline has numerous negative repercussions that usually can be reversed through eating a choline-rich diet. Choline is absolutely essential for your body?s overall functioning so it's paramount you consume enough through diet and/or supplementation.
Choline FAQs
Where can I find choline today?
You can find choline as a stand-alone ingredient or as part of a blend in multivitamins, pre-workouts, and nootropic supplements. Products that contain choline include:
Ambrosia Mental Jewels - Nootropic blend with 150mg Alpha GPC (50% Alpha-Glycerolphosphorylcholine) per 4 capsule serving
Does choline have any side effects?
Choline consumption has no serious side effects assuming you stay below the 3.5g/day upper limit for adults and 1g/day for children. [1] The first and most likely adverse effect from consuming more than 3.5g/day is low blood pressure. [2]
Luckily this condition is not permanent and can be eliminated by reducing choline consumption to amounts below the upper limit. Other less serious side effects of consuming too much choline include headaches and upset stomach.
Is choline safe to stack with other supplements?
Choline is extremely safe to stack with other supplements and has no known drug interactions. Many people recommend consuming choline alongside nootropics in the racetam family as compounds like piracetam and oxiracetam can deplete the body?s choline levels. When beginning or stacking a new supplement it's important, to begin with, the minimum recommended dosage and increase or decrease based on your body?s response.
References
1) Zeisel, Steven H. ?Choline: Clinical Nutrigenetic/Nutrigenomic Approaches for Identification of Functions and Dietary Requirements.? Journal of Nutrigenetics and Nutrigenomics 3.4-6 (2011): 209?219. PMC. Web. 2) Purves, D., G. J. Augustine, and D. Fitzpatrick. "Acetylcholine - Neuroscience 2nd edition." National Center for Biotechnology Information. Sinauer Associates, 2001. Web. 3) "Choline." PubChem Compound Database. National Center for Biotechnology Information, 16 Jan. 2016. Web. 4) Sanders, Lisa M., and Steven H. Zeisel. ?Choline: Dietary Requirements and Role in Brain Development.? Nutrition today 42.4 (2007): 181?186. PMC. Web. 5) Xu, Xinran et al. ?Choline Metabolism and Risk of Breast Cancer in a Population-Based Study.? The FASEB journal?: official publication of the Federation of American Societies for Experimental Biology 22.6 (2008): 2045?2052. PMC. Web. 6) Zeisel, S. H., et al. "Choline, an Essential Nutrient for Humans." National Center for Biotechnology Information. FASEB J, Apr. 1991. Web. 7) Zeisel, Steven H., and Kerry-Ann da Costa. ?Choline: An Essential Nutrient for Public Health.? Nutrition reviews 67.11 (2009): 615?623. PMC. Web. 8) Zeisel, S. H., and J. K. Blusztajn. "Choline and Human Nutrition." National Center for Biotechnology Information. Annu Rev Nutr, 1994. Web. 9) Zeisel, S. H., et al. "Concentrations of Choline-containing Compounds and Betaine in Common Foods." National Center for Biotechnology Information. J Nutr, May 2003. Web. 10) Orwell, Sol, et al. "Choline." Examine.com. N.p., 2016. Web. 11) Orwell, Sol, et al. "What Source of Choline Should I Use?" Examine.com. N.p., 2016. Web. 12) Kawamura, T., et al. "Glycerophosphocholine Enhances Growth Hormone Secretion and Fat Oxidation in Young Adults." National Center for Biotechnology Information. Nutrition, Dec. 2012. Web. 13) Barbagallo Sangiorgi, G. "Alpha-Glycerophosphocholine in the Mental Recovery of Cerebral Ischemic Attacks. An Italian Multicenter Clinical Trial." National Center for Biotechnology Information. Ann N Y Acad Sci, June 1994. Web. 14) Matsuoka, T., M. Kawanaka, and K. Nagai. "Effect of Cytidine Diphosphate Choline on Growth Hormone and Prolactin Secretion in Man." National Center for Biotechnology Information. Endocrinol Jpn, Feb. 1978. Web. 15) Piccoli, F., et al. "CDP-choline in the Treatment of Chronic Cerebrovasculopathies." National Center for Biotechnology Information. Arch Gerontol Geriatr, June 1994. Web. 16) Adibhatla, Rao Muralikrishna, J.F. Hatcher, and K. Tureyen. ?CDP-Choline Liposomes Provide Significant Reduction in Infarction over Free CDP-Choline in Stroke.? Brain research 1058.1-2 (2005): 193?197. PMC. Web. 17) Aslan, E., et al. "CDP-choline and Its Endogenous Metabolites, Cytidine and Choline, Promote the Nerve Regeneration and Improve the Functional Recovery of Injured Rat..." National Center for Biotechnology Information. Neurol Res, Sept. 2011. Web. 18) Zafonte, Ross et al. ?The Citicoline Brain Injury Treatment (COBRIT) Trial: Design and Methods.? Journal of Neurotrauma 26.12 (2009): 2207?2216. PMC. Web. 19) Bracken, Bethany K. et al. ?Eight Weeks of Citicoline Treatment Does Not Perturb Sleep/wake Cycles in Cocaine-Dependent Adults.? Pharmacology, biochemistry, and behavior 98.4 (2011): 518?524. PMC. Web. 20) Grieb, Pawel. ?Neuroprotective Properties of Citicoline: Facts, Doubts and Unresolved Issues.? CNS Drugs 28.3 (2014): 185?193. PMC. Web. 21) Degani, Hadassa, Galit Eliyahu, and Nimrod Maril. "Choline Metabolism: Meaning and Significance." Weizmann Institute of Science. N.p., 2006. Web. 22) Bjelland, I., et al. "Choline in Anxiety and Depression: the Hordaland Health Study." National Center for Biotechnology Information. Am J Clin Nutr, Oct. 2009. Web. 23) Zeisel, Steven H. ?What Choline Metabolism Can Tell Us About the Underlying Mechanisms of Fetal Alcohol Spectrum Disorders.? Molecular neurobiology 44.2 (2011): 185?191. PMC. Web. 24) ?Choline.? Advances in Nutrition 1.1 (2010): 46?48. PMC. Web. 25) "Cardiac Hypertrophy." Cardiothoracic Surgery - Glossary of Terms. University of Southern California Keck School of Medicine, 2016. Web. 26) Penry, J. T., and M. M. Manore. "Choline: an Important Micronutrient for Maximal Endurance-exercise Performance?" National Center for Biotechnology Information. Int J Sport Nutr Exerc Metab., Apr. 2008. Web.