Choline

Authored by Robert Chen • 
July 10, 2016

Choline is an essential nutrient that serves as a building block for important molecules including acetylcholine, an important neurotransmitter, and phosphatidylcholine, a phospholipid with anti-inflammatory and pro-longevity effects.1,2Choline serves as a source of carbon, and is an important facilitator of methyltransferase reactions, which are involved in gene and protein regulation across many areas including inflammation. Choline supplementation is known to be associated with preventing neural tube defects when taken by pregnant mothers, as well as for improving metabolism in regards to lipolysis and development of metabolic syndrome.3The most widely used nootropics serving as choline sources include CDP-choline and α-GPC (L-Alpha glycerylphosphorylcholine).

Is it safe? Are there side effects?

There are no reported major side effects of choline when taken within normal limits.

Effects on Cognition

Memory

Acute choline administration has been shown to improve working memory in some individuals.

In regards to chronic effects, chronic choline consumption has been shown to counteract age-related cognitive declines in learning and memory.4In a study involving 2,187 participants from the Framingham Heart Study Offspring Study cohort, it was found that those ingesting higher amounts of choline exhibited positive changes in verbal memory (immediate and delayed recall) as well as visual memory (immediate and delayed recall).5

One double-blind crossover study found that choline administration did not result in significant changes in spatial or working memory.

A study in 26 elderly adults with self-reported memory problems, showed that supplementation with a supplement, Cognitex (containing 600 mg α-GPC, a choline source), resulted in significantly improved levels of attention, visual learning, and executive function.6

Studies in rats have shown that pre- and postnatal dietary supplementation of choline may lead to long term improvements in memory function. A study in rats showed that prenatal supplementation (via pregnant rats) combined with post-natal supplementation for 60 days, resulted in improvements in the 12-arm and 18-arm radial maze cognitive tasks. In this task, which is a proxy for spatial memory, rats are placed in mazes with up to 18 "arms" or paths, some of which contain a reward in the form of food. The rats undergoing choline supplementation tended to discover the arms with food with fewer repetitions of traversing down arms.7

Choline and improvement in spatial memory Pre-natal and post-natal long term supplementation with choline improved spatial working memory in rats (tested with the radial maze task).

Effects on Medical Conditions

Blood Pressure

It has been found in multiple studies that intravenous choline administration can lower blood pressure in both humans and animals.1Intravenous choline injection has been shown to increase blood pressure in rat models of hypotension from acute hemorrhage8and hypotensive shock.9

Pain

It has been shown that choline can alter pain sensation in animals. In pain models in mice, it has been shown that doses of 30-120 mg choline given intracerebroventricularly or intrathecally can decrease nociception.10

Lipolysis

Choline is important for lipolysis because normally it is incorporated into phosphatidylcholine. Phosphatidylcholine is involved in the pathway for secretion of very low-density lipoproteins from tissues including the liver.1Studies have shown that humans fed deficient amounts of choline in the diet may exhibit liver dysfunctions that may be related to impaired lipolysis, therefore resulting in greater accumulation of lipids.11

In addition, phosphatidylcholine injection has been used as a method of inducing lipolysis in humans.12While phosphatidylcholine injection as a method for cosmetic fat removal has been used, studies have shown that the effects of liposuction may still be greater.13

Stroke

A study in stroke patients found that treatment with intravenous CDP-choline (1000 mg/day) for 14 days following a cerebral infarct, resulted in significantly higher levels of consciousness compared to placebo.14

Structure & Synthesis

Choline is a compound consisting of a two-carbon chain in which one end has a hydroxyl group attached and the other has an amine nitrogen. Structure of choline

Structure of choline

Choline can be supplemented from several different sources. Popular choline sources include α-GPC, but also choline bitartate and CDP-Choline. By weight, choline represents 40% of α-GPC by weight, 18% of CDP-choline by weight, and 40% of choline bitartate by weight. Choline bitartate, which is inexpensive, is not as bioavailable as α-GPC or CDP-Choline and cannot cross the brain-blood barrier. CDP-Choline is less efficient delivery mechanism of choline by weight; one needs to take more than twice as much CDP-Choline than α-GPC to get the same amount of choline.

Common foods that contain high amounts of choline include egg yolk, beef liver, chicken liver, cereals, pork, coffee, and cauliflower.

Sources of choline from food Sources of choline. Measurements are given in mg choline / 100 g of food.

Mechanisms of Action

Choline (various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation) is a chemical precursor or "building block" needed to produce acetylcholine.15

This is clinically important because there is a large body of research suggesting that learning, memory, intelligence, and mood are mediated at least in part by acetylcholine metabolism in the brain.16This effect is commonly referred to as the "cholinergic effect". Normally, acetylcholine binds to cholinergic receptors the central and peripheral nervous system.

Role of cholinergic receptors in memory

Increased binding to the cholinergic receptors has been implicated in memory.

The role of cholinergic receptors in memory has been studied extensively in animal studies where cholinergic antagonists are administered and memory is measured. Injection of cholinergic antagonists in the perirhinal cortex has resulted in impaired encoding of information for stimuli recognition.17Scopolamine (an anticholinergic drug) injection into various areas has been shown to impair cognitive functions. For example, scopolamine injection into the hippocampus impairs spatial encoding18, and infusions into the medial septum impair spatial learning and reduce acetylcholine release in the hippocampus.19

Infusions of carbachol (a cholinergic agonist) have been shown to impair memory.19Meanwhile, infusions of scopolamine into the CA3 region of the hippocampus have been shown to case impairments in memory encoding in rats as tested with the Hebb-Williams maze.20

Our Recommendation

The recommended daily amounts of choline for adults over 19 years of age are 550 mg/day for males and 425 mg/day for females.1Research has shown that supplementation with up to 300 mg/day may carry cognitive benefits in attention and memory. We recommend a daily supplementation of around 300 mg/day in the form of α-GPC or CDP-Choline.

  1. Wurtman, R. J., Cansev, M., & Ulus, I. H. (2009). Choline and its products acetylcholine and phosphatidylcholine. In Handbook of neurochemistry and molecular neurobiology (pp. 443-501). Springer US.

  2. Blusztajn, J. K., & Wurtman, R. J. (1983). Choline and cholinergic neurons. Science, 221(4611), 614-620.

  3. Ueland, P. M. (2011). Choline and betaine in health and disease. Journal of inherited metabolic disease, 34(1), 3-15.

  4. Bartus, R. T., Dean, R. L., Beer, B., & Lippa, A. S. (1982). The cholinergic hypothesis of geriatric memory dysfunction. Science, 217(4558), 408-414.

  5. Poly, C., Massaro, J. M., Seshadri, S., Wolf, P. A., Cho, E., Krall, E., ... & Au, R. (2011). The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. The American journal of clinical nutrition, 94(6), 1584-1591.

  6. Richter, Y., Herzog, Y., Eyal, I., & Cohen, T. (2011). Cognitex supplementation in elderly adults with memory complaints: an uncontrolled open label trial. Journal of dietary supplements, 8(2), 158-168.

  7. Meck, W. H., Smith, R. A., & Williams, C. L. (1988). Pre‐and postnatal choline supplementation produces long‐term facilitation of spatial memory. Developmental psychobiology, 21(4), 339-353.

  8. Ulus, I., Arslan, B. Y., Savci, V., & Kiran, B. K. (1995). Restoration of blood pressure by choline treatment in rats made hypotensive by haemorrhage. British journal of pharmacology, 116(2), 1911-1917.

  9. Savci, V., Goktalay, G., Cansev, M., Cavun, S., Yilmaz, M. S., & Ulus, I. H. (2003). Intravenously injected CDP-choline increases blood pressure and reverses hypotension in haemorrhagic shock: effect is mediated by central cholinergic activation. European journal of pharmacology, 468(2), 129-139.

  10. Damaj, M. I., Meyer, E. M., & Martin, B. R. (2000). The antinociceptive effects of α7 nicotinic agonists in an acute pain model. Neuropharmacology, 39(13), 2785-2791.

  11. Zeisel, S. H. (1992). Choline: an important nutrient in brain development, liver function and carcinogenesis. Journal of the American College of Nutrition, 11(5), 473-481.

  12. Hasegawa, T., Matsukura, T., & Ikeda, S. (2010). Mesotherapy for benign symmetric lipomatosis. Aesthetic plastic surgery, 34(2), 153-156.

  13. Rotunda, A. M., & Kolodney, M. S. (2006). Mesotherapy and phosphatidylcholine injections: historical clarification and review. Dermatologic surgery, 32(4), 465-480.

  14. Tazaki, Y., Sakai, F., Otomo, E., Kutsuzawa, T., Kameyama, M., Omae, T., ... & Sakuma, A. (1988). Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study. Stroke, 19(2), 211-216.

  15. Parnetti, L., Mignini, F., Tomassoni, D., Traini, E., & Amenta, F. (2007). Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation?. Journal of the neurological sciences, 257(1), 264-269.

  16. Hasselmo, M. E. (2006). The role of acetylcholine in learning and memory. Current opinion in neurobiology, 16(6), 710-715.

  17. Tang, Y., Mishkin, M., & Aigner, T. G. (1997). Effects of muscarinic blockade in perirhinal cortex during visual recognition. Proceedings of the National Academy of Sciences, 94(23), 12667-12669.

  18. Blokland, A., Honig, W., & Raaijmakers, W. G. (1992). Effects of intra-hippocampal scopolamine injections in a repeated spatial acquisition task in the rat. Psychopharmacology, 109(3), 373-376.

  19. Elvander, E., Schott, P. A., Sandin, J., Bjelke, B., Kehr, J., Yoshitake, T., & Ogren, S. O. (2004). Intraseptal muscarinic ligands and galanin: influence on hippocampal acetylcholine and cognition. Neuroscience, 126(3), 541-557.

  20. Rogers, J. L., & Kesner, R. P. (2003). Cholinergic modulation of the hippocampus during encoding and retrieval. Neurobiology of learning and memory, 80(3), 332-342.

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