The sometimes forgotten but essential nutrient choline

We hear a lot about vitamins and minerals such as vitamin C, B12, iron, magnesium, and so on, but one nutrient that is rarely discussed in the media is the importance of dietary choline. Choline is one of the newest nutrients to be added to the list of human vitamins and was officially recognised as an essential nutrient by the Institute of Medicine in 1998.1
Choline is a water-soluble compound that is often grouped with the B vitamin complex, since it has similar functions and properties. Its role in the body is complex and will be discussed in this blog.

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Choline can be produced endogenously in the liver, mostly as phosphatidylcholine, but the amount that the body naturally synthesises is not sufficient to meet needs.2 Therefore, some choline needs to be obtained from the diet. Because of its wide-ranging roles in metabolism, from cell structure to neurotransmitter synthesis, choline-deficiency is now thought to have an impact on diseases such as liver disease, atherosclerosis and possibly neurological disorders. Therefore, getting adequate choline in the diet is important throughout life for optimal health.

Natural sources of choline

Choline is found in a range of different foods:

• Egg yolks
• Prawns
• Liver
• Salmon
• Chicken breast
• Beef

Good plant food sources include
• Brussels sprouts
• Broccoli
• Peanut butter
• Cauliflower
• Spinach
• Flaxseeds
• Peas

Synthesis of choline

Choline can be obtained from the diet and via de novo biosynthesis through the methylation of phosphatidylethanolamine to phosphatidylcholine. However, de novo synthesis of choline alone is not enough to meet human requirements. The major fate of choline is conversion to phosphatidylcholine (the main constituent of lecithin) which is the predominant phospholipid in most mammalian membranes.

Experiments in human participants, where choline and folate intake were strictly controlled, indicated that low folate and choline feeding results in low blood levels of choline. Tests of the volunteers’ blood indicated that blood levels of choline decreased an average of 25-28% in men and women during the low-folate, low-choline periods. But those levels returned to normal when researchers provided more folate. The study concluded that healthy people cannot synthesise enough choline if both choline and folate intake are low. This is in contrast to the assumption that the body can make as much choline as it needs.3

Recent studies indicate that choline is recycled in the liver and redistributed from the kidneys, lungs and the intestine, to the liver and brain when choline supply is low.4

Functions of choline

Choline has structural and functional roles in the body, including:

Cell structure
Choline is necessary for the synthesis of phosphatidylcholine and sphingomyelin, which are phospholipids that help maintain the structural integrity of the cell membranes.

Fat transport and metabolism
Choline is necessary for turning fat and cholesterol into lipoproteins called very low density lipoproteins (VLDL).5,6 It also helps transport VLDL into the bloodstream and to the extrahepatic tissues, preventing fat and cholesterol from accumulating in the liver. A choline deficiency could result in excess fat and cholesterol build-up.7

Nervous system function
Choline is a precursor to acetylcholine, a neurotransmitter involved in various neuronal functions, including muscle control, circadian rhythm and memory.

Cell messaging
The phospholipids that are synthesised from choline also act as precursors for the intracellular messenger molecules, diacylglycerol and ceramide.
Diacylglycerol is a prolific secondary messenger that activates proteins involved in a variety of signalling cascades and its activity plays a central role in many lipid signalling pathways.

Ceramides are a family of lipid molecules, found in high concentrations within the cell membrane of cells. Ceramides play important roles in coordinating cellular responses to extracellular stimuli and to stress.

Methylation
Choline is regarded as a key partner in the process of methylation, along with folate, vitamins B6 and B12. Choline is an important source of methyl groups necessary for the synthesis of S-adenosylmethionine, the universal methyl donor.8

Methylation, the addition of a methyl group (CH3) to a compound, is involved in almost every reaction in the body and occurs billions of times per second. The functions of methylation include:

– Switching genes on and off
– Synthesis and metabolism of neurotransmitters and hormones
– Development, growth and repair – including of RNA and DNA, myelin and cell structures; and
– Detoxification

When methylation is impaired the consequences include increased homocysteine, inflammation and a wide range of key bodily functions not being performed effectively.

Lack of nutrients needed for methylation, including choline, can lead to elevated levels of blood homocysteine, which is an intermediate in the methylation cycle and recognised as a risk factor for a number of diseases and conditions such as cardiovascular disease, dementia (including Alzheimer’s), declining memory, poor concentration and judgement, fatigue, migraines and lowered mood. In addition, women with high homocysteine levels find it harder to conceive and are at risk from repeated early miscarriage. Conditions such as diabetes and osteoporosis may also be associated with raised homocysteine levels.

In the brain, raised homocysteine is associated with increased oxidative stress and inflammation, white matter damage, brain atrophy and neurofibrillary tau tangles.

Research

Hormones
In a study of healthy adult subjects deprived of dietary choline, 77% of the men and 80% of the postmenopausal women developed signs of subclinical organ dysfunction (fatty liver or muscle damage). Less than half of premenopausal women developed such signs.9 This indicates that premenopausal women might need less choline from the diet than other adults.

Phosphatidylcholine is catalysed by the enzyme phosphatidylethanolamine-N-methyltransferase (PEMT), which is induced by oestrogen. Due to lower oestrogen concentrations, postmenopausal women are more susceptible to the risk of organ dysfunction in response to a low-choline diet. A common genetic polymorphism (rs12325817) in the PEMT gene, which codes for an enzyme that synthesises phosphaditylcholine, can also increase this risk.10

Memory
Choline is required to produce acetylcholine, a neurotransmitter needed for memory storage and muscle control. Thus a choline deficiency may play a part in age-related cognitive decline, including memory loss and Alzheimer’s disease.11,12

A double-blind random controlled study of 80 healthy young adults designed to test the effect of phosphatidylcholine on explicit memory was carried out. A single dose of phosphatidylcholine was shown to enhance explicit memory in normal human subjects.13 Explicit memory is one of the two main types of long-term human memory. It is the conscious, intentional recollection of factual information, previous experiences, and concepts.

Liver Health

Non-alcoholic fatty liver disease (NAFLD) is a very common disorder and refers to a group of conditions where there is accumulation of excess fat in the liver of people who drink little or no alcohol. As the name implies, the main characteristic of NAFLD is too much fat stored in liver cells. NAFLD is linked to the following:

• Being overweight or obese
• Insulin resistance
• High blood sugar (hyperglycaemia), indicating pre-diabetes or actual type 2 diabetes
• High levels of fats, particularly triglycerides, in the blood

Low levels of phosphatidylcholine in the liver are associated with NAFLD.14–16

Because choline is needed to make phosphatidylcholine, low choline levels can limit its production. Choline deficiency can thus decrease phosphatidylcholine levels in the liver, leading to liver failure.17

A double blind randomised control trial using a combination of milk thistle and phosphatidylcholine treatment showed a significant improvement in liver enzymes, insulin resistance, and liver tissue in 179 patients with NAFLD.18

Bile acids and gall bladder health

Adequate bile production and secretion is often overlooked when exploring solutions to common health complaints such constipation, flatulence, fat digestion problems, low or high cholesterol levels, nutritional deficiencies, or imbalances of gut bacteria. The main functions of bile are:

• Breakdown and absorption of fats and cholesterol
• Absorption of fat-soluble vitamins such as A, E, D, and K
• Antimicrobial – bile kills pathogenic bacteria helping to keep the gut balanced and healthy
• Neutralising stomach acid (or ‘chyme’) before it moves to the small intestine. If stomach acid is not neutralised before it reaches the small intestine this can irritate the gut wall causing reflux, bloating, indigestion, feeling of fullness, diarrhoea and nausea, among others. The efficacy of pancreatic enzymes may be affected as they require a higher pH
• The liver excretes fat-soluble toxins into the bile for elimination via the stool. Toxins include metabolised hormones and unwanted cholesterol

Bile is composed of various components, including cholesterol, bile acids and lecithin. Some research has shown that reduced lecithin levels may be a causative factor in the development of gallstones19. Conversely, lecithin enhances bile secretion and prevents bile acid-induced cholestasis (reduction or stoppage of bile flow).20

Key Takeaways

• Choline can be synthesised in the body but it is also essential to obtain it from the diet
• The major fate of choline is conversion to phosphatidylcholine (the main constituent of lecithin)
• Choline has structural and functional roles in the body including helping maintain the structure of cell membranes, fat metabolism and synthesis of acetylcholine (a brain chemical important for memory)
• The enzyme which catalyses the production of phosphatidylcholine is induced by oestrogen. Therefore, due to lower oestrogen concentrations, postmenopausal women are more susceptible to the risks of a low-choline diet
• Low choline may contribute to poor memory, fatty liver, reduced bile flow and high homocysteine (itself linked to increased risk of cardiovascular disease, dementia and other conditions)
• Some research has shown that reduced choline levels may be a causative factor in the development of gallstones.


Relevant Cytoplan Products

Choline Bitartrate
Bitartrate is added to the choline to speed up the absorption rate within the body.

Cell-Active Phospholec: Super-strength Lecithin
This soya lecithin supplement contains a natural blend of phospholipids (phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl inositol) along with alpha linolenic (omega-3) and linoleic (omega-6) fatty acids.

R-Omega
R-Omega is a phospholipid-rich DHA and EPA omega 3 supplement sourced from phospholipid-rich herring roe. Herring roe also provides choline, as phosphatidylcholine.

Krill Oil
A high proportion of the omega-3 fatty acids in krill are bound to choline containing phospholipids.


References
1. Institute of Medicine (U.S.). Standing Committee on the Scientific Evaluation of Dietary Reference Intakes., Institute of Medicine (U.S.). Panel on Folate OBV, Institute of Medicine (U.S.). Subcommittee on Upper Reference Levels of Nutrients. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B₆, Folate, Vitamin B₁₂, Pantothenic Acid, Biotin, and Choline. National Academy Press; 1998.
2. Ross AC, Caballero BH, Cousins RJ, Tucker KL, Ziegler TR. Modern Nutrition in Health and Disease. Wolters Kluwer Health/Lippincott Williams & Wilkins; 2014.
3. Agricultural Research. Folate and Choline Interplay Investigated.; 2001.
4. Zeisel SH, Mar M-H, Howe JC, Holden JM. Concentrations of Choline-Containing Compounds and Betaine in Common Foods. J Nutr. 2003;133(5):1302-1307. doi:10.1093/jn/133.5.1302.
5. Cole LK, Vance JE, Vance DE. Phosphatidylcholine biosynthesis and lipoprotein metabolism. Biochim Biophys Acta – Mol Cell Biol Lipids. 2012;1821(5):754-761. doi:10.1016/j.bbalip.2011.09.009.
6. Yao ZM, Vance DE. The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes. J Biol Chem. 1988;263(6):2998-3004.
7. Noga AA, Zhao Y, Vance DE. An Unexpected Requirement for Phosphatidylethanolamine N -Methyltransferase in the Secretion of Very Low Density Lipoproteins. J Biol Chem. 2002;277(44):42358-42365. doi:10.1074/jbc.M204542200.
8. Zeisel SH. Dietary choline deficiency causes DNA strand breaks and alters epigenetic marks on DNA and histones. Mutat Res. 2012;733(1-2):34-38. doi:10.1016/j.mrfmmm.2011.10.008.
9. Fischer LM, daCosta KA, Kwock L, et al. Sex and menopausal status influence human dietary requirements for the nutrient choline. Am J Clin Nutr. 2007;85(5):1275-1285. doi:10.1093/ajcn/85.5.1275.
10. Fischer LM, da Costa K-A, Kwock L, Galanko J, Zeisel SH. Dietary choline requirements of women: effects of estrogen and genetic variation. Am J Clin Nutr. 2010;92(5):1113-1119. doi:10.3945/ajcn.2010.30064.
11. Poly C, Massaro JM, Seshadri S, et al. The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. Am J Clin Nutr. 2011;94(6):1584-1591. doi:10.3945/ajcn.110.008938.
12. Wurtman RJ. How Anticholinergic Drugs Might Promote Alzheimer’s Disease: More Amyloid-β and Less Phosphatidylcholine. J Alzheimer’s Dis. 2015;46(4):983-987. doi:10.3233/JAD-150290.
13. Ladd SL, Sommer SA, LaBerge S, Toscano W. Effect of phosphatidylcholine on explicit memory. Clin Neuropharmacol. 1993;16(6):540-549.
14. Ling J, Chaba T, Zhu L-F, Jacobs RL, Vance DE. Hepatic ratio of phosphatidylcholine to phosphatidylethanolamine predicts survival after partial hepatectomy in mice. Hepatology. 2012;55(4):1094-1102. doi:10.1002/hep.24782.
15. Jacobs RL, van der Veen JN, Vance DE. Finding the balance: The role of S -adenosylmethionine and phosphatidylcholine metabolism in development of nonalcoholic fatty liver disease. Hepatology. 2013;58(4):1207-1209. doi:10.1002/hep.26499.
16. Sherriff JL, O’Sullivan TA, Properzi C, Oddo J-L, Adams LA. Choline, Its Potential Role in Nonalcoholic Fatty Liver Disease, and the Case for Human and Bacterial Genes. Adv Nutr. 2016;7(1):5-13. doi:10.3945/an.114.007955.
17. Li Z, Agellon LB, Vance DE. Phosphatidylcholine Homeostasis and Liver Failure. J Biol Chem. 2005;280(45):37798-37802. doi:10.1074/jbc.M508575200.
18. Tsai C, Hayes C, Taylor GW. Glycemic control of type 2 diabetes and severe periodontal disease in the US adult population. Community Dent Oral Epidemiol. 2002;30(3):182-192.
19. Heuman R, Norrby S, Sjödahl R, Tiselius H-G, Tagesson C. Altered Gallbladder Bile Composition in Gallstone Disease: Relation to Gallbladder Wall Permeability. Scand J Gastroenterol. 1980;15(5):581-586. doi:10.3109/00365528009182219.
20. LeBlanc MJ, Gavino V, Pérea A, Yousef IM, Lévy E, Tuchweber B. The role of dietary choline in the beneficial effects of lecithin on the secretion of biliary lipids in rats. Biochim Biophys Acta. 1998;1393(2-3):223-234.


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7 thoughts on “The sometimes forgotten but essential nutrient choline

  1. Just wondering why doctors do not test for homocysteine levels, unless one has had a heart attack! Then surely it’s too late …. should be preventative.

    1. Hi Maude,

      Thank you for your question. I am not sure why doctors do not test for homocysteine levels routinely. May be it’s a question of cost. It is possible to get one of these tests done privately. For example York Tests offer a fingerprick homocysteine test which can be done at home.

      Thanks,
      Clare

  2. You mentioned a SNP in one of the PEMT genes effecting phosphaditylcholine synthesis. What other genes can be effective as well? I know of the MTHFD1 rs2236225, MTRR rs1801394, and another FADS1 gene rs174548, in which according to SNPedia is a rare genetic polymorphism.

    1. Hi Andrew,
      Thanks for your question on our blog.
      The PEMT gene is most often talked about in relation to phosphatidylcholine synthesis. The enzyme it codes for is a methyl-transferase enzyme which requires SAMe as a co-factor. SAMe is produced in the methylation cycle – so enzymes involved in methylation would all be relevant, you have mentioned a couple, MTHFR would be another relevant enzyme. Then of course it is also important for effective methylation that all nutrient co-factors are present in adequate levels.
      Best wishes,
      Clare

  3. Hi recent research (in the US I think) suggested that eggs should be avoided by men with prostate cancer and i understood this to be due to the high choline levels in eggs. Any thoughts on why this should be an issue? Thanks

    1. Hi Celine, thank you for your comment.
      A small number of studies have found that eggs may increase risk of aggressive prostate cancer due to their choline content, however, other research suggests no association with risk of prostate cancer (overall or prostate cancer-specific mortality). Prostate Cancer UK state that there isn’t strong evidence that some foods could be harmful for men with prostate cancer as different studies have had different results.
      Best wishes, Jackie

  4. Great article. Thank you. I have the MTHFR C677t mutation plus APOE 4/3 which means I don’t detox well, have reduced methylation & a higher risk of late onset Alzheimer’s. I’m 73 & started supplementing with choline a few months ago. I have noticed an improvement in my memory & the article gives me more information on the workings & necessity for continuing to supplement with this important product.

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