Heart Health

Choline and CVD Risk: A Relationship Worth Watching

Choline and CVD Risk: A Relationship Worth Watching
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Elevated blood pressure and cholesterol levels are the two best recognized cardiovascular disease (CVD) risk factors that are known to be affected by diet. There may be many more of these risk factors, however, including impaired endothelial function, arterial stiffness and elevated C-reactive protein levels.  Platelet aggregation is another risk factor that is affected by diet and the interaction appears to occur through a newly discovered pathway which involves choline.

In 2011, U.S. researchers proposed that dietary choline is transformed by gut microflora to trimethylamine, a compound that is oxidized in the liver to trimethylamine N-oxide (TMAO).1  TMAO in turn interacts with surface expression levels of macrophage scavenger receptors which are known to participate in the atherosclerotic process.

Recent research involving nearly 2,000 men and women found that fasting levels of TMAO have a dose-dependent relationship with cardiovascular disease. In both vegetarians and non-vegetarians, choline supplementation caused increases in TMAO levels that were dose-dependently associated with platelet aggregation.2  Furthermore, platelet hyper-responsiveness associated with choline supplementation and elevated TMAO levels was inhibited by aspirin administration.  Interestingly, aspirin also partially inhibited the rise in TMAO that resulted from choline supplementation, presumably by changing the composition of the intestinal microflora.2

Choline is used in the synthesis of certain phospholipids (phosphatidylcholine and sphingomyelin) that are essential structural components of cell membranes.  Phosphatidylcholine accounts for about 95% of total choline in tissues.3  Despite its link to increased risk for CVD, however, choline is an essential nutrient and intake typically falls short of recommended intakes of 425 mg for women and 550 mg for men.4  Among participants in the Framingham Offspring Study the mean intake for total choline was only 313 mg/d; moreover, there was an inverse association between choline intake and plasma total homocysteine concentration in subjects with low folate intakes.5  According to NHANES 2007-2008, mean dietary intakes of choline were approximately 260 mg/d for women and 396 mg/day for men.6

Major contributors to choline in the American diet, are meat, poultry, fish, dairy foods, pasta, rice, and egg-based dishes.7  The richest sources of choline are beef liver (418 mg/serving), chicken liver (290 mg), eggs (251 mg), bacon (125 mg), cod (84 mg) and ground beef (80 mg).8 Tofu provides about 27 mg per serving.8

Phosphatidylcholine, which is also known as lecithin, is widely used by the food industry as an emulsifier. Commercial lecithin is usually prepared from soybean, sunflower, and rapeseed, and may contain anywhere from 20%-90% phosphatidylcholine.9 Lecithin in processed food from all sources has been estimated to increase the daily consumption of phosphatidylcholine by only about 1.5 mg/kg of body weight for adults.10

Given that U.S. intake is below recommendations and that lecithin in processed foods provides modest amounts of choline, there is no reason to be concerned about the widespread use of this emulsifier. Furthermore, there are a number of potential benefits of choline.11 The possible relationship between choline and CVD warrants consideration but at this point, the evidence does not suggest altering diet habits that are consistent with current dietary guidelines.

1. Wang Z, Klipfell E, Bennett BJ, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472:57-63.
2. Zhu W, Wang Z, Tang WHW, Hazen SL. Gut microbe-generated trimethylamine N-oxide from dietary choline is prothrombotic in subjects. Circulation. 2017;135:1671-3.
3. Ueland PM. Choline and betaine in health and disease. J Inherit Metab Dis. 2011;34:3-15.
4. Jensen HH, Batres-Marquez SP, Carriquiry A, Schalinske KL. Choline in the diets of the US population: NHANES 2003–2004. FASEB J. 2007;21:1b219.
5. Cho E, Zeisel SH, Jacques P, et al. Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. Am J Clin Nutr. 2006;83:905-11.
6. Craig SA. Betaine in human nutrition. Am J Clin Nutr. 2004;80:539-49.
7. Chester DN, Goldman JD, Ahuja JK, Moshfegh AJ. Dietary intakes of choline. What we eat in American, NHANES 2007-2008. US Department of Agriculture; 2011.
8. Zeisel SH, Mar MH, Howe JC, Holden JM. Concentrations of choline-containing compounds and betaine in common foods. J Nutr. 2003;133:1302-7
9. Koc H, Mar MH, Ranasinghe A, Swenberg JA, Zeisel SH. Quantitation of choline and its metabolites in tissues and foods by liquid chromatography/electrospray ionization-isotope dilution mass spectrometry. Anal Chem. 2002;74:4734-40.
10. Food and Nutrition Board, Institute of Medicine. Choline. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington D.C.: National Academy Press; 1998:390-422.
11. Kullenberg D, Taylor LA, Schneider M, Massing U. Health effects of dietary phospholipids. Lipids Health Dis. 2012;11:3.

Dr. Mark Messina

Author Dr. Mark Messina

PhD in Nutrition, Executive Director, Soy Nutrition Institute. Expert in soyfoods and isoflavones.

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