Cardiovascular Disease: What’s Choline Got to Do With It? background image
November 01, 2017

Cardiovascular Disease: What’s Choline Got to Do With It?

Dr. Thomas Wnorowski profile image

Dr. Thomas Wnorowski

PhD, CNCC Research Director, BodyBio & Biomedical Nutritionist

Our Answer to the 2011 Study in Nature ‘Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease’

Phosphatidyl Choline (PC) is the largest of the phospholipids that comprise the membrane of our cells. PC is also prominent in egg and soy lecithin. While PC may be the largest of the phosphatides in lecithin there are other principle phospholipids, phosphatidyl-ethanolamine (PE), phosphatidyl-inositol (PI), phosphatidyl-serine and phosphatidic acid that together, constitute a higher concentration in lecithin than does PC. Soybeans are the principle source of commercial lecithin, and lecithin is the most important by-product of the soy oil processing industry because of its many applications in foods, cosmetics and industrial products. Lecithin is also available as a dietary supplement in two forms: as granular lecithin which contains ~12% PC (calcium phosphate as a flow agent), and in a concentrated form called triple lecithin at ~35% PC in capsules fluidized with soy oil (Wood and Allison 1981). While lecithin has been on the health food scene for over a half century, somehow, it picked up the perception of being called phosphatidylcholine. Many researchers used the two interchangeably as if they were the same. They are not. Lecithin is not PC, and while PC is the largest phosphatide in lecithin, technically, it is only a chemical component of lecithin. Oddly, no one reverses it by saying PC when referring to lecithin.

In April, 2011 in an article in Nature, Gut flora of phosphatidylcholine promotes cardiovascular disease, Wang et al wrote that “Foods rich in the lipid phosphatidylcholine (PC, also called lecithin)* which predominantly include eggs, milk, liver, red meat, poultry, shell fish and fish, are believed to be the major dietary sources for choline”. Note the age-old error again. However, confusing PC and lecithin pales in comparison to the egregious characterization in the title saying that “phosphatidylcholine promotes cardiovascular disease”. We must presume the authors to be knowledgeable of the long and voluminous history of PC as the largest phospholipid component of our cellular membranes and especially as a nutrient with its quite exceptional history in alleviating heart health disorders specifically cardiovascular disease. The title ‘Gut flora of phosphatidylcholine promotes cardiovascular disease’ completely disregards the scientific history of PC and casts a disturbing and untrue image of a highly valuable nutrient with a long history of lowering cholesterol and successful treatment of atherosclerosis, (Cho BH 2011, Navab M 2003, Chung BH 2005, Hajj Hassan H 2005, Koizumi J 1988, Ke Y 1996, Ovesen L 1985). The title could be correct if lecithin was used, which if intended, should have been so stated.

The disturbing title further calls in question the veracity of what appears to be significant scientific information. The implication of PC as potentially dangerous is simply wrong; however, if lecithin was used, the study becomes of significant value for shedding light on the difficulty of using lecithin as a nutrient. While there have been a large number of studies over the last 50 years using lecithin as a source for PC, the effort to achieve medical benefits have been plagued with mixed results, while the reverse of using phosphatidylcholine has consistently maintained positive medical results particularly in international studies. Research and clinical experience has revealed that PC is possibly the most prestigious nutrient of all (Yechiel and Barenholtz 1985, Cui and Howling 2002).

* The authors again make the mistake of referring to PC as Lecithin.

Rhone Poulanc, in its brochure for Lipostabil, lists 197 references for oral and i.v. administration of PC for hyperlipoproteinemia and atherosclerosis. Gundermann KJ, PhD, MD, in “The Essential Phospholipids as a Membrane Therapeutic” 1993, has 776 referenced studies in his technical manual which covers the use of PC in toxicology, hemorrheology, lipid peroxidation, alcohol and diabetic fatty liver, malnutrition, kidney, cirrhosis, gastrointestinal, neurological, lung, psoriasis, MS, cerebral circulation, elevated lipids, atherosclerosis, even drug enhancement. It is a thorough review of PC research published from 1959 to 1993, which portrays a positive image of PC quite the opposite as in the Nature study.

Using lecithin as a source of PC is a poor scientific approach because the phospholipids within lecithin are oil based. The PC used in the European studies was either egg PC, or, if soy lecithin based, the oil had been purged and the phospholipids were isolated. In the 1940s, Nattermann GMBH, successfully produced a high concentrated PC from lecithin in an oil free form called Phospholipon which was the source for the PC used in all the medical studies previously mentioned. The formation of the membrane occurs in water and cannot occur if the lipid tails of the phospholipids are immersed in oil. Oil and water do not mix, but oil and oil mix very well. All life on the planet is water based and depends on the “hydrophobic effect” to drive the formation of the membrane of all cells. There is little excuse for the continued PC / lecithin confusion or the implication of PC as a troublesome nutrient.

Under normal digestion, PC and all lipids ingested are degraded by lipases in the gut. The phospholipids and the triglycerides are reduced by enzymes PLC or PLD which attack the head groups (choline, ethanolamine, etc) with PLA1 or PLA2 doing the same for the lipid tails. The PC research reports referenced above did not use raw lecithin as a source of PC. The majority of the PC was either i.v. Essentiale (Aventis) or Lipostabil (Rhone Poulanc) or, as a PC capsule “Forte” under both labels. Forte is currently available in most European and Eastern European pharmacies, i.v. Essentiale is available in Eastern Europe and the US, all of which used phosphatidylcholine that originated from Nattermann, which, as already indicated, is no longer lecithin.

In the 2011 Nature paper by Wang et al, there are 18 listed authors from the Cleveland Clinic, UCLA, Cleveland State, and USC. It is appalling that such a prestigious journal, Nature, would permit such gross error in basic biochemistry. The article does indeed help to resolve the age-old problem of why lecithin has consistently failed to provide positive results as a phosphatidylcholine nutritional supplement, because it isn’t phosphatidyl choline. The implication of Choline and TMAO in CVD was also corroborated in a number of studies prior to the Nature study such as recent publications from Italy in 2005, UNC in 2007, Emory and Aventis in 2009 and from Germany in 2007 - 2010, to name a few. However, none of these publications mentioned lecithin or even PC as a critical choline source or of PC in promoting cardiovascular disease. In light of the abundant positive research for phosphatidyl choline for over half a century, the choice of the title in the April 2011 Nature paper borders on scientific ignorance and demands a retraction.

In the Nature study it is prudent to bear in mind that the laboratory animals were inbred strains, predisposed to CVD.

There is clear evidence that choline released from the cell membrane by ischemia-related cytolysis may be used as a predictor of cardiac events in the presence of chest pain, despite low levels of troponin. (Danne, 2007) In this regard, choline elevation is a result of tissue damage (vulnerable plaque), and is not a causative agent.

Specific gut bacteria will degrade choline to trimethylamine, which is then oxidized by the liver to TMAO. The liver enzyme, Hepatic Flavin Monooxygenase 3 (FMO3) is responsible for the conversion. (It may be important to note that this is a “flavin” enzyme, dependent upon riboflavin for its activity. Without further attention, it is unseemly to indict this B vitamin as part of the etiology of CVD.) TMAO—and its companion choline metabolite, betaine—promote upregulation of multiple macrophage scavenger receptors as part of the inflammatory cascade, following platelet activation and monocyte adhesion, but preceding the formation of macrophage foam cells from the endocytosis of oxidized LDL and the subsequent smooth muscle cell migration from vascular epithelium that forms protective fibrous caps. Foam cells that accrue from this phagocytosis comprise the fatty streaks of the plaques of atheroma in the vascular intima. Foam cells necrotize and cause the fibrous cap to rupture and form a thrombus which can lead to emboli capable of occluding smaller blood vessels.

Knowing that gut flora may generate a pro-atherosclerotic metabolite has aroused interest in probiotic research. Lactobacillus rhamnosus appears to potentiate the colonic manufacture of TMAO, while L. paracasei has inhibitory properties on the formation of TMAO. Both strains are dose-dependent. If the inflammation induced by TMAO can be eliminated, or at least curtailed, the number of related cardiac events can be limited. Disrupting the inflammatory cascade that provokes foam cell induction may be as simple as preventing the oxidation of LDL in the first place. Several dietary components have demonstrated the capability to prevent LDL oxidation, including capsaicin, curcumin, and several bioflavonoids.

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