Recent studies confirm (PC) phosphatidylcholine supplements do not raise TMAO (trimethylamine N-oxide).

Nutrasal has long maintained that dietary choline in the form of Highly Purified Phosphatidylcholine (PPC) was not increasing TMAO, platelet aggregation and CVD. We have advocated for the continued administration of PPC as a good source of biologically preferred choline and phosphatidylcholine as a cell membrane therapeutic and for use in liver, heart, brain and gut health, among others.

We based our position on the available TMAO research at the time which we believed to be tenuous at best and significantly biased in favor of creating misleading and sensational results. When analyzing the initial TMAO research we quickly realized that the body of work was limited, and it specifically never included phosphatidylcholine supplementation. Clinical studies never established a correlation between phosphatidylcholine and TMAO and any inference or assertion to PC administration contributing to TMAO and CVD was never supported by research. When we compared the limited TMAO data to the depth and breadth of clinical and pharmacological research confirming the many positive health effects and therapeutic benefits of PC it became reasonable to conclude that the administration of highly purified PC should be continued.

Now, more recent studies published in Nutrients and The American Journal of Clinical Nutrition support our conclusion. 

Phosphatidylcholine Background

The use of highly purified phosphatidylcholine has a very long and successful track record. Hundreds of clinical trials and an even greater number of pharmacological investigations have confirmed the holistic, physiological, and therapeutic effectiveness of PPC in heart disease, liver disease, brain development, cognitive and memory function, and gut health, among other indications.  Additionally, PPC has been prescribed worldwide since 1953 for liver disease and heart disease. PPC has consistently demonstrated positive results with an outstanding safety profile. Billions of doses have been administered over 70 years and no significant side effects, contraindications, or interactions are known or reported.

Physiological role of Phosphatidylcholine

Phosphatidylcholine is the main active component of lecithin and a metabolic precursor for choline. PPC is the 100 percent active form of lecithin/PC. Phosphatidylcholine is important for the structural integrity of cell membranes, cholinergic neurotransmission, transmembrane signaling, methyl metabolism, and lipid-cholesterol transport and metabolism. Choline is a precursor for phosphatidylcholine, sphingomylin, platelet-activating factor, betaine, and other phospholipids.  Phosphatidylcholine is the body’s storage mechanism for glycerophosphocholine (GPC) and for Choline. Choline speeds the synthesis and release of acetylcholine, an important neurotransmitter involved in numerous important functions in the body.

Choline is an essential nutrient since the body’s own production of choline is not always sufficient to meet human requirements for choline. Especially as we age and the need for more choline to form PC for cell membrane formation, repair, restoration and regeneration is in much higher demand.

Phosphatidylcholine is a biologically preferred dietary source for choline and an essential building block for all cell membranes and for life. Without PC cell membranes can not form and without cell membranes all organic life as we know it could not exist.  PC is fundamental to good health and to life.

Studies of Interest:

As study conducted by researchers at Cornell University and Utah State University evaluated the “Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men.”  The author’s concluded that high TMAO was more likely caused by choline bitartrate supplementation and not Phosphatidylcholine. (1)

Significant Clinical Findings and Discussion:

• Consumption of choline bitartrate, but not phosphatidylcholine, leads to greater TMAO production and that gut microbiota composition contributes to alterations in TMAO response to choline bitartrate.
• Choline bitartrate yielded 3-times higher plasma TMAO AUC and 4.4-times higher plasma TMAO maximum increase from baseline compared to phosphatidylcholine and no choline control.
• TMAO change from study-baseline and AUC after phosphatidylcholine consumption
• did not differ compared to that of no choline control despite higher circulating and urinary free choline concentrations.
• Given that phosphatidylcholine is the major form of choline in food, the absence of TMAO elevation with phosphatidylcholine counters arguments that phosphatidylcholine should be avoided due to TMAO-producing characteristics.

A study conducted by the Lerner Research Institute and the Cleveland Clinic; and published in The American Medical Journal concluded dietary choline from eggs and supplemented choline in the form of Phosphatidylcholine (PC/PPC) does not raise TMAO or contribute to platelet aggregation. (2)

Significant Clinical Findings and Discussion:

• Daily dietary free choline supplementation (especially choline bitartrate) for 28 days significantly raised fasting trimethylamine-N-oxide (TMAO) levels in plasma and urine, and increased platelet aggregation responsiveness to submaximal agonist.
• The daily consumption of eggs or phosphatidylcholine, containing an equivalent total choline content to the free choline, failed to increase TMAO or platelet aggregation.
• The form of choline in dietary nutrients differentially contributes to gut microbiota-dependent TMAO generation and systemic TMAO levels.

Conclusion

Nutrasal is of the opinion that supplemented phosphatidylcholine as a choline donator and cell membrane therapeutic does not contribute to TMAO increase, platelet aggregation and CVD.

Considering 70 years of safe and effective administration, thousands of clinical and pharmacological studies confirming the therapeutic benefits of phosphatidylcholine supplementation, and the most recent randomized and controlled studies establishing phosphatidylcholine supplements failed to increase TMAO and platelet aggregation; there should be no objection in using phosphatidylcholine as a dietary supplement.

PhosChol is the leading practitioner brand of purified PC since 1982.  For more information visit: Doctor Recommended PhosChol (nutrasal.com)

References:

1. Choe C. E. et al. Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men, Nutrients July 25, 2020
2. Wilcox, J., Skye, S. M. et al. Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. The American Journal of Medicine, Volume 134, ISSUE 9, P1160-1169.e3, September 01, 2021