Hi Steve. I’d be interested in your thoughts if any on this. —C
[To name omitted], “The attached article appeared in Nature in April 2011. It is a technological tour-de-force that 1) shows a high correlation of plasma lecithin (phosphatidyl choline, PC) and two of its metabolites (TMAO and betaine) with cardiovascular disease in a 2000 patient clinical study), and 2) shows, in an experimental piece in mice, the induction of lipid-laden macrophages and 3X increase in aortic atherosclerosis in mice that were force-fed PC. To me (pending further studies) this is the kiss of death for PC supplementation. I’m throwing away my bottle of lecithin. After reading this study (if you agree with my conclusions).”
The full pdf of the article appears online at http://perruchenautomne.eu/biblio/gut%20flora%20metabolismpromotes%20atherosclerosis%20Nature%202011.pdf
Don’t believe it yet.
But it could well be a good idea to stop lecithin, PC and PUFA supplementation. As you may well remember, but others on this cc list may not, I have been warning people for decades about the health dangers of rancid fats and the antioxidant burden of unsaturated fatty acids. Fish oils are the epitome of this risk, but lecithin is included. Vegetable lecithins are rich in unsaturated fatty acids, much higher than is normally the case with animal phosphatides.
Correlations do not determine causality, and there appear to be uncontrolled variables in this study that could make the findings artefactual.
Setting the stage: More than 50 years ago, researchers fed cholesterol to rabbits to produce cardiovascular disease. This gave birth to the cholesterol-causes-heart-disease myth. People reading the study accepted the conclusions of the authors at face value. But there were serious problems in the design of the study. For example, they used rabbits, which are herbivores. Feeding an animal product to a vegetarian animal is a poor choice and likely to produce artefactual findings. This we can blame on the researchers, as their choice was deliberate. However, the “cholesterol” that they used was not actually cholesterol, but rather rancid cholesterol. Apparently, the researchers did not know this. They merely pulled a bottle labeled cholesterol off the stockroom shelves and added it to the animal feed. Cholesterol oxides are massively atherogenic, just like rancid fats (fatty acid peroxides, hydroperoxides). So the conclusions of the authors were wrong. In reality, cholesterol’s association with heart disease is trivial. I suspect that the same is true of lecithin. I will lay out some of my reasons.
1. There was no assessment of the lecithin consumed by the study participants. Much of the lecithin in commerce today is rancid. The natural antioxidants in plant lipids are damaged by stripping tocopherols for independent sale, and some formulators who replace vitamin E use alpha-tocopheryl acetate, which has no antioxidant activity and does not prevent lecithin rancidity. Many consumers take lecithin in capsule form, which bypasses the smell receptors in the nose, the taste receptors in the back-center of the tongue and induces low-level, chronic nausea instead of high-level, acute nausea that is more likely to induce vomiting. The role that rancid-fat ingestion plays in the activation of betaine-oxidizing gut-flora enzyme induction in not considered. Neither is its role in causing or aggravating cardiovascular disease.
2. The correlation between betaine oxides and heart disease can have three causal relationships: 1) the oxides cause heart disease, 2) heart disease causes choline oxidation, or 3) something else causes both. Presumably, the statistics rules out the fourth possibility that there is no causal relationship at all. (For the purposes of this discussion, let’s completely ignore the wisdom of John Ioannidis, who repeatedly points out that first (initial) studies, even when well controlled and methodologically sound, often find higher statistical correlations than subsequent studies.)
So, let’s consider them in turn.
One: TMAO (trimethylamine oxide) causes heart disease? Certainly. This is entirely plausible. The researchers may be right. Nitrogen oxides are liver toxic, carcinogenic, mutagenic and may even be teratogenic. How would we know this? Administer TMAO by multiple routes (through the gut, and bypassing the gut) and observe the results. I will go on record in predicting that a positive effect will be observed if and when they get around to studying this relationship. However, I will also preduct that the correlation will be an order of magnitude less that what they are observing in this study. I would not be surprised that it would turn out to be 100 times less.
Two: heart disease causes TMAO. Certainly, plausible again. Host-symbiont interactions are quite complex. In addition, since the samples in this study were plasma, liver enzyme alterations could be contributing. The role of cytokines on liver enzyme induction is well established. I could say more along these lines, but I do not want to flirt with certain confidential pieces of information that I cannot talk about outside of an NDA.
Three: something else causes both. This is my favorite possibility.
Rancid lecithin in the diet would be expected to induce anti-peroxide enzymatic defenses in gut microbes which could easily oxidize small-molecule amines. Peroxides are not just toxic to humans, they are toxic to single-cell organisms as well.
Concomitant use of fish and flax oils with lecithin was not assessed. The peroxidizability of PUFAs goes up non-linearly with the degree of unsaturation. The antioxidant burden of slightly unsaturated phosphatides could be greatly overshadowed by the high unsaturation of DHA, EPA, AA and linolenic acids. Fish oils are the “cure of the decade.” Lecithin’s popularity dates back to Adele Davis. I can believe that people taking lecithin and phosphatides would be more likely to take fish-oil supplements.
The recycling of glutathione, ascorbate and tocopherol depend on NADH from mitochondrial metabolism (via the NADPH transhydrogenase enzyme). PUFAs poison mitochondrial systems and accelerate mitochondrial aging mechanisms.
Other possibilities for consideration…
3. Activation of peroxisomal metabolism.
4. Cytokine induction by pre-existing inflammatory process.
5. Suppression of phagocytosis and other modulations of immune function by fatty acid peroxides.
6. Decreased dismutation of TMAO by decreased ascorbate? (like nitrosamine dismutation)
Summary: I think that stopping lecithin and fish oil is an extremely good thing to consider when the body’s antioxidant systems are compromised, a very good thing to consider when the body does not need a specific antiinflammatory medication, a good thing to consider if you do not know the rancidity status of your PUFA-containing supplements, and possibly a bad thing if you do have inflammation that is out of control. However, if the latter condition is in effect, I would suggest that lecithin and/or fish oils be used only temporarily while 1) sources of inflammation are sleuthed and eliminated, and 2) the basal metabolic rate is raised back into a healthy range so as to restore glutathione recycling, reduce inflammation, restore healing, further reduce inflammation, restore sleep architecture, further reduce inflammation, until the cycle of deferred-healing-promoting-inflammation is broken at the causal level. Although PUFAs do compensate for low metabolic rate, they sabotage the efficacy of top-down energy mechanisms (thyroid hormone, cortisol, progesterone, testosterone) and bottom-up energy mechanisms (mitochondrial membrane function).
I’d be very interested in reading additional insights on this study by others. Please include me on responses. —Steve