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Here is a super interesting study, showing another method of bypassing the TMAO problem:

https://ahajournals.org/doi/abs/10.1161/circ.130.suppl_2.13412

Abstract 13412: 24-Hour Water-Only Fasting Acutely Reduces Trimethylamine N-Oxide: the FEELGOOD Trial

Benjamin D Horne, James E Cox, Joseph B Muhlestein, Viet T Le, Amy R Butler, Heidi T May, John F Carlquist and Jeffrey L Anderson

Originally published27 Mar 2018Circulation. 2014;130:A13412

"Abstract

Background: Routine, periodic fasting is associated with lower risk of diabetes and coronary artery disease (CAD), and may reduce weight and improve metabolic parameters. Multiple related biological pathways are acutely affected by water-only fasting, potentially leading to long-term health improvements including lower CAD. Trimethylamine N-oxide (TMAO) is produced by intestinal bacteria and may increase CAD risk. This study evaluated the change in TMAO due to fasting in apparently healthy people.

Methods: The FEELGOOD Trial (clinicaltrials.gov NCT01059760) included subjects free of cardiovascular disease who had never fasted for more than 12 hours (N=24). All individuals participated in a randomized cross-over trial of 24-hour water-only fasting and 24 hours of ad libitum eating. In this secondary analysis of stored samples, TMAO was measured by liquid chromatography-mass spectrometry.

Results: Age averaged 43.6±13.5 years, 66.7% were female, and baseline TMAO averaged 27.1 ng. TMAO was reduced at the end of the 24-hour fasting intervention compared to the eating day (14.3 ng vs. 28.2 ng, p=0.034). The change in TMAO during the fasting day averaged -10.8 ng compared to an average increase of +2.6 ng during the eating day (p=0.23). For those randomized to fast the first day, the difference in TMAO change on the fast day vs. eating day (-12.1 ng, n=12) was similar to the TMAO change of those randomized to eat on the first day (-14.6 ng, n=12). For those who fasted the first day, TMAO levels were found to have returned to baseline after the full 48 hours of the study (baseline: 22.5 ng, 48 hours: 28.8 ng, p=0.55).

Conclusion: Water-only 24-hour fasting reduced plasma levels of TMAO, a potential risk factor for CAD. The rapid resumption of TMAO production after renewed caloric intake suggests that fasting-reduced TMAO likely resulted from elimination of the substrate for TMAO production. Elimination of TMAO-producing bacteria may also account for this, but recolonization likely would take more time than it was observed to take for resumption of TMAO production. These findings suggest that routine, periodic fasting (multiple episodes over time on a regular basis) may have long-term impact on TMAO levels and related CAD risk, but this requires further investigation."

I'm on a combination of 5:2 and 16:8 diet - I attempt to leave at have 16 hours of fasting every single day, usually closer to 18 hours, so I skip breakfast and eat lunch and dinner within 6-8 hour span; additionally on two days a week (Monday and Thursday), I only eat lunch and skip dinner altogether, i.e. very low calorie days 400 cal. more or less (which also then results in a 22 hour fast). I was already thinking about transitioning from eating anything on those two days - i.e. fasting for a total of 40-42 hours on those days. That gives me two water only fasting periods a week. Now it seems might even be useful wrt. TMAO. YMMV. 

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Tom,

I’m also doing the 16-8 five days per week and 1 meal on two non-consecutive days (500 cals).

Combining that with optimal nutrition and resistance training 3 days per week.

 Clinton 

 

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Tom,  thanks for pointing out this study.   I found a more recent full text article elaborating on the same study.

Pilot Study of Novel Intermittent Fasting Effects on Metabolomic and Trimethylamine N-oxide Changes During 24-hour Water-Only Fasting in the FEELGOOD Trial (2019)

Apparently the study shows that if you eliminate the substrate for TMAO production,  TMAO production ceases,  which would seem to be quite predictable.  There appears to be no effect on the TMA-producing bacteria themselves, since upon resumption of food intake, there is a rapid resumption of TMAO production.

 

Quote

During the fasting period of the study, TMAO levels were substantially decreased during the fasting day compared to the fed day. However, during the fed period, TMAO production rapidly returned back to concentrations similar to baseline levels. The change score for the fasting day compared to the fed day was not statistically significant, but the improvement in TMAO was tightly controlled, with substantially less variation when fasting than at the fed or baseline measurement.

This TMAO reduction followed by a resumption of baseline levels is likely a result of elimination from the body of the substrate needed to produce TMAO [11].

 

The possibility that the TMA-producing bacteria are eliminated during fasting is seen as highly improbable:
 

Quote

Alternatively, the bacteria that produce TMAO may have been eliminated from the gastrointestinal tract during fasting. While more difficult to conceive of how this may occur in a 24-h period, this also would not explain the rapid resumption of TMAO produced within the day of feeding. Likely, recolonization of the bacteria within the intestine should take lontger than the one day observed for TMAO production to resume [10].

 

While fasting does give the cardiovascular system a short break from TMAO production,  it would be entirely  speculative to infer a long-term positive effect via that mechanism.

Quote

This lack of substrate  [during fasting] may be as simple as the elimination of matter from the gastrointestinal tract during fasting and could lead to a period of physiological rest from the cardiovascular risk associated with TMAO.

*  *  *  *  *

[...] The long-term effects of fasting on TMAO should be researched in future studies to determine the full implications for human health.

 

In summary,  intermittent fasting would produce intermittent breaks from TMAO production but would not reduce the total amount of TMAO production in a given extended period. Those intermittent TMAO breaks may or may not have positive effects.  

In order to reduce total TMAO production over a longer period,   it seems one would have to:  1) reduce substrate (choline, carnitine etc.) and/or 2) reduce TMA-producing gut bacteria (through diet,  cruciferous vegetables,  garlic etc. intake,  etc.), and/or 3) reduce the conversion of TMA to TMAO in the liver (as discussed previously.)

Intermittent fasting no doubt has positive effects through various mechanisms apart from TMAO reduction.  And there is still no compelling evidence that TMAO production is a problem for healthy folks on a low-calorie plant based diet who aren't supplementing with substantial amounts of choline/PC or carnitine.

Edited by Sibiriak

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11 hours ago, Sibiriak said:

.

11 hours ago, Sibiriak said:

In order to reduce total TMAO production over a longer period,   it seems one would have to:  1) reduce substrate (choline, carnitine etc.) and/or 2) reduce TMA-producing gut bacteria (through diet,  cruciferous vegetables,  garlic etc. intake,  etc.)

 

Yes.  The bottom line:  Have a good CRONnie diet, mostly plants, possibly a small amount of fish, no red or white meat,  HAVE a lot of TMAO.  The takeaway:  Dietary TMAO (as in fish) can be ignored.

Sort of similar to shrimp and LDL cholesterol:  Shrimp have cholesterol; but eating them won't raise your LDL cholesterol.

  --  Saul

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