Choline seems to be tagged as the new folate in the pregnancy world. Indeed, the evidence is accumulating and strongly suggesting that being Choline replete (like folate and B12) is important for preventing neural tube defects . Further to this, adequate maternal choline status appears to support healthy brain development and may even have positive effects on offspring temperament [1, 2]. The requirements during preconception, pregnancy and lactation can be hard to achieve with most parents and potential parents falling short of these [3-5]. Most health bodies are recommending 450mg during pregnancy and 550mg during lactation, while some authors are suggesting these targets should be higher [3, 6]. So, we find ourselves scrambling to include this in our already bulging pregnancy nutrition support recommendations. If you don’t have time to read the full blog cut to the last paragraph for our bottom line on this topic!
With this news it’s not surprising to see choline starting to be included in prenatal multivitamins and several brands have taken this a step further and brought out higher potency choline supplements, often combining choline with important prenatal nutrients like DHA and iodine. That’s a good thing right? Well, yes it probably is – although there is a catch. The form that is being included in supplements is typically Choline Bitartrate and it seems it may lead to an increase in serum trimethylamine-N-Oxide (TMAO for short) according to three human clinical intervention studies [7-9].
TMAO is gaining recognition as an important risk factor for metabolic and cardiovascular disease with dose response associations  [11-13] , which is of course, a pretty on the nose status to have. It is proposed that TMAO plays a role in vascular inflammation and calcification as well as plaque instability . Furthermore, and of particular interest here, there is preliminary evidence from cohort studies suggesting higher plasma levels of TMAO are associated with gestational diabetes, pre-eclampsia, and potentially poorer fertility [16-19], although not all study findings corroborate .
What has this got to do with the microbiome? Well, Trimethylamine-N is formed by the gut microbiota from precursors such as L-carnitine, principally from red meat and potentially from choline and betaine. [21, 22] Trimethylamine-N is further oxidized in the liver to form trimethylamine-N-oxide TMAO.  The good news is that overall dietary choline does not appear to raise TMAO for the most part, or be associated with cardiovascular disease . Further, the majority of human intervention studies looking at supplementing with eggs or choline as phosphatidylcholine do not observe a rise in TMAO associated with these interventions [8, 9, 25-27]. However, there may be some populations that are susceptible to a rise in TMAO following any choline intake and this may be in part related to microbiome and genetic features. [27, 28]
An important comment to make is that not all studies investigating choline bitrate supplementation have observed an associated TMAO rise [28, 29]. However, we feel the three studies that have suggested this give us good cause for caution and a bit of a re-think on how we support optimal choline status during preconception and pregnancy, especially with the growing awareness of TMAO being associated with poor pregnancy outcomes discussed earlier.
Of interest most of what we know about the health effects of choline during the perinatal period relate to dietary intake of this nutrient, which would commonly be found in the form of phosphatidylcholine in foods like eggs. So, the other consideration to pose is whether supplementing with Choline bitartrate would afford the same protections and health benefits clinically as dietary intake of this nutrient?
So now… with this in mind how do we get those choline levels up in a health promoting way? One possibility is recommending lecithin as a rich source of choline, and it would seem that sunflower lecithin is a particularly good source with 10g providing approximately 330mg of choline . Eggs are of course a fantastic source with the average egg providing 125mg of choline.
What about the microbiome? Well, yes this may be a target for us to work on to reduce an individual’s tendency to make TMAO in the first place. This is an area to watch as the research comes together. But the themes coming through are probably unsurprising. Diets high in plant foods, polyphenols, prebiotics and low in red meat, animal foods and saturated fat all seem to be helpful [21, 31-34]. Somewhat comforting to see is the preliminary evidence to suggest one of our favourite probiotic strains Lactobacillus rhamnoses GG could also help lower TMAO .
What’s the bottom line here? Choline is an important nutrient to take care of during preconception, pregnancy and lactation. The form we give may matter and there seems to be a potential for Choline bitartrate to be more likely to promote higher plasma TMAO which could be harmful. Balancing the risks, it is easy to argue that it is more important to have adequate choline then not, but where possible it makes sense to support optimal choline status using dietary source or supplements containing phosphatidylcholine. And finally, we may be able to prevent TMAO rises through promoting wholefood, plant-based diets and optimising microbiome health.
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2. Nicholas, D., et al., Infant Temperament: Exploring The Potential Role of Maternal Dietary Choline and Folate Consumption During Pregnancy in a Michigan Pregnancy Cohort. Curr Dev Nutr. 2022 Jun 14;6(Suppl 1):697. doi: 10.1093/cdn/nzac061.081. eCollection 2022 Jun.
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