Building babies brains - choline

Choline is a little known essential nutrient that contributes to methylation, neurotransmitter production and supports the structure of every cell in our body. And like folate, it is critical for building a strong brain. Choline is a great example of how nutrients work together. Choline metabolism is closely related to the metabolism of several B-vitamins and methionine. The requirement for choline, folate, and methionine are all interrelated. Some of the requirements for each of these nutrients may be met by more availability of one of the other nutrients in the diet. Conversely, the requirement for choline is increased when methionine or folate intakes are deficient.
This relationship between nutrients is important and is why eat for baby encourages women to eat whole foods. No nutrient ever works in isolation. We cannot build a baby with a handful of vitamins and minerals - we need it all and of course, mother nature already has our back, providing everything we need, perfectly packaged in the bounty she provides from her fertile soil.
Why do we need choline? 
We make choline in our liver and it is stored in our cells as phosphocholine and glycerophosphocholine. Choline is the precursor to (the thing that comes before) phosphatidylcholine, an essential component of cell membranes, lipoproteins, bile and surfactants. Inadequate choline intake in adults leads to fatty liver disease because of the absence of phosphatidylcholine. Phosphatidylcholine makes the envelope portion of very low density lipoproteins (VLDL) that function to move triglycerides (fats) out of our liver cells. This is critical for the function and survival of our liver cells. When we don’t have enough choline, and we don’t make enough phosphatidylcholine, our body can’t synthesise the envelope part of the VLDL which means fats aren’t removed from our liver cells, leading to fatty liver and liver cell death. 

Choline is the precursor to acetylcholine. In the central nervous system (within our brain and spinal cord), cholinergic projections support our cognitive functions (mental processes that allow us to carry out a task). Acetylcholine has an important role in our alertness/arousal when we wake, in sustaining our attention and in learning and memory. In the peripheral nervous system (outside the brain and spinal cord) acetylcholine is a neurotransmitter at the neuromuscular junction (where our nervous system meets our muscles) where it is released by motor neurons in order to activate our skeletal muscles. 

Choline is the precursor to betaine, an osmolyte and methyl donor. As an osmolyte, betaine is essential for maintaining salt and water balance in our bodies. Betaine is produced by the mitochondria during times of high temperature, high salinity (salt) or water deprivation where it increases water retention in cells. As a methyl donor, choline is oxidised to form betaine where it donates 1 carbon units to the methionine cycle.

What about during pregnancy, why do we need choline?

When we are pregnant our bodies don’t stop any of their regular functions, in fact in most cases our bodies do more of what they did before. So as mummas, our own choline needs increase during pregnancy, plus we are responsible for the supply of choline across the placenta for our babies needs. Our babies are developing their organs during pregnancy, so we need to supply lots of phosphatidylcholine across the placenta for babies lipid membranes and surfactant production, and acetylcholine for babies nervous system and muscle function. Until our babies organs are sufficiently developed to start producing their own choline, it is our responsibility.

Adequate choline for our babies is so important that the choline transport system pumps choline against a concentration gradient (the choline moves from where there is more choline - our bodies, to where there is less choline - our babies bodies), allowing depletion of our stores of choline in order to maintain adequate choline for our babies. As a result, choline concentrations in fetal blood are normally 6-7 fold greater than those in maternal blood.

Choline is also reported to play a role in placental development. The placenta is the critically important temporary organ that forms between the mother and her fetus. The placenta serves to exchange nutrients and waste products and provide an effective communication system between mother and baby. Higher dietary intake of choline improves the signalling mechanisms responsible for placental vascularisation, angiogenesis and stress reactivity of the placenta. Researchers have concluded that adequate choline during pregnancy may mitigate some of the pathological complications of preeclampsia.

What happens if we don’t have enough choline during pregnancy?

In the US, women who eat diets low in choline during pregnancy (<150mg/day) are at increased risk of having babies with neural tube defects (4 x greater risk) and orofacial cleft (1.7 x greater risk).

There is some evidence that sufficient choline intake during pregnancy may improve our babies memory when they are children. A study of 895 mother child pairs (Project Viva) found that higher maternal dietary choline intake during the second trimester of pregnancy was associated with a modestly better child visual memory at age 7 years.

Even more recently, a study of 24 mother infant pairs showed that supplemental choline during pregnancy (~RDI of choline vs ~double RDI of choline) was considered safe and lead to faster information processing in their children up to 13 months of age. Importantly, even mothers in the lower dose group, those that were exposed to choline for the greatest time during pregnancy, had children who exhibited even faster reaction times, suggesting that adequate choline over a long period of time during pregnancy may be enough to produce cognitive benefits in humans. Follow up of the children in this study to 7 years of age, shows retention of the benefits in attention, memory and problem solving. 

How do I get enough choline?

We can make some choline ourselves, but this does not meet our physiological requirements, so it is essential in our diets. During pregnancy we can make more choline than at any other time. The gene PEMT (Phosphatidylethanolamine N-methyltransferase) that encodes the protein that catalyses (accelerates the reaction for) synthesis of phosphatidylcholine is induced by estrogen and maximum expression of PEMT is reported during pregnancy. Increased phosphatidylcholine synthesis during pregnancy is great, but the synthesis of phosphatidylcholine requires choline and the methylation of phosphatidylcholine requires choline, so we need to make sure that there is enough choline in the system for the increased synthesis we are capable of during pregnancy.

The overwhelming majority of pregnant women (90-95%) do not meet the adequate intake levels of choline. In Australia, for a pregnant woman, this is 440mg /day. Choline in foods is mostly in the form of phosphatidylcholine the component of cellular membranes. If you eat milk, meat and eggs, it's very easy to meet your daily choline needs with food. Vegetarians can derive choline from toasted wheat germ (the embryonic component of wheat), peanuts, peanut butter, spinach, Brussel sprouts and broccoli. It is more difficult to obtain adequate choline from these plant sources and you need to eat rather large quantities of some of these. Milk chocolate is a favourable source of choline as a treat. Phosphatidylcholine is commonly added to milk chocolate to help keep the cocoa in suspension, 100g of  milk chocolate can yield ~60mg of choline.

Foods Naturally Containing Choline	mg choline /100g food	Approximate Household Measure
Beef liver, cooked*	426	~½ cup / 1 slice
Chicken liver, cooked*	326	~½ cup
Egg, whole, cooked, hard-boiled	262	~2 large eggs
Salmon, cooked	218	~½ cup
Wheat germ	178	~1 cup
Shiitake mushrooms	165	1.5 cups
Beef steak cooked	64	~½ cup
Brussels sprouts	64	1 cup
Almonds	52	~½ cup
Broccoli	40	~¾ cup
Soybeans, dried	115	~½ cup
Peanut Butter	63	~⅜ cup
Spinach, cooked	24	~½ cup
* Pregnant women are not recommended to exceed 50g of liver/week due to the risk of high retinol (retinol is a preformed type of vitamin A that is stored in the liver). Excess intake of retinol has been shown to increase the risk of birth defects including malformations of the eye, skull, lungs and heart. We will cover the topic of vitamin A in a blog soon, as there is controversy around this recommendation.

In the case of choline, next to chicken or beef liver, one of the richest sources is eggs, specifically the egg yolk. Eggs have been described as nature's multivitamin and it is easy to see why - packed with vitamins and minerals, as well as all the amino acids we need to build proteins - eggs really do give us a rich bounty of nutrients. Other rich sources of choline include meat (beef liver is the richest source) and fish. Vegans and vegetarians can derive their choline from soybeans, mushrooms, kidney beans, quinoa, Brussels sprouts, broccoli, peanuts, cauliflower and green peas.

During pregnancy, to achieve your daily 440mg dietary choline requirement, you could eat:
2 large eggs  - 262mg choline
A 100g piece of salmon - 218mg
OR
50g of beef liver - 213mg *
1 cup toasted wheat germ- 178mg
1 cup Brussels sprouts - 128mg

Those not eating animal products could eat:
1 cup Brussels sprouts - 128mg
1 cup toasted wheat germ - 178mg
2 cups broccoli - 110mg
OR
3 cups shiitake mushrooms - 330mg
½ cup almonds - 52mg
1.5 cups broccoli - 80mg
¼ cup wheat germ - 44mg

Of course, you aren’t just getting choline from this bounty of goodness, you are getting iron, potassium, manganese, vitamins A, C, K, E, calcium, fibre, and the list goes on. Fewer than 95% of Australians eat the recommended number of vegetables each day (6 serves/day). This means the overwhelming majority of Australian’s are missing out on the nutrient bounty that our vegetables deliver. You can start to see why we might have so many issues with poor health and vitamin and mineral deficiencies.

Supplementation

There are not currently any recommendations for supplementation of choline during pregnancy. The RDI during pregnancy is negligibly higher than for non-pregnant women (415 to 440mg). 

Are there risks associated with high choline intake?

High intakes of choline are associated with a fishy body odour, vomiting, excessive sweating and salivation, hypotension and liver toxicity. The upper limits for choline intake are 3500mg/day based on studies of dementia patients who were administered 7.5g/day choline and presented with hypotension, nausea and diarrhoea. Consumption of choline increases production of trimethylamine N-oxide (TMAO), a gut derived metabolite, which has emerged as a candidate risk factor for cardiovascular disease. Most recent evidence suggests that rather than TMAO itself being the candidate, instead it is the diversity of the gut microbiome and the ratio of Firmicutes vs Bacteriodetes that have the greatest effect. This is a current area of research debate and further results need to be made available before any further conclusions are drawn.

Eat for You Suggestions

Australian women are recommended to consume 440mg/day of choline throughout gestation, increasing to 550mg/day during the lactation period. Eating the right foods, the ones that nourish our bodies, is about so much more than looking good and maintaining a healthy weight - food is the very basis of who we are. Our bodies are literally made up of the vitamins and minerals we eat, and the cellular components and proteins and amino acids produced from the foods we eat. As mothers to be, this is our most critical job, to provide our babies cells with the very best nutrients needed to build strong cells and communication networks. Think of pregnancy as laying the foundations for your baby’s future health. Get the foundations right and the rest will take care of itself. Add choline to your list of nutrients to think about when making your whole food choices during pregnancy. We wonder if choline levels have anything to do with the mysterious pregnancy brain fog that affects many women - given its critical role as a neurotransmitter in the memory and mood parts of the brain, we think this is something that should be investigated.

Choline is one of many abundant and beneficial vitamins that we can derive from a diet high in animal materials. It will help us to thrive during pregnancy and in everyday life. Choline is easy to derive from a diet containing animal products. If you do not eat animal products you may like to choose a prenatal supplement that contains some choline to support your daily choline needs, although it is possible to achieve your daily choline needs through non-animal sources. We suggest seeking advice from your care providers on whether you need to take supplements. 

It is our position that food will always be the best option for getting our vitamins and minerals. We have shown you how easy it is to obtain your daily choline requirements from food. What we eat matters for our health, and our future babies health. Choline isn’t a nutrient we hear a lot about, but it is critical for the healthy development of our babies brain and must be considered a part of our pregnancy nutritional needs. 

References

Boeke CE, Gillman MW, Hughes MD, Rifas-Shiman SL, Villamor E, Oken E. 2013. Choline intake during pregnancy and child cognition at age 7 years. American journal of epidemiology. 177(12):1338-1347

Caudill MA, Strupp BJ, Muscalu L, Nevins JEH, Canfield RL. 2018. Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study. FASEB J 32(4):2172-2180

Kovacheva VP, Mellott TJ, Davison JM, Wagner N, Lopez-Coviella I, Schnitzler AC, Blusztajn JK. 2007. Gestational choline deficiency causes global and Igf2 gene DNA hypermethylation by up-regulation of Dnmt1 expression. J Biol Chem. 282(43):31777-88.

Ozarda IY, Uncu G, Ulus IH. 2002. Free and phospholipid-bound choline concentrations in serum during pregnancy, after delivery and in newborns. Arch. Physiol. Biochem. 110:393–99

Zeisel SH, Wurtman RJ. 1981. Developmental changes in rat blood choline concentration. Biochem. J. 198:565– 70

Zeisel SH, Mar M-H, Zhou Z-W, da Costa K-A. 1995. Pregnancy and lactation are associated with diminished concentrations of choline and its metabolites in rat liver. J. Nutr. 125:3049–54

Zeisel SH, Mar MH, Howe JC, Holden JM. 2003. Concentrations of choline containing compounds and betaine in common foods. J. Nutr. 133:1302–7

Ziesel SH. 2013. Nutrition in pregnancy: the argument for including a source of choline. International Journal of Women’s Health. 5:193-199

Wallace TC, Blusztajn JK, Caudill, MA, Klatt KC, Natker E, Zeisel SH, Zelman KM. 2018 Choline. The underconsumed and underappreciated essential nutrient. Nutrition Today. 53(6):240-253

Written by

Dr Hayley Dickinson, PhD

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