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Choline and Memory

Choline is an essential nutrients in humans and because it is only produced in very small amounts, it needs to be ingested either in food or as supplement. There are overwhelming clinical evidence that choline can improve memory, and it does this through multiple mechanisms. Read on to find out why choline is important and why early supplementation is advised to prevent cognitive decline.
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What is Choline?

Choline refers to a group of water-soluble, quaternary ammonium salts. It is an essential nutrient and also sometimes classified as part of the B vitamins.

Choline is especially renowned as a precursor of acetylcholine, an important neurotransmitter in the brain involved in memory, muscle activities and other functions. Choline is also essential in the body because it is used to make structural components (phospholipids) of cell membranes.

Since the human body only makes a small amount of choline, dietary sources of the nutrient are very important.

The recommended adequate intake value for choline varies by age and sex. Children normally require 125 – 250 mg/day. Adult males need 550 mg/day of choline while adult females need 425 mg/day. The upper limit for choline is 3500 mg/day for adults, 3000 mg/day for teenagers and 1000 mg/day for children.

The choline demand by the body increasing during pregnancy and lactation. This is because choline is essential support the development of the nervous systems of fetuses and infants. Therefore, the recommended daily intake of choline for pregnant women is 450 mg/day and for lactating women, the value is 550 mg/day.

Excellent dietary sources of choline include raw beef liver, hardboiled egg, chicken, cod fish, cauliflower, wheat germ, low-fat milk, soy lecithin, tofu, spinach, almonds, peanuts and cooked brown rice.

Given that choline is required for the structural integrity of cell membranes, for cellular communication and for synthesizing acetylcholine, its deficiency can have some serious effects.

Signs of choline deficiency include growth impairment, hypertension and infertility.

This deficiency will also cause bone abnormalities, fatty liver and liver necrosis. Choline deficiency has also been shown to cause and increase carcinogenic activities in the body.

Although, it is estimated that most of the population consume less than the recommended daily intake of choline, those at the greatest risk of choline deficiency include vegans, vegetarians and endurance athletes. Drinking a lot of alcohol can also cause choline deficiency.

Choline Dietary Supplements

There are different forms of choline supplements. The most popular source of choline supplementation is the food additive, lecithin, derived from either soy or egg yolks.

Phosphatidylcholine is another supplementary source of choline. It is sold as a pill and powder.

However, it is choline chloride and choline bitartrate that are usually referred to as choline supplements. The chloride salt is usually preferred because it does not have the gastrointestinal side effects of phosphatidylcholine.

In addition, infant formula that are not prepared from cow’s milk are required to add choline.

A number of studies in different animal models has proven that choline supplementation during pregnancy can improve cognition in offspring. However, care should be taken with choline supplementation in pregnant women who smokes because while choline supports and protects certain parts of the brain, it actually causes brain damage in some other parts when combined with nicotine.

The choline supplied to the body in supplements can easily cross the blood-brain barrier.

Choline may be insoluble in lipids but a special transporter ferries it across and into the brain where it can enhance memory and other aspects of cognition.

Choline supplements are also sometimes used as drugs in the treatment of glaucoma, atherosclerosis, hepatitis, Alzheimer’s disease, bipolar disorders and other neurological disorders.

Choline is also a common supplement to help those suffering from alcoholism.

Choline and Brain Development

During Pregnancy

During pregnancy, the body’s demand of choline rises as its store of the compound falls. Also at this stage, most of the choline found in pregnant women accumulates in the placenta.

Usually, there is ten times as much choline in the amniotic fluid than in the mother’s blood.

The high demand for choline during pregnancy and lactation fills both the needs of mother and child. However, it is the special role of choline in brain development that takes up most of the choline supply.

Choline is used for making cellular membranes which is required during the period of rapid growth of human brain (from third trimester of pregnancy to the fifth year of the child). The body uses choline to make phosphatidylcholine which is then turned into sphingomyelin, the material used to insulate nerve fibers.

Choline is also turned to acetylcholine which is required for producing new nerve cells, sheathing neurons with myelin, establishing neurons and organizing the neuronal networks that make up whole sections of the brain.

While there are other uses for choline in the developing fetus, the priority remains the production of phospholipids for neurons.

Choline is also required for neural tube closure (the primarily role of folic acid in the prenatal vitamins given to pregnant women). This is because the synthetic pathways of choline and folic acid are interwoven. For example, both compounds convert homocysteine to methionine.

The importance of choline supplementation (during pregnancy) to the functioning of the hippocampus has been demonstrated in animal studies.

A summary of these studies establishes that feeding mothers choline-deficient diets leads to irreversible suppression of hippocampus functioning which presents mostly as impaired long-term memory capacity.

In animals (rodents, mostly), the mental capacity and memory of the offspring can be enhanced by increasing the amount of choline given to their mothers while pregnant.

Given that human brain development goes on even after gestation, choline-rich diets during pregnancy may not determine cognitive function in humans as much as in rodents. However, choline-supplementation of infant formulas is widely advised since infancy is another period of rapid brain development in humans.

During Breast-feeding

Even more than in pregnant women, breastfeeding mothers have a high demand for choline.

Choline gets into the breast milk either through maternal blood or nutrients produced in the epithelium of the mammary glands. In breast milk choline can be found free or as choline nutrients such as phosphatidylcholine, phosphocholine (the major form of choline in human breast milk), glycerophosphocholine and sphingomyelin.

Just like for the placenta and brain, choline is pushed into breast milk against a concentration gradient by a specific transporter.

In addition, the amount of choline present in breast milk directly correlates to the amount of blood choline levels in the infant feeding on such milk.

Although, studies have found that the breast milk obtained from mothers who had premature births contains less choline than those who reached full term, the preterm breast milk is still superior to infant formulas in choline content.

Preterm babies fed breast milk soon catch up with full term babies fed breast milk too and even outperform babies fed formula in cognition tests.

The table below gives a summary of the choline content of mature human milk, cow milk (and infant formulas derived from it) and soy lecithin.

Milks and Cholines: A Comparison

Free Choline: Lower in human milk than cow milk and infant formulas

Phosphocholine: Highest in human milk

Glycerophosphocholine: Cow milk > Human milk > Soy infant formulas

Phosphatidylcholine:  Soy infant formulas > Human milk & Cow milk

Sphingomyelin: Human milk > Soy infant formulas

Other important nutrients found in breast milk but missing in infant formulas especially soy-derived ones include enzymes such as peroxidase and lysozume, nerve growth factor, neurotensin, TSH (thyroid stimulating hormone), long chain polyunsaturated fatty acids and sialyated oligosaccharides.

An analysis of the available studies done on the benefits of choline in breast milk shows that children who were breastfed scored higher in cognitive development including tests of long-term memory and IQ.

This advantage was sustained later in life and increased with the duration of breastfeeding.

Choline Consumption and Memory Scores in Adults

The benefits of choline on cognitive development are not restricted to infants and children.

A number of studies have also established that choline consumption in adults can have a marked difference on memory and other aspects of cognition.

In one study done by researchers from Boston University School of Medicine, the dietary data of a group of 1400 adults between the ages of 36 and 83 were examined. The data was gathered between 1991 and 1995, and then the group were given memory tests and MRI brain scans between 1998 and 2001.

The researchers discovered that adults who ate choline-rich foods scored highest in the memory tests.

To remove any other contributing factors, the researchers corrected for the consumption of fats, neuroprotective vitamins such as vitamins B6 and B12 as well as caloric intake and even the subjects’ education.

Even after then the results still showed that the subjects who ate choline-rich diets performed significantly better than those who did not.

Furthermore, the choline-eating subjects had lesser chance of developing white matter hyperintensity (seen from the MRI scans). This is a form of brain damage caused by weakened vessels and known to cause dementia and increase the risk of stroke.

In a smaller but more direct study done by researchers at Florida International University, 41 subjects between the ages of 50 and 81 were given 500 mg of choline (in the form of lecithin granules) daily for 5 weeks.

After the supplementation, the group improved in memory tests (everyday memory tasks such as name recollection etc.) more than those who did not receive choline supplements. The results revealed that choline supplementation was able to reduce memory lapses from an average of 35 per week to 19.

Even though choline can help improve memory in adults, experts are quick to warn that the best benefits of choline are obtained when given early in life while brain development is still rapid and before some aspects of brain functioning are set in place.

The major challenge of choline supplementation in adults is getting choline into the brain.

The transporter respond for ferrying choline across the blood-brain barrier has a low affinity and is, therefore inefficient.

Therefore, it is possible to increase blood levels of choline in adults without seeing an attendant improvement in cognitive function especially where neurodegenerative disorders, such as Alzheimer’s disease, are already in progress.

Animal Model Studies on Choline and Memory

Animal models (especially rodents such as rats and mice) are commonly used in testing the effects of various agents on memories. Often, the results closely resembles the ones obtained in human trial.

The 3 studies discussed below represents a summary of studies in this area, and they have contributed immensely to our understanding of the effects of choline on memory.

In a 1985 study published in the journal, Neurobiology of Aging, mice fed with choline-rich diet were able to reverse the memory loss induced in them by the drug, anisomycin.

Anisomycin works by increasing the activities of the enzymes choline acetyltransferase and tyrosine hydroxylase in the brain. This means that these enzymes destroy choline and tyrosine by converting them to other compounds (in the case of choline, it is converted to acetylcholine).

However, choline supplementation was enough to reduce the activity of choline acetyltransferase and improve long-term memory.

This study shows that choline improves memory in other ways than simply serving as acetylcholine precursor.

Another study published in 1988 in the journal, Developmental Psychobiology, built on an earlier demonstration that increasing acetylcholine levels (through choline supplementation) can improve short-term memories in rats by examining the effect of choline on long-term spatial memory when given prenatal and postnatal.

The tested rats were exposed to choline chloride prenatal or postnatal or not at all. The results showed that long-term spatial memory was improved in the rats given choline but was better when given prenatally.

A 1984 study published in the journal, Pharmacology Biochemistry and Behavior, discussed the effects of choline, piracetam and different combinations of these 2 agents on the ability of mice to retain memory.

Piracetam is a nootropic (memory enhancer) drug derived from GABA (gamma aminobutyric acid, a neurotransmitter in the brain). Its chief indication is in the treatment of muscle spasms. However, it has a number of off-label uses including in the treatment of cognitive impairment and dementia.

Piracetam has been shown to improve memory in humans. It has also been demonstrated to reverse the effects of aging in the brains of mice and rats by reducing the levels of a lipofuscin.

In this study, a very high dose of piracetam (no less than 2000 mg/kg) was found to be required to improve memory in the test mice. Alternatively, a combination of low dose choline and piracetam (50 mg/kg of each drug) was found to produce a comparable improvement in memory.

While this study shows a possible benefit for combining piracetam with choline for improving memory, such opportunity has not be exploited or approved in humans.





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