A lot is made of this or that supplement–from fat-burners to nootropics. Within the supplement world, another trend has started up: comparing ingredients from label to label. A primary focus of this website isn’t to compare but to demystify. Too many people, the only information they have on a supplement or an ingredient is what the see on the company website.
Not so, here. I’ll provide some of the best scientific literature to date on a nootropic ingredient making the rounds: Choline. I’ll break down what it is, whether it works, and if there are any side effects.
What You Need to Know
Choline: a Brief Definition
Choline is a helper-chemical, in that it supports cell strength, carries fat from the liver, and works in the brain to help neurotransmitters communicate to other brain cells. It is this last mechanism we’ll consider for this article. In the brain, Choline combines with an acidic enzyme to form acetylcholine (ACh), which travels from the end of one neuron (brain cell) to the other, triggering an action–a thought, a memory, an eye movement, what have you.
Choline is produced naturally in most animal bodies, but because of the larger brain capacity of humans, we need far more of it than can be produced in our bodies. Choline is present in most animal products (milk, meat, liver, etc.), and can be obtained through supplementation.
Having come to understand what Choline is, and how it functions in the brain for everything from mood to memory, scientists have recently set about trying to find out if increasing the amount people take can provide additional benefit.
Primary Studies
Our first large-scale study came from a well-known group of observational research subjects known as the Framingham Heart Study. This group of volunteers formed the basis for much of what we understand about heart disease, stroke, and many other health risks associated with everything from diet to genetics.
Descendents of this famous test group were invited in the early 2000s to take part in another 10 year observational study of dietary Choline intake and brain health. Researchers found that all the Choline supplement participants had significantly better scores for Verbal Memory and Visual Memory. These data held at a statistical confidence of over 99%, for over 1,300 participants.
Another large-scale study repeated these results with data from 26 hospitals and 4,071 people in China. These data revealed that Choline levels were associated with better scores on the Mini-Mental State Examination–results in this study were so strong that researchers were able to reverse the function: Choline levels could be used to predict better scores on mental aptitude tests.
Animal Studies
I’ve discussed in previous articles the ethics issues related with human and animal study. In brief, once a nutrient like Choline has been deemed essential, it isn’t ethical to test depriving humans of it to study the effects.
Right or wrong, that’s not so for animals. Scientists publishing in Current Alzheimer’s Research found that controlling (limiting) choline in weaning mice and their offspring severely increased the risks of Down Syndrome and Alzheimer’s.
Another team of researchers found that controlled versus supplemented Choline mice had markedly different brain chemistry, spatial memory capacity, and even microglial activity. For the Choline group, spatial memory brain cells were significantly higher, and microglial activity was significantly better managed.
More Recent Choline Human Studies
Finally we have a human study with direct Choline supplementation in healthy adults. A partner compound in the process of Choline impacting cellular mechanisms, citicoline (cytidine diphosphate-choline (CDP-Choline)), was studied in a double-blind, randomized, placebo-controlled trial of 99 healthy men and women.
In the study, the test (citicoline) group had significantly improved short-term and long-term memory compared to the placebo group. Additionally, no adverse effects were noted during the study.
Another collated study of over 16 human trials (and 38 animal studies) found that there is a “consistent body of evidence that choline plays a significant role in proper neurodevelopment and brain function,” especially in the first 3 years of life. Perhaps most importantly, they also found that around 90% of people don’t get enough Choline in their diets.
This last detail is perhaps the most important for correlation to Choline supplements. With many essential nutrients, the question isn’t whether the vitamin or mineral is important–it’s whether anyone needs a supplement for it. In this case, it appears that the overwhelming majority of people are not getting enough Choline–making the benefits of supplementation more stark in contrast to deficiencies.
L-alpha-glycerylphosphorylcholine (αGPC)
A burgeoning use of Choline in supplements is a compound called αGPC. (Full name above, though some labels shorten it to glycerylphosphorylcholine). This compound of Choline has been shown to increase the amount of Acetylcholine in the brain (the main trigger of neuron function).
In one study comparing αGPC, caffeine, and placebo, there was no statistically clear benefit to αGPC for all metrics tested. But the researchers did note that it did improve certain mental functions, which data called for more research.
Pursuant to that, later researchers just a couple of years ago conducted a placebo controlled trial with two outcomes: lethargy versus motivation; and anxiety versus relief. While the trial didn’t yield any difference in anxiety between the subjects (both groups improved, most probably due to the placebo effect), there was a significant improvement in the Choline group for motivation, especially at night.
Neither of these two tests showed any side effects, and both did note a higher degree of Choline with αGPC consumption.
A Serious Study of Stroke Risk
While no study noted in this article yet has observed Choline side effects, and the two short-term trials of αGPC did not report side effects, a very recent cohort, observational study of data has noted a staggering health warning for long-term αGPC use.
In a paper published in the Journal of the American Medical Association found that people taking αGPC had a 46% higher risk of stroke. This datum arose from matched cohorts of over 12 million people, aged 50 or older.
It is not clear from this data that there is a direct cause of αGPC and stroke, but the results are compelling, to say the least. These data are also very, very new, and it will be some time before deterministic correlations can be made–that is, anyone deciding whether to take αGPC should consult their physician on a case-by-case basis. This study, alone, is not enough to determine health outcomes for all individuals.
Conclusion
The scientific community has established, through decades of research in laboratory and observational settings, that Choline is absolutely necessary for proper and healthy brain function. In more limited settings, there is promising data that various supplement forms of Choline (citicoline and αGPC) may also present benefits to healthy adults.
In addition, it appears from at least some of the data that most adults are not reaching adequate levels of Choline, strongly suggesting a benefit to taking Choline as a supplement. There is, however, some notable risk associated with at least one form of supplement Choline, though more study is needed to determine the level of risk and mechanisms.