Friday, January 24, 2014

Will Choline Make You Smarter?

 Will Choline make you smarter?  Here are the key points you should know. 

  • Choline supplementation may improve declining cognitive abilities of individuals with Alzheimer's disease and similar cerebral health issues.
  • The only well-designed human study on choline in healthy individuals thus far shows a small benefit for increasing attention span in middle-aged women, using doses of up to 500 mg of supplemental choline per day.
  • Most studies investigating choline supplementation for cognitive performance enhancement in healthy individuals are plagued by bad experiment design, too few subjects, or both.  Further research is needed.
  • Aim for the adequate daily intake of 550 mg for men, 425 mg for women.  For reference, a normal-sized chicken egg contains about 140 mg of choline. 
  • ADDENDUM 04/15/2015: Although I still recommend obtaining the adequate daily intake of choline for possibly improved cognitive function, I DO NOT recommend obtaining choline from eggs.  There is mounting evidence that the choline in eggs vastly increases the risk of heart disease and cancer.  Read more about this issue with animal-based choline here and hereSome of the highest sources of plant-based choline can be found in pinto beans (~60mg/cup), broccoli (~30mg/cup), oats (~20mg/cup) and oranges (~15mg).

The essential nutrient,Choline

I've been hanging out on the Nootropics sub of reddit for a while now, in an attempt to find a link between food and improvements in cognitive function.  For those of you who don't know what nootropics are, here is a brief summary directly from the Nootropics FAQ:

"Nootropics, also referred to as smart drugs, memory enhancers, neuro enhancers, cognitive enhancers, and intelligence enhancers, are drugs, supplements, nutraceuticals, and functional foods that improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration.
...'Nootropics' has gradually expanded to either be synonymous with cognitive enhancers or refer to the subset of non-stimulant cognitive enhancing compounds with very few side effects and low toxicity. Nootropics are by definition cognitive enhancers, but a cognitive enhancer is not necessarily a nootropic."

Why have I been studying this field so much lately?  One of my hobbies in life is to learn as much as I can about the topics/subjects that interest me.  The potential to increase my mental abilities to better absorb and retain knowledge of those topics/subjects is very intriguing to me.  Especially when said potential comes in the form of a healthy, tasty whole food.

One such substance that I've noticed continually recommended on the Nootropics sub is choline.  Choline is nutrient usually grouped in with the B vitamins.  It is found in a wide variety of whole foods, including eggs, beans, milk and grains.  It is an essential nutrient that plays a role in maintaining liver and kidney health, among other things.  But in respect to cognitive function, choline is so interesting to scientists because it is a precursor to the neurotransmitter, Acetylcholine.

Acetylcholine is important to mental health, as it plays a role in sensory perception and attention span.  Damage to the system that synthesizes acetylcholine in the human body is correlated with the increased incidence of memory loss from Alzheimer's disease.

It would stand to reason, then, that supplementing choline would increase production of acetylcholine in the body, mitigating the effects of memory loss and inattention.  Going a step further, perhaps ingesting higher amounts of choline might even improve attention span and memory recall above baseline levels, if not in deficiency.  However, the scientific literature on choline and cognitive performance is not so clear cut.

Let's take a look at choline's potential as a nootropic.

Research on Choline and Alzheimer's Disease and Other Cerebral Trauma

Since there is supposed potential of choline to reduce the effects of Alzheimer's disease through acetylcholine production, a vast majority of the studies use subjects with Alzheimer's disease.  Although these studies won't directly show the effects of choline on cognition improvement in healthy people, they can serve as an important baseline to see if choline has any beneficial effect at all compared to a placebo.

Symptoms of Alzheimer's disease

One of the first studies investigating the link between choline and Alzheimer's disease was done by Thal et al. in 1981.  The team conducting the study gave seven volunteers with moderate cases of Alzheimer's disease varying doses of choline, up to 200 mg per kilogram of body weight per day, or a placebo.  This trial being of a crossover design, all the volunteers served as their own control. The researchers noticed no difference between any dosing level of choline and the placebo on cognitive function of the subjects.  Although there was no beneficial effect found, the results of this study are severely lacking in statistical power since there were only seven subjects.  The duration of the study was also very short, with the trial lasting only two weeks between each arm of testing.  An effect may have been seen with a larger sample size or longer duration.

Another of the earlier studies on choline and Alzheimer's disease was conducted by Caamaño et al in 1994 at the Neurosciences Research Center in Spain.  Caamaño and his team gave 20 test subjects, with an age range of 57 to 78, who had either full Alzheimer's disease or an early symptoms of Alzheimer's disease supplemental choline in the amount of 1 gram per day for a month.  They measured the performance of cognitive ability through the use of a MMSE test, which has questions based on the subjects' orientation to time and location, and basic language and math problems.  They also measured blood flow to different areas of the brain.  Measurements were made before choline was administered, and at one month post-supplementation.  After one month, the researchers reported that choline supplementation had significantly improved cognitive performance (especially orientation to location) in both subsets of patients, as well as increased blood flow to the brain.  While showing potential benefit from supplemental choline, this study's results are weakened due to the relatively short duration and complete lack of a control group.

A later study by the same research team (Caamaño et al.) in 1996 seemed to confirm the results of the previous work.  Subjects were given 1 gram of choline per day and the results were nearly identical as the earlier study... slightly improved metal performance and increase brain blood flow.  However, in this study, the researchers also discovered choline seemed to reduce levels of pro-inflammatory substances in the blood--obviously a good thing in general.  Again, no mention of a control group.  This study is also lacking the information on how long the trial lasted and the total number of subjects participating.  Even while confirming results found in the earlier study of similar methodology, these design flaws make it hard to come to a definitive conclusion on supplemental choline.  

In 1999, a much better designed study by Alvarez et al. at the EuroEspes Biomedical Research Center in Spain was conducted.  17 patients with mild to moderate Alzheimer's disease, age 57-78, were given 1 gram of supplemental choline per day for a period of 12 weeks in a double-blind fashion.  13 other subjects were given a placebo.  Cognitive performance testing and brain blood flow analysis was done before choline supplementation and after the 12 week supplementation period.  The results of this study also seemed to confirm earlier research, that 1 gram of choline per day slightly increases mental ability of Alzheimer's disease patients, and reduces inflammatory markers within the blood.  The researchers add that the supplemental choline was well tolerated and had virtually no side effects.  Aside from extremely similar results compared to previous studies, the longer duration of this experiment combined with a control (placebo) group really lends credibility to the idea that 1 gram of choline per day may be an effective treatment for Alzheimer's disease, at least to those with a milder form of the disease.

Another study investigating the therapeutic effect of choline on Alzheimer's disease was done at the National Institute of Aging in Mexico.  In this double-blind, randomized study, 261 subjects with mild to moderate dementia were given either 400mg of choline three times daily (total daily choline ingestion = 1.2 grams) or a placebo.  A large variety of cognitive function tests were given to all the subjects at the beginning of the study, again at 90 days, and again at 180 days.  Just like the results of previous research, the group taking choline improved their abilities on cognition tests compared to placebo, whose mental performance mostly stayed the same or decreased.  This study improved upon the work by Alvarez et al. by increasing the sample size, randomizing the subjects, and increasing the duration of the trial.  It also further validates the efficacy of supplementing choline to treat mild to moderate Alzheimer's disease.

Finally, we have two more studies looking at the effect of supplemental choline on subjects with cerebral issues other than Alzheimer's disease.  The first is a study done on patients with head trauma conducted in 1991 by the Department of Neurosurgery in Spain.  261 patients were apparently monitored after suffering moderate to severe head injuries.  A trend was noticed that patients taking choline while receiving conventional treatment recovered faster and were discharged from the hospital sooner than those receiving conventional treatment only.  This study's results are particularly weak, though, as there is no mention of a control group, or the how long of a duration the subjects were monitored.  It was also only single-blinded.  The other study was conducted 21 years later (2012), in Russia by Kostenko et al.  The researchers in this study attempted to determine the efficacy and safety of supplemental choline in subjects who had either a stroke or a disease characterized by reduced blood flow to the brain.  The subjects were given a 1 gram IV of choline per day for a week, followed by 1.2 grams per day orally for six weeks.  Apparently, all subjects experience better cognitive functions after supplementing with choline, although there was no mention of baseline vs. post-supplementation results of the tests.  Obviously, no control group seriously weakens this study's validity.  However, the conclusion of this study coincides with the results of similar previous research, giving it a little more credibility.

Choline may improve blood flow to the brain of Alzheimer's sufferers

Judging by this sampling of studies on choline and cerebro-vascular disease, I would think it is a pretty good bet that choline is a safe, effective treatment for memory loss and cognitive decline due to Alzheimer's disease or other similar mental disorders.  The efficacy of choline treatment is pretty well demonstrated by these studies.  Perhaps future studies should attempt to determine the optimal dosage of choline for cognitive benefits, and the mechanisms behind the effects of choline on mental health.

Choline Research for Normal People

So most of the research indicates a useful effect for people with dementia.  Great, but does that mean healthy people stand to gain cognitive benefits and improvements from ingesting supplemental choline as well?  Or is the benefit only being realized from correcting a deficiency, imbalance or some other problem in diseased populations?

There is far less research on the efficacy of choline in healthy individuals, but there are a few studies from which we might be able to form an initial hypothesis.

The oldest of these studies was published in 1984 in the Journal of the American Geriatrics Society.  258 healthy, older (average age of 72) individuals were questioned on their dietary practices and blood samples were collected to analyze the content of circulating choline.  Two cognitive abilities tests were given, and no association was seen between choline consumption and cognitive function.  Although there was no effect from choline found in this study, there is no mention of a control group or the duration of the trial.  Furthermore, the researchers relied on self-reported data of food consumption habits from the subjects themselves, making the validity of the study's conclusions highly dubious.  The self-reported data also probably explains the fact that there was no association between choline intake and choline levels in the blood.  There are a number of problems with using self-reported data in studies, especially with research that is trying to evaluate the potential efficacy of dietary substances in humans.  Not even trying to control the consumption of choline, but allowing subjects to tell the researchers how much choline they consumed from food is what makes this study so unreliable.

In 2002, the Department of Military and Emergency Medicine in the United States conducted a study to determine the effect, if any, on supplemental choline on physical performance and cognitive abilities.  The researchers gave 13 young men either a placebo or 50 mg of choline per kilogram of body weight in this double-blind, crossover study.  This dosage for a 150 lbs. man would be about 3.5 grams of choline.  Researchers confirmed that the supplemental choline was circulating in the subject's blood during each test phase, but noted that physical exertion did not deplete choline levels.  None of the subjects improved on either physical or mental aspects of the tests from choline in this study.  The major glaring weakness of this experiment is that it only studied the acute effects of a large one-time dose of choline during each of the four test conditions.  Choline's positive effects appear to be observable only in longer-duration trials, and a longer trial period may have had different results.  The sample size was also quite small, at only 13 individuals.

Another study done by Poly C et al. at the Boston University School of Medicine in the United States attempted to discern the effect of habitual dietary choline intake on cognitive performance.  Part of the study took place from 1991-1995, and another part took place from 1998-2001, with a little under 1400 individuals taking part.

I will admit that I am a little confused by the wording in this study, and I hope that someone will correct me if I am wrong in my assumptions.  The study indicates people who reported higher "concurrent" choline intake (I am assuming the meaning of "concurrent" in this context is "with food") was correlated with better mental performance, while "remote" (again, I am assuming "remote" means "not with food") choline intake reduce the odds of the brain atrophying.  I could be completely wrong due to the wording in this study, so take my conclusion on this study with a grain of salt--and correct me if you know more about it than I do!  Again, the glaringly obvious weakness of this study is the self-reported data from questionnaires.

Finally, a 2012 study published in the Journal of Food and Nutrition Sciences by E. McGlade et al. attempted to determine if supplemental choline would improve cognitive performance in the form of lengthening attention span.  60 healthy adult women, ages 40 to 60, were divided into three groups in this double-blind, randomized study: one placebo group, one group taking 250 mg of choline per day, and one group taking 500 mg of choline per day, for 28 days total.  Testing of attention spans took place before supplementing and after the 28 day trial period.  After the 28 days, the women in both choline supplement groups did better on attentional testing than did the placebo group.  This is a pretty solid study, with the only major weaknesses being the unknown applicability to a male population and short duration.  That said, this is probably the one of the few (if not only) experiments on choline in healthy populations with a solid testing foundation and beneficial results.

Eggs are a good source of choline


If you read everything up to this point, you'll definitely notice there is a measurable beneficial effect to supplementing with choline if you have a disease characterized by a decline in brain blood flow, such as Alzheimer's disease.  Doses of 1 to 1.5 grams of choline per day seem to improve cognitive function, especially correlations relating to time and location, without any serious side effects.  The mechanisms which choline use to do this are still unknown, but possible theories include chronic choline deficiency, an immosuppressive reaction to choline in the brain, and improved cerebral blood flow.

For all of us healthy folks, the answer is not quite as easy to discern.  Of the few studies done on choline supplementation in healthy individuals, most of them are plagued by self-reported data from questionnaires and surveys (a terribly inaccurate way to gauge efficacy of any substance), while another well-designed study suffers from the weakness of only studying the acute effects of choline ingestion (hint: there are no acute effects).  The only well designed, solid research we have on choline supplementation suggests that middle-aged healthy women may be able to increase their attention span slightly by consuming at least 250 mg of supplemental choline per day.

Bottom line: If you're suffering from a mental illness such as Alzheimer's disease, do yourself a favor and start consuming more choline, either through supplements or food.  It appears to reduce the symptoms of mental decline without any harsh side effects.  If you're healthy, the best idea is to hit the Adequate Intake dosage (550 mg/day for men, 425 mg/day for women) through food and leave it at that.  The latest research only indicates a very small potential increase in attention span for a specific subset of the population--women between the ages of 40 and 60.  There is minimal evidence for using choline supplements as a nootropic on its own.

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