Metabolic and Cognitive Health
Here’s Why and How to Address Choline Deficiency.
Potential health benefits of choline supplements (Citicoline/Alpha GPC) for brain functions based on experience and reviews
Why Do We Need Choline?
First of all, choline is not just another nutrient. It is essential, especially for the nervous system and metabolic pathways. Our cells need choline to preserve structural integrity. We also need choline for modulating gene expression and signaling in cell membranes and neurotransmitter synthesis.
I only write about important molecules, nutrients, and physical and mental health supplements.
I introduced several nootropics in an article before. Related to nootropics, some readers asked about the role of choline supplements in the brain as they know my interest in brain-boosting supplements, exceptionally well-researched, tested, and widely used ones.
However, my preference for nutrients is always to get from foods, and if we face deficiency, we may need supplementation with advice from qualified healthcare professionals.
Compared to other nutrients I introduced before, choline is relatively newer in medical and science communities.
Even though Adolph Strecker discovered it in 1862, the Institute of Medicine introduced Choline as an essential nutrient in 1998, as documented in a paper on Oxford Academic titled Choline: an essential nutrient for public health. Dr. Strecker isolated choline from the bile of pigs and oxen in those days.
I joined neuro-hacking communities during my cognitive science studies as the members shared their experiments with others. Finding experimental results in scientific studies is limited.
While scientific and theoretical studies are invaluable, subjective experiences also provide valuable input to our understanding of certain molecules in the brain and the body.
Alpha GPC and Citicoline are two widely discussed topics in these communities that I want to introduce in this article.
Brief Background on Choline Studies
I came across profound studies on choline in the early 1990s. For example, a clinical trial published in FASEB Journal in 1991 found:
“Healthy humans consuming a choline-deficient diet for three weeks had depleted stores of choline in tissues and developed signs of incipient liver dysfunction.”
Researchers concluded that “Choline is an essential nutrient for humans when excess methionine and folate are not available in the diet.”
This 1991 paper was influential because the paper’s authors pointed out:
“Choline is required to make essential membrane phospholipids. It is a precursor for the biosynthesis of the neurotransmitter acetylcholine and also is an important source of labile methyl groups. Mammals fed a choline-deficient diet develop liver dysfunction; however, choline is not considered an essential nutrient in humans.”
After seven years, finally, it was formally recognized as an essential nutrient.
As documented by National Health Institute:
“Choline is a source of methyl groups needed for many steps in metabolism. The body needs choline to synthesize phosphatidylcholine and sphingomyelin, two major phospholipids vital for cell membranes. Thus, all plant and animal cells need choline to preserve their structural integrity. Choline is needed to produce acetylcholine, an important neurotransmitter for memory, mood, muscle control, and other brain and nervous system functions. It also plays important roles in modulating gene expression, cell membrane signaling, lipid transport and metabolism, and early brain development.”
In my previous story related to betaine, I briefly touched on choline as the character of my story. A nutrition scientist and biohacker used betaine with choline. I want to mention the relationship briefly. Choline is cycled and transformed into various forms.
As documented in this paper, betaine is important for its role in the donation of methyl groups to homocysteine to form the essential amino acid methionine. “When the choline enters the cell, it is phosphorylated to phosphocholine, or oxidized to betaine in some cell types.”
The Role of Choline for The Brain and Parasympathetic Nervous System
I’d like to highlight the importance of choline for the parasympathetic nervous system and the brain. The brain coordinates the nervous system’s sensory information and actions by transmitting signals from parts of the body.
One of the important signals is conducted through acetylcholine which is a neurotransmitter. As a major neurotransmitter of the parasympathetic nervous system, acetylcholine dilates blood vessels, increases biological secretions, contracts smooth muscles, and slows our heart rate.
Rather than citing many papers, I’d like to provide a systematic review of multiple papers on choline’s importance. For example, a 2020 systematic review in MDPI investigated 813 published scientific papers to understand the importance of choline in the first 1000 days of life.
The study concluded that “choline as nutrient or supplement supports normal brain development, protects against neural and metabolic insults, particularly when the fetus is exposed to alcohol, and improves neural and cognitive functioning.”
The researchers highlighted:
“Overall, most offspring would benefit from increased choline supply during the first 1000 days of life, particularly about helping facilitate normal brain development. Health policies and guidelines should consider re-evaluation to help communicate and impart potential choline benefits through diet and/or supplementation approaches across this critical life stage.”
Even though research is still in the nascent stage, NIH informs:
“People with Alzheimer’s disease have lower levels of the enzyme that converts choline into acetylcholine in the brain. In addition, because phosphatidylcholine can serve as a phospholipid precursor, it might help support the structural integrity of neurons and thus might promote cognitive function in elderly adults. Some experts have therefore theorized that consuming higher levels of phosphatidylcholine could reduce the progression of dementia in people with Alzheimer’s disease. However, little research conducted to date supports this hypothesis.”
How the Body Gets Choline and Its Effects
Even though the liver can produce a small amount of choline, we need to get the required amount from foods, supplements, or both. Like all nutrients, the preferred method is food. However, if we face deficiency, we may need to supplement with the support of qualified healthcare professionals.
Deficiency is real, as pointed out in this paper published in the American Journal of Clinical Nutrition, “When deprived of dietary choline, 77% of men and 80% of postmenopausal women developed fatty liver or muscle damage. Moreover, six men developed these signs while consuming 550 mg of choline.”
Both animal and plant-based sources include choline in various amounts. The richest choline sources are liver, egg yolks, and wheat germ according to the nutrition books. Choline is also found in red meat, organ meats, fish, caviar, beans, soybeans, nuts, mushrooms, cheese, and cruciferous vegetables.
The top ten foods providing choline are based on the National Institute of Health report.
As pointed out in this paper:
“Dietary choline from a variety of choline-containing foods is absorbed by the intestine, and choline transporters mediate uptake. The major fate of choline is conversion to lecithin, which occurs in all nucleated cells.”
So my understanding of the process in the literature is choline is recycled in the liver. It redistributes to the kidney, lung, intestine, and brain when the choline supply is low in these organs.
Interestingly, there has been a dispute about whether choline is a mineral, amino acid, or vitamin. From my reviews, it is none of them. The majority of documents in the literature refer to choline as a nutrient. However, nutrition companies added it to the group of B vitamins as they see similarities. Choline is also included in some multivitamin compounds.
Like any supplement, there are also concerns about choline supplementation. While it is widely used in over-the-counter multivitamin complexes, some nutrition communities are fiercely against choline supplements for various reasons.
Even though I agree on diligence, some of the reasons in online forms are biased towards ideologies. I politely disagree with them as nutrition is a health matter, not a political one. I acknowledged that every molecule going into the body and brain might pose a risk. We are all unique.
Using supplements without reviewing our medical history by qualified health care professionals is not a good idea. I also acknowledge that a study linked choline, betaine, and carnitine supplements (as I mentioned in previous articles) to a higher risk of cardiovascular disease via “trimethylamine-N-oxide” (TMAO), a metabolite of choline by microbiota.
Regardless, like any nutrient, too much choline can be harmful and cause severe health conditions.
For example, according to the National Institute of Health, “Getting too much choline can cause a fishy body odor, vomiting, heavy sweating and salivation, low blood pressure, and liver damage. Some research also suggests that high amounts of choline may increase the risk of heart disease.”
The National Institute of Health provides the daily upper limits for choline intakes from all sources (food, beverages, and supplements). The limits are for children 1–3 years (1,000 mg), 4–8 years (1,000 mg) 9–13 years (2,000 mg) 14–18 years (3,000 mg), and adults (3,500 mg).
Citicoline and Alpha GPC Supplements
After this background, I’d like to briefly introduce two specific choline supplements, Alpha GPC and Citicoline, which I reviewed intensely and used cautiously in low doses in a short time when needed. I don’t use them anymore as my current diet provides me sufficient amount of choline and other essential nutrients.
For example, every second day, I consume around 50–100 grams of the grass-fed beef liver, which covers critical nutrients my body needs. I find liver more beneficial than multi-vitamin tablets. However, almost everyone in my family dislikes it. I rewired my brain to love it.
My review, as usual, is not a recommendation. It is wise to discuss our medical history with qualified healthcare professionals who have access to it. However, according to The National Institute of Health, the good news is that “Choline is not known to interact with any medications.”
Unfortunately, these two supplements are not available in Australia even though they are not banned. Therefore, I had to order from reliable and reputable nutrition companies in the United States.
Citicoline Supplementation
I reviewed many papers about citicoline. It is impossible to cite them in this article. However, I provide the big picture by using a 2020 review.
As documented in this systematic review:
“Citicoline is a chemical compound involved in the synthesis of cell membranes. It also has other, not yet explained functions. Research on the use of citicoline is conducted in neurology, ophthalmology, and psychiatry. Citicoline is widely available as a dietary supplement. It is often used to enhance cognitive functions.”
The review of multiple studies found:
“Citicoline has been proven to be a useful compound in preventing dementia progression. It also enhances cognitive functions among healthy individuals and improves prognosis after stroke. In an animal model of nerve damage and neuropathy, citicoline stimulated regeneration and lessened pain. Among patients who underwent brain trauma, citicoline has an unclear clinical effect. Citicoline has a wide range of effects and could be an essential substance in the treatment of many neurological diseases. Its positive impact on learning and cognitive functions among the healthy population is also worth noting.”
The main reason I use citicoline is its neuroprotective properties. It enhanced my focus, attention, memory, and task switching. In addition, based on my analysis and subjective experiments, citicoline might increase dopamine slightly. I am investigating the mechanism.
The vendor I purchased citicoline claimed that citicoline consumption promotes brain metabolism by enhancing the synthesis of acetylcholine and restoring phospholipid content in the brain, which positively affects memory and other brain activity.
I verified the validity of claims by reviewing multiple papers. The names of the products in the market might vary, but the scientific name for citicoline ingredient is cytidine diphosphocholine.
Alpha GPC Supplementation
Alpha glycerophosphocholine, known as Alpha GPC in the supplement market, is similar to citicoline. The main difference is that citicoline is a derivative of glycerophosphocholine.
However, Alpha GPC products release acetylcholine during digestion and metabolism. So Alpha GPC is believed to act faster, but there is no solid evidence.
I won’t go into the details and repeat the benefits of Alpha GPC. Like citicoline, Alpha GPC was designed to increase the neurotransmitters acetylcholine in the brain.
So understanding the importance of acetylcholine for neurological benefits explains the benefits of Alpha GPC.
When I discussed with the users of both products asking their preferences, some biohackers pointed out to prefer citicoline as they believe it can amplify the impact of other nootropics that I mentioned in this article.
As a duty of call, I want to point out that a cohort study in JAMA Network associated the use of Alpha GPC with a higher 10-year incident stroke risk in a dose-response manner after adjusting for traditional cerebrovascular risk factors.
The paper pointed out that “future studies are needed to determine the possible mechanisms behind the potential cerebrovascular risk-elevating effects of Alpha GPC.”
I don’t want to undermine the study, but I have concerns about such cohort studies. How do researchers know that those people in the group who used Alpha GPC did not have bad lifestyle habits such as smoking, eating junk food, or using drugs? It is not possible to control the lives of people for a decade.
Besides, there are myriad factors affecting microbiota. The research into the microbiome is extraordinarily complex and inconclusive.
So, the research finding does not mean much to me personally. I read many epidemiological studies which indicate healthy foods as dangerous.
My confidence in those types of confusing studies is low. I take them with a grain of salt.
Conclusions and Takeaways
The body of knowledge documented the numerous beneficial effects of choline on the body and brain. Choline is an essential nutrient for the brain, nervous system, and metabolic pathways in the body.
In addition, our cells need choline to preserve structural integrity, neurotransmitter synthesis, and signaling in cell membranes.
My preference is getting choline from the diet. Fortunately, my customized diet provides me a sufficient amount of choline. Thus, I don’t have to supplement nowadays.
However, some diets poor in choline might require supplementation as deficiency seem to cause some severe health disorders. Like any supplement, choline supplementation also requires discussion with qualified healthcare professionals, even though no drug interaction has been identified yet.
The National Institute of Health documented that “Choline deficiency can cause muscle damage, liver damage, and nonalcoholic fatty liver disease. Although most people in the United States consume less than adequate choline intake, frank choline deficiency in healthy, nonpregnant individuals is very rare, possibly because of the contribution of choline that the body synthesizes endogenously.”
However, choline seems to be vital for pregnant women.
For example, NIH points out:
“Approximately 90%–95% of pregnant women consume less choline than the adequate intake. Prenatal dietary supplements typically contain little if any choline. The risk of inadequate choline status might be greater in pregnant and lactating women who do not take folic acid supplements, those with low vitamin B12 status, and those with a common variant in methylenetetrahydrofolate dehydrogenase, all of which reduce the body’s pool of methyl groups needed for metabolism.”
Interestingly, choline also has genetic implications.
For example, this study has identified “novel genetic variants that modulate choline requirements and suggests that the dietary requirement for choline may be different across racial and ethnic groups.” Some ethnic groups might have more deficiencies than others. Thus, it is wise to discuss potential choline deficiency with our doctors.
Even though blood tests look complicated, research on choline tests is making good progress. For example, a paper in Nature proposed the measurement of plasma choline in acute coronary syndrome, pointing out that “strict sample preparation would be necessary to investigate the possible use of choline as a biomarker.”
I also wrote about other valuable nutrients. Here are the links for easy access:
Lutein/Zeaxanthin, Phosphatidylserine, Boron, Urolithin, taurine, citrulline malate, biotin, lithium orotate, alpha-lipoic acid, n-acetyl-cysteine, acetyl-l-carnitine, CoQ10, PQQ, NADH, TMG, creatine, choline, digestive enzymes, magnesium, zinc, hydrolyzed collagen, nootropics, pure nicotine, activated charcoal, Vitamin B12, Vitamin B1, Vitamin D, Vitamin K2, Omega-3 Fatty Acids, N-Acetyl L-Tyrosine, and other nutrients.
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