Choline supplement benefit and side effects, bitartrate research and review of proper dosage, medical uses and safety risk
This nutrient is helpful for brain health and for phospholipid formation
January 1
2017 by
Ray Sahelian, M.D.

Choline is an essential nutrient required by the body to make several important compounds necessary for healthy cell membranes. This nutrient helps form phosphatidylcholine, the primary phospholipid of cell membranes. It helps transport of lipids from the liver. Choline is also the precursor to acetylcholine, one of the crucial brain chemicals involved in memory. A major use in the body is the formation of betaine, an important methyl donor. Betaine is a metabolite of choline, they have a similar chemical structure but they are not the same.
   Humans eating diets low in choline develop fatty liver and liver damage. Rodents fed choline-methionine-deficient diets not only develop fatty liver, but also progress to develop fibrosis and liver cancer.

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Choline helps in the production of lipotropic agents, converts fats into useful products, and aids in the production of HDL (good) cholesterol. This supplement is 100 % natural.

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Supplement Facts
Serving Size: 1 Capsule
Servings per Container: 60 Capsules
  Amount Per Serving %DV
Choline Bitartrate (Yielding 260 mg of choline) 650 mg
† Daily Value or Recommended Daily Intake not established.

Supplement Facts
Choline bitartrate 260 mg per pill
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Usage, dosage: Take 1 choline capsule a few minutes before breakfast or lunch or as directed by your health care provider.
Our daily intake ranges between 200 to 500 mg through food. For long term daily use, it appears to be safe to take 100 to 300 mg a day as a supplement. Since some capsules contain more than this amount, you may need to open a capsule and take part of it.

With or without food?
Is it best to take choline on an empty stomach or with food? At what time of the day is most effective?
    This nutrient
is best taken early in the day since it can interfere with sleep if taken in the evening. Taking choline right before a meal is fine although it works well when taken with a meal.

Studies and research that show medical benefits of choline
Several studies have been done administering this nutrient to humans in order to evaluate the role it plays in health and disease. The results have been mixed.

Bipolar disorder, manic depression
It has also been tested in bipolar disorder, also known as manic-depression. When six patients already on lithium were given choline bitartrate, five of them had a reduction in manic symptoms.

Homocysteine reduction
A daily dose, supplemented as phosphatidyl choline, lowers fasting as well as postmethionine-loading plasma homocysteine concentrations in healthy men with mildly elevated homocysteine concentrations. If high homocysteine concentrations indeed cause cardiovascular disease, choline intake may reduce cardiovascular disease risk in humans. The mechanism may be the ability of choline to be transformed into betaine.

Choline deficiency in mice and humans is associated with increased plasma homocysteine concentration after a methionine load.
American Journal of Clinical Nutrition 2005
Our results suggest that choline, like folate, plays an important role in the metabolism of homocysteine in humans and that response to a methionine load may be useful when assessing choline nutriture.

Memory and brain function benefit
Choline is the precursor to acetylcholine, the brain chemical involved with memory. This supplement has been sold over the counter for many years. A more activated form of choline, called CDP-choline, became available in the US in 1998. Individuals who don’t have a good dietary intake of phospholipids may find that taking these nutrients leads to an improvement in learning and memory. Most young and healthy people who take phosphatidylcholine or phosphatidylserine are not likely to notice any significant changes, although supplements could help some seniors. The effects from choline, and its cousin CDP-choline, are more noticeable.

Does not work right away in young people
PLoS One. 2016. No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults. Choline is a dietary component and precursor of acetylcholine, a crucial neurotransmitter for memory-related brain functions. In two double-blind, placebo-controlled cross-over experiments, we investigated whether the food supplement choline bitartrate improved declarative memory and working memory in healthy, young students one to two hours after supplementation. In experiment 1, 28 participants performed a visuospatial working memory task. In experiment 2, 26 participants performed a declarative picture memorization task. In experiment 3, 40 participants performed a verbal working memory task in addition to the visuospatial working memory and declarative picture task. All tasks were conducted approximately 60 minutes after the ingestion of 2 to 2.5 grams of either choline bitartrate or placebo. We found that choline did not significantly enhance memory performance during any of the tasks. We conclude that choline likely has no acute effects on cholinergic memory functions in healthy human participants.

Availability as a supplement
Choline is sold in dosages ranging from 250 to 500 mg and in a number of forms including bitartrate, chloride, and citrate. Many brand names are available. It is also found in Diet Rx, a natural diet pill that helps you eat less, and in Mind Power Rx, a natural brain enhancing product.

Side effects, safety, danger, toxicity
A common side effect of choline ingestion is increased body temperature and sweating. Nausea and loss of appetite can result from very high doses. Most people notice having more focus and being more alert. A positive effect is that it helps with erections.

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Alzheimer's disease
Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally.
Brain Res. 2006; Wurtman RJ, Ulus IH, Cansev M. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, MIT, Cambridge, MA
The synthesis of brain phosphatidyl choline may utilize three circulating precursors: choline; a pyrimidine (e.g., uridine, converted via UTP to brain CTP); and a PUFA (e.g., docosahexaenoic acid); phosphatidylethanolamine may utilize two of these, a pyrimidine and a PUFA. We observe that consuming these precursors can substantially increase membrane phosphatide and synaptic protein levels in gerbil brains. Alzheimer's disease brains contain fewer and smaller synapses and reduced levels of synaptic proteins, membrane phosphatides, choline and DHA. The three phosphatide precursors might thus be useful in treating this disease.

Libido effects, sexual improvement
Choline, as it relates to sexual health, is discussed in the book Natural Sex Boosters.

I've had a libido problem for a long time. I stumbled across your website and it occurred to me that my problem might not be solely hormone related, but may be due to the inability of my brain to adequately handle stimulus. I purchased a bottle of choline bitartrate, and after almost a week of taking 1 pill per day I have noticed a difference in my sexual response. So far, it seems as if my body has become slightly more responsive to stimulus and I am actually able to become somewhat aroused.

In our diet and food sources
Choline, usually as part of
phosphatidylcholine, is widely available in a number of foods, particularly eggs, fish, legumes, nuts, and meats and vegetables, as well as in human breast milk. Dietary intake ranges from 300 to 900 mg a day. Most individuals who have a normal diet are not deficient. Its importance was emphasized in 1998 when the National Academy of Sciences classified it as an essential nutrient. In the past, it was thought that the human body made adequate amounts when needed. However, a study by Dr. Steven Zeisel, from the Department of Nutrition at the University of North Carolina at Chapel Hill, demonstrated that volunteers on a choline deficient diet were not able to produce enough of this nutrient.   

Dr. Sahelian’s experience
Within a few hours of taking a choline pill, I notice an improvement in mental focus that lasts most of the day. I have not experienced side effects with dosages smaller than 500 mg. On a dosage of 750 mg, I experience increased body warmth and slight nausea.

Choline and pregnancy, use by women who are pregnant
Pregnancy may deplete the amount of choline found in the liver resulting in reduced methylation of homocysteine. The demand during pregnancy is very high due to the transport of choline from mother to the fetus. High intake in pregnant women is important to lower the risk of neural tube defects.
   According to the results of several studies in rats, providing choline during pregnancy enhances memory and learning capacity in the fetus. Dr. Christina Williams, a behavioral neuroscientist at Duke University in Durham, North Carolina, says her study findings demonstrate, "That supplementation with choline during the last third of pregnancy has fairly dramatic and long-lasting effects on the memory of offspring." A 1997 study published in Advances in Pediatrics by Dr. Zeisel showed that choline reserves are depleted during pregnancy and lactation (Zeisel 1997). This depletion may affect normal brain development and memory in the offspring. The National Academy of Sciences suggests that pregnant women consume at least 450 milligrams per day.

Behav Brain Res. 2015. High maternal choline consumption during pregnancy and nursing alleviates deficits in social interaction and improves anxiety-like behaviors in the BTBR T+Itpr3tf/J mouse model of autism.

Recommendations and review
Individuals whose diet includes a wide variety of foods are not likely to suffer from choline deficiency. Growing infants, pregnant or lactating women, and individuals with liver cirrhosis may potentially be deficient (Zeisel 1994). Whether supplements benefit older individuals with age related memory decline has not yet been adequately determined. Because of its relative safety, and potential benefits, I recommend small amounts in the elderly who have age related cognitive decline. Choline can be taken occasionally by younger individuals on days when better concentration and focus would be helpful.

Various forms of supplements available online and in health food stores
You can find this nutrient as part of phosphatidyl choline (lecithin), choline chloride, CDP, choline bitartrate, choline inositol combination, etc.

Choline deficiency
In many mammals, including baboons, long term (weeks to months) ingestion of a diet deficient in choline but adequate, though limited, in methionine and folate leads to hepatic, renal, pancreatic, memory, and growth disorders. Muscle damage also occurs from choline deficiency.
   A choline -deficient diet increased DNA damage in humans. Subjects in whom these diets induced liver or muscle dysfunction also had higher rates of apoptosis in their peripheral lymphocytes than did subjects who did not develop organ dysfunction. Assessment of DNA damage and apoptosis in lymphocytes appears to be a clinically useful measure in humans (such as those receiving parenteral nutrition) in whom choline deficiency is suspected.

The Memory Nutrients - Choline Phospholipids, from the book Mind Boosters by Ray Sahelian, M.D.
Like omega-3 fatty acids, phospholipids are important for optimal brain health. They are made of the combination of lipids (fats) and the mineral phosphorus. Phospholipids are found in high concentrations in the lining of practically every cell of the body, including brain cells. They help brain cells communicate and influence how well receptors function. Although present in many foods, phospholipids are found in higher concentrations in soy, eggs and the brain tissue of animals. There may actually be a biochemical rational for the folk wisdom that says eating brain makes one smarter. The two most common phospholipid supplements sold over the counter are phosphatidylcholine and Phosphatidylserine. Phosphatidylcholine is also known as lecithin.

Which Conditions Can Choline and Phospholipids Benefit?
The clinical application of these nutrients has not yet been fully evaluated, but scientists have studied their role in age related cognitive decline (ARCD), Alzheimer’s disease, and Parkinson’s disease. No firm conclusions are yet available as to whether phosphatidylserine and phosphatidylcholine help these conditions. Choline could potentially be beneficial in age related cognitive decline and Alzheimer’s disease.

Choline Research studies
Oral choline decreases brain purine levels in lithium-treated subjects with rapid-cycling bipolar disorder: a double-blind trial using proton and lithium magnetic resonance spectroscopy.
Brain Imaging Center, McLean Hospital, Belmont, MA, Bipolar Disord. 2003.
Oral choline administration has been reported to increase brain phosphatidylcholine levels. As phospholipid synthesis for maintaining membrane integrity in mammalian brain cells consumes approximately 10-15% of the total adenosine triphosphate (ATP) pool, an increased availability of brain choline may lead to an increase in ATP consumption. The current study reports that oral choline supplementation resulted in a significant decrease in brain purine levels over a 12-week treatment period in lithium-treated patients with DSM-IV bipolar disorder, rapid-cycling type, which may be related to the anti-manic effects of adjuvant choline. This result is consistent with mitochondrial dysfunction in bipolar disorder inadequately meeting the demand for increased ATP production as exogenous oral choline administration increases membrane phospholipid synthesis.

Combining with dietary supplements
I've decided to try choline bitartrate of 250 mg. Can I take it together with a regular multivitamin pill? Will this help a lot with my studies which involves a lot of memorization? Can I take vitamin B6 together with choline? What about taurine, does it functions like choline?
    It is best to learn how each supplement works for you by itself before combining. We don't have as much experience with taurine to know for sure how well it works for memory or mental enhancement.

I have heard that taking choline can help some people with liver problems. My problem is my local doctor and I have been unable to locate someone or some place that can conduct a blood test that will measure a serum choline level to identify if there is a deficiency.
    Choline deficiency is extremely rare and may occur in those who have malnutrition or are eating a very restrictive diet. Testing for choline in the blood is unlikely to reveal any information that would be clinically helpful. Anyone with suspected liver problems should have blood liver function tests and if abnormal, further studies can be done to determine the problem and course of action.

I found the following information on a web site interesting: One of the lesser-known functions of acetylcholine is helping to maintain sleep. Acetylcholine controls the amount of sensory input. It strengthens the so-called stimulus barrier, making it possible to sleep through minor noises and other disturbances. As we age, we tend to become "light sleepers," easily roused from sleep. Menopausal women, who experience a sudden drop in acetylcholine levels due to estrogen withdrawal, often complain about having suddenly become "light sleepers." The same stimulus barrier also helps us concentrate and solve problems. Too little acetylcholine makes us distracted and irritable as too many unimportant stimuli bombard us, in essence preventing us from thinking. I have tried it, but it didn't seem to help, so perhaps I wasn't using enough. I plan on experimenting with higher doses by taking choline chloride.
    Based on my understanding of this supplement and how it effects users, it actually causes alertness rather than help with sleep if you take it in the evening. However, I am not sure how it effects sleep if taken in the morning.

Can you tell me the difference of choline bitrate and chloride?
    Practically speaking there is not too much difference between bitartrate and chloride, but no human studies have been done comparing these two forms to see whether in the long run one form is better than the other.