In the fall of 2019, Emma Derbyshire, a public health nutritionist in the United Kingdom, posed the question, “Could we be overlooking a potential choline crisis in the United Kingdom?” (1). The article expressed concern that current eating trends towards meat reduction and plant-based diets might be lacking in sources of the nutrient choline.
Though this article stirred up some perplexing headlines, there is no need for confusion. Animal products are not the only sources of choline nor are they the healthiest. Ms. Derbyshire’s article was an opinion piece, not a study on choline, and did not offer any new research findings. In its first version the author declared “no competing interests”. It took two subsequent article updates during the five days immediately following first publication to reveal that Ms. Derbyshire did indeed have competing interests. She had “consulted for and advised: The Meat Advisory Panel, Marlow Foods (Quorn), the Health Supplement Information Service and the British Egg Information Service, amongst others.” (1)
Nonetheless, choline is an interesting and important nutrient that is involved in many aspects of the function of the human body so let’s take a closer look at it.
First of all, what is choline?
Choline is an organic, water-soluble compound. It is not a vitamin but is often grouped with B vitamins due to some similarities. Choline was deemed an “essential nutrient” in 1998, meaning that it is required for normal body functioning and cannot be synthesized in the body in the amounts required for good health. The human liver is able to produce choline although generally not at levels high enough to meet the needs of most people through all stages of life. Thus some of the choline we need must be obtained through the diet (2,3,4).
Choline is a nutrient that has wide-ranging effects in human function. Among other things, it is involved in cell structure, cell messaging, transport and metabolism of lipids, synthesis of DNA and the health of the nervous system (2,3).
Choline may be important in cognitive function and brain development. Demand for choline increases during pregnancy and animal studies have suggested that choline is required for optimal neurological development of a fetus in the womb. However, this has not been established in humans. Currently there is no evidence that choline supplementation during pregnancy improves cognitive performance in the offspring (3,5).
Choline is required for the production of acetylcholine, an important neurotransmitter involved in memory, circadian rhythm and muscle function including the regulation of the heartbeat (2,3,6).
Choline is also involved in the regulation of homocysteine concentration in the blood. High homocysteine is associated with greater risks of chronic diseases such as cardiovascular disease. However, there is no convincing evidence that higher choline intake can benefit cardiovascular health by lowering blood homocysteine levels. On the contrary, certain microbial species in the human gut generate trimethylamine (TMA) from choline which may increase harmful cardiovascular events (more on this later) (3,7).
How much choline do we need?
There is no agreed recommended daily intake for choline because not enough is known about this nutrient. In 1998, the US set an Adequate Intake (AI) for choline of 550 mg daily for men and 425 mg for women, with increases to 450 mg during pregnancy and 550 mg while breastfeeding. These levels were based on a single study conducted in men where only one choline dose was used and were thought to represent the amount of choline needed to prevent liver damage (2). Europe reviewed the existing data in 2016 and set a new AI for choline of 400 mg daily for all adults, to be increased to 480 mg for pregnant women and to 520 mg daily during breastfeeding. These updated recommendations are based upon the mean choline intake of healthy populations in Europe (8).
It is interesting to note that intakes below the official AI do not necessarily indicate inadequate intake of choline. Many people are healthy on low consumption of choline while others appear to need more (2,4,6,9,10). There is little data regarding the need for choline in the diet at all stages of the life cycle. It is hypothesized that choline requirements can be met through choline synthesized by the body at some stages of life (12). On the other hand, some people who are consuming choline at the AI level show symptoms of choline deficiency (13). Choline requirements appear to depend on the individual, varying significantly with factors such as gender; age; stage of life (especially pregnancy, lactation, pre- or post-menopause); genetic makeup; amounts of betaine, folate and methionine in the diet; and ability of individuals to produce their own choline. The bottom line is that low body levels of choline are rare, especially in healthy, non-pregnant individuals. This is thought to be due to the presence of choline in many foods and the contribution of choline derived from the body’s own production (2).
Situations in which inadequate choline status is more likely to occur (2);
Pregnant and lactating women, especially in those who are not eating enough folate-containing foods or taking folic acid supplements, or those who are low in vitamin B12.
People with genetic alterations in the metabolism of choline, folate and methionine.
Patients who are not able to receive any food by mouth. In this case, it must be ensured that choline is a part of their feeding formulations.
Choline is essential for the transport of fats out of the liver and choline deficiency causes accumulation of fat in the liver. This increases the risk of NAFLD (non-alcoholic fatty liver disease) (2,3).
Some studies have suggested a possible link between low blood choline levels during pregnancy and neural tube defects in the infant. However, recent research has found no associations between maternal blood concentrations of choline during pregnancy and risk of neural tube defects. More study is necessary to determine the relationship, if any, between choline levels and neural tube defects (11,2,3).
Choline Excess (2,6)
Though consuming too much choline can have potentially harmful side effects, it is almost impossible to reach damaging choline levels through diet alone. Supplements however can raise choline intake above the UL (tolerable upper intake level – the highest amount that is unlikely to cause harm). The daily UL for choline in adults is 3500 mg per day.
High intakes of choline are toxic to the liver.
Symptoms of choline excess include excessive sweating and salivation, a fishy body odour, diarrhea, nausea, vomiting and low blood pressure.
Other Health Effects of Choline
Cognitive Effects in Adults
Alzheimer patients have lower levels of the enzyme that converts choline into acetylcholine in the brain. In addition, choline plays a part in the structural integrity of neurons. Consequently, it has been theorized that consuming higher levels of choline might reduce the progression of Alzheimer’s disease. Research in this area has been mixed however. A 2015 systematic review found no clear improvements in the cognition of healthy adults ingesting choline supplements. An earlier Cochrane review also saw no benefit of choline supplements in Alzheimer’s disease or dementia from Parkinson’s disease. More studies are needed to clarify any relationship between choline intake and cognitive function (2,3,5).
Cardiovascular Disease, Atherosclerosis and TMAO
The TMAO story is an example of the complex interplay between the foods we eat, the way we metabolize them and our health. In 2013, researchers at the Cleveland Clinic discovered a connection between diet, the gut microbiome and atherosclerosis, the build-up of cholesterol and other inflammatory substances in the walls of arteries that can lead to heart attack, stroke and death. The scientists showed that, when either of two nutrients found primarily in animal foods are consumed, certain species of microbes in the gut metabolize them into a toxic substance called trimethylamine (TMA). Within an hour of eating one of these nutrients, the TMA produced from them is oxidized in the liver into trimethylamine-N-oxide (TMAO) that then travels through the blood vessels, injuring the lining of the arteries, creating inflammation, increasing blood clotting and escalating the development of atherosclerosis (14,15,16).
Each individual person may or may not have the players needed to result in the production of damaging TMAO. If specific nutrients are not present in the diet or exist in low amounts, TMAO will not be produced. If the gut microbiome does not contain the precise microbial species capable of metabolizing the specific nutrients into TMA, TMAO will not be produced.
What are the nutrients involved?
The first one is choline. Choline is present in many foods with higher levels found in animal-sourced foods compared to plants. Choline from the diet, along with the body’s ability to produce some choline on its own, can provide the amount of choline needed for health.
The second nutrient is carnitine, a derivative of the amino acid lysine, which is used in transporting fatty acids into the cell mitochondria where they are oxidized to produce energy. It is not necessary to consume any carnitine at all because the human body can produce all that it requires. Carnitine is found mainly in animal products such as meat (including fish and poultry) and milk. Some vegetables such as asparagus also contain carnitine but in amounts that are much smaller than those found in animal-sourced foods (17).
What microorganisms create TMA?
Diet plays an integral role in the types and species of microorganisms that live in our guts. Eating animal products encourages gut flora that is able to digest carnitine and choline into TMA. The carnitine/choline to TMA conversion appears to be at least a two-step process with each step utilizing different microbial species (18). Conversely, people who do not eat animal products harbour few or none of these particular microorganisms in their gut. In one study, long-term vegans ate an 8-ounce steak, and their TMAO levels remained very low. Vegans simply do not have very many of the microorganisms that turn carnitine or choline into TMA and little TMA means low TMAO. A different arm of the same study found that, after a week of taking a broad-spectrum antibiotic by meat-eating subjects, eating an 8-ounce steak resulted in no increase in TMAO. Three weeks later, after the gut microbes had time to recover from the effects of the antibiotic, re-challenge with the meat resulted in a spike in TMAO, illustrating the critical role that gut microbes play in TMAO production (14).
Much research on TMAO has been completed in the eight years since the discovery of the link between TMAO and atherosclerosis. It is now known that people with the most TMAO circulating in their bloodstream increase their risk of stroke, myocardial infarction and death by two and a half times. This increase in cardiovascular events remains after adjustment for traditional risk factors (14,19,20). Research in 2016 reported that, among its 2235 participants with stable coronary artery disease, high blood TMAO levels were linked to higher rates of premature death and a four-fold greater risk of dying from any cause over the next five years (21). A 2017 meta-analysis of eleven prospective cohort studies found that higher circulating TMAO was associated with a 23% higher risk of cardiovascular events and a 55% higher risk of mortality (22).
Why don’t plant-based eaters have the same TMAO trouble from the choline they obtain from plants? First of all, choline levels in plants are much lower than the amounts found in animal-based foods. Secondly, the gut microbiome of a person eating completely plant-based will not contain a significant number of the microorganisms that digest carnitine and choline into TMA. Thirdly, choline originating from plants appears to result in small amounts of TMA with a lower propensity to be turned into TMAO by the liver. A study illustrated that eating two cups of Brussels sprouts daily for three weeks actually decreased blood TMAO levels. This vegetable (and presumably other similar vegetables in the cruciferous family) has the ability to downregulate the enzyme in the liver that converts TMA to TMAO (23).
Dietary Sources of Choline
Choline is present in a wide variety of foods including both animal-based and plant-based foods.
Infants require large amounts of choline to support their rapid growth rate and attain optimal development. Human breast milk is the ideal source of choline for infants. Choline concentrations in human milk double during the first week after birth and remain relatively constant thereafter (27).
FOOD SOURCES OF CHOLINE IN COMMON SERVING SIZES (2,3,24,25)
FOOD AMOUNT CHOLINE CONTENT
Beef or chicken liver 3 ounces 356 mg
Eggs, hard-boiled 1 medium 147 mg
Bacon, pan-fried 3 ounces 130 mg
Soybeans, roasted ½ cup 107 mg
Tofu, cooked 3 ounces 106 mg
Ham, roasted 3 ounces 100 mg
Ground beef 3 ounces 100 mg
Sweet peppers, green ½ cup 89 mg
Chicken or beef 3 ounces 72 mg
Fish (Atlantic Cod) 3 ounces 71 mg
Fish (Tuna) 3 ounces 25 mg
Edamame, frozen, prepared ½ cup 70 mg
Potato, baked 1 large 57 mg
Sun-dried tomatoes 2 ounces 55 mg
Tomato paste ½ cup 50 mg
Broccoli, boiled ½ cup 50 mg
Cauliflower, boiled ½ cup 48 mg
Navy beans ½ cup 56 mg
Baked beans ½ cup 49 mg
Kidney beans ½ cup 45 mg
Pistachios ¼ cup 45 mg
Peanut butter 2 tbsp 40 mg
Cashews ¼ cup 38 mg
Almonds ¼ cup 33 mg
Mushrooms, cooked ½ cup 37 mg
Asparagus, cooked ½ cup 33 mg
Brussels sprouts, boiled ½ cup 32 mg
Green peas, boiled ½ cup 28 mg
Bread, whole-wheat 2 slices 27 mg
Peanuts, dry roasted ¼ cup 24 mg
Quinoa, cooked ½ cup 21 mg
Sunflower seeds, roasted ¼ cup 19 mg
Rice, brown, cooked ½ cup 10 mg
Other Nutrients that Affect Choline
Betaine is a nutrient that can be obtained through the diet or produced from choline. Betaine, like choline, can reduce blood levels of homocysteine, a substance associated with higher risk of many chronic diseases including cardiovascular disease, cancer, cognitive decline and bone fractures.
Betaine obtained from the diet can lower choline requirements by decreasing the amount of choline needed to synthesize betaine. Foods high in betaine include spinach, quinoa, beets, wheat flour (whole-grain and refined) and pasta (whole-grain and refined).
Both folate and choline are necessary for proper brain development in humans, the formation of genetic material (DNA) and the reduction of homocysteine levels.
When folate levels are low, the body can compensate by substituting with choline. Under these conditions, more choline will be needed, either by increased consumption or higher production by the body. Conversely, if choline is in limited supply, the demand for folate will be increased.
For best health, both folate and choline sources should be part of the diet. Folate is highest in plant sources such as spinach, asparagus and Brussels sprouts. Liver is also a good source of folate. Other sources include vegetables, especially dark green leafy vegetables; fruits, especially berries; beans and peas; nuts; and grain products, both whole grains and products fortified with folate. Seafood, eggs, dairy products, meat and poultry contain lower amounts. Supplements containing folic acid, a synthetic form of folate, are also available. A 2016 study illustrated that vegans have four times higher levels of folate than meat eaters (30).
So, is there a Potential Choline Crisis?
A recent report on dietary choline intake from nine European countries showed that total choline intake in adults ranges from 284 to 468 mg/day for men and from 263 to 374 mg/day for women. Compared to the established AI levels, these results are low. Studies from the US, where the most commonly eaten diet is high in the animal products that contain choline in the highest concentrations, show that only about 10% of US citizens in all age groups meet the AI for choline (31). It must be remembered that the AIs in both the US and Europe were based on assumptions, not scientifically-derived data (32). Though intake levels above the AI imply a low probability of inadequate intake, intake below the AI does not necessarily mean inadequacy (27).
Plant-based whole food diets are consistently linked with good health. The largest organization of nutritional professionals in the world, the Academy of Nutrition and Dietetics, has stated that “appropriately planned vegetarian, including vegan, diets are healthful, nutritionally adequate and may provide health benefits in the prevention and treatment of certain diseases. These diets are appropriate for all stages of the life cycle, including pregnancy, lactation, infancy, childhood, adolescence, older adulthood and for athletes.” (33).
Only a whole food plant-based dietary pattern has been clearly demonstrated to reduce the risk of most chronic diseases and is associated with improved wellbeing in all aspects of human health (34,35,36). A whole food plant-based diet is also the only diet ever proven to reverse heart disease (37,38).
We can conclude that there is no need to worry about a choline crisis, especially one caused by eating a plant-based diet. Choline is present in many plants. A diet made up of a wide variety of plants- will provide all the choline you need for a healthy life but not enough to cause adverse effects.
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