Eggs are one of the best sources of choline. In a new study, Biodesign researchers argue that a lifelong dietary regimen of choline holds the potential to prevent Alzheimer's. Learn about choline's potential to help the brain and why choline may be risky for the heart.
In a new study14, Biodesign researchers reveal that a lifelong dietary regimen of choline holds the potential to significantly lower the risk of Alzheimer's disease (AD).
Dietary Choline
Choline is an important and essential nutrient. It is naturally present in many foods, particularly in eggs (see food chart below), and can be used as a dietary supplement. People with Alzheimer’s disease have lower levels of the enzyme that converts choline into acetylcholine in the brain [9]. Acetylcholine is essential to good memory and thinking. It is the neurochemical that gets boosted by popular Alzheimer's drugs like Aricept® - donepezil.Choline Supplements
As a dietary supplement, phosphatidylcholine can serve as a phospholipid precursor, as it might help support the structural integrity of neurons and thus might promote cognitive function in elderly adults [5]. Some experts have therefore theorized that consuming higher levels of phosphatidylcholine could reduce the progression of dementia in people with Alzheimer’s disease [9].In this new study, lead author Ramon Velazquez and his colleagues at the ASU-Banner Neurodegenerative Disease Research Center (NDRC) looked into how choline could alleviate the effects of Alzheimer's.
Big Studies of Choline & the Brain
Until this study was done, a few observational studies showed a link between cognitive performance in adults and both higher choline intakes and plasma concentrations.In one observational study in 2,195 adults aged 70–74 years in Norway, participants with plasma free choline concentrations lower than 8.4 mcmol/L (20th percentile of concentrations in the study population) had poorer sensorimotor speed, perceptual speed, executive function, and global cognition than those with choline concentrations higher than 8.4 mcmol/L [10].
A second study in 1,391 adults aged 36–83 years from the Framingham Offspring study who completed food frequency questionnaires from 1991 to 1995 and again from 1998 to 2001 found that those with higher choline intakes had better verbal memory and visual memory [11]. Furthermore, higher choline intakes during the earlier period were associated with smaller white matter hyperintensity volume (a high volume is a sign of small-vessel disease in the brain).
On the other hand, a 2015 systematic review of 13 studies on the relationship between choline levels and neurological outcomes in adults found that choline supplements did not result in clear improvements in cognition in healthy adults [5]. Similarly, a 2003 Cochrane review of 12 randomized trials in 265 patients with Alzheimer’s disease, 21 with Parkinsonian dementia, and 90 with self-identified memory problems found no clear clinical benefits of lecithin supplementation for treating Alzheimer’s disease or Parkinsonian dementia [9].
It seems clear from these studies that choline deficiency is connected to how well the brain functions. Future studies are still needed to clarify whether choline supplements might benefit patients with Alzheimer’s disease or other forms of dementia.
Choline Intakes and Status
Most people in the United States consume less than their minimum choline AI. (AI = Adequate Intake. [NOTE: AI is established when evidence is insufficient to develop an RDA.] )The AI for choline is:
- 550 mg / day for men
- 425 mg/day for women
Choline Deficiency
Choline deficiency can cause muscle damage, liver damage, and nonalcoholic fatty liver disease (NAFLD or hepatosteatosis) [1,2,3,7]. Although most people in the United States consume less than the AI of choline, frank choline deficiency in healthy, nonpregnant individuals is very rare, possibly because of the contribution of choline that the body synthesizes endogenously [1,4].| Food | Milligrams (mg) per serving |
Percent DV* |
|---|---|---|
| Beef liver, pan fried, 3 ounces | 356 | 65 |
| Egg, hard boiled, 1 large egg | 147 | 27 |
| Beef top round, separable lean only, braised, 3 ounces | 117 | 21 |
| Soybeans, roasted, ½ cup | 107 | 19 |
| Chicken breast, roasted, 3 ounces | 72 | 13 |
| Beef, ground, 93% lean meat, broiled, 3 ounces | 72 | 13 |
| Fish, cod, Atlantic, cooked, dry heat, 3 ounces | 71 | 13 |
| Mushrooms, shiitake, cooked, ½ cup pieces | 58 | 11 |
| Potatoes, red, baked, flesh and skin, 1 large potato | 57 | 10 |
| Wheat germ, toasted, 1 ounce | 51 | 9 |
| Beans, kidney, canned, ½ cup | 45 | 8 |
| Quinoa, cooked, 1 cup | 43 | 8 |
| Milk, 1% fat, 1 cup | 43 | 8 |
| Yogurt, vanilla, nonfat, 1 cup | 38 | 7 |
| Brussels sprouts, boiled, ½ cup | 32 | 6 |
| Broccoli, chopped, boiled, drained, ½ cup | 31 | 6 |
| Cottage cheese, nonfat, 1 cup | 26 | 5 |
| Fish, tuna, white, canned in water, drained in solids, 3 ounces | 25 | 5 |
| Peanuts, dry roasted, ¼ cup | 24 | 4 |
| Cauliflower, 1” pieces, boiled, drained, ½ cup | 24 | 4 |
| Peas, green, boiled, ½ cup | 24 | 4 |
| Sunflower seeds, oil roasted, ¼ cup | 19 | 3 |
| Rice, brown, long-grain, cooked, 1 cup | 19 | 3 |
| Bread, pita, whole wheat, 1 large (6½ inch diameter) | 17 | 3 |
| Cabbage, boiled, ½ cup | 15 | 3 |
| Tangerine (mandarin orange), sections, ½ cup | 10 | 2 |
| Beans, snap, raw, ½ cup | 8 | 1 |
| Kiwifruit, raw, ½ cup sliced | 7 | 1 |
| Carrots, raw, chopped, ½ cup | 6 | 1 |
| Apples, raw, with skin, quartered or chopped, ½ cup | 2 | 0 |
Newest Choline-Alzheimer's Study
Lead author Ramon Velazquez and his colleagues at the ASU-Banner Neurodegenerative Disease Research Center (NDRC) looked into whether this nutrient could alleviate the effects of Alzheimer's.Earlier this year, Velazquez and colleagues found transgenerational benefits of AD-like symptoms in mice whose mothers were supplemented with choline. The latest work expands this line of research by exploring the effects of choline administered in adulthood rather than in fetal mice.
The study focuses on female mice bred to develop AD-like symptoms. Given the higher prevalence of AD in human females, the study sought to establish the findings in female mice. Results showed that when these mice are given high choline in their diet throughout life, they exhibit improvements in spatial memory, compared with those receiving a normal choline regimen.
Notably, findings published in July 2019 from a group in China found benefits of lifelong choline supplementation in male mice with AD-like symptoms. "Our results nicely replicate findings by this group in females," Velazquez says.
Intriguingly, the beneficial effects of lifelong choline supplementation reduce the activation of microglia. Microglia are specialized cells that rid the brain of deleterious debris. Although they naturally occur to keep the brain healthy, if they are overactivated, brain inflammation and neuronal death, common symptoms of AD, will occur.
The observed reductions in disease-associated microglia, which are present in various neurodegenerative diseases, offer exciting new avenues of research and suggest ways of treating a broad range of disorders, including traumatic brain injuries, multiple sclerosis and Parkinson's disease.
The findings appear in the current issue of the journal Aging Cell.
Supplementing the brain with additional choline
Choline acts to protect the brain from Alzheimer's disease in at least two ways, both of which are explored in the new study.First, choline blocks the production of amyloid-beta plaques. Amyloid-beta plaques are the hallmark pathology observed in Alzheimer's disease.
Mechanistically, the reductions in microglia activation are driven by alteration of two key receptors, the alpha7 nicotinic acetylcholine and Sigma-1 receptor. A new report this year found that choline can act as an agonist for Sigma-1 receptors. These results confirm that lifelong choline supplementation can alter the expression of the Sigma-1 receptor, which thereby attenuates microglia activation. (An agonist is a substance that activates a given receptor.)
Guidelines for dietary choline
Prior research concerning Alzheimer's has indicated that there is no one factor at play. Rather, a multitude of factors that are believed to contribute to the development of the disease, including genetics, age and lifestyle. Additionally, studies suggest that diet can have a significant effect in increasing or lowering the risk of cognitive decline.A recent report suggested that plant-based diets may be determinantal due to the lack of important nutrients, including choline. Another recent report found that the increase in cases of dementia in the United Kingdom may be associated with a lack of recommendations for choline in the diet throughout life. In fact, as of August 2019, AD and other forms of dementia are now the leading cause of death in England and Wales.
How Much Choline?
The current established adequate intake (AI) level of choline for adult women (>19yrs of age) is 425mg/day, and 550mg/day for adult men. A converging line of evidence indicates that even the current recommended daily intake (RDI) may not be optimal for a proper aging process, especially in women. This is relevant, given the higher incidence of AD seen in women. This suggests that additional choline in diet may be beneficial in preventing neuropathological changes associated with the aging brain.The tolerable upper limit (TUL) of choline unlikely to cause side effects for adult females and males (>19yrs of age) is 3500mg/day, which is 8.24 times higher than the 425mg/day recommendation for females and 6.36 times higher than the 550mg/day recommendation for males. "Our choline supplemented diet regimen was only 4.5 times the RDI, which is well below the TUL and makes this a safe strategy," Velazquez says.
Choline can be found in various foods. According to the United States Department of Agriculture (USDA), high levels of choline are found in:
- chicken liver (3oz; 247mg),
- eggs (1 large egg with yolk;147mg),
- beef grass-fed steak (3oz; 55mg),
- wheat germ (1oz toast; 51mg),
- milk (8oz; 38mg), and
- Brussels sprouts (1/2 cup; 32mg).
Cardio & Choline - Brain Healthy, Heart Risky
Too much choline—a compound concentrated in eggs and other animal products—can make bodily secretions smell like rotting fish, and may increase the risk of heart disease, due to conversion in the gut to trimethylamine. The potential dangers and concerns are outlined in the following expert video by Dr. Michael Gregger from NutritionFacts.org.
Article continued below...
Effects of Choline
All plant and animal cells require choline to maintain their structural integrity. It has long been recognized that choline is particularly important for brain function.The human body uses choline to produce acetylcholine, a neurotransmitter responsible for functioning memory, muscle control and mood. Choline also is used to build cell membranes and plays a vital role in regulating gene expression. Additionally, a new report in Jan 2019 found that choline acts as an agonist for Sigma-1 receptors, which are implicated in AD pathogenesis.
In this study, researchers used a water maze to determine whether the mice with AD-like symptoms that received lifelong supplemental choline exhibited improvements in spatial memory. It was found that this was indeed the case, and subsequent examination of mouse tissue extracted from the hippocampus, a brain region known to play a central role in memory formation, confirmed changes in toxic amyloid-beta and reductions in microglia activation, which reduces brain inflammation.
Due to alterations of key microglia receptors induced by choline, the improvements in behavior may be attributed to reduced microglia activation. "We found that lifelong choline supplementation altered the alpha7 nicotinic acetylcholine and Sigma-1 receptor, which may have resulted in the reduction of diseased associated activated microglia," Velazquez said. These receptors regulate CNS immune response and their dysregulation contributes to AD pathogenesis.
Lifelong Benefits of Choline
The study's significance establishes beneficial effects of nutrient supplementation in females throughout life. "Our work nicely complements recent work showing benefits in male AD-mice on a lifelong choline supplementation regimen.""No one has shown lifelong benefits of choline supplementation in female AD-mice."
"That's what is novel about our work."
Choline is an attractive candidate for prevention of AD as it is considered a very safe alternative, compared with many pharmaceuticals. "At 4.5 times the RDI (recommended daily intake), we are well under the tolerable upper limit, making this a safe preventive therapeutic strategy."
Although the results improve the understanding of the disease, the authors suggest that clinical trials will be necessary to confirm whether choline can be used as a viable treatment in the future.
SOURCES:
- Choline - Office of Dietary Supplements, U.S. Department of Health & Human Services, National Institutes of Health
- Biodesign Institute - Arizona State University
- NutritionFacts.org
REFERENCES
- Zeisel SH, Corbin KD. Choline. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Washington, DC: Wiley-Blackwell; 2012:405-18.
- Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998.
- Zeisel SH. Choline. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2014:416-26.
- Hollenbeck CB. An introduction to the nutrition and metabolism of choline. Cent Nerv Syst Agents Med Chem 2012;12:100-13. [PubMed abstract]
- Leermakers ET, Moreira EM, Kiefte-de Jong JC, Darweesh SK, Visser T, Voortman T, et al. Effects of choline on health across the life course: a systematic review. Nutr Rev 2015;73:500-22. [PubMed abstract]
- U.S. Department of Agriculture, Agricultural Research Service. Nutrient Intakes from Food and Beverages: Mean Amounts Consumed per Individual, by Gender and Age, What We Eat in America, NHANES 2013-2014. 2016
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- Corbin KD, Zeisel SH. Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression. Curr Opin Gastroenterol 2012;28:159-65. [PubMed abstract]
- Buchman AL, Sohel M, Brown M, Jenden DJ, Ahn C, Roch M, et al. Verbal and visual memory improve after choline supplementation in long-term total parenteral nutrition: a pilot study. JPEN J Parenter Enteral Nutr 2001;25:30-5. [PubMed abstract]
- Higgins JP, Flicker L. Lecithin for dementia and cognitive impairment. Cochrane Database Syst Rev 2003:CD001015. [PubMed abstract]
- Nurk E, Refsum H, Bjelland I, Drevon CA, Tell GS, Ueland PM, et al. Plasma free choline, betaine and cognitive performance: the Hordaland Health Study. Br J Nutr 2013;109:511-9. [PubMed abstract]
- Poly C, Massaro JM, Seshadri S, Wolf PA, Cho E, Krall E, et al. The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. Am J Clin Nutr 2011;94:1584-91. [PubMed abstract]
- Naber M, Hommel B, Colzato LS. Improved human visuomotor performance and pupil constriction after choline supplementation in a placebo-controlled double-blind study. Sci Rep 2015;5:13188. [PubMed abstract]
- U.S. Department of Agriculture, Agricultural Research Service. FoodData Central, 2019.
- Ramon Velazquez, Eric Ferreira, Sara Knowles, Chaya Fux, Alexis Rodin, Wendy Winslow, Salvatore Oddo. Lifelong choline supplementation ameliorates Alzheimer’s disease pathology and associated cognitive deficits by attenuating microglia activation. Aging Cell, 2019; DOI: 10.1111/acel.13037
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