Choline: Uses, Effectiveness, and Genetics

1. Conditions Studied for Choline

Choline has been studied for various health conditions including:

• Neurological disorders such as Alzheimer's disease and other dementias
• Cardiovascular diseases
• Liver diseases, such as hepatitis and cirrhosis
• Mental health conditions like depression
• Pregnancy-related issues, to support fetal brain development
• Athletic performance enhancement

2. Effectiveness in Treating Conditions

The effectiveness of choline in treating these conditions varies:

• Choline supplementation may support cognitive function, but evidence is not strong enough to confirm effectiveness in treating Alzheimer's disease or other dementias.
• Its role in cardiovascular health is linked to the modulation of homocysteine levels, but its direct impact on heart disease is not well-established.
• Choline may be beneficial for liver health, particularly in conditions related to fat accumulation in the liver.
• There is limited evidence to support choline's role in improving mood disorders like depression.
• During pregnancy, adequate choline intake is crucial for fetal brain development, but its effects on enhancing athletic performance are inconclusive.

3. Health Benefits of Choline

Choline is an essential nutrient that offers several health benefits:

• Supports the structural integrity of cell membranes
• Is critical for the synthesis of the neurotransmitter acetylcholine, which is involved in memory and muscle control
• Contributes to normal lipid metabolism and liver function
• May reduce the risk of neural tube defects during pregnancy
• Involved in DNA synthesis and cell division

4. Downsides of Choline

While choline is important for health, it can have downsides as well:

• High intakes can lead to a fishy body odor, vomiting, excessive sweating and salivation, low blood pressure, and liver toxicity.
• Some studies suggest excessive choline may be associated with an increased risk of cardiovascular disease due to the production of trimethylamine N-oxide (TMAO) when choline is metabolized by gut bacteria.

5. Choline: Genetic Variations and Impact

The impact of choline can vary based on genetic differences:

• Individuals with certain genetic polymorphisms in the MTHFR gene may have an increased need for choline, especially when folate intake is insufficient.
• Genetic variations affecting choline metabolism can influence susceptibility to liver or muscle damage from choline deficiency.
• Some people may have a genetic predisposition that leads to the production of more TMAO from choline, potentially increasing the risk of cardiovascular diseases.

Choline Research Summary

Choline, an essential nutrient, plays a vital role in the structure of lipoproteins, blood and membrane lipids, as well as in the synthesis of the neurotransmitter acetylcholine. It is also critical for neurodevelopment and can be converted into betaine to help regulate cell water balance and connect to folate-dependent metabolism.

Supplementing with choline or betaine can lower homocysteine levels, which are linked to cardiovascular diseases. High maternal intake of choline can reduce the risk of neural tube defects in offspring.

Individuals with the MTHFR 677TT genotype may have an increased need for choline and folate. A study demonstrated that these individuals show a higher conversion of choline to betaine, which may have implications for dietary requirements.

In postmenopausal women, choline supplementation raised plasma levels of choline and betaine, potentially enhancing metabolism of homocysteine, without affecting plasma lipids or folate status.

Choline uptake in the brain appears to decrease with age, potentially contributing to age-related neurodegenerative diseases. Furthermore, gut microflora are essential for producing TMA from dietary precursors like choline.

Studies have linked the metabolism of phosphatidylcholine by gut bacteria to an increased risk of cardiovascular disease, suggesting new methods for diagnosis and treatment of heart disease related to atherosclerosis.

High maternal choline intake during pregnancy can affect epigenetic regulation of genes involved in cortisol production in the fetus, potentially impacting stress response throughout the child's life.

References:

1. Choline and betaine in health and disease
2. MTHFR C677T genotype influences the isotopic enrichment of one-carbon metabolites in folate-compromised men consuming d9-choline
3. Choline supplementation and measures of choline and betaine status: a randomised, controlled trial in postmenopausal women
4. Decreased brain choline uptake in older adults. An in vivo proton magnetic resonance spectroscopy study
5. The exogenous origin of trimethylamine in the mouse
6. Isoform specificity of trimethylamine N-oxygenation by human flavin-containing monooxygenase (FMO) and P450 enzymes: selective catalysis by FMO3
7. Dietary precursors of trimethylamine in man: a pilot study
8. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
9. Cardiovascular disease: the diet-microbe morbid union
10. Flagging flora: heart disease link
11. Recent highlights of metabolomics in cardiovascular research
12. Formation of methylamines from ingested choline and lecithin
13. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk
14. Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans
15. Effects of choline-deficient diets on the rat hepatocyte. Electron microscopic observations
16. Choline-deficiency fatty liver: impaired release of hepatic triglycerides
17. Apolipoprotein B mRNA and lipoprotein secretion are increased in McArdle RH-7777 cells by expression of betaine-homocysteine S-methyltransferase
18. The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes
19. Hepatic and renal betaine-homocysteine methyltransferase activity in pigs as affected by dietary intakes of sulfur amino acids, choline, and betaine
20. Kinetic mechanism of phosphatidylethanolamine N-methyltransferase
21. The effect of low doses of betaine on plasma homocysteine in healthy volunteers
22. Trimethylaminuria: the fish-odour syndrome
23. Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication
24. The fish-odor syndrome
25. Fish odour syndrome with features of both primary and secondary trimethylaminuria
26. Mild trimethylaminuria caused by common variants in FMO3 gene
27. Trimethylaminuria (fish odor syndrome) related to the choline concentration of infant formula
28. Fish odor syndrome