Trimethylethanolamine

Choline/Drug Interactions:

  • AnticholinergicsAnticholinergics: Atropine was shown to increase choline uptake in cortical and hippocampal regions of the rat brain (105). According to one case report, in a patient who was stabilized on choline chloride 5mg daily, propantheline 15mg four times daily reduced the choline effect, while propantheline 15mg six times daily abolished it (106).
  • Antidiabetic agentsAntidiabetic agents: According to clinical evidence, intraperitoneal administration of insulin may increase plasma choline-containing phospholipids without any change in blood glucose, body weight, or daily insulin requirements (107). However, no changes in blood glucose, body weight, or daily insulin requirements were observed. In a separate study, choline was associated with decreasing blood glucose concentrations in patients with severe hepatitis (83).
  • Antilipemic agentsAntilipemic agents: According to clinical evidence, choline chloride and lecithin administration may increase LDL cholesterol levels (84). However, these results conflict with another clinical study, which showed that lecithin supplementation in patients with Alzheimer's disease increased HDL and decreased LDL and total cholesterol levels (85).
  • CaffeineCaffeine: According to animal evidence, small doses of caffeine (50mg/kg) may enhance the effect of choline (108).
  • CNS stimulantsCNS stimulants: In animal research, choline attenuated atropine-induced depletion of acetylcholine (ACh) in the hippocampus and striatum (109). At chronic and high doses (2.5mg/kg daily for 20 days), choline was shown to increase CNS ACh and norepinephrine (NE) concentrations and to increase muscarinic receptor density (110). Oral choline chloride (8g daily for three weeks or 16g daily for one week) had no effect on electroencephalogram (EEG), as measured by spectral analysis, but it appeared to have differential effects on contingent negative variation amplitude and reaction time (111).
  • EritadenineEritadenine: According to animal evidence, diets containing 8g/kg of choline chloride fully prevented eritadenine-induced fatty liver (112).
  • FluoxetineFluoxetine: It was determined in human research on a true drug response to fluoxetine that an increase in the choline:creatine ratio may occur in the basal ganglia (113; 114). A differentiation between a true drug response and a placebo pattern response has been suggested (115).
  • IsoniazidIsoniazid: In patients with Huntington's disease, treatment with isoniazid had no effects on cerebral spinal fluid levels of choline or acetylcholinesterase activity (116).
  • LithiumLithium: In lithium-treated patients, manic symptoms and mood symptoms improved in most patients following use of choline bitartrate (117). Lithium has been associated with enhancing the ratio of brain choline to plasma choline following choline chloride administration, potentiating the effects of choline on brain acetylcholine concentrations (118). A preliminary report of a double-blind magnetic resonance spectroscopic study did not observe a significant positive relationship between increases in brain choline and increases in brain lithium (119). Lithium administration in healthy individuals did not affect brain choline:creatine (Cho:Cr) ratios (120).
  • MethotrexateMethotrexate: According to animal evidence, the addition of methotrexate to choline-deficient rats may further decrease hepatic folate levels (121).
  • MethylphenidateMethylphenidate: According to clinical evidence, administration of methylphenidate in patients with attention-deficit hyperactivity disorder (ADHD) may decrease the signal of choline-containing compounds and increase N-acetyl-aspartate (NAA) levels in the anterior cingulate cortex (ACC) (122).
  • PenicillaminePenicillamine: According to expert opinion, dietary restriction of choline may prevent transmethylation with penicillamine (49).
  • PhenothiazinePhenothiazine: According to expert opinion, dietary restriction of choline may prevent transmethylation with phenothiazine (49).
  • ScopolamineScopolamine: Although a few studies have associated choline with partially reversing the effects of scopolamine (123; 124), a later study failed to demonstrate similar effects (125).
  • Selective serotonin reuptake inhibitors (SSRIs)Selective serotonin reuptake inhibitors (SSRIs): According to clinical evidence, selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome may be associated with decreased choline:total creatine (Cho:Cre) metabolite ratios in the anterior cingulate (126). Furthermore, an increase in choline:creatine ratios may occur in the basal ganglia following fluoxetine administration (113; 114).

    • Choline/Herb/Supplement Interactions:

  • AnticholinergicsAnticholinergics: Atropine was shown to increase choline uptake in cortical and hippocampal regions of the rat brain (105). In one case report, in a patient who was stabilized on choline chloride 5mg daily, propantheline 15mg four times daily reduced the choline effect, while propantheline 15mg six times daily abolished it (106).
  • AntilipemicsAntilipemics: According to clinical evidence, choline chloride and lecithin administration may increase LDL cholesterol levels (84). However, these results conflict with another clinical study, which showed that lecithin supplementation in patients with Alzheimer's disease increased HDL and decreased LDL and total cholesterol levels (85).
  • AntioxidantsAntioxidants: According to clinical evidence, choline and carnitine supplementation in healthy women may reduce thiobarbituric acid reactive substances (TBARS) (127).
  • BetaineBetaine: According to animal evidence, choline supplementation may result in decreased betaine levels in the liver (128).
  • CaffeineCaffeine: According to animal evidence, small doses of caffeine (50mg/kg) may enhance the effect of choline (108).
  • Cardiovascular agentsCardiovascular agents: In human research, choline reduced mortality rates in individuals with proven coronary thrombosis and myocardial infarction (91).
  • CarnitineCarnitine: According to animal and clinical evidence, choline supplementation may decrease urinary excretion of carnitine (129; 130).
  • Central nervous system stimulantsCentral nervous system stimulants: In animal research, choline attenuated atropine-induced depletion of acetylcholine (ACh) in the hippocampus and striatum (109). At chronic and high doses (2.5mg/kg daily for 20 days), choline was shown to increase CNS ACh and norepinephrine (NE) concentrations and to increase muscarinic receptor density (110). Oral choline chloride (8g daily for three weeks or 16g daily for one week) had no effect on electroencephalogram (EEG), as measured by spectral analysis, but appeared to have differential effects on contingent negative variation amplitude and reaction time (111).
  • HypoglycemicsHypoglycemics: According to clinical evidence, intraperitoneal administration of insulin may increase plasma choline-containing phospholipids without any change in blood glucose, body weight, or daily insulin requirements (107). However, no changes in blood glucose, body weight, or daily insulin requirements were observed. In separate research, choline has been associated with decreasing blood glucose concentrations in patients with severe hepatitis (83).
  • LecithinLecithin: In a study to determine the effects of lecithin supplementation prior to a marathon on plasma free and urinary choline concentrations and on performance, it was observed that plasma free choline increased in the lecithin-supplemented group, with no effects on performance (131). In another study, it was observed that lecithin supplementation in triathletes did not result in changes in plasma choline concentrations during exercise, although increases were observed during periods of nonexercise (132).
  • Vitamin AVitamin A: According to clinical evidence, choline and carnitine supplementation in healthy women may increase serum vitamin A concentrations (127).
  • Vitamin EVitamin E: According to clinical evidence, choline and carnitine supplementation in healthy women may increase serum vitamin E concentrations (127).

    • Choline/Food Interactions:

  • Caffeine-containing foods and drinksCaffeine-containing foods and drinks: According to animal evidence, small doses of caffeine (50mg/kg) may enhance the effect of choline (108).

    • Choline/Lab Interactions:

  • Blood glucoseBlood glucose: Choline has been associated with decreasing blood glucose concentrations in patients with severe hepatitis (83).
  • Brain acetylcholineBrain acetylcholine: In rats, choline chloride administration led to dose-dependent increases in brain acetylcholine (133). Dietary choline deficiency in rats resulted in an 85% decrease in the concentration of acetylcholine in the striata; however, this effect could be restored by acute choline administration (105).
  • CarnitineCarnitine: Daily choline supplementation (20mg/kg of body weight; duration unknown) has been shown to decrease urinary carnitine excretion in young adult women and in guinea pigs, while no effects of choline supplementation on carnitine excretion were observed in rats (129).
  • CholesterolCholesterol: According to clinical evidence, choline chloride and lecithin administration may increase LDL cholesterol levels (84). However, these results conflict with another clinical study, which showed that lecithin supplementation in patients with Alzheimer's disease increased HDL and decreased LDL and total cholesterol levels (85). Also, supplementation with choline and/or pantothenate has been shown to significantly decrease urinary carnitine excretion and renal clearance with nonesterified carnitine (NEC) in healthy adults; however, no changes were observed in any of the serum lipids (cholesterol fractions, triacylglycerols) (130).
  • Erythrocyte choline concentrationsErythrocyte choline concentrations: High-dose lecithin was shown to increase erythrocyte choline concentrations in patients with Alzheimer's disease (134).
  • Hepatic folateHepatic folate: When compared to control rats, total hepatic folate content decreased by 31% in choline deprived rats, and by 60% in choline-deficient rats also treated with methotrexate (121).
  • HomocysteineHomocysteine: In an animal model to examine the effects of choline deficiency in decreased methylation of homocysteine, and therefore elevated levels of homocysteine, da Costa et al. showed that following a choline-deficient diet, mice administered an oral methionine load resulted in elevated homocysteine levels; similar results were observed in human males during a pilot study (135). Olthof et al. conducted a placebo controlled crossover trial to examine the effects of phosphatidylcholine supplementation (the form of choline that is naturally found in foods) on fasting and postmethionine-loading concentrations of plasma total homocysteine (tHcy) in healthy men with mildly elevated plasma tHcy concentrations (136). Phosphatidylcholine supplementation for two weeks decreased mean fasting plasma tHcy by 18%. On the first day of supplementation, a single dose of phosphatidylcholine containing 1.5g of choline reduced the postmethionine-loading increase in tHcy by 15%. Phosphatidylcholine supplementation for two weeks reduced the postmethionine-loading increase in tHcy by 29%.
  • Inflammatory markersInflammatory markers: In an epidemiological study, it was determined that a diet rich in choline (>310mg daily) and betaine was linked to lower levels of inflammatory markers, including C-reactive protein, homocysteine, interleukin-6, and tumor necrosis factor (137).