Cognizin Citicoline by Longevity Medical Clinic

POSSIBLY INEFFECTIVE

• Athletic performance. Taking oral choline before exercise does not improve athletic performance. Details: Clinical research in trained athletes shows that taking oral choline 2.43 grams as a single dose does not delay fatigue during endurance sports when compared with placebo (5164). Other clinical research in untrained adults shows that taking oral choline 8.425 grams or 50 mg/kg once prior to participating in exhaustive, load-carrying exercise does not improve dexterity, upper or lower body strength, grip strength, or run time-to-exhaustion following exercise when compared with placebo (42229,42237).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral choline is beneficial in patients with age-related cognitive decline. Details: Small clinical studies in adults with memory loss shows that taking choline 2 grams four times daily orally for 21 days does not improve memory when compared with placebo (5170). Observational research in adults over 60 years of age has found that intake of choline 187-399.5 mg daily is associated with a 33% to 42% reduced odds of low cognitive function when compared with intake of less than 187 mg daily. Intake of more than 399.5 mg daily was not associated with low cognitive function when compared with less than 187 mg daily (109100).
• Allergic rhinitis (hay fever). It is unclear if oral choline is beneficial in patients with allergic rhinitis. Details: Preliminary clinical research shows that taking oral choline, as tricholine citrate, 500 mg three times daily for 8 weeks is less effective than intranasal budesonide 200 mcg twice daily for reducing symptoms of allergic rhinitis (42252).
• Alzheimer disease. Although there has been interest in using oral choline for Alzheimer disease, there is insufficient reliable information about the clinical effects of choline for this purpose.
• Asthma. Small clinical studies suggest that oral choline may modestly improve symptoms in patients with asthma. Details: Preliminary clinical research shows that taking choline 500-1000 mg orally three times daily for 3-4 months decreases the severity of symptoms, the number of symptomatic days, and the need to use bronchodilators in patients with asthma when compared with placebo (5165,5166). Preliminary data also shows that choline 3 grams daily might be more effective than 1.5 grams daily (5165).
• Autism spectrum disorder. Oral choline has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a combination of donepezil 2.5-5 mg daily and choline bitartrate 350 mg daily for 12 weeks improves receptive language skills, but no other outcomes, for up to 6 months after treatment when compared with placebo in children aged 5-10 years with autism spectrum disorder. Also, adolescents aged 11-16 years experienced no benefits, and some experienced an increase in behavioral symptoms, such as irritability (103571). It is unclear if this effect is due to choline, donepezil, or the combination.
• Breast Cancer. It is unclear if dietary intake of choline reduces the risk of breast cancer. Details: A meta-analysis of 6 low to moderate-quality observational studies suggests that neither high nor low dietary intake of choline is associated with breast cancer risk. This finding is largely influenced by inclusion of the European Prospective Investigation into Cancer and nutrition (EPIC) cohort study, which analyzed data from over 300,000 subjects. However, subanalysis of 3 case-control studies suggests that high dietary intake of choline may be associated with a decreased risk of breast cancer when compared with low choline intake (111416). The interpretation of these findings is limited by the heterogeneity of the included studies, self-reported data, and a small number of studies.
• Bronchitis. Although there has been interest in using oral and inhaled choline for bronchitis, there is insufficient reliable information about the clinical effects of choline for this purpose.
• Cancer. It is unclear if dietary choline intake reduces the risk for cancer. Details: A meta-analysis of 11 low-quality population studies has found that high dietary intake of choline is associated with an 18% lower risk of cancer when compared with low choline intake. High dietary intake of both choline and betaine was associated with a 40% lower risk of cancer (97390).
• Cardiovascular disease (CVD). It is unclear if dietary choline intake reduces the risk of CVD or improves outcomes in patients with CVD. Details: A meta-analysis of population research has found that high intake of dietary choline is not associated with a lower risk of coronary artery disease, stroke, or mortality when compared with a diet low in choline (97388). A more recent population study has found that energy-adjusted total choline intake is not associated with the incidence of CVD over ten years. However, the highest intake of free choline is associated with a 34% reduced risk of CVD when compared with the lowest intake (109104).
• Cerebellar ataxia. It is unclear if oral choline is beneficial in patients with cerebellar ataxia. Details: Despite some anecdotal reports suggesting that taking choline improves motor function, preliminary clinical research shows that taking choline 4-5 grams orally daily for 4 days to 6 weeks does not reduce cerebellar ataxia (5161,5173,23679).
• Cognitive function. It is unclear if oral choline is beneficial for improving cognitive function in healthy adults. Details: Preliminary clinical research shows that taking a single dose of choline 50 mg/kg orally prior to participating in an exhaustive, load-carrying task does not improve reaction time, reasoning, memory, or serial addition and subtraction ability following the task when compared with placebo (42237). Also, preliminary clinical research in patients requiring long-term total parenteral nutrition (TPN) shows that adding choline chloride 2 grams daily to TPN for 24 weeks might improve delayed visual memory, but does not improve other measures of cognitive performance, when compared with TPN alone (42232).
• Cirrhosis. Although there has been interest in using oral choline for cirrhosis, there is insufficient reliable information about the clinical effects of choline for this purpose.
• Complex partial seizures. Although there has been interest in using oral choline for complex partial seizures, there is insufficient reliable information about the clinical effects of choline for this purpose.
• Dementia. Although there has been interest in using oral choline for dementia, there is insufficient reliable information about the clinical effects of choline for this purpose.
• Depression. It is unclear if oral choline is beneficial for the treatment or prevention of depression. Details: Observational research has found that dietary choline intake of at least 198 mg daily is associated with a 32% to 43% decreased risk of depressive symptoms when compared with intakes of less than 198 mg daily (109106). It is unclear if choline supplementation is beneficial for depression.
• Diabetes. It is unclear if oral choline is beneficial for the treatment or prevention of type 2 diabetes; the available research is conflicting. Details: Preliminary clinical research shows that taking oral choline bitartrate 1000 mg daily for 2 months does not affect coagulation parameters or levels of triglycerides, low-density lipoprotein (LDL) cholesterol, or high-density lipoprotein (HDL) cholesterol in patients with type 2 diabetes (103569). Choline has also been evaluated for the prevention of type 2 diabetes. In Finnish males, observational research has found that dietary intake of total choline at levels of more than 482 mg daily, especially as phosphatidylcholine, is associated with a 25% lower risk of developing type 2 diabetes over the following 19.3 years when compared with intakes of less than 382 mg daily (103567). However, in males and females in the US, additional observational research has found no association between dietary choline and risk of type 2 diabetes over a mean of 9 years (103570). In addition, a sub-analysis found that the highest intakes of choline (a median of 487 mg daily) were associated with a 54% higher risk of type 2 diabetes among females, but not males, when compared with the lowest intakes (a median of 175 mg daily) (103570). Population research in patients with diabetes has found that an intake of dietary choline in amounts of at least 279 mg daily is associated with a 2.1-fold increased odds of diabetic retinopathy in females, but not males, when compared with an intake less than 206 mg daily (109102). It is unclear if choline itself is responsible for the increased odds of diabetic retinopathy in this population.
• Fetal alcohol spectrum disorders (FASD). It is unclear if oral choline improves cognition in children with fetal alcohol spectrum disorders (FASD). Details: Clinical research in children aged 2.5-5 years with FASD shows that taking oral choline bitartrate, providing choline 500 mg, daily for 9 months does not improve global cognitive development or hippocampal-dependent memory when compared with placebo. However, a subgroup analysis of only children aged 2.5-4 years suggests that choline may improve hippocampal-dependent memory (92112). Follow-up of this study at 7 years shows that choline improves motor speed and suggests a trend towards improved color naming, which are components of executive functioning testing, when compared with placebo (111745). The validity of these findings is limited by the high rate of patient discontinuation which limits statistical power. A small clinical trial in children 5-10 years old with FASD shows that taking oral glycerophosphocholine, providing choline 625 mg, daily for 6 weeks does not improve cognitive function, executive function, attention, or hyperactivity when compared with placebo (97389).
• Hepatitis. Although there has been interest in using oral choline for hepatitis, there is insufficient reliable information about the clinical effects of choline for this purpose.
• Huntington disease. Although there has been interest in using oral choline for Huntington disease, there is insufficient reliable information about the clinical effects of choline for this purpose.
• Hypertension. It is unclear if oral choline is beneficial for the prevention or treatment of hypertension. Details: Population research has found that every 100-mg increase in daily dietary choline intake is associated with a 15% decreased risk of developing hypertension over the next 4.6 to 9.1 years (109098). However, it is unclear if any benefits are specifically related to dietary choline or whether choline supplementation is beneficial.
• Infant development. It is unclear if oral choline intake during pregnancy is beneficial for infant development; the available research is conflicting. Details: Two observational studies have found that higher intake of choline during the second and third trimesters of pregnancy is associated with improvement in offspring cognitive development and visual memory at the age of 18 months and 7 years, respectively, when compared with lower choline intake (94654,94657). One of these studies found that each 1 mcmol/L increase in maternal blood levels of choline at 16 weeks' gestation was associated with a 2.23-point increase in cognitive skill score based on the Bayley Scales of Infant Development (BSID-III) at 18 months of age (94657). Also, some observational research has found that higher plasma levels of choline during pregnancy are associated with higher processing speed and decreased social withdrawal at 4 years of age in the offspring (109101). In contrast, 3 observational studies have found that higher intake of choline during pregnancy, as well as higher maternal and cord blood levels of choline, are not associated with improved offspring intelligence at 5 years of age or cognitive performance at 3 or 7 years of age (94654,94655,94656). However, many of these observational studies, including those with positive findings, included populations with a mean intake of choline that was below the recommended adequate intake of 450 mg daily (94654,94656). It's possible that higher intake of choline is needed to observe a benefit; however, research on the effects of choline supplementation is limited. One small clinical trial shows that taking choline 930 mg daily during the third trimester modestly improves sustained attention in the child at 7 years of age when compared with taking 480 mg daily (109105).
• Metabolic syndrome. It is unclear if oral choline is beneficial in patients with metabolic syndrome. Details: Preliminary clinical research in adults with metabolic syndrome shows that taking oral choline 400 mg daily for 4 weeks does not decrease body weight, blood pressure, plasma glucose levels, or low-density lipoprotein (LDL) cholesterol levels, or increase high-density lipoprotein (HDL) cholesterol levels, when compared with baseline (105731).
• Neural tube birth defects. It is unclear if oral choline intake is beneficial for preventing neural tube defects. Details: Population research has found that females who have a high dietary choline intake around the time of conception have a lower risk of having offspring with a neural tube defect when compared to those with lower intake (13134).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral choline is beneficial in patients with nonalcoholic fatty liver disease (NAFLD). Details: A cross-sectional analysis of results from observational and clinical research shows that low dietary intake of choline is associated with increased fibrosis in postmenopausal adults with NAFLD, but not in children, males, or premenopausal adults with NAFLD. Dietary choline intake was not associated with steatosis severity in any patient subgroup (92109).
• Schizophrenia. Although there has been interest in using oral choline for schizophrenia, there is insufficient reliable information about the clinical effects of choline for this purpose.
• Tourette syndrome. Although there has been interest in using oral choline for Tourette syndrome, there is insufficient reliable information about the clinical effects of choline for this purpose.
• TPN-associated hepatic steatosis. It is unclear if intravenous choline is beneficial in patients with TPN-associated hepatic steatosis. Details: In patients receiving long-term total parenteral nutrition (TPN), plasma levels of choline can decrease. Small, low-quality clinical studies show that administering intravenous choline 1-4 grams daily for 24 weeks improves some markers of TPN-associated hepatic steatosis when compared with baseline or placebo (5174,42235). More evidence is needed to rate choline for these uses.

(Read more about CHOLINE)

POSSIBLY EFFECTIVE

• Age-related cognitive decline. Clinical research in elderly patients shows that taking oral or intravenous citicoline daily improves some memory scores, short-term. Details: Several small clinical studies in people 50-85 years of age with age-related cognitive decline shows that taking citicoline 500-2000 mg daily, either orally or by intravenous infusion, for up to 12 weeks moderately improves memory scores when compared with placebo (12130,12131,43284,109016). Citicoline consistently improves short-term recall and verbal memory, but the effects on other domains are less clear (12130,12131,43284). In one clinical study, a specific citicoline product (Cognizin, Kyowa Hakko) 500 mg daily for 12 weeks was used (109016).
• Glaucoma. Clinical research shows that oral, intramuscular, or ophthalmic citicoline may improve vision or slow the rate of vision loss in patients with glaucoma. However, these different routes of administration have not been directly compared. Details: Preliminary clinical research in adults with open-angle glaucoma shows that taking citicoline 1600 mg orally daily for 60 days improves visual evoked potentials, but not intraocular pressure (IOP), when compared with baseline (43256). Other preliminary clinical research in patients with rapidly progressing glaucoma shows that taking a specific citicoline product (Neukron Ofta, Omikron), 500 mg orally daily for 4 four-month cycles over the course of 2 years, reduces the rate of visual field loss when compared with baseline (98448). The validity of both of these studies is limited by the lack of a comparator group. Small clinical studies in adults with open-angle glaucoma also show that treatment with intramuscular citicoline 1000 mg daily for 60 days improves visual evoked potentials, but not IOP, when compared with placebo or baseline (12173,43219,43256). Also, one clinical study shows that using a specific citicoline 2% eye drop (OMK1, Omicron) three times a day for 3 years reduces the loss of retinal nerve fibers and decreases visual field progression rates in patients with open-angle glaucoma and controlled IOP when compared with placebo (104827). Citicoline has also been used as part of a combination product. Preliminary clinical research in adults with primary open-angle glaucoma and controlled IOP shows that taking citicoline 500 mg, homotaurine 50 mg, and vitamin E 12 mg orally once daily for 4 months improves visual contrast sensitivity scores by less than 10% and self-reported quality of life scores by about 10% when compared with no additional interventions (104786). It is unclear if these effects are clinically relevant or if they are due to citicoline, other ingredients, or the combination.

POSSIBLY INEFFECTIVE

• Stroke. Oral or intravenous citicoline, started within 12-24 hours of onset of ischemic stroke symptoms, does not seem to improve outcomes in most patients. However, it may be modestly beneficial in those who are not candidates for recombinant tissue plasminogen activator (rtPA). Details: A meta-analysis of 10 trials shows that treatment with oral or intravenous citicoline 500-2000 mg daily for up to 6 weeks after ischemic stroke does not improve mortality, ability to complete activities of daily living, or neurologic function when compared with placebo or no intervention (104828). A different meta-analysis of 10 trials shows that treatment with oral or intravenous citicoline 250-2000 mg daily for up to 6 weeks after ischemic stroke increases the odds of recovery to independence by 56% and decreases the mortality rate and long-term disability by 10-12% when compared with placebo. However, this second meta-analysis included older, lower-quality trials in which the standard of care with conventional medicines was lower and ischemic stroke diagnoses were not confirmed via imaging (98228). Higher-quality trials have not confirmed these benefits, especially when patients receive early treatment with rtPA (98228,104828). A third meta-analysis of 7 trials with more limited inclusion criteria also did not demonstrate benefit on mortality or functional independence when compared with control (98447). Also, a large clinical trial of patients with moderate to severe acute ischemic stroke who received standard of care stroke management, including rtPA when indicated, shows that citicoline 1000 mg, administered intravenously over 30-60 minutes every 12 hours for 3 days and started within 24 hours of symptom onset, does not increase the rate of recovery at 90 days when compared with placebo (98444).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. It is unclear if oral citicoline is beneficial in patients with Alzheimer disease. Details: Preliminary clinical research in adults with Alzheimer disease shows that taking citicoline 1000 mg orally daily for 12 weeks modestly improves cognitive function scores when compared with placebo (43222). Observational research in adults with Alzheimer disease has also found that taking citicoline 1000 mg orally in conjunction with memantine and rivastigmine for up to 12 months is associated with clinically non-significant improvements in cognitive function scores when compared with memantine and rivastigmine alone. In addition, taking citicoline was not associated with improvement in depression scores or activities of daily living (105730).
• Amblyopia. It is unclear if oral or intramuscular citicoline is beneficial in patients with amblyopia. Details: Preliminary clinical research in children with amblyopia shows that taking citicoline orally once daily, in combination with covering the affected eye with a patch, for 12 months moderately improves visual acuity when compared with the patch alone. Children aged less than 5 years took 250 mg daily and children aged 5-13 years took 500 mg daily (98442). Retrospective research in children aged 5-6 years with amblyopia has also found that citicoline treatment for up to 8 months is associated with modest improvements in visual acuity when compared with baseline. However, preliminary subgroup analyses suggest that benefits may not last longer than 3-4 months (109017). Preliminary clinical research in older patients with amblyopia, aged 9-37 years, shows that treatment with intramuscular citicoline 1000 mg daily for 15 days improves visual acuity in both eyes for 92% of patients when compared with baseline (43281). The validity of this study is limited by the lack of a comparator group.
• Attention deficit-hyperactivity disorder (ADHD). Although there has been interest in using oral citicoline for ADHD, there is insufficient reliable information about the clinical effects of citicoline for this purpose.
• Bipolar disorder. It is unclear if oral citicoline is beneficial in patients with bipolar disorder. Details: Preliminary clinical research in adults with bipolar disorder and cocaine dependence shows that taking citicoline orally for 12 weeks improves verbal learning scores, but not symptoms of depression or mania, when compared with placebo. Citicoline was titrated from 500 mg daily to 2000 mg daily over the first 6 weeks and then continued at 2000 mg daily for 6 weeks (43248).
• Cardiac arrest. It is unclear if intravenous citicoline can improve outcomes in children with cardiac arrest. Details: A small clinical study in children 1-12 years of age with successful resuscitation from cardiac arrest shows that using citicoline 10 mg/kg intravenously every 12 hours for 6 weeks improves disability and coma scores at 12 weeks when compared with no intervention. This study also suggests that using citicoline reduces mortality by 80% and duration of hospitalization by 12% when compared with no intervention (105729). However, the small size of this study limits the reliability of these findings.
• Cerebrovascular disease. It is unclear if oral, intramuscular, or intravenous citicoline is beneficial in patients with cerebrovascular disease. Details: Several small clinical trials in adults with chronic cerebrovascular disease shows that treatment with citicoline 600-1000 mg orally daily for up to 12 months or 600-1000 mg intramuscularly or intravenously daily for up to 12 weeks moderately improves memory and behavior scores when compared with placebo or no intervention (12131,43240,43288,98443). One of these clinical trials failed to show improvement in activities of daily living, although the study may have been inadequately powered to detect a difference between groups (98443).
• Cocaine dependence. It is unclear if oral citicoline is beneficial in patients with cocaine dependence. Details: Preliminary clinical research in adults with cocaine dependence and bipolar disorder shows that taking citicoline orally for 12 weeks reduces the likelihood of positive urine cocaine test results when compared with placebo. Citicoline was titrated from 500 mg daily to 2000 mg daily over the first 6 weeks and then continued at 2000 mg daily for 6 weeks (43248). However, a post-hoc analysis suggests that the effects of citicoline on abstaining from cocaine use decline over time and were no different than placebo in the last weeks of the study (98230). In addition, other clinical research in adults with cocaine dependence that also received weekly counseling shows that taking citicoline 500 mg orally twice daily for 8 weeks does not reduce cocaine craving or consumption levels when compared with placebo (98445).
• Delirium. Although there has been interest in using oral citicoline for delirium, there is insufficient reliable information about the clinical effects of citicoline for this purpose.
• Depression. It is unclear if oral citicoline is beneficial in patients with depression. Details: Preliminary clinical research in patients with major depressive disorder shows that adding citicoline 100 mg orally twice daily for 6 weeks to citalopram therapy improves symptoms of depression, as measured by the Hamilton Depression Rating Scale, and increases the relative rate of remission by 64% when compared with placebo. These results suggest that for every 4 patients treated with citicoline, remission is expected in one additional patient (98446).
• Diabetic retinopathy. Citicoline eye drops have only been evaluated in combination with other ingredients; the effect of citicoline when used alone is unclear. Details: Preliminary clinical research in patients with mild diabetic retinopathy shows that using a specific ophthalmic solution containing citicoline 2% and cyanocobalamin 0.05% (OMK2, Omikron Italia) three times a day for 3 years decreases visual field progression rates and stabilizes retinal nerve fiber thickness when compared with placebo (104825).
• Intracranial hemorrhage. It is unclear if intravenous citicoline is beneficial in patients with intracranial hemorrhage. Details: Preliminary clinical research in patients with non-traumatic intracerebral hemorrhage shows that using citicoline 250 mg intravenously twice daily for 14 days improves muscular strength by 25% when compared with placebo (43252).
• Ischemic optic neuropathy. It is unclear if oral citicoline is beneficial in patients with ischemic optic neuropathy. Details: Preliminary clinical research in patients with non-arteritic ischemic optic neuropathy shows that taking a specific type of citicoline (Cebrolux-Tubilux) 1600 mg orally daily for 60 days improves visual acuity and visual evoked potentials when compared with no intervention (43250).
• Methamphetamine use disorder. It is unclear if oral citicoline is beneficial in patients with methamphetamine use disorder. Details: Preliminary clinical research in adults with methamphetamine dependence shows that taking citicoline 1000 mg orally twice daily for 8 weeks reduces the severity of cravings when compared with baseline, but not when compared with placebo. Taking citicoline also did not reduce the number of methamphetamine positive urine samples when compared with placebo (109015). This study may have been inadequately powered to detect a difference between groups.
• Parkinson disease. It is unclear if oral or intramuscular citicoline is beneficial in patients with Parkinson disease. Details: Preliminary clinical research shows that taking citicoline 1200 mg orally daily for one month improves Parkinson disease symptom scores when compared with no intervention (43259). Other preliminary clinical research in adults with Parkinson disease shows that treatment with citicoline 500 mg orally daily or citicoline 500-1000 mg intramuscularly daily for 30 days improves rigidity and bradykinesia scores, but not tremor scores, when compared with baseline (43253,43262). The validity of these studies is limited by the lack of a comparator group.
• Schizophrenia. It is unclear if oral citicoline is beneficial in patients with schizophrenia. Details: Preliminary clinical research in patients with chronic, stable schizophrenia shows that taking citicoline 1250 mg twice daily for 8 weeks as an add-on to risperidone therapy modestly reduces negative symptoms, but not positive symptoms, of schizophrenia when compared with placebo plus risperidone (100988). Other preliminary clinical research in patients with chronic, stable schizophrenia shows that taking citicoline 500 mg, 1000 mg, or 2000 mg as a single dose does not improve sensory gating when compared with placebo (100987). However, both studies may have been inadequately powered to detect a difference between groups.
• Traumatic brain injury (TBI). It is unclear if oral citicoline is beneficial in patients with TBI; the available research is conflicting. Details: A meta-analysis of 5 low-quality studies in patients with TBI shows that treatment with oral or intravenous citicoline up to 2000 mg daily for up to 9 days does not improve Glasgow outcome scores or cognitive performance. Additionally, one study included in this analysis showed no improvement in survival with citicoline when compared with placebo (98227). However, a very small clinical study not included in this analysis shows that taking citicoline 1000 mg orally daily improves memory, learning, and verbal ability in patients with TBI (43287). Some observational research has found that continuous intravenous infusion of citicoline 3000 mg over 24 hours for up to 21 days is associated with 6.7-fold greater odds of survival while in the intensive care unit (ICU) when compared with matched controls not receiving citicoline. Citicoline therapy was also linked to 2.6-fold greater odds of having a favorable outcome after 6 months, defined as a score of 5-8 on the extended version of the Glasgow Outcome Scale (100989). The discrepant results may be explained by differences in the severity of TBI at baseline and the doses of citicoline used in these studies.
• Vascular dementia. It is unclear if oral citicoline is beneficial in patients with vascular dementia. Details: Preliminary clinical research in adults with vascular dementia shows that taking citicoline 500 mg orally twice daily for 12 months does not improve neuropsychological symptom scores when compared with placebo (12135). More evidence is needed to rate citicoline for these uses.

(Read more about CITICOLINE)

LIKELY SAFE ...when used orally and appropriately. Choline is safe in adults when taken in doses below the tolerable upper intake level (UL) of 3.5 grams daily (3094) ...when used intravenously and appropriately. Intravenous choline 1-4 grams daily for up to 24 weeks has been used with apparent safety (5173,5174).

POSSIBLY UNSAFE ...when used orally in doses above the tolerable upper intake level (UL) of 3. 5 grams daily. Higher doses can increase the risk of adverse effects (3094).

CHILDREN: LIKELY SAFE
when used orally and appropriately (3094). Choline is safe in children when taken in doses below the tolerable upper intake level (UL), which is 1 gram daily for children 1-8 years of age, 2 grams daily for children 9-13 years of age, and 3 grams daily for children 14-18 years of age (3094).

CHILDREN: POSSIBLY UNSAFE
when used orally in doses above the UL. High doses can increase the risk of adverse effects (3094).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately. Choline is safe when taken in doses below the tolerable upper intake level (UL), which is 3 grams daily during pregnancy and lactation in those up to 18 years of age and 3.5 grams daily for those 19 years and older (3094,92114). There is insufficient reliable information available about the safety of choline used in higher doses during pregnancy and lactation.

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POSSIBLY SAFE ...when used orally and appropriately, short-term (12131). Citicoline 1000-2000 mg daily has been used with apparent safety for up to 12 weeks (12130,43248,98230,104828,109015,109016). Citicoline 2500 mg daily has also been used with apparent safety for up to 7 weeks (100988). ...when citicoline is used intravenously or intramuscularly under medical supervision (12131). Citicoline has been administered intravenously with apparent safety at a dose of 500 mg daily for 7 days, or 2000 mg daily for 3 days (43229,98444,104828). ...when used topically on the eye. Citicoline 2% eye drops have been used with apparent safety for up to 3 years alone or in combination with cyanocobalamin 0.05% (98229,104824,104825,104826,104827).

CHILDREN: POSSIBLY SAFE
when citicoline is used orally and appropriately. Citicoline has been used with apparent safety for up to 1 year at a dose of 250 mg daily in children under 5 years of age and 500 mg daily in children 5-13 years of age (98442). There is insufficient reliable information available about the safety of citicoline when used intravenously in children.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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ATROPINE Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, choline might decrease the effects of atropine in the brain.  Details Animal research shows that administering choline one hour before administering atropine can attenuate atropine-induced decreases in brain levels of acetylcholine (42240). Theoretically, concomitant use of choline and atropine may decrease the effects of atropine.

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General ...Orally, choline is well tolerated when used appropriately. Adverse effects have been reported with doses exceeding the tolerable upper intake level (UL) of 3.5 grams daily.
Most Common Adverse Effects:
Orally: Fishy body odor. At high doses of at least 9 grams daily, choline has been reported to cause diarrhea, nausea, salivation, sweating, and vomiting.

Cardiovascular ...Orally, doses of choline greater than 7. 5 grams daily may cause low blood pressure (94648).

Gastrointestinal ...Orally, large doses of choline can cause nausea, vomiting, salivation, and anorexia (42275,91231). Gastrointestinal discomfort has reportedly occurred with doses of 9 grams daily, while gastroenteritis has reportedly occurred with doses of 32 grams daily (42291,42310). Doses of lecithin 100 grams standardized to 3.5% choline have reportedly caused diarrhea and fecal incontinence (42312).

Genitourinary ...Orally, large doses of choline greater than 9 grams daily have been reported to cause urinary incontinence (42291).

Neurologic/CNS ...Orally, high intake of choline may cause sweating due to peripheral cholinergic effects (42275).

Oncologic ...In one population study, consuming large amounts of choline was associated with an increased risk of colorectal cancer in females, even after adjusting for red meat intake (14845). However, more research is needed to confirm this finding.

Psychiatric ...Orally, large doses of choline (9 grams daily) have been associated with onset of depression in patients taking neuroleptics. Further research is needed to clarify this finding (42270).

Other ...Orally, choline intake may cause a fishy body odor due to intestinal metabolism of choline to trimethylamine (42285,42275,42310,92111,92112).

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General ...Orally, intramuscularly, and intravenously, citicoline seems to be well-tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, back pain, blurred vision, constipation, diarrhea, edema, headache, insomnia, nausea, rash.

Cardiovascular ...Orally, citicoline may cause chest pain, palpitations, hypotension, bradycardia, tachycardia, and peripheral edema in some patients, although the incidence is likely similar to placebo (12130,12131,12132,43225).

Dermatologic ...Orally, citicoline may cause skin rash in some patients (12130,12132,43248).

Gastrointestinal ...Orally, citicoline may cause abdominal pain, constipation, diarrhea, and nausea in some patients (12130,12132,98846,100988,105730,109015).

Musculoskeletal ...Orally, citicoline may cause back pain in some patients (43225).

Neurologic/CNS ...Orally, citicoline may cause headache and insomnia in some patients (12130,43230,43273,98846,100988,109015,109016).

Ocular/Otic ...Orally, citicoline may cause blurred vision in some patients (12130,12132).

Other ...Orally, citicoline may cause edema of the extremities in some patients (43225).

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