Quaternary ammonium compound

Water-soluble nutrient

Precursor to several vital compounds

Can be synthesized from methionine (amino acid) with folate, B12, and B6

Endogenous production insufficient for most people

Most abundant choline form in food

Found in egg yolks, soybeans, organ meats

Contains ~13-15% choline by weight

Must be broken down to release free choline

Common supplement form (soy or sunflower lecithin)

Used as emulsifier in food manufacturing

Common, inexpensive supplement form

~41% choline by weight

Water-soluble salt

Good bioavailability

May cause fishy body odor in some people at high doses

Doesn't cross blood-brain barrier as well as other forms

Similar to bitartrate

~75% choline by weight

Used in animal feed and some supplements

Very hygroscopic (absorbs moisture)

Cytidine 5'-diphosphocholine

~18% choline by weight

Crosses blood-brain barrier efficiently

Converts to both choline and cytidine (nucleotide)

Superior for cognitive benefits

More expensive than choline bitartrate

Well-researched for brain health

~40% choline by weight

Crosses blood-brain barrier very well

Preferred for cognitive enhancement

Expensive compared to bitartrate

Well-absorbed and utilized

Popular in nootropic community

Various forms (citrate, malate, etc.)

Different choline content by weight

Bioavailability varies

Critical neurotransmitter

Made from choline + acetyl-CoA

Essential for memory, learning, muscle control

Parasympathetic nervous system signaling

Cholinergic neurons throughout brain and body

Major component of cell membranes

Especially abundant in brain

Provides structural integrity

Involved in cell signaling

Oxidation product of choline

Methyl donor in homocysteine metabolism

Alternative to choline for some functions

Can spare choline requirements

Used in supplements

Structural component of myelin sheath

Protects nerve fibers

Contains choline in structure

Essential nutrient (inadequate endogenous synthesis)

Water-soluble

Can be synthesized from methionine (but usually insufficient)

Required for synthesis cannot be replaced by other nutrients

Stored primarily in liver as phosphatidylcholine

Excreted as trimethylamine oxide (TMAO) and other metabolites

Major component of phosphatidylcholine

Maintains cell membrane integrity

Structural role in all cells

Particularly important in liver and brain

Lipid trafficking and metabolism

Cell signaling

Precursor to acetylcholine

Essential for cholinergic neurotransmission

Memory and learning

Muscle control and movement

Autonomic nervous system function

Parasympathetic signaling

Required for VLDL (very low-density lipoprotein) formation

Prevents fat accumulation in liver

Exports fat from liver

Essential for normal lipid metabolism

Prevents fatty liver disease

Converted to betaine (methyl donor)

Homocysteine metabolism (with folate, B12, B6)

Alternative methylation pathway

DNA methylation and gene expression

Epigenetic modifications

Reduces choline needs if adequate methionine

Critical during fetal development

Neurogenesis (new neuron formation)

Synaptogenesis (synapse formation)

Brain structure and organization

Myelin formation

Lifelong brain health

Second messenger systems

Calcium signaling

Inflammation regulation

Apoptosis (programmed cell death)

Supports memory formation and recall

Enhances learning capacity

Improves attention and focus

May slow cognitive decline with aging

Supports processing speed

Executive function

Protects against neurodegeneration

May reduce Alzheimer's disease risk

Supports stroke recovery

Traumatic brain injury recovery

Age-related cognitive decline prevention

Myelin sheath maintenance

Prevents non-alcoholic fatty liver disease (NAFLD)

Supports fat metabolism and export

Protects against liver damage

Helps reverse fatty liver

Supports detoxification

Important for alcohol metabolism

Critical for neural tube formation

Brain development throughout pregnancy

Reduces risk of neural tube defects

Cognitive development of child

May reduce risk of cleft palate

Impacts lifelong cognitive function

Lowers homocysteine (via betaine conversion)

May reduce cardiovascular disease risk

Supports healthy blood pressure

Anti-inflammatory effects

Vascular function

Note: TMAO concern (discussed in toxicity section)

Acetylcholine for muscle contraction

May improve power output

Reduces fatigue in some studies

Supports neuromuscular function

Popular in sports supplements

May help with anxiety

Supports mood regulation

Important for neurotransmitter balance

May help depression (limited evidence)

Membrane integrity in mitochondria

Energy production

Cellular respiration

Epigenetic modifications

DNA methylation

Histone modifications

Long-term gene regulation

Infants 0-6 months: 125 mg

Infants 7-12 months: 150 mg

Children 1-3 years: 200 mg

Children 4-8 years: 250 mg

Children 9-13 years: 375 mg

Males 14+ years: 550 mg

Females 14-18 years: 400 mg

Females 19+ years: 425 mg

Pregnancy: 450 mg

Breastfeeding: 550 mg

Adults: 3,500 mg daily

Concern: Fishy body odor, hypotension, liver toxicity

Most people: well under this amount

Supplements: typically provide 250-1,000 mg

Most people: meet AI (425-550 mg) from food + endogenous synthesis

Many fall short: especially women, vegetarians, pregnant women

Optimal: 450-550 mg daily total (food + supplements)

AI: 450 mg (likely insufficient)

Optimal: 600-900 mg daily

Critical period: throughout pregnancy and breastfeeding

Higher needs: for fetal brain development

Most prenatal vitamins: contain little to no choline

AI: 550 mg

Optimal: 550-1,000 mg daily

Breast milk: concentrated source for infant

Maternal stores: depleted if intake inadequate

General support: 250-500 mg daily

Cognitive decline: 500-1,000 mg daily

Alpha-GPC or CDP-choline: 300-600 mg daily (more potent)

Varies by form: due to different choline content

NAFLD prevention: 450-550 mg daily

Fatty liver treatment: 1,000-3,000 mg daily (phosphatidylcholine)

With other liver support: comprehensive approach

Standard: 250-500 mg daily

Pre-workout: 500-1,000 mg

Alpha-GPC popular: 300-600 mg pre-exercise

Pregnancy and breastfeeding (highest needs)

Genetic variations (PEMT gene polymorphisms)

Postmenopausal women (reduced estrogen affects synthesis)

Vegetarian/vegan diets (lower intake from food)

High alcohol consumption

Intense exercise

Low folate, B12, or B6 (impairs endogenous synthesis)

High methionine intake (can reduce needs via methylation)

Liver disease

Certain medications

Phosphatidylethanolamine N-methyltransferase

Enzyme that synthesizes choline from methionine

Common polymorphisms: reduce enzyme activity

Postmenopausal women: especially affected (estrogen regulates PEMT)

Higher dietary needs: if PEMT variant

May explain why many people deficient

Affects folate metabolism

Folate needed for choline synthesis from methionine

MTHFR variants: may increase choline needs

Complex interaction: with one-carbon metabolism

Beef liver: 356 mg per 3 oz (highest common source)

Chicken liver: 247 mg per 3 oz

Eggs (whole): 147 mg per large egg (mostly in yolk)

Beef: 117 mg per 3 oz

Salmon: 187 mg per 3 oz

Cod: 190 mg per 3 oz

Shrimp: 115 mg per 3 oz

Chicken breast: 73 mg per 3 oz

Turkey: 70 mg per 3 oz

Pork chops: 94 mg per 3 oz

Scallops: 94 mg per 3 oz

Soybeans (cooked): 107 mg per cup

Kidney beans: 67 mg per cup (cooked)

Quinoa: 43 mg per cup (cooked)

Milk: 43 mg per cup

Yogurt: 38 mg per cup

Brussels sprouts: 63 mg per cup (cooked)

Broccoli: 63 mg per cup (cooked)

Cauliflower: 48 mg per cup (cooked)

Peas: 47 mg per cup

Peanuts: 24 mg per 1/4 cup

Almonds: 15 mg per 1/4 cup

Whole wheat bread: 13 mg per slice

Brown rice: 19 mg per cup (cooked)

Spinach: 25 mg per cup (cooked)

Mushrooms: 21 mg per cup

Tomatoes: 13 mg per cup

Potatoes: 57 mg per medium (with skin)

Egg yolks: richest concentrated source

Animal products: generally higher than plant foods

Processing: minimal loss in most cooking methods

Whole foods: preferred over refined

Variety: important for adequate intake

Vegetarian/vegan: need to be more intentional

Lower overall intake: animal products richest sources

Key plant sources: soybeans, quinoa, cruciferous vegetables, beans

Lecithin supplements: soy or sunflower derived

May need supplements: to meet optimal intake

Fortified foods: some plant milks fortified with choline

Most common and cheapest form

41% choline by weight (1,000 mg bitartrate = 410 mg choline)

Good bioavailability for general needs

Less efficient brain delivery than Alpha-GPC or CDP-choline

May cause fishy odor at high doses (varies individually)

Good for: liver health, general supplementation, pregnancy

Dosage: 250-1,000 mg choline (from bitartrate)

40% choline by weight

Superior brain delivery (crosses blood-brain barrier efficiently)

Preferred for cognitive enhancement

More expensive (3-5x cost of bitartrate)

Well-researched for memory and cognition

May increase growth hormone (some evidence)

Good for: cognitive function, Alzheimer's, athletic performance, brain health

Dosage: 300-600 mg daily (provides 120-240 mg choline)

18% choline by weight

Provides both choline and cytidine

Excellent brain delivery

Extensively researched for stroke, cognitive decline

Neuroprotective properties

More expensive than bitartrate

Unique benefits beyond just choline delivery

Good for: stroke recovery, traumatic brain injury, cognitive decline, focus

Dosage: 250-1,000 mg daily (provides 45-180 mg choline)

13-15% choline by weight

Whole phospholipid, not just choline

Soy or sunflower sources

Gentle and well-tolerated

Supports liver health specifically

Less concentrated than other forms

Good for: liver health, general supplementation, high-dose therapy

Dosage: 1,000-10,000+ mg daily (provides 130-1,500+ mg choline)

75% choline by weight (most concentrated)

Hygroscopic (absorbs moisture)

Less common in consumer supplements

More common in animal feed

Dosage: 250-500 mg choline (from chloride)

Cost-effective general supplementation

Liver health and fatty liver

Pregnancy (proven safe)

Meeting daily choline needs

Most economical option

General health maintenance

Cognitive enhancement and nootropic use

Memory improvement

Alzheimer's disease or dementia

Athletic performance (pre-workout)

Brain health focus

Age-related cognitive decline

Worth extra cost for brain-specific benefits

Stroke recovery or prevention

Traumatic brain injury

Cognitive decline and dementia

Focus and attention

Neuroprotection

Unique benefits beyond choline alone

Research-backed for specific conditions

Liver health (especially fatty liver)

High-dose therapy

Gentle, well-tolerated supplementation

Whole phospholipid benefits

Pregnant women preferring whole food-like form

Those sensitive to other forms

Assess diet: calculate choline from food

Supplement gap: 250-550 mg total daily

Choose form: bitartrate or lecithin cost-effective

With meals: enhances absorption

Start preconception: build stores

Throughout pregnancy: 450-900 mg total daily

Continue breastfeeding: 550-1,000 mg daily

Prenatal vitamin: most lack adequate choline, supplement separately

Form: bitartrate or phosphatidylcholine safe and effective

Alpha-GPC: 300-600 mg daily

CDP-choline: 250-500 mg daily

Timing: morning or before cognitively demanding tasks

Cycling: some take breaks (not necessary)

Combination: can combine with other nootropics

Phosphatidylcholine: 1,000-3,000 mg daily

Choline bitartrate: 500-1,000 mg choline daily

Duration: several months for fatty liver

Medical supervision: for diagnosed liver disease

Lifestyle: diet and exercise also critical

Alpha-GPC: 300-600 mg pre-workout (30-60 min before)

Choline bitartrate: 500-1,000 mg pre-workout

Not daily: typically just before training/competition

Individual response: varies considerably

With meals: generally recommended for absorption

Morning: if using for cognitive enhancement

Pre-workout: 30-60 minutes before exercise

Consistent daily: for general health and pregnancy

Divide doses: if taking high amounts (>1,000 mg)

Methylation pathway: choline and folate work together

Can partially substitute: for some choline functions

Mutual sparing: adequate folate reduces choline needs

Pregnancy: both critical for neural tube development

Always combine: especially during pregnancy

Methylation pathway: works with folate and choline

Homocysteine metabolism: all three needed

Betaine pathway: alternative to folate/B12 pathway

Nerve function: both important

Homocysteine metabolism: third member of trio

Neurotransmitter synthesis: both involved

One-carbon metabolism: integrated pathways

All B vitamins: work together in metabolism

Prevents imbalances: from high single B vitamins

Comprehensive support: for methylation and energy

Synergistic for brain: choline + DHA particularly important

Cell membranes: both structural components

Phosphatidylcholine + DHA: form complex membrane lipids

Pregnancy: both essential for fetal brain

Cognitive function: complementary mechanisms

Inflammation: both anti-inflammatory

Phospholipid synthesis: combines with choline

CDP-choline provides: both choline and uridine (as cytidine)

Synergistic for brain: membrane synthesis

Popular stack: uridine + choline + DHA

Neurite outgrowth: supports new neural connections

Membrane phospholipid: works with phosphatidylcholine

Cognitive benefits: complementary to choline

Stress response: both support HPA axis

Brain health: synergistic neuroprotection

Alpha-GPC or CDP-choline: 300-600 mg

Omega-3s (DHA-rich): 1-2g daily

Phosphatidylserine: 100-300 mg

Uridine: 250-500 mg

B-complex: comprehensive support

Bacopa monnieri: 300-600 mg (cholinergic effects)

Huperzine A: 100-200 mcg (acetylcholinesterase inhibitor)

Choline: 600-900 mg total daily

Folate: 600-800 mcg (methylfolate preferred)

DHA: 300-600 mg daily

B12: 500-1,000 mcg

Iron: as needed

Comprehensive prenatal: with additional choline

Phosphatidylcholine or choline bitartrate: 1,000-3,000 mg

Milk thistle (silymarin): 200-400 mg daily

NAC (N-acetylcysteine): 600-1,200 mg daily

Alpha-lipoic acid: 300-600 mg daily

Vitamin E: 400 IU (mixed tocopherols)

B-complex: methylation support

Choline (as betaine): reduces homocysteine

B12: 500-1,000 mcg (methylcobalamin)

Folate: 400-800 mcg (5-MTHF)

B6: 25-50 mg

Betaine (TMG): 500-1,500 mg (direct methyl donor)

Omega-3s: 2-3g daily

Alpha-GPC: 300-600 mg pre-workout

Caffeine: 200-400 mg (synergistic for power output)

Creatine: 3-5g daily

Beta-alanine: 3-6g daily

Citrulline: 6-8g daily

Oppose choline's effects

Used for: overactive bladder, COPD, Parkinson's

Examples: oxybutynin, tolterodine, benztropine

Choline may counteract: medication effects

Medical consultation: before combining

Alzheimer's drugs: donepezil (Aricept), rivastigmine, galantamine

Increase acetylcholine: similar to choline supplementation

Additive effects: may enhance or cause side effects

Medical supervision: coordinate supplementation

May be beneficial: but dose adjustment needed

Affects folate metabolism

May alter choline/folate balance

Medical supervision: if on methotrexate

Can be converted: to choline via PEMT pathway

High methionine: reduces choline requirements

Animal protein: high in methionine

Vegetarians: lower methionine, higher choline needs

Positive interaction: work together in methylation

Adequate B vitamins: support choline synthesis

Deficiency: increases choline requirements

Always combine: especially during pregnancy

Can substitute: for some choline functions

Methyl donor: like choline

May reduce: choline requirements

Often combined: synergistic methylation support

Dosage: 500-3,000 mg daily

Depletes choline

Increases need: for liver fat metabolism

Chronic use: significantly increases requirements

Fatty liver: choline helps prevent

Supplementation helpful: for drinkers

Increases choline needs: for lipid metabolism

VLDL formation: requires phosphatidylcholine

Liver fat export: choline-dependent

Gut bacteria: convert choline to trimethylamine (TMA)

TMA to TMAO: in liver

TMAO concern: associated with cardiovascular disease in some studies

Complex relationship: not definitively causal

Individual variation: gut microbiome differences

Eggs controversy: high choline, TMAO concerns

Current thinking: benefits likely outweigh TMAO concerns for most people

Moderation: reasonable approach

Too much acetylcholine: theoretically possible

Symptoms: nausea, diarrhea, low blood pressure, sweating

Rare with supplements: at normal doses

More concern: with cholinesterase inhibitors

Critical for fetal brain development

Neural tube formation

Lifelong cognitive effects: on child

Most prenatal vitamins: inadequate choline

600-900 mg daily: recommended

Start preconception: build stores

Throughout pregnancy: maintain intake

Not negotiable: one of most important pregnancy nutrients

High needs: 550-1,000 mg daily

Breast milk: concentrated source for infant

Infant brain development: continues postpartum

Maternal stores: depleted if inadequate intake

Essential: continue through breastfeeding

Reduced estrogen: decreases PEMT enzyme activity

Cannot synthesize: as much endogenous choline

Higher dietary needs: than premenopausal women

Genetic variations: especially problematic post-menopause

450-550 mg daily: recommended minimum

Lower intake: from plant foods vs animal products

Eggs: richest source (often excluded)

Need intentional: inclusion of choline sources

Soy products: good plant source (tofu, soybeans)

Supplementation: often beneficial

450-550 mg daily: ensure adequate total

Common polymorphisms: reduce choline synthesis

Higher dietary needs: cannot compensate via synthesis

Postmenopausal women: particularly affected

Genetic testing: can identify (not essential)

If family history: of choline-responsive conditions

550-900 mg daily: may be beneficial

Age-related cognitive decline

Alzheimer's disease: family history or risk

Memory problems: subjective or objective

Neuroprotection: preventive strategy

Alpha-GPC or CDP-choline: preferred forms

300-600 mg daily: for cognitive support

Non-alcoholic fatty liver disease

Choline deficiency: can cause fatty liver

Treatment and prevention: choline beneficial

Weight loss: still primary intervention

1,000-3,000 mg daily: therapeutic doses

Phosphatidylcholine: preferred form for liver

Increased needs: for liver fat metabolism

Fatty liver risk: alcohol-related

Choline protective: against liver damage

Supplementation: helpful alongside moderation

550-1,000+ mg daily

Acetylcholine: for muscle contraction

Choline depleted: during intense exercise

May improve: power output and performance

Pre-workout: 300-600 mg Alpha-GPC

Individual response: varies considerably

Processed food diet: low in choline

Limited eggs, meat, fish: major sources

Food insecurity: inadequate overall nutrition

Restrictive diets: various reasons

At least meet AI: 425-550 mg daily

Rare genetic disorder: cannot metabolize trimethylamine

Choline supplementation: worsens fishy body odor

Avoid supplements: or use very low doses

Dietary sources: may be better tolerated

Medical diagnosis: confirms condition

Acetylcholine and dopamine: reciprocal relationship

High choline/acetylcholine: may worsen Parkinsonian symptoms theoretically

Evidence limited: not well-studied

Medical supervision: if considering supplementation

Low doses: likely safe

Some evidence: choline may worsen depression in bipolar

Mechanism unclear

Avoid high doses: during depressive episodes

Medical consultation: essential

Standard dietary intake: likely fine

Some animal evidence: high choline may affect thyroid

Human evidence: lacking

Likely not concern: at normal doses

Monitor thyroid: if on high doses long-term

Alzheimer's medications: donepezil, rivastigmine, galantamine

Additive effects: both increase acetylcholine

May be beneficial: but medical supervision needed

Dose adjustment: may be required

Monitor for side effects: nausea, diarrhea, bradycardia

Choline may reduce: medication effectiveness

Medical consultation: before supplementation

Conditions treated: overactive bladder, COPD, Parkinson's

Coordination needed: with healthcare provider

Safe and essential: at appropriate doses

No known risks: extensive safety record

Critical nutrient: benefits far outweigh risks

600-900 mg daily: safe and beneficial

Safe at age-appropriate doses

Important for development

Adequate intake: from diet usually sufficient

Supplementation: if diet inadequate

Very safe and often beneficial

Cognitive protection

No age-related contraindications

Higher needs: in some elderly

Diabetes: safe

Heart disease: beneficial (homocysteine lowering)

Liver disease: often beneficial

Kidney disease: generally safe at normal doses

Fishy body odor: common at very high doses (varies individually)

Gastrointestinal upset: nausea, diarrhea

Low blood pressure: excessive cholinergic stimulation

Sweating: hyperhidrosis

TMAO concerns: theoretical cardiovascular risk

Based on: fishy odor and other side effects

Not true toxicity: but unpleasant effects

Most people: well below this amount

Therapeutic doses: usually under 1,500 mg

90% of Americans: don't meet AI for choline

Especially common in: pregnant women, postmenopausal women, vegetarians

Often unrecognized: deficiency symptoms subtle initially

Inadequate awareness: healthcare providers and public

Inadequate dietary intake (most common)

Increased needs (pregnancy, breastfeeding, genetics)

PEMT gene polymorphisms (reduced synthesis)

Postmenopausal (reduced estrogen affects synthesis)

Vegetarian/vegan diets (lower food sources)

Low folate, B12, B6 (impairs endogenous synthesis)

High alcohol consumption

Certain medications

Malabsorption disorders

Fatigue and low energy

Difficulty concentrating (brain fog)

Memory problems (mild)

Mood changes (irritability, anxiety)

Muscle aches and soreness

Insomnia or sleep disturbances

Often attributed: to other causes

Elevated liver enzymes: ALT, AST (asymptomatic initially)

Beginning fat accumulation: subclinical fatty liver

No obvious symptoms: yet

Detected on: blood tests or imaging

Memory impairment: more pronounced

Difficulty learning: new information

Reduced attention span

Mental fatigue: worsens throughout day

Mood disturbances: depression, anxiety

Fatty liver disease: non-alcoholic fatty liver disease (NAFLD)

Elevated liver enzymes: consistently abnormal

Liver enlargement: hepatomegaly

May progress: to inflammation and damage

Reversible: with choline repletion (if caught early)

Muscle damage: elevated creatine kinase

Muscle weakness and pain

Exercise intolerance

Delayed recovery: from physical activity

Elevated homocysteine: if also low folate/B12

Increased cardiovascular risk: over time

Endothelial dysfunction

Non-alcoholic steatohepatitis (NASH): inflammation and fibrosis

Liver dysfunction: impaired liver function

Cirrhosis: in extreme cases

May require: liver transplant if not corrected

Irreversible damage: if prolonged

Significant cognitive impairment

Memory loss: severe

Peripheral neuropathy: in some cases

Myelin damage: demyelination

Rhabdomyolysis: muscle breakdown (rare)

Severe muscle pain and weakness

Kidney damage: from muscle breakdown products

Increased liver enzyme levels

Fatty liver of pregnancy

Increased risk: of preeclampsia

Cognitive changes: brain fog worsens

Neural tube defects: increased risk

Impaired brain development: structural and functional

Reduced cognitive function: in offspring (lifelong)

Behavioral problems: in children

Increased disease risk: later in life (epigenetic programming)

Cleft palate: possible increased risk

First trimester: most critical for neural tube

Throughout pregnancy: for brain development

Third trimester: rapid brain growth period

Breastfeeding: continues to be critical

Pregnant and breastfeeding women (highest risk)

Postmenopausal women (PEMT enzyme reduced)

Vegetarians and vegans (lower dietary intake)

People with PEMT gene variations

Individuals with low folate/B12 status

Chronic alcoholics

People on total parenteral nutrition (TPN) without choline

Premature infants

People with liver disease

Fatty liver: on ultrasound or CT

Elevated liver enzymes: ALT, AST

Muscle damage: elevated creatine kinase

Cognitive symptoms: memory and concentration issues

Plasma choline: limited utility (fluctuates with diet)

Plasma betaine: may indicate status

No widely available: definitive test

Diagnosis often: clinical suspicion + response to supplementation

3,500 mg daily: for adults

Based on: fishy body odor and hypotension

Not true organ toxicity: just adverse effects

Wide safety margin: between adequate and excessive

Most common complaint

Caused by: trimethylamine (TMA) production by gut bacteria

TMA to TMAO: conversion in liver

Excreted in: sweat, breath, urine

Individual variation: genetic and microbiome differences

Some people: very sensitive, others tolerate high doses

Dose-dependent: higher doses more likely

Choline bitartrate: more likely than Alpha-GPC or CDP-choline

Nausea and vomiting

Diarrhea

Abdominal discomfort

Excessive salivation

Dose-dependent

Sweating: excessive perspiration

Low blood pressure: hypotension

Dizziness: from blood pressure drop

Bradycardia: slow heart rate (rare)

Choline converted: to TMA by gut bacteria

TMA to TMAO: in liver

TMAO associated: with cardiovascular disease in some studies

Correlation not causation: relationship unclear

Conflicting evidence: some studies show no harm

Eggs high in choline: yet associated with health benefits

Individual microbiome: dramatically affects TMAO production

Probiotics/prebiotics: may reduce TMA production

Current consensus: benefits likely outweigh TMAO concerns at normal doses

Very high acetylcholine: theoretically problematic

May affect: dopamine balance

Depression in bipolar: some case reports

Rare at normal doses

450-900 mg daily: safe and essential

Extensively studied: no adverse effects

Critical for development

Higher doses: limited long-term data but appear safe

3,000 mg daily: limited safety data in pregnancy

Stick to recommended: 450-900 mg range

No known birth defects: from supplementation

Cholinergic crisis: at massive doses (very rare)

Symptoms: severe nausea, vomiting, diarrhea, hypotension, bradycardia

Requires: medical intervention

Unlikely: with oral supplements at normal doses

Wide therapeutic window

Main side effect: fishy odor (cosmetic, not dangerous)

Benefits far outweigh: theoretical TMAO concerns

Pregnancy: safe and essential

Easy to adjust: dose based on tolerance

Measures total plasma choline

Limitations: fluctuates rapidly with recent intake

Not reliable: for assessing chronic status

Fasting sample: better but still limited

Normal range: ~7-20 μmol/L (varies by lab)

Choline metabolite

May better reflect: tissue stores

Less studied: than plasma choline

More stable: than plasma choline

Can measure: in blood

Reflects: membrane turnover and metabolism

Not routinely: available

Liver enzymes: ALT, AST (elevated in deficiency)

Creatine kinase: elevated with muscle damage

Homocysteine: may be elevated (also affected by folate/B12)

Liver imaging: ultrasound or MRI for fatty liver

Identifies polymorphisms

Indicates: higher choline needs

Available: through some genetic testing services

Not essential: clinical suspicion often sufficient

Affects folate metabolism

May influence: choline requirements

Commonly tested

No widely available: definitive test

Diagnosis usually: clinical suspicion

Response to supplementation: therapeutic trial

Unexplained elevated liver enzymes

Fatty liver disease

Muscle damage (elevated CK)

Cognitive symptoms: with suspected deficiency

Pregnancy: if concerns about intake

Research purposes

Dietary intake analysis

Symptom evaluation

Risk factor assessment

Trial of supplementation

Monitor response

No specific monitoring: needed for most people

Assess symptoms: energy, cognition, etc.

Check tolerance: fishy odor, GI symptoms

Adequate intake: ensure meeting 425-550 mg daily

Ensure adequate: 450-900 mg daily

Monitor: via dietary tracking

Prenatal care: regular checkups

No specific lab tests: usually needed

Liver enzymes: monitor if using for fatty liver

Baseline: before starting

Follow-up: every 3-6 months

Imaging: ultrasound to assess improvement

Liver function: periodic monitoring

Cardiovascular: if concerns about TMAO

Adjust dose: based on tolerance and response

Fetal brain development: rapid neurogenesis and synaptogenesis

Neural tube formation: alongside folate

Hippocampus development: memory center of brain

Cell division: all rapid growth requires choline

Epigenetic programming: affects gene expression lifelong

Lifelong effects: on child's cognition and health

Higher maternal choline: better cognitive outcomes in children

Improved memory: in offspring

Attention and processing speed: enhanced

Reduced risk: of neural tube defects

May reduce: developmental issues

First trimester: 600 mg daily minimum

Second/third trimester: 600-900 mg daily

Therapeutic studies: used 930 mg daily safely

Most prenatal vitamins: contain 0-55 mg (woefully inadequate)

Separate supplementation: essential

Food sources: eggs, meat, fish (if tolerated)

Supplements: choline bitartrate or phosphatidylcholine safe

Avoid: very high doses (>1,500 mg) without medical supervision

Combine with: folate, B12, DHA for comprehensive brain support

Preconception: start building stores 1-3 months before

Throughout pregnancy: maintain adequate intake

Breastfeeding: continue 550-1,000 mg daily

Not optional: one of most important pregnancy nutrients

Increases acetylcholine: neurotransmitter for learning and memory

Membrane synthesis: supports neuroplasticity

Neuroprotection: antioxidant and anti-inflammatory effects

Synaptic plasticity: supports long-term potentiation

Alpha-GPC: 300-600 mg daily (superior brain delivery)

CDP-choline: 250-500 mg daily (dual benefit: choline + uridine)

Choline bitartrate: less effective for brain than Alpha-GPC/CDP-choline

Alzheimer's disease: modest benefits in some studies

Age-related cognitive decline: may slow or prevent

Stroke recovery: CDP-choline well-researched

Traumatic brain injury: protective and recovery benefits

Healthy adults: mixed evidence for cognitive enhancement

Choline + DHA + uridine: "Mr. Happy Stack" for neuroplasticity

Choline + racetams: choline prevents headaches from racetams

Choline + caffeine + L-theanine: focus and attention

Comprehensive: add B-complex, phosphatidylserine

Daily: 300-600 mg Alpha-GPC or CDP-choline

Cycling: not necessary, can use continuously

Timing: morning or before cognitively demanding tasks

Response: individual variation, assess personally

VLDL formation: requires phosphatidylcholine to export fat from liver

Without adequate choline: fat accumulates in liver

Choline deficiency: direct cause of fatty liver

Reversal: choline supplementation can reverse early fatty liver

Very common: 25-30% of US adults

Choline deficiency: contributing factor in many cases

Supplementation: can help prevent and treat

Not standalone: diet, exercise, weight loss still primary

Adjunct therapy: choline as part of comprehensive approach

Prevention: 450-550 mg daily

Treatment: 1,000-3,000 mg daily

Form: phosphatidylcholine or choline bitartrate

Duration: several months minimum

Medical supervision: for diagnosed liver disease

Alcoholic fatty liver: choline helpful

Increased needs: alcohol increases choline requirements

Protection: against alcohol-induced liver damage

Not a license: to drink more, moderation still essential

Strong evidence: choline deficiency causes fatty liver

Supplementation: improves liver enzymes and fat content

Combined approach: works best (diet + exercise + choline)

Acetylcholine: required for muscle contraction

Choline depleted: during prolonged endurance exercise

Supplementation: may prevent depletion

Power output: some evidence for improvement

Mixed results: not all studies show benefit

Some studies: improved power and endurance

Alpha-GPC: most researched for athletes

Individual response: highly variable

Timing matters: pre-workout dosing

Pre-workout: 300-600 mg Alpha-GPC

Timing: 30-60 minutes before exercise

Not daily: typically just before training/competition

Trial personally: assess individual response

Popular: in pre-workout formulas

Alpha-GPC: may increase growth hormone acutely

Post-exercise: GH increase observed in some studies

Practical significance: unclear for performance

Trimethylamine N-oxide

Produced: gut bacteria convert choline → TMA → liver converts TMA → TMAO

Excreted: in urine

Observational studies: higher TMAO associated with CVD risk

Mechanism proposed: promotes atherosclerosis

Egg controversy: eggs high in choline, yet beneficial in most studies

Fish: also increases TMAO, but protective against CVD

Association not causation: TMAO may be marker, not cause

Confounding factors: diet, microbiome, genetics

Individual variation: enormous differences in TMAO production

Microbiome matters: some people's bacteria produce more TMA

Benefits likely outweigh: theoretical TMAO concerns

Don't avoid choline: benefits too important

Moderation: reasonable intake (not mega-doses)

Healthy diet: overall diet quality matters more

Microbiome support: probiotics, prebiotics, fiber

Individual assessment: if family history of CVD, discuss with doctor

Probiotics: may reduce TMA-producing bacteria

Prebiotics: support beneficial bacteria

DMB (3,3-dimethyl-1-butanol): experimental, from some foods

Red wine: may reduce TMAO (moderate consumption)

Mediterranean diet: associated with lower TMAO

Phosphatidylethanolamine N-methyltransferase enzyme

Synthesizes: choline from methionine + folate

Estrogen-regulated: more active with higher estrogen

rs12325817: common variant

rs7946: another common variant

Reduced activity: 50-70% in some variants

High prevalence: many people carry variants

Increased dietary needs: cannot synthesize enough choline

Especially: postmenopausal women (low estrogen)

Fatty liver risk: higher in variant carriers with low intake

Pregnancy: may need even more choline

Testing available: but not essential

Clinical suspicion: adequate for most

Higher intake: 550-900 mg daily if suspected

Family history: of choline-responsive conditions

Response to supplementation: good indicator

Breast milk: rich in choline (if mother adequate)

Formula: fortified with choline

Critical period: rapid brain development

Maternal status: determines breast milk content

Adequate maternal intake: essential

Growth: adequate choline important

Brain development: continues through adolescence

Diet: eggs and dairy good sources

Supplementation: if diet inadequate

Age-appropriate doses: based on AI

Brain maturation: prefrontal cortex develops

Higher needs: growth and development

Often poor diet: may benefit from supplementation

Athletes: higher needs

Maintenance: 425-550 mg daily adequate

Varies by: sex, genetics, lifestyle

Pregnancy/breastfeeding: dramatically increased needs

Assess intake: ensure meeting AI

Cognitive protection: may help prevent decline

Adequate intake: often inadequate

Medications: may interfere with metabolism

Supplementation: often beneficial

450-550 mg daily: recommended minimum

Alpha-GPC or CDP-choline: for cognitive benefits

Choline, folate, B12, B6, betaine: all interconnected

One-carbon metabolism: methylation reactions

Homocysteine: central molecule affected by all

Deficiency of one: increases needs for others

Choline (as betaine): donates methyl groups

Folate (as 5-MTHF): donates methyl groups

Can partially substitute: for each other

Adequate both: optimal for health

Two pathways: remethylation (folate/B12) and transsulfuration (B6)

Betaine pathway: alternative remethylation (from choline)

All important: for keeping homocysteine low

Cardiovascular health: all three B vitamins + choline

DNA methylation: requires methyl donors

Choline and folate: both critical

Pregnancy: affects fetal epigenetic programming

Lifelong effects: on gene expression and disease risk

Essential nutrient: inadequate endogenous synthesis for most people

Brain development: critical during pregnancy and lifelong

Liver health: prevents and treats fatty liver disease

Acetylcholine precursor: neurotransmitter for memory and muscle

90% deficient: most Americans don't meet adequate intake

Pregnancy critical: most important and most overlooked pregnancy nutrient

Very safe: wide margin between adequate and excessive

Dose: 600-900 mg daily throughout pregnancy

Start: preconception (1-3 months before)

Continue: through breastfeeding (550-1,000 mg)

Form: choline bitartrate or phosphatidylcholine safe and effective

Prenatal vitamins inadequate: most contain 0-55 mg, supplement separately

Combine with: folate (800 mcg), DHA (300-600 mg), B12 (1,000 mcg)

Not negotiable: one of most important and overlooked pregnancy nutrients

Dose: 425-550 mg daily (meet AI)

Food sources: eggs, meat, fish, soybeans

Supplement if needed: 250-550 mg to fill gap

Form: choline bitartrate cost-effective

Most people: falling short of adequate intake

Dose: 450-550 mg daily minimum

Higher needs: reduced PEMT enzyme (estrogen-dependent)

Cannot synthesize: as much endogenous choline

Supplement: often beneficial

Form: choline bitartrate or phosphatidylcholine

Dose: 300-600 mg daily

Form: Alpha-GPC or CDP-choline (superior brain delivery)

Timing: morning or before cognitive tasks

Combine with: DHA (1-2g), uridine (250-500mg), B-complex

Age-related decline: preventive strategy

Alzheimer's risk: may help slow progression

Prevention: 450-550 mg daily

Treatment: 1,000-3,000 mg daily

Form: phosphatidylcholine or choline bitartrate

Duration: several months minimum

Combine with: lifestyle changes (diet, exercise, weight loss)

Medical supervision: for diagnosed liver disease

Pre-workout: 300-600 mg Alpha-GPC

Timing: 30-60 minutes before exercise

Not daily: typically just before training/competition

Individual response: assess personally

May improve: power output and performance

Higher needs: lower intake from plant foods

Key sources: soybeans, tofu, cruciferous vegetables, quinoa

Lecithin supplements: soy or sunflower derived

450-550 mg daily: ensure adequate total

Supplementation: often beneficial

Cost-effective general supplementation

Pregnancy (safe and proven)

Liver health

Meeting daily needs

Most economical option

Cognitive enhancement and memory

Alzheimer's prevention/treatment

Athletic performance

Superior brain delivery

Worth extra cost for brain-specific goals

Stroke recovery

Traumatic brain injury

Cognitive decline

Focus and attention

Dual benefits (choline + uridine)

Research-backed for specific conditions

Liver health specifically

High-dose therapy

Gentle, whole phospholipid form

Pregnancy (some prefer)

Those sensitive to other forms

Very safe: wide therapeutic window

Main side effect: fishy body odor (dose-dependent, individual variation)

Upper limit 3,500 mg: based on side effects, not toxicity

Pregnancy safe: 600-900 mg essential and safe

TMAO concerns: theoretical, benefits likely outweigh for most

No serious toxicity: at normal supplemental doses

ALL pregnant/breastfeeding women (600-1,000 mg - essential)

Postmenopausal women (450-550 mg)

Vegetarians/vegans (450-550 mg)

People with fatty liver (1,000-3,000 mg)

Cognitive decline risk (300-600 mg Alpha-GPC)

Anyone not meeting AI from diet (425-550 mg)

Heavy alcohol consumers (550-1,000+ mg)

Athletes for performance (300-600 mg Alpha-GPC pre-workout)