Synthetic form used in most supplements and fortification

Stable and inexpensive to produce

Contains cyanide molecule (very small, non-toxic amount)

Must be converted to active forms in the body

Most extensively studied form

Long shelf life and heat-stable

Used in injections and oral supplements

Converts to methylcobalamin and adenosylcobalamin in body

Active, methylated form found in nature

Predominant form in blood and cerebrospinal fluid

Directly involved in homocysteine metabolism

Better retained in tissues according to some studies

More expensive than cyanocobalamin

Less stable (light-sensitive, shorter shelf life)

Preferred by many practitioners for neurological conditions

May be superior for methylation support

Active form found primarily in mitochondria

Essential cofactor for energy metabolism

Required for fatty acid and amino acid metabolism

Less common in supplements

Often combined with methylcobalamin

Important for mitochondrial function

More expensive and less stable

Natural form produced by bacteria

Used in some European countries for injections

Converted to active forms in body

Longer retention in body than cyanocobalamin

Preferred for cyanide poisoning treatment

May be superior for some genetic B12 disorders

Less common in oral supplements

Water-soluble but stored in liver for years

Largest and most complex vitamin structure

Only vitamin containing a metal ion (cobalt)

Requires intrinsic factor for absorption

Found exclusively in animal products

Can be synthesized only by bacteria

Red color due to cobalt center

Converts homocysteine to methionine

Generates methyl groups for DNA production

Essential for cell division

Critical for rapidly dividing cells

Works with folate in nucleotide synthesis

Required for proper chromosome replication

Myelin sheath formation and maintenance

Nerve signal transmission

Neurotransmitter synthesis

Brain development and function

Protects against neurodegeneration

Essential for cognitive function

Prevents megaloblastic anemia

Proper red blood cell maturation

Hemoglobin synthesis

Oxygen transport capacity

Works with folate for cell division

Fatty acid metabolism (adenosylcobalamin)

Amino acid metabolism

Citric acid cycle function

Mitochondrial energy production

Converts odd-chain fatty acids

Metabolizes certain amino acids (methionine, valine, isoleucine)

Generates SAMe (S-adenosylmethionine)

Gene expression regulation

Neurotransmitter production

Detoxification pathways

Homocysteine metabolism

Epigenetic modifications

Converts homocysteine to methionine (with folate)

Prevents homocysteine accumulation

Protects cardiovascular system

Prevents neurotoxicity

Essential methionine recycling

Prevents peripheral neuropathy (numbness, tingling)

Protects against cognitive decline and dementia

Supports memory and mental clarity

May help with depression and mood disorders

Protects myelin sheath (nerve insulation)

May slow progression of Alzheimer's disease

Helps maintain balance and coordination

Reduces fatigue and increases energy

Improves physical stamina

Enhances mental energy and focus

Supports mitochondrial function

Essential for metabolic energy production

Lowers homocysteine (heart disease risk factor)

Reduces stroke risk

Protects against atherosclerosis

Improves blood vessel function

Reduces cardiovascular mortality

Prevents megaloblastic anemia

Increases red blood cell count

Improves oxygen delivery

Prevents pernicious anemia

Supports healthy hemoglobin levels

Reduces depression risk and severity

Improves mood and emotional well-being

May help with anxiety

Supports neurotransmitter balance

Cognitive function and memory

Reduces fracture risk (with folate)

Lowers homocysteine (high levels harm bones)

Supports osteoblast function

May prevent osteoporosis

Supports white blood cell production

Enhances immune response

Important for cellular immunity

May reduce infection risk

Male fertility: improves sperm quality and count

Female fertility: supports ovulation

Important for fetal development

Prevents birth defects (with folate)

Supports healthy cell division

May improve skin conditions

Helps with hair growth

Strengthens nails

Infants 0-6 months: 0.4 mcg

Infants 7-12 months: 0.5 mcg

Children 1-3 years: 0.9 mcg

Children 4-8 years: 1.2 mcg

Children 9-13 years: 1.8 mcg

Males 14+ years: 2.4 mcg

Females 14+ years: 2.4 mcg

Pregnancy: 2.6 mcg

Breastfeeding: 2.8 mcg

No established upper limit due to low toxicity

Very high doses well-tolerated (1,000+ mcg daily)

No adverse effects even at massive doses

Maintenance: 100-1,000 mcg daily

Multivitamin: Usually contains 6-100 mcg

Optimal prevention: 500-1,000 mcg daily

Most supplements: 500-5,000 mcg

Oral: 1,000-2,000 mcg daily for 1-2 months

Sublingual: 1,000-5,000 mcg daily

Injection: 1,000 mcg weekly to monthly (medical administration)

Severe deficiency: may need injections initially

Maintenance after correction: 500-1,000 mcg daily

Neuropathy: 1,000-5,000 mcg daily (methylcobalamin preferred)

Cognitive decline: 1,000-2,000 mcg daily

Depression: 1,000-2,000 mcg daily

MS and other conditions: Often higher doses or injections

Homocysteine lowering: 500-1,000 mcg daily

Combined with folate (400-800 mcg) and B6 (25-50 mg)

Target homocysteine: <10 μmol/L

All adults over 50: 500-1,000 mcg daily

Reduced absorption: with aging

Preventive strategy: cognitive and cardiovascular protection

Essential supplementation: 250-1,000 mcg daily

No reliable plant sources: (except fortified foods)

Sublingual or high-dose oral: ensure absorption

Monitor status: test B12 levels regularly

Metformin (diabetes drug): 500-1,000 mcg daily

PPIs/H2 blockers: 500-1,000 mcg daily

Metformin long-term: significantly depletes B12

Age over 50 (reduced absorption)

Vegetarian/vegan diet (no dietary sources)

Pregnancy and breastfeeding

Gastrointestinal disorders (Crohn's, celiac)

Gastric bypass or stomach surgery

Pernicious anemia (autoimmune condition)

Medications (metformin, PPIs, H2 blockers)

Heavy alcohol use

Nitrous oxide exposure (dental, recreational)

Malabsorption conditions

Clams: 84 mcg per 3 oz (highest food source)

Beef liver: 70 mcg per 3 oz

Mussels: 20 mcg per 3 oz

Oysters: 16 mcg per 3 oz

Octopus: 30 mcg per 3 oz

Nutritional yeast (fortified): 2-8 mcg per tablespoon

Salmon: 4.8 mcg per 3 oz

Trout: 5.4 mcg per 3 oz

Tuna: 2.5 mcg per 3 oz

Beef (ground): 2.4 mcg per 3 oz

Haddock: 1.8 mcg per 3 oz

Fortified breakfast cereals: 1-6 mcg per serving

Chicken breast: 0.3 mcg per 3 oz

Turkey: 0.3 mcg per 3 oz

Eggs: 0.6 mcg per large egg

Milk: 1.2 mcg per cup

Yogurt: 1.1 mcg per cup

Cheese (Swiss): 0.9 mcg per oz

Cottage cheese: 0.7 mcg per cup

Fortified soy milk: 1.2 mcg per cup

Fortified almond milk: 1.5 mcg per cup

Spirulina, chlorella: contain B12 analogs (inactive in humans)

Seaweed (nori): trace amounts, unreliable

Unwashed vegetables: bacterial contamination (not recommended)

Fermented foods (tempeh, miso): analogs, not true B12

Mushrooms: essentially no B12

Cooking: minimal loss (B12 relatively heat-stable)

Long cooking: some loss in liquid

Microwave: preserves B12 well

Storage: minimal loss over time

Processing: generally well-preserved

Animal source matters: organ meats highest, muscle meat lower

No reliable plant sources exist

Fortified foods: only reliable non-animal source

Supplementation essential: for vegans

B12 analogs: in algae don't work in humans

Don't rely on: spirulina, seaweed, or fermented foods

Most common supplement form

Inexpensive and widely available

Very stable (long shelf life)

Well-studied and proven effective

Must convert to active forms

Good for most people

Oral, sublingual, or injection forms

Dosage: 100-5,000 mcg typical

Active, methylated form

Directly usable by body

Better tissue retention (some studies)

Preferred for neurological conditions

More expensive than cyanocobalamin

Less stable (light-sensitive)

May be superior for methylation support

Good for MTHFR gene variations

Dosage: 500-5,000 mcg typical

Active mitochondrial form

Important for energy metabolism

Less common in supplements

Often combined with methylcobalamin

More expensive

Good for fatigue and energy

Dosage: 1,000-3,000 mcg typical

Natural bacterial form

Longer retention than cyanocobalamin

Used in some European injections

Converts to active forms

Less common in oral supplements

May be preferred for some genetic conditions

Methylcobalamin + adenosylcobalamin: comprehensive coverage

All four forms: complete spectrum

May provide superior benefits

More expensive

Cost-effective general supplementation

Proven deficiency treatment

Long-term maintenance

Most people without specific needs

Injection preference (most common form)

Neurological conditions (neuropathy, cognitive decline)

MTHFR genetic variations

Elevated homocysteine

Depression and mental health

Pregnancy (active form preferred by some)

Methylation support

Worth extra cost for specific conditions

Energy and fatigue issues

Mitochondrial dysfunction

Often combined with methylcobalamin

Athletic performance

Comprehensive coverage

Neurological and energy support

Optimal benefits (if budget allows)

Convenient and inexpensive

High doses (1,000+ mcg) overcome absorption issues

Passive diffusion: ~1-2% absorbed even without intrinsic factor

Good for most people

Daily dosing

Dissolves under tongue

May bypass intrinsic factor requirement (debated)

Rapid absorption into bloodstream

Popular form

Similar effectiveness to oral at high doses

500-5,000 mcg typical

Rapid absorption

May be better for some

Convenient dosing

Often sublingual application

Transdermal delivery

Claims better absorption (limited evidence)

More expensive

May work for some people

Most effective for severe deficiency

Bypasses absorption completely

Requires medical administration or prescription

1,000 mcg weekly to monthly typical

Intramuscular (IM) most common

Subcutaneous also effective

Hydroxocobalamin or cyanocobalamin used

Prescription form (Nascobal)

Bypasses GI absorption

Alternative to injections

Weekly dosing (500 mcg)

Requires intrinsic factor (stomach protein)

Stomach acid releases B12 from food

Intrinsic factor binds B12

Absorbed in terminal ileum

Complex, multi-step process

~1-2% absorbed without intrinsic factor

High doses (1,000+ mcg) overcome absorption issues

Why high-dose oral works even without intrinsic factor

1,000 mcg oral ≈ 10-20 mcg absorbed

Lack of intrinsic factor (pernicious anemia)

Low stomach acid (age, PPIs, H2 blockers)

Intestinal damage (Crohn's, celiac)

Gastric bypass surgery

Bacterial overgrowth

Age over 50

With or without food: both effective for supplements

Morning preferred: may be energizing

Sublingual: hold under tongue 30+ seconds

Consistency matters: daily supplementation

Injections: weekly to monthly depending on protocol

Methyl trap: B12 converts 5-MTHF back to THF

Without B12: folate gets "trapped" and can't function

Homocysteine: both needed to lower levels

Always combine: B12 with folate

Dosage: 400-800 mcg folate with 500-1,000 mcg B12

Prevents: folate masking B12 deficiency

Homocysteine: third member of the trio

Transsulfuration pathway: B6 converts homocysteine to cysteine

Neurotransmitters: both support synthesis

Complete pathway: B6, B9, B12 together

Dosage: 25-50 mg B6 with B12 and folate

B1, B2, B3, B5: all work together in energy metabolism

B-complex: prevents imbalances

Synergistic effects: better together than alone

Complete support: comprehensive metabolic coverage

Alternative pathway: homocysteine to methionine

Methyl donor: like B12 and folate

Reduces B12 needs: supports methylation

Homocysteine: powerful combination

Liver support: additional benefit

Methylation pathway: alternative methyl donor

Works with B12: complementary pathways

Brain health: both essential

Pregnancy: both critical for fetal development

Methylation enzymes: require magnesium

Energy metabolism: works with B12

Muscle and nerve: both essential

Deficiency common: synergistic supplementation

Product of B12/folate pathway

Methyl donor: downstream from B12

Depression: both beneficial

Alternative: if B12/folate insufficient

B12: 500-1,000 mcg (methylcobalamin)

Folate: 400-800 mcg (5-MTHF preferred)

B6: 25-50 mg

Betaine: 500-1,000 mg

Choline: 250-500 mg

Omega-3s: 1-2g daily

B12: 1,000-5,000 mcg (methylcobalamin)

Folate: 400-800 mcg

B6: 50-100 mg

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

Phosphatidylserine: 100-300 mg

Alpha-lipoic acid: 300-600 mg

B12: 1,000-5,000 mcg (methyl + adenosyl)

Complete B-complex: all B vitamins

CoQ10: 100-300 mg

Iron: if deficient

Magnesium: 300-400 mg

L-carnitine: 500-2,000 mg

B12: 1,000-2,000 mcg (methylcobalamin)

Folate: 400-1,000 mcg (5-MTHF)

B6: 50-100 mg

SAMe: 400-800 mg

Omega-3s: 2-3g daily (EPA-rich)

Vitamin D: 2,000-4,000 IU

Significantly depletes B12 (30% develop deficiency)

Mechanism: interferes with calcium-dependent ileal B12 absorption

Supplementation essential: 500-1,000 mcg daily

Monitor B12 levels: annually if on long-term metformin

Higher doses may be needed: 1,000-2,000 mcg daily

Don't stop metformin: supplement and monitor instead

Omeprazole, esomeprazole, lansoprazole, etc.

Reduce stomach acid: impairs B12 release from food

Long-term use: significantly increases deficiency risk

Supplementation recommended: 500-1,000 mcg daily

High-dose oral effective: passive diffusion compensates

Monitor status: if on long-term PPIs

Ranitidine, famotidine, cimetidine

Reduce stomach acid: impairs B12 absorption

Less severe than PPIs: but still significant with long-term use

Supplementation helpful: 250-500 mcg daily

Cholestyramine, colestipol: bile acid sequestrants

May interfere with B12 absorption

Take 4+ hours apart from B12 supplements

Monitor B12 status

High doses: may reduce B12 absorption

Usually not clinically significant

Space apart from B12 supplements

May impair B12 absorption

Long-term use: monitor B12 status

Supplementation may be needed

Chloramphenicol: may interfere with B12 function

Broad-spectrum: may affect gut bacteria (produce small amount)

Usually not significant concern

Inactivates B12 irreversibly

Dental procedures: single exposure usually okay

Recreational use: very dangerous for B12 status

Chronic exposure: severe neurological damage possible

Surgery: may need B12 supplementation after

Impairs B12 absorption

Damages stomach lining: reduces intrinsic factor

Increases B12 requirements

Chronic alcoholics: high deficiency risk

Supplementation essential: 1,000+ mcg daily

May reduce B12 levels

Increases oxidative stress: higher B12 needs

Smokers: should ensure adequate intake

Very high doses (>2,000 mg): may degrade B12 in stomach

Space apart: take vitamin C 2+ hours from B12

Usually not clinically significant at normal doses

Masks B12 deficiency: corrects anemia but not neurological damage

Always combine: B12 with folate supplementation

Critical safety issue: don't take high folate without B12

Autoimmune destruction of intrinsic factor

Cannot absorb B12 from food or low-dose supplements

Requires: high-dose oral (1,000+ mcg) or injections

Lifelong supplementation: essential

Stomach lining atrophy: reduces intrinsic factor and acid

Common in elderly

High-dose oral or injections needed

Crohn's disease: especially terminal ileum

Celiac disease: malabsorption

Bacterial overgrowth: bacteria consume B12

Parasites (tapeworm): consume B12

Gastric bypass: bypasses intrinsic factor site

Gastrectomy: removes intrinsic factor production

Requires: lifelong high-dose or injection B12

No reliable plant sources exist

Deficiency inevitable: without supplementation or fortified foods

250-1,000 mcg daily: minimum

Monitor status: test B12 annually

Sublingual or high-dose oral: ensure absorption

Not optional: essential for health

10-30% have malabsorption: due to reduced stomach acid

Atrophic gastritis common: with aging

Preventive strategy: cognitive and cardiovascular protection

500-1,000 mcg daily: recommended by many experts

Monitor status: test every 1-2 years

Metformin (diabetes): 500-1,000 mcg daily essential

PPIs/H2 blockers: 500-1,000 mcg daily recommended

Long-term aspirin: may need supplementation

Multiple medications: increased risk

Pernicious anemia: high-dose or injections required

Crohn's disease: especially terminal ileum involvement

Celiac disease: malabsorption common

Atrophic gastritis: reduced intrinsic factor

Bacterial overgrowth: bacteria consume B12

Gastric bypass: lifelong supplementation essential

Peripheral neuropathy: tingling, numbness

Balance problems: ataxia

Cognitive decline: memory issues

Depression: especially treatment-resistant

Dementia prevention: high-risk individuals

Elevated homocysteine: >10-12 μmol/L

Family history: heart disease or stroke

Atherosclerosis: plaque buildup

With folate and B6: homocysteine-lowering protocol

Increased needs: fetal development

Essential with folate: neural tube defect prevention

Vegetarian mothers: supplementation critical

Breast milk: depends on maternal status

2.6-2.8 mcg minimum: higher doses reasonable

Unexplained fatigue: despite adequate sleep

Poor stamina: physical and mental

Rule out deficiency: test B12 levels

May dramatically improve energy if deficient

Depression: especially with low B12

Cognitive decline: prevention and treatment

Memory problems: rule out B12 deficiency

Mood disorders: B12 supports neurotransmitters

Megaloblastic anemia: diagnostic of B12 or folate deficiency

Macrocytic anemia: enlarged red blood cells

Unexplained anemia: test B12 and folate

Infants of vegetarian/vegan mothers: risk of severe deficiency

Elderly in institutions: often inadequate intake and absorption

Alcoholics: impaired absorption

Nitrous oxide exposure: recreational or occupational

Cyanocobalamin may worsen: cyanide sensitivity

Use hydroxocobalamin or methylcobalamin: instead

Avoid cyanocobalamin: in this rare genetic condition

Medical supervision: essential

Rare blood disorder: excess red blood cell production

B12 may worsen: stimulates red blood cell formation

Medical supervision: required

Monitor blood counts: if supplementing

B12 supports cell division: theoretical tumor promotion

No strong evidence: of harm in cancer patients

Medical consultation: for very high doses

Standard doses: likely safe

Extremely rare: cobalt in B12 structure

Allergic reactions possible: rash, itching

Discontinue if reaction occurs

Choose different form: if reaction to one type

Local pain, redness: at injection site

Usually minor: and transient

Rarely severe

Safe and essential: at appropriate doses

No known risks: from supplementation

Higher needs: during pregnancy

Critical for vegetarian mothers

Safe at age-appropriate doses

Essential for vegetarian children

Deficiency can cause: developmental delays

Supplementation important: if inadequate diet

Very safe: and highly beneficial

Often need higher doses: due to absorption issues

No age-related contraindications

Diabetes: safe and beneficial

Heart disease: protective effects

Kidney disease: generally safe (monitor levels)

Liver disease: safe

Absorption complex: many points of failure

Vegetarian/vegan diets: no dietary sources

Aging: reduced stomach acid and intrinsic factor

Medications: PPIs, metformin very common

Undiagnosed pernicious anemia

Can take years: to develop (liver stores last 3-5 years)

Fatigue and weakness: profound tiredness

Brain fog: difficulty concentrating

Memory problems: forgetfulness

Mood changes: depression, irritability

Lightheadedness: dizziness

Pale or jaundiced skin: from anemia

Shortness of breath: with exertion

Rapid heartbeat: tachycardia

Loss of appetite: reduced interest in food

Weight loss: unintentional

Sore, red tongue: glossitis

Mouth ulcers: painful sores

Burning sensation: in mouth or tongue

Peripheral neuropathy: tingling, numbness (usually starts in feet)

"Pins and needles": paresthesias

Burning sensations: in extremities

Difficulty walking: balance problems

Muscle weakness: progressive

Coordination problems: ataxia

Memory worsening: significant cognitive impairment

Megaloblastic anemia: large, immature red blood cells

Macrocytic anemia: MCV >100 fL

Low hemoglobin: significant

Pancytopenia: all blood cells reduced (severe cases)

Fatigue severe: debilitating

Depression: severe

Anxiety: increased

Paranoia: in severe cases

Hallucinations: rare but possible

Cognitive decline: significant

Elevated homocysteine: >15 μmol/L

Increased heart disease risk

Palpitations: irregular heartbeat

Subacute combined degeneration: spinal cord damage

Severe peripheral neuropathy: significant nerve damage

Ataxia: severe balance and coordination problems

Vision problems: optic neuropathy

Incontinence: bladder and bowel control loss

Paralysis: in extreme cases

Dementia: severe cognitive impairment

Psychosis: hallucinations, delusions

Irreversible damage: if untreated too long

Severe megaloblastic anemia: profound

Pancytopenia: dangerous blood cell deficiencies

Increased infection risk: low white blood cells

Bleeding risk: low platelets

Hyperpigmentation: darkened skin patches

Vitiligo: loss of skin pigmentation

Infertility: reproductive problems

Cardiovascular events: from high homocysteine

Osteoporosis: increased fracture risk

Developmental delays: significant

Failure to thrive: poor growth

Hypotonia: floppy baby syndrome

Seizures: neurological damage

Regression: loss of milestones

Brain atrophy: irreversible damage

Permanent disability: if not treated rapidly